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1. 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

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

Author

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

Published
2024

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

12. 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

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. 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

15. 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

16. Blood pressure and cardiovascular risk in relation to birth weight and urinary sodium:an individual-participant meta-analysis of European family-based population studies

Author

Yu, YL, Moliterno, P, An, DW, Raaijmakers, A, Martens, DS, Stolarz-Skrzypek, K, Tikhonoff, V, Malyutina, S, Casiglia, E, Chori, B, Filipovsky, J, Rajzer, M, Allegaert, K, Kawecka-Jaszcz, K, Verhamme, P, Nawrot, TS, Staessen, JA, Boggia, J, Yu, YL, Moliterno, P, An, DW, Raaijmakers, A, Martens, DS, Stolarz-Skrzypek, K, Tikhonoff, V, Malyutina, S, Casiglia, E, Chori, B, Filipovsky, J, Rajzer, M, Allegaert, K, Kawecka-Jaszcz, K, Verhamme, P, Nawrot, TS, Staessen, JA, and Boggia, J

Abstract

Background:Although the relation of salt intake with blood pressure (BP) is linear, it is U-shaped for mortality and cardiovascular disease (CVD). This individual-participant meta-Analysis explored whether the relation of hypertension, death or CVD with 24-h urinary sodium excretion (UVNA) or sodium-To-potassium (UNAK) ratio was modified by birth weight.Methods:Families were randomly enrolled in the Flemish Study on Genes, Environment and Health Outcomes (1985-2004) and the European Project on Genes in Hypertension (1999-2001). Categories of birth weight, UVNA and UNAK (≤2500, >2500-4000, >4000g; <2.3, 2.3-4.6 and >4.6g; and <1, 1-2, >2, respectively) were coded using deviation-from-mean coding and analyzed by Kaplan-Meier survival functions and linear and Cox regression.Results:The study population was subdivided into the Outcome (n=1945), Hypertension (n=1460) and Blood Pressure cohorts (n=1039) to analyze the incidence of mortality and cardiovascular endpoints, hypertension and BP changes as function of UVNA changes. The prevalence of low/medium/high birth weight in the Outcome cohort was 5.8/84.5/9.7%. Over 16.7years (median), rates were 4.9, 8 and 27.1% for mortality, CVD and hypertension, respectively, but were not associated with birth weight. Multivariable-Adjusted hazard ratios were not significant for any endpoint in any of the birth weight, UVNA and UNAK strata. Adult body weight tracked with birth weight (P<0.0001). The partial r in the low-birth-weight group associating changes from baseline to follow-up in UVNA and SBP was 0.68 (P=0.023) but not significant in other birth weight groups.Conclusion:This study did not substantiate its prior hypothesis but showed tracking of adult with birth weight and suggest that low birth weight increases salt sensitivity.

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. PROGNOSTIC CUT-OFF VALUES OF SERUM URIC ACID ASSOCIATED WITH FATAL AND NON FATAL INCIDENT MYOCARDIAL INFARCTION INDEPENDENTLY OF ARTERIAL HYPERTENSION IN A LARGE COHORT

Author

Casiglia, E., Virdis, A., Tikhonoff, V., Barbagallo, C.M., Cirillo, M., Desideri, G., Ferri, C., Galletti, F., Grassi, G., Giannattasio, C., Iaccarino, G., Mallamaci, F., Masi, S., Mazza, A., Muiesan, M.L., Palatini, P., Pontremoli, R., Verdecchia, P., Volpe, M., and Borghi, C.

Published
2019
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24. SERUM URIC ACID, INDEPENDENTLY OF ARTERIAL HYPERTENSION, PREDICTS NON-FATAL INCIDENT CEREBROVASCULAR EVENTS IN AN ITALIAN LARGE COHORT OF MEN AND WOMEN. SEARCH FOR A CUT-OFF VALUE

Author

Tikhonoff, V., Virdis, A., Barbagallo, C.M., Cirillo, M., Desideri, G., Ferri, C., Galletti, F., Grassi, G., Iaccarino, G., Muiesan, M.L., Nazzaro, P., Palatini, P., Parati, G., Rattazzi, M., Tocci, G., Viazzi, F., Verdecchia, P., Ungar, A., Casiglia, E., and Borghi, C.

Published
2019
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28. 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

29. 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

30. 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

31. 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

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. Mild-to-Moderate Kidney Dysfunction and Cardiovascular Disease: Observational and Mendelian Randomization Analyses

Author

Gaziano, L, Sun, L, Arnold, M, Bell, S, Cho, K, Kaptoge, SK, Song, RJ, Burgess, S, Posner, DC, Mosconi, K, Cohen, CR, Mason, AM, Bolton, TR, Tao, R, Allara, E, Schubert, P, Chen, L, Staley, JR, Staplin, N, Altay, S, Amiano, P, Arndt, PV, Arnlov, J, Barr, ELM, Bjorkelund, C, Boer, JMA, Brenner, H, Casiglia, E, Chiodini, P, Cooper, JA, Coresh, J, Cushman, M, Dankner, R, Davidson, KW, de Jongh, RT, Donfrancesco, C, Engstrom, G, Freisling, H, de la Camara, AG, Gudnason, V, Hankey, GJ, Hansson, P, Heath, AK, Hoorn, EJ, Imano, H, Jassal, SK, Kaaks, R, Katzke, V, Kauhanen, J, Kiechl, S, Koenig, W, Kronmal, RA, Kyro, C, Lawlor, DA, Ljungberg, B, MacDonald, C, Masala, G, Meisinger, C, Melander, O, Iribas, CM, Ninomiya, T, Nitsch, D, Nordestgaard, BG, OnlandMoret, C, Palmieri, L, Petrova, D, Garcia, JRQ, Rosengren, A, Sacerdote, C, Sakurai, M, Santiuste, C, Schulze, MB, Sieri, S, Sundstrom, J, Tikhonoff, V, Tjonneland, A, Tong, T, Tumino, R, Tzoulaki, I, van der Schouw, YT, Verschuren, WMM, Volzke, H, Wallace, RB, Wannamethee, SG, Weiderpass, E, Willeit, P, Woodward, M, Yamagishi, K, ZamoraRos, R, Akwo, EA, Pyarajan, S, Gagnon, DR, Tsao, PS, Muralidhar, S, Edwards, TL, Damrauer, SM, Joseph, J, Pennells, L, Wilson, PWF, Harrison, S, Gaziano, TA, Inouye, M, Baigent, C, Casas, JP, Langenberg, C, Wareham, N, Riboli, E, Gaziano, JM, Danesh, J, Hung, AM, Butterworth, AS, Wood, AM, Di Angelantonio, E, Gaziano, L, Sun, L, Arnold, M, Bell, S, Cho, K, Kaptoge, SK, Song, RJ, Burgess, S, Posner, DC, Mosconi, K, Cohen, CR, Mason, AM, Bolton, TR, Tao, R, Allara, E, Schubert, P, Chen, L, Staley, JR, Staplin, N, Altay, S, Amiano, P, Arndt, PV, Arnlov, J, Barr, ELM, Bjorkelund, C, Boer, JMA, Brenner, H, Casiglia, E, Chiodini, P, Cooper, JA, Coresh, J, Cushman, M, Dankner, R, Davidson, KW, de Jongh, RT, Donfrancesco, C, Engstrom, G, Freisling, H, de la Camara, AG, Gudnason, V, Hankey, GJ, Hansson, P, Heath, AK, Hoorn, EJ, Imano, H, Jassal, SK, Kaaks, R, Katzke, V, Kauhanen, J, Kiechl, S, Koenig, W, Kronmal, RA, Kyro, C, Lawlor, DA, Ljungberg, B, MacDonald, C, Masala, G, Meisinger, C, Melander, O, Iribas, CM, Ninomiya, T, Nitsch, D, Nordestgaard, BG, OnlandMoret, C, Palmieri, L, Petrova, D, Garcia, JRQ, Rosengren, A, Sacerdote, C, Sakurai, M, Santiuste, C, Schulze, MB, Sieri, S, Sundstrom, J, Tikhonoff, V, Tjonneland, A, Tong, T, Tumino, R, Tzoulaki, I, van der Schouw, YT, Verschuren, WMM, Volzke, H, Wallace, RB, Wannamethee, SG, Weiderpass, E, Willeit, P, Woodward, M, Yamagishi, K, ZamoraRos, R, Akwo, EA, Pyarajan, S, Gagnon, DR, Tsao, PS, Muralidhar, S, Edwards, TL, Damrauer, SM, Joseph, J, Pennells, L, Wilson, PWF, Harrison, S, Gaziano, TA, Inouye, M, Baigent, C, Casas, JP, Langenberg, C, Wareham, N, Riboli, E, Gaziano, JM, Danesh, J, Hung, AM, Butterworth, AS, Wood, AM, and Di Angelantonio, E

Abstract

BACKGROUND: End-stage renal disease is associated with a high risk of cardiovascular events. It is unknown, however, whether mild-to-moderate kidney dysfunction is causally related to coronary heart disease (CHD) and stroke. METHODS: Observational analyses were conducted using individual-level data from 4 population data sources (Emerging Risk Factors Collaboration, EPIC-CVD [European Prospective Investigation into Cancer and Nutrition-Cardiovascular Disease Study], Million Veteran Program, and UK Biobank), comprising 648 135 participants with no history of cardiovascular disease or diabetes at baseline, yielding 42 858 and 15 693 incident CHD and stroke events, respectively, during 6.8 million person-years of follow-up. Using a genetic risk score of 218 variants for estimated glomerular filtration rate (eGFR), we conducted Mendelian randomization analyses involving 413 718 participants (25 917 CHD and 8622 strokes) in EPIC-CVD, Million Veteran Program, and UK Biobank. RESULTS: There were U-shaped observational associations of creatinine-based eGFR with CHD and stroke, with higher risk in participants with eGFR values <60 or >105 mL·min-1·1.73 m-2, compared with those with eGFR between 60 and 105 mL·min-1·1.73 m-2. Mendelian randomization analyses for CHD showed an association among participants with eGFR <60 mL·min-1·1.73 m-2, with a 14% (95% CI, 3%-27%) higher CHD risk per 5 mL·min-1·1.73 m-2 lower genetically predicted eGFR, but not for those with eGFR >105 mL·min-1·1.73 m-2. Results were not materially different after adjustment for factors associated with the eGFR genetic risk score, such as lipoprotein(a), triglycerides, hemoglobin A1c, and blood pressure. Mendelian randomization results for stroke were nonsignificant but broadly similar to those for CHD. CONCLUSIONS: In people without manifest cardiovascular disease or diabetes, mild-to-moderate kidney dysfunction is causally related to risk of CHD, highlighting the potential value of preventive approaches th

Published
2022

34. PROGNOSTIC CUTOFF OF TRIGLYCERIDES PREDICTING CARDIOVASCULAR OUTCOME IN A LARGE REGIONAL-BASED ITALIAN DATABASE

Author

Tikhonoff, V, Casiglia, E, Virdis, A, Barbagallo, C, Cirillo, M, Desideri, G, Ferri, C, Galletti, F, Grassi, G, Giannattasio, C, Iaccarino, G, Mazza, A, Muiesan, M, Palatini, P, Parati, G, Pontremoli, R, Verdecchia, P, Volpe, M, Ungar, A, Borghi, C, Tikhonoff, Valerie, Casiglia, Edoardo, Virdis, Agostino, Barbagallo, Carlo, Cirillo, Massimo, Desideri, Giambattista, Ferri, Claudio, Galletti, Ferruccio, Grassi, Guido, Giannattasio, Cristina, Iaccarino, Guido, Mazza, Alberto, Muiesan, Maria Lorenza, Palatini, Paolo, Parati, Gianfranco, Pontremoli, Roberto, Verdecchia, Paolo, Volpe, Massimo, Ungar, Andrea, Borghi, Caludio, Tikhonoff, V, Casiglia, E, Virdis, A, Barbagallo, C, Cirillo, M, Desideri, G, Ferri, C, Galletti, F, Grassi, G, Giannattasio, C, Iaccarino, G, Mazza, A, Muiesan, M, Palatini, P, Parati, G, Pontremoli, R, Verdecchia, P, Volpe, M, Ungar, A, Borghi, C, Tikhonoff, Valerie, Casiglia, Edoardo, Virdis, Agostino, Barbagallo, Carlo, Cirillo, Massimo, Desideri, Giambattista, Ferri, Claudio, Galletti, Ferruccio, Grassi, Guido, Giannattasio, Cristina, Iaccarino, Guido, Mazza, Alberto, Muiesan, Maria Lorenza, Palatini, Paolo, Parati, Gianfranco, Pontremoli, Roberto, Verdecchia, Paolo, Volpe, Massimo, Ungar, Andrea, and Borghi, Caludio

Abstract

Objective: Searching for a prognostic cut-off value of triglycerides (TG) in predicting cardiovascular (CV) outcome in a large regional-based Italian database of men and women. Design and method: A nationwide multicentre database collects data on subjects aged 18 to 95 years recruited on a regional community basis from all the territory of Italy with at least 1 measure of TG and a mean follow-up of 110.1 ± 64.3 months. A total of 18,784 subjects were included in the analysis. CV outcome was defined on the basis of ICD10 codes and double-checked with general practitioners and hospital files. Multivariate dichotomic Cox regression models having CV outcome as dependent variable, adjusted for age, sex, serum uric acid, body mass index, total and HDL-cholesterol, arterial hypertension, diabetes, chronic renal disease, smoking habit, use of antihypertensive and lipid lowering drugs were preliminarily used to search for an association between TG log-transformed as a continuous variable and CV event. The conventional cut-off value of TG (150 mg/d) and the prognostic cut-off value of TG identified by means of receiver operating characteristics (ROC) curves, both able to discriminate between subjects developing a CV event, were used as independent predictors in further multivariate Cox models adjusted for the confounders listed above. Results: During 172,329 person-years of follow-up, 1910 participants experienced CV events (11.1 per 1000 age-adjusted person-years). In Cox analysis, TG as a continuous variable was a significant predictor of CV event [odds ratio, OR, 1.189 (1.060-1.334), p = 0.003]. ROC curve showed that > 105 mg/dl (95%CI 75.8-129.3, sensitivity 61.7, specificity 48.8, p < 0.0001) was the prognostic cut-off value for CV event. The conventional cut-off (150 mg/dl) and that identified by ROC curve (105 mg/dl) were both accepted as multivariate predictors in separate Cox analyses, the hazard ratios being 1.157 (95%CI 1.037-1.290, p = 0.009) and 1.137 (95%C

Published
2022

35. SERUM URIC ACID, LEFT VENTRICULAR MASS AND CARDIOVASCULAR DEATH. THE URIC ACID RIGHT FOR HEART HEALTH (URRAH) STUDY

Author

Muiesan, M, Salvetti, M, Paini, A, Rosei, C, Virdis, A, Casiglia, E, Tikhonoff, V, Barbagallo, C, Cirillo, M, Desideri, G, Ferri, C, Galletti, F, Giannattasio, C, Iaccarino, G, Mallamaci, F, Masi, S, Mazza, A, Palatini, P, Pontremoli, R, Verdecchia, P, Volpe, M, Grassi, G, Borghi, C, Muiesan, Maria Lorenza, Salvetti, Massimo, Paini, Anna, Rosei, Claudia Agabiti, Virdis, Agostino, Casiglia, Edoardo, Tikhonoff, Valerie, Barbagallo, Carlo Maria, Desideri, Giovanbattista, Ferri, Claudio, Galletti, Ferruccio, Giannattasio, Cristina, Iaccarino, Guido, Mallamaci, Francesca, Masi, Stefano, Mazza, Alberto, Palatini, Paolo, Pontremoli, Roberto, Verdecchia, Paolo, Volpe, Massimo, Grassi, Guido, Borghi, Claudio, Muiesan, M, Salvetti, M, Paini, A, Rosei, C, Virdis, A, Casiglia, E, Tikhonoff, V, Barbagallo, C, Cirillo, M, Desideri, G, Ferri, C, Galletti, F, Giannattasio, C, Iaccarino, G, Mallamaci, F, Masi, S, Mazza, A, Palatini, P, Pontremoli, R, Verdecchia, P, Volpe, M, Grassi, G, Borghi, C, Muiesan, Maria Lorenza, Salvetti, Massimo, Paini, Anna, Rosei, Claudia Agabiti, Virdis, Agostino, Casiglia, Edoardo, Tikhonoff, Valerie, Barbagallo, Carlo Maria, Desideri, Giovanbattista, Ferri, Claudio, Galletti, Ferruccio, Giannattasio, Cristina, Iaccarino, Guido, Mallamaci, Francesca, Masi, Stefano, Mazza, Alberto, Palatini, Paolo, Pontremoli, Roberto, Verdecchia, Paolo, Volpe, Massimo, Grassi, Guido, and Borghi, Claudio

Abstract

Objective: A relationship between serum uric acid(UA)and CV events has been documented in the URRAH study.The association between UA and left ventricular mass index(LVMI)has been investigated with heterogeneous results.Aim of this study was to investigate the association between UA and LVMI and whether UA and LVMI or they combination may predict the incidence of death for CV disease(CVM)in a large Italian cohort in the frame of the Working Group on Uric Acid and Cardiovascular Risk of the Italian Society of Hypertension(SIIA). Design and method: URRAH study is a nationwide,multicentre,observational cohort study involving data on subjects aged 18to95years,recruited on a community basis from all regions of Italy under the patronage of the SIIA.CVM was defined as death due to fatal myocardial infarction,stroke,sudden cardiac death,or heart failure.Multivariate Cox regression models having CVM as dependent variables,adjusted for age,sex,BMI, SBP,glycemia,total cholesterol,triglycerides,HDL-cholesterol,smoking and estimated glomerular filtration rate(eGFR)were used to search for an association between UAandLVMI as a continuous variable and CVM.LVH was defined asLVMI> 95 g/m2 in women and 115 g/m2 in men. Results: 10733 subjects(mean age,54years;51þmale)with echocardiographic LVMI measurements were included in the analysis study.A significant association between UA and LVMI was confirmed in multiple regression analysis in both sexes(men:beta0,095,F5.47,P < 0.001;women:beta0,069,F4.36,P < 0.001).During follow-up(median 130months),319subjects died for a CVevent,including myocardial infarction, angina pectoris, congestive heart failure and cerebrovascular disease.Previously identified sex specific cut off values(5.6 mg/dl men,5.1 mg/dl women)and LVH were used to define 4 different groups(normal UA and LVMI,increased UA and no LVH,normal UA and LVH,increased UA and LVH).Kaplan-Meier curves showed a significantly poorer survival rate in the group with higher UA and LV

Published
2022

36. 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

37. 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

43. Ambulatory blood pressure monitoring for risk stratification in obese and non-obese subjects from 10 populations

Author

Hansen, T W, Thijs, L, Li, Y, Boggia, J, Liu, Y, Asayama, K, Kikuya, M, Björklund-Bodegård, K, Ohkubo, T, Jeppesen, J, Torp-Pedersen, C, Dolan, E, Kuznetsova, T, Stolarz-Skrzypek, K, Tikhonoff, V, Malyutina, S, Casiglia, E, Nikitin, Y, Lind, L, Sandoya, E, Kawecka-Jaszcz, K, Filipovský, J, Imai, Y, Wang, J, O'Brien, E, and Staessen, J A

Published
2014
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45. 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

47. 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

48. 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

50. RELATIONSHIP BETWEEN DIURETIC RELATED HYPERURICEMIA AND CARDIOVASCULAR EVENTS: DATA FROM THE URRAH (URIC ACID RIGHT FOR HEART HEALTH) STUDY

Author

Maloberti, Alessandro, primary, Bombelli, M., additional, Facchetti, R., additional, Virdis, A., additional, Casiglia, E., additional, Tikhonoff, V., additional, Barbagallo, C.m., additional, Cirillo, M., additional, Desideri, G., additional, Ferri, C., additional, Galletti, F., additional, Iaccarino, G., additional, Mallamaci, F., additional, Masi, S., additional, Mazza, A., additional, Muiesan, M.l., additional, Salvetti, M., additional, Palatini, P., additional, Pontremoli, R., additional, Verdecchia, P., additional, Volpe, M., additional, Grassi, G., additional, Giannattasio, C., additional, and Borghi, C., additional

Published
2021
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