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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. Blood pressure-lowering treatment for prevention of major cardiovascular diseases in people with and without type 2 diabetes: an individual participant-level data meta-analysis

Author

Agodoa, L, Algra, A, Asselbergs, F W, Beckett, N, Berge, E, Black, H, Brouwers, F P J, Brown, M, Bulpitt, C J, Byington, B, Cutler, J, Devereaux, R B, Dwyer, J, Estacio, R, Fagard, R, Fox, K, Fukui, T, Imai, Y, Ishii, M, Julius, S, Kanno, Y, Kjeldsen, S E, Kostis, J, Kuramoto, K, Lanke, J, Lewis, E, Lewis, J, Lievre, M, Lindholm, L H, Lueders, S, MacMahon, S, Mancia, G, Matsuzaki, M, Mehlum, M H, Nissen, S, Ogawa, H, Ogihara, T, Ohkubo, T, Palmer, C, Patel, A, Pfeffer, M, Poulter, N R, Rakugi, H, Reboldi, G, Reid, C, Remuzzi, G, Ruggenenti, P, Saruta, T, Schrader, J, Schrier, R, Sever, P, Sleight, P, Staessen, J A, Suzuki, H, Thijs, L, Ueshima, K, Umemoto, S, van Gilst, W H, Verdecchia, P, Wachtell, K, Whelton, P, Wing, L, Yui, Y, Yusuf, S, Zanchetti, A, Zhang, Z Y, Anderson, C, Baigent, C, Brenner, BM, Collins, R, de Zeeuw, D, Lubsen, J, Malacco, E, Neal, B, Perkovic, V, Pitt, B, Rodgers, A, Rothwell, P, Salimi-Khorshidi, G, Sundström, J, Turnbull, F, Viberti, G, Wang, J, Nazarzadeh, Milad, Bidel, Zeinab, Canoy, Dexter, Copland, Emma, Bennett, Derrick A, Dehghan, Abbas, Davey Smith, George, Holman, Rury R, Woodward, Mark, Gupta, Ajay, Adler, Amanda I, Wamil, Malgorzata, Sattar, Naveed, Cushman, William C, McManus, Richard J, Teo, Koon, Davis, Barry R, Chalmers, John, Pepine, Carl J, and Rahimi, Kazem

Published
2022
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3. Antihypertensive treatment and risk of cancer: an individual participant data meta-analysis

Author

Adler, A, Agodoa, L, Algra, A, Asselbergs, F W, Beckett, N, Berge, E, Black, H, Brouwers, F P J, Brown, M, Bulpitt, C J, Byington, B, Chalmers, J, Cushman, W C, Cutler, J, Davis, B R, Devereaux, R B, Dwyer, J, Estacio, R, Fagard, R, Fox, K, Fukui, T, Gupta, A K, Holman, R R, Imai, Y, Ishii, M, Julius, S, Kanno, Y, Kjeldsen, S E, Kostis, J, Kuramoto, K, Lanke, J, Lewis, E, Lewis, J, Lievre, M, Lindholm, L H, Lueders, S, MacMahon, S, Mancia, G, Matsuzaki, M, Mehlum, M H, Nissen, S, Ogawa, H, Ogihara, T, Ohkubo, T, Palmer, C, Patel, A, Pepine, C J, Pfeffer, M, Poulter, N R, Rakugi, H, Reboldi, G, Reid, C, Remuzzi, G, Ruggenenti, P, Saruta, T, Schrader, J, Schrier, R, Sever, P, Sleight, P, Staessen, J A, Suzuki, H, Thijs, L, Ueshima, K, Umemoto, S, van Gilst, W H, Verdecchia, P, Wachtell, K, Whelton, P, Wing, L, Woodward, M, Yui, Y, Yusuf, S, Zanchetti, A, Zhang, Z Y, Anderson, C, Baigent, C, Brenner, BM, Collins, R, de Zeeuw, D, Lubsen, J, Malacco, E, Neal, B, Perkovic, V, Pitt, B, Rodgers, A, Rothwell, P, Salimi-Khorshidi, G, Sundström, J, Turnbull, F, Viberti, G, Wang, J, Copland, Emma, Canoy, Dexter, Nazarzadeh, Milad, Bidel, Zeinab, Ramakrishnan, Rema, Woodward, Mark, Chalmers, John, Teo, Koon K, Pepine, Carl J, Davis, Barry R, Kjeldsen, Sverre, Sundström, Johan, and Rahimi, Kazem

Published
2021
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4. 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

5. 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

6. 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

7. 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

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

Author

Muiesan, M, Agabiti Rosei, C, Paini, A, Casiglia, E, Cirillo, M, Grassi, G, Iaccarino, G, Mallamaci, F, Maloberti, A, Mazza, A, Mengozzi, A, Palatini, P, Parati, G, Reboldi, G, Rivasi, G, Russo, E, Salvetti, M, Tikhonoff, V, Tocci, G, Borghi, C, Angeli, F, Barbagallo, C, Bombelli, M, Cianci, R, Ciccarelli, M, Cicero, A, Cirillo, P, Dell'Oro, R, Medica, C, D'Elia, L, Desideri, G, Ferri, C, Galletti, F, Gesualdo, L, Giannattasio, C, Lippa, L, Masi, S, Masulli, M, Nazzaro, P, Pontremoli, R, Quarti-Trevano, F, Rattazzi, M, Ungar, A, Verdecchia, P, Viazzi, F, Virdis, A, Volpe, M, Muiesan M. L., Agabiti Rosei C., Paini A., Casiglia E., Cirillo M., Grassi G., Iaccarino G., Mallamaci F., Maloberti A., Mazza A., Mengozzi A., Palatini P., Parati G., Reboldi G., Rivasi G., Russo E., Salvetti M., Tikhonoff V., Tocci G., Borghi C., Angeli F., Barbagallo C. M., Bombelli M., Cianci R., Ciccarelli M., Cicero A. F. G., Cirillo P., Dell'Oro R., Medica C., D'Elia L., Desideri G., Ferri C., Galletti F., Gesualdo L., Giannattasio C., Lippa L., Masi S., Masulli M., Nazzaro P., Pontremoli R., Quarti-Trevano F., Rattazzi M., Ungar A., Verdecchia P., Viazzi F., Virdis A., Volpe M., Muiesan, M, Agabiti Rosei, C, Paini, A, Casiglia, E, Cirillo, M, Grassi, G, Iaccarino, G, Mallamaci, F, Maloberti, A, Mazza, A, Mengozzi, A, Palatini, P, Parati, G, Reboldi, G, Rivasi, G, Russo, E, Salvetti, M, Tikhonoff, V, Tocci, G, Borghi, C, Angeli, F, Barbagallo, C, Bombelli, M, Cianci, R, Ciccarelli, M, Cicero, A, Cirillo, P, Dell'Oro, R, Medica, C, D'Elia, L, Desideri, G, Ferri, C, Galletti, F, Gesualdo, L, Giannattasio, C, Lippa, L, Masi, S, Masulli, M, Nazzaro, P, Pontremoli, R, Quarti-Trevano, F, Rattazzi, M, Ungar, A, Verdecchia, P, Viazzi, F, Virdis, A, Volpe, M, Muiesan M. L., Agabiti Rosei C., Paini A., Casiglia E., Cirillo M., Grassi G., Iaccarino G., Mallamaci F., Maloberti A., Mazza A., Mengozzi A., Palatini P., Parati G., Reboldi G., Rivasi G., Russo E., Salvetti M., Tikhonoff V., Tocci G., Borghi C., Angeli F., Barbagallo C. M., Bombelli M., Cianci R., Ciccarelli M., Cicero A. F. G., Cirillo P., Dell'Oro R., Medica C., D'Elia L., Desideri G., Ferri C., Galletti F., Gesualdo L., Giannattasio C., Lippa L., Masi S., Masulli M., Nazzaro P., Pontremoli R., Quarti-Trevano F., Rattazzi M., Ungar A., Verdecchia P., Viazzi F., Virdis A., and Volpe M.

Abstract

Unlabelled: A relationship between serum uric acid (SUA) and cardiovascular (CV) events has been documented in the Uric Acid Right for Heart Health (URRAH) study. Aim: of this study was to investigate the association between SUA and left ventricular mass index (LVMI) and whether SUA and LVMI or their combination may predict the incidence of CV death. Methods: Subjects with echocardiographic measurement of LVMI included in the URRAH study (n=10733) were part of this analysis. LV hypertrophy (LVH) was defined as LVMI > 95 g/m2 in women and 115 g/m2 in men. Results: A significant association between SUA and LVMI was observed in multiple regression analysis in men: beta 0,095, F 5.47, P< 0.001 and women: beta 0,069, F 4.36, P<0.001. During follow-up 319 CV deaths occurred. Kaplan-Meier curves showed a significantly poorer survival rate in subjects with higher SUA (> 5.6 mg/dl in men and 5.1 mg/dl in women) and LVH (log-rank chi-square 298.105; P<0.0001). At multivariate Cox regression analysis in women LVH alone and the combination of higher SUA and LVH but not hyperuricemia alone, were associated with a higher risk of CV death, while in men hyperuricemia without LVH, LVH without hyperuricemia and their combination were all associated with a higher incidence of CV death. Conclusions: Our findings demonstrate that SUA is independently associated with LVMI and suggest that the combination of hyperuricemia with LVH is an independent and powerful predictor for CV death both in men and women.

Published
2023

9. 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

10. 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

11. 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

12. 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

13. 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

14. 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

15. 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

18. Blood pressure-lowering treatment for prevention of major cardiovascular diseases in people with and without type 2 diabetes: an individual participant-level data meta-analysis

Author

Nazarzadeh, Milad, primary, Bidel, Zeinab, additional, Canoy, Dexter, additional, Copland, Emma, additional, Bennett, Derrick A, additional, Dehghan, Abbas, additional, Davey Smith, George, additional, Holman, Rury R, additional, Woodward, Mark, additional, Gupta, Ajay, additional, Adler, Amanda I, additional, Wamil, Malgorzata, additional, Sattar, Naveed, additional, Cushman, William C, additional, McManus, Richard J, additional, Teo, Koon, additional, Davis, Barry R, additional, Chalmers, John, additional, Pepine, Carl J, additional, Rahimi, Kazem, additional, Agodoa, L, additional, Algra, A, additional, Asselbergs, F W, additional, Beckett, N, additional, Berge, E, additional, Black, H, additional, Brouwers, F P J, additional, Brown, M, additional, Bulpitt, C J, additional, Byington, B, additional, Cutler, J, additional, Devereaux, R B, additional, Dwyer, J, additional, Estacio, R, additional, Fagard, R, additional, Fox, K, additional, Fukui, T, additional, Imai, Y, additional, Ishii, M, additional, Julius, S, additional, Kanno, Y, additional, Kjeldsen, S E, additional, Kostis, J, additional, Kuramoto, K, additional, Lanke, J, additional, Lewis, E, additional, Lewis, J, additional, Lievre, M, additional, Lindholm, L H, additional, Lueders, S, additional, MacMahon, S, additional, Mancia, G, additional, Matsuzaki, M, additional, Mehlum, M H, additional, Nissen, S, additional, Ogawa, H, additional, Ogihara, T, additional, Ohkubo, T, additional, Palmer, C, additional, Patel, A, additional, Pfeffer, M, additional, Poulter, N R, additional, Rakugi, H, additional, Reboldi, G, additional, Reid, C, additional, Remuzzi, G, additional, Ruggenenti, P, additional, Saruta, T, additional, Schrader, J, additional, Schrier, R, additional, Sever, P, additional, Sleight, P, additional, Staessen, J A, additional, Suzuki, H, additional, Thijs, L, additional, Ueshima, K, additional, Umemoto, S, additional, van Gilst, W H, additional, Verdecchia, P, additional, Wachtell, K, additional, Whelton, P, additional, Wing, L, additional, Yui, Y, additional, Yusuf, S, additional, Zanchetti, A, additional, Zhang, Z Y, additional, Anderson, C, additional, Baigent, C, additional, Brenner, BM, additional, Collins, R, additional, de Zeeuw, D, additional, Lubsen, J, additional, Malacco, E, additional, Neal, B, additional, Perkovic, V, additional, Pitt, B, additional, Rodgers, A, additional, Rothwell, P, additional, Salimi-Khorshidi, G, additional, Sundström, J, additional, Turnbull, F, additional, Viberti, G, additional, and Wang, J, additional

Published
2022
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19. Age-stratified and blood-pressure-stratified effects of blood-pressure-lowering pharmacotherapy for the prevention of cardiovascular disease and death: an individual participant-level data meta-analysis

Author

Rahimi, K, Bidel, Z, Nazarzadeh, M, Copland, E, Canoy, D, Wamil, M, Majert, J, Mcmanus, R, Adler, A, Agodoa, L, Algra, A, Asselbergs, F, Beckett, N, Berge, E, Black, H, Boersma, E, Brouwers, F, Brown, M, Brugts, J, Bulpitt, C, Byington, R, Cushman, W, Cutler, J, Devereaux, R, Dwyer, J, Estacio, R, Fagard, R, Fox, K, Fukui, T, Gupta, A, Holman, R, Imai, Y, Ishii, M, Julius, S, Kanno, Y, Kjeldsen, S, Kostis, J, Kuramoto, K, Lanke, J, Lewis, E, Lewis, J, Lievre, M, Lindholm, L, Lueders, S, Macmahon, S, Mancia, G, Matsuzaki, M, Mehlum, M, Nissen, S, Ogawa, H, Ogihara, T, Ohkubo, T, Palmer, C, Patel, A, Pfeffer, M, Pitt, B, Poulter, N, Rakugi, H, Reboldi, G, Reid, C, Remuzzi, G, Ruggenenti, P, Saruta, T, Schrader, J, Schrier, R, Sever, P, Sleight, P, Staessen, J, Suzuki, H, Thijs, L, Ueshima, K, Umemoto, S, van Gilst, W, Verdecchia, P, Wachtell, K, Whelton, P, Wing, L, Woodward, M, Yui, Y, Yusuf, S, Zanchetti, A, Zhang, Z, Anderson, C, Baigent, C, Brenner, B, Collins, R, de Zeeuw, D, Lubsen, J, Malacco, E, Neal, B, Perkovic, V, Rodgers, A, Rothwell, P, Salimi-Khorshidi, G, Sundstrom, J, Turnbull, F, Viberti, G, Wang, J, Chalmers, J, Davis, B, Pepine, C, Teo, K, Rahimi K., Bidel Z., Nazarzadeh M., Copland E., Canoy D., Wamil M., Majert J., McManus R., Adler A., Agodoa L., Algra A., Asselbergs F. W., Beckett N. S., Berge E., Black H., Boersma E., Brouwers F. P. J., Brown M., Brugts J. J., Bulpitt C. J., Byington R. P., Cushman W. C., Cutler J., Devereaux R. B., Dwyer J. P., Estacio R., Fagard R., Fox K., Fukui T., Gupta A. K., Holman R. R., Imai Y., Ishii M., Julius S., Kanno Y., Kjeldsen S. E., Kostis J., Kuramoto K., Lanke J., Lewis E., Lewis J. B., Lievre M., Lindholm L. H., Lueders S., MacMahon S., Mancia G., Matsuzaki M., Mehlum M. H., Nissen S., Ogawa H., Ogihara T., Ohkubo T., Palmer C. R., Patel A., Pfeffer M. A., Pitt B., Poulter N. R., Rakugi H., Reboldi G., Reid C., Remuzzi G., Ruggenenti P., Saruta T., Schrader J., Schrier R., Sever P., Sleight P., Staessen J. A., Suzuki H., Thijs L., Ueshima K., Umemoto S., van Gilst W. H., Verdecchia P., Wachtell K., Whelton P., Wing L., Woodward M., Yui Y., Yusuf S., Zanchetti A., Zhang Z. -Y., Anderson C., Baigent C., Brenner B. M., Collins R., de Zeeuw D., Lubsen J., Malacco E., Neal B., Perkovic V., Rodgers A., Rothwell P., Salimi-Khorshidi G., Sundstrom J., Turnbull F., Viberti G., Wang J., Chalmers J., Davis B. R., Pepine C. J., Teo K. K., Rahimi, K, Bidel, Z, Nazarzadeh, M, Copland, E, Canoy, D, Wamil, M, Majert, J, Mcmanus, R, Adler, A, Agodoa, L, Algra, A, Asselbergs, F, Beckett, N, Berge, E, Black, H, Boersma, E, Brouwers, F, Brown, M, Brugts, J, Bulpitt, C, Byington, R, Cushman, W, Cutler, J, Devereaux, R, Dwyer, J, Estacio, R, Fagard, R, Fox, K, Fukui, T, Gupta, A, Holman, R, Imai, Y, Ishii, M, Julius, S, Kanno, Y, Kjeldsen, S, Kostis, J, Kuramoto, K, Lanke, J, Lewis, E, Lewis, J, Lievre, M, Lindholm, L, Lueders, S, Macmahon, S, Mancia, G, Matsuzaki, M, Mehlum, M, Nissen, S, Ogawa, H, Ogihara, T, Ohkubo, T, Palmer, C, Patel, A, Pfeffer, M, Pitt, B, Poulter, N, Rakugi, H, Reboldi, G, Reid, C, Remuzzi, G, Ruggenenti, P, Saruta, T, Schrader, J, Schrier, R, Sever, P, Sleight, P, Staessen, J, Suzuki, H, Thijs, L, Ueshima, K, Umemoto, S, van Gilst, W, Verdecchia, P, Wachtell, K, Whelton, P, Wing, L, Woodward, M, Yui, Y, Yusuf, S, Zanchetti, A, Zhang, Z, Anderson, C, Baigent, C, Brenner, B, Collins, R, de Zeeuw, D, Lubsen, J, Malacco, E, Neal, B, Perkovic, V, Rodgers, A, Rothwell, P, Salimi-Khorshidi, G, Sundstrom, J, Turnbull, F, Viberti, G, Wang, J, Chalmers, J, Davis, B, Pepine, C, Teo, K, Rahimi K., Bidel Z., Nazarzadeh M., Copland E., Canoy D., Wamil M., Majert J., McManus R., Adler A., Agodoa L., Algra A., Asselbergs F. W., Beckett N. S., Berge E., Black H., Boersma E., Brouwers F. P. J., Brown M., Brugts J. J., Bulpitt C. J., Byington R. P., Cushman W. C., Cutler J., Devereaux R. B., Dwyer J. P., Estacio R., Fagard R., Fox K., Fukui T., Gupta A. K., Holman R. R., Imai Y., Ishii M., Julius S., Kanno Y., Kjeldsen S. E., Kostis J., Kuramoto K., Lanke J., Lewis E., Lewis J. B., Lievre M., Lindholm L. H., Lueders S., MacMahon S., Mancia G., Matsuzaki M., Mehlum M. H., Nissen S., Ogawa H., Ogihara T., Ohkubo T., Palmer C. R., Patel A., Pfeffer M. A., Pitt B., Poulter N. R., Rakugi H., Reboldi G., Reid C., Remuzzi G., Ruggenenti P., Saruta T., Schrader J., Schrier R., Sever P., Sleight P., Staessen J. A., Suzuki H., Thijs L., Ueshima K., Umemoto S., van Gilst W. H., Verdecchia P., Wachtell K., Whelton P., Wing L., Woodward M., Yui Y., Yusuf S., Zanchetti A., Zhang Z. -Y., Anderson C., Baigent C., Brenner B. M., Collins R., de Zeeuw D., Lubsen J., Malacco E., Neal B., Perkovic V., Rodgers A., Rothwell P., Salimi-Khorshidi G., Sundstrom J., Turnbull F., Viberti G., Wang J., Chalmers J., Davis B. R., Pepine C. J., and Teo K. K.

Abstract

Background: The effects of pharmacological blood-pressure-lowering on cardiovascular outcomes in individuals aged 70 years and older, particularly when blood pressure is not substantially increased, is uncertain. We compared the effects of blood-pressure-lowering treatment on the risk of major cardiovascular events in groups of patients stratified by age and blood pressure at baseline. Methods: We did a meta-analysis using individual participant-level data from randomised controlled trials of pharmacological blood-pressure-lowering versus placebo or other classes of blood-pressure-lowering medications, or between more versus less intensive treatment strategies, which had at least 1000 persons-years of follow-up in each treatment group. Participants with previous history of heart failure were excluded. Data were obtained from the Blood Pressure Lowering Treatment Triallists' Collaboration. We pooled the data and categorised participants into baseline age groups (<55 years, 55–64 years, 65–74 years, 75–84 years, and ≥85 years) and blood pressure categories (in 10 mm Hg increments from <120 mm Hg to ≥170 mm Hg systolic blood pressure and from <70 mm Hg to ≥110 mm Hg diastolic). We used a fixed effects one-stage approach and applied Cox proportional hazard models, stratified by trial, to analyse the data. The primary outcome was defined as either a composite of fatal or non-fatal stroke, fatal or non-fatal myocardial infarction or ischaemic heart disease, or heart failure causing death or requiring hospital admission. Findings: We included data from 358 707 participants from 51 randomised clinical trials. The age of participants at randomisation ranged from 21 years to 105 years (median 65 years [IQR 59–75]), with 42 960 (12·0%) participants younger than 55 years, 128 437 (35·8%) aged 55–64 years, 128 506 (35·8%) 65–74 years, 54 016 (15·1%) 75–84 years, and 4788 (1·3%) 85 years and older. The hazard ratios for the risk of major cardiovascular events per 5 mm Hg

Published
2021

20. Pharmacological blood pressure lowering for primary and secondary prevention of cardiovascular disease across different levels of blood pressure: an individual participant-level data meta-analysis

Author

Adler, A, Agodoa, L, Algra, A, Asselbergs, F, Beckett, N, Berge, E, Black, H, Brouwers, F, Brown, M, Bulpitt, C, Byington, R, Chalmers, J, Cushman, W, Cutler, J, Davis, B, Devereaux, R, Dwyer, J, Estacio, R, Fagard, R, Fox, K, Fukui, T, Gupta, A, Holman, R, Imai, Y, Ishii, M, Julius, S, Kanno, Y, Kjeldsen, S, Kostis, J, Kuramoto, K, Lanke, J, Lewis, E, Lewis, J, Lievre, M, Lindholm, L, Lueders, S, Macmahon, S, Mancia, G, Matsuzaki, M, Mehlum, M, Nissen, S, Ogawa, H, Ogihara, T, Ohkubo, T, Palmer, C, Patel, A, Pepine, C, Pfeffer, M, Pitt, B, Poulter, N, Rakugi, H, Reboldi, G, Reid, C, Remuzzi, G, Ruggenenti, P, Saruta, T, Schrader, J, Schrier, R, Sever, P, Sleight, P, Staessen, J, Suzuki, H, Thijs, L, Ueshima, K, Umemoto, S, van Gilst, W, Verdecchia, P, Wachtell, K, Whelton, P, Wing, L, Woodward, M, Yui, Y, Yusuf, S, Zanchetti, A, Zhang, Z, Anderson, C, Baigent, C, Brenner, B, Collins, R, de Zeeuw, D, Lubsen, J, Malacco, E, Neal, B, Perkovic, V, Rodgers, A, Rothwell, P, Salimi-Khorshidi, G, Sundstrom, J, Turnbull, F, Viberti, G, Wang, J, Adler A., Agodoa L., Algra A., Asselbergs F. W., Beckett N. S., Berge E., Black H., Brouwers F. P. J., Brown M., Bulpitt C. J., Byington R. P., Chalmers J., Cushman W. C., Cutler J., Davis B. R., Devereaux R. B., Dwyer J., Estacio R., Fagard R., Fox K., Fukui T., Gupta A. K., Holman R. R., Imai Y., Ishii M., Julius S., Kanno Y., Kjeldsen S. E., Kostis J., Kuramoto K., Lanke J., Lewis E., Lewis J. B., Lievre M., Lindholm L. H., Lueders S., MacMahon S., Mancia G., Matsuzaki M., Mehlum M. H., Nissen S., Ogawa H., Ogihara T., Ohkubo T., Palmer C. R., Patel A., Pepine C. J., Pfeffer M. A., Pitt B., Poulter N. R., Rakugi H., Reboldi G., Reid C., Remuzzi G., Ruggenenti P., Saruta T., Schrader J., Schrier R., Sever P., Sleight P., Staessen J. A., Suzuki H., Thijs L., Ueshima K., Umemoto S., van Gilst W. H., Verdecchia P., Wachtell K., Whelton P., Wing L., Woodward M., Yui Y., Yusuf S., Zanchetti A., Zhang Z. -Y., Anderson C., Baigent C., Brenner B. M., Collins R., de Zeeuw D., Lubsen J., Malacco E., Neal B., Perkovic V., Rodgers A., Rothwell P., Salimi-Khorshidi G., Sundstrom J., Turnbull F., Viberti G., Wang J., Adler, A, Agodoa, L, Algra, A, Asselbergs, F, Beckett, N, Berge, E, Black, H, Brouwers, F, Brown, M, Bulpitt, C, Byington, R, Chalmers, J, Cushman, W, Cutler, J, Davis, B, Devereaux, R, Dwyer, J, Estacio, R, Fagard, R, Fox, K, Fukui, T, Gupta, A, Holman, R, Imai, Y, Ishii, M, Julius, S, Kanno, Y, Kjeldsen, S, Kostis, J, Kuramoto, K, Lanke, J, Lewis, E, Lewis, J, Lievre, M, Lindholm, L, Lueders, S, Macmahon, S, Mancia, G, Matsuzaki, M, Mehlum, M, Nissen, S, Ogawa, H, Ogihara, T, Ohkubo, T, Palmer, C, Patel, A, Pepine, C, Pfeffer, M, Pitt, B, Poulter, N, Rakugi, H, Reboldi, G, Reid, C, Remuzzi, G, Ruggenenti, P, Saruta, T, Schrader, J, Schrier, R, Sever, P, Sleight, P, Staessen, J, Suzuki, H, Thijs, L, Ueshima, K, Umemoto, S, van Gilst, W, Verdecchia, P, Wachtell, K, Whelton, P, Wing, L, Woodward, M, Yui, Y, Yusuf, S, Zanchetti, A, Zhang, Z, Anderson, C, Baigent, C, Brenner, B, Collins, R, de Zeeuw, D, Lubsen, J, Malacco, E, Neal, B, Perkovic, V, Rodgers, A, Rothwell, P, Salimi-Khorshidi, G, Sundstrom, J, Turnbull, F, Viberti, G, Wang, J, Adler A., Agodoa L., Algra A., Asselbergs F. W., Beckett N. S., Berge E., Black H., Brouwers F. P. J., Brown M., Bulpitt C. J., Byington R. P., Chalmers J., Cushman W. C., Cutler J., Davis B. R., Devereaux R. B., Dwyer J., Estacio R., Fagard R., Fox K., Fukui T., Gupta A. K., Holman R. R., Imai Y., Ishii M., Julius S., Kanno Y., Kjeldsen S. E., Kostis J., Kuramoto K., Lanke J., Lewis E., Lewis J. B., Lievre M., Lindholm L. H., Lueders S., MacMahon S., Mancia G., Matsuzaki M., Mehlum M. H., Nissen S., Ogawa H., Ogihara T., Ohkubo T., Palmer C. R., Patel A., Pepine C. J., Pfeffer M. A., Pitt B., Poulter N. R., Rakugi H., Reboldi G., Reid C., Remuzzi G., Ruggenenti P., Saruta T., Schrader J., Schrier R., Sever P., Sleight P., Staessen J. A., Suzuki H., Thijs L., Ueshima K., Umemoto S., van Gilst W. H., Verdecchia P., Wachtell K., Whelton P., Wing L., Woodward M., Yui Y., Yusuf S., Zanchetti A., Zhang Z. -Y., Anderson C., Baigent C., Brenner B. M., Collins R., de Zeeuw D., Lubsen J., Malacco E., Neal B., Perkovic V., Rodgers A., Rothwell P., Salimi-Khorshidi G., Sundstrom J., Turnbull F., Viberti G., and Wang J.

Abstract

Background: The effects of pharmacological blood pressure lowering at normal or high-normal blood pressure ranges in people with or without pre-existing cardiovascular disease remains uncertain. We analysed individual participant data from randomised trials to investigate the effects of blood pressure lowering treatment on the risk of major cardiovascular events by baseline levels of systolic blood pressure. Methods: We did a meta-analysis of individual participant-level data from 48 randomised trials of pharmacological blood pressure lowering medications versus placebo or other classes of blood pressure-lowering medications, or between more versus less intensive treatment regimens, which had at least 1000 persons-years of follow-up in each group. Trials exclusively done with participants with heart failure or short-term interventions in participants with acute myocardial infarction or other acute settings were excluded. Data from 51 studies published between 1972 and 2013 were obtained by the Blood Pressure Lowering Treatment Trialists' Collaboration (Oxford University, Oxford, UK). We pooled the data to investigate the stratified effects of blood pressure-lowering treatment in participants with and without prevalent cardiovascular disease (ie, any reports of stroke, myocardial infarction, or ischaemic heart disease before randomisation), overall and across seven systolic blood pressure categories (ranging from <120 to ≥170 mm Hg). The primary outcome was a major cardiovascular event (defined as a composite of fatal and non-fatal stroke, fatal or non-fatal myocardial infarction or ischaemic heart disease, or heart failure causing death or requiring admission to hospital), analysed as per intention to treat. Findings: Data for 344 716 participants from 48 randomised clinical trials were available for this analysis. Pre-randomisation mean systolic/diastolic blood pressures were 146/84 mm Hg in participants with previous cardiovascular disease (n=157 728) and 157/8

Published
2021

22. Present and future of kidney replacement therapy in Italy: the perspective from Italian Dialysis and Transplantation Registry (IDTR)

Author

Nordio, M, Limido, A, Postorino, M, Bolignano, D, Cirillo, M, Conte, F, Di Napoli, A, Fabbian, F, Ferraro, Pm, Gibertoni, D, Lentini, Pl, Reboldi, G, Nordio M., Limido A., Postorino M., Bolignano D., Cirillo M., Conte F., Di Napoli A., Fabbian F., Ferraro P.M., Gibertoni D., Lentini P.L., Reboldi G., Nordio, M., Limido, A., Postorino, M., Bolignano, D., Cirillo, M., Conte, F., Di Napoli, A., Fabbian, F., Ferraro, P. M., Gibertoni, D., Lentini, P. L., and Reboldi, G.

Subjects
Adult, medicine.medical_specialty, medicine.medical_treatment, Population, 030232 urology & nephrology, 030204 cardiovascular system & hematology, NO, Peritoneal dialysis, 03 medical and health sciences, 0302 clinical medicine, Renal Dialysis, Internal medicine, Prevalence, Medicine, Settore MED/14 - NEFROLOGIA, Humans, Registries, education, Dialysis, Kidney transplantation, Aged, End stage kidney disease, Kidney registry, Kidney replacement therapy, education.field_of_study, business.industry, Incidence (epidemiology), Mortality rate, Incidence, Middle Aged, medicine.disease, Kidney Transplantation, Transplantation, Renal Replacement Therapy, Years of potential life lost, Italy, Nephrology, Kidney Failure, Chronic, business
Abstract

Incidence of kidney replacement therapy (KRT) stabilizes or declines both in Europe and in the US; however, it is predictable that global prevalence of KRT will double by 2030. In this paper, we focus on the patterns of incidence, mortality, and prevalence of KRT in Italy, and we compare, when possible, the findings with other countries. The Italian Dialysis and Transplantation Registry (IDTR) currently collects aggregate data from regional registries. In Italy, KRT yearly incidence is around 160 patients per million population (pmp). This incidence showed an increasing trend up until 2011 with an average annual percentage change (AAPC) of 1.8%, after which it stabilized. Older age is an important determinant for KRT incidence, and it is strongly associated with the variability between Italian regions. Incidence is very stable within patients less than 50years old; however, it greatly differs between regions for patients over 75years old, ranging from 400 to 900 pmp. Moreover, the incidence for patients over 50years old declined from 366 pmp in 2011 to 285 in 2017. An age-period-cohort (APC) model showed a very strong cohort effect, which shows the decline in incidence seems mainly due to the better health conditions of people born after 1940. Mortality rate in KRT patients was 109 per 1000 patient-year (py) between 2011 and 2017 with great differences among treatment modalities: 162 per 1000 py in haemodialysis, 117 per 1000 py in peritoneal dialysis, and 16 per 1000 py in kidney transplantation. Premature death is better detected by the standard expected years of life lost (YLL). The distribution of YLL rate per age shows a sharp increase between 40 and 70years old both in haemodialysis and peritoneal dialysis patients with an AAPC of 5.2% and 4.1% respectively. Transplanted patients experience a very low YLL rate at any age. KRT prevalence was 1118 pmp in 2017 and it should be close to 1175 pmp by 2025 with a projected increase of transplanted patients’ prevalence to 500 pmp, and a decrease of dialysis patients from 714 to 680 pmp. The proportion of patients treated with one of the three modalities strictly depends on age, with a sharp increase of haemodialysis after the age of 50. All data suggests the necessity to improve the care of middle and older age patients who experience the higher incidence of disease and mortality.

Published
2020

23. 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

25. [Hypertension after COVID-19 vaccination]

Author

Angeli, F., Reboldi, G., Trapasso, M., and Verdecchia, P.

Subjects
COVID-19 Vaccines, SARS-CoV-2, Hypertension, Vaccination, Humans, COVID-19
Abstract

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) rapidly spread across the world, killing more than 4 million individuals globally, with 240 million individuals being confirmed by laboratory tests. Among different therapeutic strategies to prevent SARS-CoV-2 infection, vaccines are the most promising approach for curbing the pandemic. They elicit an immune neutralizing response and thus offer protection against coronavirus disease 2019 (COVID-19). However, some questions regarding the safety of COVID-19 vaccines have been raised and based on sparse reports of severe systemic reactions after vaccination. Among these, evidences on the potential effect of vaccination on the acute rise in blood pressure have been recently accrued. Approved vaccines in Europe increase the endogenous synthesis of SARS-CoV-2 Spike proteins from a variety of cells. Once synthetized in the cells reached by the vaccine, the Spike proteins first assemble in the cytoplasm and then migrate to the cell surface to protrude with a native-like conformation. Spike proteins are recognized by the immune system which rapidly develops an immune response. Furthermore, the Spike proteins assembled in the cells which are eventually destroyed by the immune response circulate in the blood as free-floating forms. Free-floating Spike proteins may interact with angiotensin-converting enzyme 2 (ACE2) receptors leading to internalization, degradation, and dysregulation of the catalytic activities of these receptors. The consequent loss of ACE2 receptor activity leads to a rapid drop in the generation of angiotensin1,7 resulting from inactivation of angiotensin II. The imbalance between angiotensin II (overactivity) and of angiotensin1,7 (deficiency) might play a role in the genesis of acute elevation in blood pressure.

Published
2022

26. Hypertension after anti-COVID-19 vaccination

Author

Angeli, F, Reboldi, G, Trapasso, M, and Verdecchia, P

Subjects
Adverse event, Vaccines, SARS-CoV-2, Renin-angiotensin-aldosterone system, ACE2, COVID-19, Chronic disease
Published
2022

27. Risk factors and action thresholds for the novel coronavirus pandemic. Insights from the Italian Society of Nephrology COVID-19 Survey

Author

Nordio, M., Reboldi, G., Di Napoli, A., Quintaliani, G., Alberici, F., Postorino, M., Aucella, F., Messa, P., Brunori, G., Bosco, M., Malberti, F., Mandreoli, M., Mazzaferro, S., Movilli, E., Ravera, M., Salomone, M., Santoro, D., Postorinolimido, M. A., Bonomini, M., Stingone, A., Maccarone, M., Di Loreto, E., Stacchiotti, L., Malandra, R., Chiarella, S., D'Agostino, F., Fuiano, G., Nicodemo, L., Bonofiglio, R., Greco, S., Mallamaci, F., Barreca, E., Caserta, C., Bruzzese, V., Galati, D., Tramontana, D., Viscione, M., Chiuchiolo, L., Tuccillo, S., Sepe, M., Vitale, F., Ciriana, E., Martignetti, V., Caserta, D., Stizzo, A., Romano, A., Iulianiello, G., Cascone, E., Minicone, P., Chiricone, D., Delgado, G., Barbato, A., Celentano, S., Molfino, I., Coppola, S., Raiola, I., Abategiovanni, M., Borrelli, S., Margherita, C., Bruno, F., Ida, M., Aliperti, E., Potito, D., Cuomo, G., De Luca, M., Merola, M., Botta, C., Garofalo, G., Alinei, P., Paglionico, C., Roano, M., Vitale, S., Ierardi, R., Fimiani, V., Conte, G., Di Natale, G., Romano, M., Di Marino, V., Scafarto, A., Meccariello, S., Pecoraro, C., Di Stazio, E., Di Meglio, E., Cuomo, A., Maresca, B., Rotaia, E., Capasso, G., Auricchio, M., Pluvio, C., Maddalena, L., De Maio, A., Palladino, G., Buono, F., Gigliotti, G., Mancini, E., La Manna, G., Storari, A., Mosconi, G., Cappelli, G., Scarpioni, R., Gregorini, M., Rigotti, A., Mancini, W., Bianco, F., Boscutti, G., Amici, G., Tosto, M., Fini, R., Pace, G., Cioffi, A., Boccia, E., Di Lullo, L., Di Zazzo, G., Simonelli, R., Bondatti, F., Miglio, L., Rifici, N., Treglia, A., Muci, M., Baldinelli, G., Rizzi, E., Lonzi, M., De Cicco, C., Forte, F., De Paolis, P., Grandaliano, Giuseppe, Cuzziol, C., Torre, V. M., Sfregola, P., Rossi, V., Fabio, G., Flammini, A., Filippini, A., Onorato, L., Vendola, F., Di Daniela, N., Alfarone, C., Scabbia, L., Ferrazzano, M., Grotta, B. D., Gamberini, M., Fazzari, L., Mene, P., Morgia, A., Catucci, A., Palumbo, R., Puliti, M., Marinelli, R., Polito, P., Marrocco, F., Morabito, S., Rocca, R., Nazzaro, L., Lavini, R., Iamundo, V., Chiappini, M., Casarci, M., Morosetti, M., Hassan, S., Firmi, G., Galliani, M., Serraiocco, M., Feriozzi, S., Valentini, W., Sacco, P., Garibotto, G., Cappelli, V., Saffioti, C., Repetto, M., Rolla, D., Lorenz, M., Pedrini, L., Polonioli, D., Galli, E., Ruggenenti, P., Scolari, F., Bove, S., Costantino, E., Bracchi, M., Mangano, S., Depetri, G., La Milia, V., Farina, M., Zecchini, S., Savino, R., Melandri, M., Guastoni, C., Paparella, M., Gallieni, M., Minetti, E., Bisegna, S., Righetti, M., Badalamenti, S., Alberghini, E., Bertoli, S., Fabbrini, P., Albrizio, P., Rampino, T., Colturi, C., Rombola, G., Lucatello, A., Guerrini, E., Ranghino, A., Lenci, F., Fanciulli, E., Santarelli, S., Damiani, C., Garofalo, D., Sopranzi, F., Santoferrara, A., Di Luca, M., Galiotta, P., Brigante, M., Manganaro, M., Maffei, S., Berto, I., Besso, L., Viglino, G., Cusinato, S., Chiarinottichiappero, D. F., Tognarelli, G., Gianoglio, B., Forneris, G., Biancone, L., Savoldi, S., Vitale, C., Boero, R., Filiberti, O., Borzumati, M., Gesualdo, L., Lomonte, C., Gernone, G., Pallotta, G., Di Paolo, S., Vernaglione, L., Specchio, A., Stallone, G., Dell'Aquila, R., Sandri, G., Russo, F., Napoli, M., Marangi, A., Morrone, L., Di Stratis, C., Fresu, A., Cicu, F., Murtas, S., Manca, O., Pani, A., Pilloni, M., Pistis, R., Cadoni, M., Contu, B., Logias, F., Ivaldi, R., Fancello, S., Cossu, M., Lepori, G., Vittoria, S., Battiati, E., Arnone, M., Rome, M., Barbera, A., Granata, A., Collura, G., Dico, C. L., Pugliese, G., Di Natale, E., Rizzari, G., Cottone, L., Longo, N., Battaglia, G., Marcantoni, C., Giannetto, G., Tumino, G., Randazzo, F., Bellissimo, L., Faro, F. L., Grippaldi, F., Urso, S., Quattrone, G., Todaro, I., Vincenzo, D., Murgo, A., Masuzzo, M., Pisacane, A., Monardo, P., Pontorierro, M., Quari, C., Bauro, A., Chimenz, R. R., Alfio, D., Girasole, F., Cascio, A. L., Caviglia, A., Tornese, F., Sirna, F., Altieri, C., Cusumano, R., Saveriano, V., La Corte, A., Locascio, G., Rotolo, U., Musso, S., Risuglia, L., Blanco, G., Minardo, G., Castellino, S., Zappulla, Z., Randone, S., Di Francesca, M., Cassetti, C. C., Oddo, G., Buscaino, G., Mucaria, F., Barraco, V. I., Di Martino, A., Rallo, D., Dani, L., Campolo, G., Manescalchi, F., Biagini, M., Agate, M., Panichi, V., Casani, A., Traversari, L., Garosi, G., Tabbi, M., Selvi, A., Cencioni, L., Fagugli, R., Timio, F., Leveque, A., Manes, M., Mennella, G., Calo, L., Fiorini, F., Abaterusso, C., Calzavara, P., Meneghel, G., Bonesso, C., Gambaro, G., Gammaro, L., Rugiu, C., Ronco, C., Nordio M., Reboldi G., Di Napoli A., Quintaliani G., Alberici F., Postorino M., Aucella F., Messa P., Brunori G., Bosco M., Malberti F., Mandreoli M., Mazzaferro S., Movilli E., Ravera M., Salomone M., Santoro D., PostorinoLimido M.A., Bonomini M., Stingone A., Maccarone M., Di Loreto E., Stacchiotti L., Malandra R., Chiarella S., D'Agostino F., Fuiano G., Nicodemo L., Bonofiglio R., Greco S., Mallamaci F., Barreca E., Caserta C., Bruzzese V., Galati D., Tramontana D., Viscione M., Chiuchiolo L., Tuccillo S., Sepe M., Vitale F., Ciriana E., Martignetti V., Caserta D., Stizzo A., Romano A., Iulianiello G., Cascone E., Minicone P., Chiricone D., Delgado G., Barbato A., Celentano S., Molfino I., Coppola S., Raiola I., Abategiovanni M., Borrelli S., Margherita C., Bruno F., Ida M., Aliperti E., Potito D., Cuomo G., De Luca M., Merola M., Botta C., Garofalo G., Alinei P., Paglionico C., Roano M., Vitale S., Ierardi R., Fimiani V., Conte G., Di Natale G., Romano M., Di Marino V., Scafarto A., Meccariello S., Pecoraro C., Di Stazio E., Di Meglio E., Cuomo A., Maresca B., Rotaia E., Capasso G., Auricchio M., Pluvio C., Maddalena L., De Maio A., Palladino G., Buono F., Gigliotti G., Mancini E., La Manna G., Storari A., Mosconi G., Cappelli G., Scarpioni R., Gregorini M., Rigotti A., Mancini W., Bianco F., Boscutti G., Amici G., Tosto M., Fini R., Pace G., Cioffi A., Boccia E., Di Lullo L., Di Zazzo G., Simonelli R., Bondatti F., Miglio L., Rifici N., Treglia A., Muci M., Baldinelli G., Rizzi E., Lonzi M., De Cicco C., Forte F., De Paolis P., Grandaliano G., Cuzziol C., Torre V.M., Sfregola P., Rossi V., Fabio G., Flammini A., Filippini A., Onorato L., Vendola F., Di Daniela N., Alfarone C., Scabbia L., Ferrazzano M., Grotta B.D., Gamberini M., Fazzari L., Mene P., Morgia A., Catucci A., Palumbo R., Puliti M., Marinelli R., Polito P., Marrocco F., Morabito S., Rocca R., Nazzaro L., Lavini R., Iamundo V., Chiappini M., Casarci M., Morosetti M., Hassan S., Firmi G., Galliani M., Serraiocco M., Feriozzi S., Valentini W., Sacco P., Garibotto G., Cappelli V., Saffioti C., Repetto M., Rolla D., Lorenz M., Pedrini L., Polonioli D., Galli E., Ruggenenti P., Scolari F., Bove S., Costantino E., Bracchi M., Mangano S., Depetri G., La Milia V., Farina M., Zecchini S., Savino R., Melandri M., Guastoni C., Paparella M., Gallieni M., Minetti E., Bisegna S., Righetti M., Badalamenti S., Alberghini E., Bertoli S., Fabbrini P., Albrizio P., Rampino T., Colturi C., Rombola G., Lucatello A., Guerrini E., Ranghino A., Lenci F., Fanciulli E., Santarelli S., Damiani C., Garofalo D., Sopranzi F., Santoferrara A., Di Luca M., Galiotta P., Brigante M., Manganaro M., Maffei S., Berto I., Besso L., Viglino G., Cusinato S., ChiarinottiChiappero D.F., Tognarelli G., Gianoglio B., Forneris G., Biancone L., Savoldi S., Vitale C., Boero R., Filiberti O., Borzumati M., Gesualdo L., Lomonte C., Gernone G., Pallotta G., Di Paolo S., Vernaglione L., Specchio A., Stallone G., Dell'Aquila R., Sandri G., Russo F., Napoli M., Marangi A., Morrone L., Di Stratis C., Fresu A., Cicu F., Murtas S., Manca O., Pani A., Pilloni M., Pistis R., Cadoni M., Contu B., Logias F., Ivaldi R., Fancello S., Cossu M., Lepori G., Vittoria S., Battiati E., Arnone M., Rome M., Barbera A., Granata A., Collura G., Dico C.L., Pugliese G., Di Natale E., Rizzari G., Cottone L., Longo N., Battaglia G., Marcantoni C., Giannetto G., Tumino G., Randazzo F., Bellissimo L., Faro F.L., Grippaldi F., Urso S., Quattrone G., Todaro I., Vincenzo D., Murgo A., Masuzzo M., Pisacane A., Monardo P., Pontorierro M., Quari C., Bauro A., Chimenz R.R., Alfio D., Girasole F., Cascio A.L., Caviglia A., Tornese F., Sirna F., Altieri C., Cusumano R., Saveriano V., La Corte A., Locascio G., Rotolo U., Musso S., Risuglia L., Blanco G., Minardo G., Castellino S., Zappulla Z., Randone S., Di Francesca M., Cassetti C.C., Oddo G., Buscaino G., Mucaria F., Barraco V.I., Di Martino A., Rallo D., Dani L., Campolo G., Manescalchi F., Biagini M., Agate M., Panichi V., Casani A., Traversari L., Garosi G., Tabbi M., Selvi A., Cencioni L., Fagugli R., Timio F., Leveque A., Manes M., Mennella G., Calo L., Fiorini F., Abaterusso C., Calzavara P., Meneghel G., Bonesso C., Gambaro G., Gammaro L., Rugiu C., and Ronco C.

Subjects
Male, Contextual analysis, medicine.medical_treatment, Population, 030232 urology & nephrology, Recursive partitioning, 030204 cardiovascular system & hematology, Rate ratio, Risk Assessment, 03 medical and health sciences, 0302 clinical medicine, Classification tree, COVID-19, Renal replacement therapy, Risk Factors, Medical, Surveys and Questionnaires, Health care, medicine, Settore MED/14 - NEFROLOGIA, Humans, education, Pandemics, Societies, Medical, Female, Italy, Nephrology, education.field_of_study, business.industry, Multilevel model, Decision rule, Confidence interval, Original Article, Hemodialysis, business, Contextual analysi, Societies, Demography
Abstract

Background and aim: Over 80% (365/454) of the nation’s centers participated in the Italian Society of Nephrology COVID-19 Survey. Out of 60,441 surveyed patients, 1368 were infected as of April 23rd, 2020. However, center-specific proportions showed substantial heterogeneity. We therefore undertook new analyses to identify explanatory factors, contextual effects, and decision rules for infection containment. Methods: We investigated fixed factors and contextual effects by multilevel modeling. Classification and Regression Tree (CART) analysis was used to develop decision rules. Results: Increased positivity among hemodialysis patients was predicted by center location [incidence rate ratio (IRR) 1.34, 95% confidence interval (CI) 1.20–1.51], positive healthcare workers (IRR 1.09, 95% CI 1.02–1.17), test-all policy (IRR 5.94, 95% CI 3.36–10.45), and infected proportion in the general population (IRR 1.002, 95% CI 1.001–1.003) (all p < 0.01). Conversely, lockdown duration exerted a protective effect (IRR 0.95, 95% CI 0.94–0.98) (p < 0.01). The province-contextual effects accounted for 10% of the total variability. Predictive factors for peritoneal dialysis and transplant cases were center location and infected proportion in the general population. Using recursive partitioning, we identified decision thresholds at general population incidence ≥ 229 per 100,000 and at ≥ 3 positive healthcare workers. Conclusions: Beyond fixed risk factors, shared with the general population, the increased and heterogeneous proportion of positive patients is related to the center’s testing policy, the number of positive patients and healthcare workers, and to contextual effects at the province level. Nephrology centers may adopt simple decision rules to strengthen containment measures timely.

Published
2021

28. Novel Strategies to Increase Sodium Removal and to Reduce Glucose Exposures in Peritoneal Dialysis

Author

Carlo Garofalo, Silvio Borrelli, Di Liberato L, Centi A, Palumbo R, Mario Bonomini, Michele Provenzano, Divino Jc, Netti A, Reboldi G, De Nicola L, Giuseppe Conte, Polese L, Peruzzu N, Roberto Minutolo, Arduini A, Borrelli, S, Garofalo, C, Peruzzu, N, Polese, L, Netti, A, Minutolo, R, De Nicola, L, Provenzano, M, Conte, G, Palumbo, R, Centi, A, Reboldi, G, Bonomini, M, Di Liberato, L, Arduini, A, and Divino, Jc

Subjects
Dialysis adequacy, medicine.medical_specialty, business.industry, Sodium, medicine.medical_treatment, Urology, chemistry.chemical_element, General Medicine, Xylitol, Icodextrin, Peritoneal dialysis, chemistry.chemical_compound, chemistry, medicine, business
Abstract

The success of Peritoneal Dialysis (PD) as renal replacement treatment is mainly due to the achievement of dialysis adequacy with a good adaptability to the patients’ needs.

Published
2019

29. Antihypertensive treatment and risk of cancer: an individual participant data meta-analysis

Author

Copland, Emma, primary, Canoy, Dexter, additional, Nazarzadeh, Milad, additional, Bidel, Zeinab, additional, Ramakrishnan, Rema, additional, Woodward, Mark, additional, Chalmers, John, additional, Teo, Koon K, additional, Pepine, Carl J, additional, Davis, Barry R, additional, Kjeldsen, Sverre, additional, Sundström, Johan, additional, Rahimi, Kazem, additional, Adler, A, additional, Agodoa, L, additional, Algra, A, additional, Asselbergs, F W, additional, Beckett, N, additional, Berge, E, additional, Black, H, additional, Brouwers, F P J, additional, Brown, M, additional, Bulpitt, C J, additional, Byington, B, additional, Chalmers, J, additional, Cushman, W C, additional, Cutler, J, additional, Davis, B R, additional, Devereaux, R B, additional, Dwyer, J, additional, Estacio, R, additional, Fagard, R, additional, Fox, K, additional, Fukui, T, additional, Gupta, A K, additional, Holman, R R, additional, Imai, Y, additional, Ishii, M, additional, Julius, S, additional, Kanno, Y, additional, Kjeldsen, S E, additional, Kostis, J, additional, Kuramoto, K, additional, Lanke, J, additional, Lewis, E, additional, Lewis, J, additional, Lievre, M, additional, Lindholm, L H, additional, Lueders, S, additional, MacMahon, S, additional, Mancia, G, additional, Matsuzaki, M, additional, Mehlum, M H, additional, Nissen, S, additional, Ogawa, H, additional, Ogihara, T, additional, Ohkubo, T, additional, Palmer, C, additional, Patel, A, additional, Pepine, C J, additional, Pfeffer, M, additional, Poulter, N R, additional, Rakugi, H, additional, Reboldi, G, additional, Reid, C, additional, Remuzzi, G, additional, Ruggenenti, P, additional, Saruta, T, additional, Schrader, J, additional, Schrier, R, additional, Sever, P, additional, Sleight, P, additional, Staessen, J A, additional, Suzuki, H, additional, Thijs, L, additional, Ueshima, K, additional, Umemoto, S, additional, van Gilst, W H, additional, Verdecchia, P, additional, Wachtell, K, additional, Whelton, P, additional, Wing, L, additional, Woodward, M, additional, Yui, Y, additional, Yusuf, S, additional, Zanchetti, A, additional, Zhang, Z Y, additional, Anderson, C, additional, Baigent, C, additional, Brenner, BM, additional, Collins, R, additional, de Zeeuw, D, additional, Lubsen, J, additional, Malacco, E, additional, Neal, B, additional, Perkovic, V, additional, Pitt, B, additional, Rodgers, A, additional, Rothwell, P, additional, Salimi-Khorshidi, G, additional, Sundström, J, additional, Turnbull, F, additional, Viberti, G, additional, and Wang, J, additional

Published
2021
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30. [ACE-inhibitors, angiotensin receptor blockers and severe acute respiratory syndrome caused by coronavirus]

Author

Verdecchia, P., Reboldi, G., Cavallini, C., Mazzotta, G., and Angeli, F.

Subjects
SARS-CoV-2, Ischemic heart disease, Pneumonia, Viral, COVID-19, Heart failure, Angiotensin-Converting Enzyme Inhibitors, Pneumonia, Angiotensin receptor blockers, Cell Line, Coronavirus, Betacoronavirus, ACE-inhibitors, Hypertension, Humans, Viral, Coronavirus Infections, Pandemics
Abstract

Some Authors recently suggested that angiotensin-converting enzyme (ACE) inhibitors and angiotensin II receptor blockers (ARBs) should be discontinued, even temporarily, given the current pandemic of SARS-CoV-2 virus. The suggestion is based on the hypothesis that ACE-inhibitors and ARBs may favor the entry and diffusion of SARS-CoV-2 virus into the human cells. ACE-inhibitors and ARBs may increase the expression of ACE2 receptors, which are the sites of viral entry into the human organism. ACE2 receptors are ubiquitous, although they are extremely abundant on the cell surface of type 2 pneumocytes. Type 2 pneumocytes are small cylindrical alveolar cells located in close vicinity to pulmonary capillaries and responsible for the synthesis of alveolar surfactant, which is known to facilitate gas exchanges. The increased expression of ACE2 for effect of ACE-inhibitors and ARBs can be detected by increased production of angiotensin1-7 and mRNA related to ACE2. There is the fear that the increased expression of ACE2 induced by ACE-inhibitors and ARBs may ultimately facilitate the entry and diffusion of the SARS-CoV-2 virus. However, there is no clinical evidence to support this hypothesis. Furthermore, available data are conflicting and some counter-intuitive findings suggest that ARBs may be beneficial, not harmful. Indeed, studies conducted in different laboratories demonstrated that ACE2 receptors show a down-regulation (i.e. the opposite of what would happen with ACE-inhibitors and ARBs) for effect of their interaction with the virus. In animal studies, down-regulation of ACE2 has been found as prevalent in the pulmonary areas infected by virus, but not in the surrounding areas. In these studies, virus-induced ACE2 down-regulation would lead to a reduced formation of angiotensin1-7 (because ACE2 degrades angiotensin II into angiotensin1-7) with consequent accumulation of angiotensin II. The excess angiotensin II would favor pulmonary edema and inflammation, a phenomenon directly associated with angiotensin II levels, along with worsening in pulmonary function. Such detrimental effects have been blocked by ARBs in experimental models. In the light of the above considerations, it is reasonable to conclude that the suggestion to discontinue ACE-inhibitors or ARBs in all patients with the aim of preventing or limiting the diffusion of SARS-CoV-2 virus is not based on clinical evidence. Conversely, experimental studies suggest that ARBs might be useful in these patients to limit pulmonary damage through the inhibition of type 1 angiotensin II receptors. Controlled clinical studies in this area are eagerly awaited. This review discusses facts and theories on the potential impact of ACE-inhibitors and ARBs in the setting of the SARS-CoV-2 pandemic.

Published
2020

31. Present and future of kidney replacement therapy in Italy: the perspective from Italian Dialysis and Transplantation Registry (IDTR)

Author

Nordio, M., Limido, A., Postorino, M., Bolignano, D., Cirillo, M., Conte, F., Di Napoli, A., Fabbian, F., Ferraro, P. M., Gibertoni, D., Lentini, P. L., Reboldi, G., Ferraro P. M. (ORCID:0000-0002-1379-022X), Nordio, M., Limido, A., Postorino, M., Bolignano, D., Cirillo, M., Conte, F., Di Napoli, A., Fabbian, F., Ferraro, P. M., Gibertoni, D., Lentini, P. L., Reboldi, G., and Ferraro P. M. (ORCID:0000-0002-1379-022X)

Abstract

Incidence of kidney replacement therapy (KRT) stabilizes or declines both in Europe and in the US; however, it is predictable that global prevalence of KRT will double by 2030. In this paper, we focus on the patterns of incidence, mortality, and prevalence of KRT in Italy, and we compare, when possible, the findings with other countries. The Italian Dialysis and Transplantation Registry (IDTR) currently collects aggregate data from regional registries. In Italy, KRT yearly incidence is around 160 patients per million population (pmp). This incidence showed an increasing trend up until 2011 with an average annual percentage change (AAPC) of 1.8%, after which it stabilized. Older age is an important determinant for KRT incidence, and it is strongly associated with the variability between Italian regions. Incidence is very stable within patients less than 50 years old; however, it greatly differs between regions for patients over 75 years old, ranging from 400 to 900 pmp. Moreover, the incidence for patients over 50 years old declined from 366 pmp in 2011 to 285 in 2017. An age-period-cohort (APC) model showed a very strong cohort effect, which shows the decline in incidence seems mainly due to the better health conditions of people born after 1940. Mortality rate in KRT patients was 109 per 1000 patient-year (py) between 2011 and 2017 with great differences among treatment modalities: 162 per 1000 py in haemodialysis, 117 per 1000 py in peritoneal dialysis, and 16 per 1000 py in kidney transplantation. Premature death is better detected by the standard expected years of life lost (YLL). The distribution of YLL rate per age shows a sharp increase between 40 and 70 years old both in haemodialysis and peritoneal dialysis patients with an AAPC of 5.2% and 4.1% respectively. Transplanted patients experience a very low YLL rate at any age. KRT prevalence was 1118 pmp in 2017 and it should be close to 1175 pmp by 2025 with a projected increase of transpla

Published
2020

35. Managing hypertension in 2018: Which guideline to follow?

Author

Angeli, F., Kumar, S., Reboldi, G., Trapasso, M., Aita, A., and Verdecchia, P.

Subjects
medicine.medical_specialty, hypertension, EBM, Cardiovascular risk factors, South asian population, Blood pressure, Guidelines, Prevention, quality of care and outcomes, 030204 cardiovascular system & hematology, Clinical Practice, 03 medical and health sciences, 0302 clinical medicine, Asian country, Medicine, 030212 general & internal medicine, Stroke, business.industry, Public health, Guideline, Hypertension prevention, medicine.disease, Cardiology and Cardiovascular Medicine, business, Demography
Abstract

Hypertension is a global public health issue and a major cause of morbidity and mortality. Its prevalence is increasing in many Asian countries, with a number of countries with blood pressure above the global average. Although the average systolic blood pressure is decreasing worldwide since the 1980s at the rate of about 1 mm Hg systolic blood pressure per decade, it is increasing in low-income and middle-income countries, especially in the East and South Asian population. Of note, the much larger base Asian population results in a considerably larger absolute number of individuals affected. When compared with Western countries, hypertension among Asian populations has unique features in terms of its onset, clustering of associated cardiovascular risk factors, complications and outcomes. Moreover, only a minority of hypertensive individuals are receiving treatment and achieving control. Projected number of deaths related to hypertension dramatically increased in the last 25 years in some Asian regions with a disproportionately high mortality and morbidity from stroke compared with Western countries. The relation between blood pressure and the risk of stroke is stronger in Asia than in Western regions. Although new Guidelines for hypertension diagnosis and management have been recently released from Europe and North America, the unique features of Asian hypertensive patients raise concerns on the clinical applicability of Western Guidelines to Asian populations. To this purpose, we critically reviewed key elements from the most updated Guidelines. We also discussed their core concepts to verify the impact on hypertension prevention and management in Asian countries.

Published
2019

44. Panethnic differences in blood pressure in Europe: A systematic review and meta-analysis

Author

Modesti, Pietro Amedeo, Reboldi, Gianpaolo, Cappuccio, Francesco P, Agyemang, Charles, Remuzzi, Giuseppe, Rapi, Stefano, Perruolo, Eleonora, Parati, Gianfranco, ESH Working Group on CV Risk in Low Resource Settings: Modesti, P. A., Parati, G., Agostoni, P., Agyemang, C., Barros, H., Basu, S., Benetos, A., Cappuccio, F. P., Ceriello, A., DEL PRATO, Stefano, Kalyesubula, R., Kilama, M. O., O'Brien, E., Perlini, S., Picano, E., Reboldi, G., Redon, J., Remuzzi, . G, Stuckler, D., Van Bortel, L. M., Zhao, D., Bamoshmoosh, M., Perruolo, E., Bennet, L., Bruno, ROSA MARIA, Carlsson, A. C., Cifkova, R., Fadnes, L. T., Grech, H., Klocek, M., Kumar, B., Lalic, N., Manolis, A. J., Nørredam, M., Massetti, L., de Courten, M. P., Pereira, M., Pratali, L., Rapi, S., Siegert, A., Szklarska, A., Tendera, M., Twagirumukiza, M., Volodina, A., Watfa, G., Karaye, K. M., Phanzu, B. K., Dzudie, A., N'Guetta, R., Kiiza, M. C., Gudina, E. K., Longo Mbenza, B., Mucumbitsi, J., Anisiuba, B., Ibrahim, T. A., Okechukwu, O. S., Modesti, P, Reboldi, G, Cappuccio, F, Agyemang, C, Remuzzi, G, Rapi, S, Perruolo, E, and Parati, G

Subjects
Male, Epidemiology, Ethnic group, Risk-Factor, lcsh:Medicine, Social Sciences, Blood Pressure, Vascular Medicine, Cultural Anthropology, Geographical Locations, 0302 clinical medicine, Endocrinology, Mathematical and Statistical Techniques, Sociology, Medicine and Health Sciences, Ethnicity, Medicine, Ethnicities, 030212 general & internal medicine, Adult, Europe, Female, Humans, Ethnic Groups, Different Ethnic-Group, lcsh:Science, media_common, Multidisciplinary, Traditional medicine, Religion, Cross-Sectional Data, Meta-analysis, Physical Sciences, Hypertension, Origin Population, Statistics (Mathematics), Research Article, Endocrine Disorders, Research and Analysis Methods, Ethnic Epidemiology, 03 medical and health sciences, South Asian Adult, Diabetes mellitus, hypertension, diabetes, ethnicity, Diabetes Mellitus, media_common.cataloged_instance, Body-Mass Index, European union, Statistical Methods, business.industry, Insulin-Resistance, lcsh:R, Publication bias, medicine.disease, Blood pressure, Metabolic Disorders, Anthropology, People and Places, Observational study, lcsh:Q, Population Groupings, business, Coronary-Heart-Disease, Body mass index, Publication Bias, 030217 neurology & neurosurgery, Mathematics, Demography, RC, Africans, Meta-Analysis, Cardiovascular Risk
Abstract

Background:\ud \ud People of Sub Saharan Africa (SSA) and South Asians(SA) ethnic minorities living in Europe have higher risk of stroke than native Europeans(EU). Study objective is to provide an assessment of gender specific absolute differences in office systolic(SBP) and diastolic(DBP) blood pressure(BP) levels between SSA, SA, and EU.\ud \ud Methods and Findings:\ud \ud We performed a systematic review and meta-analysis of observational studies conducted in Europe that examined BP in non-selected adult SSA, SA and EU subjects. Medline, PubMed, Embase, Web of Science, and Scopus were searched from their inception through January 31st 2015, for relevant articles. Outcome measures were mean SBP and DBP differences between minorities and EU, using a random effects model and tested for heterogeneity. Twenty-one studies involving 9,070 SSA, 18,421 SA, and 130,380 EU were included. Compared with EU, SSA had higher values of both SBP (3.38 mmHg, 95% CI 1.28 to 5.48 mmHg; and 6.00 mmHg, 95% CI 2.22 to 9.78 in men and women respectively) and DBP (3.29 mmHg, 95% CI 1.80 to 4.78; 5.35 mmHg, 95% CI 3.04 to 7.66). SA had lower SBP than EU(-4.57 mmHg, 95% CI -6.20 to -2.93; -2.97 mmHg, 95% CI -5.45 to -0.49) but similar DBP values. Meta-analysis by subgroup showed that SA originating from countries where Islam is the main religion had lower SBP and DBP values than EU. In multivariate meta-regression analyses, SBP difference between minorities and EU populations, was influenced by panethnicity and diabetes prevalence.\ud \ud Conclusions:\ud \ud 1) The higher BP in SSA is maintained over decades, suggesting limited efficacy of prevention strategies in such group in Europe;2) The lower BP in Muslim populations suggests that yet untapped lifestyle and behavioral habits may reveal advantages towards the development of hypertension;3) The additive effect of diabetes, emphasizes the need of new strategies for the control of hypertension in groups at high prevalence of diabetes.

Published
2016

45. Systolic and diastolic blood pressure changes in relation with myocardial infarction and stroke in patients with coronary artery disease

Author

Verdecchia, P, Reboldi, G, Angeli, F, Trimarco, B, Mancia, G, Pogue, J, Gao, P, Peter, S, Teo, K, Yusuf, S, Verdecchia P., Reboldi G., Angeli F., Trimarco B., Mancia G., Pogue J., Gao P., Peter S., Teo K., Yusuf S., Verdecchia, P, Reboldi, G, Angeli, F, Trimarco, B, Mancia, G, Pogue, J, Gao, P, Peter, S, Teo, K, Yusuf, S, Verdecchia P., Reboldi G., Angeli F., Trimarco B., Mancia G., Pogue J., Gao P., Peter S., Teo K., and Yusuf S.

Abstract

Excessively high and low achieved blood pressure (BP) may be associated with a bad outcome in patients with coronary artery disease, the J curve phenomenon. The effect of BP changes from baseline in relation with the subsequent risk of stroke and myocardial infarction (MI) is unknown. Of the 25 620 patients randomized in the Ongoing Telmisartan Alone and in combination with Ramipril Global Endpoint Trial (ONTARGET) study, we selected 19 102 patients with coronary artery disease at baseline. BP at entry was 141/82 mm Hg, and its average decrease during follow-up was 7/6 mm Hg. BP entered the analysis as time-varying variable modeled with restricted cubic splines. After adjustment for several potential determinants of reverse causality, a change in BP from baseline by -34/-21 mm Hg (10th percentile) was associated with a lesser risk of stroke without any significant increase in the risk of MI. A rise in systolic/diastolic BP from baseline by 20/10 mm Hg (90th percentile) was associated with an increased risk of stroke, whereas the risk of MI increased with systolic BP and not with diastolic BP. In conclusion, in patients with coronary artery disease and initially free from congestive heart failure, a BP reduction from baseline over the examined BP range had little effect on the risk of MI and predicted a lower risk of stroke. An increase in systolic BP from baseline increased the risk of stroke and MI. The relationships of BP with risk were much steeper for stroke than for MI. A treatment-induced BP reduction over the explored range seems to be safe in patients with coronary artery disease.

Published
2015

46. Knowledge of risk factors for diabetes or cardiovascular disease (CVD) is poor among individuals with risk factors for CVD

Author

Reboldi, G, Kilkenny, MF, Dunstan, L, Busingye, D, Purvis, T, Reyneke, M, Orgill, M, Cadilhac, DA, Reboldi, G, Kilkenny, MF, Dunstan, L, Busingye, D, Purvis, T, Reyneke, M, Orgill, M, and Cadilhac, DA

Abstract

BACKGROUND: There is limited evidence on whether having pre-existing cardiovascular disease (CVD) or risk factors for CVD such as diabetes, ensures greater knowledge of risk factors important for motivating preventative behaviours. Our objective was to compare knowledge among the Australian public participating in a health check program and their risk status. METHODS: Data from the Stroke Foundation 'Know your numbers' program were used. Staff in community pharmacies provided opportunistic health checks (measurement of blood pressure and diabetes risk assessment) among their customers. Participants were categorised: 1) CVD ± risk of CVD: history of stroke, heart disease or kidney disease, and may have risk factors; 2) risk of CVD only: reported having high blood pressure, high cholesterol, diabetes or atrial fibrillation; and 3) CVD risk free (no CVD or risk of CVD). Multivariable logistic regression analyses were performed including adjustment for age and sex. FINDINGS: Among 4,647 participants, 12% had CVD (55% male, 85% aged 55+ years), 47% were at risk of CVD (40% male, 72% 55+ years) and 41% were CVD risk free (33% male, 27% 55+ years). Participants with CVD (OR: 0.66; 95% CI: 0.55, 0.80) or risk factors for CVD (OR: 0.65; 95% CI: 0.57, 0.73) had poorer knowledge of the risk factors for diabetes/CVD compared to those who were CVD risk free. After adjustment, only participants with risk factors for CVD (OR: 0.80; 95% CI: 0.69, 0.93) had poorer knowledge. Older participants (55+ years) and men had poorer knowledge of diabetes/CVD risk factors and complications of diabetes. CONCLUSIONS: Participants with poorer knowledge of risk factors were older, more often male or were at risk of developing CVD compared with those who were CVD risk free. Health education in these high risk groups should be a priority, as diabetes and CVD are increasing in prevalence throughout the world.

Published
2017

47. Tight Versus Standard Blood Pressure Control in Patients With Hypertension With and Without Cardiovascular Disease

Author

Reboldi, G, Angeli, F, de Simone, G, Staessen, Ja, Verdecchia, P, Cardio Sis Investigators, Porcellati, C, Fornari, G, Sclavo, Mg, Scherillo, M, Raucci, D, Faggiano, P, Porcu, M, Pistis, L, Vancheri, F, Curcio, M, Ieva, M, Muscella, A, Guerrieri, M, Dembech, C, Gulizia, Mm, Francese, Gm, Perticone, F, Iemma, G, Zanolini, G, Pierdomenico, Sd, Mezzetti, A, Benemio, G, Gattobigio, R, Sacchi, N, Cocchieri, M, Prosciutti, L, Garognoli, O, Pirelli, S, Emanuelli, C, Galeazzi, G, Abrignani, Mg, Lombardo, R, Braschi, Gb, Leoncini, G, Igidbashian, D, Marini, R, Mandorla, S, Buccolieri, M, Picchi, L, Casolo, G, Pardini, M, Galletti, F, Barbato, A, Cavallini, C, Borgioni, C, Sardone, Mg, Cipollini, F, Seghieri, G, Arcangeli, E, Boddi, W, Palermo, C, Lembo, G, Malatino, L, Leonardis, D, Gentile, C, Boccanelli, A, Mureddu, Gf, Colivicchi, F, Uguccioni, M, Zanata, G, Martin, G, Mos, L, Martina, S, Dialti, V, Pede, S, Pede, Sa, Ganau, A, Farina, G, Tripodi, E, Miserrafiti, B, Stornello, M, Valvo, Ev, Proietti, G, Bernardinangeli, M, Poddighe, G, Marras, Ma, Biscottini, B, Panciarola, R, Veglio, Franco, Mulatero, Paolo, Caserta, Ma, Chiatto, M, Cioffi, G, Bonazza, G, Achilli, A, Achilli, P., Reboldi, G, Angeli, F, DE SIMONE, Giovanni, Staessen, Ja, Verdecchia, P., Galletti, Ferruccio, Epidemiologie, RS: CARIM - R3 - Vascular biology, and Health Services Research

Subjects
Male, systolic blood pressure, Time Factors, Blood Pressure, Disease, law.invention, Electrocardiography, Randomized controlled trial, cardiovascular disease, law, Prospective Studies, Myocardial infarction, Stroke, Incidence, clinical trial, stroke, 3. Good health, Survival Rate, PROGNOSTIC VALUE, left ventricular geometry, myocardial infarction, CARDIO-SIS, Italy, Cardiology, Female, Hypertrophy, Left Ventricular, hypertrophy, medicine.medical_specialty, hypertension, Randomization, LEFT-VENTRICULAR HYPERTROPHY, Internal medicine, Internal Medicine, medicine, Humans, In patient, LVH, Antihypertensive Agents, Aged, randomized controlled trial, left ventricular, prognosis, J-CURVE PHENOMENON, Proportional hazards model, business.industry, Blood Pressure Determination, medicine.disease, RANDOMIZED-TRIAL, Blood pressure, ARTERIAL-HYPERTENSION, business, Follow-Up Studies
Abstract

An excessive blood pressure (BP) reduction might be dangerous in high-risk patients with cardiovascular disease. In the Studio Italiano Sugli Effetti CARDIOvascolari del Controllo della Pressione Arteriosa SIStolica (Cardio-Sis), 1111 nondiabetic patients with systolic BP ≥150 mm Hg were randomly assigned to a systolic BP target P for interaction=0.82). The main secondary end point, a composite of cardiovascular events and all-cause death, occurred less frequently in the tight than in the standard control group both in patients without (1.47 versus 3.68 patient-years; P =0.016) and with (7.87 versus 11.22 patient-years; P =0.049) previous cardiovascular disease. In a multivariable Cox model, allocation to tight BP control reduced the risk of cardiovascular events to a similar extent in patients with or without overt cardiovascular disease at randomization ( P for interaction=0.43). In conclusion, an intensive treatment aimed to lower systolic BP

Published
2014

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