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1. Prevalence, Clustering, and Current Management of Cardiovascular Risk Factors Upon First Referral to Hypertension Specialists: the APPROACH Study

Author: Del Pinto, R, Agabiti Rosei, C, Di Guardo, A, Giannattasio, C, Izzo, R, Mazza, A, Pucci, G, Sarzani, R, Tocci, G, Veglio, F, Volpe, M, Grassi, G, Muiesan, M, Ferri, C, Del Pinto R, Agabiti Rosei C, Di Guardo A, Giannattasio C, Izzo R, Mazza A, Pucci G, Sarzani R, Tocci G, Veglio F, Volpe M, Grassi G, Muiesan ML, Ferri C, Del Pinto, R, Agabiti Rosei, C, Di Guardo, A, Giannattasio, C, Izzo, R, Mazza, A, Pucci, G, Sarzani, R, Tocci, G, Veglio, F, Volpe, M, Grassi, G, Muiesan, M, Ferri, C, Del Pinto R, Agabiti Rosei C, Di Guardo A, Giannattasio C, Izzo R, Mazza A, Pucci G, Sarzani R, Tocci G, Veglio F, Volpe M, Grassi G, Muiesan ML, and Ferri C
Abstract: Introduction: Several observational studies have been conducted to assess the prevalence of cardiovascular risk factors in hypertensive patients; however, none has yet investigated prevalence, clustering, and current management of cardiovascular risk factors upon first referral to hypertension specialists, which is the aim of the present study. Methods: Consecutive adult outpatients with essential/secondary hypertension were included at the time of their first referral to hypertension specialists at 13 Italian centers in the period April 2022-2023 if they had at least one additional major cardiovascular risk factor among LDL-hypercholesterolemia, type 2 diabetes, and cigarette smoking. Prevalence, degree of control, and current management strategies of cardiovascular risk factors were assessed. Results: A total of 255 individuals were included, 40.2% women and 98.4% Caucasian. Mean age was 60.3±13.3 years and mean blood pressure [BP] was 140.3±17.9/84.8±12.3 mmHg). Most participants were smokers (55.3%), had a sedentary lifestyle (75.7%), suffered from overweight/obesity (51%) or high LDL-cholesterol (41.6%), had never adopted strategies to lose weight (55.7%), and were not on a low-salt diet (57.4%). Only a minority of patients reported receiving specialist counseling, and 27.9% had never received recommendations to correct unhealthy lifestyle habits. Nearly 90% of individuals with an estimated high/very high cardiovascular risk profile did not achieve recommended LDL-cholesterol targets. Conclusions: In patients with hypertension, both pharmacological and lifestyle therapeutic advice are yet to improve before referral to hypertension specialists. This should be considered in the primary care setting in order to optimize cardiovascular risk management strategies.
Published: 2024

2. May Measure Month 2022 in Italy: A Focus on Fixed-dose Combination, Therapeutic Adherence, and Medical Inertia in a Nationwide Survey

Author: Del Pinto, R, Agabiti Rosei, C, Borghi, C, Cipollini, F, Cottone, S, De Giorgi, G, Di Guardo, A, Dugnani, M, Fabris, B, Giannattasio, C, Giacchetti, G, Minuz, P, Mulè, G, Nazzaro, P, Parati, G, Rattazzi, M, Saladini, F, Salvetti, M, Sarzani, R, Savoia, C, Tocci, G, Veglio, F, Volpe, M, Vulpis, V, Baldini, G, Ferri, C, Muiesan, M, Del Pinto R., Agabiti Rosei C., Borghi C., Cipollini F., Cottone S., De Giorgi G. A., Di Guardo A., Dugnani M., Fabris B., Giannattasio C., Giacchetti G., Minuz P., Mulè G., Nazzaro P., Parati G., Rattazzi M., Saladini F., Salvetti M., Sarzani R., Savoia C., Tocci G., Veglio F., Volpe M., Vulpis V., Baldini G., Ferri C., Muiesan M. L., Del Pinto, R, Agabiti Rosei, C, Borghi, C, Cipollini, F, Cottone, S, De Giorgi, G, Di Guardo, A, Dugnani, M, Fabris, B, Giannattasio, C, Giacchetti, G, Minuz, P, Mulè, G, Nazzaro, P, Parati, G, Rattazzi, M, Saladini, F, Salvetti, M, Sarzani, R, Savoia, C, Tocci, G, Veglio, F, Volpe, M, Vulpis, V, Baldini, G, Ferri, C, Muiesan, M, Del Pinto R., Agabiti Rosei C., Borghi C., Cipollini F., Cottone S., De Giorgi G. A., Di Guardo A., Dugnani M., Fabris B., Giannattasio C., Giacchetti G., Minuz P., Mulè G., Nazzaro P., Parati G., Rattazzi M., Saladini F., Salvetti M., Sarzani R., Savoia C., Tocci G., Veglio F., Volpe M., Vulpis V., Baldini G., Ferri C., and Muiesan M. L.
Abstract: Introduction: Hypertension is the main risk factor for cardiovascular diseases (CVD). Notably, only about half of hypertensive patients manage to achieve the recommended blood pressure (BP) control. Main reasons for the persistence of uncontrolled BP during treatment are lack of compliance on the patients' side, and therapeutic inertia on physicians' side. Methods: During the global BP screening campaign "May Measure Month" (MMM) (May 1st to July 31st, 2022), a nationwide, cross-sectional, opportunistic study endorsed by the Italian Society of Hypertension was conducted on volunteer adults ≥ 18 years to raise awareness of the health issues surrounding high BP. A questionnaire on demographic/clinical features and questions on the use of fixed-dose single-pills for the treatment of hypertension was administered. BP was measured with standard procedures. Results: A total of 1612 participants (mean age 60.0±15.41 years; 44.7% women) were enrolled. Their mean BP was 128.5±18.1/77.1±10.4 mmHg. About half of participants were sedentary, or overweight/obese, or hypertensive. 55.5% individuals with complete BP assessment had uncontrolled hypertension. Most were not on a fixed-dose combination of antihypertensive drugs and did not regularly measure BP at home. Self-reported adherence to BP medications was similar between individuals with controlled and uncontrolled BP (95% vs 95.5%). Conclusions: This survey identified a remarkable degree of therapeutic inertia and poor patients' involvement in the therapeutic process and its monitoring in the examined population, underlining the importance of prevention campaigns to identify areas of unsatisfactory management of hypertension, to increase risk factors' awareness in the population with the final purpose of reducing cardiovascular risk.
Published: 2024

3. Prognostic Value and Relative Cutoffs of Triglycerides Predicting Cardiovascular Outcome in a Large Regional‐Based Italian Database

Author: Tikhonoff, V, Casiglia, E, Virdis, A, Grassi, G, Angeli, F, Arca, M, Barbagallo, C, Bombelli, M, Cappelli, F, Cianci, R, Cicero, A, Cirillo, M, Cirillo, P, Dell'Oro, R, D'Elia, L, Desideri, G, Ferri, C, Galletti, F, Gesualdo, L, Giannattasio, C, Iaccarino, G, Mallamaci, F, Maloberti, A, Masi, S, Masulli, M, Mazza, A, Mengozzi, A, Muiesan, M, Nazzaro, P, Palatini, P, Parati, G, Pontremoli, R, Quarti-Trevano, F, Rattazzi, M, Reboldi, G, Rivasi, G, Russo, E, Salvetti, M, Temporelli, P, Tocci, G, Ungar, A, Verdecchia, P, Viazzi, F, Volpe, M, Borghi, C, Tikhonoff V., Casiglia E., Virdis A., Grassi G., Angeli F., Arca M., Barbagallo C. M., Bombelli M., Cappelli F., Cianci R., Cicero A. F. G., Cirillo M., Cirillo P., Dell'oro R., D'elia L., Desideri G., Ferri C., Galletti F., Gesualdo L., Giannattasio C., Iaccarino G., Mallamaci F., Maloberti A., Masi S., Masulli M., Mazza A., Mengozzi A., Muiesan M. L., Nazzaro P., Palatini P., Parati G., Pontremoli R., Quarti-Trevano F., Rattazzi M., Reboldi G., Rivasi G., Russo E., Salvetti M., Temporelli P. L., Tocci G., Ungar A., Verdecchia P., Viazzi F., Volpe M., Borghi C., Tikhonoff, V, Casiglia, E, Virdis, A, Grassi, G, Angeli, F, Arca, M, Barbagallo, C, Bombelli, M, Cappelli, F, Cianci, R, Cicero, A, Cirillo, M, Cirillo, P, Dell'Oro, R, D'Elia, L, Desideri, G, Ferri, C, Galletti, F, Gesualdo, L, Giannattasio, C, Iaccarino, G, Mallamaci, F, Maloberti, A, Masi, S, Masulli, M, Mazza, A, Mengozzi, A, Muiesan, M, Nazzaro, P, Palatini, P, Parati, G, Pontremoli, R, Quarti-Trevano, F, Rattazzi, M, Reboldi, G, Rivasi, G, Russo, E, Salvetti, M, Temporelli, P, Tocci, G, Ungar, A, Verdecchia, P, Viazzi, F, Volpe, M, Borghi, C, Tikhonoff V., Casiglia E., Virdis A., Grassi G., Angeli F., Arca M., Barbagallo C. M., Bombelli M., Cappelli F., Cianci R., Cicero A. F. G., Cirillo M., Cirillo P., Dell'oro R., D'elia L., Desideri G., Ferri C., Galletti F., Gesualdo L., Giannattasio C., Iaccarino G., Mallamaci F., Maloberti A., Masi S., Masulli M., Mazza A., Mengozzi A., Muiesan M. L., Nazzaro P., Palatini P., Parati G., Pontremoli R., Quarti-Trevano F., Rattazzi M., Reboldi G., Rivasi G., Russo E., Salvetti M., Temporelli P. L., Tocci G., Ungar A., Verdecchia P., Viazzi F., Volpe M., and Borghi C.
Abstract: BACKGROUND: Despite longstanding epidemiologic data on the association between increased serum triglycerides and cardiovascular events, the exact level at which risk begins to rise is unclear. The Working Group on Uric Acid and Cardiovascular Risk of the Italian Society of Hypertension has conceived a protocol aimed at searching for the prognostic cutoff value of triglycerides in predicting cardiovascular events in a large regional-based Italian cohort. METHODS AND RESULTS: Among 14 189 subjects aged 18 to 95 years followed-up for 11.2 (5.3–13.2) years, the prognostic cutoff value of triglycerides, able to discriminate combined cardiovascular events, was identified by means of receiver operating characteristic curve. The conventional (150 mg/dL) and the prognostic cutoff values of triglycerides were used as independent predictors in separate multivariable Cox regression models adjusted for age, sex, body mass index, total and high-density lipoprotein cholesterol, serum uric acid, arterial hypertension, diabetes, chronic renal disease, smoking habit, and use of an-tihypertensive and lipid-lowering drugs. During 139 375 person-years of follow-up, 1601 participants experienced cardiovascular events. Receiver operating characteristic curve showed that 89 mg/dL (95% CI, 75.8–103.3, sensitivity 76.6, specificity 34.1, P<0.0001) was the prognostic cutoff value for cardiovascular events. Both cutoff values of triglycerides, the conventional and the newly identified, were accepted as multivariate predictors in separate Cox analyses, the hazard ratios being 1.211 (95% CI, 1.063–1.378, P=0.004) and 1.150 (95% CI, 1.021–1.295, P=0.02), respectively. CONCLUSIONS: Lower (89 mg/dL) than conventional (150 mg/dL) prognostic cutoff value of triglycerides for cardiovascular events does exist and is associated with increased cardiovascular risk in an Italian cohort.
Published: 2024

4. The Interaction Between Glomerular Filtration Rate (Gfr)-Adjusted Uricemia And Insulin Resistance In Predicting Mortality: The Urrah Project

Author: Russo, E, Viazzi, F, Pontremoli, R, Casiglia, E, Desideri, G, D’Elia, L, Ferri, C, Galletti, F, Masulli, M, Muiesan, M, Tikhonoff, V, Virdis, A, Grassi, G, Borghi, C, Muiesan, ML, Russo, E, Viazzi, F, Pontremoli, R, Casiglia, E, Desideri, G, D’Elia, L, Ferri, C, Galletti, F, Masulli, M, Muiesan, M, Tikhonoff, V, Virdis, A, Grassi, G, Borghi, C, and Muiesan, ML
Published: 2024

5. Prevalence, Awareness And Treatment Of Cardiovascular Risk Factors In Health Professionals In The Cardiovascular Field: The Protecto Esh-Siia Study

Author: Agabiti Rosei, C, Del Pinto, R, Giannattasio, C, Bombelli, M, Dell'Oro, R, Muiesan, M, Grassi, G, Ferri, C, Muiesan, ML, Agabiti Rosei, C, Del Pinto, R, Giannattasio, C, Bombelli, M, Dell'Oro, R, Muiesan, M, Grassi, G, Ferri, C, and Muiesan, ML
Published: 2024

6. Serum Uric Acid, Hypertriglyceridemia, and Carotid Plaques: A Sub-Analysis of the URic Acid Right for Heart Health (URRAH) Study

Author: Agabiti Rosei, C, Paini, A, Buso, G, Maloberti, A, Giannattasio, C, Salvetti, M, Casiglia, E, Tikhonoff, V, Angeli, F, Barbagallo, C, Bombelli, M, Cappelli, F, Cianci, R, Ciccarelli, M, Cicero, A, Cirillo, M, Cirillo, P, Dell'Oro, R, D'Elia, L, Desideri, G, Ferri, C, Galletti, F, Gesualdo, L, Grassi, G, Iaccarino, G, Lippa, L, Mallamaci, F, Masi, S, Masulli, M, Mazza, A, Mengozzi, A, Nazzaro, P, Palatini, P, Parati, G, Pontremoli, R, Quarti-Trevano, F, Rattazzi, M, Reboldi, G, Rivasi, G, Russo, E, Tocci, G, Ungar, A, Verdecchia, P, Viazzi, F, Volpe, M, Virdis, A, Muiesan, M, Borghi, C, Agabiti Rosei, Claudia, Paini, Anna, Buso, Giacomo, Maloberti, Alessandro, Giannattasio, Cristina, Salvetti, Massimo, Casiglia, Edoardo, Tikhonoff, Valerie, Angeli, Fabio, Barbagallo, Carlo Maria, Bombelli, Michele, Cappelli, Federica, Cianci, Rosario, Ciccarelli, Michele, Cicero, Arrigo Francesco Giuseppe, Cirillo, Massimo, Cirillo, Pietro, Dell'Oro, Raffaella, D'Elia, Lanfranco, Desideri, Giovambattista, Ferri, Claudio, Galletti, Ferruccio, Gesualdo, Loreto, Grassi, Guido, Iaccarino, Guido, Lippa, Luciano, Mallamaci, Francesca, Masi, Stefano, Masulli, Maria, Mazza, Alberto, Mengozzi, Alessandro, Nazzaro, Pietro, Palatini, Paolo, Parati, Gianfranco, Pontremoli, Roberto, Quarti-Trevano, Fosca, Rattazzi, Marcello, Reboldi, Gianpaolo, Rivasi, Giulia, Russo, Elisa, Tocci, Giuliano, Ungar, Andrea, Verdecchia, Paolo, Viazzi, Francesca, Volpe, Massimo, Virdis, Agostino, Muiesan, Maria Lorenza, Borghi, Claudio, Agabiti Rosei, C, Paini, A, Buso, G, Maloberti, A, Giannattasio, C, Salvetti, M, Casiglia, E, Tikhonoff, V, Angeli, F, Barbagallo, C, Bombelli, M, Cappelli, F, Cianci, R, Ciccarelli, M, Cicero, A, Cirillo, M, Cirillo, P, Dell'Oro, R, D'Elia, L, Desideri, G, Ferri, C, Galletti, F, Gesualdo, L, Grassi, G, Iaccarino, G, Lippa, L, Mallamaci, F, Masi, S, Masulli, M, Mazza, A, Mengozzi, A, Nazzaro, P, Palatini, P, Parati, G, Pontremoli, R, Quarti-Trevano, F, Rattazzi, M, Reboldi, G, Rivasi, G, Russo, E, Tocci, G, Ungar, A, Verdecchia, P, Viazzi, F, Volpe, M, Virdis, A, Muiesan, M, Borghi, C, Agabiti Rosei, Claudia, Paini, Anna, Buso, Giacomo, Maloberti, Alessandro, Giannattasio, Cristina, Salvetti, Massimo, Casiglia, Edoardo, Tikhonoff, Valerie, Angeli, Fabio, Barbagallo, Carlo Maria, Bombelli, Michele, Cappelli, Federica, Cianci, Rosario, Ciccarelli, Michele, Cicero, Arrigo Francesco Giuseppe, Cirillo, Massimo, Cirillo, Pietro, Dell'Oro, Raffaella, D'Elia, Lanfranco, Desideri, Giovambattista, Ferri, Claudio, Galletti, Ferruccio, Gesualdo, Loreto, Grassi, Guido, Iaccarino, Guido, Lippa, Luciano, Mallamaci, Francesca, Masi, Stefano, Masulli, Maria, Mazza, Alberto, Mengozzi, Alessandro, Nazzaro, Pietro, Palatini, Paolo, Parati, Gianfranco, Pontremoli, Roberto, Quarti-Trevano, Fosca, Rattazzi, Marcello, Reboldi, Gianpaolo, Rivasi, Giulia, Russo, Elisa, Tocci, Giuliano, Ungar, Andrea, Verdecchia, Paolo, Viazzi, Francesca, Volpe, Massimo, Virdis, Agostino, Muiesan, Maria Lorenza, and Borghi, Claudio
Abstract: High levels of serum uric acid (SUA) and triglycerides (TG) might promote high-cardiovascular-risk phenotypes, including subclinical atherosclerosis. An interaction between plaques xanthine oxidase (XO) expression, SUA, and HDL-C has been recently postulated. Subjects from the URic acid Right for heArt Health (URRAH) study with carotid ultrasound and without previous cardiovascular diseases (CVD) (n = 6209), followed over 20 years, were included in the analysis. Hypertriglyceridemia (hTG) was defined as TG ≥ 150 mg/dL. Higher levels of SUA (hSUA) were defined as ≥5.6 mg/dL in men and 5.1 mg/dL in women. A carotid plaque was identified in 1742 subjects (28%). SUA and TG predicted carotid plaque (HR 1.09 [1.04-1.27], p < 0.001 and HR 1.25 [1.09-1.45], p < 0.001) in the whole population, independently of age, sex, diabetes, systolic blood pressure, HDL and LDL cholesterol and treatment. Four different groups were identified (normal SUA and TG, hSUA and normal TG, normal SUA and hTG, hSUA and hTG). The prevalence of plaque was progressively greater in subjects with normal SUA and TG (23%), hSUA and normal TG (31%), normal SUA and hTG (34%), and hSUA and hTG (38%) (Chi-square, 0.0001). Logistic regression analysis showed that hSUA and normal TG [HR 1.159 (1.002 to 1.341); p = 0.001], normal SUA and hTG [HR 1.305 (1.057 to 1.611); p = 0.001], and the combination of hUA and hTG [HR 1.539 (1.274 to 1.859); p = 0.001] were associated with a higher risk of plaque. Our findings demonstrate that SUA is independently associated with the presence of carotid plaque and suggest that the combination of hyperuricemia and hypertriglyceridemia is a stronger determinant of carotid plaque than hSUA or hTG taken as single risk factors. The association between SUA and CVD events may be explained in part by a direct association of UA with carotid plaques.
Published: 2024

7. Risk of Cardiovascular Events in Metabolically Healthy Overweight or Obese Adults: Role of LDL-Cholesterol in the Stratification of Risk

Author: Palatini, P, Virdis, A, Masi, S, Mengozzi, A, Casiglia, E, Tikhonoff, V, Cicero, A, Ungar, A, Parati, G, Rivasi, G, Salvetti, M, Barbagallo, C, Bombelli, M, Dell'Oro, R, Bruno, B, Lippa, L, D'Elia, L, Masulli, M, Verdecchia, P, Reboldi, G, Angeli, F, Cianci, R, Mallamaci, F, Cirillo, M, Rattazzi, M, Cirillo, P, Gesualdo, L, Russo, E, Mazza, A, Giannattasio, C, Maloberti, A, Volpe, M, Tocci, G, Iaccarino, G, Nazzaro, P, Galletti, F, Ferri, C, Desideri, G, Viazzi, F, Pontremoli, R, Muiesan, M, Grassi, G, Borghi, C, Palatini, Paolo, Virdis, Agostino, Masi, Stefano, Mengozzi, Alessandro, Casiglia, Edoardo, Tikhonoff, Valerie, Cicero, Arrigo F G, Ungar, Andrea, Parati, Gianfranco, Rivasi, Giulia, Salvetti, Massimo, Barbagallo, Carlo Maria, Bombelli, Michele, Dell'Oro, Raffaella, Bruno, Berardino, Lippa, Luciano, D'Elia, Lanfranco, Masulli, Maria, Verdecchia, Paolo, Reboldi, Gianpaolo, Angeli, Fabio, Cianci, Rosario, Mallamaci, Francesca, Cirillo, Massimo, Rattazzi, Marcello, Cirillo, Pietro, Gesualdo, Loreto, Russo, Elisa, Mazza, Alberto, Giannattasio, Cristina, Maloberti, Alessandro, Volpe, Massimo, Tocci, Giuliano, Iaccarino, Guido, Nazzaro, Pietro, Galletti, Ferruccio, Ferri, Claudio, Desideri, Giovambattista, Viazzi, Francesca, Pontremoli, Roberto, Muiesan, Maria Lorenza, Grassi, Guido, Borghi, Claudio, Palatini, P, Virdis, A, Masi, S, Mengozzi, A, Casiglia, E, Tikhonoff, V, Cicero, A, Ungar, A, Parati, G, Rivasi, G, Salvetti, M, Barbagallo, C, Bombelli, M, Dell'Oro, R, Bruno, B, Lippa, L, D'Elia, L, Masulli, M, Verdecchia, P, Reboldi, G, Angeli, F, Cianci, R, Mallamaci, F, Cirillo, M, Rattazzi, M, Cirillo, P, Gesualdo, L, Russo, E, Mazza, A, Giannattasio, C, Maloberti, A, Volpe, M, Tocci, G, Iaccarino, G, Nazzaro, P, Galletti, F, Ferri, C, Desideri, G, Viazzi, F, Pontremoli, R, Muiesan, M, Grassi, G, Borghi, C, Palatini, Paolo, Virdis, Agostino, Masi, Stefano, Mengozzi, Alessandro, Casiglia, Edoardo, Tikhonoff, Valerie, Cicero, Arrigo F G, Ungar, Andrea, Parati, Gianfranco, Rivasi, Giulia, Salvetti, Massimo, Barbagallo, Carlo Maria, Bombelli, Michele, Dell'Oro, Raffaella, Bruno, Berardino, Lippa, Luciano, D'Elia, Lanfranco, Masulli, Maria, Verdecchia, Paolo, Reboldi, Gianpaolo, Angeli, Fabio, Cianci, Rosario, Mallamaci, Francesca, Cirillo, Massimo, Rattazzi, Marcello, Cirillo, Pietro, Gesualdo, Loreto, Russo, Elisa, Mazza, Alberto, Giannattasio, Cristina, Maloberti, Alessandro, Volpe, Massimo, Tocci, Giuliano, Iaccarino, Guido, Nazzaro, Pietro, Galletti, Ferruccio, Ferri, Claudio, Desideri, Giovambattista, Viazzi, Francesca, Pontremoli, Roberto, Muiesan, Maria Lorenza, Grassi, Guido, and Borghi, Claudio
Abstract: The objective of this study was to investigate the longitudinal association of metabolically healthy overweight/obese adults with major adverse cardiovascular events (MACE) and the effect of LDL-cholesterol levels on this association. This study was conducted with 15,904 participants from the URRAH study grouped according to BMI and metabolic status. Healthy metabolic status was identified with and without including LDL-cholesterol. The risk of MACE during 11.8 years of follow-up was evaluated with multivariable Cox regressions. Among the participants aged <70 years, high BMI was associated with an increased risk of MACE, whereas among the older subjects it was associated with lower risk. Compared to the group with normal weight/healthy metabolic status, the metabolically healthy participants aged <70 years who were overweight/obese had an increased risk of MACE with an adjusted hazard ratio of 3.81 (95% CI, 1.34-10.85, p = 0.012). However, when LDL-cholesterol < 130 mg/dL was included in the definition of healthy metabolic status, no increase in risk was found in the overweight/obese adults compared to the normal weight individuals (hazard ratio 0.70 (0.07-6.71, p = 0.75). The present data show that the risk of MACE is increased in metabolically healthy overweight/obese individuals identified according to standard criteria. However, when LDL-cholesterol is included in the definition, metabolically healthy individuals who are overweight/obese have no increase in risk.
Published: 2024

8. Triglyceride-glucose Index and Mortality in a Large Regional-based Italian Database (Urrah Project)

Author: D'Elia, L, Masulli, M, Virdis, A, Casiglia, E, Tikhonoff, V, Angeli, F, Barbagallo, C, Bombelli, M, Cappelli, F, Cianci, R, Ciccarelli, M, Cicero, A, Cirillo, M, Cirillo, P, Dell'Oro, R, Desideri, G, Ferri, C, Gesualdo, L, Giannattasio, C, Grassi, G, Iaccarino, G, Lippa, L, Mallamaci, F, Maloberti, A, Masi, S, Mazza, A, Mengozzi, A, Muiesan, M, Nazzaro, P, Palatini, P, Parati, G, Pontremoli, R, Quarti-Trevano, F, Rattazzi, M, Reboldi, G, Rivasi, G, Russo, E, Salvetti, M, Tocci, G, Ungar, A, Verdecchia, P, Viazzi, F, Volpe, M, Borghi, C, Galletti, F, D'Elia, Lanfranco, Masulli, Maria, Virdis, Agostino, Casiglia, Edoardo, Tikhonoff, Valerie, Angeli, Fabio, Barbagallo, Carlo Maria, Bombelli, Michele, Cappelli, Federica, Cianci, Rosario, Ciccarelli, Michele, Cicero, Arrigo F G, Cirillo, Massimo, Cirillo, Pietro, Dell'Oro, Raffaella, Desideri, Giovambattista, Ferri, Claudio, Gesualdo, Loreto, Giannattasio, Cristina, Grassi, Guido, Iaccarino, Guido, Lippa, Luciano, Mallamaci, Francesca, Maloberti, Alessandro, Masi, Stefano, Mazza, Alberto, Mengozzi, Alessandro, Muiesan, Maria Lorenza, Nazzaro, Pietro, Palatini, Paolo, Parati, Gianfranco, Pontremoli, Roberto, Quarti-Trevano, Fosca, Rattazzi, Marcello, Reboldi, Gianpaolo, Rivasi, Giulia, Russo, Elisa, Salvetti, Massimo, Tocci, Giuliano, Ungar, Andrea, Verdecchia, Paolo, Viazzi, Francesca, Volpe, Massimo, Borghi, Claudio, Galletti, Ferruccio, D'Elia, L, Masulli, M, Virdis, A, Casiglia, E, Tikhonoff, V, Angeli, F, Barbagallo, C, Bombelli, M, Cappelli, F, Cianci, R, Ciccarelli, M, Cicero, A, Cirillo, M, Cirillo, P, Dell'Oro, R, Desideri, G, Ferri, C, Gesualdo, L, Giannattasio, C, Grassi, G, Iaccarino, G, Lippa, L, Mallamaci, F, Maloberti, A, Masi, S, Mazza, A, Mengozzi, A, Muiesan, M, Nazzaro, P, Palatini, P, Parati, G, Pontremoli, R, Quarti-Trevano, F, Rattazzi, M, Reboldi, G, Rivasi, G, Russo, E, Salvetti, M, Tocci, G, Ungar, A, Verdecchia, P, Viazzi, F, Volpe, M, Borghi, C, Galletti, F, D'Elia, Lanfranco, Masulli, Maria, Virdis, Agostino, Casiglia, Edoardo, Tikhonoff, Valerie, Angeli, Fabio, Barbagallo, Carlo Maria, Bombelli, Michele, Cappelli, Federica, Cianci, Rosario, Ciccarelli, Michele, Cicero, Arrigo F G, Cirillo, Massimo, Cirillo, Pietro, Dell'Oro, Raffaella, Desideri, Giovambattista, Ferri, Claudio, Gesualdo, Loreto, Giannattasio, Cristina, Grassi, Guido, Iaccarino, Guido, Lippa, Luciano, Mallamaci, Francesca, Maloberti, Alessandro, Masi, Stefano, Mazza, Alberto, Mengozzi, Alessandro, Muiesan, Maria Lorenza, Nazzaro, Pietro, Palatini, Paolo, Parati, Gianfranco, Pontremoli, Roberto, Quarti-Trevano, Fosca, Rattazzi, Marcello, Reboldi, Gianpaolo, Rivasi, Giulia, Russo, Elisa, Salvetti, Massimo, Tocci, Giuliano, Ungar, Andrea, Verdecchia, Paolo, Viazzi, Francesca, Volpe, Massimo, Borghi, Claudio, and Galletti, Ferruccio
Abstract: Purpose: Recently, a novel index (triglyceride-glucose index-TyG) was considered a surrogate marker of insulin resistance (IR); in addition, it was estimated to be a better expression of IR than widely used tools. Few and heterogeneous data are available on the relationship between this index and mortality risk in non-Asian populations. Therefore, we estimated the predictive role of baseline TyG on the incidence of all-cause and cardiovascular (CV) mortality in a large sample of the general population. Moreover, in consideration of the well-recognized role of serum uric acid (SUA) on CV risk and the close correlation between SUA and IR, we also evaluated the combined effect of TyG and SUA on mortality risk. Methods: The analysis included 16,649 participants from the URRAH cohort. The risk of all-cause and CV mortality was evaluated by the Kaplan-Meier estimator and Cox multivariate analysis. Results: During a median follow-up of 144 months, 2569 deaths occurred. We stratified the sample by the optimal cut-off point for all-cause (4.62) and CV mortality (4.53). In the multivariate Cox regression analyses, participants with TyG above cut-off had a significantly higher risk of all-cause and CV mortality, than those with TyG below the cut-off. Moreover, the simultaneous presence of high levels of TyG and SUA was associated with a higher mortality risk than none or only one of the two factors. Conclusions: The results of this study indicate that these TyG (a low-cost and simple non-invasive marker) thresholds are predictive of an increased risk of mortality in a large and homogeneous general population. In addition, these results show a synergic effect of TyG and SUA on the risk of mortality.
Published: 2024

9. Serum Uric Acid/Serum Creatinine Ratio and Cardiovascular Mortality in Diabetic Individuals—The Uric Acid Right for Heart Health (URRAH) Project

Author: D’Elia, L, Masulli, M, Cirillo, P, Virdis, A, Casiglia, E, Tikhonoff, V, Angeli, F, Barbagallo, C, Bombelli, M, Cappelli, F, Cianci, R, Ciccarelli, M, Cicero, A, Cirillo, M, Dell’Oro, R, Desideri, G, Ferri, C, Gesualdo, L, Giannattasio, C, Grassi, G, Iaccarino, G, Lippa, L, Mallamaci, F, Maloberti, A, Masi, S, Mazza, A, Mengozzi, A, Muiesan, M, Nazzaro, P, Palatini, P, Parati, G, Pontremoli, R, Quarti-Trevano, F, Rattazzi, M, Reboldi, G, Rivasi, G, Russo, E, Salvetti, M, Tocci, G, Ungar, A, Verdecchia, P, Viazzi, F, Volpe, M, Borghi, C, Galletti, F, D’Elia, Lanfranco, Masulli, Maria, Cirillo, Pietro, Virdis, Agostino, Casiglia, Edoardo, Tikhonoff, Valerie, Angeli, Fabio, Barbagallo, Carlo Maria, Bombelli, Michele, Cappelli, Federica, Cianci, Rosario, Ciccarelli, Michele, Cicero, Arrigo F. G., Cirillo, Massimo, Dell’Oro, Raffaella, Desideri, Giovambattista, Ferri, Claudio, Gesualdo, Loreto, Giannattasio, Cristina, Grassi, Guido, Iaccarino, Guido, Lippa, Luciano, Mallamaci, Francesca, Maloberti, Alessandro, Masi, Stefano, Mazza, Alberto, Mengozzi, Alessandro, Muiesan, Maria Lorenza, Nazzaro, Pietro, Palatini, Paolo, Parati, Gianfranco, Pontremoli, Roberto, Quarti-Trevano, Fosca, Rattazzi, Marcello, Reboldi, Gianpaolo, Rivasi, Giulia, Russo, Elisa, Salvetti, Massimo, Tocci, Giuliano, Ungar, Andrea, Verdecchia, Paolo, Viazzi, Francesca, Volpe, Massimo, Borghi, Claudio, Galletti, Ferruccio, D’Elia, L, Masulli, M, Cirillo, P, Virdis, A, Casiglia, E, Tikhonoff, V, Angeli, F, Barbagallo, C, Bombelli, M, Cappelli, F, Cianci, R, Ciccarelli, M, Cicero, A, Cirillo, M, Dell’Oro, R, Desideri, G, Ferri, C, Gesualdo, L, Giannattasio, C, Grassi, G, Iaccarino, G, Lippa, L, Mallamaci, F, Maloberti, A, Masi, S, Mazza, A, Mengozzi, A, Muiesan, M, Nazzaro, P, Palatini, P, Parati, G, Pontremoli, R, Quarti-Trevano, F, Rattazzi, M, Reboldi, G, Rivasi, G, Russo, E, Salvetti, M, Tocci, G, Ungar, A, Verdecchia, P, Viazzi, F, Volpe, M, Borghi, C, Galletti, F, D’Elia, Lanfranco, Masulli, Maria, Cirillo, Pietro, Virdis, Agostino, Casiglia, Edoardo, Tikhonoff, Valerie, Angeli, Fabio, Barbagallo, Carlo Maria, Bombelli, Michele, Cappelli, Federica, Cianci, Rosario, Ciccarelli, Michele, Cicero, Arrigo F. G., Cirillo, Massimo, Dell’Oro, Raffaella, Desideri, Giovambattista, Ferri, Claudio, Gesualdo, Loreto, Giannattasio, Cristina, Grassi, Guido, Iaccarino, Guido, Lippa, Luciano, Mallamaci, Francesca, Maloberti, Alessandro, Masi, Stefano, Mazza, Alberto, Mengozzi, Alessandro, Muiesan, Maria Lorenza, Nazzaro, Pietro, Palatini, Paolo, Parati, Gianfranco, Pontremoli, Roberto, Quarti-Trevano, Fosca, Rattazzi, Marcello, Reboldi, Gianpaolo, Rivasi, Giulia, Russo, Elisa, Salvetti, Massimo, Tocci, Giuliano, Ungar, Andrea, Verdecchia, Paolo, Viazzi, Francesca, Volpe, Massimo, Borghi, Claudio, and Galletti, Ferruccio
Abstract: Several studies have detected a direct association between serum uric acid (SUA) and cardiovascular (CV) risk. In consideration that SUA largely depends on kidney function, some studies explored the role of the serum creatinine (sCr)-normalized SUA (SUA/sCr) ratio in different settings. Previously, the URRAH (URic acid Right for heArt Health) Study has identified a cut-off value of this index to predict CV mortality at 5.35 Units. Therefore, given that no SUA/sCr ratio threshold for CV risk has been identified for patients with diabetes, we aimed to assess the relationship between this index and CV mortality and to validate this threshold in the URRAH subpopulation with diabetes; the URRAH participants with diabetes were studied (n = 2230). The risk of CV mortality was evaluated by the Kaplan–Meier estimator and Cox multivariate analysis. During a median follow-up of 9.2 years, 380 CV deaths occurred. A non-linear inverse association between baseline SUA/sCr ratio and risk of CV mortality was detected. In the whole sample, SUA/sCr ratio > 5.35 Units was not a significant predictor of CV mortality in diabetic patients. However, after stratification by kidney function, values > 5.35 Units were associated with a significantly higher mortality rate only in normal kidney function, while, in participants with overt kidney dysfunction, values of SUA/sCr ratio > 7.50 Units were associated with higher CV mortality. The SUA/sCr ratio threshold, previously proposed by the URRAH Study Group, is predictive of an increased risk of CV mortality in people with diabetes and preserved kidney function. While, in consideration of the strong association among kidney function, SUA, and CV mortality, a different cut-point was detected for diabetics with impaired kidney function. These data highlight the different predictive roles of SUA (and its interaction with kidney function) in CV risk, pointing out the difference in metabolic- and kidney-dependent SUA levels also in diabetic
Published: 2024

10. Serum uric acid and left ventricular mass index independently predict cardiovascular mortality: The uric acid right for heart health (URRAH) project

Author: Muiesan, M, Agabiti Rosei, C, Paini, A, Casiglia, E, Cirillo, M, Grassi, G, Iaccarino, G, Mallamaci, F, Maloberti, A, Mazza, A, Mengozzi, A, Palatini, P, Parati, G, Reboldi, G, Rivasi, G, Russo, E, Salvetti, M, Tikhonoff, V, Tocci, G, Borghi, C, Angeli, F, Barbagallo, C, Bombelli, M, Cianci, R, Ciccarelli, M, Cicero, A, Cirillo, P, Dell'Oro, R, Medica, C, D'Elia, L, Desideri, G, Ferri, C, Galletti, F, Gesualdo, L, Giannattasio, C, Lippa, L, Masi, S, Masulli, M, Nazzaro, P, Pontremoli, R, Quarti-Trevano, F, Rattazzi, M, Ungar, A, Verdecchia, P, Viazzi, F, Virdis, A, Volpe, M, Muiesan M. L., Agabiti Rosei C., Paini A., Casiglia E., Cirillo M., Grassi G., Iaccarino G., Mallamaci F., Maloberti A., Mazza A., Mengozzi A., Palatini P., Parati G., Reboldi G., Rivasi G., Russo E., Salvetti M., Tikhonoff V., Tocci G., Borghi C., Angeli F., Barbagallo C. M., Bombelli M., Cianci R., Ciccarelli M., Cicero A. F. G., Cirillo P., Dell'Oro R., Medica C., D'Elia L., Desideri G., Ferri C., Galletti F., Gesualdo L., Giannattasio C., Lippa L., Masi S., Masulli M., Nazzaro P., Pontremoli R., Quarti-Trevano F., Rattazzi M., Ungar A., Verdecchia P., Viazzi F., Virdis A., Volpe M., Muiesan, M, Agabiti Rosei, C, Paini, A, Casiglia, E, Cirillo, M, Grassi, G, Iaccarino, G, Mallamaci, F, Maloberti, A, Mazza, A, Mengozzi, A, Palatini, P, Parati, G, Reboldi, G, Rivasi, G, Russo, E, Salvetti, M, Tikhonoff, V, Tocci, G, Borghi, C, Angeli, F, Barbagallo, C, Bombelli, M, Cianci, R, Ciccarelli, M, Cicero, A, Cirillo, P, Dell'Oro, R, Medica, C, D'Elia, L, Desideri, G, Ferri, C, Galletti, F, Gesualdo, L, Giannattasio, C, Lippa, L, Masi, S, Masulli, M, Nazzaro, P, Pontremoli, R, Quarti-Trevano, F, Rattazzi, M, Ungar, A, Verdecchia, P, Viazzi, F, Virdis, A, Volpe, M, Muiesan M. L., Agabiti Rosei C., Paini A., Casiglia E., Cirillo M., Grassi G., Iaccarino G., Mallamaci F., Maloberti A., Mazza A., Mengozzi A., Palatini P., Parati G., Reboldi G., Rivasi G., Russo E., Salvetti M., Tikhonoff V., Tocci G., Borghi C., Angeli F., Barbagallo C. M., Bombelli M., Cianci R., Ciccarelli M., Cicero A. F. G., Cirillo P., Dell'Oro R., Medica C., D'Elia L., Desideri G., Ferri C., Galletti F., Gesualdo L., Giannattasio C., Lippa L., Masi S., Masulli M., Nazzaro P., Pontremoli R., Quarti-Trevano F., Rattazzi M., Ungar A., Verdecchia P., Viazzi F., Virdis A., and Volpe M.
Abstract: Unlabelled: A relationship between serum uric acid (SUA) and cardiovascular (CV) events has been documented in the Uric Acid Right for Heart Health (URRAH) study. Aim: of this study was to investigate the association between SUA and left ventricular mass index (LVMI) and whether SUA and LVMI or their combination may predict the incidence of CV death. Methods: Subjects with echocardiographic measurement of LVMI included in the URRAH study (n=10733) were part of this analysis. LV hypertrophy (LVH) was defined as LVMI > 95 g/m2 in women and 115 g/m2 in men. Results: A significant association between SUA and LVMI was observed in multiple regression analysis in men: beta 0,095, F 5.47, P< 0.001 and women: beta 0,069, F 4.36, P<0.001. During follow-up 319 CV deaths occurred. Kaplan-Meier curves showed a significantly poorer survival rate in subjects with higher SUA (> 5.6 mg/dl in men and 5.1 mg/dl in women) and LVH (log-rank chi-square 298.105; P<0.0001). At multivariate Cox regression analysis in women LVH alone and the combination of higher SUA and LVH but not hyperuricemia alone, were associated with a higher risk of CV death, while in men hyperuricemia without LVH, LVH without hyperuricemia and their combination were all associated with a higher incidence of CV death. Conclusions: Our findings demonstrate that SUA is independently associated with LVMI and suggest that the combination of hyperuricemia with LVH is an independent and powerful predictor for CV death both in men and women.
Published: 2023

11. Management of mixed cryoglobulinemia with rituximab: evidence and consensus-based recommendations from the Italian Study Group of Cryoglobulinemia (GISC)

Author: Quartuccio, L, Bortoluzzi, A, Scire, C, Marangoni, A, Del Frate, G, Treppo, E, Castelnovo, L, Saccardo, F, Zani, R, Candela, M, Fraticelli, P, Mazzaro, C, Renoldi, P, Scaini, P, Filippini, D, Visentini, M, Scarpato, S, Giuggioli, D, Mascia, M, Sebastiani, M, Zignego, A, Lauletta, G, Fiorilli, M, Casato, M, Ferri, C, Pietrogrande, M, Pioltelli, P, De Vita, S, Monti, G, Galli, M, Quartuccio L., Bortoluzzi A., Scire C. A., Marangoni A., Del Frate G., Treppo E., Castelnovo L., Saccardo F., Zani R., Candela M., Fraticelli P., Mazzaro C., Renoldi P., Scaini P., Filippini D. A., Visentini M., Scarpato S., Giuggioli D., Mascia M. T., Sebastiani M., Zignego A. L., Lauletta G., Fiorilli M., Casato M., Ferri C., Pietrogrande M., Pioltelli P. E., De Vita S., Monti G., Galli M., Quartuccio, L, Bortoluzzi, A, Scire, C, Marangoni, A, Del Frate, G, Treppo, E, Castelnovo, L, Saccardo, F, Zani, R, Candela, M, Fraticelli, P, Mazzaro, C, Renoldi, P, Scaini, P, Filippini, D, Visentini, M, Scarpato, S, Giuggioli, D, Mascia, M, Sebastiani, M, Zignego, A, Lauletta, G, Fiorilli, M, Casato, M, Ferri, C, Pietrogrande, M, Pioltelli, P, De Vita, S, Monti, G, Galli, M, Quartuccio L., Bortoluzzi A., Scire C. A., Marangoni A., Del Frate G., Treppo E., Castelnovo L., Saccardo F., Zani R., Candela M., Fraticelli P., Mazzaro C., Renoldi P., Scaini P., Filippini D. A., Visentini M., Scarpato S., Giuggioli D., Mascia M. T., Sebastiani M., Zignego A. L., Lauletta G., Fiorilli M., Casato M., Ferri C., Pietrogrande M., Pioltelli P. E., De Vita S., Monti G., and Galli M.
Abstract: Cryoglobulinemic vasculitis (CV) or mixed cryoglobulinemic syndrome (MCS) is a systemic small-vessel vasculitis characterized by the proliferation of B-cell clones producing pathogenic immune complexes, called cryoglobulins. It is often secondary to hepatitis C virus (HCV), autoimmune diseases, and hematological malignancies. CV usually has a mild benign clinical course, but severe organ damage and life-threatening manifestations can occur. Recently, evidence in favor of rituximab (RTX), an anti-CD 20 monoclonal antibody, is emerging in CV: nevertheless, questions upon the safety of this therapeutic approach, especially in HCV patients, are still being issued and universally accepted recommendations that can help physicians in MCS treatment are lacking. A Consensus Committee provided a prioritized list of research questions to perform a systematic literature review (SLR). A search was made in Medline, Embase, and Cochrane library, updated to August 2021. Of 1227 article abstracts evaluated, 27 studies were included in the SLR, of which one SLR, 4 RCTs, and 22 observational studies. Seventeen recommendations for the management of mixed cryoglobulinemia with rituximab from the Italian Study Group of Cryoglobulinemia (GISC) were developed to give a valuable tool to the physician approaching RTX treatment in CV.
Published: 2023

12. Systemic sclerosis sine scleroderma: clinical and serological features and relationship with other cutaneous subsets in a large series of patients from the national registry 'SPRING' of the Italian Society for Rheumatology

Author: De Angelis, R, Ferri, C, Giuggioli, D, Bajocchi, G, Dagna, L, Bellando-Randone, S, Zanframundo, G, Foti, R, Cacciapaglia, F, Cuomo, G, Ariani, A, Rosato, E, Lepri, G, Girelli, F, Riccieri, V, Zanatta, E, Bosello, S, Cavazzana, I, Ingegnoli, F, De Santis, M, Murdaca, G, Abignano, G, Romeo, N, Della Rossa, A, Caminiti, M, Iuliano, A, Ciano, G, Beretta, L, Bagnato, G, Lubrano, E, De Andres, I, Giollo, A, Saracco, M, Agnes, C, Cipolletta, E, Lumetti, F, Spinella, A, Magnani, L, Campochiaro, C, De Luca, G, Codullo, V, Visalli, E, Di Vico, C, Gigante, A, Pellagrino, G, Pigatto, E, Lazzaroni, M, Franceschini, F, Generali, E, Mennillo, G, Barsotti, S, Mariano, G, Furini, F, Vultaggio, L, Parisi, S, Peroni, C, Rozza, D, Zanetti, A, Carrara, G, Landolfi, G, Scire, C, Bianchi, G, Fusaro, E, Sebastiani, G, Govoni, M, D'Angelo, S, Cozzi, F, Guiducci, S, Doria, A, Salvarani, C, Iannone, F, Matucci-Cerinic, M, Giorgio, A, Alessia, B, Francesca, C, Renato, C, Dall'Ara, F, Angelo, D, Marica, D, Gianluca, S, Rossella, T, De Angelis R., Ferri C., Giuggioli D., Bajocchi G., Dagna L., Bellando-Randone S., Zanframundo G., Foti R., Cacciapaglia F., Cuomo G., Ariani A., Rosato E., Lepri G., Girelli F., Riccieri V., Zanatta E., Bosello S. L., Cavazzana I., Ingegnoli F., De Santis M., Murdaca G., Abignano G., Romeo N., Della Rossa A., Caminiti M., Iuliano A. M., Ciano G., Beretta L., Bagnato G., Lubrano E., De Andres I., Giollo A., Saracco M., Agnes C., Cipolletta E., Lumetti F., Spinella A., Magnani L., Campochiaro C., De Luca G., Codullo V., Visalli E., Di Vico C., Gigante A., Pellagrino G., Pigatto E., Lazzaroni M. -G., Franceschini F., Generali E., Mennillo G., Barsotti S., Mariano G. P., Furini F., Vultaggio L., Parisi S., Peroni C. L., Rozza D., Zanetti A., Carrara G., Landolfi G., Scire C. A., Bianchi G., Fusaro E., Sebastiani G. D., Govoni M., D'Angelo S., Cozzi F., Guiducci S., Doria A., Salvarani C., Iannone F., Matucci-Cerinic M., Giorgio A., Alessia B., Francesca C., Renato C., Dall'Ara F., Angelo D. C., Marica D., Gianluca S., Rossella T., De Angelis, R, Ferri, C, Giuggioli, D, Bajocchi, G, Dagna, L, Bellando-Randone, S, Zanframundo, G, Foti, R, Cacciapaglia, F, Cuomo, G, Ariani, A, Rosato, E, Lepri, G, Girelli, F, Riccieri, V, Zanatta, E, Bosello, S, Cavazzana, I, Ingegnoli, F, De Santis, M, Murdaca, G, Abignano, G, Romeo, N, Della Rossa, A, Caminiti, M, Iuliano, A, Ciano, G, Beretta, L, Bagnato, G, Lubrano, E, De Andres, I, Giollo, A, Saracco, M, Agnes, C, Cipolletta, E, Lumetti, F, Spinella, A, Magnani, L, Campochiaro, C, De Luca, G, Codullo, V, Visalli, E, Di Vico, C, Gigante, A, Pellagrino, G, Pigatto, E, Lazzaroni, M, Franceschini, F, Generali, E, Mennillo, G, Barsotti, S, Mariano, G, Furini, F, Vultaggio, L, Parisi, S, Peroni, C, Rozza, D, Zanetti, A, Carrara, G, Landolfi, G, Scire, C, Bianchi, G, Fusaro, E, Sebastiani, G, Govoni, M, D'Angelo, S, Cozzi, F, Guiducci, S, Doria, A, Salvarani, C, Iannone, F, Matucci-Cerinic, M, Giorgio, A, Alessia, B, Francesca, C, Renato, C, Dall'Ara, F, Angelo, D, Marica, D, Gianluca, S, Rossella, T, De Angelis R., Ferri C., Giuggioli D., Bajocchi G., Dagna L., Bellando-Randone S., Zanframundo G., Foti R., Cacciapaglia F., Cuomo G., Ariani A., Rosato E., Lepri G., Girelli F., Riccieri V., Zanatta E., Bosello S. L., Cavazzana I., Ingegnoli F., De Santis M., Murdaca G., Abignano G., Romeo N., Della Rossa A., Caminiti M., Iuliano A. M., Ciano G., Beretta L., Bagnato G., Lubrano E., De Andres I., Giollo A., Saracco M., Agnes C., Cipolletta E., Lumetti F., Spinella A., Magnani L., Campochiaro C., De Luca G., Codullo V., Visalli E., Di Vico C., Gigante A., Pellagrino G., Pigatto E., Lazzaroni M. -G., Franceschini F., Generali E., Mennillo G., Barsotti S., Mariano G. P., Furini F., Vultaggio L., Parisi S., Peroni C. L., Rozza D., Zanetti A., Carrara G., Landolfi G., Scire C. A., Bianchi G., Fusaro E., Sebastiani G. D., Govoni M., D'Angelo S., Cozzi F., Guiducci S., Doria A., Salvarani C., Iannone F., Matucci-Cerinic M., Giorgio A., Alessia B., Francesca C., Renato C., Dall'Ara F., Angelo D. C., Marica D., Gianluca S., and Rossella T.
Abstract: Objective To describe demographic, clinical and laboratory features of systemic sclerosis sine scleroderma (ssSSc) in a large multicentre systemic sclerosis (SSc) cohort. Methods Data involving 1808 SSc patients from Italian Systemic sclerosis PRogression INvestiGation registry were collected. The ssSSc was defined by the absence of any cutaneous sclerosis and/or puffy fingers. Clinical and serological features of ssSSc were compared with limited cutaneous (lcSSc) and diffuse cutaneous (dcSSc) subsets. Results Among patients with SSc, only 61 (3.4%) were classified as having ssSSc (F/M=19/1). Time from Raynaud's phenomenon (RP) onset to diagnosis was longer in ssSSc (3 years, IQR 1-16.5) than lcSSc (2 years, IQR 0-7), and dcSSc (1 year, IQR 0-3) (p<0.001). Clinical ssSSc phenotype was comparable to lcSSc, except for digital pitting scars (DPS) (19.7% vs 42%, p=0.01), but significantly milder than dcSSc, particularly for digital ulcers (DU) (6.6% vs 35.7%, p<0.001), oesophagus (46.2% vs 63.5%, p=0.009), lung (mean diffusion capacity for carbon monoxide 72.2±19.6 vs 62.4±22.8, p=0.009; mean forced vital capacity 105.6±21.7 vs 89.2±20.9, p<0.001) and major videocapillaroscopic alterations (late pattern 8.6% vs 47.6%, p<0.001). Moreover, in ssSSc the percentages of anticentromere and antitopoisomerase were comparable to lcSSc (40% and 18.3% vs 36.7% and 26.6%), but divergent respect to dcSSc (8.6% and 67.4%, p<0.001). Conclusion The ssSSc is a quite rare disease variant characterised by clinico-serological features comparable to lcSSc, but significantly different from dcSSc. Overall, longer RP duration, low percentages of DPS and peripheral microvascular abnormalities, and increased anti-centromere seropositivity distinguish ssSSc. Further investigations based on national registries might provide useful insights on the actual relevance of the ssSSc within the scleroderma spectrum.
Published: 2023

13. Whole-genome sequencing reveals host factors underlying critical COVID-19

Author: Kousathanas, A, Pairo-Castineira, E, Rawlik, K, Stuckey, A, Odhams, C, Walker, S, Russell, C, Malinauskas, T, Wu, Y, Millar, J, Shen, X, Elliott, K, Griffiths, F, Oosthuyzen, W, Morrice, K, Keating, S, Wang, B, Rhodes, D, Klaric, L, Zechner, M, Parkinson, N, Siddiq, A, Goddard, P, Donovan, S, Maslove, D, Nichol, A, Semple, M, Zainy, T, Maleady-Crowe, F, Todd, L, Salehi, S, Knight, J, Elgar, G, Chan, G, Arumugam, P, Patch, C, Rendon, A, Bentley, D, Kingsley, C, Kosmicki, J, Horowitz, J, Baras, A, Abecasis, G, Ferreira, M, Justice, A, Mirshahi, T, Oetjens, M, Rader, D, Ritchie, M, Verma, A, Fowler, T, Shankar-Hari, M, Summers, C, Hinds, C, Horby, P, Ling, L, Mcauley, D, Montgomery, H, Openshaw, P, Elliott, P, Walsh, T, Tenesa, A, Shelton, J, Shastri, A, Ye, C, Weldon, C, Filshtein-Sonmez, T, Coker, D, Symons, A, Esparza-Gordillo, J, Aslibekyan, S, Auton, A, Pathak, G, Karjalainen, J, Stevens, C, Andrews, S, Kanai, M, Cordioli, M, Polimanti, R, Pirinen, M, Harerimana, N, Veerapen, K, Wolford, B, Nguyen, H, Solomonson, M, Liao, R, Chwialkowska, K, Trankiem, A, Balaconis, M, Hayward, C, Richmond, A, Campbell, A, Morris, M, Fawns-Ritchie, C, Glessner, J, Shaw, D, Chang, X, Polikowski, H, Petty, L, Chen, H, Wanying, Z, Hakonarson, H, Porteous, D, Below, J, North, K, Mccormick, J, Timmers, P, Wilson, J, D'Mellow, K, Kerr, S, Niemi, M, Nkambul, L, von Hohenstaufen, K, Sobh, A, Eltoukhy, M, Yassen, A, Hegazy, M, Okasha, K, Eid, M, Moahmed, H, Shahin, D, El-Sherbiny, Y, Elhadidy, T, Abd Elghafar, M, El-Jawhari, J, Mohamed, A, Elnagdy, M, Samir, A, Abdel-Aziz, M, Khafaga, W, El-Lawaty, W, Torky, M, El-shanshory, M, Batini, C, Lee, P, Shrine, N, Williams, A, Tobin, M, Guyatt, A, John, C, Packer, R, Ali, A, Free, R, Wang, X, Wain, L, Hollox, E, Venn, L, Bee, C, Adams, E, Niavarani, A, Sharififard, B, Aliannejad, R, Amirsavadkouhi, A, Naderpour, Z, Tadi, H, Aleagha, A, Ahmadi, S, Moghaddam, S, Adamsara, A, Saeedi, M, Abdollahi, H, Hosseini, A, Chariyavilaskul, P, Chamnanphon, M, Suttichet, T, Shotelersuk, V, Pongpanich, M, Phokaew, C, Chetruengchai, W, Jantarabenjakul, W, Putchareon, O, Torvorapanit, P, Puthanakit, T, Suchartlikitwong, P, Hirankarn, N, Nilaratanakul, V, Sodsai, P, Brumpton, B, Hveem, K, Willer, C, Zhou, W, Rogne, T, Solligard, E, Asvold, B, Abedalthagafi, M, Alaamery, M, Alqahtani, S, Barakeh, D, Al Harthi, F, Alsolm, E, Safieh, L, Alowayn, A, Alqubaishi, F, Al Mutairi, A, Mangul, S, Alshareef, A, Sawaji, M, Almutairi, M, Aljawini, N, Albesher, N, Arabi, Y, Mahmoud, E, Khattab, A, Halawani, R, Alahmadey, Z, Albakri, J, Felemban, W, Suliman, B, Hasanato, R, Al-Awdah, L, Alghamdi, J, Alzahrani, D, Aljohani, S, Al-Afghani, H, Alrashed, M, Aldhawi, N, Albardis, H, Alkwai, S, Alswailm, M, Almalki, F, Albeladi, M, Almohammed, I, Barhoush, E, Albader, A, Massadeh, S, Almalik, A, Alotaibi, S, Alghamdi, B, Jung, J, Fawzy, M, Lee, Y, Magnus, P, Trogstad, L, Helgeland, O, Harris, J, Mangino, M, Spector, T, Duncan, E, Smieszek, S, Przychodzen, B, Polymeropoulos, C, Polymeropoulos, V, Polymeropoulos, M, Fernandez-Cadenas, I, Perez-Tur, J, Llucia-Carol, L, Cullell, N, Muino, E, Carcel-Marquez, J, Dediego, M, Iglesias, L, Planas, A, Soriano, A, Rico, V, Aguero, D, Bedini, J, Lozano, F, Domingo, C, Robles, V, Ruiz-Jaen, F, Marquez, L, Gomez, J, Coto, E, Albaiceta, G, Garcia-Clemente, M, Dalmau, D, Arranz, M, Dietl, B, Serra-Llovich, A, Soler, P, Colobran, R, Martin-Nalda, A, Martinez, A, Bernardo, D, Rojo, S, Fiz-Lopez, A, Arribas, E, de la Cal-Sabater, P, Segura, T, Gonzalez-Villa, E, Serrano-Heras, G, Marti-Fabregas, J, Jimenez-Xarrie, E, de Felipe Mimbrera, A, Masjuan, J, Garcia-Madrona, S, Dominguez-Mayoral, A, Villalonga, J, Menendez-Valladares, P, Chasman, D, Buring, J, Ridker, P, Franco, G, Sesso, H, Manson, J, Medina-Gomez, C, Uitterlinden, A, Ikram, M, Kristiansson, K, Koskelainen, S, Perola, M, Donner, K, Kivinen, K, Palotie, A, Ripatti, S, Ruotsalainen, S, Kaunisto, M, Nakanishi, T, Butler-Laporte, G, Forgetta, V, Morrison, D, Ghosh, B, Laurent, L, Belisle, A, Henry, D, Abdullah, T, Adeleye, O, Mamlouk, N, Kimchi, N, Afrasiabi, Z, Rezk, N, Vulesevic, B, Bouab, M, Guzman, C, Petitjean, L, Tselios, C, Xue, X, Schurr, E, Afilalo, J, Afilalo, M, Oliveira, M, Brenner, B, Lepage, P, Ragoussis, J, Auld, D, Brassard, N, Durand, M, Chasse, M, Kaufmann, D, Lathrop, G, Mooser, V, Richards, J, Li, R, Adra, D, Rahmouni, S, Georges, M, Moutschen, M, Misset, B, Darcis, G, Guiot, J, Guntz, J, Azarzar, S, Gofflot, S, Beguin, Y, Claassen, S, Malaise, O, Huynen, P, Meuris, C, Thys, M, Jacques, J, Leonard, P, Frippiat, F, Giot, J, Sauvage, A, von Frenckell, C, Belhaj, Y, Lambermont, B, Pigazzini, S, Nkambule, L, Daya, M, Shortt, J, Rafaels, N, Wicks, S, Crooks, K, Barnes, K, Gignoux, C, Chavan, S, Laisk, T, Lall, K, Lepamets, M, Magi, R, Esko, T, Reimann, E, Milani, L, Alavere, H, Metsalu, K, Puusepp, M, Metspalu, A, Naaber, P, Laane, E, Pesukova, J, Peterson, P, Kisand, K, Tabri, J, Allos, R, Hensen, K, Starkopf, J, Ringmets, I, Tamm, A, Kallaste, A, Bochud, P, Rivolta, C, Bibert, S, Quinodoz, M, Kamdar, D, Boillat, N, Nussle, S, Albrich, W, Suh, N, Neofytos, D, Erard, V, Voide, C, de Cid, R, Galvan-Femenia, I, Blay, N, Carreras, A, Cortes, B, Farre, X, Sumoy, L, Moreno, V, Mercader, J, Guindo-Martinez, M, Torrents, D, Kogevinas, M, Garcia-Aymerich, J, Castano-Vinyals, G, Dobano, C, Renieri, A, Mari, F, Fallerini, C, Daga, S, Benetti, E, Baldassarri, M, Fava, F, Frullanti, E, Valentino, F, Doddato, G, Giliberti, A, Tita, R, Amitrano, S, Bruttini, M, Croci, S, Meloni, I, Mencarelli, M, Rizzo, C, Pinto, A, Beligni, G, Tommasi, A, Di Sarno, L, Palmieri, M, Carriero, M, Alaverdian, D, Busani, S, Bruno, R, Vecchia, M, Belli, M, Picchiotti, N, Sanarico, M, Gori, M, Furini, S, Mantovani, S, Ludovisi, S, Mondelli, M, Castelli, F, Quiros-Roldan, E, Antoni, M, Zanella, I, Vaghi, M, Rusconi, S, Siano, M, Montagnani, F, Emiliozzi, A, Fabbiani, M, Rossetti, B, Bargagli, E, Bergantini, L, D'Alessandro, M, Cameli, P, Bennett, D, Anedda, F, Marcantonio, S, Scolletta, S, Franchi, F, Mazzei, M, Guerrini, S, Conticini, E, Cantarini, L, Frediani, B, Tacconi, D, Spertilli, C, Feri, M, Donati, A, Scala, R, Guidelli, L, Spargi, G, Corridi, M, Nencioni, C, Croci, L, Bandini, M, Caldarelli, G, Piacentini, P, Desanctis, E, Cappelli, S, Canaccini, A, Verzuri, A, Anemoli, V, Ognibene, A, Pancrazzi, A, Lorubbio, M, D'Arminio Monforte, A, Miraglia, F, Girardis, M, Venturelli, S, Cossarizza, A, Antinori, A, Vergori, A, Gabrieli, A, Riva, A, Francisci, D, Schiaroli, E, Paciosi, F, Scotton, P, Andretta, F, Panese, S, Scaggiante, R, Gatti, F, Parisi, S, Baratti, S, Della Monica, M, Piscopo, C, Capasso, M, Russo, R, Andolfo, I, Iolascon, A, Fiorentino, G, Carella, M, Castori, M, Merla, G, Squeo, G, Aucella, F, Raggi, P, Marciano, C, Perna, R, Bassetti, M, Di Biagio, A, Sanguinetti, M, Masucci, L, Valente, S, Mandala, M, Giorli, A, Salerni, L, Zucchi, P, Parravicini, P, Menatti, E, Trotta, T, Giannattasio, F, Coiro, G, Lena, F, Coviello, D, Mussini, C, Martinelli, E, Mancarella, S, Tavecchia, L, Crotti, L, Gabbi, C, Rizzi, M, Maggiolo, F, Ripamonti, D, Bachetti, T, La Rovere, M, Sarzi-Braga, S, Bussotti, M, Ceri, S, Pinoli, P, Raimondi, F, Biscarini, F, Stella, A, Zguro, K, Capitani, K, Suardi, C, Dei, S, Parati, G, Ravaglia, S, Artuso, R, Botta, G, Di Domenico, P, Rancan, I, Perrella, A, Bianchi, F, Romani, D, Bergomi, P, Catena, E, Colombo, R, Tanfoni, M, Vincenti, A, Ferri, C, Grassi, D, Pessina, G, Tumbarello, M, Di Pietro, M, Sabrina, R, Luchi, S, Barbieri, C, Acquilini, D, Andreucci, E, Segala, F, Tiseo, G, Falcone, M, Lista, M, Poscente, M, De Vivo, O, Petrocelli, P, Guarnaccia, A, Baroni, S, Smith, A, Boughton, A, Li, K, Lefaive, J, Annis, A, Chittoor, G, Josyula, N, Leader, J, Carey, D, Gass, M, Cantor, M, Yadav, A, van Heel, D, Hunt, K, Mason, D, Huang, Q, Finer, S, Trivedi, B, Griffiths, C, Martin, H, Wright, J, Trembath, R, Soranzo, N, Zhao, J, Butterworth, A, Danesh, J, Di Angelantonio, E, Franke, L, Boezen, M, Deelen, P, Claringbould, A, Lopera, E, Warmerdam, R, Vonk, J, van Blokland, I, Lanting, P, Ori, A, Zollner, S, Wang, J, Beck, A, Peloso, G, Ho, Y, Sun, Y, Huffman, J, O'Donnell, C, Cho, K, Tsao, P, Gaziano, J, Nivard, M, de Geus, E, Bartels, M, Jan Hottenga, J, Weiss, S, Karlson, E, Smoller, J, Green, R, Feng, Y, Murphy, S, Meigs, J, Woolley, A, Perez, E, Li, B, Verma, S, Lucas, A, Bradford, Y, Zeberg, H, Frithiof, R, Hultstrom, M, Lipcsey, M, Tardif, N, Rooyackers, O, Grip, J, Maricic, T, Karczewski, K, Atkinson, E, Tsuo, K, Baya, N, Turley, P, Gupta, R, Callier, S, Walters, R, Palmer, D, Sarma, G, Cheng, N, Lu, W, Bryant, S, Churchhouse, C, Cusick, C, Goldstein, J, King, D, Seed, C, Finucane, H, Martin, A, Satterstrom, F, Wilson, D, Armstrong, J, Rudkin, J, Band, G, Earle, S, Lin, S, Arning, N, Crook, D, Wyllie, D, O'Connell, A, Spencer, C, Koelling, N, Caulfield, M, Scott, R, Moutsianas, L, Pasko, D, Ball, C, Hong, E, Rand, K, Girshick, A, Guturu, H, Baltzell, A, Roberts, G, Park, D, Coignet, M, Mccurdy, S, Knight, S, Partha, R, Rhead, B, Zhang, M, Berkowitz, N, Gaddis, M, Noto, K, Ruiz, L, Pavlovic, M, Sloofman, L, Charney, A, Beckmann, N, Schadt, E, Jordan, D, Thompson, R, Gettler, K, Abul-Husn, N, Ascolillo, S, Buxbaum, J, Chaudhary, K, Cho, J, Itan, Y, Kenny, E, Belbin, G, Sealfon, S, Sebra, R, Salib, I, Collins, B, Levy, T, Britvan, B, Keller, K, Tang, L, Peruggia, M, Hiester, L, Niblo, K, Aksentijevich, A, Labkowsky, A, Karp, A, Zlatopolsky, M, Preuss, M, Loos, R, Nadkarni, G, Do, R, Hoggart, C, Choi, S, Underwood, S, O'Reilly, P, Huckins, L, Zyndorf, M, Daly, M, Neale, B, Ganna, A, Fawkes, A, Murphy, L, Rowan, K, Ponting, C, Vitart, V, Yang, J, Bretherick, A, Hendry, S, Law, A, Baillie, J, Kousathanas A., Pairo-Castineira E., Rawlik K., Stuckey A., Odhams C. A., Walker S., Russell C. D., Malinauskas T., Wu Y., Millar J., Shen X., Elliott K. S., Griffiths F., Oosthuyzen W., Morrice K., Keating S., Wang B., Rhodes D., Klaric L., Zechner M., Parkinson N., Siddiq A., Goddard P., Donovan S., Maslove D., Nichol A., Semple M. G., Zainy T., Maleady-Crowe F., Todd L., Salehi S., Knight J., Elgar G., Chan G., Arumugam P., Patch C., Rendon A., Bentley D., Kingsley C., Kosmicki J. A., Horowitz J. E., Baras A., Abecasis G. R., Ferreira M. A. R., Justice A., Mirshahi T., Oetjens M., Rader D. J., Ritchie M. D., Verma A., Fowler T. A., Shankar-Hari M., Summers C., Hinds C., Horby P., Ling L., McAuley D., Montgomery H., Openshaw P. J. M., Elliott P., Walsh T., Tenesa A., Shelton J. F., Shastri A. J., Ye C., Weldon C. H., Filshtein-Sonmez T., Coker D., Symons A., Esparza-Gordillo J., Aslibekyan S., Auton A., Pathak G. A., Karjalainen J., Stevens C., Andrews S. J., Kanai M., Cordioli M., Polimanti R., Pirinen M., Harerimana N., Veerapen K., Wolford B., Nguyen H., Solomonson M., Liao R. G., Chwialkowska K., Trankiem A., Balaconis M. K., Hayward C., Richmond A., Campbell A., Morris M., Fawns-Ritchie C., Glessner J. T., Shaw D. M., Chang X., Polikowski H., Petty L. E., Chen H. -H., Wanying Z., Hakonarson H., Porteous D. J., Below J., North K., McCormick J. B., Timmers P. R. H. J., Wilson J. F., D'Mellow K., Kerr S. M., Niemi M. E. K., Nkambul L., von Hohenstaufen K. A., Sobh A., Eltoukhy M. M., Yassen A. M., Hegazy M. A. F., Okasha K., Eid M. A., Moahmed H. S., Shahin D., El-Sherbiny Y. M., Elhadidy T. A., Abd Elghafar M. S., El-Jawhari J. J., Mohamed A. A. S., Elnagdy M. H., Samir A., Abdel-Aziz M., Khafaga W. T., El-Lawaty W. M., Torky M. S., El-shanshory M. R., Batini C., Lee P. H., Shrine N., Williams A. T., Tobin M. D., Guyatt A. L., John C., Packer R. J., Ali A., Free R. C., Wang X., Wain L. V., Hollox E. J., Venn L. D., Bee C. E., Adams E. L., Niavarani A., Sharififard B., Aliannejad R., Amirsavadkouhi A., Naderpour Z., Tadi H. A., Aleagha A. E., Ahmadi S., Moghaddam S. B. M., Adamsara A., Saeedi M., Abdollahi H., Hosseini A., Chariyavilaskul P., Chamnanphon M., Suttichet T. B., Shotelersuk V., Pongpanich M., Phokaew C., Chetruengchai W., Jantarabenjakul W., Putchareon O., Torvorapanit P., Puthanakit T., Suchartlikitwong P., Hirankarn N., Nilaratanakul V., Sodsai P., Brumpton B. M., Hveem K., Willer C., Zhou W., Rogne T., Solligard E., Asvold B. O., Abedalthagafi M., Alaamery M., Alqahtani S., Barakeh D., Al Harthi F., Alsolm E., Safieh L. A., Alowayn A. M., Alqubaishi F., Al Mutairi A., Mangul S., Alshareef A., Sawaji M., Almutairi M., Aljawini N., Albesher N., Arabi Y. M., Mahmoud E. S., Khattab A. K., Halawani R. T., Alahmadey Z. Z., Albakri J. K., Felemban W. A., Suliman B. A., Hasanato R., Al-Awdah L., Alghamdi J., AlZahrani D., AlJohani S., Al-Afghani H., Alrashed M., AlDhawi N., AlBardis H., Alkwai S., Alswailm M., Almalki F., Albeladi M., Almohammed I., Barhoush E., Albader A., Massadeh S., AlMalik A., Alotaibi S., Alghamdi B., Jung J., Fawzy M. S., Lee Y., Magnus P., Trogstad L. -I. S., Helgeland O., Harris J. R., Mangino M., Spector T. D., Duncan E., Smieszek S. P., Przychodzen B. P., Polymeropoulos C., Polymeropoulos V., Polymeropoulos M. H., Fernandez-Cadenas I., Perez-Tur J., Llucia-Carol L., Cullell N., Muino E., Carcel-Marquez J., DeDiego M. L., Iglesias L. L., Planas A. M., Soriano A., Rico V., Aguero D., Bedini J. L., Lozano F., Domingo C., Robles V., Ruiz-Jaen F., Marquez L., Gomez J., Coto E., Albaiceta G. M., Garcia-Clemente M., Dalmau D., Arranz M. J., Dietl B., Serra-Llovich A., Soler P., Colobran R., Martin-Nalda A., Martinez A. P., Bernardo D., Rojo S., Fiz-Lopez A., Arribas E., de la Cal-Sabater P., Segura T., Gonzalez-Villa E., Serrano-Heras G., Marti-Fabregas J., Jimenez-Xarrie E., de Felipe Mimbrera A., Masjuan J., Garcia-Madrona S., Dominguez-Mayoral A., Villalonga J. M., Menendez-Valladares P., Chasman D. I., Buring J. E., Ridker P. M., Franco G., Sesso H. D., Manson J. A. E., Glessner J. R., Medina-Gomez C., Uitterlinden A. G., Ikram M. A., Kristiansson K., Koskelainen S., Perola M., Donner K., Kivinen K., Palotie A., Ripatti S., Ruotsalainen S., Kaunisto M., Nakanishi T., Butler-Laporte G., Forgetta V., Morrison D. R., Ghosh B., Laurent L., Belisle A., Henry D., Abdullah T., Adeleye O., Mamlouk N., Kimchi N., Afrasiabi Z., Rezk N., Vulesevic B., Bouab M., Guzman C., Petitjean L., Tselios C., Xue X., Schurr E., Afilalo J., Afilalo M., Oliveira M., Brenner B., Lepage P., Ragoussis J., Auld D., Brassard N., Durand M., Chasse M., Kaufmann D. E., Lathrop G. M., Mooser V., Richards J. B., Li R., Adra D., Rahmouni S., Georges M., Moutschen M., Misset B., Darcis G., Guiot J., Guntz J., Azarzar S., Gofflot S., Beguin Y., Claassen S., Malaise O., Huynen P., Meuris C., Thys M., Jacques J., Leonard P., Frippiat F., Giot J. -B., Sauvage A. -S., von Frenckell C., Belhaj Y., Lambermont B., Pigazzini S., Nkambule L., Daya M., Shortt J., Rafaels N., Wicks S. J., Crooks K., Barnes K. C., Gignoux C. R., Chavan S., Laisk T., Lall K., Lepamets M., Magi R., Esko T., Reimann E., Milani L., Alavere H., Metsalu K., Puusepp M., Metspalu A., Naaber P., Laane E., Pesukova J., Peterson P., Kisand K., Tabri J., Allos R., Hensen K., Starkopf J., Ringmets I., Tamm A., Kallaste A., Bochud P. -Y., Rivolta C., Bibert S., Quinodoz M., Kamdar D., Boillat N., Nussle S. G., Albrich W., Suh N., Neofytos D., Erard V., Voide C., de Cid R., Galvan-Femenia I., Blay N., Carreras A., Cortes B., Farre X., Sumoy L., Moreno V., Mercader J. M., Guindo-Martinez M., Torrents D., Kogevinas M., Garcia-Aymerich J., Castano-Vinyals G., Dobano C., Renieri A., Mari F., Fallerini C., Daga S., Benetti E., Baldassarri M., Fava F., Frullanti E., Valentino F., Doddato G., Giliberti A., Tita R., Amitrano S., Bruttini M., Croci S., Meloni I., Mencarelli M. A., Rizzo C. L., Pinto A. M., Beligni G., Tommasi A., Di Sarno L., Palmieri M., Carriero M. L., Alaverdian D., Busani S., Bruno R., Vecchia M., Belli M. A., Picchiotti N., Sanarico M., Gori M., Furini S., Mantovani S., Ludovisi S., Mondelli M. U., Castelli F., Quiros-Roldan E., Antoni M. D., Zanella I., Vaghi M., Rusconi S., Siano M., Montagnani F., Emiliozzi A., Fabbiani M., Rossetti B., Bargagli E., Bergantini L., D'Alessandro M., Cameli P., Bennett D., Anedda F., Marcantonio S., Scolletta S., Franchi F., Mazzei M. A., Guerrini S., Conticini E., Cantarini L., Frediani B., Tacconi D., Spertilli C., Feri M., Donati A., Scala R., Guidelli L., Spargi G., Corridi M., Nencioni C., Croci L., Bandini M., Caldarelli G. P., Piacentini P., Desanctis E., Cappelli S., Canaccini A., Verzuri A., Anemoli V., Ognibene A., Pancrazzi A., Lorubbio M., D'Arminio Monforte A., Miraglia F. G., Girardis M., Venturelli S., Cossarizza A., Antinori A., Vergori A., Gabrieli A., Riva A., Francisci D., Schiaroli E., Paciosi F., Scotton P. G., Andretta F., Panese S., Scaggiante R., Gatti F., Parisi S. G., Baratti S., Della Monica M., Piscopo C., Capasso M., Russo R., Andolfo I., Iolascon A., Fiorentino G., Carella M., Castori M., Merla G., Squeo G. M., Aucella F., Raggi P., Marciano C., Perna R., Bassetti M., Di Biagio A., Sanguinetti M., Masucci L., Valente S., Mandala M., Giorli A., Salerni L., Zucchi P., Parravicini P., Menatti E., Trotta T., Giannattasio F., Coiro G., Lena F., Coviello D. A., Mussini C., Martinelli E., Mancarella S., Tavecchia L., Crotti L., Gabbi C., Rizzi M., Maggiolo F., Ripamonti D., Bachetti T., La Rovere M. T., Sarzi-Braga S., Bussotti M., Ceri S., Pinoli P., Raimondi F., Biscarini F., Stella A., Zguro K., Capitani K., Suardi C., Dei S., Parati G., Ravaglia S., Artuso R., Botta G., Di Domenico P., Rancan I., Perrella A., Bianchi F., Romani D., Bergomi P., Catena E., Colombo R., Tanfoni M., Vincenti A., Ferri C., Grassi D., Pessina G., Tumbarello M., Di Pietro M., Sabrina R., Luchi S., Barbieri C., Acquilini D., Andreucci E., Segala F. V., Tiseo G., Falcone M., Lista M., Poscente M., De Vivo O., Petrocelli P., Guarnaccia A., Baroni S., Smith A. V., Boughton A. P., Li K. W., LeFaive J., Annis A., Justice A. E., Chittoor G., Josyula N. S., Leader J. B., Carey D. J., Gass M. C., Cantor M. N., Yadav A., van Heel D. A., Hunt K. A., Mason D., Huang Q. Q., Finer S., Trivedi B., Griffiths C. J., Martin H. C., Wright J., Trembath R. C., Soranzo N., Zhao J. 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A., Hasanato R., Al-Awdah L., Alghamdi J., AlZahrani D., AlJohani S., Al-Afghani H., Alrashed M., AlDhawi N., AlBardis H., Alkwai S., Alswailm M., Almalki F., Albeladi M., Almohammed I., Barhoush E., Albader A., Massadeh S., AlMalik A., Alotaibi S., Alghamdi B., Jung J., Fawzy M. S., Lee Y., Magnus P., Trogstad L. -I. S., Helgeland O., Harris J. R., Mangino M., Spector T. D., Duncan E., Smieszek S. P., Przychodzen B. P., Polymeropoulos C., Polymeropoulos V., Polymeropoulos M. H., Fernandez-Cadenas I., Perez-Tur J., Llucia-Carol L., Cullell N., Muino E., Carcel-Marquez J., DeDiego M. L., Iglesias L. L., Planas A. M., Soriano A., Rico V., Aguero D., Bedini J. L., Lozano F., Domingo C., Robles V., Ruiz-Jaen F., Marquez L., Gomez J., Coto E., Albaiceta G. M., Garcia-Clemente M., Dalmau D., Arranz M. J., Dietl B., Serra-Llovich A., Soler P., Colobran R., Martin-Nalda A., Martinez A. P., Bernardo D., Rojo S., Fiz-Lopez A., Arribas E., de la Cal-Sabater P., Segura T., Gonzalez-Villa E., Serrano-Heras G., Marti-Fabregas J., Jimenez-Xarrie E., de Felipe Mimbrera A., Masjuan J., Garcia-Madrona S., Dominguez-Mayoral A., Villalonga J. M., Menendez-Valladares P., Chasman D. I., Buring J. E., Ridker P. M., Franco G., Sesso H. D., Manson J. A. E., Glessner J. R., Medina-Gomez C., Uitterlinden A. G., Ikram M. A., Kristiansson K., Koskelainen S., Perola M., Donner K., Kivinen K., Palotie A., Ripatti S., Ruotsalainen S., Kaunisto M., Nakanishi T., Butler-Laporte G., Forgetta V., Morrison D. R., Ghosh B., Laurent L., Belisle A., Henry D., Abdullah T., Adeleye O., Mamlouk N., Kimchi N., Afrasiabi Z., Rezk N., Vulesevic B., Bouab M., Guzman C., Petitjean L., Tselios C., Xue X., Schurr E., Afilalo J., Afilalo M., Oliveira M., Brenner B., Lepage P., Ragoussis J., Auld D., Brassard N., Durand M., Chasse M., Kaufmann D. E., Lathrop G. M., Mooser V., Richards J. B., Li R., Adra D., Rahmouni S., Georges M., Moutschen M., Misset B., Darcis G., Guiot J., Guntz J., Azarzar S., Gofflot S., Beguin Y., Claassen S., Malaise O., Huynen P., Meuris C., Thys M., Jacques J., Leonard P., Frippiat F., Giot J. -B., Sauvage A. -S., von Frenckell C., Belhaj Y., Lambermont B., Pigazzini S., Nkambule L., Daya M., Shortt J., Rafaels N., Wicks S. J., Crooks K., Barnes K. C., Gignoux C. R., Chavan S., Laisk T., Lall K., Lepamets M., Magi R., Esko T., Reimann E., Milani L., Alavere H., Metsalu K., Puusepp M., Metspalu A., Naaber P., Laane E., Pesukova J., Peterson P., Kisand K., Tabri J., Allos R., Hensen K., Starkopf J., Ringmets I., Tamm A., Kallaste A., Bochud P. -Y., Rivolta C., Bibert S., Quinodoz M., Kamdar D., Boillat N., Nussle S. G., Albrich W., Suh N., Neofytos D., Erard V., Voide C., de Cid R., Galvan-Femenia I., Blay N., Carreras A., Cortes B., Farre X., Sumoy L., Moreno V., Mercader J. M., Guindo-Martinez M., Torrents D., Kogevinas M., Garcia-Aymerich J., Castano-Vinyals G., Dobano C., Renieri A., Mari F., Fallerini C., Daga S., Benetti E., Baldassarri M., Fava F., Frullanti E., Valentino F., Doddato G., Giliberti A., Tita R., Amitrano S., Bruttini M., Croci S., Meloni I., Mencarelli M. A., Rizzo C. L., Pinto A. M., Beligni G., Tommasi A., Di Sarno L., Palmieri M., Carriero M. L., Alaverdian D., Busani S., Bruno R., Vecchia M., Belli M. A., Picchiotti N., Sanarico M., Gori M., Furini S., Mantovani S., Ludovisi S., Mondelli M. U., Castelli F., Quiros-Roldan E., Antoni M. D., Zanella I., Vaghi M., Rusconi S., Siano M., Montagnani F., Emiliozzi A., Fabbiani M., Rossetti B., Bargagli E., Bergantini L., D'Alessandro M., Cameli P., Bennett D., Anedda F., Marcantonio S., Scolletta S., Franchi F., Mazzei M. A., Guerrini S., Conticini E., Cantarini L., Frediani B., Tacconi D., Spertilli C., Feri M., Donati A., Scala R., Guidelli L., Spargi G., Corridi M., Nencioni C., Croci L., Bandini M., Caldarelli G. P., Piacentini P., Desanctis E., Cappelli S., Canaccini A., Verzuri A., Anemoli V., Ognibene A., Pancrazzi A., Lorubbio M., D'Arminio Monforte A., Miraglia F. G., Girardis M., Venturelli S., Cossarizza A., Antinori A., Vergori A., Gabrieli A., Riva A., Francisci D., Schiaroli E., Paciosi F., Scotton P. G., Andretta F., Panese S., Scaggiante R., Gatti F., Parisi S. G., Baratti S., Della Monica M., Piscopo C., Capasso M., Russo R., Andolfo I., Iolascon A., Fiorentino G., Carella M., Castori M., Merla G., Squeo G. M., Aucella F., Raggi P., Marciano C., Perna R., Bassetti M., Di Biagio A., Sanguinetti M., Masucci L., Valente S., Mandala M., Giorli A., Salerni L., Zucchi P., Parravicini P., Menatti E., Trotta T., Giannattasio F., Coiro G., Lena F., Coviello D. A., Mussini C., Martinelli E., Mancarella S., Tavecchia L., Crotti L., Gabbi C., Rizzi M., Maggiolo F., Ripamonti D., Bachetti T., La Rovere M. T., Sarzi-Braga S., Bussotti M., Ceri S., Pinoli P., Raimondi F., Biscarini F., Stella A., Zguro K., Capitani K., Suardi C., Dei S., Parati G., Ravaglia S., Artuso R., Botta G., Di Domenico P., Rancan I., Perrella A., Bianchi F., Romani D., Bergomi P., Catena E., Colombo R., Tanfoni M., Vincenti A., Ferri C., Grassi D., Pessina G., Tumbarello M., Di Pietro M., Sabrina R., Luchi S., Barbieri C., Acquilini D., Andreucci E., Segala F. V., Tiseo G., Falcone M., Lista M., Poscente M., De Vivo O., Petrocelli P., Guarnaccia A., Baroni S., Smith A. V., Boughton A. P., Li K. W., LeFaive J., Annis A., Justice A. E., Chittoor G., Josyula N. S., Leader J. B., Carey D. J., Gass M. C., Cantor M. N., Yadav A., van Heel D. A., Hunt K. A., Mason D., Huang Q. Q., Finer S., Trivedi B., Griffiths C. J., Martin H. C., Wright J., Trembath R. C., Soranzo N., Zhao J. H., Butterworth A. S., Danesh J., Di Angelantonio E., Franke L., Boezen M., Deelen P., Claringbould A., Lopera E., Warmerdam R., Vonk J. M., van Blokland I., Lanting P., Ori A. P. S., Zollner S., Wang J., Beck A., Peloso G., Ho Y. -L., Sun Y. V., Huffman J. E., O'Donnell C. J., Cho K., Tsao P., Gaziano J. M., Nivard M., de Geus E., Bartels M., Jan Hottenga J., Weiss S. T., Karlson E. W., Smoller J. W., Green R. C., Feng Y. -C. A., Mercader J., Murphy S. N., Meigs J. B., Woolley A. E., Perez E. F., Rader D., Li B., Verma S. S., Lucas A., Bradford Y., Zeberg H., Frithiof R., Hultstrom M., Lipcsey M., Tardif N., Rooyackers O., Grip J., Maricic T., Karczewski K. J., Atkinson E. G., Tsuo K., Baya N., Turley P., Gupta R., Callier S., Walters R. K., Palmer D. S., Sarma G., Cheng N., Lu W., Bryant S., Churchhouse C., Cusick C., Goldstein J. I., King D., Seed C., Finucane H., Martin A. R., Satterstrom F. K., Wilson D. J., Armstrong J., Rudkin J. K., Band G., Earle S. G., Lin S. -K., Arning N., Crook D. W., Wyllie D. H., O'Connell A. M., Spencer C. C. A., Koelling N., Caulfield M. J., Scott R. H., Fowler T., Moutsianas L., Pasko D., Ball C. A., Hong E. L., Rand K., Girshick A., Guturu H., Baltzell A. H., Roberts G., Park D., Coignet M., McCurdy S., Knight S., Partha R., Rhead B., Zhang M., Berkowitz N., Gaddis M., Noto K., Ruiz L., Pavlovic M., Sloofman L. G., Charney A. W., Beckmann N. D., Schadt E. E., Jordan D. M., Thompson R. C., Gettler K., Abul-Husn N. S., Ascolillo S., Buxbaum J. D., Chaudhary K., Cho J. H., Itan Y., Kenny E. E., Belbin G. M., Sealfon S. C., Sebra R. P., Salib I., Collins B. L., Levy T., Britvan B., Keller K., Tang L., Peruggia M., Hiester L. L., Niblo K., Aksentijevich A., Labkowsky A., Karp A., Zlatopolsky M., Preuss M., Loos R. J. F., Nadkarni G. N., Do R., Hoggart C., Choi S., Underwood S. J., O'Reilly P., Huckins L. M., Zyndorf M., Daly M. J., Neale B. M., Ganna A., Fawkes A., Murphy L., Rowan K., Ponting C. P., Vitart V., Yang J., Bretherick A. D., Hendry S. C., Law A., and Baillie J. K.
Abstract: Critical COVID-19 is caused by immune-mediated inflammatory lung injury. Host genetic variation influences the development of illness requiring critical care1 or hospitalization2–4 after infection with SARS-CoV-2. The GenOMICC (Genetics of Mortality in Critical Care) study enables the comparison of genomes from individuals who are critically ill with those of population controls to find underlying disease mechanisms. Here we use whole-genome sequencing in 7,491 critically ill individuals compared with 48,400 controls to discover and replicate 23 independent variants that significantly predispose to critical COVID-19. We identify 16 new independent associations, including variants within genes that are involved in interferon signalling (IL10RB and PLSCR1), leucocyte differentiation (BCL11A) and blood-type antigen secretor status (FUT2). Using transcriptome-wide association and colocalization to infer the effect of gene expression on disease severity, we find evidence that implicates multiple genes—including reduced expression of a membrane flippase (ATP11A), and increased expression of a mucin (MUC1)—in critical disease. Mendelian randomization provides evidence in support of causal roles for myeloid cell adhesion molecules (SELE, ICAM5 and CD209) and the coagulation factor F8, all of which are potentially druggable targets. Our results are broadly consistent with a multi-component model of COVID-19 pathophysiology, in which at least two distinct mechanisms can predispose to life-threatening disease: failure to control viral replication; or an enhanced tendency towards pulmonary inflammation and intravascular coagulation. We show that comparison between cases of critical illness and population controls is highly efficient for the detection of therapeutically relevant mechanisms of disease.
Published: 2022

14. Identification of a plausible serum uric acid cut-off value as prognostic marker of stroke: the Uric Acid Right for Heart Health (URRAH) study

Author: Tikhonoff, V, Casiglia, E, Spinella, P, Barbagallo, C, Bombelli, M, Cicero, A, Cirillo, M, Cirillo, P, Desideri, G, D'Elia, L, Ferri, C, Galletti, F, Gesualdo, L, Giannattasio, C, Iaccarino, G, Mallamaci, F, Maloberti, A, Masi, S, Mazza, A, Muiesan, M, Nazzaro, P, Palatini, P, Parati, G, Pontremoli, R, Quarti-Trevano, F, Rattazzi, M, Rivasi, G, Salvetti, M, Tocci, G, Ungar, A, Verdecchia, P, Viazzi, F, Virdis, A, Volpe, M, Grassi, G, Borghi, C, Tikhonoff V., Casiglia E., Spinella P., Barbagallo C. M., Bombelli M., Cicero A. F. G., Cirillo M., Cirillo P., Desideri G., D'elia L., Ferri C., Galletti F., Gesualdo L., Giannattasio C., Iaccarino G., Mallamaci F., Maloberti A., Masi S., Mazza A., Muiesan M. L., Nazzaro P., Palatini P., Parati G., Pontremoli R., Quarti-Trevano F., Rattazzi M., Rivasi G., Salvetti M., Tocci G., Ungar A., Verdecchia P., Viazzi F., Virdis A., Volpe M., Grassi G., Borghi C., Tikhonoff, V, Casiglia, E, Spinella, P, Barbagallo, C, Bombelli, M, Cicero, A, Cirillo, M, Cirillo, P, Desideri, G, D'Elia, L, Ferri, C, Galletti, F, Gesualdo, L, Giannattasio, C, Iaccarino, G, Mallamaci, F, Maloberti, A, Masi, S, Mazza, A, Muiesan, M, Nazzaro, P, Palatini, P, Parati, G, Pontremoli, R, Quarti-Trevano, F, Rattazzi, M, Rivasi, G, Salvetti, M, Tocci, G, Ungar, A, Verdecchia, P, Viazzi, F, Virdis, A, Volpe, M, Grassi, G, Borghi, C, Tikhonoff V., Casiglia E., Spinella P., Barbagallo C. M., Bombelli M., Cicero A. F. G., Cirillo M., Cirillo P., Desideri G., D'elia L., Ferri C., Galletti F., Gesualdo L., Giannattasio C., Iaccarino G., Mallamaci F., Maloberti A., Masi S., Mazza A., Muiesan M. L., Nazzaro P., Palatini P., Parati G., Pontremoli R., Quarti-Trevano F., Rattazzi M., Rivasi G., Salvetti M., Tocci G., Ungar A., Verdecchia P., Viazzi F., Virdis A., Volpe M., Grassi G., and Borghi C.
Abstract: The Working Group on Uric Acid and Cardiovascular Risk of the Italian Society of Hypertension conceived and designed an ad hoc study aimed at searching for prognostic cut-off values of serum uric acid (SUA) in predicting combined (fatal and non-fatal) cerebrovascular (CBV) events in the whole database. The URic acid Right for heArt Health study is a nationwide, multicenter, observational cohort study involving data on subjects aged 18–95 years recruited on a regional community basis from all the territory of Italy under the patronage of the Italian Society of Hypertension with a mean follow-up period of 120.7 ± 61.8 months. A total of 14,588 subjects were included in the analysis. A prognostic cut-off value of SUA able to discriminate combined CBV events (>4.79 mg/dL or >284.91 µmol/L) was identified by means of receiver operating characteristic curve in the whole database. Multivariate Cox regression analysis adjusted for confounders (age, sex, arterial hypertension, diabetes, chronic kidney disease, smoking habit, ethanol intake, body mass index, low-density lipoprotein cholesterol, and use of diuretics) identified an independent association between SUA and combined CBV events in the whole database (HR 1.249, 95% confidence interval, 1.041–1.497, p = 0.016). The results of the present study confirm that SUA is an independent risk marker for CBV events after adjusting for potential confounding variables, including arterial hypertension, and demonstrate that >4.79 mg/dL is a valid prognostic cut-off value.
Published: 2022

15. Geographical heterogeneity of clinical and serological phenotypes of systemic sclerosis observed at tertiary referral centres. The experience of the Italian SIR-SPRING registry and review of the world literature

Author: Ferri, C, De Angelis, R, Giuggioli, D, Bajocchi, G, Dagna, L, Zanframundo, G, Foti, R, Cacciapaglia, F, Cuomo, G, Ariani, A, Rosato, E, Guiducci, S, Girelli, F, Riccieri, V, Zanatta, E, Bosello, S, Cavazzana, I, Ingegnoli, F, De Santis, M, Murdaca, G, Abignano, G, Romeo, N, Della Rossa, A, Caminiti, M, Iuliano, A, Ciano, G, Beretta, L, Bagnato, G, Lubrano, E, De Andres, I, Giollo, A, Saracco, M, Agnes, C, Lumetti, F, Spinella, A, Magnani, L, Campochiaro, C, De Luca, G, Codullo, V, Visalli, E, Masini, F, Gigante, A, Bellando-Randone, S, Pellegrino, G, Pigatto, E, Lazzaroni, M, Franceschini, F, Generali, E, Mennillo, G, Barsotti, S, Mariano, G, Calabrese, F, Furini, F, Vultaggio, L, Parisi, S, Peroni, C, Rozza, D, Zanetti, A, Carrara, G, Landolfi, G, Scire, C, Bianchi, G, Fusaro, E, Sebastiani, G, Govoni, M, D'Angelo, S, Cozzi, F, Doria, A, Iannone, F, Salvarani, C, Matucci-Cerinic, M, Ferri C., De Angelis R., Giuggioli D., Bajocchi G., Dagna L., Zanframundo G., Foti R., Cacciapaglia F., Cuomo G., Ariani A., Rosato E., Guiducci S., Girelli F., Riccieri V., Zanatta E., Bosello S., Cavazzana I., Ingegnoli F., De Santis M., Murdaca G., Abignano G., Romeo N., Della Rossa A., Caminiti M., Iuliano A., Ciano G., Beretta L., Bagnato G., Lubrano E., De Andres I., Giollo A., Saracco M., Agnes C., Lumetti F., Spinella A., Magnani L., Campochiaro C., De Luca G., Codullo V., Visalli E., Masini F., Gigante A., Bellando-Randone S., Pellegrino G., Pigatto E., Lazzaroni M. G., Franceschini F., Generali E., Mennillo G., Barsotti S., Mariano G. P., Calabrese F., Furini F., Vultaggio L., Parisi S., Peroni C. L., Rozza D., Zanetti A., Carrara G., Landolfi G., Scire C. A., Bianchi G., Fusaro E., Sebastiani G. D., Govoni M., D'Angelo S., Cozzi F., Doria A., Iannone F., Salvarani C., Matucci-Cerinic M., Ferri, C, De Angelis, R, Giuggioli, D, Bajocchi, G, Dagna, L, Zanframundo, G, Foti, R, Cacciapaglia, F, Cuomo, G, Ariani, A, Rosato, E, Guiducci, S, Girelli, F, Riccieri, V, Zanatta, E, Bosello, S, Cavazzana, I, Ingegnoli, F, De Santis, M, Murdaca, G, Abignano, G, Romeo, N, Della Rossa, A, Caminiti, M, Iuliano, A, Ciano, G, Beretta, L, Bagnato, G, Lubrano, E, De Andres, I, Giollo, A, Saracco, M, Agnes, C, Lumetti, F, Spinella, A, Magnani, L, Campochiaro, C, De Luca, G, Codullo, V, Visalli, E, Masini, F, Gigante, A, Bellando-Randone, S, Pellegrino, G, Pigatto, E, Lazzaroni, M, Franceschini, F, Generali, E, Mennillo, G, Barsotti, S, Mariano, G, Calabrese, F, Furini, F, Vultaggio, L, Parisi, S, Peroni, C, Rozza, D, Zanetti, A, Carrara, G, Landolfi, G, Scire, C, Bianchi, G, Fusaro, E, Sebastiani, G, Govoni, M, D'Angelo, S, Cozzi, F, Doria, A, Iannone, F, Salvarani, C, Matucci-Cerinic, M, Ferri C., De Angelis R., Giuggioli D., Bajocchi G., Dagna L., Zanframundo G., Foti R., Cacciapaglia F., Cuomo G., Ariani A., Rosato E., Guiducci S., Girelli F., Riccieri V., Zanatta E., Bosello S., Cavazzana I., Ingegnoli F., De Santis M., Murdaca G., Abignano G., Romeo N., Della Rossa A., Caminiti M., Iuliano A., Ciano G., Beretta L., Bagnato G., Lubrano E., De Andres I., Giollo A., Saracco M., Agnes C., Lumetti F., Spinella A., Magnani L., Campochiaro C., De Luca G., Codullo V., Visalli E., Masini F., Gigante A., Bellando-Randone S., Pellegrino G., Pigatto E., Lazzaroni M. G., Franceschini F., Generali E., Mennillo G., Barsotti S., Mariano G. P., Calabrese F., Furini F., Vultaggio L., Parisi S., Peroni C. L., Rozza D., Zanetti A., Carrara G., Landolfi G., Scire C. A., Bianchi G., Fusaro E., Sebastiani G. D., Govoni M., D'Angelo S., Cozzi F., Doria A., Iannone F., Salvarani C., and Matucci-Cerinic M.
Abstract: Introduction: Systemic sclerosis (SSc) is characterized by a complex etiopathogenesis encompassing both host genetic and environmental -infectious/toxic- factors responsible for altered fibrogenesis and diffuse microangiopathy. A wide spectrum of clinical phenotypes may be observed in patients' populations from different geographical areas. We investigated the prevalence of specific clinical and serological phenotypes in patients with definite SSc enrolled at tertiary referral centres in different Italian geographical macro-areas. The observed findings were compared with those reported in the world literature. Materials and methods: The clinical features of 1538 patients (161 M, 10.5%; mean age 59.8 ± 26.9 yrs.; mean disease duration 8.9 ± 7.7 yrs) with definite SSc recruited in 38 tertiary referral centres of the SPRING (Systemic sclerosis Progression INvestiGation Group) registry promoted by Italian Society of Rheumatology (SIR) were obtained and clustered according to Italian geographical macroareas. Results: Patients living in Southern Italy were characterized by more severe clinical and/or serological SSc phenotypes compared to those in Northern and Central Italy; namely, they show increased percentages of diffuse cutaneous SSc, digital ulcers, sicca syndrome, muscle involvement, arthritis, cardiopulmonary symptoms, interstitial lung involvement at HRCT, as well increased prevalence of serum anti-Scl70 autoantibodies. In the same SSc population immunusppressive drugs were frequently employed. The review of the literature underlined the geographical heterogeneity of SSc phenotypes, even if the observed findings are scarcely comparable due to the variability of methodological approaches. Conclusion: The phenotypical differences among SSc patients' subgroups from Italian macro-areas might be correlated to genetic/environmental co-factors, and possibly to a not equally distributed national network of information and healthcare facilities.
Published: 2022

16. Whole-genome sequencing reveals host factors underlying critical COVID-19

Author: Kousathanas, A, Pairo-Castineira, E, Rawlik, K, Stuckey, A, Odhams, C, Walker, S, Russell, C, Malinauskas, T, Wu, Y, Millar, J, Shen, X, Elliott, K, Griffiths, F, Oosthuyzen, W, Morrice, K, Keating, S, Wang, B, Rhodes, D, Klaric, L, Zechner, M, Parkinson, N, Siddiq, A, Goddard, P, Donovan, S, Maslove, D, Nichol, A, Semple, M, Zainy, T, Maleady-Crowe, F, Todd, L, Salehi, S, Knight, J, Elgar, G, Chan, G, Arumugam, P, Patch, C, Rendon, A, Bentley, D, Kingsley, C, Kosmicki, J, Horowitz, J, Baras, A, Abecasis, G, Ferreira, M, Justice, A, Mirshahi, T, Oetjens, M, Rader, D, Ritchie, M, Verma, A, Fowler, T, Shankar-Hari, M, Summers, C, Hinds, C, Horby, P, Ling, L, Mcauley, D, Montgomery, H, Openshaw, P, Elliott, P, Walsh, T, Tenesa, A, Shelton, J, Shastri, A, Ye, C, Weldon, C, Filshtein-Sonmez, T, Coker, D, Symons, A, Esparza-Gordillo, J, Aslibekyan, S, Auton, A, Pathak, G, Karjalainen, J, Stevens, C, Andrews, S, Kanai, M, Cordioli, M, Polimanti, R, Pirinen, M, Harerimana, N, Veerapen, K, Wolford, B, Nguyen, H, Solomonson, M, Liao, R, Chwialkowska, K, Trankiem, A, Balaconis, M, Hayward, C, Richmond, A, Campbell, A, Morris, M, Fawns-Ritchie, C, Glessner, J, Shaw, D, Chang, X, Polikowski, H, Petty, L, Chen, H, Wanying, Z, Hakonarson, H, Porteous, D, Below, J, North, K, Mccormick, J, Timmers, P, Wilson, J, D'Mellow, K, Kerr, S, Niemi, M, Nkambul, L, von Hohenstaufen, K, Sobh, A, Eltoukhy, M, Yassen, A, Hegazy, M, Okasha, K, Eid, M, Moahmed, H, Shahin, D, El-Sherbiny, Y, Elhadidy, T, Abd Elghafar, M, El-Jawhari, J, Mohamed, A, Elnagdy, M, Samir, A, Abdel-Aziz, M, Khafaga, W, El-Lawaty, W, Torky, M, El-shanshory, M, Batini, C, Lee, P, Shrine, N, Williams, A, Tobin, M, Guyatt, A, John, C, Packer, R, Ali, A, Free, R, Wang, X, Wain, L, Hollox, E, Venn, L, Bee, C, Adams, E, Niavarani, A, Sharififard, B, Aliannejad, R, Amirsavadkouhi, A, Naderpour, Z, Tadi, H, Aleagha, A, Ahmadi, S, Moghaddam, S, Adamsara, A, Saeedi, M, Abdollahi, H, Hosseini, A, Chariyavilaskul, P, Chamnanphon, M, Suttichet, T, Shotelersuk, V, Pongpanich, M, Phokaew, C, Chetruengchai, W, Jantarabenjakul, W, Putchareon, O, Torvorapanit, P, Puthanakit, T, Suchartlikitwong, P, Hirankarn, N, Nilaratanakul, V, Sodsai, P, Brumpton, B, Hveem, K, Willer, C, Zhou, W, Rogne, T, Solligard, E, Asvold, B, Abedalthagafi, M, Alaamery, M, Alqahtani, S, Barakeh, D, Al Harthi, F, Alsolm, E, Safieh, L, Alowayn, A, Alqubaishi, F, Al Mutairi, A, Mangul, S, Alshareef, A, Sawaji, M, Almutairi, M, Aljawini, N, Albesher, N, Arabi, Y, Mahmoud, E, Khattab, A, Halawani, R, Alahmadey, Z, Albakri, J, Felemban, W, Suliman, B, Hasanato, R, Al-Awdah, L, Alghamdi, J, Alzahrani, D, Aljohani, S, Al-Afghani, H, Alrashed, M, Aldhawi, N, Albardis, H, Alkwai, S, Alswailm, M, Almalki, F, Albeladi, M, Almohammed, I, Barhoush, E, Albader, A, Massadeh, S, Almalik, A, Alotaibi, S, Alghamdi, B, Jung, J, Fawzy, M, Lee, Y, Magnus, P, Trogstad, L, Helgeland, O, Harris, J, Mangino, M, Spector, T, Duncan, E, Smieszek, S, 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P., Bernardo D., Rojo S., Fiz-Lopez A., Arribas E., de la Cal-Sabater P., Segura T., Gonzalez-Villa E., Serrano-Heras G., Marti-Fabregas J., Jimenez-Xarrie E., de Felipe Mimbrera A., Masjuan J., Garcia-Madrona S., Dominguez-Mayoral A., Villalonga J. M., Menendez-Valladares P., Chasman D. I., Buring J. E., Ridker P. M., Franco G., Sesso H. D., Manson J. A. E., Glessner J. R., Medina-Gomez C., Uitterlinden A. G., Ikram M. A., Kristiansson K., Koskelainen S., Perola M., Donner K., Kivinen K., Palotie A., Ripatti S., Ruotsalainen S., Kaunisto M., Nakanishi T., Butler-Laporte G., Forgetta V., Morrison D. R., Ghosh B., Laurent L., Belisle A., Henry D., Abdullah T., Adeleye O., Mamlouk N., Kimchi N., Afrasiabi Z., Rezk N., Vulesevic B., Bouab M., Guzman C., Petitjean L., Tselios C., Xue X., Schurr E., Afilalo J., Afilalo M., Oliveira M., Brenner B., Lepage P., Ragoussis J., Auld D., Brassard N., Durand M., Chasse M., Kaufmann D. E., Lathrop G. M., Mooser V., Richards J. B., Li R., Adra D., Rahmouni S., Georges M., Moutschen M., Misset B., Darcis G., Guiot J., Guntz J., Azarzar S., Gofflot S., Beguin Y., Claassen S., Malaise O., Huynen P., Meuris C., Thys M., Jacques J., Leonard P., Frippiat F., Giot J. -B., Sauvage A. -S., von Frenckell C., Belhaj Y., Lambermont B., Pigazzini S., Nkambule L., Daya M., Shortt J., Rafaels N., Wicks S. J., Crooks K., Barnes K. C., Gignoux C. R., Chavan S., Laisk T., Lall K., Lepamets M., Magi R., Esko T., Reimann E., Milani L., Alavere H., Metsalu K., Puusepp M., Metspalu A., Naaber P., Laane E., Pesukova J., Peterson P., Kisand K., Tabri J., Allos R., Hensen K., Starkopf J., Ringmets I., Tamm A., Kallaste A., Bochud P. -Y., Rivolta C., Bibert S., Quinodoz M., Kamdar D., Boillat N., Nussle S. G., Albrich W., Suh N., Neofytos D., Erard V., Voide C., de Cid R., Galvan-Femenia I., Blay N., Carreras A., Cortes B., Farre X., Sumoy L., Moreno V., Mercader J. M., Guindo-Martinez M., Torrents D., Kogevinas M., Garcia-Aymerich J., Castano-Vinyals G., Dobano C., Renieri A., Mari F., Fallerini C., Daga S., Benetti E., Baldassarri M., Fava F., Frullanti E., Valentino F., Doddato G., Giliberti A., Tita R., Amitrano S., Bruttini M., Croci S., Meloni I., Mencarelli M. A., Rizzo C. L., Pinto A. M., Beligni G., Tommasi A., Di Sarno L., Palmieri M., Carriero M. L., Alaverdian D., Busani S., Bruno R., Vecchia M., Belli M. A., Picchiotti N., Sanarico M., Gori M., Furini S., Mantovani S., Ludovisi S., Mondelli M. U., Castelli F., Quiros-Roldan E., Antoni M. D., Zanella I., Vaghi M., Rusconi S., Siano M., Montagnani F., Emiliozzi A., Fabbiani M., Rossetti B., Bargagli E., Bergantini L., D'Alessandro M., Cameli P., Bennett D., Anedda F., Marcantonio S., Scolletta S., Franchi F., Mazzei M. A., Guerrini S., Conticini E., Cantarini L., Frediani B., Tacconi D., Spertilli C., Feri M., Donati A., Scala R., Guidelli L., Spargi G., Corridi M., Nencioni C., Croci L., Bandini M., Caldarelli G. P., Piacentini P., Desanctis E., Cappelli S., Canaccini A., Verzuri A., Anemoli V., Ognibene A., Pancrazzi A., Lorubbio M., D'Arminio Monforte A., Miraglia F. G., Girardis M., Venturelli S., Cossarizza A., Antinori A., Vergori A., Gabrieli A., Riva A., Francisci D., Schiaroli E., Paciosi F., Scotton P. G., Andretta F., Panese S., Scaggiante R., Gatti F., Parisi S. G., Baratti S., Della Monica M., Piscopo C., Capasso M., Russo R., Andolfo I., Iolascon A., Fiorentino G., Carella M., Castori M., Merla G., Squeo G. M., Aucella F., Raggi P., Marciano C., Perna R., Bassetti M., Di Biagio A., Sanguinetti M., Masucci L., Valente S., Mandala M., Giorli A., Salerni L., Zucchi P., Parravicini P., Menatti E., Trotta T., Giannattasio F., Coiro G., Lena F., Coviello D. A., Mussini C., Martinelli E., Mancarella S., Tavecchia L., Crotti L., Gabbi C., Rizzi M., Maggiolo F., Ripamonti D., Bachetti T., La Rovere M. T., Sarzi-Braga S., Bussotti M., Ceri S., Pinoli P., Raimondi F., Biscarini F., Stella A., Zguro K., Capitani K., Suardi C., Dei S., Parati G., Ravaglia S., Artuso R., Botta G., Di Domenico P., Rancan I., Perrella A., Bianchi F., Romani D., Bergomi P., Catena E., Colombo R., Tanfoni M., Vincenti A., Ferri C., Grassi D., Pessina G., Tumbarello M., Di Pietro M., Sabrina R., Luchi S., Barbieri C., Acquilini D., Andreucci E., Segala F. V., Tiseo G., Falcone M., Lista M., Poscente M., De Vivo O., Petrocelli P., Guarnaccia A., Baroni S., Smith A. V., Boughton A. P., Li K. W., LeFaive J., Annis A., Justice A. E., Chittoor G., Josyula N. S., Leader J. B., Carey D. J., Gass M. C., Cantor M. N., Yadav A., van Heel D. A., Hunt K. A., Mason D., Huang Q. Q., Finer S., Trivedi B., Griffiths C. J., Martin H. C., Wright J., Trembath R. C., Soranzo N., Zhao J. H., Butterworth A. S., Danesh J., Di Angelantonio E., Franke L., Boezen M., Deelen P., Claringbould A., Lopera E., Warmerdam R., Vonk J. M., van Blokland I., Lanting P., Ori A. P. S., Zollner S., Wang J., Beck A., Peloso G., Ho Y. -L., Sun Y. V., Huffman J. E., O'Donnell C. J., Cho K., Tsao P., Gaziano J. M., Nivard M., de Geus E., Bartels M., Jan Hottenga J., Weiss S. T., Karlson E. W., Smoller J. W., Green R. C., Feng Y. -C. A., Mercader J., Murphy S. N., Meigs J. B., Woolley A. E., Perez E. F., Rader D., Li B., Verma S. S., Lucas A., Bradford Y., Zeberg H., Frithiof R., Hultstrom M., Lipcsey M., Tardif N., Rooyackers O., Grip J., Maricic T., Karczewski K. J., Atkinson E. G., Tsuo K., Baya N., Turley P., Gupta R., Callier S., Walters R. K., Palmer D. S., Sarma G., Cheng N., Lu W., Bryant S., Churchhouse C., Cusick C., Goldstein J. I., King D., Seed C., Finucane H., Martin A. R., Satterstrom F. K., Wilson D. J., Armstrong J., Rudkin J. K., Band G., Earle S. G., Lin S. -K., Arning N., Crook D. W., Wyllie D. H., O'Connell A. M., Spencer C. C. A., Koelling N., Caulfield M. J., Scott R. H., Fowler T., Moutsianas L., Pasko D., Ball C. A., Hong E. L., Rand K., Girshick A., Guturu H., Baltzell A. H., Roberts G., Park D., Coignet M., McCurdy S., Knight S., Partha R., Rhead B., Zhang M., Berkowitz N., Gaddis M., Noto K., Ruiz L., Pavlovic M., Sloofman L. G., Charney A. W., Beckmann N. D., Schadt E. E., Jordan D. M., Thompson R. C., Gettler K., Abul-Husn N. S., Ascolillo S., Buxbaum J. D., Chaudhary K., Cho J. H., Itan Y., Kenny E. E., Belbin G. M., Sealfon S. C., Sebra R. P., Salib I., Collins B. L., Levy T., Britvan B., Keller K., Tang L., Peruggia M., Hiester L. L., Niblo K., Aksentijevich A., Labkowsky A., Karp A., Zlatopolsky M., Preuss M., Loos R. J. F., Nadkarni G. N., Do R., Hoggart C., Choi S., Underwood S. J., O'Reilly P., Huckins L. M., Zyndorf M., Daly M. J., Neale B. M., Ganna A., Fawkes A., Murphy L., Rowan K., Ponting C. P., Vitart V., Yang J., Bretherick A. D., Hendry S. C., Law A., and Baillie J. K.
Abstract: Critical COVID-19 is caused by immune-mediated inflammatory lung injury. Host genetic variation influences the development of illness requiring critical care1 or hospitalization2–4 after infection with SARS-CoV-2. The GenOMICC (Genetics of Mortality in Critical Care) study enables the comparison of genomes from individuals who are critically ill with those of population controls to find underlying disease mechanisms. Here we use whole-genome sequencing in 7,491 critically ill individuals compared with 48,400 controls to discover and replicate 23 independent variants that significantly predispose to critical COVID-19. We identify 16 new independent associations, including variants within genes that are involved in interferon signalling (IL10RB and PLSCR1), leucocyte differentiation (BCL11A) and blood-type antigen secretor status (FUT2). Using transcriptome-wide association and colocalization to infer the effect of gene expression on disease severity, we find evidence that implicates multiple genes—including reduced expression of a membrane flippase (ATP11A), and increased expression of a mucin (MUC1)—in critical disease. Mendelian randomization provides evidence in support of causal roles for myeloid cell adhesion molecules (SELE, ICAM5 and CD209) and the coagulation factor F8, all of which are potentially druggable targets. Our results are broadly consistent with a multi-component model of COVID-19 pathophysiology, in which at least two distinct mechanisms can predispose to life-threatening disease: failure to control viral replication; or an enhanced tendency towards pulmonary inflammation and intravascular coagulation. We show that comparison between cases of critical illness and population controls is highly efficient for the detection of therapeutically relevant mechanisms of disease.
Published: 2022

17. Serum uric acid levels threshold for mortality in diabetic individuals: The URic acid Right for heArt Health (URRAH) project

Author: Masulli, M, D'Elia, L, Angeli, F, Barbagallo, C, Bilancio, G, Bombelli, M, Bruno, B, Casiglia, E, Cianci, R, Cicero, A, Cirillo, M, Cirillo, P, Dell'Oro, R, Desideri, G, Ferri, C, Gesualdo, L, Giannattasio, C, Grassi, G, Iaccarino, G, Lippa, L, Mallamaci, F, Maloberti, A, Masi, S, Mazza, A, Mengozzi, A, Muiesan, M, Nazzaro, P, Palatini, P, Parati, G, Pontremoli, R, Quarti-Trevano, F, Rattazzi, M, Reboldi, G, Rivasi, G, Salvetti, M, Tikhonoff, V, Tocci, G, Ungar, A, Verdecchia, P, Viazzi, F, Virdis, A, Volpe, M, Borghi, C, Galletti, F, Masulli M., D'Elia L., Angeli F., Barbagallo C. M., Bilancio G., Bombelli M., Bruno B., Casiglia E., Cianci R., Cicero A. F. G., Cirillo M., Cirillo P., Dell'Oro R., Desideri G., Ferri C., Gesualdo L., Giannattasio C., Grassi G., Iaccarino G., Lippa L., Mallamaci F., Maloberti A., Masi S., Mazza A., Mengozzi A., Muiesan M. L., Nazzaro P., Palatini P., Parati G., Pontremoli R., Quarti-Trevano F., Rattazzi M., Reboldi G., Rivasi G., Salvetti M., Tikhonoff V., Tocci G., Ungar A., Verdecchia P., Viazzi F., Virdis A., Volpe M., Borghi C., Galletti F., Masulli, M, D'Elia, L, Angeli, F, Barbagallo, C, Bilancio, G, Bombelli, M, Bruno, B, Casiglia, E, Cianci, R, Cicero, A, Cirillo, M, Cirillo, P, Dell'Oro, R, Desideri, G, Ferri, C, Gesualdo, L, Giannattasio, C, Grassi, G, Iaccarino, G, Lippa, L, Mallamaci, F, Maloberti, A, Masi, S, Mazza, A, Mengozzi, A, Muiesan, M, Nazzaro, P, Palatini, P, Parati, G, Pontremoli, R, Quarti-Trevano, F, Rattazzi, M, Reboldi, G, Rivasi, G, Salvetti, M, Tikhonoff, V, Tocci, G, Ungar, A, Verdecchia, P, Viazzi, F, Virdis, A, Volpe, M, Borghi, C, Galletti, F, Masulli M., D'Elia L., Angeli F., Barbagallo C. M., Bilancio G., Bombelli M., Bruno B., Casiglia E., Cianci R., Cicero A. F. G., Cirillo M., Cirillo P., Dell'Oro R., Desideri G., Ferri C., Gesualdo L., Giannattasio C., Grassi G., Iaccarino G., Lippa L., Mallamaci F., Maloberti A., Masi S., Mazza A., Mengozzi A., Muiesan M. L., Nazzaro P., Palatini P., Parati G., Pontremoli R., Quarti-Trevano F., Rattazzi M., Reboldi G., Rivasi G., Salvetti M., Tikhonoff V., Tocci G., Ungar A., Verdecchia P., Viazzi F., Virdis A., Volpe M., Borghi C., and Galletti F.
Abstract: Background and aim: The URRAH (URic acid Right for heArt Health) Study has identified cut-off values of serum uric acid (SUA) predictive of total mortality at 4.7 mg/dl, and cardiovascular (CV) mortality at 5.6 mg/dl. Our aim was to validate these SUA thresholds in people with diabetes. Methods and results: The URRAH subpopulation of people with diabetes was studied. All-cause and CV deaths were evaluated at the end of follow-up. A total of 2570 diabetic subjects were studied. During a median follow-up of 107 months, 744 deaths occurred. In the multivariate Cox regression analyses adjusted for several confounders, subjects with SUA ≥5.6 mg/dl had higher risk of total (HR: 1.23, 95%CI: 1.04–1.47) and CV mortality (HR:1.31, 95%CI:1.03–1.66), than those with SUA <5.6 mg/dl. Increased all-cause mortality risk was shown in participants with SUA ≥4.7 mg/dl vs SUA below 4.7 mg/dl, but not statistically significant after adjustment for all confounders. Conclusions: SUA thresholds previously proposed by the URRAH study group are predictive of total and CV mortality also in people with diabetes. The threshold of 5.6 mg/dl can predict both total and CV mortality, and so is candidate to be a clinical cut-off for the definition of hyperuricemia in patients with diabetes.
Published: 2022

18. Reduction of High Cholesterol Levels by a Preferably Fixed-Combination Strategy as the First Step in the Treatment of Hypertensive Patients with Hypercholesterolemia and High/Very High Cardiovascular Risk: A Consensus Document by the Italian Society of Hypertension

Author: Grassi, G, Del Pinto, R, Agabiti Rosei, C, Agnoletti, D, Borghi, C, Cicero, A, De Ciuceis, C, Desideri, G, Grassi, D, Muiesan, M, Paini, A, Salvetti, M, Tocci, G, Veglio, F, Volpe, M, Ferri, C, Grassi G., Del Pinto R., Agabiti Rosei C., Agnoletti D., Borghi C., Cicero A. F. G., De Ciuceis C., Desideri G., Grassi D., Muiesan M. L., Paini A., Salvetti M., Tocci G., Veglio F., Volpe M., Ferri C., Grassi, G, Del Pinto, R, Agabiti Rosei, C, Agnoletti, D, Borghi, C, Cicero, A, De Ciuceis, C, Desideri, G, Grassi, D, Muiesan, M, Paini, A, Salvetti, M, Tocci, G, Veglio, F, Volpe, M, Ferri, C, Grassi G., Del Pinto R., Agabiti Rosei C., Agnoletti D., Borghi C., Cicero A. F. G., De Ciuceis C., Desideri G., Grassi D., Muiesan M. L., Paini A., Salvetti M., Tocci G., Veglio F., Volpe M., and Ferri C.
Abstract: The primary and secondary prevention strategies of atherosclerotic cardiovascular disease (ASCVD) largely rely on the management of arterial hypertension and hypercholesterolemia, two major risk factors possibly linked in pathophysiological terms by the renin-angiotensin system activation and that often coexist in the same patient synergistically increasing cardiovascular risk. The classic pharmacologic armamentarium to reduce hypercholesterolemia has been based in the last two decades on statins, ezetimibe, and bile acid sequestrants. More recently numerous novel, additive resources targeting different pathways in LDL cholesterol metabolism have emerged. They include drugs targeting the proprotein convertase subtilisin/kexin type 9 (PCSK9) (inhibitory antibodies; small-interfering RNAs), the angiopoietin-like protein 3 (inhibitory antibodies), and the ATP-citrate lyase (the inhibitory oral prodrug, bempedoic acid), with PCSK9 inhibitors and bempedoic acid already approved for clinical use. With the potential of at least halving LDL cholesterol levels faster and more effectively with the addition of ezetimibe than with high-intensity statin alone, and even more with the addition of the novel available drugs, this document endorsed by the Italian Society of Hypertension proposes a novel paradigm for the treatment of the hypertensive patient with hypercholesterolemia at high and very high ASCVD risk. Our proposal is based on the use as a first-line of a preferably fixed combination of lipid-lowering drugs, under the motto “Our goal: achieve control. No setback: combine and check”.
Published: 2022

19. Sex-related Differences in Systemic Sclerosis: A Multicenter Cross-sectional Study From the National Registry of the Italian Society for Rheumatology

Author: De Angelis, R, Giuggioli, D, Bajocchi, G, Dagna, L, Zanframundo, G, Foti, R, Cacciapaglia, F, Cuomo, G, Ariani, A, Rosato, E, Guiducci, S, Girelli, F, Riccieri, V, Zanatta, E, Bosello, S, Cavazzana, I, Ingegnoli, F, Santis, M, Murdaca, G, Abignano, G, Romeo, N, Della Rossa, A, Caminiti, M, Iuliano, A, Ciano, G, Beretta, L, Bagnato, G, Lubrano, E, De Andres, I, Giollo, A, Saracco, M, Agnes, C, Lumetti, F, Spinella, A, Magnani, L, Campochiaro, C, De Luca, G, Codullo, V, Visalli, E, Masini, F, Gigante, A, Bellando-Randone, S, Pellegrino, G, Pigatto, E, Dall'Ara, F, Lazzaroni, M, Generali, E, Mennillo, G, Barsotti, S, Mariano, G, Calabrese, F, Furini, F, Vultaggio, L, Parisi, S, Peroni, C, Risa, A, Rozza, D, Zanetti, A, Carrara, G, Landolfi, G, Scire, C, Bianchi, G, Fusaro, E, Sebastiani, G, Govoni, M, D'Angelo, S, Cozzi, F, Doria, A, Iannone, F, Salvarani, C, Matucci-Cerinic, M, Ferri, C, De Angelis R., Giuggioli D., Bajocchi G., Dagna L., Zanframundo G., Foti R., Cacciapaglia F., Cuomo G., Ariani A., Rosato E., Guiducci S., Girelli F., Riccieri V., Zanatta E., Bosello S., Cavazzana I., Ingegnoli F., Santis M., Murdaca G., Abignano G., Romeo N., Della Rossa A., Caminiti M., Iuliano A., Ciano G., Beretta L., Bagnato G., Lubrano E., De Andres I., Giollo A., Saracco M., Agnes C., Lumetti F., Spinella A., Magnani L., Campochiaro C., De Luca G., Codullo V., Visalli E., Masini F., Gigante A., Bellando-Randone S., Pellegrino G., Pigatto E., Dall'Ara F., Lazzaroni M. G., Generali E., Mennillo G., Barsotti S., Mariano G. P., Calabrese F., Furini F., Vultaggio L., Parisi S., Peroni C. L., Risa A. M., Rozza D., Zanetti A., Carrara G., Landolfi G., Scire C. A., Bianchi G., Fusaro E., Sebastiani G. D., Govoni M., D'Angelo S., Cozzi F., Doria A., Iannone F., Salvarani C., Matucci-Cerinic M., Ferri C., De Angelis, R, Giuggioli, D, Bajocchi, G, Dagna, L, Zanframundo, G, Foti, R, Cacciapaglia, F, Cuomo, G, Ariani, A, Rosato, E, Guiducci, S, Girelli, F, Riccieri, V, Zanatta, E, Bosello, S, Cavazzana, I, Ingegnoli, F, Santis, M, Murdaca, G, Abignano, G, Romeo, N, Della Rossa, A, Caminiti, M, Iuliano, A, Ciano, G, Beretta, L, Bagnato, G, Lubrano, E, De Andres, I, Giollo, A, Saracco, M, Agnes, C, Lumetti, F, Spinella, A, Magnani, L, Campochiaro, C, De Luca, G, Codullo, V, Visalli, E, Masini, F, Gigante, A, Bellando-Randone, S, Pellegrino, G, Pigatto, E, Dall'Ara, F, Lazzaroni, M, Generali, E, Mennillo, G, Barsotti, S, Mariano, G, Calabrese, F, Furini, F, Vultaggio, L, Parisi, S, Peroni, C, Risa, A, Rozza, D, Zanetti, A, Carrara, G, Landolfi, G, Scire, C, Bianchi, G, Fusaro, E, Sebastiani, G, Govoni, M, D'Angelo, S, Cozzi, F, Doria, A, Iannone, F, Salvarani, C, Matucci-Cerinic, M, Ferri, C, De Angelis R., Giuggioli D., Bajocchi G., Dagna L., Zanframundo G., Foti R., Cacciapaglia F., Cuomo G., Ariani A., Rosato E., Guiducci S., Girelli F., Riccieri V., Zanatta E., Bosello S., Cavazzana I., Ingegnoli F., Santis M., Murdaca G., Abignano G., Romeo N., Della Rossa A., Caminiti M., Iuliano A., Ciano G., Beretta L., Bagnato G., Lubrano E., De Andres I., Giollo A., Saracco M., Agnes C., Lumetti F., Spinella A., Magnani L., Campochiaro C., De Luca G., Codullo V., Visalli E., Masini F., Gigante A., Bellando-Randone S., Pellegrino G., Pigatto E., Dall'Ara F., Lazzaroni M. G., Generali E., Mennillo G., Barsotti S., Mariano G. P., Calabrese F., Furini F., Vultaggio L., Parisi S., Peroni C. L., Risa A. M., Rozza D., Zanetti A., Carrara G., Landolfi G., Scire C. A., Bianchi G., Fusaro E., Sebastiani G. D., Govoni M., D'Angelo S., Cozzi F., Doria A., Iannone F., Salvarani C., Matucci-Cerinic M., and Ferri C.
Abstract: OBJECTIVE: There is still a great deal to learn about the influence of sex in systemic sclerosis (SSc). In this respect, national registries provide large and homogeneous patient cohorts for analytical studies. We therefore investigated a wide-ranging and well-characterized SSc series with the aim of identifying sex differences in disease expression, with a special focus on demographic, clinical, and serological characteristics. METHODS: A multicenter SSc cohort of 2281 patients, including 247 men, was recruited in the Italian Systemic sclerosis PRogression INvestiGation (SPRING) registry. Demographic data, disease manifestations, serological profile, and internal organ involvement were compared. RESULTS: The overall female/male ratio was 8.2:1. Female/male ratios for limited cutaneous SSc, diffuse cutaneous SSc, and SSc sine scleroderma subsets were 8.7:1, 4.9:1, and 10.7:1, respectively. A shorter time from onset of Raynaud phenomenon to SSc diagnosis, an increased prevalence of the diffuse cutaneous subset, renal crisis, and digital ulcers were found in males, whereas a significantly higher percentage of sicca syndrome, serum antinuclear antibodies, antiextractable nuclear antigens, anti-La/SSB, and anticentromere protein B was detected in the female group. Males exhibited lower left ventricular ejection fraction, as well as higher prevalence of conduction blocks, arrhythmias, ground glass, and honeycombing. Moreover, forced vital capacity and total lung capacity were medially lower in men than in women. Finally, males were more frequently treated with immunosuppressive drugs. CONCLUSION: Our study further supports the presence of several sex-related differences in patients with SSc. These differences were pronounced in the severity of cutaneous, peripheral vascular, and cardiopulmonary involvement for male patients, whereas an increased prevalence of sicca syndrome and a specific autoantibody profile characterized the female sex.
Published: 2022

20. The association of uric acid with mortality modifies at old age: Data from the uric acid right for heart health (URRAH) study

Author: Ungar, A, Rivasi, G, Di Bari, M, Virdis, A, Casiglia, E, Masi, S, Mengozzi, A, Barbagallo, C, Bombelli, M, Bruno, B, Cicero, A, Cirillo, M, Cirillo, P, Desideri, G, D'Elia, L, Ferri, C, Galletti, F, Gesualdo, L, Giannattasio, C, Iaccarino, G, Ciccarelli, M, Lippa, L, Mallamaci, F, Maloberti, A, Mazza, A, Muiesan, M, Nazzaro, P, Palatini, P, Parati, G, Pontremoli, R, Quarti-Trevano, F, Rattazzi, M, Salvetti, M, Tikhonoff, V, Tocci, G, Cianci, R, Verdecchia, P, Viazzi, F, Volpe, M, Grassi, G, Borghi, C, Ungar A., Rivasi G., Di Bari M., Virdis A., Casiglia E., Masi S., Mengozzi A., Barbagallo C. M., Bombelli M., Bruno B., Cicero A. F. G., Cirillo M., Cirillo P., Desideri G., D'elia L., Ferri C., Galletti F., Gesualdo L., Giannattasio C., Iaccarino G., Ciccarelli M., Lippa L., Mallamaci F., Maloberti A., Mazza A., Muiesan M. L., Nazzaro P., Palatini P., Parati G., Pontremoli R., Quarti-Trevano F., Rattazzi M., Salvetti M., Tikhonoff V., Tocci G., Cianci R., Verdecchia P., Viazzi F., Volpe M., Grassi G., Borghi C., Ungar, A, Rivasi, G, Di Bari, M, Virdis, A, Casiglia, E, Masi, S, Mengozzi, A, Barbagallo, C, Bombelli, M, Bruno, B, Cicero, A, Cirillo, M, Cirillo, P, Desideri, G, D'Elia, L, Ferri, C, Galletti, F, Gesualdo, L, Giannattasio, C, Iaccarino, G, Ciccarelli, M, Lippa, L, Mallamaci, F, Maloberti, A, Mazza, A, Muiesan, M, Nazzaro, P, Palatini, P, Parati, G, Pontremoli, R, Quarti-Trevano, F, Rattazzi, M, Salvetti, M, Tikhonoff, V, Tocci, G, Cianci, R, Verdecchia, P, Viazzi, F, Volpe, M, Grassi, G, Borghi, C, Ungar A., Rivasi G., Di Bari M., Virdis A., Casiglia E., Masi S., Mengozzi A., Barbagallo C. M., Bombelli M., Bruno B., Cicero A. F. G., Cirillo M., Cirillo P., Desideri G., D'elia L., Ferri C., Galletti F., Gesualdo L., Giannattasio C., Iaccarino G., Ciccarelli M., Lippa L., Mallamaci F., Maloberti A., Mazza A., Muiesan M. L., Nazzaro P., Palatini P., Parati G., Pontremoli R., Quarti-Trevano F., Rattazzi M., Salvetti M., Tikhonoff V., Tocci G., Cianci R., Verdecchia P., Viazzi F., Volpe M., Grassi G., and Borghi C.
Abstract: Objectives: In older individuals, the role of serum uric acid (SUA) as risk factor for mortality is debated. This study investigated the association of SUA with all-cause and cardiovascular (CV) mortality in older adults participating in the large multicentre observational uric acid right for heart health (URRAH) study. Methods: Eight thousand URRAH participants aged 65R were included in the analysis. The predictive role of SUA was assessed using Cox regression models stratified according to the cut-off age of 75. SUA was tested as continuous and categorical variable (age-specific quartiles). The prognostic threshold of SUA for mortality was analysed using receiver operating characteristic curves. Results: Among participants aged 65–74, multivariate Cox regression analysis adjusted for CV risk factors and comorbidities identified an independent association of SUA with both all-cause mortality (hazard ratio [HR] 1.169, 95% confidence interval [CI] 1.107–1.235) and CV mortality (HR 1.146, 95% CI 1.064–1.235). The cut-off value of 4.8mg/dl discriminated mortality status. In participants aged 75R, we observed a J-shaped relationship of SUA with all-cause and CV mortality, with risk increasing at extreme SUA levels. Conclusions: These results confirmed the predictive role of SUA for all-cause and CV mortality in older adults, while revealing considerable age-related differences. Mortality risk increased at higher SUA levels in participants aged 65–74, with a prognostic threshold of 4.8mg/dl. The relationship between SUA and mortality was J-shaped in oldest participants. Large interventional studies are needed to clarify the benefits and possible risks of urate-lowering treatments in older adults.
Published: 2022

21. Erratum: Gender differences in predictors of intensive care units admission among COVID-19 patients: The results of the SARS-RAS study of the Italian Society of Hypertension (PLoS ONE (2020) 15:10 (e0237297) DOI: 10.1371/journal.pone.0237297)

Author: Iaccarino G., Iaccarino, G, Grassi, G, Borghi, C, Carugo, S, Fallo, F, Ferri, C, Giannattasio, C, Grassi, D, Letizia, C, Mancusi, C, Minuz, P, Perlini, S, Pucci, G, Rizzoni, D, Salvetti, M, Sarzani, R, Sechi, L, Veglio, F, Volpe, M, Iaccarino G., Grassi G., Borghi C., Carugo S., Fallo F., Ferri C., Giannattasio C., Grassi D., Letizia C., Mancusi C., Minuz P., Perlini S., Pucci G., Rizzoni D., Salvetti M., Sarzani R., Sechi L., Veglio F., Volpe M., Iaccarino G., Iaccarino, G, Grassi, G, Borghi, C, Carugo, S, Fallo, F, Ferri, C, Giannattasio, C, Grassi, D, Letizia, C, Mancusi, C, Minuz, P, Perlini, S, Pucci, G, Rizzoni, D, Salvetti, M, Sarzani, R, Sechi, L, Veglio, F, Volpe, M, Iaccarino G., Grassi G., Borghi C., Carugo S., Fallo F., Ferri C., Giannattasio C., Grassi D., Letizia C., Mancusi C., Minuz P., Perlini S., Pucci G., Rizzoni D., Salvetti M., Sarzani R., Sechi L., Veglio F., and Volpe M.
Abstract: There is an error in the third sentence of the second paragraph of the Introduction section of this article [1]. Prior to the publication of this article [1], reference 6 was retracted by The New England Journal of Medicine and should not have been cited [2]. The correct reference is: WHO. Gender and COVID-19: Advocacy brief [Internet]. 2020 [cited 2021 Jun 10]. Available from: https://www.who.int/publications/i/item/WHO-2019-nCoV-Advocacy_brief-Gender2020.1 As a result of this correction to the references, the following text in the second paragraph of the discussion is removed: “[odds ratio 0.79 (CI 0.65–0.95)] in an extensive observational database collecting patients from Asia, Europe, and the United States.” The authors provide the following additional clarifications: As stated in the article’s Discussion, the study design does not allow conclusions to be drawn about causal relationships. As such, the authors provide revised wording for the first sentence of the Conclusions section of the Abstract, and the first sentence of the Conclusions section of the Discussion. The correct sentences are, respectively, “Our study demonstrates that gender may be the primary determinant of the disease’s severity among COVID-19” and “Our study demonstrates a possible gender effect for women in COVID-19 that are protected from more severe clinical presentations of the disease.” In the study registry [3], the registered timeframe for the secondary outcome “Number and type of anthropometric and clinical parameters that associate with COVID19 and COVID-19 severity” was 3 months. The article reports a shorter observation period between March 9th and April 29th 2020. The authors wish to clarify that the study design included a steering committee that performed an interim analysis. The number of required patients was collected more quickly than expected.
Published: 2022

22. Hypertension and periodontitis: A joint report by the Italian society of hypertension (SIIA) and the Italian society of periodontology and implantology (SIdP)

Author: Del Pinto, R, Landi, L, Grassi, G, Marco Sforza, N, Cairo, F, Citterio, F, Paolantoni, G, D'Aiuto, F, Ferri, C, Monaco, A, Pietropaoli, D, Del Pinto, Rita, Landi, Luca, Grassi, Guido, Marco Sforza, Nicola, Cairo, Francesco, Citterio, Filippo, Paolantoni, Guerino, D'aiuto, Francesco, Ferri, Claudio, Monaco, Annalisa, Pietropaoli, Davide, Del Pinto, R, Landi, L, Grassi, G, Marco Sforza, N, Cairo, F, Citterio, F, Paolantoni, G, D'Aiuto, F, Ferri, C, Monaco, A, Pietropaoli, D, Del Pinto, Rita, Landi, Luca, Grassi, Guido, Marco Sforza, Nicola, Cairo, Francesco, Citterio, Filippo, Paolantoni, Guerino, D'aiuto, Francesco, Ferri, Claudio, Monaco, Annalisa, and Pietropaoli, Davide
Abstract: An accumulating body of evidence supports an independent association between high blood pressure (BP) and periodontitis, possibly mediated by low-grade inflammation. This joint report by the Italian Society of Hypertension (SIIA) and the Italian Society of Periodontology and Implantology (SIdP) working group on Hypertension and Periodontitis (Hy-Per Group) provides a review of the evidence on this topic encompassing epidemiology, biological plausibility, relevance, magnitude, and treatment management. Consensus recommendations are provided for health professionals on how to manage BP in individuals showing signs of poor oral health. In summary, (1) large epidemiological studies highlight that individuals with periodontal diseases have increased risk for high/uncontrolled BP independent of confounders; (2) mechanistically, low-grade inflammation might have a causal role in the association; (3) BP profile and control might benefit from periodontal treatment in pre-hypertensive and hypertensive individuals; (4) oral health status should be evaluated as a potential risk factor for high/uncontrolled BP, and effective oral care should be included as an adjunct lifestyle measure during hypertension management. Further research is needed to optimize BP management in individuals with poor oral health.
Published: 2023

23. Telemedicine and Digital Medicine in the Clinical Management of Hypertension and Hypertension-Related Cardiovascular Diseases: A Position Paper of the Italian Society of Arterial Hypertension (SIIA)

Author: Minuz, P, Albini, F, Imbalzano, E, Izzo, R, Masi, S, Pengo, M, Pucci, G, Scalise, F, Salvetti, M, Tocci, G, Cicero, A, Iaccarino, G, Savoia, C, Sechi, L, Parati, G, Borghi, C, Volpe, M, Ferri, C, Grassi, G, Muiesan, M, Minuz, Pietro, Albini, Fabio Lucio, Imbalzano, Egidio, Izzo, Raffaele, Masi, Stefano, Pengo, Martino F, Pucci, Giacomo, Scalise, Filippo, Salvetti, Massimo, Tocci, Giuliano, Cicero, Arrigo, Iaccarino, Guido, Savoia, Carmine, Sechi, Leonardo, Parati, Gianfranco, Borghi, Claudio, Volpe, Massimo, Ferri, Claudio, Grassi, Guido, Muiesan, Maria Lorenza, Minuz, P, Albini, F, Imbalzano, E, Izzo, R, Masi, S, Pengo, M, Pucci, G, Scalise, F, Salvetti, M, Tocci, G, Cicero, A, Iaccarino, G, Savoia, C, Sechi, L, Parati, G, Borghi, C, Volpe, M, Ferri, C, Grassi, G, Muiesan, M, Minuz, Pietro, Albini, Fabio Lucio, Imbalzano, Egidio, Izzo, Raffaele, Masi, Stefano, Pengo, Martino F, Pucci, Giacomo, Scalise, Filippo, Salvetti, Massimo, Tocci, Giuliano, Cicero, Arrigo, Iaccarino, Guido, Savoia, Carmine, Sechi, Leonardo, Parati, Gianfranco, Borghi, Claudio, Volpe, Massimo, Ferri, Claudio, Grassi, Guido, and Muiesan, Maria Lorenza
Abstract: High blood pressure is the leading cause of death and disability globally and an important treatable risk factor for cardiovascular, cerebrovascular and chronic kidney diseases. Digital technology, including mobile health solutions and digital therapy, is expanding rapidly in clinical medicine and has the potential to improve the quality of care and effectiveness of drug treatment by making medical interventions timely, tailored to hypertensive patients' needs and by improving treatment adherence. Thus, the systematic application of digital technologies could support diagnosis and awareness of hypertension and its complications, ultimately leading to improved BP control at the population level. The progressive implementation of digital medicine in the national health systems must be accompanied by the supervision and guidance of health authorities and scientific societies to ensure the correct use of these new technologies with consequent maximization of the potential benefits. The role of scientific societies in relation to the rapid adoption of digital technologies, therefore, should encompass the entire spectrum of activities pertaining to their institutional role: information, training, promotion of research, scientific collaboration and advice, evaluation and validation of technological tools, and collaboration with regulatory and health authorities.
Published: 2023

24. The Results of the URRAH (Uric Acid Right for Heart Health) Project: A Focus on Hyperuricemia in Relation to Cardiovascular and Kidney Disease and its Role in Metabolic Dysregulation

Author: Maloberti, A, Mengozzi, A, Russo, E, Cicero, A, Angeli, F, Agabiti Rosei, E, Barbagallo, C, Bernardino, B, Bombelli, M, Cappelli, F, Casiglia, E, Cianci, R, Ciccarelli, M, Cirillo, M, Cirillo, P, Desideri, G, D'Elia, L, Dell'Oro, R, Facchetti, R, Ferri, C, Galletti, F, Giannattasio, C, Gesualdo, L, Iaccarino, G, Lippa, L, Mallamaci, F, Masi, S, Masulli, M, Mazza, A, Muiesan, M, Nazzaro, P, Parati, G, Palatini, P, Pauletto, P, Pontremoli, R, Pugliese, N, Quarti-Trevano, F, Rattazzi, M, Reboldi, G, Rivasi, G, Salvetti, M, Tikhonoff, V, Tocci, G, Ungar, A, Verdecchia, P, Viazzi, F, Volpe, M, Virdis, A, Grassi, G, Borghi, C, Maloberti, Alessandro, Mengozzi, Alessandro, Russo, Elisa, Cicero, Arrigo Francesco Giuseppe, Angeli, Fabio, Agabiti Rosei, Enrico, Barbagallo, Carlo Maria, Bernardino, Bruno, Bombelli, Michele, Cappelli, Federica, Casiglia, Edoardo, Cianci, Rosario, Ciccarelli, Michele, Cirillo, Massimo, Cirillo, Pietro, Desideri, Giovambattista, D'Elia, Lanfranco, Dell'Oro, Raffaella, Facchetti, Rita, Ferri, Claudio, Galletti, Ferruccio, Giannattasio, Cristina, Gesualdo, Loreto, Iaccarino, Guido, Lippa, Luciano, Mallamaci, Francesca, Masi, Stefano, Masulli, Maria, Mazza, Alberto, Muiesan, Maria Lorenza, Nazzaro, Pietro, Parati, Gianfranco, Palatini, Paolo, Pauletto, Paolo, Pontremoli, Roberto, Pugliese, Nicola Riccardo, Quarti-Trevano, Fosca, Rattazzi, Marcello, Reboldi, Gianpaolo, Rivasi, Giulia, Salvetti, Massimo, Tikhonoff, Valerie, Tocci, Giuliano, Ungar, Andrea, Verdecchia, Paolo, Viazzi, Francesca, Volpe, Massimo, Virdis, Agostino, Grassi, Guido, Borghi, Claudio, Maloberti, A, Mengozzi, A, Russo, E, Cicero, A, Angeli, F, Agabiti Rosei, E, Barbagallo, C, Bernardino, B, Bombelli, M, Cappelli, F, Casiglia, E, Cianci, R, Ciccarelli, M, Cirillo, M, Cirillo, P, Desideri, G, D'Elia, L, Dell'Oro, R, Facchetti, R, Ferri, C, Galletti, F, Giannattasio, C, Gesualdo, L, Iaccarino, G, Lippa, L, Mallamaci, F, Masi, S, Masulli, M, Mazza, A, Muiesan, M, Nazzaro, P, Parati, G, Palatini, P, Pauletto, P, Pontremoli, R, Pugliese, N, Quarti-Trevano, F, Rattazzi, M, Reboldi, G, Rivasi, G, Salvetti, M, Tikhonoff, V, Tocci, G, Ungar, A, Verdecchia, P, Viazzi, F, Volpe, M, Virdis, A, Grassi, G, Borghi, C, Maloberti, Alessandro, Mengozzi, Alessandro, Russo, Elisa, Cicero, Arrigo Francesco Giuseppe, Angeli, Fabio, Agabiti Rosei, Enrico, Barbagallo, Carlo Maria, Bernardino, Bruno, Bombelli, Michele, Cappelli, Federica, Casiglia, Edoardo, Cianci, Rosario, Ciccarelli, Michele, Cirillo, Massimo, Cirillo, Pietro, Desideri, Giovambattista, D'Elia, Lanfranco, Dell'Oro, Raffaella, Facchetti, Rita, Ferri, Claudio, Galletti, Ferruccio, Giannattasio, Cristina, Gesualdo, Loreto, Iaccarino, Guido, Lippa, Luciano, Mallamaci, Francesca, Masi, Stefano, Masulli, Maria, Mazza, Alberto, Muiesan, Maria Lorenza, Nazzaro, Pietro, Parati, Gianfranco, Palatini, Paolo, Pauletto, Paolo, Pontremoli, Roberto, Pugliese, Nicola Riccardo, Quarti-Trevano, Fosca, Rattazzi, Marcello, Reboldi, Gianpaolo, Rivasi, Giulia, Salvetti, Massimo, Tikhonoff, Valerie, Tocci, Giuliano, Ungar, Andrea, Verdecchia, Paolo, Viazzi, Francesca, Volpe, Massimo, Virdis, Agostino, Grassi, Guido, and Borghi, Claudio
Abstract: The relationship between Serum Uric Acid (UA) and Cardiovascular (CV) diseases has already been extensively evaluated, and it was found to be an independent predictor of all-cause and cardiovascular mortality but also acute coronary syndrome, stroke and heart failure. Similarly, also many papers have been published on the association between UA and kidney function, while less is known on the role of UA in metabolic derangement and, particularly, in metabolic syndrome. Despite the substantial number of publications on the topic, there are still some elements of doubt: (1) the better cut-off to be used to refine CV risk (also called CV cut-off); (2) the needing for a correction of UA values for kidney function; and (3) the better definition of its role in metabolic syndrome: is UA simply a marker, a bystander or a key pathological element of metabolic dysregulation?. The Uric acid Right for heArt Health (URRAH) project was designed by the Working Group on uric acid and CV risk of the Italian Society of Hypertension to answer the first question. After the first papers that individuates specific cut-off for different CV disease, subsequent articles have been published responding to the other relevant questions. This review will summarise most of the results obtained so far from the URRAH research project.
Published: 2023

25. Prevalence of Cardiovascular Risk Factors and Related Medical and Lifestyle Interventions Among Italian Cardiovascular Specialists: A Proof-of-Concept Study

Author: Agabiti Rosei, C, Del Pinto, R, Grassi, G, Muiesan, M, Ferri, C, Agabiti Rosei, Claudia, Del Pinto, Rita, Grassi, Guido, Muiesan, Maria Lorenza, Ferri, Claudio, Agabiti Rosei, C, Del Pinto, R, Grassi, G, Muiesan, M, Ferri, C, Agabiti Rosei, Claudia, Del Pinto, Rita, Grassi, Guido, Muiesan, Maria Lorenza, and Ferri, Claudio
Abstract: Introduction: Physicians and researchers in the cardiovascular field are constantly engaged in the promotion of guidelines-directed preventive measures, but whether they are themselves adherent to the same recommendations was only sporadically examined. Aim: To assess awareness of self-exposure to cardiovascular risk factors and related management among cardiovascular specialists. Methods: During the National Conference of the Italian Society of Hypertension (October 2022), a pilot observational study on consecutive volunteer cardiovascular specialists was conducted. Participants underwent standard sitting and standing blood pressure (BP) measurements and answered a questionnaire regarding modifiable/non modifiable cardiovascular risk factors and related treatments. Based on self-declarations and actual measurements, BP was classified as optimal, normal, high-normal BP, and new hypertension in untreated participants, and as treated/untreated pre-existing hypertension. Controlled hypertension was defined as BP < 140/90 mmHg; age-adjusted lower targets were also applied, according to guidelines. Results: In total, 62 participants (30 F, mean age 43.2 ± 14.8 years) were enrolled; 79% reported regular physical activity; 53% of women and 38% of men were on a low-salt diet. After smoke (19.4%), dyslipidemia was the second most common risk factor (17.7%), often occurring with high BP (26.3%) and left untreated (36.7%). Pre-existing hypertension (11.3%) was often uncontrolled (57.1%) and associated with non-adherence to guidelines-directed lifestyle recommendations. About one in 12 participants was unaware of having high measured BP values. Conclusions: Despite the specific professional exposure, a margin for improvement in self cardiovascular risk factors awareness and management remains in this exploratory sample of cardiovascular specialists. This pilot research anticipates forthcoming, larger studies during national and international conferences.
Published: 2023

26. Systemic sclerosis sine scleroderma: clinical and serological features and relationship with other cutaneous subsets in a large series of patients from the national registry 'SPRING' of the Italian Society for Rheumatology

Author: De Angelis, R., Ferri, C., Giuggioli, D., Bajocchi, G., Dagna, L., Bellando-Randone, S., Zanframundo, G., Foti, Roberta, Cacciapaglia, F., Cuomo, G., Ariani, A., Rosato, E., Lepri, G., Girelli, F., Riccieri, V., Zanatta, E., Bosello, Silvia Laura, Cavazzana, I., Ingegnoli, F., De Santis, M., Murdaca, G., Abignano, G., Romeo, N., Della Rossa, A., Caminiti, M., Iuliano, A. M., Ciano, G., Beretta, Carlo Luigi, Bagnato, G., Lubrano, E., De Andres, I., Giollo, A., Saracco, M., Agnes, C., Cipolletta, Eleonora, Lumetti, F., Spinella, A., Magnani, L., Campochiaro, C., De Luca, G., Codullo, V., Visalli, E., Di Vico, C., Gigante, A., Pellagrino, G., Pigatto, E., Lazzaroni, M. -G., Franceschini, F., Generali, E., Mennillo, G., Barsotti, S., Mariano, G. P., Furini, F., Vultaggio, L., Parisi, S., Peroni, C. L., Rozza, D., Zanetti, Maria Assunta, Carrara, Giancarlo, Landolfi, G., Scire, C. A., Bianchi, G., Fusaro, Enrica Maria, Sebastiani, Gian Domenico, Govoni, M., D'Angelo, S., Cozzi, F., Guiducci, S., Doria, A., Salvarani, C., Iannone, F., Matucci-Cerinic, M., Giorgio, A., Alessia, B., Francesca, C., Renato, C., Dall'Ara, F., Angelo, D. C., Marica, D., Gianluca, S., Rossella, T., Foti R., Bosello S. L. (ORCID:0000-0002-4837-447X), Beretta L. (ORCID:0000-0001-9924-2066), Cipolletta E., Zanetti A., Carrara G., Fusaro E., Sebastiani G. D., De Angelis, R., Ferri, C., Giuggioli, D., Bajocchi, G., Dagna, L., Bellando-Randone, S., Zanframundo, G., Foti, Roberta, Cacciapaglia, F., Cuomo, G., Ariani, A., Rosato, E., Lepri, G., Girelli, F., Riccieri, V., Zanatta, E., Bosello, Silvia Laura, Cavazzana, I., Ingegnoli, F., De Santis, M., Murdaca, G., Abignano, G., Romeo, N., Della Rossa, A., Caminiti, M., Iuliano, A. M., Ciano, G., Beretta, Carlo Luigi, Bagnato, G., Lubrano, E., De Andres, I., Giollo, A., Saracco, M., Agnes, C., Cipolletta, Eleonora, Lumetti, F., Spinella, A., Magnani, L., Campochiaro, C., De Luca, G., Codullo, V., Visalli, E., Di Vico, C., Gigante, A., Pellagrino, G., Pigatto, E., Lazzaroni, M. -G., Franceschini, F., Generali, E., Mennillo, G., Barsotti, S., Mariano, G. P., Furini, F., Vultaggio, L., Parisi, S., Peroni, C. L., Rozza, D., Zanetti, Maria Assunta, Carrara, Giancarlo, Landolfi, G., Scire, C. A., Bianchi, G., Fusaro, Enrica Maria, Sebastiani, Gian Domenico, Govoni, M., D'Angelo, S., Cozzi, F., Guiducci, S., Doria, A., Salvarani, C., Iannone, F., Matucci-Cerinic, M., Giorgio, A., Alessia, B., Francesca, C., Renato, C., Dall'Ara, F., Angelo, D. C., Marica, D., Gianluca, S., Rossella, T., Foti R., Bosello S. L. (ORCID:0000-0002-4837-447X), Beretta L. (ORCID:0000-0001-9924-2066), Cipolletta E., Zanetti A., Carrara G., Fusaro E., and Sebastiani G. D.
Abstract: Objective To describe demographic, clinical and laboratory features of systemic sclerosis sine scleroderma (ssSSc) in a large multicentre systemic sclerosis (SSc) cohort. Methods Data involving 1808 SSc patients from Italian Systemic sclerosis PRogression INvestiGation registry were collected. The ssSSc was defined by the absence of any cutaneous sclerosis and/or puffy fingers. Clinical and serological features of ssSSc were compared with limited cutaneous (lcSSc) and diffuse cutaneous (dcSSc) subsets. Results Among patients with SSc, only 61 (3.4%) were classified as having ssSSc (F/M=19/1). Time from Raynaud's phenomenon (RP) onset to diagnosis was longer in ssSSc (3 years, IQR 1-16.5) than lcSSc (2 years, IQR 0-7), and dcSSc (1 year, IQR 0-3) (p<0.001). Clinical ssSSc phenotype was comparable to lcSSc, except for digital pitting scars (DPS) (19.7% vs 42%, p=0.01), but significantly milder than dcSSc, particularly for digital ulcers (DU) (6.6% vs 35.7%, p<0.001), oesophagus (46.2% vs 63.5%, p=0.009), lung (mean diffusion capacity for carbon monoxide 72.2±19.6 vs 62.4±22.8, p=0.009; mean forced vital capacity 105.6±21.7 vs 89.2±20.9, p<0.001) and major videocapillaroscopic alterations (late pattern 8.6% vs 47.6%, p<0.001). Moreover, in ssSSc the percentages of anticentromere and antitopoisomerase were comparable to lcSSc (40% and 18.3% vs 36.7% and 26.6%), but divergent respect to dcSSc (8.6% and 67.4%, p<0.001). Conclusion The ssSSc is a quite rare disease variant characterised by clinico-serological features comparable to lcSSc, but significantly different from dcSSc. Overall, longer RP duration, low percentages of DPS and peripheral microvascular abnormalities, and increased anti-centromere seropositivity distinguish ssSSc. Further investigations based on national registries might provide useful insights on the actual relevance of the ssSSc within the scleroderma spectrum.
Published: 2023

27. Serum Uric Acid Predicts All-Cause and Cardiovascular Mortality Independently of Hypertriglyceridemia in Cardiometabolic Patients without Established CV Disease: A Sub-Analysis of the URic acid Right for heArt Health (URRAH) Study

Author: Mengozzi, A, Pugliese, N, Desideri, G, Masi, S, Angeli, F, Barbagallo, C, Bombelli, M, Cappelli, F, Casiglia, E, Cianci, R, Ciccarelli, M, Cicero, A, Cirillo, M, Cirillo, P, Dell’Oro, R, D’Elia, L, Ferri, C, Galletti, F, Gesualdo, L, Giannattasio, C, Grassi, G, Iaccarino, G, Lippa, L, Mallamaci, F, Maloberti, A, Masulli, M, Mazza, A, Muiesan, M, Nazzaro, P, Palatini, P, Parati, G, Pontremoli, R, Quarti-Trevano, F, Rattazzi, M, Reboldi, G, Rivasi, G, Russo, E, Salvetti, M, Tikhonoff, V, Tocci, G, Ungar, A, Verdecchia, P, Viazzi, F, Volpe, M, Borghi, C, Virdis, A, Mengozzi, Alessandro, Pugliese, Nicola Riccardo, Desideri, Giovambattista, Masi, Stefano, Angeli, Fabio, Barbagallo, Carlo Maria, Bombelli, Michele, Cappelli, Federica, Casiglia, Edoardo, Cianci, Rosario, Ciccarelli, Michele, Cicero, Arrigo F. G., Cirillo, Massimo, Cirillo, Pietro, Dell’Oro, Raffaella, D’Elia, Lanfranco, Ferri, Claudio, Galletti, Ferruccio, Gesualdo, Loreto, Giannattasio, Cristina, Grassi, Guido, Iaccarino, Guido, Lippa, Luciano, Mallamaci, Francesca, Maloberti, Alessandro, Masulli, Maria, Mazza, Alberto, Muiesan, Maria Lorenza, Nazzaro, Pietro, Palatini, Paolo, Parati, Gianfranco, Pontremoli, Roberto, Quarti-Trevano, Fosca, Rattazzi, Marcello, Reboldi, Gianpaolo, Rivasi, Giulia, Russo, Elisa, Salvetti, Massimo, Tikhonoff, Valerie, Tocci, Giuliano, Ungar, Andrea, Verdecchia, Paolo, Viazzi, Francesca, Volpe, Massimo, Borghi, Claudio, Virdis, Agostino, Mengozzi, A, Pugliese, N, Desideri, G, Masi, S, Angeli, F, Barbagallo, C, Bombelli, M, Cappelli, F, Casiglia, E, Cianci, R, Ciccarelli, M, Cicero, A, Cirillo, M, Cirillo, P, Dell’Oro, R, D’Elia, L, Ferri, C, Galletti, F, Gesualdo, L, Giannattasio, C, Grassi, G, Iaccarino, G, Lippa, L, Mallamaci, F, Maloberti, A, Masulli, M, Mazza, A, Muiesan, M, Nazzaro, P, Palatini, P, Parati, G, Pontremoli, R, Quarti-Trevano, F, Rattazzi, M, Reboldi, G, Rivasi, G, Russo, E, Salvetti, M, Tikhonoff, V, Tocci, G, Ungar, A, Verdecchia, P, Viazzi, F, Volpe, M, Borghi, C, Virdis, A, Mengozzi, Alessandro, Pugliese, Nicola Riccardo, Desideri, Giovambattista, Masi, Stefano, Angeli, Fabio, Barbagallo, Carlo Maria, Bombelli, Michele, Cappelli, Federica, Casiglia, Edoardo, Cianci, Rosario, Ciccarelli, Michele, Cicero, Arrigo F. G., Cirillo, Massimo, Cirillo, Pietro, Dell’Oro, Raffaella, D’Elia, Lanfranco, Ferri, Claudio, Galletti, Ferruccio, Gesualdo, Loreto, Giannattasio, Cristina, Grassi, Guido, Iaccarino, Guido, Lippa, Luciano, Mallamaci, Francesca, Maloberti, Alessandro, Masulli, Maria, Mazza, Alberto, Muiesan, Maria Lorenza, Nazzaro, Pietro, Palatini, Paolo, Parati, Gianfranco, Pontremoli, Roberto, Quarti-Trevano, Fosca, Rattazzi, Marcello, Reboldi, Gianpaolo, Rivasi, Giulia, Russo, Elisa, Salvetti, Massimo, Tikhonoff, Valerie, Tocci, Giuliano, Ungar, Andrea, Verdecchia, Paolo, Viazzi, Francesca, Volpe, Massimo, Borghi, Claudio, and Virdis, Agostino
Abstract: High serum uric acid (SUA) and triglyceride (TG) levels might promote high-cardiovascular risk phenotypes across the cardiometabolic spectrum. However, SUA predictive power in the presence of normal and high TG levels has never been investigated. We included 8124 patients from the URic acid Right for heArt Health (URRAH) study cohort who were followed for over 20 years and had no established cardiovascular disease or uncontrolled metabolic disease. All-cause mortality (ACM) and cardiovascular mortality (CVM) were explored by the Kaplan–Meier estimator and Cox multivariable regression, adopting recently defined SUA cut-offs for ACM (≥4.7 mg/dL) and CVM (≥5.6 mg/dL). Exploratory analysis across cardiometabolic subgroups and a sensitivity analysis using SUA/serum creatinine were performed as validation. SUA predicted ACM (HR 1.25 [1.12–1.40], p < 0.001) and CVM (1.31 [1.11–1.74], p < 0.001) in the whole study population, and according to TG strata: ACM in normotriglyceridemia (HR 1.26 [1.12–1.43], p < 0.001) and hypertriglyceridemia (1.31 [1.02–1.68], p = 0.033), and CVM in normotriglyceridemia (HR 1.46 [1.23–1.73], p < 0.001) and hypertriglyceridemia (HR 1.31 [0.99–1.64], p = 0.060). Exploratory and sensitivity analyses confirmed our findings, suggesting a substantial role of SUA in normotriglyceridemia and hypertriglyceridemia. In conclusion, we report that SUA can predict ACM and CVM in cardiometabolic patients without established cardiovascular disease, independent of TG levels.
Published: 2023

28. Practical Guidelines for Patients with Hypertension and Periodontitis

Author: Pietropaoli, D, Cairo, F, Citterio, F, D'Aiuto, F, Ferri, C, Grassi, G, Landi, L, Letizia, C, Masi, S, Muiesan, M, Paolantoni, G, Sforza, N, Del Pinto, R, Pietropaoli, Davide, Cairo, Francesco, Citterio, Filippo, D'Aiuto, Francesco, Ferri, Claudio, Grassi, Guido, Landi, Luca, Letizia, Claudio, Masi, Stefano, Muiesan, Maria Lorenza, Paolantoni, Guerino, Sforza, Nicola Marco, Del Pinto, Rita, Pietropaoli, D, Cairo, F, Citterio, F, D'Aiuto, F, Ferri, C, Grassi, G, Landi, L, Letizia, C, Masi, S, Muiesan, M, Paolantoni, G, Sforza, N, Del Pinto, R, Pietropaoli, Davide, Cairo, Francesco, Citterio, Filippo, D'Aiuto, Francesco, Ferri, Claudio, Grassi, Guido, Landi, Luca, Letizia, Claudio, Masi, Stefano, Muiesan, Maria Lorenza, Paolantoni, Guerino, Sforza, Nicola Marco, and Del Pinto, Rita
Abstract: Arterial hypertension (AH) and periodontitis are among the most common non-communicable chronic diseases worldwide. Besides sharing common risk factors, an increasing body of evidence supports an independent association between the two conditions, with low-grade systemic inflammation acting as the plausible biological link with increased cardiovascular risk. In 2021, the Italian Society of Arterial Hypertension (SIIA) and the Italian Society of Periodontology and Implantology (SIdP) have joined forces and published a joint report on the relationships between AH and periodontitis, reviewing the existing scientific evidence and underlining the need to increase awareness of the strong connection between the two conditions and promote treatment strategies for the control of gums inflammation in patients with AH. The current document extends the previous joint report, providing clinical practical guidelines aimed to support clinicians in the management of patients who suffer from or are at risk of being affected by both conditions. These recommendations are based on careful consideration of the available evidence as well as of the current guidelines on the management of periodontitis and AH and are supported by SIIA and SIdP.
Published: 2023

29. Machine Learning in Hypertension Detection: A Study on World Hypertension Day Data

Author: Montagna, S, Pengo, M, Ferretti, S, Borghi, C, Ferri, C, Grassi, G, Muiesan, M, Parati, G, Muiesan, ML, Montagna, S, Pengo, M, Ferretti, S, Borghi, C, Ferri, C, Grassi, G, Muiesan, M, Parati, G, and Muiesan, ML
Abstract: Many modifiable and non-modifiable risk factors have been associated with hypertension. However, current screening programs are still failing in identifying individuals at higher risk of hypertension. Given the major impact of high blood pressure on cardiovascular events and mortality, there is an urgent need to find new strategies to improve hypertension detection. We aimed to explore whether a machine learning (ML) algorithm can help identifying individuals predictors of hypertension. We analysed the data set generated by the questionnaires administered during the World Hypertension Day from 2015 to 2019. A total of 20206 individuals have been included for analysis. We tested five ML algorithms, exploiting different balancing techniques. Moreover, we computed the performance of the medical protocol currently adopted in the screening programs. Results show that a gain of sensitivity reflects in a loss of specificity, bringing to a scenario where there is not an algorithm and a configuration which properly outperforms against the others. However, Random Forest provides interesting performances (0.818 sensitivity – 0.629 specificity) compared with medical protocols (0.906 sensitivity – 0.230 specificity). Detection of hypertension at a population level still remains challenging and a machine learning approach could help in making screening programs more precise and cost effective, when based on accurate data collection. More studies are needed to identify new features to be acquired and to further improve the performances of ML models.
Published: 2023

30. Hyperuricemia increases the risk of cardiovascular mortality associated with very high HdL-cholesterol level

Author: Palatini, P, Virdis, A, Masi, S, Mengozzi, A, Casiglia, E, Tikhonoff, V, Cicero, A, Ungar, A, Parati, G, Rivasi, G, Salvetti, M, Barbagallo, C, Bombelli, M, Dell'Oro, R, Bruno, B, Lippa, L, D'Elia, L, Masulli, M, Verdecchia, P, Reboldi, G, Angeli, F, Mallamaci, F, Cirillo, M, Rattazzi, M, Cirillo, P, Gesualdo, L, Mazza, A, Giannattasio, C, Maloberti, A, Volpe, M, Tocci, G, Iaccarino, G, Nazzaro, P, Galletti, F, Ferri, C, Desideri, G, Viazzi, F, Pontremoli, R, Muiesan, M, Grassi, G, Borghi, C, Palatini, Paolo, Virdis, Agostino, Masi, Stefano, Mengozzi, Alessandro, Casiglia, Edoardo, Tikhonoff, Valerie, Cicero, Arrigo F G, Ungar, Andrea, Parati, Gianfranco, Rivasi, Giulia, Salvetti, Massimo, Barbagallo, Carlo M, Bombelli, Michele, Dell'Oro, Raffaella, Bruno, Berardino, Lippa, Luciano, D'Elia, Lanfranco, Masulli, Maria, Verdecchia, Paolo, Reboldi, Gianpaolo, Angeli, Fabio, Mallamaci, Francesca, Cirillo, Massimo, Rattazzi, Marcello, Cirillo, Pietro, Gesualdo, Loreto, Mazza, Alberto, Giannattasio, Cristina, Maloberti, Alessandro, Volpe, Massimo, Tocci, Giuliano, Iaccarino, Guido, Nazzaro, Pietro, Galletti, Ferruccio, Ferri, Claudio, Desideri, Giovambattista, Viazzi, Francesca, Pontremoli, Roberto, Muiesan, Maria Lorenza, Grassi, Guido, Borghi, Claudio, Palatini, P, Virdis, A, Masi, S, Mengozzi, A, Casiglia, E, Tikhonoff, V, Cicero, A, Ungar, A, Parati, G, Rivasi, G, Salvetti, M, Barbagallo, C, Bombelli, M, Dell'Oro, R, Bruno, B, Lippa, L, D'Elia, L, Masulli, M, Verdecchia, P, Reboldi, G, Angeli, F, Mallamaci, F, Cirillo, M, Rattazzi, M, Cirillo, P, Gesualdo, L, Mazza, A, Giannattasio, C, Maloberti, A, Volpe, M, Tocci, G, Iaccarino, G, Nazzaro, P, Galletti, F, Ferri, C, Desideri, G, Viazzi, F, Pontremoli, R, Muiesan, M, Grassi, G, Borghi, C, Palatini, Paolo, Virdis, Agostino, Masi, Stefano, Mengozzi, Alessandro, Casiglia, Edoardo, Tikhonoff, Valerie, Cicero, Arrigo F G, Ungar, Andrea, Parati, Gianfranco, Rivasi, Giulia, Salvetti, Massimo, Barbagallo, Carlo M, Bombelli, Michele, Dell'Oro, Raffaella, Bruno, Berardino, Lippa, Luciano, D'Elia, Lanfranco, Masulli, Maria, Verdecchia, Paolo, Reboldi, Gianpaolo, Angeli, Fabio, Mallamaci, Francesca, Cirillo, Massimo, Rattazzi, Marcello, Cirillo, Pietro, Gesualdo, Loreto, Mazza, Alberto, Giannattasio, Cristina, Maloberti, Alessandro, Volpe, Massimo, Tocci, Giuliano, Iaccarino, Guido, Nazzaro, Pietro, Galletti, Ferruccio, Ferri, Claudio, Desideri, Giovambattista, Viazzi, Francesca, Pontremoli, Roberto, Muiesan, Maria Lorenza, Grassi, Guido, and Borghi, Claudio
Abstract: Background and aims: Whether the association between very high HDL-cholesterol levels and cardiovascular mortality (CVM) is modulated by some facilitating factors is unclear. Aim of the study was to investigate whether the risk of CVM associated with very high HDL-cholesterol is increased in subjects with hyperuricemia. Methods and results: Multivariable Cox analyses were made in 18,072 participants from the multicentre URRAH study stratified by sex and HDL-cholesterol category. During a median follow-up of 11.4 years there were 1307 cases of CVM. In multivariable Cox models a J-shaped association was found in the whole population, with the highest risk being present in the high HDL-cholesterol group [>80 mg/dL, adjusted hazard ratio (HR), 1.28; 95%CI, 1.02–1.61; p = 0.031)]. However, a sex-specific analysis revealed that this association was present only in women (HR, 1.34; 95%CI, 1.02–1.77; p = 0.034) but not in men. The risk of CVM related to high HDL-cholesterol was much greater in the women with high uric acid (>0.30 mmol/L, HR 1.61; 95%CI, 1.08–2.39) than in those with low uric acid (HR, 1.17; 95%CI, 0.80–1.72, p for interaction = 0.016). In women older than 70 years with hyperuricemia the risk related to high HDL-cholesterol was 1.83 (95%CI, 1.19–2.80, p < 0.005). Inclusion of BMI in the models weakened the strength of the associations. Conclusion: Our data indicate that very high HDL-cholesterol levels in women are associated with CVM in a J-shaped fashion. The risk of CVM is increased by concomitant hyperuricemia suggesting that a proinflammatory/oxidative state can enhance the detrimental cardiovascular effects associated with high HDL-cholesterol.
Published: 2023

31. Serum uric acid / serum creatinine ratio as a predictor of cardiovascular events. Detection of prognostic cardiovascular cut-off values

Author: Casiglia, E, Tikhonoff, V, Virdis, A, Grassi, G, Angeli, F, Barbagallo, C, Bombelli, M, Cicero, A, Cirillo, M, Cirillo, P, Dell'Oro, R, D'Elia, L, Desideri, G, Ferri, C, Galletti, F, Gesualdo, L, Giannattasio, C, Iaccarino, G, Lippa, L, Mallamaci, F, Masi, S, Maloberti, A, Masulli, M, Mazza, A, Mengozzi, A, Muiesan, M, Nazzaro, P, Palatini, P, Parati, G, Pontremoli, R, Quarti-Trevano, F, Rattazzi, M, Reboldi, G, Rivasi, G, Salvetti, M, Tocci, G, Ungar, A, Verdecchia, P, Viazzi, F, Volpe, M, Borghi, C, Casiglia, Edoardo, Tikhonoff, Valérie, Virdis, Agostino, Grassi, Guido, Angeli, Fabio, Barbagallo, Carlo M, Bombelli, Michele, Cicero, Arrigo F G, Cirillo, Massimo, Cirillo, Pietro, Dell'Oro, Raffaella, D'elia, Lanfranco, Desideri, Giovambattista, Ferri, Claudio, Galletti, Ferruccio, Gesualdo, Loreto, Giannattasio, Cristina, Iaccarino, Guido, Lippa, Luciano, Mallamaci, Francesca, Masi, Stefano, Maloberti, Alessandro, Masulli, Maria, Mazza, Alberto, Mengozzi, Alessandro, Muiesan, Maria Lorenza, Nazzaro, Pietro, Palatini, Paolo, Parati, Gianfranco, Pontremoli, Roberto, Quarti-Trevano, Fosca, Rattazzi, Marcello, Reboldi, Gianpaolo, Rivasi, Giulia, Salvetti, Massimo, Tocci, Giuliano, Ungar, Andrea, Verdecchia, Paolo, Viazzi, Francesca, Volpe, Massimo, Borghi, Claudio, Casiglia, E, Tikhonoff, V, Virdis, A, Grassi, G, Angeli, F, Barbagallo, C, Bombelli, M, Cicero, A, Cirillo, M, Cirillo, P, Dell'Oro, R, D'Elia, L, Desideri, G, Ferri, C, Galletti, F, Gesualdo, L, Giannattasio, C, Iaccarino, G, Lippa, L, Mallamaci, F, Masi, S, Maloberti, A, Masulli, M, Mazza, A, Mengozzi, A, Muiesan, M, Nazzaro, P, Palatini, P, Parati, G, Pontremoli, R, Quarti-Trevano, F, Rattazzi, M, Reboldi, G, Rivasi, G, Salvetti, M, Tocci, G, Ungar, A, Verdecchia, P, Viazzi, F, Volpe, M, Borghi, C, Casiglia, Edoardo, Tikhonoff, Valérie, Virdis, Agostino, Grassi, Guido, Angeli, Fabio, Barbagallo, Carlo M, Bombelli, Michele, Cicero, Arrigo F G, Cirillo, Massimo, Cirillo, Pietro, Dell'Oro, Raffaella, D'elia, Lanfranco, Desideri, Giovambattista, Ferri, Claudio, Galletti, Ferruccio, Gesualdo, Loreto, Giannattasio, Cristina, Iaccarino, Guido, Lippa, Luciano, Mallamaci, Francesca, Masi, Stefano, Maloberti, Alessandro, Masulli, Maria, Mazza, Alberto, Mengozzi, Alessandro, Muiesan, Maria Lorenza, Nazzaro, Pietro, Palatini, Paolo, Parati, Gianfranco, Pontremoli, Roberto, Quarti-Trevano, Fosca, Rattazzi, Marcello, Reboldi, Gianpaolo, Rivasi, Giulia, Salvetti, Massimo, Tocci, Giuliano, Ungar, Andrea, Verdecchia, Paolo, Viazzi, Francesca, Volpe, Massimo, and Borghi, Claudio
Abstract: Objective:In the frame of the Uric Acid Right for Heart Health (URRAH) study, a nationwide multicenter study involving adult participants recruited on a regional community basis from all the territory of Italy under the patronage of the Working Group on Uric Acid and Cardiovascular Risk of the Italian Society of Hypertension, we searched for the cut-off values of the ratio between serum uric acid (SUA) and serum creatinine (sCr) able to predict cardiovascular (CV) events.Methods:Among 20 724 participants followed-up for 126 ± 64 months, after detecting cut-off by the receiver operating characteristic curves, we calculated by Cox models adjusted for confounders having CV events as dependent variable the hazard ratio (HR) of SUA/sCr > cut-off. We also verified if the role of cut-off varied with increasing SUA/sCr.Results:A plausible prognostic cut-off of SUA/sCr was found and was the same in the whole database, in men and in women (>5.35). The HR of SUA/sCr > cut-off was 1.159 (95% confidence interval [CI] 1.092-1.131, P < 0.03) in all, 1.161 (95% CI 1.021-1.335, P < 0.02) in men, and 1.444 (95% CI 1.012-1.113, P < 0.03) in women. In increasing quintiles of SUA/sCr the cut-offs were >3.08, >4.87, >5.35, >6.22 and >7.58, respectively. The HRs significantly increased from the 3rd to the 5th quintile (1.21, 95% CI 1.032-1.467, P = 0.018; 1.294, 95% CI 1.101-1.521, P = 0.002; and 1.642, 95% CI 1.405-1.919, P < 0.0001; respectively), that is, over 5.35, whereas the 2nd quintile was not significantly different from the 1st (reference).Conclusion:Having SUA/sCr >5.35 is an independent CV risk indicator both in men and women. The cut-off is dynamic and significantly increases with increasing SUA/sCr.
Published: 2023

32. Corrigendum to: High heart rate amplifies the risk of cardiovascular mortality associated with elevated uric acid

Author: Palatini, P, Palatini, P, Parati, G, Virdis, A, Reboldi, G, Masi, S, Mengozzi, A, Casiglia, E, Tikhonoff, V, Cicero, A, Ungar, A, Rivasi, G, Salvetti, M, Barbagallo, C, Bombelli, M, Dell'Oro, R, Bruno, B, Lippa, L, D'Elia, L, Verdecchia, P, Angeli, F, Mallamaci, F, Cirillo, M, Rattazzi, M, Cirillo, P, Gesualdo, L, Mazza, A, Giannattasio, C, Maloberti, A, Volpe, M, Tocci, G, Georgiopoulos, G, Iaccarino, G, Nazzaro, P, Galletti, F, Ferri, C, Desideri, G, Viazzi, F, Pontremoli, R, Muiesan, M, Grassi, G, Borghi, C, Cicero, AFG, Barbagallo, CM, Muiesan, ML, Palatini, P, Palatini, P, Parati, G, Virdis, A, Reboldi, G, Masi, S, Mengozzi, A, Casiglia, E, Tikhonoff, V, Cicero, A, Ungar, A, Rivasi, G, Salvetti, M, Barbagallo, C, Bombelli, M, Dell'Oro, R, Bruno, B, Lippa, L, D'Elia, L, Verdecchia, P, Angeli, F, Mallamaci, F, Cirillo, M, Rattazzi, M, Cirillo, P, Gesualdo, L, Mazza, A, Giannattasio, C, Maloberti, A, Volpe, M, Tocci, G, Georgiopoulos, G, Iaccarino, G, Nazzaro, P, Galletti, F, Ferri, C, Desideri, G, Viazzi, F, Pontremoli, R, Muiesan, M, Grassi, G, Borghi, C, Cicero, AFG, Barbagallo, CM, and Muiesan, ML
Published: 2023

33. Impact of COVID-19 and vaccination campaign on 1,755 systemic sclerosis patients during first three years of pandemic. Possible risks for individuals with impaired immunoreactivity to vaccine, ongoing immunomodulating treatments, and disease-related lung involvement during the next pandemic phase

Author: Ferri, C., Raimondo, V., Giuggioli, D., Gragnani, L., Lorini, S., Dagna, L., Bosello, Silvia Laura, Foti, R., Riccieri, V., Guiducci, S., Cuomo, G., Tavoni, A., De Angelis, R., Cacciapaglia, F., Zanatta, E., Cozzi, F., Murdaca, G., Cavazzana, I., Romeo, N., Codullo, V., Pellegrini, R., Varcasia, G., De Santis, M., Selmi, C., Abignano, G., Caminiti, M., L'Andolina, M., Olivo, D., Lubrano, E., Spinella, A., Lumetti, F., De Luca, G., Ruscitti, P., Urraro, T., Visentini, M., Bellando-Randone, S., Visalli, E., Testa, D., Sciascia, G., Masini, F., Pellegrino, G., Saccon, F., Balestri, E., Elia, G., Ferrari, S. M., Tonutti, A., Dall'Ara, F., Pagano Mariano, G., Pettiti, G., Zanframundo, G., Brittelli, R., Aiello, V., Dal Bosco, Y., Di Cola, I., Scorpiniti, D., Fusaro, E., Ferrari, T., Gigliotti, P., Campochiaro, C., Francioso, F., Iandoli, C., Caira, V., Zignego, A. L., D'Angelo, S., Franceschini, F., Matucci-Cerinic, M., Giacomelli, R., Doria, A., Santini, Stefano Angelo, Fallahi, P., Iannone, F., Antonelli, A., Bosello S. L. (ORCID:0000-0002-4837-447X), Santini S. A. (ORCID:0000-0003-1956-5899), Ferri, C., Raimondo, V., Giuggioli, D., Gragnani, L., Lorini, S., Dagna, L., Bosello, Silvia Laura, Foti, R., Riccieri, V., Guiducci, S., Cuomo, G., Tavoni, A., De Angelis, R., Cacciapaglia, F., Zanatta, E., Cozzi, F., Murdaca, G., Cavazzana, I., Romeo, N., Codullo, V., Pellegrini, R., Varcasia, G., De Santis, M., Selmi, C., Abignano, G., Caminiti, M., L'Andolina, M., Olivo, D., Lubrano, E., Spinella, A., Lumetti, F., De Luca, G., Ruscitti, P., Urraro, T., Visentini, M., Bellando-Randone, S., Visalli, E., Testa, D., Sciascia, G., Masini, F., Pellegrino, G., Saccon, F., Balestri, E., Elia, G., Ferrari, S. M., Tonutti, A., Dall'Ara, F., Pagano Mariano, G., Pettiti, G., Zanframundo, G., Brittelli, R., Aiello, V., Dal Bosco, Y., Di Cola, I., Scorpiniti, D., Fusaro, E., Ferrari, T., Gigliotti, P., Campochiaro, C., Francioso, F., Iandoli, C., Caira, V., Zignego, A. L., D'Angelo, S., Franceschini, F., Matucci-Cerinic, M., Giacomelli, R., Doria, A., Santini, Stefano Angelo, Fallahi, P., Iannone, F., Antonelli, A., Bosello S. L. (ORCID:0000-0002-4837-447X), and Santini S. A. (ORCID:0000-0003-1956-5899)
Abstract: Introduction: The impact of COVID-19 pandemic represents a serious challenge for ‘frail’ patients' populations with inflammatory autoimmune systemic diseases such as systemic sclerosis (SSc). We investigated the prevalence and severity of COVID-19, as well the effects of COVID-19 vaccination campaign in a large series of SSc patients followed for the entire period (first 38 months) of pandemic. Patients and method: This prospective survey study included 1755 unselected SSc patients (186 M, 1,569F; mean age 58.7 ± 13.4SD years, mean disease duration 8.8 ± 7.3SD years) recruited in part by telephone survey at 37 referral centers from February 2020 to April 2023. The following parameters were carefully evaluated: i. demographic, clinical, serological, and therapeutical features; ii. prevalence and severity of COVID-19; and iii. safety, immunogenicity, and efficacy of COVID-19 vaccines. Results: The prevalence of COVID-19 recorded during the whole pandemic was significantly higher compared to Italian general population (47.3 % vs 43.3 %, p < 0.000), as well the COVID-19-related mortality (1.91 % vs 0.72 %, p < 0.001). As regards the putative prognostic factors of worse outcome, COVID-19 positive patients with SSc-related interstitial lung involvement showed significantly higher percentage of COVID-19-related hospitalization compared to those without (5.85 % vs 1.73 %; p < 0.0001), as well as of mortality rate (2.01 % vs 0.4 %; p = 0.002). Over half of patients (56.3 %) received the first two plus one booster dose of vaccine; while a fourth dose was administered to 35.6 %, and only few of them (1.99 %) had five or more doses of vaccine. Of note, an impaired seroconversion was recorded in 25.6 % of individuals after the first 2 doses of vaccine, and in 8.4 % of patients also after the booster dose. Furthermore, the absence of T-cell immunoreactivity was observed in 3/7 patients tested by QuantiFERON® SARSCoV-2 Starter Set (Qiagen). The efficacy of vaccines, evalu
Published: 2023

34. COVID-19 and Mixed Cryoglobulinemia Syndrome: Long-Term Survey Study on the Prevalence and Outcome, Vaccine Safety, and Immunogenicity

Author: Gragnani, L., Visentini, M., Lorini, S., Santini, Stefano Angelo, Lauletta, G., Mazzaro, C., Urraro, T., Quartuccio, L., Cacciapaglia, F., Ruscitti, P., Tavoni, A., Marri, S., Cusano, G., Petraccia, L., Naclerio, C., Treppo, E., del Frate, G., Di Cola, I., Raimondo, V., Scorpiniti, D., Monti, M., Puccetti, L., Elia, G., Fallahi, P., Basili, S., Scarpato, S., Iannone, F., Casato, M., Antonelli, A., Zignego, A. L., Ferri, C., Santini S. A. (ORCID:0000-0003-1956-5899), Gragnani, L., Visentini, M., Lorini, S., Santini, Stefano Angelo, Lauletta, G., Mazzaro, C., Urraro, T., Quartuccio, L., Cacciapaglia, F., Ruscitti, P., Tavoni, A., Marri, S., Cusano, G., Petraccia, L., Naclerio, C., Treppo, E., del Frate, G., Di Cola, I., Raimondo, V., Scorpiniti, D., Monti, M., Puccetti, L., Elia, G., Fallahi, P., Basili, S., Scarpato, S., Iannone, F., Casato, M., Antonelli, A., Zignego, A. L., Ferri, C., and Santini S. A. (ORCID:0000-0003-1956-5899)
Abstract: Purpose: Mixed cryoglobulinemia syndrome (MCs) is a rare immunoproliferative systemic disorder with cutaneous and multiple organ involvement. Our multicenter survey study aimed to investigate the prevalence and outcome of COVID-19 and the safety and immunogenicity of COVID-19 vaccines in a large MCs series. Methods: The survey included 430 unselected MCs patients (130 M, 300 F; mean age 70 ± 10.96 years) consecutively collected at 11 Italian referral centers. Disease classification, clinico-serological assessment, COVID-19 tests, and vaccination immunogenicity were carried out according to current methodologies. Results: A significantly higher prevalence of COVID-19 was found in MCs patients compared to Italian general population (11.9% vs 8.0%, p < 0.005), and the use of immunomodulators was associated to a higher risk to get infected (p = 0.0166). Moreover, higher mortality rate was recorded in MCs with COVID-19 compared to those without (p < 0.01). Patients’ older age (≥ 60 years) correlated with worse COVID-19 outcomes. The 87% of patients underwent vaccination and 50% a booster dose. Of note, vaccine-related disease flares/worsening were significantly less frequent than those associated to COVID-19 (p = 0.0012). Impaired vaccination immunogenicity was observed in MCs patients compared to controls either after the first vaccination (p = 0.0039) and also after the booster dose (p = 0.05). Finally, some immunomodulators, namely, rituximab and glucocorticoids, hampered the vaccine-induced immunogenicity (p = 0.029). Conclusions: The present survey revealed an increased prevalence and morbidity of COVID-19 in MCs patients, as well an impaired immunogenicity even after booster vaccination with high rate of no response. Therefore, MCs can be included among frail populations at high risk of infection and severe COVID-19 manifestations, suggesting the need of a close monitoring and specific preventive/therapeutical measures during the ongoing pandemic.
Published: 2023

35. Hypertension and Periodontitis: An Upcoming Joint Report by the Italian Society of Hypertension (SIIA) and the Italian Society of Periodontology and Implantology (SIdP)

Author: Landi, L, Grassi, G, Sforza, N, Ferri, C, Cairo, F, Citterio, F, D'Aiuto, F, Del Pinto, R, Paolantoni, G, Pietropaoli, D, Landi L., Grassi G., Sforza N. M., Ferri C., Cairo F., Citterio F., D'Aiuto F., Del Pinto R., Paolantoni G., Pietropaoli D., Landi, L, Grassi, G, Sforza, N, Ferri, C, Cairo, F, Citterio, F, D'Aiuto, F, Del Pinto, R, Paolantoni, G, Pietropaoli, D, Landi L., Grassi G., Sforza N. M., Ferri C., Cairo F., Citterio F., D'Aiuto F., Del Pinto R., Paolantoni G., and Pietropaoli D.
Published: 2021

36. May Measurement Month 2019: An analysis of blood pressure screening results from Italy

Author: Torlasco, C, Faini, A, Pengo, M, Borghi, C, Grassi, G, Ferri, C, Muiesan, M, Salvetti, M, Sechi, L, Minuz, P, Mulatero, P, Pucci, G, Volpe, M, Carugo, S, Sarzani, R, Mule, G, Beaney, T, Poulter, N, Xia, X, Parati, G, Torlasco C., Faini A., Pengo M., Borghi C., Grassi G., Ferri C., Muiesan M. L., Salvetti M., Sechi L., Minuz P., Mulatero P., Pucci G., Volpe M., Carugo S., Sarzani R., Mule G., Beaney T., Poulter N. R., Xia X., Parati G., Torlasco, C, Faini, A, Pengo, M, Borghi, C, Grassi, G, Ferri, C, Muiesan, M, Salvetti, M, Sechi, L, Minuz, P, Mulatero, P, Pucci, G, Volpe, M, Carugo, S, Sarzani, R, Mule, G, Beaney, T, Poulter, N, Xia, X, Parati, G, Torlasco C., Faini A., Pengo M., Borghi C., Grassi G., Ferri C., Muiesan M. L., Salvetti M., Sechi L., Minuz P., Mulatero P., Pucci G., Volpe M., Carugo S., Sarzani R., Mule G., Beaney T., Poulter N. R., Xia X., and Parati G.
Abstract: Cardiovascular (CV) diseases are burdened by high mortality and morbidity, being responsible for half of the deaths in Europe. Although hypertension is recognized as the most important CV risk factor, hypertension awareness, and blood pressure (BP) control are still unsatisfactory. In 2017 and 2018, respectively >10 000 and >5000 individuals took part in the May Measurement Month (MMM) campaign in Italy, of whom 30.6% and 26.3% were found to have high BP, respectively. To raise public awareness on the importance of hypertension and to collect BP data on a nation-wide scale in Italy. In the frame of the MMM campaign, an opportunistic cross-sectional survey of volunteers aged ≥18 years was carried out in May 2019. BP measurement, the definition of hypertension, and statistical analysis followed the standard MMM protocol. Screening was conducted in multiple sites by health personnel. Among the 10 182 people screened (females: 52.3%, mean age 58 ± 16years) mean BP was 127/78 mmHg, and 3171 (31.1%) participants had arterial hypertension, of whom 62.1% were aware of being hypertensive. Diabetes, body mass index >25 kg/m2 were associated with higher BP and previous myocardial infarction with lower BP. For the third consecutive year we collected a nation-wide snapshot of BP control in a large sample of individuals. The high participation, with some yearly fluctuations likely due to the limitations of the sampling technique, confirms the power of this kind of health campaign in reaching a significant number of people to raise awareness on health topics.
Published: 2021

37. The importance of including uric acid in the definition of metabolic syndrome when assessing the mortality risk

Author: Pugliese, N, Mengozzi, A, Virdis, A, Casiglia, E, Tikhonoff, V, Cicero, A, Ungar, A, Rivasi, G, Salvetti, M, Barbagallo, C, Bombelli, M, Dell'Oro, R, Bruno, B, Lippa, L, D'Elia, L, Verdecchia, P, Mallamaci, F, Cirillo, M, Rattazzi, M, Cirillo, P, Gesualdo, L, Mazza, A, Giannattasio, C, Maloberti, A, Volpe, M, Tocci, G, Georgiopoulos, G, Iaccarino, G, Nazzaro, P, Parati, G, Palatini, P, Galletti, F, Ferri, C, Desideri, G, Viazzi, F, Pontremoli, R, Muiesan, M, Grassi, G, Masi, S, Borghi, C, Pugliese N. R., Mengozzi A., Virdis A., Casiglia E., Tikhonoff V., Cicero A. F. G., Ungar A., Rivasi G., Salvetti M., Barbagallo C. M., Bombelli M., Dell'Oro R., Bruno B., Lippa L., D'Elia L., Verdecchia P., Mallamaci F., Cirillo M., Rattazzi M., Cirillo P., Gesualdo L., Mazza A., Giannattasio C., Maloberti A., Volpe M., Tocci G., Georgiopoulos G., Iaccarino G., Nazzaro P., Parati G., Palatini P., Galletti F., Ferri C., Desideri G., Viazzi F., Pontremoli R., Muiesan M. L., Grassi G., Masi S., Borghi C., Pugliese, N, Mengozzi, A, Virdis, A, Casiglia, E, Tikhonoff, V, Cicero, A, Ungar, A, Rivasi, G, Salvetti, M, Barbagallo, C, Bombelli, M, Dell'Oro, R, Bruno, B, Lippa, L, D'Elia, L, Verdecchia, P, Mallamaci, F, Cirillo, M, Rattazzi, M, Cirillo, P, Gesualdo, L, Mazza, A, Giannattasio, C, Maloberti, A, Volpe, M, Tocci, G, Georgiopoulos, G, Iaccarino, G, Nazzaro, P, Parati, G, Palatini, P, Galletti, F, Ferri, C, Desideri, G, Viazzi, F, Pontremoli, R, Muiesan, M, Grassi, G, Masi, S, Borghi, C, Pugliese N. R., Mengozzi A., Virdis A., Casiglia E., Tikhonoff V., Cicero A. F. G., Ungar A., Rivasi G., Salvetti M., Barbagallo C. M., Bombelli M., Dell'Oro R., Bruno B., Lippa L., D'Elia L., Verdecchia P., Mallamaci F., Cirillo M., Rattazzi M., Cirillo P., Gesualdo L., Mazza A., Giannattasio C., Maloberti A., Volpe M., Tocci G., Georgiopoulos G., Iaccarino G., Nazzaro P., Parati G., Palatini P., Galletti F., Ferri C., Desideri G., Viazzi F., Pontremoli R., Muiesan M. L., Grassi G., Masi S., and Borghi C.
Abstract: Introduction: Serum uric acid (SUA) has been depicted as a contributory causal factor in metabolic syndrome (MS), which in turn, portends unfavourable prognosis. Aim: We assessed the prognostic role of SUA in patients with and without MS. Methods: We used data from the multicentre Uric Acid Right for Heart Health study and considered cardiovascular mortality (CVM) as death due to fatal myocardial infarction, stroke, sudden cardiac death, or heart failure. Results: A total of 9589 subjects (median age 58.5 years, 45% males) were included in the analysis, and 5100 (53%) patients had a final diagnosis of MS. After a median follow-up of 142 months, we observed 558 events. Using a previously validated cardiovascular SUA cut-off to predict CVM (> 5.1 mg/dL in women and 5.6 mg/dL in men), elevated SUA levels were significantly associated to a worse outcome in patients with and without MS (all p < 0.0001) and provided a significant net reclassification improvement of 7.1% over the diagnosis of MS for CVM (p = 0.004). Cox regression analyses identified an independent association between SUA and CVM (Hazard Ratio: 1.79 [95% CI, 1.15–2.79]; p < 0.0001) after the adjustment for MS, its single components and renal function. Three specific combinations of the MS components were associated with higher CVM when increasing SUA levels were reported, and systemic hypertension was the only individual component ever-present (all p < 0.0001). Conclusion: Increasing SUA levels are associated with a higher CVM risk irrespective of the presence of MS: a cardiovascular SUA threshold may improve risk stratification. Graphic abstract: [Figure not available: see fulltext.]
Published: 2021

38. Possible Advantages Deriving from Patiromer Use in Hypertensive Patients Made Hyperkalemic by Renin–Angiotensin–Aldosterone Blocking Agents

Author: Borghi, C, Ferri, C, Pontremoli, R, Sechi, L, Grassi, G, Borghi C., Ferri C., Pontremoli R., Sechi L., Grassi G., Borghi, C, Ferri, C, Pontremoli, R, Sechi, L, Grassi, G, Borghi C., Ferri C., Pontremoli R., Sechi L., and Grassi G.
Abstract: Hyperkalemia is an elevated level of serum potassium (K+) and does represent a life-threatening condition. In clinical practice, hyperkalemia mainly derives from an impaired renal K+ excretion which, in turn, is usually caused by either acute or chronic renal failure. In concordance with this, hyperkalemia is very common in several chronic conditions, such as kidney disease, diabetes mellitus, heart failure, hypertension, and coronary heart disease. In all of these conditions the use of Renin–Angiotensin–Aldosterone System inhibitors (RAASIs), such as angiotensin-converting enzyme inhibitors (ACEIs) and angiotensin receptor blockers (ARBs), and mineralocorticoid receptor antagonist is widely recommended and further increases the risk of hyperkalemia. As hypertension is concerned, clinical trials suggest that the risk of hyperkalemia associated with RAASIs ranges from 2 to 10%. This often leads to a reduction or complete cessation of RAASIs, leaving patients without protective medications. Patiromer, a new oral potassium-binding agent, has been approved for clinical use in several countries, including Europe and US. Clinical studies have demonstrated that patiromer is effective in inducing a rapid and sustained K+ reduction in various patient settings, including those where RAASIs are a fundamental component of cardiorenal protection. Patiromer is generally well tolerated and characterised by a good safety profile. Most importantly, patiromer use might allow the continuation of ACEIs and ARBs in hypertensive patients developing hyperkalemia during treatment and thereby favour a more effective and long-lasting cardiorenal protection.
Published: 2021

39. Hypertension and Periodontitis: A Joint Report by the Italian Society of Hypertension (SIIA) and the Italian Society of Periodontology and Implantology (SIdP)

Author: Del Pinto, R, Landi, L, Grassi, G, Sforza, N, Cairo, F, Citterio, F, Paolantoni, G, D'Aiuto, F, Ferri, C, Monaco, A, Pietropaoli, D, Del Pinto R., Landi L., Grassi G., Sforza N. M., Cairo F., Citterio F., Paolantoni G., D'Aiuto F., Ferri C., Monaco A., Pietropaoli D., Del Pinto, R, Landi, L, Grassi, G, Sforza, N, Cairo, F, Citterio, F, Paolantoni, G, D'Aiuto, F, Ferri, C, Monaco, A, Pietropaoli, D, Del Pinto R., Landi L., Grassi G., Sforza N. M., Cairo F., Citterio F., Paolantoni G., D'Aiuto F., Ferri C., Monaco A., and Pietropaoli D.
Abstract: An accumulating body of evidence supports an independent association between high blood pressure (BP) and periodontitis, possibly mediated by low-grade inflammation. This joint report by the Italian Society of Hypertension (SIIA) and the Italian Society of Periodontology and Implantology (SIdP) working group on Hypertension and Periodontitis (Hy-Per Group) provides a review of the evidence on this topic encompassing epidemiology, biological plausibility, relevance, magnitude, and treatment management. Consensus recommendations are provided for health professionals on how to manage BP in individuals showing signs of poor oral health. In summary, (1) large epidemiological studies highlight that individuals with periodontal diseases have increased risk for high/uncontrolled BP independent of confounders; (2) mechanistically, low-grade inflammation might have a causal role in the association; (3) BP profile and control might benefit from periodontal treatment in pre-hypertensive and hypertensive individuals; (4) oral health status should be evaluated as a potential risk factor for high/uncontrolled BP, and effective oral care should be included as an adjunct lifestyle measure during hypertension management. Further research is needed to optimize BP management in individuals with poor oral health.
Published: 2021

40. Real-World Hypertension Prevalence, Awareness, Treatment, and Control in Adult Diabetic Individuals: An Italian Nationwide Epidemiological Survey

Author: De Feo, M, Del Pinto, R, Pagliacci, S, Grassi, D, Ferri, C, Grassi, G, Muiesan, M, Salvetti, M, Sechi, L, Cicero, A, Iaccarino, G, Minuz, P, Mulatero, P, Mule, G, Pucci, G, Savoia, C, Borghi, C, Volpe, M, De Feo M., Del Pinto R., Pagliacci S., Grassi D., Ferri C., Grassi G., Muiesan M. L., Salvetti M., Sechi L., Cicero A. F. G., Iaccarino G., Minuz P., Mulatero P., Mule G., Pucci G., Savoia C., Borghi C., Volpe M., De Feo, M, Del Pinto, R, Pagliacci, S, Grassi, D, Ferri, C, Grassi, G, Muiesan, M, Salvetti, M, Sechi, L, Cicero, A, Iaccarino, G, Minuz, P, Mulatero, P, Mule, G, Pucci, G, Savoia, C, Borghi, C, Volpe, M, De Feo M., Del Pinto R., Pagliacci S., Grassi D., Ferri C., Grassi G., Muiesan M. L., Salvetti M., Sechi L., Cicero A. F. G., Iaccarino G., Minuz P., Mulatero P., Mule G., Pucci G., Savoia C., Borghi C., and Volpe M.
Abstract: Introduction: Hypertesion is the leading cause of morbidity and mortality, worldwide, and its prevalence has been increasing in several countries, including Italy. Aims: To assess hypertension prevalence, awareness, treatment, and control in a real-world sample of adults with self-reported diabetes compared with nondiabetic individuals. Methods: Following the 2018 World Hypertension Day, a nationwide, cross-sectional epidemiological survey on cardiovascular risk factors (“Abbasso la Pressione!”) in 3956 Italian pharmacies enrolled 47217 self-presenting volunteers (≥ 18 years). Participants underwent standardized blood pressure (BP) measurements and answered a questionnaire on cardiovascular risk factors and lifestyle habits. Questions included if they had an established diagnosis of diabetes, hypertension or were on a BP medication. Hypertension prevalence was defined as systolic BP ≥ 140 and/or diastolic BP ≥ 90 mmHg. A double definition for hypertension control based on the recent European and US guidelines on hypertension was applied. Results: Diabetic individuals (N = 5695, 12%) had higher rates of hypertension prevalence (80% vs. 54.7%, p < 0.001), awareness (85.6% vs 77.3%, p < 0.001) and treatment (85.8% vs. 76.7%, p < 0.001), but lower hypertension control rates (36.1% vs. 39.6% according to the 2018 European guidelines, p < 0.001; 25.4% vs 30.8% according to the 2017 US guidelines, p < 0.001) than nondiabetics. Diabetic participants tended to be older, sedentary, overweight/obese, dyslipidemic men, with higher 10-years cardiovascular risk than nondiabetics (p < 0.001). Uncontrolled hypertension was associated with male gender, diabetes, body mass index, unhealthy lifestyle habits, and older age. Conclusions: Elevated hypertension awareness and treatment rates in diabetic adults do not translate into adequate BP control in the real world. Concomitant unfavorable metabolic features and unhealthy lifestyle habits migh
Published: 2021

41. The UrgeRe (Urgenze Ipertensive: Un Progetto Educazionale Fondato Sulla Vita Reale, Hypertensive Urgencies: A Project in the Real World) Project

Author: Muiesan, M, Rosei, E, Borghi, C, De Luca, N, Ghiadoni, L, Grassi, G, Perlini, S, Pucci, G, Salvetti, M, Volpe, M, Ferri, C, Muiesan M. L., Rosei E. A., Borghi C., De Luca N., Ghiadoni L., Grassi G., Perlini S., Pucci G., Salvetti M., Volpe M., Ferri C., Muiesan, M, Rosei, E, Borghi, C, De Luca, N, Ghiadoni, L, Grassi, G, Perlini, S, Pucci, G, Salvetti, M, Volpe, M, Ferri, C, Muiesan M. L., Rosei E. A., Borghi C., De Luca N., Ghiadoni L., Grassi G., Perlini S., Pucci G., Salvetti M., Volpe M., and Ferri C.
Abstract: The approach to hypertensive emergiencies (HE) and urgencies (HU) may be different according to local clinical practice, despite recent guidelines and position papers recommendations. The Italian Society of Hypertension (Società Italiana della Ipertensione Arteriosa, SIIA) developed an online survey, in order to explore the awareness, management and treatment of HU in Italy, sending by e mail a 12 items questionnaire to the members of the SIIA. The results show that the definition of HU was correctly identified by 62% of the responders. Most physicians identified the role of pharmacological therapy or legal/illegal substances abuse as possible cause of BP elevation; the use of a benzodiazepine drugs was considered worthwhile by 65% of responders. The prescription of diagnostic test and drug administration significantly differed from guidelines recommendations and only 57% of the physicians reported to treat HU with oral drug administration. Sub-lingual nifedipine was prescribed by 13% or responders. This survey shows the need to further spread the updated scientific information on the management and treatment of HE and HU, along with the improvement of the interrelationship with the general practitioner health system in Italy.
Published: 2021

42. Relationships between diuretic-related hyperuricemia and cardiovascular events: data from the URic acid Right for heArt Health study

Author: Maloberti, A, Bombelli, M, Facchetti, R, Barbagallo, C, Bernardino, B, Rosei, E, Casiglia, E, Cicero, A, Cirillo, M, Cirillo, P, Desideri, G, D'Elia, L, Dell'Oro, R, Ferri, C, Galletti, F, Giannattasio, C, Loreto, G, Iaccarino, G, Lippa, L, Mallamaci, F, Masi, S, Mazza, A, Muiesan, M, Nazzaro, P, Parati, G, Palatini, P, Pauletto, P, Pontremoli, R, Quarti-Trevano, F, Rattazzi, M, Rivasi, G, Salvetti, M, Tikhonoff, V, Tocci, G, Ungar, A, Verdecchia, P, Viazzi, F, Volpe, M, Virdis, A, Grassi, G, Borghi, C, Maloberti A., Bombelli M., Facchetti R., Barbagallo C. M., Bernardino B., Rosei E. A., Casiglia E., Cicero A. F. G., Cirillo M., Cirillo P., Desideri G., D'elia L., Dell'Oro R., Ferri C., Galletti F., Giannattasio C., Loreto G., Iaccarino G., Lippa L., Mallamaci F., Masi S., Mazza A., Muiesan M. L., Nazzaro P., Parati G., Palatini P., Pauletto P., Pontremoli R., Quarti-Trevano F., Rattazzi M., Rivasi G., Salvetti M., Tikhonoff V., Tocci G., Ungar A., Verdecchia P., Viazzi F., Volpe M., Virdis A., Grassi G., Borghi C., Maloberti, A, Bombelli, M, Facchetti, R, Barbagallo, C, Bernardino, B, Rosei, E, Casiglia, E, Cicero, A, Cirillo, M, Cirillo, P, Desideri, G, D'Elia, L, Dell'Oro, R, Ferri, C, Galletti, F, Giannattasio, C, Loreto, G, Iaccarino, G, Lippa, L, Mallamaci, F, Masi, S, Mazza, A, Muiesan, M, Nazzaro, P, Parati, G, Palatini, P, Pauletto, P, Pontremoli, R, Quarti-Trevano, F, Rattazzi, M, Rivasi, G, Salvetti, M, Tikhonoff, V, Tocci, G, Ungar, A, Verdecchia, P, Viazzi, F, Volpe, M, Virdis, A, Grassi, G, Borghi, C, Maloberti A., Bombelli M., Facchetti R., Barbagallo C. M., Bernardino B., Rosei E. A., Casiglia E., Cicero A. F. G., Cirillo M., Cirillo P., Desideri G., D'elia L., Dell'Oro R., Ferri C., Galletti F., Giannattasio C., Loreto G., Iaccarino G., Lippa L., Mallamaci F., Masi S., Mazza A., Muiesan M. L., Nazzaro P., Parati G., Palatini P., Pauletto P., Pontremoli R., Quarti-Trevano F., Rattazzi M., Rivasi G., Salvetti M., Tikhonoff V., Tocci G., Ungar A., Verdecchia P., Viazzi F., Volpe M., Virdis A., Grassi G., and Borghi C.
Abstract: Objective: Although the relationship between hyperuricemia and cardiovascular events has been extensively examined, data on the role of diuretic-related hyperuricemia are still scanty. The present study was designed to collect information on the relationship between diuretic-related hyperuricemia and cardiovascular events. Methods: The URic acid Right for heArt Health (URRAH) study is a nationwide, multicentre, observational cohort study involving data on individuals recruited from all the Italy territory under the patronage of the Italian Society of Hypertension with an average follow-up period of 122.3±66.9 months. Patients were classified into four groups according to the diuretic use (yes vs. no) and serum uric acid (SUA) levels (higher vs. lower than the median value of 4.8 mg/dl). All-cause death, cardiovascular deaths and first cardiovascular event were considered as outcomes. Results: Seventeen thousand, seven hundred and fortyseven individuals were included in the analysis. Mean age was 57.1±15.2 years, men were 45.3% and SBP and DBP amounted to 144.1±24.6 and 85.2±13.2 mmHg. 17.2% of individuals take diuretics of whom 58% had SUA higher than median value. Patients with hyperuricemia without diuretic use served as reference group. In multivariate adjusted analysis (sex, age, SBP, BMI, glucose, total cholesterol, and glomerular filtration rate) individuals with hyperuricemia and diuretic use exhibit a similar risk for the three outcomes as compared with the reference group. Conclusion: Our study showed that diuretic-related hyperuricemia carry a similar risk of cardiovascular events and all-cause mortality when compared with individuals that present hyperuricemia in absence of diuretic therapy.
Published: 2021

43. Association between sleep disordered breathing, neurocognitive impairment and diastolic function in acute heart failure patients: an insight after the vulnerable phase of the hospitalization

Author: D'Elia, E, Stamerra, C, Vecchi, A, Duino, V, Grosu, A, Abete, R, Baio, P, Gori, M, Gavazzi, A, Ferri, C, Senni, M, D'Elia E, Stamerra CA, Vecchi A, Duino V, Grosu A, Abete R, Baio P, Gori M, Gavazzi A, Ferri C, Senni M, D'Elia, E, Stamerra, C, Vecchi, A, Duino, V, Grosu, A, Abete, R, Baio, P, Gori, M, Gavazzi, A, Ferri, C, Senni, M, D'Elia E, Stamerra CA, Vecchi A, Duino V, Grosu A, Abete R, Baio P, Gori M, Gavazzi A, Ferri C, and Senni M
Abstract: Sleep disordered breathing (SDB) and neurocognitive impairment (NI) are a typical feature of HF (heart failure), especially with preserved ejection fraction (HFpEF). So far, very few data exist regarding changes in the severity of SDB, the degree of NI, and the diastolic function in acute HF (AHF) patients and during follow up. In a population of 24 AHF patients (12 with reduced ejection fraction-HFrEF- and 12 HFpEF) with SDB a complete echocardiogram, a set of NI tests, and a polysomnography were performed in the acute phase and after 90 days. A control group of 12 non-HF patients hospitalized for other cardiovascular causes was considered. At baseline, SDB were present both in HFpEF and HFrEF, and a consistent reduction of apneic events was observed at follow up. Improvements in diastolic and right ventricular function were documented at three months compared to baseline, both in HFpEF and in HFrEF. Compared to HFrEF patients and controls, HFpEF patients showed lower NI scores at baseline tests, but a more significant improvement at three months follow-up. In AHF patients with SDB the achievement of a better compensation could lead to important beneficial effect not only on echocardiographic variables and nocturnal respiratory profile, but also on NI, especially in HFpEF.
Published: 2021

44. A Smart Framework for Automatically Analyzing Electrocardiograms

Author: Persia, F, Costantini, S, Ferri, C, De, L, L, D'Auria, D, Persia F, Costantini S, Ferri C, de Lauretis, D'Auria D, Persia, F, Costantini, S, Ferri, C, De, L, L, D'Auria, D, Persia F, Costantini S, Ferri C, de Lauretis, and D'Auria D
Abstract: In the last months, due to the pandemic, telemedicine has been emerging more and more as a vital technology for providing medical care to patients, while also attempting to minimize COVID-19 transmission among patients, families, and medical doctors. This involves developing and exploiting virtual platforms enabling clinicians to remotely monitor patients' vitals, such as the blood pressure or the electrocardiogram (ECG). In this context, this paper aims at defining a smart framework for automatically analyzing electrocardiograms, to be used at the patient's home or at the entrance of First Aids, allowing to: (i) efficiently and effectively discover normal and anomalous situations in patient's ECGs; (ii) automatically collect ECGs from commercial and effective ECG devices; (iii) be integrated into a smart app, supported by intelligent agents, which promptly provides patients with feedback about their health status.
Published: 2021

45. How to Apply European and American Guidelines on High Blood Pressure in Children and Adolescents. A Position Paper Endorsed by the Italian Society of Hypertension and the Italian Society of Pediatrics

Author: Genovesi, S, Parati, G, Giussani, M, Bona, G, Fava, C, Maffeis, C, Ferri, C, Giordano, U, Genovesi S., Parati G., Giussani M., Bona G., Fava C., Maffeis C., Ferri C., Giordano U., Genovesi, S, Parati, G, Giussani, M, Bona, G, Fava, C, Maffeis, C, Ferri, C, Giordano, U, Genovesi S., Parati G., Giussani M., Bona G., Fava C., Maffeis C., Ferri C., and Giordano U.
Abstract: Children are defined as hypertensive when their blood pressure values equal or exceed the 95th percentile of the blood pressure value distribution in a pediatric population, according to gender, age and height. The population on which reference tables are based is of fundamental importance to establish the threshold values for the diagnosis of hypertension in pediatric age. Before 2017, both American and European guidelines used nomograms created in the same reference population which included children of all weight classes. Given the close and well-known association between hypertension and excess weight in childhood, the 2017 American guidelines proposed new reference nomograms excluding subjects with overweight and obesity from the “historical” reference population. Furthermore, the new American guidelines suggested a fixed cut-off of 130/80 mmHg, starting from 13 years and regardless of gender and height, to make the diagnosis of hypertension. In this document, the Italian Hypertension Society (SIIA) and the Italian Pediatric Society (SIP) jointly discuss a number of issues raised by the new American guidelines that involve the entire medical community, and also address the definition of arterial hypertension in the transition phase between childhood and adulthood.
Published: 2020

46. Systemic sclerosis Progression INvestiGation (SPRING) Italian registry: demographic and clinico-serological features of scleroderma spectrum

Author: Ferri, C, Giuggioli, D, Guiducci, S, Lumetti, F, Bajocchi, G, Magnani, L, Codullo, V, Ariani, A, Girelli, F, Riccieri, V, Pellegrino, G, Bosello, S, Foti, R, Visalli, E, Amato, G, Benenati, A, Cuomo, G, Iannone, F, Cacciapaglia, F, De Angelis, R, Ingegnoli, F, Talotta, R, Campochiaro, C, Dagna, L, De Luca, G, Bellando-Randone, S, Spinella, A, Murdaca, G, Romeo, N, De Santis, M, Generali, E, Barsotti, S, Della Rossa, A, Cavazzana, I, Dall'Ara, F, Lazzaroni, M, Cozzi, F, Doria, A, Pigatto, E, Zanatta, E, Ciano, G, Beretta, L, Abignano, G, D'Angelo, S, Mennillo, G, Bagnato, G, Calabrese, F, Caminiti, M, Pagano Mariano, G, Battaglia, E, Lubrano, E, Zanframundo, G, Iuliano, A, Furini, F, Zanetti, A, Carrara, G, Rumi, F, Scirè, C, Matucci-Cerinic, M, Ferri C, Giuggioli D, Guiducci S, Lumetti F, Bajocchi G, Magnani L, Codullo V, Ariani A, Girelli F, Riccieri V, Pellegrino G, Bosello S, Foti R, Visalli E, Amato G, Benenati A, Cuomo G, Iannone F, Cacciapaglia F, De Angelis R, Ingegnoli F, Talotta R, Campochiaro C, Dagna L, De Luca G, Bellando-Randone S, Spinella A, Murdaca G, Romeo N, De Santis M, Generali E, Barsotti S, Della Rossa A, Cavazzana I, Dall'Ara F, Lazzaroni MG, Cozzi F, Doria A, Pigatto E, Zanatta E, Ciano G, Beretta L, Abignano G, D'Angelo S, Mennillo G, Bagnato G, Calabrese F, Caminiti M, Pagano Mariano G, Battaglia E, Lubrano E, Zanframundo G, Iuliano A, Furini F, Zanetti A, Carrara G, Rumi F, Scirè CA, Matucci-Cerinic M, Ferri, C, Giuggioli, D, Guiducci, S, Lumetti, F, Bajocchi, G, Magnani, L, Codullo, V, Ariani, A, Girelli, F, Riccieri, V, Pellegrino, G, Bosello, S, Foti, R, Visalli, E, Amato, G, Benenati, A, Cuomo, G, Iannone, F, Cacciapaglia, F, De Angelis, R, Ingegnoli, F, Talotta, R, Campochiaro, C, Dagna, L, De Luca, G, Bellando-Randone, S, Spinella, A, Murdaca, G, Romeo, N, De Santis, M, Generali, E, Barsotti, S, Della Rossa, A, Cavazzana, I, Dall'Ara, F, Lazzaroni, M, Cozzi, F, Doria, A, Pigatto, E, Zanatta, E, Ciano, G, Beretta, L, Abignano, G, D'Angelo, S, Mennillo, G, Bagnato, G, Calabrese, F, Caminiti, M, Pagano Mariano, G, Battaglia, E, Lubrano, E, Zanframundo, G, Iuliano, A, Furini, F, Zanetti, A, Carrara, G, Rumi, F, Scirè, C, Matucci-Cerinic, M, Ferri C, Giuggioli D, Guiducci S, Lumetti F, Bajocchi G, Magnani L, Codullo V, Ariani A, Girelli F, Riccieri V, Pellegrino G, Bosello S, Foti R, Visalli E, Amato G, Benenati A, Cuomo G, Iannone F, Cacciapaglia F, De Angelis R, Ingegnoli F, Talotta R, Campochiaro C, Dagna L, De Luca G, Bellando-Randone S, Spinella A, Murdaca G, Romeo N, De Santis M, Generali E, Barsotti S, Della Rossa A, Cavazzana I, Dall'Ara F, Lazzaroni MG, Cozzi F, Doria A, Pigatto E, Zanatta E, Ciano G, Beretta L, Abignano G, D'Angelo S, Mennillo G, Bagnato G, Calabrese F, Caminiti M, Pagano Mariano G, Battaglia E, Lubrano E, Zanframundo G, Iuliano A, Furini F, Zanetti A, Carrara G, Rumi F, Scirè CA, and Matucci-Cerinic M
Abstract: Objectives: Systemic sclerosis (SSc) is a severe multiple-organ disease characterised by unpredictable clinical course, inadequate response to treatment, and poor prognosis. National SSc registries may provide large and representative patients cohorts required for descriptive and prognostic studies. Therefore, the Italian Society for Rheumatology promoted the registry SPRING (Systemic sclerosis Progression INvestiGation). Methods: The SPRING is a multi-centre rheumatological cohort study encompassing the wide scleroderma spectrum, namely the primary Raynaud's phenomenon (pRP), suspected secondary RP, Very Early Diagnosis of Systemic Sclerosis (VEDOSS), and definite SSc. Here we describe the demographic and clinical characteristics of a population of 2,028 Italian patients at the initial phase of enrolment, mainly focusing on the cohort of 1,538 patients with definite SSc. Results: Definite SSc showed a significantly higher prevalence of digital ulcers, capillaroscopic 'late' pattern, oesophageal and cardio-pulmonary involvement compared to VEDOSS, as expected on the basis of the followed classification criteria. The in-depth analysis of definite SSc revealed that male gender, diffuse cutaneous subset, and anti-Scl70 seropositivity were significantly associated with increased prevalence of the most harmful disease manifestations. Similarly, patients with very short RP duration (≤1 year) at SSc diagnosis showed a statistically increased prevalence of unfavourable clinico-serological features. Conclusions: Nationwide registries with suitable subsetting of patients and follow-up studies since the prodromal phase of the disease may give us valuable insights into the SSc natural history and main prognostic factors.
Published: 2020

47. Italian Society of Arterial Hypertension (SIIA) Position Paper on the Role of Renal Denervation in the Management of the Difficult-to-Treat Hypertensive Patient

Author: Bruno, R, Taddei, S, Borghi, C, Colivicchi, F, Desideri, G, Grassi, G, Mazza, A, Muiesan, M, Parati, G, Pontremoli, R, Trimarco, B, Volpe, M, Ferri, C, Bruno R. M., Taddei S., Borghi C., Colivicchi F., Desideri G., Grassi G., Mazza A., Muiesan M. L., Parati G., Pontremoli R., Trimarco B., Volpe M., Ferri C., Bruno, R, Taddei, S, Borghi, C, Colivicchi, F, Desideri, G, Grassi, G, Mazza, A, Muiesan, M, Parati, G, Pontremoli, R, Trimarco, B, Volpe, M, Ferri, C, Bruno R. M., Taddei S., Borghi C., Colivicchi F., Desideri G., Grassi G., Mazza A., Muiesan M. L., Parati G., Pontremoli R., Trimarco B., Volpe M., and Ferri C.
Abstract: Renal denervation is a device-based procedure for hypertension for which safety and efficacy has been demonstrated. At present, its clinical use is still matter of debate, despite the most recent clinical trials have shown promising results with new-generation devices in various hypertensive populations. This position paper was deemed necessary by the Italian Society of Arterial Hypertension, in order to provide indications about the applications of renal denervation in the clinical setting. A state-of-the art review of the literature, focusing on safety and efficacy data, is provided. Furthermore, based on current evidence and expert consensus, clinical profiles of possible candidates for renal denervation are proposed. The selection process should take into account not only blood pressure values, global cardiovascular risk profile, but also drug adherence and tolerability and patient preferences. This position paper also defines minimum requirements for renal denervation selection centers and a flowchart for the difficult-to-treat hypertensive patient. Further studies are needed to support these preliminary indications, which are based on expert-consensus only.
Published: 2020

48. Reduction of blood pressure variability: An additional protective cardiovascular effect of vasodilating beta-blockers?

Author: Del Pinto, R, Ferri, C, Parati, G, Del Pinto R., Ferri C., Parati G., Del Pinto, R, Ferri, C, Parati, G, Del Pinto R., Ferri C., and Parati G.
Published: 2020

49. World Hypertension Day 2021 in Italy: Results of a Nationwide Survey

Author: Del Pinto, R, Grassi, G, Lorenza Muiesan, M, Borghi, C, Carugo, S, Cicero, A, Di Meo, L, Iaccarino, G, Minuz, P, Mulatero, P, Mulè, G, Parati, G, Pucci, G, Salvetti, M, Sarzani, R, Savoia, C, Sechi, L, Tocci, G, Volpe, M, Vulpis, V, Ferri, C, Rita Del Pinto, Guido Grassi, Maria Lorenza Muiesan, Claudio Borghi, Stefano Carugo, Arrigo F. G. Cicero, Luciano Di Meo, Guido Iaccarino, Pietro Minuz, Paolo Mulatero, Giuseppe Mulè, Gianfranco Parati, Giacomo Pucci, Massimo Salvetti, Riccardo Sarzani, Carmine Savoia, Leonardo Sechi, Giuliano Tocci, Massimo Volpe, Vito Vulpis, Claudio Ferri, Del Pinto, R, Grassi, G, Lorenza Muiesan, M, Borghi, C, Carugo, S, Cicero, A, Di Meo, L, Iaccarino, G, Minuz, P, Mulatero, P, Mulè, G, Parati, G, Pucci, G, Salvetti, M, Sarzani, R, Savoia, C, Sechi, L, Tocci, G, Volpe, M, Vulpis, V, Ferri, C, Rita Del Pinto, Guido Grassi, Maria Lorenza Muiesan, Claudio Borghi, Stefano Carugo, Arrigo F. G. Cicero, Luciano Di Meo, Guido Iaccarino, Pietro Minuz, Paolo Mulatero, Giuseppe Mulè, Gianfranco Parati, Giacomo Pucci, Massimo Salvetti, Riccardo Sarzani, Carmine Savoia, Leonardo Sechi, Giuliano Tocci, Massimo Volpe, Vito Vulpis, and Claudio Ferri
Abstract: Introduction: Hypertension is the biggest contributor to the global burden of cardiovascular diseases and related death, but the rates of hypertension awareness, treatment, and control remain largely perfectible. Methods: During the XVII World Hypertension Day (May 17th, 2021), a nationwide cross-sectional opportunistic study endorsed by the Italian Society of Hypertension was conducted on volunteer adults ≥ 18 years to raise awareness of high blood pressure (BP). A questionnaire on major demographic/clinical features (sex, age, employment, education, BP status awareness, hypertension family/personal history, antihypertensive medications use) and BP measurement habits (≥1 BP measurement in the previous month/week) was administered. Due to the ongoing SARS-CoV-2 pandemic, BP was measured with standard procedures in a subset of participants (24.4%). Results: A total of 1354 participants (mean age 56.3 ± 15.3 years; 57.3% women; mean BP: 131.2 ± 17.5/81.6 ± 10.5 mmHg; 42.3% self-declared hypertensive; 41.4% on antihypertensive medications) were enrolled; 73.6% declared being aware of their BP status. Among treated individuals with measured BP, 26.9% showed BP levels within the predefined therapeutic goals. Interestingly, BP status awareness rates were the highest among individuals with uncontrolled hypertension (85.1%) and the lowest among those with normal measured BP (54.4%). Conclusions: This survey provides an updated insight into hypertension awareness and control in a setting of daily clinical practice, emphasizing the centricity of patients in the therapeutic alliance for a successful reduction of cardiovascular risk.
Published: 2022

50. Sex-related Differences in Systemic Sclerosis: A Multicenter Cross-sectional Study From the National Registry of the Italian Society for Rheumatology

Author: de Angelis, R., Giuggioli, D., Bajocchi, G., Dagna, L., Zanframundo, G., Foti, R., Cacciapaglia, F., Cuomo, G., Ariani, A., Rosato, E., Guiducci, S., Girelli, F., Riccieri, V., Zanatta, E., Bosello, Silvia Laura, Cavazzana, I., Ingegnoli, F., de Santis, M., Murdaca, G., Abignano, G., Romeo, N., Rossa, A. D., Caminiti, M., Iuliano, A., Ciano, G., Beretta, L., Bagnato, G., Lubrano, E., de Andres, I., Giollo, A., Saracco, M., Agnes, C., Lumetti, F., Spinella, A., Magnani, L., Campochiaro, C., de Luca, G., Codullo, V., Visalli, E., Masini, F., Gigante, A., Bellando-Randone, S., Pellegrino, G., Pigatto, E., Dall'Ara, F., Lazzaroni, M. G., Generali, E., Mennillo, G., Barsotti, S., Mariano, G. P., Calabrese, F., Furini, F., Vultaggio, L., Parisi, S., Peroni, C. L., Risa, A. M., Rozza, D., Zanetti, A., Carrara, G., Landolfi, G., Scire, C. A., Bianchi, G., Fusaro, E., Sebastiani, Gian Domenico, Govoni, M., D'Angelo, S., Cozzi, F., Doria, A., Iannone, F., Salvarani, C., Matucci-Cerinic, M., Ferri, C., Bosello S. (ORCID:0000-0002-4837-447X), Sebastiani G. D., de Angelis, R., Giuggioli, D., Bajocchi, G., Dagna, L., Zanframundo, G., Foti, R., Cacciapaglia, F., Cuomo, G., Ariani, A., Rosato, E., Guiducci, S., Girelli, F., Riccieri, V., Zanatta, E., Bosello, Silvia Laura, Cavazzana, I., Ingegnoli, F., de Santis, M., Murdaca, G., Abignano, G., Romeo, N., Rossa, A. D., Caminiti, M., Iuliano, A., Ciano, G., Beretta, L., Bagnato, G., Lubrano, E., de Andres, I., Giollo, A., Saracco, M., Agnes, C., Lumetti, F., Spinella, A., Magnani, L., Campochiaro, C., de Luca, G., Codullo, V., Visalli, E., Masini, F., Gigante, A., Bellando-Randone, S., Pellegrino, G., Pigatto, E., Dall'Ara, F., Lazzaroni, M. G., Generali, E., Mennillo, G., Barsotti, S., Mariano, G. P., Calabrese, F., Furini, F., Vultaggio, L., Parisi, S., Peroni, C. L., Risa, A. M., Rozza, D., Zanetti, A., Carrara, G., Landolfi, G., Scire, C. A., Bianchi, G., Fusaro, E., Sebastiani, Gian Domenico, Govoni, M., D'Angelo, S., Cozzi, F., Doria, A., Iannone, F., Salvarani, C., Matucci-Cerinic, M., Ferri, C., Bosello S. (ORCID:0000-0002-4837-447X), and Sebastiani G. D.
Abstract: Objective. There is still a great deal to learn about the influence of sex in systemic sclerosis (SSc). In this respect, national registries provide large and homogeneous patient cohorts for analytical studies. We therefore investigated a wide-ranging and well-characterized SSc series with the aim of identifying sex differences in disease expression, with a special focus on demographic, clinical, and serological characteristics. Methods. A multicenter SSc cohort of 2281 patients, including 247 men, was recruited in the Italian Systemic sclerosis PRogression INvestiGation (SPRING) registry. Demographic data, disease manifestations, serological profile, and internal organ involvement were compared. Results. The overall female/male ratio was 8.2:1. Female/male ratios for limited cutaneous SSc, diffuse cutaneous SSc, and SSc sine scleroderma subsets were 8.7:1, 4.9:1, and 10.7:1, respectively. A shorter time from onset of Raynaud phenomenon to SSc diagnosis, an increased prevalence of the diffuse cutaneous subset, renal crisis, and digital ulcers were found in males, whereas a significantly higher percentage of sicca syndrome, serum antinuclear antibodies, antiextractable nuclear antigens, anti-La/SSB, and anticentromere protein B was detected in the female group. Males exhibited lower left ventricular ejection fraction, as well as higher prevalence of conduction blocks, arrhythmias, ground glass, and honeycombing. Moreover, forced vital capacity and total lung capacity were medially lower in men than in women. Finally, males were more frequently treated with immunosuppressive drugs. Conclusion. Our study further supports the presence of several sex-related differences in patients with SSc. These differences were pronounced in the severity of cutaneous, peripheral vascular, and cardiopulmonary involvement for male patients, whereas an increased prevalence of sicca syndrome and a specific autoantibody profile characterized the female sex.
Published: 2022

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