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1. Supine hypertension: A state of the art

Author: Mantovani, G., Marozzi, I., Rafanelli, M., Rivasi, G., Volpato, S., and Ungar, A.
Published: 2022
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2. 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

3. 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

4. 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

5. 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

6. 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

7. 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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8. 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

9. Detection of impending reflex syncope by means of an integrated multisensor patch-type recorder

Author: Groppelli, A, Rafanelli, M, Testa, G, Agusto, S, Rivasi, G, Carbone, E, Soranna, D, Zambon, A, Castiglioni, P, Ungar, A, Brignole, M, Parati, G, Groppelli A., Rafanelli M., Testa G. D., Agusto S., Rivasi G., Carbone E., Soranna D., Zambon A., Castiglioni P., Ungar A., Brignole M., Parati G., Groppelli, A, Rafanelli, M, Testa, G, Agusto, S, Rivasi, G, Carbone, E, Soranna, D, Zambon, A, Castiglioni, P, Ungar, A, Brignole, M, Parati, G, Groppelli A., Rafanelli M., Testa G. D., Agusto S., Rivasi G., Carbone E., Soranna D., Zambon A., Castiglioni P., Ungar A., Brignole M., and Parati G.
Abstract: We assessed the capability of an integrated multisensory patch-type monitor (RootiRx®) in detecting episodes of reflex (pre)syncope induced by tilt table test (TTT). Firstly, we performed an intrapatient comparison of cuffless systolic blood pressure (SBP), R–R interval (RRI) and variability (power spectrum analysis) obtained by means of the RootiRx® with those obtained with conventional methods (CONV) with validated finger pressure devices at baseline in supine position and repeatedly during TTT in 32 patients affected by likely reflex syncope. Secondly, the LF/HF values obtained with RootiRx® during TTT were analyzed in 50 syncope patients. Compared with baseline supine recordings, during TTT a decrement of median SBP was observed with CONV (−53.5 mmHg) but not with RootiRx® ®(−1 mmHg). Conversely, RRI reduction (CONV: 102 ms; RootiRx®: 127 ms) and RRI Low Frequency/High Frequency powers ratio (LF/HF) increase (CONV: 1.6; RootiRx®: 2.5) were similar. The concordance was good for RRI (0.97 [95% CI 0.96–0.98]) and fair for LF/HF ratio (0.69 [95% CI 0.46-0.83]). During the first 5 min of TTT the LF/HF ratio was higher in patients who later developed syncope than in no-syncope patients. This ratio was significantly different among patients with syncope, presyncope or without symptoms at the time of syncope (p value = 0.02). In conclusion, cuffless RootiRx® was unable to detect rapid drops of SBP occurring during impending reflex syncope and thus cannot be used as a diagnostic tool for hypotensive syncope. On the other hand, RRI mean values and LF/HF power ratios obtained with RootiRx® were consistent with those simultaneously obtained using conventional methods.
Published: 2023

10. 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

11. Feasibility of Blood Pressure Measurement With a Wearable (Watch-Type) Monitor During Impending Syncopal Episodes

Author: Groppelli, A, Rafanelli, M, Testa, G, Agusto, S, Rivasi, G, Ungar, A, Carbone, E, Soranna, D, Zambon, A, Brignole, M, Parati, G, Groppelli A., Rafanelli M., Testa G. D., Agusto S., Rivasi G., Ungar A., Carbone E., Soranna D., Zambon A., Brignole M., Parati G., Groppelli, A, Rafanelli, M, Testa, G, Agusto, S, Rivasi, G, Ungar, A, Carbone, E, Soranna, D, Zambon, A, Brignole, M, Parati, G, Groppelli A., Rafanelli M., Testa G. D., Agusto S., Rivasi G., Ungar A., Carbone E., Soranna D., Zambon A., Brignole M., and Parati G.
Abstract: BACKGROUND: We assessed the reliability and feasibility of blood pressure (BP) measurements by means of a new wearable watch-type BP monitor (HeartGuide) in detecting episodes of hypotensive (pre)syncope induced by tilt table test. METHODS AND RESULTS: An intrapatient comparison between systolic BP (SBP) measured by means of the HeartGuide device and noninvasive finger beat-to-beat BP monitoring was undertaken both at baseline in supine position and repeatedly during tilt table test in patients evaluated for reflex syncope. Intrapatient fall of systolic BP from baseline was measured. Eighty-one patients (mean age, 61±19 years; 46 women) were included. Overall, HeartGuide was able to yield BP values at the time of BP nadir in 58 (72%) patients (average HeartGuide SBP 102±18 mm Hg, versus finger SBP 101±19 mm Hg). Compared with baseline, the maximum SBP decrease was on average −28.5±27.8 and −30.3±33.9 mm Hg respectively (Lin’s concordance correlation coefficient=0.78, r=0.79, P=0.001). In the subgroup of 38 patients with tilt table test induced (pre)syncope, the average HeartGuide SBP during symptoms was 97±16 mm Hg, and the finger SBP was 94±18 mm Hg. Compared with baseline, the maximum SBP decrease was on average −35.2±29.3 and −43.3±31.8 mm Hg, respectively (Lin’s concordance correlation coefficient=0.83, r=0.87, P=0.001). CONCLUSIONS: Our data indicate that the HeartGuide BP monitor can detect low BP during presyncope and that its measure of SBP change is consistent with that simultaneously obtained through continuous BP monitoring, despite some intrapatient variability. Thus, this device might be useful in determining the hypotensive nature of spontaneous (pre)syncopal symptoms, a possibility that should be verified by field studies.
Published: 2022

12. Association between hypotension during 24 h ambulatory blood pressure monitoring and reflex syncope: the SynABPM 1 study

Author: Rivasi, G, Groppelli, A, Brignole, M, Soranna, D, Zambon, A, Bilo, G, Pengo, M, Sharad, B, Hamrefors, V, Rafanelli, M, Testa, G, Rice, C, Kenny, R, Sutton, R, Ungar, A, Fedorowski, A, Parati, G, Rivasi G., Groppelli A., Brignole M., Soranna D., Zambon A., Bilo G., Pengo M., Sharad B., Hamrefors V., Rafanelli M., Testa G. D., Rice C., Kenny R. A., Sutton R., Ungar A., Fedorowski A., Parati G., Rivasi, G, Groppelli, A, Brignole, M, Soranna, D, Zambon, A, Bilo, G, Pengo, M, Sharad, B, Hamrefors, V, Rafanelli, M, Testa, G, Rice, C, Kenny, R, Sutton, R, Ungar, A, Fedorowski, A, Parati, G, Rivasi G., Groppelli A., Brignole M., Soranna D., Zambon A., Bilo G., Pengo M., Sharad B., Hamrefors V., Rafanelli M., Testa G. D., Rice C., Kenny R. A., Sutton R., Ungar A., Fedorowski A., and Parati G.
Abstract: Aims: Diagnostic criteria for ambulatory blood pressure monitoring (ABPM) in patients with suspected reflex syncope are lacking. The study hypothesis was that patients with reflex syncope have a higher prevalence of systolic blood pressure (SBP) drops on ABPM. Methods and results: ABPM data from reflex syncope patients and controls, matched by average 24h SBP, age, sex, and hypertension were compared. Patients with constitutional hypotension, orthostatic hypotension, and predominant cardioinhibition during carotid sinus massage or prolonged electrocardiogram monitoring or competing causes of syncope were excluded. Daytime and nighttime SBP drops (<110, 100, 90, 80mmHg) were assessed. Findings were validated in an independent sample. In the derivation sample, daytime SBP drops were significantly more common in 158 syncope patients than 329 controls. One or more daytime drops <90mmHg achieved 91% specificity and 32% sensitivity [odds ratio (OR) 4.6, P < 0.001]. Two or more daytime drops <100mmHg achieved 84% specificity and 40% sensitivity (OR 3.5, P = 0.001). Results were confirmed in the validation sample of 164 syncope patients and 164 controls: one or more daytime SBP drops <90mmHg achieved 94% specificity and 29% sensitivity (OR 6.2, P < 0.001), while two or more daytime SBP drops <100mmHg achieved 83% specificity and 35% sensitivity (OR 2.6, P < 0.001) Conclusion: SBP drops during ABPM are more common in reflex syncope patients than in controls. Cut-off values that may be applied in clinical practice are defined. This study expands the current indications for ABPM to patients with reflex syncope.
Published: 2022

13. 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

14. Truly unexplained falls after evaluation for syncope: A new diagnostic entity with severe prognosis

Author: Ungar, A, Ceccofiglio, A, Mussi, C, Bo, M, Rivasi, G, Rafanelli, M, Martone, A, Bellelli, G, Nicosia, F, Riccio, D, Boccardi, V, Tonon, E, Curcio, F, Landi, F, Abete, P, Mossello, E, Ungar A., Ceccofiglio A., Mussi C., Bo M., Rivasi G., Rafanelli M., Martone A. M., Bellelli G., Nicosia F., Riccio D., Boccardi V., Tonon E., Curcio F., Landi F., Abete P., Mossello E., Ungar, A, Ceccofiglio, A, Mussi, C, Bo, M, Rivasi, G, Rafanelli, M, Martone, A, Bellelli, G, Nicosia, F, Riccio, D, Boccardi, V, Tonon, E, Curcio, F, Landi, F, Abete, P, Mossello, E, Ungar A., Ceccofiglio A., Mussi C., Bo M., Rivasi G., Rafanelli M., Martone A. M., Bellelli G., Nicosia F., Riccio D., Boccardi V., Tonon E., Curcio F., Landi F., Abete P., and Mossello E.
Abstract: Objective: To compare one-year mortality risk associated with syncope and unexplained fall in older adults with dementia. Methods: 522 patients (aged >65 years) with dementia and history of transient loss of consciousness and/or unexplained falls were evaluated. The diagnosis of syncope was based on European Society of Cardiology guidelines. A “Syncopal Fall” was defined in patients with an initial clinical presentation of unexplained fall, but a final diagnosis of syncope after complete assessment. A “Truly Unexplained Fall” was defined in patients with an initial clinical presentation of unexplained fall, in whom a diagnosis of syncope had been excluded after the diagnostic work-up. One-year follow-up was assessed by phone interview. Results: Follow-up data were available for 501 participants (mean age 83 ± 6 years, 65% female). After a mean follow-up of 324 ± 93 days, death from any cause was reported in 188 participants (24%). Advanced age, male sex, cognitive and functional impairment were associated with a higher mortality rate. Patients with “Truly Unexplained Falls” had a higher mortality risk compared with syncope and “Syncopal Fall”. A diagnosis of “Truly Unexplained Falls” remained an independent predictor of one-year all-cause mortality in multivariate model. Conclusions: We propose the novel diagnostic category of “Truly Unexplained Fall”, resulting from the application of syncope guidelines to subjects with unexplained falls. This condition in older adults with dementia is a predictor of one-year all-cause mortality. For this new high risk profile, we advice a comprehensive geriatric assessment focused on risk factors for fall, aimed at a possible improvement of prognosis.
Published: 2022

15. 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

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

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

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

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

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

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

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

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

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

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

21. Association of uric acid with kidney function and albuminuria: the Uric Acid Right for heArt Health (URRAH) Project

Author: Russo E, Viazzi F, Pontremoli R, Barbagallo CM, Bombelli M, Casiglia E, Cicero AFG, Cirillo M, Cirillo P, Desideri G, D'Elia L, Ferri C, Galletti F, Gesualdo L, Giannattasio C, Iaccarino G, Leoncini G, Mallamaci F, Maloberti A, Masi S, Mengozzi A, Mazza A, Muiesan ML, Nazzaro P, Palatini P, Parati G, Rattazzi M, Rivasi G, Salvetti M, Tikhonoff V, Tocci G, Ungar A, Verdecchia P, Virdis A, Volpe M, Grassi G, Borghi C, Working Group on Uric Acid and Cardiovascular Risk of the Italian Society of Hypertension, Russo, E, Viazzi, F, Pontremoli, R, Barbagallo, C, Bombelli, M, Casiglia, E, Cicero, A, Cirillo, M, Cirillo, P, Desideri, G, D'Elia, L, Ferri, C, Galletti, F, Gesualdo, L, Giannattasio, C, Iaccarino, G, Leoncini, G, Mallamaci, F, Maloberti, A, Masi, S, Mengozzi, A, Mazza, A, Muiesan, M, Nazzaro, P, Palatini, P, Parati, G, Rattazzi, M, Rivasi, G, Salvetti, M, Tikhonoff, V, Tocci, G, Ungar, A, Verdecchia, P, Virdis, A, Volpe, M, Grassi, G, Borghi, C, Russo E, Viazzi F, Pontremoli R, Barbagallo CM, Bombelli M, Casiglia E, Cicero AFG, Cirillo M, Cirillo P, Desideri G, D'Elia L, Ferri C, Galletti F, Gesualdo L, Giannattasio C, Iaccarino G, Leoncini G, Mallamaci F, Maloberti A, Masi S, Mengozzi A, Mazza A, Muiesan ML, Nazzaro P, Palatini P, Parati G, Rattazzi M, Rivasi G, Salvetti M, Tikhonoff V, Tocci G, Ungar A, Verdecchia P, Virdis A, Volpe M, Grassi G, Borghi C, Working Group on Uric Acid and Cardiovascular Risk of the Italian Society of Hypertension, and Russo E, Viazzi F, Pontremoli R, Barbagallo CM, Bombelli M, Casiglia E, Cicero AFG, Cirillo M, Cirillo P, Desideri G, D'Elia L, Ferri C, Galletti F, Gesualdo L, Giannattasio C, Iaccarino G, Leoncini G, Mallamaci F, Maloberti A, Masi S, Mengozzi A, Mazza A, Muiesan ML, Nazzaro P, Palatini P, Parati G, Rattazzi M, Rivasi G, Salvetti M, Tikhonoff V, Tocci G, Ungar A, Verdecchia P, Virdis A, Volpe M, Grassi G, Borghi C
Subjects: Nephrology, Adult, Male, medicine.medical_specialty, Settore MED/09 - Medicina Interna, 030232 urology & nephrology, Allopurinol, Renal function, Hyperuricemia, 030204 cardiovascular system & hematology, Kidney, urologic and male genital diseases, Gastroenterology, 03 medical and health sciences, chemistry.chemical_compound, 0302 clinical medicine, Serum uric acid, Risk Factors, Internal medicine, Diabetes mellitus, medicine, eGFR, Humans, Albuminuria, Renal Insufficiency, Chronic, Aged, business.industry, Cardiovascular risk, nutritional and metabolic diseases, Middle Aged, medicine.disease, Uric Acid, chemistry, Uric acid, Original Article, Female, medicine.symptom, business, medicine.drug, Kidney disease, Glomerular Filtration Rate
Abstract: Background Hyperuricemia is commonly observed in patients with chronic kidney disease (CKD). However, a better understanding of the relationship among uric acid (UA) values, glomerular filtration rate (GFR) and albuminuria may shed light on the mechanisms underlying the excess of cardiovascular mortality associated with both chronic kidney disease and hyperuricemia and lead to better risk stratification. Our main goal was to study the relationships between serum uric acid and kidney disease measures (namely estimated GFR [eGFR] and albuminuria) in a large cohort of individuals at cardiovascular risk from the URic acid Right for heArt Health (URRAH) Project database. Methods Clinical data of 26,971 individuals were analyzed. Factors associated with the presence of hyperuricemia defined on the basis of previously determined URRAH cutoffs for cardiovascular and all-cause mortality were evaluated through multivariate analysis. Chronic kidney disease was defined as eGFR 2 and/or abnormal urinary albumin excretion diagnosed as: (i) microalbuminuria if urinary albumin concentration was > 30 and ≤ 300 mg/L, or if urinary albumin-to-creatinine ratio (ACR) was > 3.4 mg/mmol and ≤ 34 mg/mmol; (ii) macroalbuminuria if urinary albumin concentration was > 300 mg/L, or if ACR was > 34 mg/mmol. Results Mean age was 58 ± 15 years (51% males, 62% with hypertension and 12% with diabetes), mean eGFR was 81 ml/min per 1.73m22with a prevalence of eGFR Conclusions The lower the eGFR the higher the prevalence of hyperuricemia and gout. In subjects with eGFR 90 ml/min. The percentage of individuals treated with allopurinol was below 2% when GFR was above 60 ml/min, it increased to 20% in the presence of CKD 3b and rose further to 35% in individuals with macroalbuminuria. Graphic abstract
Published: 2022

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

Author: Casiglia E, Tikhonoff V, Virdis A, Grassi G, Angeli F, Barbagallo CM, Bombelli M, Cicero AFG, Cirillo M, Cirillo P, Dell'Oro R, D'elia L, Desideri G, Ferri C, Galletti F, Gesualdo L, Giannattasio C, Iaccarino G, Lippa L, Mallamaci F, Masi S, Maloberti A, Masulli M, Mazza A, Mengozzi A, Muiesan ML, Nazzaro P, Palatini P, Parati G, Pontremoli R, Quarti-Trevano F, Rattazzi M, Reboldi G, Rivasi G, Salvetti M, Tocci G, Ungar A, Verdecchia P, Viazzi F, Volpe M, Borghi C, Working Group on Uric Acid and Cardiovascular Risk of the Italian Society of Hypertension (SIIA)., Casiglia E, Tikhonoff V, Virdis A, Grassi G, Angeli F, Barbagallo CM, Bombelli M, Cicero AFG, Cirillo M, Cirillo P, Dell'Oro R, D'elia L, Desideri G, Ferri C, Galletti F, Gesualdo L, Giannattasio C, Iaccarino G, Lippa L, Mallamaci F, Masi S, Maloberti A, Masulli M, Mazza A, Mengozzi A, Muiesan ML, Nazzaro P, Palatini P, Parati G, Pontremoli R, Quarti-Trevano F, Rattazzi M, Reboldi G, Rivasi G, Salvetti M, Tocci G, Ungar A, Verdecchia P, Viazzi F, Volpe M, Borghi C, Working Group on Uric Acid and Cardiovascular Risk of the Italian Society of Hypertension (SIIA)., Casiglia, E, Tikhonoff, V, Virdis, A, Grassi, G, Angeli, F, Barbagallo, C, Bombelli, M, Cicero, A, Cirillo, M, Cirillo, P, Dell'Oro, R, D'Elia, L, Desideri, G, Ferri, C, Galletti, F, Gesualdo, L, Giannattasio, C, Iaccarino, G, Lippa, L, Mallamaci, F, Masi, S, Maloberti, A, Masulli, M, Mazza, A, Mengozzi, A, Muiesan, M, Nazzaro, P, Palatini, P, Parati, G, Pontremoli, R, Quarti-Trevano, F, Rattazzi, M, Reboldi, G, Rivasi, G, Salvetti, M, Tocci, G, Ungar, A, Verdecchia, P, Viazzi, F, Volpe, M, and Borghi, C
Subjects: Adult, Male, CI, confidence interval(s), cut-off, Physiology, ICD-10, International Classification of Diseases – 10th Revision, cardiovascular, CV, cardiovascular, creatinine, epidemiology, uric acid, URRAH, Uric Acid Right for Heart Health, OR, odds ratio (s), Prognosis, Cardiovascular System, ROC, receiver operating characteristic, Hypertension, Internal Medicine, SUA, serum uric acid, Humans, Female, sCr, serum creatinine, Cardiology and Cardiovascular Medicine, HR, hazard ratio(s)
Abstract: Objective: In the frame of the Uric Acid Right for Heart Health (URRAH) study, a nationwide multicenter study involving adult participants recruited on a regional community basis from all the territory of Italy under the patronage of the Working Group on Uric Acid and Cardiovascular Risk of the Italian Society of Hypertension, we searched for the cut-off values of the ratio between serum uric acid (SUA) and serum creatinine (sCr) able to predict cardiovascular (CV) events. Methods: Among 20 724 participants followed-up for 126 ± 64 months, after detecting cut-off by the receiver operating characteristic curves, we calculated by Cox models adjusted for confounders having CV events as dependent variable the hazard ratio (HR) of SUA/sCr > cut-off. We also verified if the role of cut-off varied with increasing SUA/sCr. Results: A plausible prognostic cut-off of SUA/sCr was found and was the same in the whole database, in men and in women (>5.35). The HR of SUA/sCr > cut-off was 1.159 (95% confidence interval [CI] 1.092-1.131, P < 0.03) in all, 1.161 (95% CI 1.021-1.335, P < 0.02) in men, and 1.444 (95% CI 1.012-1.113, P < 0.03) in women. In increasing quintiles of SUA/sCr the cut-offs were >3.08, >4.87, >5.35, >6.22 and >7.58, respectively. The HRs significantly increased from the 3rd to the 5th quintile (1.21, 95% CI 1.032-1.467, P = 0.018; 1.294, 95% CI 1.101-1.521, P = 0.002; and 1.642, 95% CI 1.405-1.919, P < 0.0001; respectively), that is, over 5.35, whereas the 2nd quintile was not significantly different from the 1st (reference). Conclusion: Having SUA/sCr >5.35 is an independent CV risk indicator both in men and women. The cut-off is dynamic and significantly increases with increasing SUA/sCr.
Published: 2022

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

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

24. Low-blood pressure phenotype underpins the tendency to reflex syncope

Author: Brignole, M, Rivasi, G, Sutton, R, Kenny, R, Morillo, C, Sheldon, R, Raj, S, Ungar, A, Furlan, R, van Dijk, G, Hamdan, M, Hamrefors, V, Engstrom, G, Park, C, Soranna, D, Zambon, A, Parati, G, Fedorowski, A, Brignole M., Rivasi G., Sutton R., Kenny R. A., Morillo C. A., Sheldon R., Raj S. R., Ungar A., Furlan R., van Dijk G., Hamdan M., Hamrefors V., Engstrom G., Park C., Soranna D., Zambon A., Parati G., Fedorowski A., Brignole, M, Rivasi, G, Sutton, R, Kenny, R, Morillo, C, Sheldon, R, Raj, S, Ungar, A, Furlan, R, van Dijk, G, Hamdan, M, Hamrefors, V, Engstrom, G, Park, C, Soranna, D, Zambon, A, Parati, G, Fedorowski, A, Brignole M., Rivasi G., Sutton R., Kenny R. A., Morillo C. A., Sheldon R., Raj S. R., Ungar A., Furlan R., van Dijk G., Hamdan M., Hamrefors V., Engstrom G., Park C., Soranna D., Zambon A., Parati G., and Fedorowski A.
Abstract: Background:We hypothesized that cardiovascular physiology differs in reflex syncope patients compared with the general population, predisposing such individuals to vasovagal reflex.Methods:In this multicohort cross-sectional study, we compared aggregate data of resting SBP, DBP, pulse pressure (PP) and heart rate (HR), collected from six community-based cohort studies (64 968 observations) with those from six databases of reflex syncope patients (6516 observations), subdivided by age decades and sex.Results:Overall, in male individuals with reflex syncope, SBP (-3.4 mmHg) and PP (-9.2 mmHg) were lower and DBP (+2.8 mmHg) and HR (+5.1 bpm) were higher than in the general population; the difference in SBP was higher at ages above 60 years. In female individuals, PP (-6.0 mmHg) was lower and DBP (+4.7 mmHg) and HR (+4.5 bpm) were higher than in the general population; differences in SBP were less pronounced, becoming evident only above 60 years. Compared with male individuals, SBP in female individuals exhibited slower increase until age 40 years, and then demonstrated steeper increase that continued throughout remaining life.Conclusion:The patients prone to reflex syncope demonstrate a different resting cardiovascular haemodynamic profile as compared with a general population, characterized by lower SBP and PP, reflecting reduced venous return and lower stroke volume, and a higher HR and DBP, suggesting the activation of compensatory mechanisms. Our data contribute to a better understanding why some individuals with similar demographic characteristics develop reflex syncope and others do not.Video abstract:http://links.lww.com/HJH/B580.
Published: 2021

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

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

26. New definition of hypotension in patients with reflex syncope using 24-hour ambulatory blood pressure monitoring (SynABPM Study)

Author: Rivasi, G, primary, Brignole, M, additional, Groppelli, A, additional, Soranna, D, additional, Zambon, A, additional, Sutton, R, additional, Kenny, R A, additional, Ungar, A, additional, Fedorowski, A, additional, and Parati, G, additional
Published: 2022
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27. The importance of including uric acid in the definition of metabolic syndrome when assessing the mortality risk

Author: Pugliese NR, Mengozzi A, Virdis A, Casiglia E, Tikhonoff V, Cicero AFG, Ungar A, Rivasi G, Salvetti M, Barbagallo CM, Bombelli M, Dell'Oro R, Bruno B, Lippa L, D'Elia L, Verdecchia P, Mallamaci F, Cirillo M, Rattazzi M, Cirillo P, Gesualdo L, Mazza A, Giannattasio C, Maloberti A, Volpe M, Tocci G, Georgiopoulos G, Iaccarino G, Nazzaro P, Parati G, Palatini P, Galletti F, Ferri C, Desideri G, Viazzi F, Pontremoli R, Muiesan ML, Grassi G, Masi S, Borghi C, Working Group on Uric Acid and Cardiovascular Risk of the Italian Society of Hypertension, Pugliese NR, Mengozzi A, Virdis A, Casiglia E, Tikhonoff V, Cicero AFG, Ungar A, Rivasi G, Salvetti M, Barbagallo CM, Bombelli M, Dell'Oro R, Bruno B, Lippa L, D'Elia L, Verdecchia P, Mallamaci F, Cirillo M, Rattazzi M, Cirillo P, Gesualdo L, Mazza A, Giannattasio C, Maloberti A, Volpe M, Tocci G, Georgiopoulos G, Iaccarino G, Nazzaro P, Parati G, Palatini P, Galletti F, Ferri C, Desideri G, Viazzi F, Pontremoli R, Muiesan ML, Grassi G, Masi S, Borghi C, Pugliese, Nicola Riccardo, Mengozzi, Alessandro, Virdis, Agostino, Casiglia, Edoardo, Tikhonoff, Valerie, Cicero, Arrigo F G, Ungar, Andrea, Rivasi, Giulia, Salvetti, Massimo, Barbagallo, Carlo M, Bombelli, Michele, Dell'Oro, Raffaella, Bruno, Berardino, Lippa, Luciano, D'Elia, Lanfranco, Verdecchia, Paolo, Mallamaci, Francesca, Cirillo, Massimo, Rattazzi, Marcello, Cirillo, Pietro, Gesualdo, Loreto, Mazza, Alberto, Giannattasio, Cristina, Maloberti, Alessandro, Volpe, Massimo, Tocci, Giuliano, Georgiopoulos, Georgio, Iaccarino, Guido, Nazzaro, Pietro, Parati, Gianfranco, Palatini, Paolo, Galletti, Ferruccio, Ferri, Claudio, Desideri, Giovambattista, Viazzi, Francesca, Pontremoli, Roberto, Muiesan, Maria Lorenza, Grassi, Guido, Masi, Stefano, Borghi, Claudio, Working Group on Uric Acid and Cardiovascular Risk of the Italian Society of Hypertension, Cicero AFG, Pugliese, N, Mengozzi, A, Virdis, A, Casiglia, E, Tikhonoff, V, Cicero, A, Ungar, A, Rivasi, G, Salvetti, M, Barbagallo, C, Bombelli, M, Dell'Oro, R, Bruno, B, Lippa, L, D'Elia, L, Verdecchia, P, Mallamaci, F, Cirillo, M, Rattazzi, M, Cirillo, P, Gesualdo, L, Mazza, A, Giannattasio, C, Maloberti, A, Volpe, M, Tocci, G, Georgiopoulos, G, Iaccarino, G, Nazzaro, P, Parati, G, Palatini, P, Galletti, F, Ferri, C, Desideri, G, Viazzi, F, Pontremoli, R, Muiesan, M, Grassi, G, Masi, S, and Borghi, C
Subjects: Male, medicine.medical_specialty, Settore MED/09 - Medicina Interna, Cardiovascular mortality, Prognosi, Sudden cardiac death, chemistry.chemical_compound, Serum uric acid, Risk Factors, Internal medicine, Cause of Death, medicine, Humans, Myocardial infarction, Metabolic syndrome, Prognosis, Stroke, Retrospective Studies, Original Paper, business.industry, Proportional hazards model, Hazard ratio, General Medicine, Middle Aged, medicine.disease, Uric Acid, Survival Rate, chemistry, Italy, Cardiovascular Diseases, Heart failure, Cardiology, Uric acid, Female, Cardiology and Cardiovascular Medicine, business, Biomarkers, Follow-Up Studies
Abstract: Introduction Serum uric acid (SUA) has been depicted as a contributory causal factor in metabolic syndrome (MS), which in turn, portends unfavourable prognosis. Aim We assessed the prognostic role of SUA in patients with and without MS. Methods We used data from the multicentre Uric Acid Right for Heart Health study and considered cardiovascular mortality (CVM) as death due to fatal myocardial infarction, stroke, sudden cardiac death, or heart failure. Results A total of 9589 subjects (median age 58.5 years, 45% males) were included in the analysis, and 5100 (53%) patients had a final diagnosis of MS. After a median follow-up of 142 months, we observed 558 events. Using a previously validated cardiovascular SUA cut-off to predict CVM (> 5.1 mg/dL in women and 5.6 mg/dL in men), elevated SUA levels were significantly associated to a worse outcome in patients with and without MS (all p p = 0.004). Cox regression analyses identified an independent association between SUA and CVM (Hazard Ratio: 1.79 [95% CI, 1.15–2.79]; p p Conclusion Increasing SUA levels are associated with a higher CVM risk irrespective of the presence of MS: a cardiovascular SUA threshold may improve risk stratification. Graphic abstract
Published: 2021

28. Relationships between diuretic related hyperuricemia and cardiovascular events: data from the URRAH (URic acid Right for heArt Health) study

Author: Maloberti, A, Bombelli, M, Facchetti, R, Desideri, G, Cicero, AFG, Muiesan, Ml, Agabiti Rosei, E, Salvetti, S, Ungar, A, Rivasi, G, Pontremoli, R, Viazzi, V, Ferri, C, Bernardino, B, Galletti, F, D'elia, L, Palatini, P, Casiglia, E, Tikhonoff, V, Barbagallo, CM, Verdecchia, P, Masi, S, Mallamaci, M, Cirillo, M, Rattazzi, M, Pauletto, P, Cirillo, P, Gesualdo, L, Mazza, A, Volpe, M, Tocci, G, Iaccarino, G, Nazzato, P, Lippa, L, Parati, G, Dell'Oro, R, Quarti Trevano, F, Giannattasio, C, Virdis, A, Grassi, G, Borghi, C, Working Group on Uric Acid and Cardiovascular Risk of the Italian Society of Hypertension., Maloberti, A, Bombelli, M, Facchetti, R, Desideri, G, Cicero, Afg, Muiesan, Ml, Agabiti, Rosei, E, Salvetti, S, Ungar, A, Rivasi, G, Pontremoli, R, Viazzi, V, Ferri, C, Bernardino, B, Galletti, F, D'Elia, L, Palatini, P, Casiglia, E, Tikhonoff, V, Barbagallo, Cm, Verdecchia, P, Masi, S, Mallamaci, M, Cirillo, M, Rattazzi, M, Pauletto, P, Cirillo, P, Gesualdo, L, Mazza, A, Volpe, M, Tocci, G, Iaccarino, G, Nazzato, P, Lippa, L, Parati, G, Dell'Oro, R, Quarti, Trevano, F, Giannattasio, C, Virdis, A, Grassi, G, Borghi, C, Working Group on Uric Acid and Cardiovascular Risk of the Italian Society of, Hypertension., Maloberti A, Bombelli M, Facchetti R, Barbagallo CM, Bernardino B, Rosei EA, Casiglia E, Cicero AFG, Cirillo M, Cirillo P, Desideri G, D'elia L, Dell'Oro R, Ferri C, Galletti F, Giannattasio C, Loreto G, Iaccarino G, Lippa L, Mallamaci F, Masi S, Mazza A, Muiesan ML, Nazzaro P, Parati G, Palatini P, Pauletto P, Pontremoli R, Quarti-Trevano F, Rattazzi M, Rivasi G, Salvetti M, Tikhonoff V, Tocci G, Ungar A, Verdecchia P, Viazzi F, Volpe M, Virdis A, Grassi G, Borghi C, Maloberti A, Bombelli M, Facchetti R, Barbagallo CM, Bernardino B, Rosei EA, Casiglia E, Giuseppe Cicero AF, Cirillo M, Cirillo P, Desideri G, D'elia L, Dell'Oro R, Ferri C, Galletti F, Giannattasio C, Loreto G, Iaccarino G, Lippa L, Mallamaci F, Masi S, Mazza A, Muiesan ML, Nazzaro P, Parati G, Palatini P, Pauletto P, Pontremoli R, Quarti-Trevano F, Rattazzi M, Rivasi G, Salvetti M, Tikhonoff V, Tocci G, Ungar A, Verdecchia P, Viazzi F, Volpe M, Virdis A, Grassi G, Borghi C, Barbagallo, C, Rosei, E, Cicero, A, Loreto, G, Mallamaci, F, Muiesan, M, Nazzaro, P, Quarti-Trevano, F, Salvetti, M, and Viazzi, F
Subjects: Cardiovascular event, Male, medicine.medical_specialty, Settore MED/09 - Medicina Interna, Physiology, medicine.medical_treatment, diuretic, Renal function, Hyperuricemia, cardiovascular events, cardiovascular mortality, uric acid, 030204 cardiovascular system & hematology, 03 medical and health sciences, chemistry.chemical_compound, 0302 clinical medicine, Risk Factors, Internal medicine, Internal Medicine, medicine, Humans, 030212 general & internal medicine, Diuretics, Heart health, Uric acid, cardiovascular events, diuretics, epidemiology, cardiovascular events, cardiovascular mortality, diuretic, uric acid, business.industry, Serum uric acid, Middle Aged, medicine.disease, chemistry, Hypertension, Uric acid, Diuretic, Cardiology and Cardiovascular Medicine, business, Cohort study
Abstract: Objective Although the relationship between hyperuricemia and cardiovascular events has been extensively examined, data on the role of diuretic-related hyperuricemia are still scanty. The present study was designed to collect information on the relationship between diuretic-related hyperuricemia and cardiovascular events. Methods The URic acid Right for heArt Health (URRAH) study is a nationwide, multicentre, observational cohort study involving data on individuals recruited from all the Italy territory under the patronage of the Italian Society of Hypertension with an average follow-up period of 122.3 ± 66.9 months. Patients were classified into four groups according to the diuretic use (yes vs. no) and serum uric acid (SUA) levels (higher vs. lower than the median value of 4.8 mg/dl). All-cause death, cardiovascular deaths and first cardiovascular event were considered as outcomes. Results Seventeen thousand, seven hundred and forty-seven individuals were included in the analysis. Mean age was 57.1 ± 15.2 years, men were 45.3% and SBP and DBP amounted to 144.1 ± 24.6 and 85.2 ± 13.2 mmHg. 17.2% of individuals take diuretics of whom 58% had SUA higher than median value. Patients with hyperuricemia without diuretic use served as reference group. In multivariate adjusted analysis (sex, age, SBP, BMI, glucose, total cholesterol, and glomerular filtration rate) individuals with hyperuricemia and diuretic use exhibit a similar risk for the three outcomes as compared with the reference group. Conclusion Our study showed that diuretic-related hyperuricemia carry a similar risk of cardiovascular events and all-cause mortality when compared with individuals that present hyperuricemia in absence of diuretic therapy.
Published: 2021

29. Accuracy of home blood pressure measurement: the ACCURAPRESS study–a proposal of Young Investigator Group of the Italian Hypertension Society (Società Italiana dell’Ipertensione Arteriosa)

Author: Mancusi, C, Bisogni, V, Maloberti, A, Manzi, M, Visco, V, Biolcati, M, Giani, V, Spannella, F, Monticone, S, Saladini, F, Rivasi, G, Turrin, G, Pucci, G, Pengo, M, Bertacchini, F, Ferri, C, Grassi, G, Muiesan, M, Mancusi, Costantino, Bisogni, Valeria, Maloberti, Alessandro, Manzi, Maria Virginia, Visco, Valeria, Biolcati, Marco, Giani, Valentina, Spannella, Francesco, Monticone, Silvia, Saladini, Francesca, Rivasi, Giulia, Turrin, Giada, Pucci, Giacomo, Pengo, Martino, Bertacchini, Fabio, Ferri, Claudio, Grassi, Guido, Muiesan, Maria Lorenza, Mancusi, C, Bisogni, V, Maloberti, A, Manzi, M, Visco, V, Biolcati, M, Giani, V, Spannella, F, Monticone, S, Saladini, F, Rivasi, G, Turrin, G, Pucci, G, Pengo, M, Bertacchini, F, Ferri, C, Grassi, G, Muiesan, M, Mancusi, Costantino, Bisogni, Valeria, Maloberti, Alessandro, Manzi, Maria Virginia, Visco, Valeria, Biolcati, Marco, Giani, Valentina, Spannella, Francesco, Monticone, Silvia, Saladini, Francesca, Rivasi, Giulia, Turrin, Giada, Pucci, Giacomo, Pengo, Martino, Bertacchini, Fabio, Ferri, Claudio, Grassi, Guido, and Muiesan, Maria Lorenza
Abstract: Purpose: Home blood pressure monitoring (HBPM) might be considered a valid alternative to ambulatory blood pressure monitoring (ABPM) for both the diagnosis and management of hypertension. Correct information on how to perform HBPM are crucial for its reliability. The aim of the present survey was to assess if hypertensive patients followed current recommendation on how to correctly perform HBPM measurements. Materials and methods: The survey included 30 different items on how to perform the HBPM. It was developed by the ‘Young Investigators’ group of the Italian Society of Arterial Hypertension (SIIA) and it was administered during the office visit between May 2019 and December 2021. Results: A total of 643 hypertensive patients participated in the study. Main results show that, despite the rate of informed patients was relatively high (71% of the whole population), unacceptable number of patients did not follow indications on how to perform a correct HBPM. Patients who were informed on how to measure home BP had a significantly higher rate of correct position during measurement (78 vs. 22%, p < 0.01), avoidance of talking and moving during measurement (68 vs. 32%, p < 0.0001), and correct number and time interval between two measurements (85 vs. 15%, p < 0.001). More accurate measurements of home BP were associated with less prevalence of carotid plaque. Conclusions: Correct performance for HBPM is low among patients treated in Italian hypertension centers. These findings shed light on the importance of correct HBPM measurements for the detection of accurate BP values for the proper management of hypertensive patients.
Published: 2022

30. Association of uric acid with kidney function and albuminuria: the Uric Acid Right for heArt Health (URRAH) Project

Author: Russo, E, Viazzi, F, Pontremoli, R, Barbagallo, C, Bombelli, M, Casiglia, E, Cicero, A, Cirillo, M, Cirillo, P, Desideri, G, D'Elia, L, Ferri, C, Galletti, F, Gesualdo, L, Giannattasio, C, Iaccarino, G, Leoncini, G, Mallamaci, F, Maloberti, A, Masi, S, Mengozzi, A, Mazza, A, Muiesan, M, Nazzaro, P, Palatini, P, Parati, G, Rattazzi, M, Rivasi, G, Salvetti, M, Tikhonoff, V, Tocci, G, Ungar, A, Verdecchia, P, Virdis, A, Volpe, M, Grassi, G, Borghi, C, Russo, Elisa, Viazzi, Francesca, Pontremoli, Roberto, Barbagallo, Carlo Maria, Bombelli, Michele, Casiglia, Edoardo, Cicero, Arrigo Francesco Giuseppe, Cirillo, Massimo, Cirillo, Pietro, Desideri, Giovambattista, D'Elia, Lanfranco, Ferri, Claudio, Galletti, Ferruccio, Gesualdo, Loreto, Giannattasio, Cristina, Iaccarino, Guido, Leoncini, Giovanna, Mallamaci, Francesca, Maloberti, Alessandro, Masi, Stefano, Mengozzi, Alessandro, Mazza, Alberto, Muiesan, Maria Lorenza, Nazzaro, Pietro, Palatini, Paolo, Parati, Gianfranco, Rattazzi, Marcello, Rivasi, Giulia, Salvetti, Massimo, Tikhonoff, Valérie, Tocci, Giuliano, Ungar, Andrea, Verdecchia, Paolo, Virdis, Agostino, Volpe, Massimo, Grassi, Guido, Borghi, Claudio, Russo, E, Viazzi, F, Pontremoli, R, Barbagallo, C, Bombelli, M, Casiglia, E, Cicero, A, Cirillo, M, Cirillo, P, Desideri, G, D'Elia, L, Ferri, C, Galletti, F, Gesualdo, L, Giannattasio, C, Iaccarino, G, Leoncini, G, Mallamaci, F, Maloberti, A, Masi, S, Mengozzi, A, Mazza, A, Muiesan, M, Nazzaro, P, Palatini, P, Parati, G, Rattazzi, M, Rivasi, G, Salvetti, M, Tikhonoff, V, Tocci, G, Ungar, A, Verdecchia, P, Virdis, A, Volpe, M, Grassi, G, Borghi, C, Russo, Elisa, Viazzi, Francesca, Pontremoli, Roberto, Barbagallo, Carlo Maria, Bombelli, Michele, Casiglia, Edoardo, Cicero, Arrigo Francesco Giuseppe, Cirillo, Massimo, Cirillo, Pietro, Desideri, Giovambattista, D'Elia, Lanfranco, Ferri, Claudio, Galletti, Ferruccio, Gesualdo, Loreto, Giannattasio, Cristina, Iaccarino, Guido, Leoncini, Giovanna, Mallamaci, Francesca, Maloberti, Alessandro, Masi, Stefano, Mengozzi, Alessandro, Mazza, Alberto, Muiesan, Maria Lorenza, Nazzaro, Pietro, Palatini, Paolo, Parati, Gianfranco, Rattazzi, Marcello, Rivasi, Giulia, Salvetti, Massimo, Tikhonoff, Valérie, Tocci, Giuliano, Ungar, Andrea, Verdecchia, Paolo, Virdis, Agostino, Volpe, Massimo, Grassi, Guido, and Borghi, Claudio
Abstract: Background: Hyperuricemia is commonly observed in patients with chronic kidney disease (CKD). However, a better understanding of the relationship among uric acid (UA) values, glomerular filtration rate (GFR) and albuminuria may shed light on the mechanisms underlying the excess of cardiovascular mortality associated with both chronic kidney disease and hyperuricemia and lead to better risk stratification. Our main goal was to study the relationships between serum uric acid and kidney disease measures (namely estimated GFR [eGFR] and albuminuria) in a large cohort of individuals at cardiovascular risk from the URic acid Right for heArt Health (URRAH) Project database. Methods: Clinical data of 26,971 individuals were analyzed. Factors associated with the presence of hyperuricemia defined on the basis of previously determined URRAH cutoffs for cardiovascular and all-cause mortality were evaluated through multivariate analysis. Chronic kidney disease was defined as eGFR < 60 ml/min per 1.73 m2 and/or abnormal urinary albumin excretion diagnosed as: (i) microalbuminuria if urinary albumin concentration was > 30 and ≤ 300 mg/L, or if urinary albumin-to-creatinine ratio (ACR) was > 3.4 mg/mmol and ≤ 34 mg/mmol; (ii) macroalbuminuria if urinary albumin concentration was > 300 mg/L, or if ACR was > 34 mg/mmol. Results: Mean age was 58 ± 15 years (51% males, 62% with hypertension and 12% with diabetes), mean eGFR was 81 ml/min per 1.73m22with a prevalence of eGFR < 60 and micro- or macroalbuminuria of 16, 15 and 4%, respectively. Serum uric acid showed a trend towards higher values along with decreasing renal function. Both the prevalence of gout and the frequency of allopurinol use increased significantly with the reduction of eGFR and the increase in albuminuria. Hyperuricemia was independently related to male gender, eGFR strata, and signs of insulin resistance such as body mass index (BMI) and triglycerides. Conclusions: The lower the eGFR the higher th
Published: 2022

31. High heart rate amplifies the risk of cardiovascular mortality associated with elevated uric acid

Author: Palatini, P, Parati, G, Virdis, A, Reboldi, G, Masi, S, Mengozzi, A, Casiglia, E, Tikhonoff, V, Cicero, A, Ungar, A, Rivasi, G, Salvetti, M, Barbagallo, C, Bombelli, M, Dell'Oro, R, Bruno, B, Lippa, L, D'Elia, L, Verdecchia, P, Angeli, F, Mallamaci, F, Cirillo, M, Rattazzi, M, Cirillo, P, Gesualdo, L, Mazza, A, Giannattasio, C, Maloberti, A, Volpe, M, Tocci, G, Georgiopoulos, G, Iaccarino, G, Nazzaro, P, Galletti, F, Ferri, C, Desideri, G, Viazzi, F, Pontremoli, R, Muiesan, M, Grassi, G, Borghi, C, Palatini, Paolo, Parati, Gianfranco, Virdis, Agostino, Reboldi, Gianpaolo, Masi, Stefano, Mengozzi, Alessandro, Casiglia, Edoardo, Tikhonoff, Valerie, Cicero, Arrigo F G, Ungar, Andrea, Rivasi, Giulia, Salvetti, Massimo, Barbagallo, Carlo M, Bombelli, Michele, Dell'Oro, Raffaella, Bruno, Berardino, Lippa, Luciano, D'Elia, Lanfranco, Verdecchia, Paolo, Angeli, Fabio, Mallamaci, Francesca, Cirillo, Massimo, Rattazzi, Marcello, Cirillo, Pietro, Gesualdo, Loreto, Mazza, Alberto, Giannattasio, Cristina, Maloberti, Alessandro, Volpe, Massimo, Tocci, Giuliano, Georgiopoulos, Georgios, Iaccarino, Guido, Nazzaro, Pietro, Galletti, Ferruccio, Ferri, Claudio, Desideri, Giovambattista, Viazzi, Francesca, Pontremoli, Roberto, Muiesan, Maria Lorenza, Grassi, Guido, Borghi, Claudio, Palatini, P, Parati, G, Virdis, A, Reboldi, G, Masi, S, Mengozzi, A, Casiglia, E, Tikhonoff, V, Cicero, A, Ungar, A, Rivasi, G, Salvetti, M, Barbagallo, C, Bombelli, M, Dell'Oro, R, Bruno, B, Lippa, L, D'Elia, L, Verdecchia, P, Angeli, F, Mallamaci, F, Cirillo, M, Rattazzi, M, Cirillo, P, Gesualdo, L, Mazza, A, Giannattasio, C, Maloberti, A, Volpe, M, Tocci, G, Georgiopoulos, G, Iaccarino, G, Nazzaro, P, Galletti, F, Ferri, C, Desideri, G, Viazzi, F, Pontremoli, R, Muiesan, M, Grassi, G, Borghi, C, Palatini, Paolo, Parati, Gianfranco, Virdis, Agostino, Reboldi, Gianpaolo, Masi, Stefano, Mengozzi, Alessandro, Casiglia, Edoardo, Tikhonoff, Valerie, Cicero, Arrigo F G, Ungar, Andrea, Rivasi, Giulia, Salvetti, Massimo, Barbagallo, Carlo M, Bombelli, Michele, Dell'Oro, Raffaella, Bruno, Berardino, Lippa, Luciano, D'Elia, Lanfranco, Verdecchia, Paolo, Angeli, Fabio, Mallamaci, Francesca, Cirillo, Massimo, Rattazzi, Marcello, Cirillo, Pietro, Gesualdo, Loreto, Mazza, Alberto, Giannattasio, Cristina, Maloberti, Alessandro, Volpe, Massimo, Tocci, Giuliano, Georgiopoulos, Georgios, Iaccarino, Guido, Nazzaro, Pietro, Galletti, Ferruccio, Ferri, Claudio, Desideri, Giovambattista, Viazzi, Francesca, Pontremoli, Roberto, Muiesan, Maria Lorenza, Grassi, Guido, and Borghi, Claudio
Abstract: Aims: Whether the association between uric acid (UA) and cardiovascular disease is influenced by some facilitating factors is unclear. The aim of this study was to investigate whether the risk of cardiovascular mortality (CVM) associated with elevated UA was modulated by the level of resting heart rate (HR). Methods and results: Multivariable Cox analyses were made in 19 128 participants from the multicentre Uric acid Right for heArt Health study. During a median follow-up of 11.2 years, there were 1381 cases of CVM. In multivariable Cox models both UA and HR, either considered as continuous or categorical variables were independent predictors of CVM both improving risk discrimination (P ≤ 0.003) and reclassification (P < 0.0001) over a multivariable model. However, the risk of CVM related to high UA (≥5.5 mg/dL, top tertile) was much lower in the subjects with HR
Published: 2022

32. Serum uric acid and fatal myocardial infarction: Detection of prognostic cut-off values: The URRAH (Uric Acid Right for Heart Health) study

Author: Casiglia E, Tikhonoff V, Virdis A, Masi S, Barbagallo CM, Bombelli M, Bruno B, Cicero AFG, Cirillo M, Cirillo P, Desideri G, D'Elia L, Ferri C, Galletti F, Gesualdo L, Giannattasio C, Iaccarino G, Lippa L, Mallamaci F, Maloberti A, Mazza A, Muiesan ML, 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, Volpe M, Grassi G, Borghi C, Working Group on Uric Acid and Cardiovascular Risk of the Italian Society of Hypertension (SIIA)., Casiglia E, Tikhonoff V, Virdis A, Masi S, Barbagallo CM, Bombelli M, Bruno B, Cicero AFG, Cirillo M, Cirillo P, Desideri G, D'Elia L, Ferri C, Galletti F, Gesualdo L, Giannattasio C, Iaccarino G, Lippa L, Mallamaci F, Maloberti A, Mazza A, Muiesan ML, 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, Volpe M, Grassi G, Borghi C, Casiglia, E, Tikhonoff, V, Virdis, A, Masi, S, 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, Lippa, L, Mallamaci, F, Maloberti, A, 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, Volpe, M, Grassi, G, Borghi, C, Working Group on Uric Acid and Cardiovascular Risk of the Italian Society of Hypertension (SIIA)., Casiglia, Edoardo, Tikhonoff, Valérie, Virdis, Agostino, Masi, Stefano, Barbagallo, Carlo M, Bombelli, Michele, Bruno, Bernardino, Cicero, Arrigo F G, Cirillo, Massimo, Cirillo, Pietro, Desideri, Giovambattista, D'Elia, Lanfranco, Ferri, Claudio, Galletti, Ferruccio, Gesualdo, Loreto, Giannattasio, Cristina, Iaccarino, Guido, Lippa, Luciano, Mallamaci, Francesca, Maloberti, Alessandro, Mazza, Alberto, Muiesan, Maria Lorenza, Nazzaro, Pietro, Palatini, Paolo, Parati, Gianfranco, Pontremoli, Roberto, Quarti-Trevano, Fosca, Rattazzi, Marcello, Rivasi, Giulia, Salvetti, Massimo, Tocci, Giuliano, Ungar, Andrea, Verdecchia, Paolo, Viazzi, Francesca, Volpe, Massimo, Grassi, Guido, and Borghi, Claudio
Subjects: Adult, Male, medicine.medical_specialty, Adolescent, Physiology, cut-off value, 030204 cardiovascular system & hematology, 03 medical and health sciences, chemistry.chemical_compound, Young Adult, 0302 clinical medicine, uric acid, Internal medicine, Internal Medicine, medicine, ORIGINAL PAPERS: Epidemiology, Humans, sex, 030212 general & internal medicine, Hyperuricemia, Myocardial infarction, Risk factor, Aged, Aged, 80 and over, uric acid, cardiovascular, arterial hypertension, cut-off value, mortality, myocardial infarction,sex, uric acid, Proportional hazards model, business.industry, cut-off value, mortality, myocardial infarction, sex, uric acid, Hazard ratio, Middle Aged, medicine.disease, Prognosis, mortality, Confidence interval, Uric acid, myocardial infarction, epidemiology, myocardial infarction, chemistry, Italy, Hypertension, ComputingMethodologies_DOCUMENTANDTEXTPROCESSING, Uric acid, Female, Cardiology and Cardiovascular Medicine, business, Cohort study
Abstract: Supplemental Digital Content is available in the text, Objective: 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 fatal myocardial infaction (MI) in women and men. Methods: The URic acid Right for heArt Health study is a nationwide, multicentre, observational cohort study involving data on individuals 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 122.3 ± 66.9 months. Results: A total of 23 467 individuals were included in the analysis. Cut-off values of SUA able to discriminate MI status were identified by mean of receiver operating characteristic curves in the whole database (>5.70 mg/dl), in women (>5.26 mg/dl) and in men (>5.49 mg/dl). Multivariate Cox regression analyses adjusted for confounders (age, arterial hypertension, diabetes, chronic kidney disease, smoking habit, ethanol intake, BMI, haematocrit, LDL cholesterol and use of diuretics) identified an independent association between SUA and fatal MI in the whole database (hazard ratio 1.381, 95% confidence intervals, 1.096–1.758, P = 0.006) and in women (hazard ratio 1.514, confidence intervals 1.105–2.075, P
Published: 2020

33. Lifelong and mature-onset syncope in older adults may have different mechanisms

Author: Torabi, P, primary, Rivasi, G, additional, Hamrefors, V, additional, Sutton, R, additional, Brignole, M, additional, and Fedorowski, A, additional
Published: 2021
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34. Evaluation of Unattended Automated Office, Conventional Office and Ambulatory Blood Pressure Measurements and Their Correlation with Target Organ Damage in an Outpatient Population of Hypertensives: Study Design and Methodological Aspects

Author: Mancusi, C, Saladini, F, Pucci, G, Bertacchini, F, Bisogni, V, Bruno, R, Rivasi, G, Maloberti, A, Manzi, M, Rosticci, M, Monticone, S, de Feo, M, Del Pinto, R, Geraci, G, Canciello, G, Pengo, M, Parati, G, Mancusi C., Saladini F., Pucci G., Bertacchini F., Bisogni V., Bruno R. M., Rivasi G., Maloberti A., Manzi M. V., Rosticci M., Monticone S., de Feo M., Del Pinto R., Geraci G., Canciello G., Pengo M., Parati G., Mancusi, C, Saladini, F, Pucci, G, Bertacchini, F, Bisogni, V, Bruno, R, Rivasi, G, Maloberti, A, Manzi, M, Rosticci, M, Monticone, S, de Feo, M, Del Pinto, R, Geraci, G, Canciello, G, Pengo, M, Parati, G, Mancusi C., Saladini F., Pucci G., Bertacchini F., Bisogni V., Bruno R. M., Rivasi G., Maloberti A., Manzi M. V., Rosticci M., Monticone S., de Feo M., Del Pinto R., Geraci G., Canciello G., Pengo M., and Parati G.
Abstract: Accurate measurement of blood pressure (BP) has a pivotal role in the management of patients with arterial hypertension. Recently, introduction of unattended office BP measurement has been proposed as a method allowing more accurate management of hypertensive patients and prediction of hypertension-mediated target organ damage (HMOD). This approach to BP measurement has been in particular proposed to avoid the white coat effect (WCE), which can be easily assessed once both attended and unattended BP measurements are obtained. In spite of its interest, the role of WCE in predicting HMOD remains largely unexplored. To fill this gap the Young Investigator Group of the Italian Hypertension Society (SIIA) conceived the study “Evaluation of unattended automated office, conventional office and ambulatory blood pressure measurements and their correlation with target organ damage in an outpatient population of hypertensives”. This is a no-profit multicenter observational study aiming to correlate attended and unattended BP measurements for quantification of WCE and to correlate WCE with markers of HMOD, such us left ventricular hypertrophy, left atrial dilatation, and peripheral atherosclerosis. The Ethical committee of the Federico II University hospital has approved the study.
Published: 2019

35. Orthostatic hypotension and health outcomes: an umbrella review of observational studies

Author: Soysal, P., Veronese, N., Smith, L., Torbahn, G., Jackson, S. E., Yang, L., Ungar, A., Rivasi, G., Rafanelli, M., Petrovic, M., Maggi, S., Isik, A. T., Demurtas, J., The Special Interest Groups in Systematic Reviews and Meta-analyses for Healthy Ageing, and Cardiovascular Medicine of the European Society of Geriatric Medicine (EuGMS), SOYSAL, PINAR, Soysal, P., Veronese, N., Smith, L., Torbahn, G., Jackson, S.E., Yang, L., Ungar, A., Rivasi, G., Rafanelli, M., Petrovic, M., Maggi, S., Isik, A.T., Demurtas, J., and The Special Interest Groups in Systematic Reviews and Meta-analyses for Healthy Ageing, and Cardiovascular Medicine of the European Society of Geriatric Medicine (EuGMS)
Subjects: medicine.medical_specialty, 030214 geriatrics, Heart disease, business.industry, medicine.disease, Lower risk, an umbrella review of observational studies-, EUROPEAN GERIATRIC MEDICINE, cilt.10, ss.863-870, 2019 [SOYSAL P., Veronese N., Smith L., Torbahn G., Jackson S. E. , Yang L., Ungar A., Rivasi G., Rafanelli M., Petrovic M., et al., -Orthostatic hypotension and health outcomes], 03 medical and health sciences, Orthostatic vital signs, 0302 clinical medicine, Heart failure, Internal medicine, Meta-analysis, medicine, Dementia, Observational study, 030212 general & internal medicine, business, Stroke, Orthostatic hypotension · Umbrella review · Meta-analysis · Mortality · Fall · Heart failure · Heart disease · Stroke
Abstract: To investigate potential relationships between orthostatic hypotension (OH) and negative health outcomes and mortality, through an umbrella review with integrated meta-analyses. Orthostatic hypotension is significantly associated with several negative outcomes in older people, but a suggestive evidence is available only for higher risk of coronary heart disease congestive heart failure, stroke, falls dementia, and all-cause mortality. Orthostatic hypotension seems to be significantly associated with several negative health outcomes in older people, even if only associations with coronary heart disease, congestive heart failure, stroke, falls, dementia, and all-cause mortality are supported by suggestive evidence. Orthostatic hypotension (OH) is associated with older age and many negative clinical outcomes in geriatric practice. We aimed to capture the breadth of outcomes that have been associated with the presence of OH and systematically assess the quality, strength and credibility of these associations using an umbrella review with integrated meta-analyses. We systematically searched several major databases from their commencements through to 16th May 2019 for meta-analyses of observational studies of OH and any health-related outcome. We used these metrics to categorize the strength of evidence of significant outcomes (p
Published: 2019

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

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

37. Serum uric acid, predicts heart failure in a large Italian cohort: search for a cut-off value the URic acid Right for heArt Health study

Author: Muiesan, M, Salvetti, M, Virdis, A, Masi, S, Casiglia, E, Tikhonoff, V, Barbagallo, C, Bombelli, M, Cicero, A, Cirillo, M, Cirillo, P, Desideri, G, D’Eliak, L, Ferri, C, Galletti, F, Gesualdo, L, Giannattasio, C, Iaccarino, G, Mallamaci, F, Maloberti, A, Mazza, A, Nazzaro, P, Palatini, P, Parati, G, Pontremoli, R, Rattazzi, M, Rivasi, G, Tocci, G, Ungar, A, Verdecchia, P, Viazzi, F, Volpe, M, Grassi, G, Borghi, C, Muiesan, Maria L., Salvetti, Massimo, Virdis, Agostino, Masi, Stefano, Casiglia, Edoardo, Tikhonoff, Valérie, Barbagallo, Carlo M., Bombelli, Michele, Cicero, Arrigo F. G., Cirillo, Massimo, Cirillo, Pietro, Desideri, Giovambattista, D’Eliak, Lanfranco, Ferri, Claudio, Galletti, Ferruccio, Gesualdo, Loreto, Giannattasio, Cristina, Iaccarino, Guido, Mallamaci, Francesca, Maloberti, Alessandro, Mazza, Alberto, Nazzaro, Pietro, Palatini, Paolo, Parati, Gianfranco, Pontremoli, Roberto, Rattazzi, Marcello, Rivasi, Giulia, Tocci, Giuliano, Ungar, Andrea, Verdecchia, Paolo, Viazzi, Francesca, Volpe, Massimo, Grassi, Guido, Borghi, Claudio, Muiesan, M, Salvetti, M, Virdis, A, Masi, S, Casiglia, E, Tikhonoff, V, Barbagallo, C, Bombelli, M, Cicero, A, Cirillo, M, Cirillo, P, Desideri, G, D’Eliak, L, Ferri, C, Galletti, F, Gesualdo, L, Giannattasio, C, Iaccarino, G, Mallamaci, F, Maloberti, A, Mazza, A, Nazzaro, P, Palatini, P, Parati, G, Pontremoli, R, Rattazzi, M, Rivasi, G, Tocci, G, Ungar, A, Verdecchia, P, Viazzi, F, Volpe, M, Grassi, G, Borghi, C, Muiesan, Maria L., Salvetti, Massimo, Virdis, Agostino, Masi, Stefano, Casiglia, Edoardo, Tikhonoff, Valérie, Barbagallo, Carlo M., Bombelli, Michele, Cicero, Arrigo F. G., Cirillo, Massimo, Cirillo, Pietro, Desideri, Giovambattista, D’Eliak, Lanfranco, Ferri, Claudio, Galletti, Ferruccio, Gesualdo, Loreto, Giannattasio, Cristina, Iaccarino, Guido, Mallamaci, Francesca, Maloberti, Alessandro, Mazza, Alberto, Nazzaro, Pietro, Palatini, Paolo, Parati, Gianfranco, Pontremoli, Roberto, Rattazzi, Marcello, Rivasi, Giulia, Tocci, Giuliano, Ungar, Andrea, Verdecchia, Paolo, Viazzi, Francesca, Volpe, Massimo, Grassi, Guido, and Borghi, Claudio
Abstract: OBJECTIVE: To assess the prognostic cut-off values of serum uric acid (SUA) in predicting fatal and morbid heart failure in a large Italian cohort in the frame of the Working Group on Uric Acid and Cardiovascular Risk of the Italian Society of Hypertension. METHODS: The URic acid Right for heArt Health (URRAH) study is a nationwide, multicentre, cohort study involving data on individuals aged 18-95 years, recruited on a community basis from all regions of Italy under the patronage of the Italian Society of Hypertension with a mean follow-up period of 128 ± 65 months. Incident heart failure was defined on the basis of International Classification of Diseases Tenth Revision codes and double-checked with general practitioners and hospital files. Multivariate Cox regression models having fatal and morbid heart failure as dependent variables, adjusted for sex, age, SBP, diabetes, estimated glomerular filtration rate, smoking habit, ethanol intake, BMI, haematocrit, LDL cholesterol, previous diagnosis of heart failure and use of diuretics as possible confounders, were used to search for an association between SUA as a continuous variable and heart failure. By means of receiver operating characteristic curves, two prognostic cut-off values (one for all heart failure and one for fatal heart failure) were identified as able to discriminate between individuals doomed to develop the event. These cut-off values were used as independent predictors to divide individuals according to prognostic cut-off values in a multivariate Cox models, adjusted for confounders. RESULTS: A total of 21 386 individuals were included in the analysis. In Cox analyses, SUA as a continuous variable was a significant predictor of all [hazard ratio 1.29 (1.23-1.359), P < 0.0001] and fatal [hazard ratio 1.268 (1.121-1.35), P < 0.0001] incident heart failure. Cut-off values of SUA able to discriminate all and fatal heart failure status were identified by mean of receiver operating characteristic cur
Published: 2021

38. Serum Uric Acid and Kidney Disease Measures Independently Predict Cardiovascular and Total Mortality: The Uric Acid Right for Heart Health (URRAH) Project

Author: Russo, E, Viazzi, F, Pontremoli, R, Barbagallo, C, Bombelli, M, Casiglia, E, Cicero, A, Cirillo, M, Cirillo, P, Desideri, G, D'Elia, L, Dell'Oro, R, Ferri, C, Galletti, F, Gesualdo, L, Giannattasio, C, Iaccarino, G, Leoncini, G, Mallamaci, F, Maloberti, A, Masi, S, Mengozzi, A, Mazza, A, Muiesan, M, Nazzaro, P, Palatini, P, Parati, G, Rattazzi, M, Rivasi, G, Salvetti, M, Tikhonoff, V, Tocci, G, Quarti Trevano, F, Ungar, A, Verdecchia, P, Virdis, A, Volpe, M, Grassi, G, Borghi, C, Russo, Elisa, Viazzi, Francesca, Pontremoli, Roberto, Barbagallo, Carlo M, Bombelli, Michele, Casiglia, Edoardo, Cicero, Arrigo F G, Cirillo, Massimo, Cirillo, Pietro, Desideri, Giovambattista, D'Elia, Lanfranco, Dell'Oro, Raffaella, Ferri, Claudio, Galletti, Ferruccio, Gesualdo, Loreto, Giannattasio, Cristina, Iaccarino, Guido, Leoncini, Giovanna, Mallamaci, Francesca, Maloberti, Alessandro, Masi, Stefano, Mengozzi, Alessandro, Mazza, Alberto, Muiesan, Maria L, Nazzaro, Pietro, Palatini, Paolo, Parati, Gianfranco, Rattazzi, Marcello, Rivasi, Giulia, Salvetti, Massimo, Tikhonoff, Valérie, Tocci, Giuliano, Quarti Trevano, Fosca A L, Ungar, Andrea, Verdecchia, Paolo, Virdis, Agostino, Volpe, Massimo, Grassi, Guido, Borghi, Claudio, Russo, E, Viazzi, F, Pontremoli, R, Barbagallo, C, Bombelli, M, Casiglia, E, Cicero, A, Cirillo, M, Cirillo, P, Desideri, G, D'Elia, L, Dell'Oro, R, Ferri, C, Galletti, F, Gesualdo, L, Giannattasio, C, Iaccarino, G, Leoncini, G, Mallamaci, F, Maloberti, A, Masi, S, Mengozzi, A, Mazza, A, Muiesan, M, Nazzaro, P, Palatini, P, Parati, G, Rattazzi, M, Rivasi, G, Salvetti, M, Tikhonoff, V, Tocci, G, Quarti Trevano, F, Ungar, A, Verdecchia, P, Virdis, A, Volpe, M, Grassi, G, Borghi, C, Russo, Elisa, Viazzi, Francesca, Pontremoli, Roberto, Barbagallo, Carlo M, Bombelli, Michele, Casiglia, Edoardo, Cicero, Arrigo F G, Cirillo, Massimo, Cirillo, Pietro, Desideri, Giovambattista, D'Elia, Lanfranco, Dell'Oro, Raffaella, Ferri, Claudio, Galletti, Ferruccio, Gesualdo, Loreto, Giannattasio, Cristina, Iaccarino, Guido, Leoncini, Giovanna, Mallamaci, Francesca, Maloberti, Alessandro, Masi, Stefano, Mengozzi, Alessandro, Mazza, Alberto, Muiesan, Maria L, Nazzaro, Pietro, Palatini, Paolo, Parati, Gianfranco, Rattazzi, Marcello, Rivasi, Giulia, Salvetti, Massimo, Tikhonoff, Valérie, Tocci, Giuliano, Quarti Trevano, Fosca A L, Ungar, Andrea, Verdecchia, Paolo, Virdis, Agostino, Volpe, Massimo, Grassi, Guido, and Borghi, Claudio
Abstract: Background: Serum uric acid predicts the onset and progression of kidney disease, and the occurrence of cardiovascular and all-cause mortality. Nevertheless, it is unclear which is the appropriate definition of hyperuricemia in presence of chronic kidney disease (CKD). Our goal was to study the independent impact of uric acid and CKD on mortality.Methods: We retrospectively investigated 21,963 patients from the URRAH study database. Hyperuricemia was defined on the basis of outcome specific cut-offs separately identified by ROC curves according to eGFR strata. The primary endpoints were cardiovascular and all-cause mortality.Results: After a mean follow-up of 9.8 year, there were 1,582 (7.20%) cardiovascular events and 3,130 (14.25%) deaths for all causes. The incidence of cardiovascular and all-cause mortality increased in parallel with reduction of eGFR strata and with progressively higher uric acid quartiles. During 215,618 person-years of follow-up, the incidence rate for cardiovascular mortality, stratified based on eGFR (>90, between 60 and 90 and <60 ml/min) was significantly higher in patients with hyperuricemia and albuminuria (3.8, 22.1 and 19.1, respectively) as compared to those with only one risk factor or none (0.4, 2.8 and 3.1, respectively). Serum uric acid and eGFR significantly interact in determining cardiovascular and all-cause mortality. For each SUA increase of 1 mg/dl the risk for mortality increased by 10% even after adjustment for potential confounding factors included eGFR and the presence of albuminuria.Conclusions: hyperuricemia is a risk factor for cardiovascular and all-cause mortality additively to eGFR strata and albuminuria, in patients at cardiovascular risk.
Published: 2021

39. Exploration into Uric and Cardiovascular Disease: Uric Acid Right for heArt Health (URRAH) Project, A Study Protocol for a Retrospective Observational Study

Author: 644 Desideri, G, Virdis, A, Casiglia, E, Borghi, C, Cicero, A, Muiesan, M, Agabiti-Rosei, E, Salvetti, M, Ungar, A, Rivasi, G, Pontremoli, R, Viazzi, Grassi, G, Bombelli, M, Facchetti, R, Ferri, C, Bernardino, B, Galetti, F, D’Elia, L, Palatini, P, Tickhonoff, V, Barbagallo, C, Verdecchia, P, Masi, S, Mallamaci, F, Cirillo, M, Gesualdo, L, Mazza, A, Giannattasio, C, Maloberti, A, Ratazzi, M, Pauletto, P, Volpe, M, Tocci, G, Iaccarino, G, Nazzaro, P, 644 Desideri G, Virdis A, Casiglia E, Borghi C, Cicero A, Muiesan ML, Agabiti-Rosei E, Salvetti M, Ungar A, Rivasi G, Pontremoli R, GRASSI G, Bombelli M, Facchetti R, Ferri C, Bernardino B, Galetti F, D’Elia L, Palatini P, Tickhonoff V, Barbagallo CM, Verdecchia P, Masi S, Mallamaci F, Cirillo M, Gesualdo L, Mazza A, giannattasio C, Maloberti A, Ratazzi M, Pauletto P, Volpe M, Tocci G, Iaccarino G, Nazzaro P, 644 Desideri, G, Virdis, A, Casiglia, E, Borghi, C, Cicero, A, Muiesan, M, Agabiti-Rosei, E, Salvetti, M, Ungar, A, Rivasi, G, Pontremoli, R, Viazzi, Grassi, G, Bombelli, M, Facchetti, R, Ferri, C, Bernardino, B, Galetti, F, D’Elia, L, Palatini, P, Tickhonoff, V, Barbagallo, C, Verdecchia, P, Masi, S, Mallamaci, F, Cirillo, M, Gesualdo, L, Mazza, A, Giannattasio, C, Maloberti, A, Ratazzi, M, Pauletto, P, Volpe, M, Tocci, G, Iaccarino, G, Nazzaro, P, 644 Desideri G, Virdis A, Casiglia E, Borghi C, Cicero A, Muiesan ML, Agabiti-Rosei E, Salvetti M, Ungar A, Rivasi G, Pontremoli R, GRASSI G, Bombelli M, Facchetti R, Ferri C, Bernardino B, Galetti F, D’Elia L, Palatini P, Tickhonoff V, Barbagallo CM, Verdecchia P, Masi S, Mallamaci F, Cirillo M, Gesualdo L, Mazza A, giannattasio C, Maloberti A, Ratazzi M, Pauletto P, Volpe M, Tocci G, Iaccarino G, and Nazzaro P
Abstract: The relevance of cardiovascular role played by levels of serum uric acid is dramatically growing, especially as cardiovascular risk factor potentially able to exert either a direct deleterious impact or a synergic effect with other cardiovascular risk factors. At the present time, it still remains undefined the threshold level of serum uric acid able to contribute to the cardiovascular risk. Indeed, the available epidemiological case studies are not homogeneous, and some preliminary data suggest that the so-called “cardiovascular threshold limit” may substantially differ from that identified as a cut-off able to trigger the acute gout attack. In such scenario, there is the necessity to clarify and quantify this threshold value, to insert it in the stratification of risk algorithm scores and, in turn, to adopt proper prevention and correction strategies. The clarification of the relationship between circulating levels of uric acid and cardio-nephro-metabolic disorders in a broad sample representative of general population is critical to identify the threshold value of serum uric acid better discriminating the increased risk associated with uric acid. The Uric acid Right for heArt Health (URRAH) project has been designed to define, as primary objective, the level of uricemia above which the independent risk of cardiovascular disease may increase in a significantly manner in a general Italian population.
Published: 2018

40. Identification of the Uric Acid Thresholds Predicting an Increased Total and Cardiovascular Mortality over 20 Years

Author: Virdis, A. Masi, S. Casiglia, E. Tikhonoff, V. Cicero, A.F.G. Ungar, A. Rivasi, G. Salvetti, M. Barbagallo, C.M. Bombelli, M. Dell'Oro, R. Bruno, B. Lippa, L. D'Elia, L. Verdecchia, P. Mallamaci, F. Cirillo, M. Rattazzi, M. Cirillo, P. Gesualdo, L. Mazza, A. Giannattasio, C. Maloberti, A. Volpe, M. Tocci, G. Georgiopoulos, G. Iaccarino, G. Nazzaro, P. Parati, G. Palatini, P. Galletti, F. Ferri, C. Desideri, G. Viazzi, F. Pontremoli, R. Muiesan, M.L. Grassi, G. Borghi, C.
Abstract: Serum uric acid (SUA) levels discriminating across the different strata of cardiovascular risk is still unknown. By utilizing a large population-based database, we assessed the threshold of SUA that increases the risk of total mortality and cardiovascular mortality (CVM). The URRAH study (Uric Acid Right for Heart Health) is a multicentre retrospective, observational study, which collected data from several large population-based longitudinal studies in Italy and subjects recruited in the hypertension clinics of the Italian Society of Hypertension. Total mortality was defined as mortality for any cause, CVM as death due to fatal myocardial infarction, stroke, sudden cardiac death, or heart failure. A total of 22 714 subjects were included in the analysis. Multivariate Cox regression analyses identified an independent association between SUA and total mortality (hazard ratio, 1.53 [95% CI, 1.21-1.93]) or CVM (hazard ratio, 2.08 [95% CI, 1.146-2.97]; P
Published: 2020

41. Blood pressure management in hypertensive patients with syncope: how to balance hypotensive and cardiovascular risk

Author: Rivasi, G, Brignole, M, Rafanelli, M, Bilo, G, Pengo, M, Ungar, A, Parati, G, Rivasi, G, Brignole, M, Rafanelli, M, Bilo, G, Pengo, M, Ungar, A, and Parati, G
Abstract: Managing hypertension in syncope patients requires the accurate balancing of hypotensive and cardiovascular risks. On the basis of the available literature, this study analyses the complex inter-relationship between these clinical problems and presents an algorithm strategy to guide hypertension management in patients affected by syncope episodes. A SBP target of 120mmHg is recommended in patients with a low syncope risk and a high cardiovascular risk. In patients with a high syncope risk and a low cardiovascular risk, and in older (70R) frail individuals, a less intensive treatment is advisable, targeting SBP of 140 mmHg. SBP values up to 160mmHg can be tolerated in severe frailty or disability. Patients with hypertension and syncope may benefit from team-based care by a 'Blood Pressure Team' including experts on hypertension and syncope and a geriatrician. The team should carry out a multidimensional assessment to balance syncope and cardiovascular risk and develop therapeutic strategies customized to individuals' frailty and functional status.
Published: 2020

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

Author: Maloberti, A, Giannattasio, C, Bombelli, M, Desideri, G, Cicero, A, Muiesan, M, Rosei, E, 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, 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, Borghi, C, Maloberti, Alessandro, Cicero, A F G, Muiesan, M L, Rosei, E A, Barbagallo, C M, Maloberti, A, Giannattasio, C, Bombelli, M, Desideri, G, Cicero, A, Muiesan, M, Rosei, E, 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, 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, Borghi, C, Maloberti, Alessandro, Cicero, A F G, Muiesan, M L, Rosei, E A, and Barbagallo, C M
Abstract: The latest European Guidelines of Arterial Hypertension have officially introduced uric acid evaluation among the cardiovascular risk factors that should be evaluated in order to stratify patient’s risk. In fact, it has been extensively evaluated and demonstrated to be an independent predictor not only of all-cause and cardiovascular mortality, but also of myocardial infraction, stroke and heart failure. Despite the large number of studies on this topic, an important open question that still need to be answered is the identification of a cardiovascular uric acid cut-off value. The actual hyperuricemia cut-off (> 6 mg/dL in women and 7 mg/dL in men) is principally based on the saturation point of uric acid but previous evidence suggests that the negative impact of cardiovascular system could occur also at lower levels. In this context, the Working Group on uric acid and CV risk of the Italian Society of Hypertension has designed the Uric acid Right for heArt Health project. The primary objective of this project is to define the level of uricemia above which the independent risk of CV disease may increase in a significantly manner. In this review we will summarize the first results obtained and describe the further planned analysis.
Published: 2020

43. Identification of the Uric Acid Thresholds Predicting an Increased Total and Cardiovascular Mortality Over 20 Years

Author: Virdis, A, Masi, S, Casiglia, E, Tikhonoff, V, Cicero, A, Ungar, A, Rivasi, G, Salvetti, M, Barbagallo, C, Bombelli, M, Dell'Oro, R, Bruno, B, Lippa, L, D'Elia, L, Verdecchia, P, Mallamaci, F, Cirillo, M, Rattazzi, M, Cirillo, P, Gesualdo, L, Mazza, A, Giannattasio, C, Maloberti, A, Volpe, M, Tocci, G, Georgiopoulos, G, Iaccarino, G, Nazzaro, P, Parati, G, Palatini, P, Galletti, F, Ferri, C, Desideri, G, Viazzi, F, Pontremoli, R, Muiesan, M, Grassi, G, Borghi, C, Virdis, Agostino, Masi, Stefano, Casiglia, Edoardo, Tikhonoff, Valerie, Cicero, Arrigo F G, Ungar, Andrea, Rivasi, Giulia, Salvetti, Massimo, Barbagallo, Carlo M, Bombelli, Michele, Dell'Oro, Raffaella, Bruno, Berardino, Lippa, Luciano, D'Elia, Lanfranco, Verdecchia, Paolo, Mallamaci, Francesca, Cirillo, Massimo, Rattazzi, Marcello, Cirillo, Pietro, Gesualdo, Loreto, Mazza, Alberto, Giannattasio, Cristina, Maloberti, Alessandro, Volpe, Massimo, Tocci, Giuliano, Georgiopoulos, Georgios, Iaccarino, Guido, Nazzaro, Pietro, Parati, Gianfranco, Palatini, Paolo, Galletti, Ferruccio, Ferri, Claudio, Desideri, Giovambattista, Viazzi, Francesca, Pontremoli, Roberto, Muiesan, Maria Lorenza, Grassi, Guido, Borghi, Claudio, Virdis, A, Masi, S, Casiglia, E, Tikhonoff, V, Cicero, A, Ungar, A, Rivasi, G, Salvetti, M, Barbagallo, C, Bombelli, M, Dell'Oro, R, Bruno, B, Lippa, L, D'Elia, L, Verdecchia, P, Mallamaci, F, Cirillo, M, Rattazzi, M, Cirillo, P, Gesualdo, L, Mazza, A, Giannattasio, C, Maloberti, A, Volpe, M, Tocci, G, Georgiopoulos, G, Iaccarino, G, Nazzaro, P, Parati, G, Palatini, P, Galletti, F, Ferri, C, Desideri, G, Viazzi, F, Pontremoli, R, Muiesan, M, Grassi, G, Borghi, C, Virdis, Agostino, Masi, Stefano, Casiglia, Edoardo, Tikhonoff, Valerie, Cicero, Arrigo F G, Ungar, Andrea, Rivasi, Giulia, Salvetti, Massimo, Barbagallo, Carlo M, Bombelli, Michele, Dell'Oro, Raffaella, Bruno, Berardino, Lippa, Luciano, D'Elia, Lanfranco, Verdecchia, Paolo, Mallamaci, Francesca, Cirillo, Massimo, Rattazzi, Marcello, Cirillo, Pietro, Gesualdo, Loreto, Mazza, Alberto, Giannattasio, Cristina, Maloberti, Alessandro, Volpe, Massimo, Tocci, Giuliano, Georgiopoulos, Georgios, Iaccarino, Guido, Nazzaro, Pietro, Parati, Gianfranco, Palatini, Paolo, Galletti, Ferruccio, Ferri, Claudio, Desideri, Giovambattista, Viazzi, Francesca, Pontremoli, Roberto, Muiesan, Maria Lorenza, Grassi, Guido, and Borghi, Claudio
Abstract: Serum uric acid (SUA) levels discriminating across the different strata of cardiovascular risk is still unknown. By utilizing a large population-based database, we assessed the threshold of SUA that increases the risk of total mortality and cardiovascular mortality (CVM). The URRAH study (Uric Acid Right for Heart Health) is a multicentre retrospective, observational study, which collected data from several large population-based longitudinal studies in Italy and subjects recruited in the hypertension clinics of the Italian Society of Hypertension. Total mortality was defined as mortality for any cause, CVM as death due to fatal myocardial infarction, stroke, sudden cardiac death, or heart failure. A total of 22 714 subjects were included in the analysis. Multivariate Cox regression analyses identified an independent association between SUA and total mortality (hazard ratio, 1.53 [95% CI, 1.21-1.93]) or CVM (hazard ratio, 2.08 [95% CI, 1.146-2.97]; P<0.001). Cutoff values of SUA able to discriminate total mortality (4.7 mg/dL [95% CI, 4.3-5.1 mg/dL]) and CVM status (5.6 mg/dL [95% CI, 4.99-6.21 mg/dL]) were identified. The information on SUA levels provided a significant net reclassification improvement of 0.26 and of 0.27 over the Heart Score risk chart for total mortality and CVM, respectively (P<0.001). Sex-specific cutoff values for total mortality and CVM were also identified and validated. In conclusion, SUA levels increasing the risk of total mortality and CVM are significantly lower than those used for the definition of hyperuricemia in clinical practice. Our data provide evidence of a cardiovascular SUA threshold that might contribute in clinical practice to improve identification of patients at higher risk of CVM.
Published: 2020

44. Serum uric acid and fatal myocardial infarction: detection of prognostic cut-off values: The URRAH (Uric Acid Right for Heart Health) study

Author: Casiglia, E, Tikhonoff, V, Virdis, A, Masi, S, 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, Lippa, L, Mallamaci, F, Maloberti, A, 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, Volpe, M, Grassi, G, Borghi, C, Casiglia, Edoardo, Tikhonoff, Valérie, Virdis, Agostino, Masi, Stefano, Barbagallo, Carlo M, Bombelli, Michele, Bruno, Bernardino, Cicero, Arrigo F G, Cirillo, Massimo, Cirillo, Pietro, Desideri, Giovambattista, D'Elia, Lanfranco, Ferri, Claudio, Galletti, Ferruccio, Gesualdo, Loreto, Giannattasio, Cristina, Iaccarino, Guido, Lippa, Luciano, Mallamaci, Francesca, Maloberti, Alessandro, Mazza, Alberto, Muiesan, Maria Lorenza, Nazzaro, Pietro, Palatini, Paolo, Parati, Gianfranco, Pontremoli, Roberto, Quarti-Trevano, Fosca, Rattazzi, Marcello, Rivasi, Giulia, Salvetti, Massimo, Tocci, Giuliano, Ungar, Andrea, Verdecchia, Paolo, Viazzi, Francesca, Volpe, Massimo, Grassi, Guido, Borghi, Claudio, Casiglia, E, Tikhonoff, V, Virdis, A, Masi, S, 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, Lippa, L, Mallamaci, F, Maloberti, A, 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, Volpe, M, Grassi, G, Borghi, C, Casiglia, Edoardo, Tikhonoff, Valérie, Virdis, Agostino, Masi, Stefano, Barbagallo, Carlo M, Bombelli, Michele, Bruno, Bernardino, Cicero, Arrigo F G, Cirillo, Massimo, Cirillo, Pietro, Desideri, Giovambattista, D'Elia, Lanfranco, Ferri, Claudio, Galletti, Ferruccio, Gesualdo, Loreto, Giannattasio, Cristina, Iaccarino, Guido, Lippa, Luciano, Mallamaci, Francesca, Maloberti, Alessandro, Mazza, Alberto, Muiesan, Maria Lorenza, Nazzaro, Pietro, Palatini, Paolo, Parati, Gianfranco, Pontremoli, Roberto, Quarti-Trevano, Fosca, Rattazzi, Marcello, Rivasi, Giulia, Salvetti, Massimo, Tocci, Giuliano, Ungar, Andrea, Verdecchia, Paolo, Viazzi, Francesca, Volpe, Massimo, Grassi, Guido, and Borghi, Claudio
Abstract: Objective: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 fatal myocardial infaction (MI) in women and men.Methods:The URic acid Right for heArt Health study is a nationwide, multicentre, observational cohort study involving data on individuals 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 122.3 ± 66.9 months.Results:A total of 23 467 individuals were included in the analysis. Cut-off values of SUA able to discriminate MI status were identified by mean of receiver operating characteristic curves in the whole database (>5.70 mg/dl), in women (>5.26 mg/dl) and in men (>5.49 mg/dl). Multivariate Cox regression analyses adjusted for confounders (age, arterial hypertension, diabetes, chronic kidney disease, smoking habit, ethanol intake, BMI, haematocrit, LDL cholesterol and use of diuretics) identified an independent association between SUA and fatal MI in the whole database (hazard ratio 1.381, 95% confidence intervals, 1.096-1.758, P = 0.006) and in women (hazard ratio 1.514, confidence intervals 1.105-2.075, P < 0.01), but not in men.Conclusion:The results of the current study confirm that SUA is an independent risk factor for fatal MI after adjusting for potential confounding variables, and demonstrate that a prognostic cut-off value associated to fatal MI can be identified at least in women.
Published: 2020

45. Exploration into Uric and Cardiovascular Disease: Uric Acid Right for heArt Health (URRAH) Project, A Study Protocol for a Retrospective Observational Study

Author: Desideri, Giovambattista, Virdis, Agostino, Casiglia, Edoardo, Borghi Claudio, Cicero AFG, Muiesan ML, Rosei EA, Salvetti M, Ungar A, Rivasi G, Pontremoli R, Viazzi F, Desideri G, Grassi G, Bombelli M, Facchetti R, Ferri C, Bernardino B, Galletti F, D'Elia L, Palatini P, Casiglia E, Tikhonoff V, Barbagallo CM, Verdecchia P, Virdis, Pietrina, Masi S, Mallamaci F, Cirillo M, Rattazzi M, Pauletto P, Cirillo P, Gesualdo L, Mazza A, Giannattasio C, Maloberti A, Volpe M, Tocci G, Iaccarino G, Nazzaro, Desideri, Giovambattista, Virdis, Agostino, Casiglia, Edoardo, Borghi, Claudio, 644 Desideri, G, Virdis, A, Casiglia, E, Borghi, C, Cicero, A, Muiesan, M, Agabiti-Rosei, E, Salvetti, M, Ungar, A, Rivasi, G, Pontremoli, R, Viazzi, Grassi, G, Bombelli, M, Facchetti, R, Ferri, C, Bernardino, B, Galetti, F, D’Elia, L, Palatini, P, Tickhonoff, V, Barbagallo, C, Verdecchia, P, Masi, S, Mallamaci, F, Cirillo, M, Gesualdo, L, Mazza, A, Giannattasio, C, Maloberti, A, Ratazzi, M, Pauletto, P, Volpe, M, Tocci, G, Iaccarino, G, Nazzaro, P, Cicero, Afg, Muiesan, Ml, Rosei, Ea, Viazzi, F, Desideri, G, Galletti, F, D'Elia, L, Tikhonoff, V, Barbagallo, Cm, Virdis, Pietrina, Rattazzi, M, Cirillo, P, and Nazzaro
Subjects: medicine.medical_specialty, Settore MED/09 - Medicina Interna, Prognosi, Epidemiology, Population, Disease, Hyperuricemia, 030204 cardiovascular system & hematology, Risk Assessment, Cardiovascular disease, Uric acid, Biomarkers, Cardiovascular Diseases, Humans, Italy, Prognosis, Research Design, Retrospective Studies, Risk Factors, Uric Acid, Internal Medicine, Cardiology and Cardiovascular Medicine, 03 medical and health sciences, chemistry.chemical_compound, 0302 clinical medicine, Retrospective Studie, Internal medicine, medicine, Risk factor, education, 030203 arthritis & rheumatology, education.field_of_study, business.industry, Risk Factor, Retrospective cohort study, Biomarker, medicine.disease, chemistry, business, Risk assessment, Human
Abstract: The relevance of cardiovascular role played by levels of serum uric acid is dramatically growing, especially as cardiovascular risk factor potentially able to exert either a direct deleterious impact or a synergic effect with other cardiovascular risk factors. At the present time, it still remains undefined the threshold level of serum uric acid able to contribute to the cardiovascular risk. Indeed, the available epidemiological case studies are not homogeneous, and some preliminary data suggest that the so-called "cardiovascular threshold limit" may substantially differ from that identified as a cut-off able to trigger the acute gout attack. In such scenario, there is the necessity to clarify and quantify this threshold value, to insert it in the stratification of risk algorithm scores and, in turn, to adopt proper prevention and correction strategies. The clarification of the relationship between circulating levels of uric acid and cardio-nephro-metabolic disorders in a broad sample representative of general population is critical to identify the threshold value of serum uric acid better discriminating the increased risk associated with uric acid. The Uric acid Right for heArt Health (URRAH) project has been designed to define, as primary objective, the level of uricemia above which the independent risk of cardiovascular disease may increase in a significantly manner in a general Italian population.
Published: 2018

46. Near-infrared spectroscopy in evaluating psychogenic pseudosyncope—a novel diagnostic approach

Author: Claffey, P, primary, Pérez-Denia, L, primary, Rivasi, G, primary, Finucane, C, primary, and Kenny, R A, primary
Published: 2019
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47. P5678Near-infrared spectroscopy (NIRS) in the evaluation of psychogenic pseudosyncope - Moving towards a simplified diagnostic pathway

Author: Claffey, P, primary, Perez-Denia, L, additional, Rivasi, G, additional, Ungar, A, additional, Finucane, C, additional, and Kenny, R A, additional
Published: 2019
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48. Near-infrared spectroscopy in evaluating psychogenic pseudosyncope—a novel diagnostic approach.

Author: Claffey, P, Pérez-Denia, L, Rivasi, G, Finucane, C, and Kenny, R A
Subjects: SYNCOPE, BLOOD pressure, LOSS of consciousness, SPECTROMETRY, CONVERSION disorder, HEART beat
Abstract: Background Psychogenic pseudosyncope (PPS), a conversion disorder and syncope mimic, accounts for a large proportion of 'unexplained syncope'. PPS is diagnosed by reproduction of patients' symptoms during head-up tilt (HUT). Electroencephalogram (EEG), a time consuming and resource intensive technology, is used during HUT to demonstrate absence of cerebral hypoperfusion during transient loss of consciousness (TLOC). Near-infrared spectroscopy (NIRS) is a simple, non-invasive technology for continuous monitoring of cerebral perfusion. We present a series of patients for whom PPS diagnosis was supported by NIRS during HUT. Methods Eight consecutive patients with suspected PPS referred to a syncope unit underwent evaluation. During HUT, continuous beat-to-beat blood pressure (BP), heart rate (HR) and NIRS-derived tissue saturation index (TSI) were measured. BP, HR and TSI at baseline, time of first symptom, presyncope and apparent TLOC were measured. Patients were given feedback and followed for symptom recurrence. Results Eight predominantly female patients (6/8, 75%) aged 31 years (16–54) were studied with (5/8, 63%) having comorbid psychiatric diagnoses, and (5/8, 63%) presenting with frequent episodes of prolonged TLOC with eyes closed (6/8, 75%). All patients experienced reproduction of typical events during HUT. Systolic BP (mmHg) increased from baseline (129.7 (interquartile range [IQR] 124.9–133.4)) at TLOC (153.0 (IQR 146.7–159.0)) (P -value = 0.012). HR (bpm) increased from baseline 78 (IQR 68.6–90.0) to 115.7 (IQR 93.5–127.9) (P -value = 0.012). TSI (%) remained stable throughout, 71.4 (IQR 67.5–72.9) at baseline vs. 71.0 (IQR 68.2–73.0) at TLOC (P -value = 0.484). Conclusions NIRS provides a non-invasive surrogate of cerebral perfusion during HUT. We propose HUT incorporating NIRS monitoring in the diagnostic algorithm for patients with suspected PPS. [ABSTRACT FROM AUTHOR]
Published: 2020
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49. 073_16760 Predictors of Syncopal Recurrence after Cardiac Pacing in Patients with Carotid Sinus Syndrome

Author: Rafanelli, M., primary, Rivasi, G., additional, Solari, D., additional, Tesi, F., additional, Ceccofiglio, A., additional, Sacco, F.C., additional, Venzo, S., additional, Giannini, I., additional, Brignole, M., additional, and Ungar, A., additional
Published: 2017
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50. [PP.03.17] HYPERTENSION AND COGNITIVE FUNCTION IN THE ELDERLY

Author: Bulgaresi, M., primary, Menozzi, L., additional, Rivasi, G., additional, Sgrilli, F., additional, Giordano, A., additional, Latini, E., additional, Martella, L., additional, Mossello, E., additional, Ungar, A., additional, and Marchionni, N., additional
Published: 2017
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