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2. [Untitled]

Author

Albrecht M, Nica M, Colombo D, Ferri C, Tadini P, Introini U, and Bandello F

Subjects
Medical technology, R855-855.5
Published
2018
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3. 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

4. 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

5. 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

6. POS0821 MENOPAUSE AND SYSTEMIC SCLEROSIS: THE LINK BETWEEN MENOPAUSAL AGE, DISEASE ONSET AND CLINICAL MANIFESTATIONS IN AN ANALYSIS OF THE SPRING-SIR REGISTRY

Author

Orlandi, M., primary, Giuggioli, D., additional, De Angelis, R., additional, Riccieri, V., additional, Ingegnoli, F., additional, Cacciapaglia, F., additional, Campochiaro, C., additional, Codullo, V., additional, Guiducci, S., additional, Bellando-Randone, S., additional, Ferri, C., additional, Matucci-Cerinic, M., additional, and Bruni, C., additional

Published
2024
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7. AB1183 THE USE OF MYCOPHENOLATE MOFETIL IN LIMITED CUTANEOUS SYSTEMIC SCLEROSIS IS ASSOCIATED WITH A REDUCED RISK OF VASCULAR COMPLICATIONS REQUIRING PHARMACOLOGICAL INTERVENTION UPGRADES

Author

De Lorenzis, E., primary, Bosello, S. L., additional, Cacciapaglia, F., additional, De Angelis, R., additional, Cipolletta, E., additional, Natalello, G., additional, D’agostino, M. A., additional, Codullo, V., additional, De Luca, G., additional, Giuggioli, D., additional, Ingegnoli, F., additional, Riccieri, V., additional, Ferri, C., additional, and Matucci-Cerinic, M., additional

Published
2024
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8. POS1479-HPR TRAVEL DISTANCE TO TERTIARY HEALTHCARE REFLECTS DISEASE SEVERITY AND MEDICATION ACCESS IN SYSTEMIC SCLEROSIS PATIENTS: INSIGHTS FROM THE ITALIAN SPRING REGISTRY

Author

De Lorenzis, E., primary, Natalello, G., additional, Cacciapaglia, F., additional, De Angelis, R., additional, Cipolletta, E., additional, D’agostino, M. A., additional, Codullo, V., additional, De Luca, G., additional, Giuggioli, D., additional, Ingegnoli, F., additional, Riccieri, V., additional, Ferri, C., additional, Matucci-Cerinic, M., additional, and Bosello, S. L., additional

Published
2024
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14. AB1197 THE PREDICTIVE ROLE OF THE TAPSE/sPAP RATIO FOR CARDIOVASCULAR EVENTS AND MORTALITY IN SYSTEMIC SCLEROSIS COMPLICATED BY PULMONARY HYPERTENSION

Author

De Pinto, M., primary, Coppi, F., additional, Spinella, A., additional, Pagnoni, G., additional, Morgante, V., additional, Macripo’, P., additional, Guerra, A. F., additional, Secchi, O., additional, Orlandi, M., additional, Amati, G., additional, Lumetti, F., additional, Sandri, G., additional, Rossi, R., additional, Boriani, G., additional, Mattioli, A. V., additional, Ferri, C., additional, and Giuggioli, D., additional

Published
2024
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15. 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

17. 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

18. 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

19. 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

20. 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

21. Interplay of disorder and geometrical frustration in doped Gadolinium Gallium Garnet

Author

Woo, N., Silevitch, D. M., Ferri, C., Ghosh, S., and Rosenbaum, T. F.

Subjects
Condensed Matter - Strongly Correlated Electrons, Condensed Matter - Disordered Systems and Neural Networks
Abstract

The geometrically-frustrated, triangular antiferromagnet GGG exhibits a rich mix of short-range order and isolated quantum states. We investigate the effects of up to 1% Neodymium substitution for Gallium on the ac magnetic response at temperatures below 1 K in both the linear and nonlinear regimes. Substitutional disorder actually drives the system towards a more perfectly frustrated state, apparently compensating for the effect of imperfect Gadolinium/Gallium stoichiometry, while at the same time more closely demarcating the boundaries of isolated, coherent clusters composed of hundreds of spins. Optical measurements of the local Nd environment substantiate the picture of an increased frustration index with doping., Comment: 5 pages, 5 figures

Published
2015
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25. Hyperuricemia and Risk of Cardiovascular Outcomes: The Experience of the URRAH (Uric Acid Right for Heart Health) Project

Author

Maloberti, Alessandro, Giannattasio, C., Bombelli, M., Desideri, G., Cicero, A. F. G., Muiesan, M. L., Rosei, E. A., Salvetti, M., Ungar, A., Rivasi, G., Pontremoli, R., Viazzi, F., Facchetti, R., Ferri, C., Bernardino, B., Galletti, F., D’Elia, L., Palatini, P., Casiglia, E., Tikhonoff, V., Barbagallo, C. M., Verdecchia, P., Masi, S., Mallamaci, F., Cirillo, M., Rattazzi, M., Pauletto, P., Cirillo, P., Gesualdo, L., Mazza, A., Volpe, M., Tocci, G., Iaccarino, G., Nazzaro, P., Lippa, L., Parati, G., Dell’Oro, R., Quarti-Trevano, F., Grassi, G., Virdis, A., and Borghi, C.

Published
2020
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26. 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

27. 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

28. 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

33. May Measurement Month 2017: an analysis of blood pressure screening results worldwide

Author

Napiza-Granada, C, Sevilla, Ma. RC, Atilano, AA, Ona, DID, More, A, Jose, AP, Maheshwari, A, Kondal, D, Yu, W, Li, W, Xu, S, Yu, J, Zhang, H, Widyantoro, B, Turana, Y, Situmorang, TD, Sofiatin, Y, Barack, R, Lin, H-J, Wang, T-D, Chen, W-J, Sirenko, Y, Evstigneeva, O, Negresku, E, Yousif, ME, Medani, SA, Beheiry, HM, Ali, IA, Zilberman, JM, Marin, MJ, Rodriguez, PD, Garcia-Vasquez, F, Kramoh, KE, Ekoua, D, Lopez-Jaramillo, P, Otero, J, Sanchez, G, Narvaez, C, Accini, JL, Hernandez-Hernandez, R, Octavio, JA, Morr, I, Lopez-Rivera, J, Ojji, D, Arije, A, Babatunte, A, Wahab, KW, Fernandes, M, Pereira, SV, Valentim, M, Dzudie, A, Kingue, S, Djomou Ngongang, DA, Ogola, EN, Barasa, FA, Gitura, B, Malik, F-T-N, Choudhury, SR, Al Mamun, MA, Minh, VH, Viet, NL, Cao Truong, S, Ferri, C, Parati, G, Torlasco, C, Borghi, C, Goma, FM, Syatalimi, C, Zelveian, PH, Barbosa, E, Sebba Barroso, W, Penaherrera, E, Jarrin, E, Yusufali, A, Bazargani, N, Tsinamdzgvrishvili, B, Trapaidze, D, Neupane, D, Mishra, SR, Jozwiak, J, Malyszko, J, Konradi, A, Chazova, I, Ishaq, M, Memon, F, Heagerty, AM, Keitley, J, Brady, AJB, Cockcroft, JR, McDonnell, BJ, Lanas, F, Chia, Y-C, Ndhlovu, H, Kiss, I, Ruilope, LM, Ellenga Mbolla, BF, Milhailidou, AS, Woodiwiss, AJ, Perl, S, Dolan, E, Azevedo, V, Garre, L, Boggia, JG, Lee, VWY, Kowlessur, S, Miglinas, M, Sukackiene, D, Wainford, RD, Habonimana, D, Masupe, T, Ortellado, J, Wuerzner, G, Alcocer, L, Burazeri, G, Sanchez Delgado, E, Lovic, D, Mondo, CK, Mostafa, A, Nadar, SK, Valdez Tiburcio, O, Leiba, A, Dorobantu, M, De Backer, T, Chifamba, J, Stergiou, G, Nwokocha, CR, Sokolovic, S, Toure, AI, Connell, KL, Khan, NA, Burger, D, De Carvalho Rodrigues, M, Kramer, BK, Schmieder, RE, Unger, T, Wyss, FS, Yameogo, NV, Beistline, H, Kenerson, JG, Alfonso, B, Olsen, MH, Soares, M, Beaney, Thomas, Schutte, Aletta E, Tomaszewski, Maciej, Ariti, Cono, Burrell, Louise M, Castillo, Rafael R, Charchar, Fadi J, Damasceno, Albertino, Kruger, Ruan, Lackland, Daniel T, Nilsson, Peter M, Prabhakaran, Dorairaj, Ramirez, Agustin J, Schlaich, Markus P, Wang, Jiguang, Weber, Michael A, and Poulter, Neil R

Published
2018
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35. 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, ML, Parati, G, Montagna S, Pengo MF, Ferretti S, Borghi C, Ferri C, Grassi G, Muiesan ML, Parati G., Montagna, S, Pengo, M, Ferretti, S, Borghi, C, Ferri, C, Grassi, G, Muiesan, M, and Parati, G

Subjects
Hypertension Data analysis Prevention, Health Information Management, Prevention, Hypertension, Medicine (miscellaneous), Health Informatics, Data analysi, Information Systems
Abstract

Background: 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. Aim: We aimed to explore whether a machine learning (ML) algorithm can help identifying individuals predictors of hypertension. Methods: 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: 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). Conclusion: 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

36. 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. 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.

Subjects
Scleroderma, Systemic, Settore MED/16 - REUMATOLOGIA, Epidemiology, Immunology, Systemic, Autoimmunity, Autoimmune Disease, Autoimmune Diseases, Scleroderma, Rheumatology, Immunology and Allergy, Seasons, Human
Abstract

ObjectiveTo describe demographic, clinical and laboratory features of systemic sclerosis sine scleroderma (ssSSc) in a large multicentre systemic sclerosis (SSc) cohort.MethodsData 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.ResultsAmong 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) (pConclusionThe 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

37. Plasmon-induced enhancement of intra-ensemble FRET in quantum dots on wrinkled thin films

Author

Ferri, C. G. L, Inman, R. H, Rich, B., Gopinathan, A., Khine, M., and Ghosh, S.

Subjects
Energy-Transfer, Photoluminescence, Clusters, delta-opioid receptors, root ganglion neurons, trans-golgi network, knockout mice, in-vivo, functional competence, actin polymerization, activated receptor-2, binding proteins, cofilin activity
Published
2013

38. 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, 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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

39. 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

40. 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

41. 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

42. 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

43. 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

44. 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

45. 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

49. A first update on mapping the human genetic architecture of COVID-19

Author

COVID-19 Host Genetics Initiative, Pathak, GA, Karjalainen, J, Stevens, C, Neale, BM, Daly, M, Ganna, A, Andrews, SJ, Kanai, M, Cordioli, M, Polimanti, R, Harerimana, N, Pirinen, M, Liao, RG, Chwialkowska, K, Trankiem, A, Balaconis, MK, Nguyen, H, Solomonson, M, Veerapen, K, Wolford, B, Roberts, G, Park, D, Ball, CA, Coignet, M, McCurdy, S, Knight, S, Partha, R, Rhead, B, Zhang, M, Berkowitz, N, Gaddis, M, Noto, K, Ruiz, L, Pavlovic, M, Hong, EL, Rand, K, Girshick, A, Guturu, H, Baltzell, AH, Niemi, MEK, Rahmouni, S, Guntz, J, Beguin, Y, Pigazzini, S, Nkambule, L, Georges, M, Moutschen, M, Misset, B, Darcis, G, Guiot, J, Azarzar, S, Gofflot, S, Claassen, S, Malaise, O, Huynen, P, Meuris, C, Thys, M, Jacques, J, Leonard, P, Frippiat, F, Giot, J-B, Sauvage, A-S, Frenckell, CV, Belhaj, Y, Lambermont, B, Nakanishi, T, Morrison, DR, Mooser, V, Richards, JB, Butler-Laporte, G, Forgetta, V, Li, 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, Afilalo, J, Afilalo, M, Oliveira, M, Brenner, B, Brassard, N, Durand, M, Schurr, E, Lepage, P, Ragoussis, J, Auld, D, Chassé, M, Kaufmann, DE, Lathrop, GM, Adra, D, Hayward, C, Glessner, JT, Shaw, DM, Campbell, A, Morris, M, Hakonarson, H, Porteous, DJ, Below, J, Richmond, A, Chang, X, Polikowski, H, Lauren, PE, Chen, H-H, Wanying, Z, Fawns-Ritchie, C, North, K, McCormick, JB, Glessner, JR, Gignoux, CR, Wicks, SJ, Crooks, K, Barnes, KC, Daya, M, Shortt, J, Rafaels, N, Chavan, S, Timmers, PRHJ, Wilson, JF, Tenesa, A, Kerr, SM, D’Mellow, K, Shahin, D, El-Sherbiny, YM, von Hohenstaufen, KA, Sobh, A, Eltoukhy, MM, Nkambul, L, Elhadidy, TA, Abd Elghafar, MS, El-Jawhari, JJ, Mohamed, AAS, Elnagdy, MH, Samir, A, Abdel-Aziz, M, Khafaga, WT, El-Lawaty, WM, Torky, MS, El-shanshory, MR, Yassen, AM, Hegazy, MAF, Okasha, K, Eid, MA, Moahmed, HS, Medina-Gomez, C, Ikram, MA, Uitterlinden, AG, Mägi, R, Milani, L, Metspalu, A, Laisk, T, Läll, K, Lepamets, M, Esko, T, Reimann, E, Naaber, P, Laane, E, Pesukova, J, Peterson, P, Kisand, K, Tabri, J, Allos, R, Hensen, K, Starkopf, J, Ringmets, I, Tamm, A, Kallaste, A, Alavere, H, Metsalu, K, Puusepp, M, Batini, C, Tobin, MD, Venn, LD, Lee, PH, Shrine, N, Williams, AT, Guyatt, AL, John, C, Packer, RJ, Ali, A, Free, RC, Wang, X, Wain, LV, Hollox, EJ, Bee, CE, Adams, EL, Palotie, A, Ripatti, S, Ruotsalainen, S, Kristiansson, K, Koskelainen, S, Perola, M, Donner, K, Kivinen, K, Kaunisto, M, Rivolta, C, Bochud, P-Y, Bibert, S, Boillat, N, Nussle, SG, Albrich, W, Quinodoz, M, Kamdar, D, Suh, N, Neofytos, D, Erard, V, Voide, C, Friolet, R, Vollenweider, P, Pagani, JL, Oddo, M, zu Bentrup, FM, Conen, A, Clerc, O, Marchetti, O, Guillet, A, Guyat-Jacques, C, Foucras, S, Rime, M, Chassot, J, Jaquet, M, Viollet, RM, Lannepoudenx, Y, Portopena, L, Bochud, PY, Desgranges, F, Filippidis, P, Guéry, B, Haefliger, D, Kampouri, EE, Manuel, O, Munting, A, Papadimitriou-Olivgeris, M, Regina, J, Rochat-Stettler, L, Suttels, V, Tadini, E, Tschopp, J, Van Singer, M, Viala, B, Boillat-Blanco, N, Brahier, T, Hügli, O, Meuwly, JY, Pantet, O, Gonseth Nussle, S, Bochud, M, D’Acremont, V, Estoppey Younes, S, Albrich, WC, Cerny, A, O’Mahony, L, von Mering, C, Frischknecht, M, Kleger, G-R., Filipovic, M, Kahlert, CR, Wozniak, H, Negro, TR, Pugin, J, Bouras, K, Knapp, C, Egger, T, Perret, A, Montillier, P, di Bartolomeo, C, Barda, B, de Cid, R, Carreras, A, Moreno, V, Kogevinas, M, Galván-Femenía, I, Blay, N, Farré, X, Sumoy, L, Cortés, B, Mercader, JM, Guindo-Martinez, M, Torrents, D, Garcia-Aymerich, J, Castaño-Vinyals, G, Dobaño, C, Gori, M, Renieri, A, Mari, F, Mondelli, MU, Castelli, F, Vaghi, M, Rusconi, S, Montagnani, F, Bargagli, E, Franchi, F, Mazzei, MA, Cantarini, L, Tacconi, D, Feri, M, Scala, R, Spargi, G, Nencioni, C, Bandini, M, Caldarelli, GP, Canaccini, A, Ognibene, A, D’Arminio Monforte, A, Girardis, M, Antinori, A, Francisci, D, Schiaroli, E, Scotton, PG, Panese, S, Scaggiante, R, Monica, MD, Capasso, M, Fiorentino, G, Castori, M, Aucella, F, Biagio, AD, Masucci, L, Valente, S, Mandalà, M, Zucchi, P, Giannattasio, F, Coviello, DA, Mussini, C, Tavecchia, L, Crotti, L, Rizzi, M, Rovere, MTL, Sarzi-Braga, S, Bussotti, M, Ravaglia, S, Artuso, R, Perrella, A, Romani, D, Bergomi, P, Catena, E, Vincenti, A, Ferri, C, Grassi, D, Pessina, G, Tumbarello, M, Pietro, MD, Sabrina, R, Luchi, S, Furini, S, Dei, S, Benetti, E, Picchiotti, N, Sanarico, M, Ceri, S, Pinoli, P, Raimondi, F, Biscarini, F, Stella, A, Zguro, K, Capitani, K, Tanfoni, M, Fallerini, C, Daga, S, Baldassarri, M, Fava, F, Frullanti, E, Valentino, F, Doddato, G, Giliberti, A, Tita, R, Amitrano, S, Bruttini, M, Croci, S, Meloni, I, Mencarelli, MA, Rizzo, CL, Pinto, AM, Beligni, G, Tommasi, A, Sarno, LD, Palmieri, M, Carriero, ML, Alaverdian, D, Busani, S, Bruno, R, Vecchia, M, Belli, MA, Mantovani, S, Ludovisi, S, Quiros-Roldan, E, Antoni, MD, Zanella, I, Siano, M, Emiliozzi, A, Fabbiani, M, Rossetti, B, Bergantini, L, D’Alessandro, M, Cameli, P, Bennett, D, Anedda, F, Marcantonio, S, Scolletta, S, Guerrini, S, Conticini, E, Frediani, B, Spertilli, C, Donati, A, Guidelli, L, Corridi, M, Croci, L, Piacentini, P, Desanctis, E, Cappelli, S, Verzuri, A, Anemoli, V, Pancrazzi, A, Lorubbio, M, Miraglia, FG, Venturelli, S, Cossarizza, A, Vergori, A, Gabrieli, A, Riva, A, Paciosi, F, Andretta, F, Gatti, F, Parisi, SG, Baratti, S, Piscopo, C, Russo, R, Andolfo, I, Iolascon, A, Carella, M, Merla, G, Squeo, GM, Raggi, P, Marciano, C, Perna, R, Bassetti, M, Sanguinetti, M, Giorli, A, Salerni, L, Parravicini, P, Menatti, E, Trotta, T, Coiro, G, Lena, F, Martinelli, E, Mancarella, S, Gabbi, C, Maggiolo, F, Ripamonti, D, Bachetti, T, Suardi, C, Parati, G, Bottà, G, Domenico, PD, Rancan, I, Bianchi, F, Colombo, R, Barbieri, C, Acquilini, D, Andreucci, E, Segala, FV, Tiseo, G, Falcone, M, Lista, M, Poscente, M, Vivo, OD, Petrocelli, P, Guarnaccia, A, Baroni, S, van Heel, DA, Hunt, KA, Trembath, RC, Huang, QQ, Martin, HC, Mason, D, Trivedi, B, Wright, J, Finer, S, Akhtar, S, Anwar, M, Arciero, E, Ashraf, S, Breen, G, Chung, R, Curtis, CJ, Chowdhury, M, Colligan, G, Deloukas, P, Durham, C, Griffiths, C, Hurles, M, Hussain, S, Islam, K, Khan, A, Lavery, C, Lee, SH, Lerner, R, MacArthur, D, MacLaughlin, B, Martin, H, Miah, S, Newman, B, Safa, N, Tahmasebi, F, Griffiths, CJ, Smith, AV, Boughton, AP, Li, KW, LeFaive, J, Annis, A, Niavarani, A, Aliannejad, R, Sharififard, B, Amirsavadkouhi, A, Naderpour, Z, Tadi, HA, Aleagha, AE, Ahmadi, S, Moghaddam, SBM, Adamsara, A, Saeedi, M, Abdollahi, H, Hosseini, A, Chariyavilaskul, P, Jantarabenjakul, W, Hirankarn, N, Chamnanphon, M, Suttichet, TB, Shotelersuk, V, Pongpanich, M, Phokaew, C, Chetruengchai, W, Putchareon, O, Torvorapanit, P, Puthanakit, T, Suchartlikitwong, P, Nilaratanakul, V, Sodsai, P, Brumpton, BM, Hveem, K, Willer, C, Zhou, W, Rogne, T, Solligard, E, Åsvold, BO, Franke, L, Boezen, M, Deelen, P, Claringbould, A, Lopera, E, Warmerdam, R, Vonk, JM, van Blokland, I, Lanting, P, Ori, APS, Feng, Y-CA, Mercader, J, Weiss, ST, Karlson, EW, Smoller, JW, Murphy, SN, Meigs, JB, Woolley, AE, Green, RC, Perez, EF, Zöllner, S, Wang, J, Beck, A, Sloofman, LG, Ascolillo, S, Sebra, RP, Collins, BL, Levy, T, Buxbaum, JD, Sealfon, SC, Jordan, DM, Thompson, RC, Gettler, K, Chaudhary, K, Belbin, GM, Preuss, M, Hoggart, C, Choi, S, Underwood, SJ, Salib, I, Britvan, B, Keller, K, Tang, L, Peruggia, M, Hiester, LL, Niblo, K, Aksentijevich, A, Labkowsky, A, Karp, A, Zlatopolsky, M, Zyndorf, M, Charney, AW, Beckmann, ND, Schadt, EE, Abul-Husn, NS, Cho, JH, Itan, Y, Kenny, EE, Loos, RJF, Nadkarni, GN, Do, R, O’Reilly, P, Huckins, LM, Ferreira, MAR, Abecasis, GR, Leader, JB, Cantor, MN, Justice, AE, Carey, DJ, Chittoor, G, Josyula, NS, Kosmicki, JA, Horowitz, JE, Baras, A, Gass, MC, Yadav, A, Mirshahi, T, Hottenga, JJ, Bartels, M, de geus, EEJC, Nivard, MMG, Verma, A, Ritchie, MD, Rader, D, Li, B, Verma, SS, Lucas, A, Bradford, Y, Abedalthagafi, M, Alaamery, M, Alshareef, A, Sawaji, M, Massadeh, S, AlMalik, A, Alqahtani, S, Baraka, D, Harthi, FA, Alsolm, E, Safieh, LA, Alowayn, AM, Alqubaishi, F, Mutairi, AA, Mangul, S, Almutairi, M, Aljawini, N, Albesher, N, Arabi, YM, Mahmoud, ES, Khattab, AK, Halawani, RT, Alahmadey, ZZ, Albakri, JK, Felemban, WA, Suliman, BA, Hasanato, R, Al-Awdah, L, Alghamdi, J, AlZahrani, D, AlJohani, S, Al-Afghani, H, AlDhawi, N, AlBardis, H, Alkwai, S, Alswailm, M, Almalki, F, Albeladi, M, Almohammed, I, Barhoush, E, Albader, A, Alotaibi, S, Alghamdi, B, Jung, J, fawzy, MS, Alrashed, M, Zeberg, H, Frithiof, R, Hultström, M, Lipcsey, M, Tardif, N, Rooyackers, O, Grip, J, Maricic, T, Helgeland, Ø, Magnus, P, Trogstad, L-IS, Lee, Y, Harris, JR, Mangino, M, Spector, TD, Emma, D, Moutsianas, L, Caulfield, MJ, Scott, RH, Kousathanas, A, Pasko, D, Walker, S, Stuckey, A, Odhams, CA, Rhodes, D, Fowler, T, Rendon, A, Chan, G, Arumugam, P, Karczewski, KJ, Martin, AR, Wilson, DJ, Spencer, CCA, Crook, DW, Wyllie, DH, O’Connell, AM, Atkinson, EG, Tsuo, K, Baya, N, Turley, P, Gupta, R, Walters, RK, Palmer, DS, Sarma, G, Cheng, N, Lu, W, Churchhouse, C, Goldstein, JI, King, D, Seed, C, Daly, MJ, Finucane, H, Bryant, S, Satterstrom, FK, Band, G, Earle, SG, Lin, S-K, Arning, N, Koelling, N, Armstrong, J, Rudkin, JK, Callier, S, Cusick, C, Soranzo, N, Zhao, JH, Danesh, J, Angelantonio, ED, Butterworth, AS, Sun, YV, Huffman, JE, Cho, K, O’Donnell, CJ, Tsao, P, Gaziano, JM, Peloso, G, Ho, Y-L, Smieszek, SP, Polymeropoulos, C, Polymeropoulos, V, Polymeropoulos, MH, Przychodzen, BP, Fernandez-Cadenas, I, Planas, AM, Perez-Tur, J, Llucià-Carol, L, Cullell, N, Muiño, E, Cárcel-Márquez, J, DeDiego, ML, Iglesias, LL, Soriano, A, Rico, V, Agüero, D, Bedini, JL, Lozano, F, Domingo, C, Robles, V, Ruiz-Jaén, F, Márquez, L, Gomez, J, Coto, E, Albaiceta, GM, García-Clemente, M, Dalmau, D, Arranz, MJ, Dietl, B, Serra-Llovich, A, Soler, P, Colobrán, R, Martín-Nalda, A, Martínez, AP, Bernardo, D, Rojo, S, Fiz-López, A, Arribas, E, de la Cal-Sabater, P, Segura, T, González-Villa, E, Serrano-Heras, G, Martí-Fàbregas, J, Jiménez-Xarrié, E, de Felipe Mimbrera, A, Masjuan, J, García-Madrona, S, Domínguez-Mayoral, A, Villalonga, JM, Menéndez-Valladares, P, Chasman, DI, Sesso, HD, Manson, JE, Buring, JE, Ridker, PM, Franco, G, Davis, L, Lee, S, Priest, J, Sankaran, VG, van Heel, D, Biesecker, L, Kerchberger, VE, Baillie, JK, Pathak, Gita A., Karjalainen, Juha, Stevens, Christine, Neale, Benjamin M., Daly, Mark, Ganna, Andrea, Andrews, Shea J., Kanai, Masahiro, Cordioli, Mattia, Polimanti, Renato, Harerimana, Nadia, Pirinen, Matti, Liao, Rachel G., Chwialkowska, Karolina, Trankiem, Amy, Balaconis, Mary K., Nguyen, Huy, Solomonson, Matthew, Veerapen, Kumar, Wolford, Brooke, Roberts, Genevieve, Park, Danny, Ball, Catherine A., Coignet, Marie, McCurdy, Shannon, Knight, Spencer, Partha, Raghavendran, Rhead, Brooke, Zhang, Miao, Berkowitz, Nathan, Gaddis, Michael, Noto, Keith, Ruiz, Luong, Pavlovic, Milo, Hong, Eurie L., Rand, Kristin, Girshick, Ahna, Guturu, Harendra, Baltzell, Asher Haug, Niemi, Mari E. K., Rahmouni, Souad, Guntz, Julien, Beguin, Yve, Pigazzini, Sara, Nkambule, Lindokuhle, Georges, Michel, Moutschen, Michel, Misset, Benoit, Darcis, Gille, Guiot, Julien, Azarzar, Samira, Gofflot, Stéphanie, Claassen, Sabine, Malaise, Olivier, Huynen, Pascale, Meuris, Christelle, Thys, Marie, Jacques, Jessica, Léonard, Philippe, Frippiat, Frederic, Giot, Jean-Baptiste, Sauvage, Anne-Sophie, Frenckell, Christian Von, Belhaj, Yasmine, Lambermont, Bernard, Nakanishi, Tomoko, Morrison, David R., Mooser, Vincent, Richards, J. Brent, Butler-Laporte, Guillaume, Forgetta, Vincenzo, Li, Rui, Ghosh, Biswarup, Laurent, Laetitia, Belisle, Alexandre, Henry, Danielle, Abdullah, Tala, Adeleye, Olumide, Mamlouk, Noor, Kimchi, Nofar, Afrasiabi, Zaman, Rezk, Nardin, Vulesevic, Branka, Bouab, Meriem, Guzman, Charlotte, Petitjean, Loui, Tselios, Chri, Xue, Xiaoqing, Afilalo, Jonathan, Afilalo, Marc, Oliveira, Maureen, Brenner, Bluma, Brassard, Nathalie, Durand, Madeleine, Schurr, Erwin, Lepage, Pierre, Ragoussis, Jianni, Auld, Daniel, Chassé, Michaël, Kaufmann, Daniel E., Lathrop, G. Mark, Adra, Darin, Hayward, Caroline, Glessner, Joseph T., Shaw, Douglas M., Campbell, Archie, Morris, Marcela, Hakonarson, Hakon, Porteous, David J., Below, Jennifer, Richmond, Anne, Chang, Xiao, Polikowski, Hannah, Lauren, Petty E., Chen, Hung-Hsin, Wanying, Zhu, Fawns-Ritchie, Chloe, North, Kari, McCormick, Joseph B., Glessner, Joseph R., Gignoux, Christopher R., Wicks, Stephen J., Crooks, Kristy, Barnes, Kathleen C., Daya, Michelle, Shortt, Jonathan, Rafaels, Nichola, Chavan, Sameer, Timmers, Paul R. H. J., Wilson, James F., Tenesa, Albert, Kerr, Shona M., D’Mellow, Kenton, Shahin, Doaa, El-Sherbiny, Yasser M., von Hohenstaufen, Kathrin Aprile, Sobh, Ali, Eltoukhy, Madonna M., Nkambul, Lindokuhle, Elhadidy, Tamer A., Abd Elghafar, Mohamed S., El-Jawhari, Jehan J., Mohamed, Attia A. S., Elnagdy, Marwa H., Samir, Amr, Abdel-Aziz, Mahmoud, Khafaga, Walid T., El-Lawaty, Walaa M., Torky, Mohamed S., El-shanshory, Mohamed R., Yassen, Amr M., Hegazy, Mohamed A. F., Okasha, Kamal, Eid, Mohammed A., Moahmed, Hanteera S., Medina-Gomez, Carolina, Ikram, M. Arfan, Uitterlinden, Andre G., Mägi, Reedik, Milani, Lili, Metspalu, Andre, Laisk, Triin, Läll, Kristi, Lepamets, Maarja, Esko, Tõnu, Reimann, Ene, Naaber, Paul, Laane, Edward, Pesukova, Jaana, Peterson, Pärt, Kisand, Kai, Tabri, Jekaterina, Allos, Raili, Hensen, Kati, Starkopf, Joel, Ringmets, Inge, Tamm, Anu, Kallaste, Anne, Alavere, Helene, Metsalu, Kristjan, Puusepp, Mairo, Batini, Chiara, Tobin, Martin D., Venn, Laura D., Lee, Paul H., Shrine, Nick, Williams, Alexander T., Guyatt, Anna L., John, Catherine, Packer, Richard J., Ali, Altaf, Free, Robert C., Wang, Xueyang, Wain, Louise V., Hollox, Edward J., Bee, Catherine E., Adams, Emma L., Palotie, Aarno, Ripatti, Samuli, Ruotsalainen, Sanni, Kristiansson, Kati, Koskelainen, Sami, Perola, Marku, Donner, Kati, Kivinen, Katja, Kaunisto, Mari, Rivolta, Carlo, Bochud, Pierre-Yve, Bibert, Stéphanie, Boillat, Noémie, Nussle, Semira Gonseth, Albrich, Werner, Quinodoz, Mathieu, Kamdar, Dhryata, Suh, Noémie, Neofytos, Dionysio, Erard, Véronique, Voide, Cathy, Friolet, R., Vollenweider, P., Pagani, J. L., Oddo, M., zu Bentrup, F. Meyer, Conen, A., Clerc, O., Marchetti, O., Guillet, A., Guyat-Jacques, C., Foucras, S., Rime, M., Chassot, J., Jaquet, M., Viollet, R. Merlet, Lannepoudenx, Y., Portopena, L., Bochud, P. Y., Desgranges, F., Filippidis, P., Guéry, B., Haefliger, D., Kampouri, E. E., Manuel, O., Munting, A., Papadimitriou-Olivgeris, M., Regina, J., Rochat-Stettler, L., Suttels, V., Tadini, E., Tschopp, J., Van Singer, M., Viala, B., Boillat-Blanco, N., Brahier, T., Hügli, O., Meuwly, J. Y., Pantet, O., Gonseth Nussle, S., Bochud, M., D’Acremont, V., Estoppey Younes, S., Albrich, W. C., Suh, N., Cerny, A., O’Mahony, L., von Mering, C., Frischknecht, M., Kleger, G-R., Filipovic, M., Kahlert, C. R., Wozniak, H., Negro, T. Rochat, Pugin, J., Bouras, K., Knapp, C., Egger, T., Perret, A., Montillier, P., di Bartolomeo, C., Barda, B., de Cid, Rafael, Carreras, Anna, Moreno, Victor, Kogevinas, Manoli, Galván-Femenía, Iván, Blay, Natalia, Farré, Xavier, Sumoy, Lauro, Cortés, Beatriz, Mercader, Josep Maria, Guindo-Martinez, Marta, Torrents, David, Garcia-Aymerich, Judith, Castaño-Vinyals, Gemma, Dobaño, Carlota, Gori, Marco, Renieri, Alessandra, Mari, Francesca, Mondelli, Mario Umberto, Castelli, Francesco, Vaghi, Massimo, Rusconi, Stefano, Montagnani, Francesca, Bargagli, Elena, Franchi, Federico, Mazzei, Maria Antonietta, Cantarini, Luca, Tacconi, Danilo, Feri, Marco, Scala, Raffaele, Spargi, Genni, Nencioni, Cesira, Bandini, Maria, Caldarelli, Gian Piero, Canaccini, Anna, Ognibene, Agostino, D’Arminio Monforte, Antonella, Girardis, Massimo, Antinori, Andrea, Francisci, Daniela, Schiaroli, Elisabetta, Scotton, Pier Giorgio, Panese, Sandro, Scaggiante, Renzo, Monica, Matteo Della, Capasso, Mario, Fiorentino, Giuseppe, Castori, Marco, Aucella, Filippo, Biagio, Antonio Di, Masucci, Luca, Valente, Serafina, Mandalà, Marco, Zucchi, Patrizia, Giannattasio, Ferdinando, Coviello, Domenico A., Mussini, Cristina, Tavecchia, Luisa, Crotti, Lia, Rizzi, Marco, Rovere, Maria Teresa La, Sarzi-Braga, Simona, Bussotti, Maurizio, Ravaglia, Sabrina, Artuso, Rosangela, Perrella, Antonio, Romani, Davide, Bergomi, Paola, Catena, Emanuele, Vincenti, Antonella, Ferri, Claudio, Grassi, Davide, Pessina, Gloria, Tumbarello, Mario, Pietro, Massimo Di, Sabrina, Ravaglia, Luchi, Sauro, Furini, Simone, Dei, Simona, Benetti, Elisa, Picchiotti, Nicola, Sanarico, Maurizio, Ceri, Stefano, Pinoli, Pietro, Raimondi, Francesco, Biscarini, Filippo, Stella, Alessandra, Zguro, Kristina, Capitani, Katia, Tanfoni, Marco, Fallerini, Chiara, Daga, Sergio, Baldassarri, Margherita, Fava, Francesca, Frullanti, Elisa, Valentino, Floriana, Doddato, Gabriella, Giliberti, Annarita, Tita, Rossella, Amitrano, Sara, Bruttini, Mirella, Croci, Susanna, Meloni, Ilaria, Mencarelli, Maria Antonietta, Rizzo, Caterina Lo, Pinto, Anna Maria, Beligni, Giada, Tommasi, Andrea, Sarno, Laura Di, Palmieri, Maria, Carriero, Miriam Lucia, Alaverdian, Diana, Busani, Stefano, Bruno, Raffaele, Vecchia, Marco, Belli, Mary Ann, Mantovani, Stefania, Ludovisi, Serena, Quiros-Roldan, Eugenia, Antoni, Melania Degli, Zanella, Isabella, Siano, Matteo, Emiliozzi, Arianna, Fabbiani, Massimiliano, Rossetti, Barbara, Bergantini, Laura, D’Alessandro, Miriana, Cameli, Paolo, Bennett, David, Anedda, Federico, Marcantonio, Simona, Scolletta, Sabino, Guerrini, Susanna, Conticini, Edoardo, Frediani, Bruno, Spertilli, Chiara, Donati, Alice, Guidelli, Luca, Corridi, Marta, Croci, Leonardo, Piacentini, Paolo, Desanctis, Elena, Cappelli, Silvia, Verzuri, Agnese, Anemoli, Valentina, Pancrazzi, Alessandro, Lorubbio, Maria, Miraglia, Federica Gaia, Venturelli, Sophie, Cossarizza, Andrea, Vergori, Alessandra, Gabrieli, Arianna, Riva, Agostino, Paciosi, Francesco, Andretta, Francesca, Gatti, Francesca, Parisi, Saverio Giuseppe, Baratti, Stefano, Piscopo, Carmelo, Russo, Roberta, Andolfo, Immacolata, Iolascon, Achille, Carella, Massimo, Merla, Giuseppe, Squeo, Gabriella Maria, Raggi, Pamela, Marciano, Carmen, Perna, Rita, Bassetti, Matteo, Sanguinetti, Maurizio, Giorli, Alessia, Salerni, Lorenzo, Parravicini, Pierpaolo, Menatti, Elisabetta, Trotta, Tullio, Coiro, Gabriella, Lena, Fabio, Martinelli, Enrico, Mancarella, Sandro, Gabbi, Chiara, Maggiolo, Franco, Ripamonti, Diego, Bachetti, Tiziana, Suardi, Claudia, Parati, Gianfranco, Bottà, Giordano, Domenico, Paolo Di, Rancan, Ilaria, Bianchi, Francesco, Colombo, Riccardo, Barbieri, Chiara, Acquilini, Donatella, Andreucci, Elena, Segala, Francesco Vladimiro, Tiseo, Giusy, Falcone, Marco, Lista, Mirjam, Poscente, Monica, Vivo, Oreste De, Petrocelli, Paola, Guarnaccia, Alessandra, Baroni, Silvia, van Heel, David A., Hunt, Karen A., Trembath, Richard C., Huang, Qin Qin, Martin, Hilary C., Mason, Dan, Trivedi, Bhavi, Wright, John, Finer, Sarah, Akhtar, Shaheen, Anwar, Mohammad, Arciero, Elena, Ashraf, Samina, Breen, Gerome, Chung, Raymond, Curtis, Charles J., Chowdhury, Maharun, Colligan, Grainne, Deloukas, Pano, Durham, Ceri, Griffiths, Chri, Hurles, Matt, Hussain, Shapna, Islam, Kamrul, Khan, Ahsan, Khan, Amara, Lavery, Cath, Lee, Sang Hyuck, Lerner, Robin, MacArthur, Daniel, MacLaughlin, Bev, Martin, Hilary, Miah, Shefa, Newman, Bill, Safa, Nishat, Tahmasebi, Farah, Griffiths, Christopher J., Smith, Albert V., Boughton, Andrew P., Li, Kevin W., LeFaive, Jonathon, Annis, Aubrey, Niavarani, Ahmadreza, Aliannejad, Rasoul, Sharififard, Bahareh, Amirsavadkouhi, Ali, Naderpour, Zeinab, Tadi, Hengameh Ansari, Aleagha, Afshar Etemadi, Ahmadi, Saeideh, Moghaddam, Seyed Behrooz Mohseni, Adamsara, Alireza, Saeedi, Morteza, Abdollahi, Hamed, Hosseini, Abdolmajid, Chariyavilaskul, Pajaree, Jantarabenjakul, Watsamon, Hirankarn, Nattiya, Chamnanphon, Monpat, Suttichet, Thitima B., Shotelersuk, Vorasuk, Pongpanich, Monnat, Phokaew, Chureerat, Chetruengchai, Wanna, Putchareon, Opa, Torvorapanit, Pattama, Puthanakit, Thanyawee, Suchartlikitwong, Pintip, Nilaratanakul, Voraphoj, Sodsai, Pimpayao, Brumpton, Ben M., Hveem, Kristian, Willer, Cristen, Zhou, Wei, Rogne, Tormod, Solligard, Erik, Åsvold, Bjørn Olav, Franke, Lude, Boezen, Marike, Deelen, Patrick, Claringbould, Annique, Lopera, Esteban, Warmerdam, Robert, Vonk, Judith. M., van Blokland, Irene, Lanting, Pauline, Ori, Anil P. S., Feng, Yen-Chen Anne, Mercader, Josep, Weiss, Scott T., Karlson, Elizabeth W., Smoller, Jordan W., Murphy, Shawn N., Meigs, James B., Woolley, Ann E., Green, Robert C., Perez, Emma F., Zöllner, Sebastian, Wang, Jiongming, Beck, Andrew, Sloofman, Laura G., Ascolillo, Steven, Sebra, Robert P., Collins, Brett L., Levy, Te, Buxbaum, Joseph D., Sealfon, Stuart C., Jordan, Daniel M., Thompson, Ryan C., Gettler, Kyle, Chaudhary, Kumardeep, Belbin, Gillian M., Preuss, Michael, Hoggart, Clive, Choi, Sam, Underwood, Slayton J., Salib, Irene, Britvan, Bari, Keller, Katherine, Tang, Lara, Peruggia, Michael, Hiester, Liam L., Niblo, Kristi, Aksentijevich, Alexandra, Labkowsky, Alexander, Karp, Avromie, Zlatopolsky, Menachem, Zyndorf, Marissa, Charney, Alexander W., Beckmann, Noam D., Schadt, Eric E., Abul-Husn, Noura S., Cho, Judy H., Itan, Yuval, Kenny, Eimear E., Loos, Ruth J. F., Nadkarni, Girish N., Do, Ron, O’Reilly, Paul, Huckins, Laura M., Ferreira, Manuel A. R., Abecasis, Goncalo R., Leader, Joseph B., Cantor, Michael N., Justice, Anne E., Carey, Dave J., Chittoor, Geetha, Josyula, Navya Shilpa, Kosmicki, Jack A., Horowitz, Julie E., Baras, Ari, Gass, Matthew C., Yadav, Ashish, Mirshahi, Tooraj, Hottenga, Jouke Jan, Bartels, Meike, de geus, Eco E. J. C., Nivard, Michel M. G., Verma, Anurag, Ritchie, Marylyn D., Rader, Daniel, Li, Binglan, Verma, Shefali S., Lucas, Anastasia, Bradford, Yuki, Abedalthagafi, Malak, Alaamery, Manal, Alshareef, Abdulraheem, Sawaji, Mona, Massadeh, Salam, AlMalik, Abdulaziz, Alqahtani, Saleh, Baraka, Dona, Harthi, Fawz Al, Alsolm, Ebtehal, Safieh, Leen Abu, Alowayn, Albandary M., Alqubaishi, Fatimah, Mutairi, Amal Al, Mangul, Serghei, Almutairi, Mansour, Aljawini, Nora, Albesher, Nour, Arabi, Yaseen M., Mahmoud, Ebrahim S., Khattab, Amin K., Halawani, Roaa T., Alahmadey, Ziab Z., Albakri, Jehad K., Felemban, Walaa A., Suliman, Bandar A., Hasanato, Rana, Al-Awdah, Laila, Alghamdi, Jahad, AlZahrani, Deema, AlJohani, Sameera, Al-Afghani, Hani, AlDhawi, Nouf, AlBardis, Hadeel, Alkwai, Sarah, Alswailm, Moneera, Almalki, Faisal, Albeladi, Maha, Almohammed, Iman, Barhoush, Eman, Albader, Anoud, Alotaibi, Sara, Alghamdi, Bader, Jung, Junghyun, fawzy, Mohammad S., Alrashed, May, Zeberg, Hugo, Nkambul, Lindo, Frithiof, Robert, Hultström, Michael, Lipcsey, Miklo, Tardif, Nicola, Rooyackers, Olav, Grip, Jonathan, Maricic, Tomislav, Helgeland, Øyvind, Magnus, Per, Trogstad, Lill-Iren S., Lee, Yunsung, Harris, Jennifer R., Mangino, Massimo, Spector, Tim D., Emma, Duncan, Moutsianas, Louka, Caulfield, Mark J., Scott, Richard H., Kousathanas, Athanasio, Pasko, Dorota, Walker, Susan, Stuckey, Alex, Odhams, Christopher A., Rhodes, Daniel, Fowler, Tom, Rendon, Augusto, Chan, Georgia, Arumugam, Prabhu, Karczewski, Konrad J., Martin, Alicia R., Wilson, Daniel J., Spencer, Chris C. A., Crook, Derrick W., Wyllie, David H., O’Connell, Anne Marie, Atkinson, Elizabeth G., Tsuo, Kristin, Baya, Nikola, Turley, Patrick, Gupta, Rahul, Walters, Raymond K., Palmer, Duncan S., Sarma, Gopal, Cheng, Nathan, Lu, Wenhan, Churchhouse, Claire, Goldstein, Jacqueline I., King, Daniel, Seed, Cotton, Daly, Mark J., Finucane, Hilary, Bryant, Sam, Satterstrom, F. Kyle, Band, Gavin, Earle, Sarah G., Lin, Shang-Kuan, Arning, Nicola, Koelling, Nil, Armstrong, Jacob, Rudkin, Justine K., Callier, Shawneequa, Cusick, Caroline, Soranzo, Nicole, Zhao, Jing Hua, Danesh, John, Angelantonio, Emanuele Di, Butterworth, Adam S., Sun, Yan V., Huffman, Jennifer E., Cho, Kelly, O’Donnell, Christopher J., Tsao, Phil, Gaziano, J. Michael, Peloso, Gina, Ho, Yuk-Lam, Smieszek, Sandra P., Polymeropoulos, Christo, Polymeropoulos, Vasilio, Polymeropoulos, Mihael H., Przychodzen, Bartlomiej P., Fernandez-Cadenas, Israel, Planas, Anna M., Perez-Tur, Jordi, Llucià-Carol, Laia, Cullell, Natalia, Muiño, Elena, Cárcel-Márquez, Jara, DeDiego, Marta L., Iglesias, Lara Lloret, Soriano, Alex, Rico, Veronica, Agüero, Daiana, Bedini, Josep L., Lozano, Francisco, Domingo, Carlo, Robles, Veronica, Ruiz-Jaén, Francisca, Márquez, Leonardo, Gomez, Juan, Coto, Eliecer, Albaiceta, Guillermo M., García-Clemente, Marta, Dalmau, David, Arranz, Maria J., Dietl, Beatriz, Serra-Llovich, Alex, Soler, Pere, Colobrán, Roger, Martín-Nalda, Andrea, Martínez, Alba Parra, Bernardo, David, Rojo, Silvia, Fiz-López, Aida, Arribas, Elisa, de la Cal-Sabater, Paloma, Segura, Tomá, González-Villa, Esther, Serrano-Heras, Gemma, Martí-Fàbregas, Joan, Jiménez-Xarrié, Elena, de Felipe Mimbrera, Alicia, Masjuan, Jaime, García-Madrona, Sebastian, Domínguez-Mayoral, Anna, Villalonga, Joan Montaner, Menéndez-Valladares, Paloma, Chasman, Daniel I., Sesso, Howard D., Manson, JoAnn E., Buring, Julie E., Ridker, Paul M., Franco, Giulianini, Davis, Lea, Lee, Sulggi, Priest, Jame, Sankaran, Vijay G., van Heel, David, Biesecker, Le, Kerchberger, V. Eric, Baillie, J. Kenneth, APH - Personalized Medicine, APH - Health Behaviors & Chronic Diseases, Biological Psychology, APH - Mental Health, AMS - Sports, AMS - Ageing & Vitality, APH - Methodology, Mccurdy, Shannon, Mccormick, Joseph B., Macarthur, Daniel, Maclaughlin, Bev, Lefaive, Jonathon, Almalik, Abdulaziz, Alzahrani, Deema, Aljohani, Sameera, Aldhawi, Nouf, Albardis, Hadeel, Fawzy, Mohammad S., Dediego, Marta L., Stem Cell Aging Leukemia and Lymphoma (SALL), Groningen Institute for Gastro Intestinal Genetics and Immunology (3GI), Life Course Epidemiology (LCE), Groningen Research Institute for Asthma and COPD (GRIAC), University of Zurich, COVID-19 Host Genetics Initiative, Barcelona Supercomputing Center, COVID-19 Genetics Initiative, including authors, Institute for Molecular Medicine Finland, and Data Science Genetic Epidemiology Lab

Subjects
Informàtica::Aplicacions de la informàtica::Bioinformàtica [Àrees temàtiques de la UPC], Quantitative Trait Loci, MUC5B PROMOTER POLYMORPHISM, Genome-wide association studies, COVID-19 (Malaltia), UFSP13-7 Evolution in Action: From Genomes to Ecosystems, COVID-19 (Disease), Settore BIO/12 - BIOCHIMICA CLINICA E BIOLOGIA MOLECOLARE CLINICA, SDG 3 - Good Health and Well-being, Humans, genetics, Genetic variation, Genomes, Medicinsk genetik, 1000 Multidisciplinary, Multidisciplinary, Chromosome Mapping, COVID-19, Human Genetics, 10124 Institute of Molecular Life Sciences, covid-19, 3121 General medicine, internal medicine and other clinical medicine, 570 Life sciences, biology, Medical Genetics
Abstract

Matters arising from: Mapping the human genetic architecture of COVID-19 Original Article published on 08 July 2021 https://www.nature.com/articles/s41586-021-03767-x The COVID-19 pandemic continues to pose a major public health threat, especially in countries with low vaccination rates. To better understand the biological underpinnings of SARS-CoV-2 infection and COVID-19 severity, we formed the COVID-19 Host Genetics Initiative1. Here we present a genome-wide association study meta-analysis of up to 125,584 cases and over 2.5 million control individuals across 60 studies from 25 countries, adding 11 genome-wide significant loci compared with those previously identified2. Genes at new loci, including SFTPD, MUC5B and ACE2, reveal compelling insights regarding disease susceptibility and severity. Here we present meta-analyses bringing together 60 studies from 25 countries (Fig. 1 and Supplementary Table 1) for three COVID-19-related phenotypes: (1) individuals critically ill with COVID-19 on the basis of requiring respiratory support in hospital or who died as a consequence of the disease (9,376 cases, of which 3,197 are new in this data release, and 1,776,645 control individuals); (2) individuals with moderate or severe COVID-19 defined as those hospitalized due to symptoms associated with the infection (25,027 cases, 11,386 new and 2,836,272 control individuals); and (3) all cases with reported SARS-CoV-2 infection regardless of symptoms (125,584 cases, 76,022 new and 2,575,347 control individuals). Most studies have reported results before the roll out of the COVID-19 vaccination campaign. An overview of the study design is provided in Supplementary Fig. 1. We found a total of 23 genome-wide significant loci (P

Published
2022

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