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

Author

Russo E, Viazzi F, Pontremoli R, Barbagallo CM, Bombelli M, Casiglia E, Cicero AFG, Cirillo M, Cirillo P, Desideri G, D'Elia L, Ferri C, Galletti F, Gesualdo L, Giannattasio C, Iaccarino G, Leoncini G, Mallamaci F, Maloberti A, Masi S, Mengozzi A, Mazza A, Muiesan ML, Nazzaro P, Palatini P, Parati G, Rattazzi M, Rivasi G, Salvetti M, Tikhonoff V, Tocci G, Ungar A, Verdecchia P, Virdis A, Volpe M, Grassi G, Borghi C, Working Group on Uric Acid and Cardiovascular Risk of the Italian Society of Hypertension, Russo, E, Viazzi, F, Pontremoli, R, Barbagallo, C, Bombelli, M, Casiglia, E, Cicero, A, Cirillo, M, Cirillo, P, Desideri, G, D'Elia, L, Ferri, C, Galletti, F, Gesualdo, L, Giannattasio, C, Iaccarino, G, Leoncini, G, Mallamaci, F, Maloberti, A, Masi, S, Mengozzi, A, Mazza, A, Muiesan, M, Nazzaro, P, Palatini, P, Parati, G, Rattazzi, M, Rivasi, G, Salvetti, M, Tikhonoff, V, Tocci, G, Ungar, A, Verdecchia, P, Virdis, A, Volpe, M, Grassi, G, Borghi, C, Russo E, Viazzi F, Pontremoli R, Barbagallo CM, Bombelli M, Casiglia E, Cicero AFG, Cirillo M, Cirillo P, Desideri G, D'Elia L, Ferri C, Galletti F, Gesualdo L, Giannattasio C, Iaccarino G, Leoncini G, Mallamaci F, Maloberti A, Masi S, Mengozzi A, Mazza A, Muiesan ML, Nazzaro P, Palatini P, Parati G, Rattazzi M, Rivasi G, Salvetti M, Tikhonoff V, Tocci G, Ungar A, Verdecchia P, Virdis A, Volpe M, Grassi G, Borghi C, Working Group on Uric Acid and Cardiovascular Risk of the Italian Society of Hypertension, and Russo E, Viazzi F, Pontremoli R, Barbagallo CM, Bombelli M, Casiglia E, Cicero AFG, Cirillo M, Cirillo P, Desideri G, D'Elia L, Ferri C, Galletti F, Gesualdo L, Giannattasio C, Iaccarino G, Leoncini G, Mallamaci F, Maloberti A, Masi S, Mengozzi A, Mazza A, Muiesan ML, Nazzaro P, Palatini P, Parati G, Rattazzi M, Rivasi G, Salvetti M, Tikhonoff V, Tocci G, Ungar A, Verdecchia P, Virdis A, Volpe M, Grassi G, Borghi C

Subjects
Nephrology, Adult, Male, medicine.medical_specialty, Settore MED/09 - Medicina Interna, 030232 urology & nephrology, Allopurinol, Renal function, Hyperuricemia, 030204 cardiovascular system & hematology, Kidney, urologic and male genital diseases, Gastroenterology, 03 medical and health sciences, chemistry.chemical_compound, 0302 clinical medicine, Serum uric acid, Risk Factors, Internal medicine, Diabetes mellitus, medicine, eGFR, Humans, Albuminuria, Renal Insufficiency, Chronic, Aged, business.industry, Cardiovascular risk, nutritional and metabolic diseases, Middle Aged, medicine.disease, Uric Acid, chemistry, Uric acid, Original Article, Female, medicine.symptom, business, medicine.drug, Kidney disease, Glomerular Filtration Rate
Abstract

Background Hyperuricemia is commonly observed in patients with chronic kidney disease (CKD). However, a better understanding of the relationship among uric acid (UA) values, glomerular filtration rate (GFR) and albuminuria may shed light on the mechanisms underlying the excess of cardiovascular mortality associated with both chronic kidney disease and hyperuricemia and lead to better risk stratification. Our main goal was to study the relationships between serum uric acid and kidney disease measures (namely estimated GFR [eGFR] and albuminuria) in a large cohort of individuals at cardiovascular risk from the URic acid Right for heArt Health (URRAH) Project database. Methods Clinical data of 26,971 individuals were analyzed. Factors associated with the presence of hyperuricemia defined on the basis of previously determined URRAH cutoffs for cardiovascular and all-cause mortality were evaluated through multivariate analysis. Chronic kidney disease was defined as eGFR 2 and/or abnormal urinary albumin excretion diagnosed as: (i) microalbuminuria if urinary albumin concentration was > 30 and ≤ 300 mg/L, or if urinary albumin-to-creatinine ratio (ACR) was > 3.4 mg/mmol and ≤ 34 mg/mmol; (ii) macroalbuminuria if urinary albumin concentration was > 300 mg/L, or if ACR was > 34 mg/mmol. Results Mean age was 58 ± 15 years (51% males, 62% with hypertension and 12% with diabetes), mean eGFR was 81 ml/min per 1.73m22with a prevalence of eGFR Conclusions The lower the eGFR the higher the prevalence of hyperuricemia and gout. In subjects with eGFR 90 ml/min. The percentage of individuals treated with allopurinol was below 2% when GFR was above 60 ml/min, it increased to 20% in the presence of CKD 3b and rose further to 35% in individuals with macroalbuminuria. Graphic abstract

Published
2022

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

Author

Pugliese NR, Mengozzi A, Virdis A, Casiglia E, Tikhonoff V, Cicero AFG, Ungar A, Rivasi G, Salvetti M, Barbagallo CM, Bombelli M, Dell'Oro R, Bruno B, Lippa L, D'Elia L, Verdecchia P, Mallamaci F, Cirillo M, Rattazzi M, Cirillo P, Gesualdo L, Mazza A, Giannattasio C, Maloberti A, Volpe M, Tocci G, Georgiopoulos G, Iaccarino G, Nazzaro P, Parati G, Palatini P, Galletti F, Ferri C, Desideri G, Viazzi F, Pontremoli R, Muiesan ML, Grassi G, Masi S, Borghi C, Working Group on Uric Acid and Cardiovascular Risk of the Italian Society of Hypertension, Pugliese NR, Mengozzi A, Virdis A, Casiglia E, Tikhonoff V, Cicero AFG, Ungar A, Rivasi G, Salvetti M, Barbagallo CM, Bombelli M, Dell'Oro R, Bruno B, Lippa L, D'Elia L, Verdecchia P, Mallamaci F, Cirillo M, Rattazzi M, Cirillo P, Gesualdo L, Mazza A, Giannattasio C, Maloberti A, Volpe M, Tocci G, Georgiopoulos G, Iaccarino G, Nazzaro P, Parati G, Palatini P, Galletti F, Ferri C, Desideri G, Viazzi F, Pontremoli R, Muiesan ML, Grassi G, Masi S, Borghi C, Pugliese, Nicola Riccardo, Mengozzi, Alessandro, Virdis, Agostino, Casiglia, Edoardo, Tikhonoff, Valerie, Cicero, Arrigo F G, Ungar, Andrea, Rivasi, Giulia, Salvetti, Massimo, Barbagallo, Carlo M, Bombelli, Michele, Dell'Oro, Raffaella, Bruno, Berardino, Lippa, Luciano, D'Elia, Lanfranco, Verdecchia, Paolo, Mallamaci, Francesca, Cirillo, Massimo, Rattazzi, Marcello, Cirillo, Pietro, Gesualdo, Loreto, Mazza, Alberto, Giannattasio, Cristina, Maloberti, Alessandro, Volpe, Massimo, Tocci, Giuliano, Georgiopoulos, Georgio, Iaccarino, Guido, Nazzaro, Pietro, Parati, Gianfranco, Palatini, Paolo, Galletti, Ferruccio, Ferri, Claudio, Desideri, Giovambattista, Viazzi, Francesca, Pontremoli, Roberto, Muiesan, Maria Lorenza, Grassi, Guido, Masi, Stefano, Borghi, Claudio, Working Group on Uric Acid and Cardiovascular Risk of the Italian Society of Hypertension, Cicero AFG, Pugliese, N, Mengozzi, A, Virdis, A, Casiglia, E, Tikhonoff, V, Cicero, A, Ungar, A, Rivasi, G, Salvetti, M, Barbagallo, C, Bombelli, M, Dell'Oro, R, Bruno, B, Lippa, L, D'Elia, L, Verdecchia, P, Mallamaci, F, Cirillo, M, Rattazzi, M, Cirillo, P, Gesualdo, L, Mazza, A, Giannattasio, C, Maloberti, A, Volpe, M, Tocci, G, Georgiopoulos, G, Iaccarino, G, Nazzaro, P, Parati, G, Palatini, P, Galletti, F, Ferri, C, Desideri, G, Viazzi, F, Pontremoli, R, Muiesan, M, Grassi, G, Masi, S, and Borghi, C

Subjects
Male, medicine.medical_specialty, Settore MED/09 - Medicina Interna, Cardiovascular mortality, Prognosi, Sudden cardiac death, chemistry.chemical_compound, Serum uric acid, Risk Factors, Internal medicine, Cause of Death, medicine, Humans, Myocardial infarction, Metabolic syndrome, Prognosis, Stroke, Retrospective Studies, Original Paper, business.industry, Proportional hazards model, Hazard ratio, General Medicine, Middle Aged, medicine.disease, Uric Acid, Survival Rate, chemistry, Italy, Cardiovascular Diseases, Heart failure, Cardiology, Uric acid, Female, Cardiology and Cardiovascular Medicine, business, Biomarkers, Follow-Up Studies
Abstract

Introduction Serum uric acid (SUA) has been depicted as a contributory causal factor in metabolic syndrome (MS), which in turn, portends unfavourable prognosis. Aim We assessed the prognostic role of SUA in patients with and without MS. Methods We used data from the multicentre Uric Acid Right for Heart Health study and considered cardiovascular mortality (CVM) as death due to fatal myocardial infarction, stroke, sudden cardiac death, or heart failure. Results A total of 9589 subjects (median age 58.5 years, 45% males) were included in the analysis, and 5100 (53%) patients had a final diagnosis of MS. After a median follow-up of 142 months, we observed 558 events. Using a previously validated cardiovascular SUA cut-off to predict CVM (> 5.1 mg/dL in women and 5.6 mg/dL in men), elevated SUA levels were significantly associated to a worse outcome in patients with and without MS (all p p = 0.004). Cox regression analyses identified an independent association between SUA and CVM (Hazard Ratio: 1.79 [95% CI, 1.15–2.79]; p p Conclusion Increasing SUA levels are associated with a higher CVM risk irrespective of the presence of MS: a cardiovascular SUA threshold may improve risk stratification. Graphic abstract

Published
2021

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

Author

Maloberti, A, Bombelli, M, Facchetti, R, Desideri, G, Cicero, AFG, Muiesan, Ml, Agabiti Rosei, E, Salvetti, S, Ungar, A, Rivasi, G, Pontremoli, R, Viazzi, V, Ferri, C, Bernardino, B, Galletti, F, D'elia, L, Palatini, P, Casiglia, E, Tikhonoff, V, Barbagallo, CM, Verdecchia, P, Masi, S, Mallamaci, M, Cirillo, M, Rattazzi, M, Pauletto, P, Cirillo, P, Gesualdo, L, Mazza, A, Volpe, M, Tocci, G, Iaccarino, G, Nazzato, P, Lippa, L, Parati, G, Dell'Oro, R, Quarti Trevano, F, Giannattasio, C, Virdis, A, Grassi, G, Borghi, C, Working Group on Uric Acid and Cardiovascular Risk of the Italian Society of Hypertension., Maloberti, A, Bombelli, M, Facchetti, R, Desideri, G, Cicero, Afg, Muiesan, Ml, Agabiti, Rosei, E, Salvetti, S, Ungar, A, Rivasi, G, Pontremoli, R, Viazzi, V, Ferri, C, Bernardino, B, Galletti, F, D'Elia, L, Palatini, P, Casiglia, E, Tikhonoff, V, Barbagallo, Cm, Verdecchia, P, Masi, S, Mallamaci, M, Cirillo, M, Rattazzi, M, Pauletto, P, Cirillo, P, Gesualdo, L, Mazza, A, Volpe, M, Tocci, G, Iaccarino, G, Nazzato, P, Lippa, L, Parati, G, Dell'Oro, R, Quarti, Trevano, F, Giannattasio, C, Virdis, A, Grassi, G, Borghi, C, Working Group on Uric Acid and Cardiovascular Risk of the Italian Society of, Hypertension., Maloberti A, Bombelli M, Facchetti R, Barbagallo CM, Bernardino B, Rosei EA, Casiglia E, Cicero AFG, Cirillo M, Cirillo P, Desideri G, D'elia L, Dell'Oro R, Ferri C, Galletti F, Giannattasio C, Loreto G, Iaccarino G, Lippa L, Mallamaci F, Masi S, Mazza A, Muiesan ML, Nazzaro P, Parati G, Palatini P, Pauletto P, Pontremoli R, Quarti-Trevano F, Rattazzi M, Rivasi G, Salvetti M, Tikhonoff V, Tocci G, Ungar A, Verdecchia P, Viazzi F, Volpe M, Virdis A, Grassi G, Borghi C, Maloberti A, Bombelli M, Facchetti R, Barbagallo CM, Bernardino B, Rosei EA, Casiglia E, Giuseppe Cicero AF, Cirillo M, Cirillo P, Desideri G, D'elia L, Dell'Oro R, Ferri C, Galletti F, Giannattasio C, Loreto G, Iaccarino G, Lippa L, Mallamaci F, Masi S, Mazza A, Muiesan ML, Nazzaro P, Parati G, Palatini P, Pauletto P, Pontremoli R, Quarti-Trevano F, Rattazzi M, Rivasi G, Salvetti M, Tikhonoff V, Tocci G, Ungar A, Verdecchia P, Viazzi F, Volpe M, Virdis A, Grassi G, Borghi C, Barbagallo, C, Rosei, E, Cicero, A, Loreto, G, Mallamaci, F, Muiesan, M, Nazzaro, P, Quarti-Trevano, F, Salvetti, M, and Viazzi, F

Subjects
Cardiovascular event, Male, medicine.medical_specialty, Settore MED/09 - Medicina Interna, Physiology, medicine.medical_treatment, diuretic, Renal function, Hyperuricemia, cardiovascular events, cardiovascular mortality, uric acid, 030204 cardiovascular system & hematology, 03 medical and health sciences, chemistry.chemical_compound, 0302 clinical medicine, Risk Factors, Internal medicine, Internal Medicine, medicine, Humans, 030212 general & internal medicine, Diuretics, Heart health, Uric acid, cardiovascular events, diuretics, epidemiology, cardiovascular events, cardiovascular mortality, diuretic, uric acid, business.industry, Serum uric acid, Middle Aged, medicine.disease, chemistry, Hypertension, Uric acid, Diuretic, Cardiology and Cardiovascular Medicine, business, Cohort study
Abstract

Objective Although the relationship between hyperuricemia and cardiovascular events has been extensively examined, data on the role of diuretic-related hyperuricemia are still scanty. The present study was designed to collect information on the relationship between diuretic-related hyperuricemia and cardiovascular events. Methods The URic acid Right for heArt Health (URRAH) study is a nationwide, multicentre, observational cohort study involving data on individuals recruited from all the Italy territory under the patronage of the Italian Society of Hypertension with an average follow-up period of 122.3 ± 66.9 months. Patients were classified into four groups according to the diuretic use (yes vs. no) and serum uric acid (SUA) levels (higher vs. lower than the median value of 4.8 mg/dl). All-cause death, cardiovascular deaths and first cardiovascular event were considered as outcomes. Results Seventeen thousand, seven hundred and forty-seven individuals were included in the analysis. Mean age was 57.1 ± 15.2 years, men were 45.3% and SBP and DBP amounted to 144.1 ± 24.6 and 85.2 ± 13.2 mmHg. 17.2% of individuals take diuretics of whom 58% had SUA higher than median value. Patients with hyperuricemia without diuretic use served as reference group. In multivariate adjusted analysis (sex, age, SBP, BMI, glucose, total cholesterol, and glomerular filtration rate) individuals with hyperuricemia and diuretic use exhibit a similar risk for the three outcomes as compared with the reference group. Conclusion Our study showed that diuretic-related hyperuricemia carry a similar risk of cardiovascular events and all-cause mortality when compared with individuals that present hyperuricemia in absence of diuretic therapy.

Published
2021

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

Author

Casiglia E, Tikhonoff V, Virdis A, Masi S, Barbagallo CM, Bombelli M, Bruno B, Cicero AFG, Cirillo M, Cirillo P, Desideri G, D'Elia L, Ferri C, Galletti F, Gesualdo L, Giannattasio C, Iaccarino G, Lippa L, Mallamaci F, Maloberti A, Mazza A, Muiesan ML, Nazzaro P, Palatini P, Parati G, Pontremoli R, Quarti-Trevano F, Rattazzi M, Rivasi G, Salvetti M, Tocci G, Ungar A, Verdecchia P, Viazzi F, Volpe M, Grassi G, Borghi C, Working Group on Uric Acid and Cardiovascular Risk of the Italian Society of Hypertension (SIIA)., Casiglia E, Tikhonoff V, Virdis A, Masi S, Barbagallo CM, Bombelli M, Bruno B, Cicero AFG, Cirillo M, Cirillo P, Desideri G, D'Elia L, Ferri C, Galletti F, Gesualdo L, Giannattasio C, Iaccarino G, Lippa L, Mallamaci F, Maloberti A, Mazza A, Muiesan ML, Nazzaro P, Palatini P, Parati G, Pontremoli R, Quarti-Trevano F, Rattazzi M, Rivasi G, Salvetti M, Tocci G, Ungar A, Verdecchia P, Viazzi F, Volpe M, Grassi G, Borghi C, Casiglia, E, Tikhonoff, V, Virdis, A, Masi, S, Barbagallo, C, Bombelli, M, Bruno, B, Cicero, A, Cirillo, M, Cirillo, P, Desideri, G, D'Elia, L, Ferri, C, Galletti, F, Gesualdo, L, Giannattasio, C, Iaccarino, G, Lippa, L, Mallamaci, F, Maloberti, A, Mazza, A, Muiesan, M, Nazzaro, P, Palatini, P, Parati, G, Pontremoli, R, Quarti-Trevano, F, Rattazzi, M, Rivasi, G, Salvetti, M, Tocci, G, Ungar, A, Verdecchia, P, Viazzi, F, Volpe, M, Grassi, G, Borghi, C, Working Group on Uric Acid and Cardiovascular Risk of the Italian Society of Hypertension (SIIA)., Casiglia, Edoardo, Tikhonoff, Valérie, Virdis, Agostino, Masi, Stefano, Barbagallo, Carlo M, Bombelli, Michele, Bruno, Bernardino, Cicero, Arrigo F G, Cirillo, Massimo, Cirillo, Pietro, Desideri, Giovambattista, D'Elia, Lanfranco, Ferri, Claudio, Galletti, Ferruccio, Gesualdo, Loreto, Giannattasio, Cristina, Iaccarino, Guido, Lippa, Luciano, Mallamaci, Francesca, Maloberti, Alessandro, Mazza, Alberto, Muiesan, Maria Lorenza, Nazzaro, Pietro, Palatini, Paolo, Parati, Gianfranco, Pontremoli, Roberto, Quarti-Trevano, Fosca, Rattazzi, Marcello, Rivasi, Giulia, Salvetti, Massimo, Tocci, Giuliano, Ungar, Andrea, Verdecchia, Paolo, Viazzi, Francesca, Volpe, Massimo, Grassi, Guido, and Borghi, Claudio

Subjects
Adult, Male, medicine.medical_specialty, Adolescent, Physiology, cut-off value, 030204 cardiovascular system & hematology, 03 medical and health sciences, chemistry.chemical_compound, Young Adult, 0302 clinical medicine, uric acid, Internal medicine, Internal Medicine, medicine, ORIGINAL PAPERS: Epidemiology, Humans, sex, 030212 general & internal medicine, Hyperuricemia, Myocardial infarction, Risk factor, Aged, Aged, 80 and over, uric acid, cardiovascular, arterial hypertension, cut-off value, mortality, myocardial infarction,sex, uric acid, Proportional hazards model, business.industry, cut-off value, mortality, myocardial infarction, sex, uric acid, Hazard ratio, Middle Aged, medicine.disease, Prognosis, mortality, Confidence interval, Uric acid, myocardial infarction, epidemiology, myocardial infarction, chemistry, Italy, Hypertension, ComputingMethodologies_DOCUMENTANDTEXTPROCESSING, Uric acid, Female, Cardiology and Cardiovascular Medicine, business, Cohort study
Abstract

Supplemental Digital Content is available in the text, Objective: The Working Group on Uric Acid and Cardiovascular Risk of the Italian Society of Hypertension conceived and designed an ad-hoc study aimed at searching for prognostic cut-off values of serum uric acid (SUA) in predicting fatal myocardial infaction (MI) in women and men. Methods: The URic acid Right for heArt Health study is a nationwide, multicentre, observational cohort study involving data on individuals aged 18–95 years recruited on a regional community basis from all the territory of Italy under the patronage of the Italian Society of Hypertension with a mean follow-up period of 122.3 ± 66.9 months. Results: A total of 23 467 individuals were included in the analysis. Cut-off values of SUA able to discriminate MI status were identified by mean of receiver operating characteristic curves in the whole database (>5.70 mg/dl), in women (>5.26 mg/dl) and in men (>5.49 mg/dl). Multivariate Cox regression analyses adjusted for confounders (age, arterial hypertension, diabetes, chronic kidney disease, smoking habit, ethanol intake, BMI, haematocrit, LDL cholesterol and use of diuretics) identified an independent association between SUA and fatal MI in the whole database (hazard ratio 1.381, 95% confidence intervals, 1.096–1.758, P = 0.006) and in women (hazard ratio 1.514, confidence intervals 1.105–2.075, P

Published
2020

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

Author

Soysal, P., Veronese, N., Smith, L., Torbahn, G., Jackson, S. E., Yang, L., Ungar, A., Rivasi, G., Rafanelli, M., Petrovic, M., Maggi, S., Isik, A. T., Demurtas, J., The Special Interest Groups in Systematic Reviews and Meta-analyses for Healthy Ageing, and Cardiovascular Medicine of the European Society of Geriatric Medicine (EuGMS), SOYSAL, PINAR, Soysal, P., Veronese, N., Smith, L., Torbahn, G., Jackson, S.E., Yang, L., Ungar, A., Rivasi, G., Rafanelli, M., Petrovic, M., Maggi, S., Isik, A.T., Demurtas, J., and The Special Interest Groups in Systematic Reviews and Meta-analyses for Healthy Ageing, and Cardiovascular Medicine of the European Society of Geriatric Medicine (EuGMS)

Subjects
medicine.medical_specialty, 030214 geriatrics, Heart disease, business.industry, medicine.disease, Lower risk, an umbrella review of observational studies-, EUROPEAN GERIATRIC MEDICINE, cilt.10, ss.863-870, 2019 [SOYSAL P., Veronese N., Smith L., Torbahn G., Jackson S. E. , Yang L., Ungar A., Rivasi G., Rafanelli M., Petrovic M., et al., -Orthostatic hypotension and health outcomes], 03 medical and health sciences, Orthostatic vital signs, 0302 clinical medicine, Heart failure, Internal medicine, Meta-analysis, medicine, Dementia, Observational study, 030212 general & internal medicine, business, Stroke, Orthostatic hypotension · Umbrella review · Meta-analysis · Mortality · Fall · Heart failure · Heart disease · Stroke
Abstract

To investigate potential relationships between orthostatic hypotension (OH) and negative health outcomes and mortality, through an umbrella review with integrated meta-analyses. Orthostatic hypotension is significantly associated with several negative outcomes in older people, but a suggestive evidence is available only for higher risk of coronary heart disease congestive heart failure, stroke, falls dementia, and all-cause mortality. Orthostatic hypotension seems to be significantly associated with several negative health outcomes in older people, even if only associations with coronary heart disease, congestive heart failure, stroke, falls, dementia, and all-cause mortality are supported by suggestive evidence. Orthostatic hypotension (OH) is associated with older age and many negative clinical outcomes in geriatric practice. We aimed to capture the breadth of outcomes that have been associated with the presence of OH and systematically assess the quality, strength and credibility of these associations using an umbrella review with integrated meta-analyses. We systematically searched several major databases from their commencements through to 16th May 2019 for meta-analyses of observational studies of OH and any health-related outcome. We used these metrics to categorize the strength of evidence of significant outcomes (p

Published
2019

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

Author

Desideri, Giovambattista, Virdis, Agostino, Casiglia, Edoardo, Borghi Claudio, Cicero AFG, Muiesan ML, Rosei EA, Salvetti M, Ungar A, Rivasi G, Pontremoli R, Viazzi F, Desideri G, Grassi G, Bombelli M, Facchetti R, Ferri C, Bernardino B, Galletti F, D'Elia L, Palatini P, Casiglia E, Tikhonoff V, Barbagallo CM, Verdecchia P, Virdis, Pietrina, Masi S, Mallamaci F, Cirillo M, Rattazzi M, Pauletto P, Cirillo P, Gesualdo L, Mazza A, Giannattasio C, Maloberti A, Volpe M, Tocci G, Iaccarino G, Nazzaro, Desideri, Giovambattista, Virdis, Agostino, Casiglia, Edoardo, Borghi, Claudio, 644 Desideri, G, Virdis, A, Casiglia, E, Borghi, C, Cicero, A, Muiesan, M, Agabiti-Rosei, E, Salvetti, M, Ungar, A, Rivasi, G, Pontremoli, R, Viazzi, Grassi, G, Bombelli, M, Facchetti, R, Ferri, C, Bernardino, B, Galetti, F, D’Elia, L, Palatini, P, Tickhonoff, V, Barbagallo, C, Verdecchia, P, Masi, S, Mallamaci, F, Cirillo, M, Gesualdo, L, Mazza, A, Giannattasio, C, Maloberti, A, Ratazzi, M, Pauletto, P, Volpe, M, Tocci, G, Iaccarino, G, Nazzaro, P, Cicero, Afg, Muiesan, Ml, Rosei, Ea, Viazzi, F, Desideri, G, Galletti, F, D'Elia, L, Tikhonoff, V, Barbagallo, Cm, Virdis, Pietrina, Rattazzi, M, Cirillo, P, and Nazzaro

Subjects
medicine.medical_specialty, Settore MED/09 - Medicina Interna, Prognosi, Epidemiology, Population, Disease, Hyperuricemia, 030204 cardiovascular system & hematology, Risk Assessment, Cardiovascular disease, Uric acid, Biomarkers, Cardiovascular Diseases, Humans, Italy, Prognosis, Research Design, Retrospective Studies, Risk Factors, Uric Acid, Internal Medicine, Cardiology and Cardiovascular Medicine, 03 medical and health sciences, chemistry.chemical_compound, 0302 clinical medicine, Retrospective Studie, Internal medicine, medicine, Risk factor, education, 030203 arthritis & rheumatology, education.field_of_study, business.industry, Risk Factor, Retrospective cohort study, Biomarker, medicine.disease, chemistry, business, Risk assessment, Human
Abstract

The relevance of cardiovascular role played by levels of serum uric acid is dramatically growing, especially as cardiovascular risk factor potentially able to exert either a direct deleterious impact or a synergic effect with other cardiovascular risk factors. At the present time, it still remains undefined the threshold level of serum uric acid able to contribute to the cardiovascular risk. Indeed, the available epidemiological case studies are not homogeneous, and some preliminary data suggest that the so-called "cardiovascular threshold limit" may substantially differ from that identified as a cut-off able to trigger the acute gout attack. In such scenario, there is the necessity to clarify and quantify this threshold value, to insert it in the stratification of risk algorithm scores and, in turn, to adopt proper prevention and correction strategies. The clarification of the relationship between circulating levels of uric acid and cardio-nephro-metabolic disorders in a broad sample representative of general population is critical to identify the threshold value of serum uric acid better discriminating the increased risk associated with uric acid. The Uric acid Right for heArt Health (URRAH) project has been designed to define, as primary objective, the level of uricemia above which the independent risk of cardiovascular disease may increase in a significantly manner in a general Italian population.

Published
2018

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

Author

Elisa Russo, Francesca Viazzi, Roberto Pontremoli, Carlo M. Barbagallo, Michele Bombelli, Edoardo Casiglia, Arrigo F. G. Cicero, Massimo Cirillo, Pietro Cirillo, Giovambattista Desideri, Lanfranco D'Elia, Raffaella Dell'Oro, Claudio Ferri, Ferruccio Galletti, Loreto Gesualdo, Cristina Giannattasio, Guido Iaccarino, Giovanna Leoncini, Francesca Mallamaci, Alessandro Maloberti, Stefano Masi, Alessandro Mengozzi, Alberto Mazza, Maria L. Muiesan, Pietro Nazzaro, Paolo Palatini, Gianfranco Parati, Marcello Rattazzi, Giulia Rivasi, Massimo Salvetti, Valérie Tikhonoff, Giuliano Tocci, Fosca A. L. Quarti Trevano, Andrea Ungar, Paolo Verdecchia, Agostino Virdis, Massimo Volpe, Guido Grassi, Claudio Borghi, Russo, Elisa, Viazzi, Francesca, Pontremoli, Roberto, Barbagallo, Carlo M, Bombelli, Michele, Casiglia, Edoardo, Cicero, Arrigo F G, Cirillo, Massimo, Cirillo, Pietro, Desideri, Giovambattista, D'Elia, Lanfranco, Dell'Oro, Raffaella, Ferri, Claudio, Galletti, Ferruccio, Gesualdo, Loreto, Giannattasio, Cristina, Iaccarino, Guido, Leoncini, Giovanna, Mallamaci, Francesca, Maloberti, Alessandro, Masi, Stefano, Mengozzi, Alessandro, Mazza, Alberto, Muiesan, Maria L, Nazzaro, Pietro, Palatini, Paolo, Parati, Gianfranco, Rattazzi, Marcello, Rivasi, Giulia, Salvetti, Massimo, Tikhonoff, Valérie, Tocci, Giuliano, Quarti Trevano, Fosca A L, Ungar, Andrea, Verdecchia, Paolo, Virdis, Agostino, Volpe, Massimo, Grassi, Guido, Borghi, Claudio, Russo E, Viazzi F, Pontremoli R, Barbagallo CM, Bombelli M, Casiglia E, Cicero AFG, Cirillo M, Cirillo P, Desideri G, D'Elia L, Dell'Oro R, Ferri C, Galletti F, Gesualdo L, Giannattasio C, Iaccarino G, Leoncini G, Mallamaci F, Maloberti A, Masi S, Mengozzi A, Mazza A, Muiesan ML, Nazzaro P, Palatini P, Parati G, Rattazzi M, Rivasi G, Salvetti M, Tikhonoff V, Tocci G, Quarti Trevano FAL, Ungar A, Verdecchia P, Virdis A, Volpe M, Grassi G, Borghi C., Russo, E, Viazzi, F, Pontremoli, R, Barbagallo, C, Bombelli, M, Casiglia, E, Cicero, A, Cirillo, M, Cirillo, P, Desideri, G, D'Elia, L, Dell'Oro, R, Ferri, C, Galletti, F, Gesualdo, L, Giannattasio, C, Iaccarino, G, Leoncini, G, Mallamaci, F, Maloberti, A, Masi, S, Mengozzi, A, Mazza, A, Muiesan, M, Nazzaro, P, Palatini, P, Parati, G, Rattazzi, M, Rivasi, G, Salvetti, M, Tikhonoff, V, Tocci, G, Quarti Trevano, F, Ungar, A, Verdecchia, P, Virdis, A, Volpe, M, Grassi, G, Borghi, C, and Elisa Russo, Francesca Viazzi, Roberto Pontremoli, Carlo M Barbagallo, Michele Bombelli, Edoardo Casiglia, Arrigo F G Cicero, Massimo Cirillo, Pietro Cirillo, Giovambattista Desideri, Lanfranco D'Elia, Raffaella Dell'Oro, Claudio Ferri, Ferruccio Galletti, Loreto Gesualdo, Cristina Giannattasio, Guido Iaccarino, Giovanna Leoncini, Francesca Mallamaci, Alessandro Maloberti , Stefano Masi, Alessandro Mengozzi, Alberto Mazza, Maria L Muiesan, Pietro Nazzaro, Paolo Palatini, Gianfranco Parati, Marcello Rattazzi, Giulia Rivasi, Massimo Salvetti, Valérie Tikhonoff, Giuliano Tocci, Fosca A L Quarti Trevano, Andrea Ungar, Paolo Verdecchia, Agostino Virdis, Massimo Volpe, Guido Grassi, Claudio Borghi

Subjects
medicine.medical_specialty, hyperuricemia, Cardiovascular Medicine, urologic and male genital diseases, Gastroenterology, albuminuria, chemistry.chemical_compound, cardiovascular mortality, Internal medicine, medicine, eGFR, Diseases of the circulatory (Cardiovascular) system, Hyperuricemia, Risk factor, Original Research, business.industry, Incidence (epidemiology), Confounding, all-cause mortality, hyperuricemia, eGFR, albuminuria, cardiovascular mortality, all-cause mortality, medicine.disease, chemistry, Quartile, RC666-701, Albuminuria, Uric acid, medicine.symptom, Cardiology and Cardiovascular Medicine, business, Kidney disease
Abstract

Background: Serum uric acid predicts the onset and progression of kidney disease, and the occurrence of cardiovascular and all-cause mortality. Nevertheless, it is unclear which is the appropriate definition of hyperuricemia in presence of chronic kidney disease (CKD). Our goal was to study the independent impact of uric acid and CKD on mortality.Methods: We retrospectively investigated 21,963 patients from the URRAH study database. Hyperuricemia was defined on the basis of outcome specific cut-offs separately identified by ROC curves according to eGFR strata. The primary endpoints were cardiovascular and all-cause mortality.Results: After a mean follow-up of 9.8 year, there were 1,582 (7.20%) cardiovascular events and 3,130 (14.25%) deaths for all causes. The incidence of cardiovascular and all-cause mortality increased in parallel with reduction of eGFR strata and with progressively higher uric acid quartiles. During 215,618 person-years of follow-up, the incidence rate for cardiovascular mortality, stratified based on eGFR (>90, between 60 and 90 and Conclusions: hyperuricemia is a risk factor for cardiovascular and all-cause mortality additively to eGFR strata and albuminuria, in patients at cardiovascular risk.

Published
2021

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

Author

Claudio Ferri, Agostino Virdis, Marcello Rattazzi, Alessandro Maloberti, Arrigo F G Cicero, Massimo Cirillo, Andrea Ungar, Maria Lorenza Muiesan, Pietro Nazzaro, Francesca Viazzi, Giuliano Tocci, Guido Grassi, Ferruccio Galletti, Valérie Tikhonoff, Michele Bombelli, Paolo Verdecchia, Francesca Mallamaci, Giovambattista Desideri, Cristina Giannattasio, Gianfranco Parati, Paolo Palatini, Massimo Salvetti, Carlo M. Barbagallo, Alberto Mazza, Claudio Borghi, Massimo Volpe, Pietro Cirillo, Roberto Pontremoli, Guido Iaccarino, Edoardo Casiglia, Loreto Gesualdo, Giulia Rivasi, Lanfranco D'Eliak, Stefano Masi, Muiesan ML, Salvetti M, Virdis A, Masi S, Casiglia E, Tikhonoff V, Barbagallo CM, Bombelli M, Cicero AFG, Cirillo M, Cirillo P, Desideri G, D'Eliak L, Ferri C, Galletti F, Gesualdo L, Giannattasio C, Iaccarino G, Mallamaci F, Maloberti A, Mazza A, Nazzaro P, Palatini P, Parati G, Pontremoli R, Rattazzi M, Rivasi G, Tocci G, Ungar A, Verdecchia P, Viazzi F, Volpe M, Grassi G, Borghi C, Muiesan, M, Salvetti, M, Virdis, A, Masi, S, Casiglia, E, Tikhonoff, V, Barbagallo, C, Bombelli, M, Cicero, A, Cirillo, M, Cirillo, P, Desideri, G, D’Eliak, L, Ferri, C, Galletti, F, Gesualdo, L, Giannattasio, C, Iaccarino, G, Mallamaci, F, Maloberti, A, Mazza, A, Nazzaro, P, Palatini, P, Parati, G, Pontremoli, R, Rattazzi, M, Rivasi, G, Tocci, G, Ungar, A, Verdecchia, P, Viazzi, F, Volpe, M, Grassi, G, Borghi, C, Muiesan, Maria L, Salvetti, Massimo, Virdis, Agostino, Masi, Stefano, Casiglia, Edoardo, Tikhonoff, Valérie, Barbagallo, Carlo M, Bombelli, Michele, Cicero, Arrigo F G, Cirillo, Massimo, Cirillo, Pietro, Desideri, Giovambattista, D'Eliak, Lanfranco, Ferri, Claudio, Galletti, Ferruccio, Gesualdo, Loreto, Giannattasio, Cristina, Iaccarino, Guido, Mallamaci, Francesca, Maloberti, Alessandro, Mazza, Alberto, Nazzaro, Pietro, Palatini, Paolo, Parati, Gianfranco, Pontremoli, Roberto, Rattazzi, Marcello, Rivasi, Giulia, Tocci, Giuliano, Ungar, Andrea, Verdecchia, Paolo, Viazzi, Francesca, Volpe, Massimo, Grassi, Guido, and Borghi, Claudio

Subjects
medicine.medical_specialty, Settore MED/09 - Medicina Interna, Physiology, Epidemiology, Cut-off value, 030204 cardiovascular system & hematology, Cohort Studies, 03 medical and health sciences, 0302 clinical medicine, Risk Factors, Internal medicine, Diabetes mellitus, Internal Medicine, Medicine, Humans, 030212 general & internal medicine, Mortality, Risk factor, Cut-off value, heart failure, mortality, uric acid, Heart Failure, business.industry, Proportional hazards model, Hazard ratio, Confounding, cut-off value, heart failure, mortality, uric acid, medicine.disease, Uric Acid, Italy, Heart failure, Cohort, Hypertension, Cardiology, Cardiology and Cardiovascular Medicine, business, Cohort study
Abstract

Objective: To assess the prognostic cut-off values of serum uric acid (SUA) in predicting fatal and morbid heart failure in a large Italian cohort in the frame of the Working Group on Uric Acid and Cardiovascular Risk of the Italian Society of Hypertension. Methods: The URic acid Right for heArt Health (URRAH) study is a nationwide, multicentre, cohort study involving data on individuals aged 18-95 years, recruited on a community basis from all regions of Italy under the patronage of the Italian Society of Hypertension with a mean follow-up period of 128 ± 65 months. Incident heart failure was defined on the basis of International Classification of Diseases Tenth Revision codes and double-checked with general practitioners and hospital files. Multivariate Cox regression models having fatal and morbid heart failure as dependent variables, adjusted for sex, age, SBP, diabetes, estimated glomerular filtration rate, smoking habit, ethanol intake, BMI, haematocrit, LDL cholesterol, previous diagnosis of heart failure and use of diuretics as possible confounders, were used to search for an association between SUA as a continuous variable and heart failure. By means of receiver operating characteristic curves, two prognostic cut-off values (one for all heart failure and one for fatal heart failure) were identified as able to discriminate between individuals doomed to develop the event. These cut-off values were used as independent predictors to divide individuals according to prognostic cut-off values in a multivariate Cox models, adjusted for confounders. Results: A total of 21 386 individuals were included in the analysis. In Cox analyses, SUA as a continuous variable was a significant predictor of all [hazard ratio 1.29 (1.23-1.359), P < 0.0001] and fatal [hazard ratio 1.268 (1.121-1.35), P < 0.0001] incident heart failure. Cut-off values of SUA able to discriminate all and fatal heart failure status were identified by mean of receiver operating characteristic curves in the whole database: SUA more than 5.34 mg/dl (confidence interval 4.37-5.6, sensitivity 52.32, specificity 63.96, P < 0.0001) was the univariate prognostic cut-off value for all heart failure, whereas SUA more than 4.89 mg/dl (confidence interval 4.78-5.78, sensitivity 68.29, specificity 49.11, P < 0.0001) for fatal heart failure. The cut-off for all heart failure and the cut-off value for fatal heart failure were accepted as independent predictors in the Cox analysis models, the hazard ratios being 1.645 (1.284-2.109, P < 0.0001) for all heart failure and 1.645 (1.284-2.109, P < 0.0001) for fatal heart failure, respectively. Conclusion: The results of the current study confirm that SUA is an independent risk factor for all heart failure and fatal heart failure, after adjusting for potential confounding variables and demonstrate that a prognostic cut-off value can be identified for all heart failure (>5.34 mg/dl) and for fatal heart failure (>4.89 mg/dl).

Published
2021

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

Author

Guido Grassi, Francesca Viazzi, Andrea Ungar, Lanfranco D'Elia, Massimo Salvetti, Paolo Spinella, Massimo Volpe, Agostino Virdis, Gianfranco Parati, Roberto Pontremoli, Stefano Masi, Giulia Rivasi, Loreto Gesualdo, Giuliano Tocci, Claudio Ferri, Ferruccio Galletti, Francesca Mallamaci, Alessandro Maloberti, Maria Lorenza Muiesan, Pietro Nazzaro, Valérie Tikhonoff, Michele Bombelli, Massimo Cirillo, Cristina Giannattasio, Paolo Palatini, Carlo M. Barbagallo, Paolo Verdecchia, Marcello Rattazzi, Alberto Mazza, Claudio Borghi, Edoardo Casiglia, Guido Iaccarino, Fosca Quarti-Trevano, Pietro Cirillo, Giovambattista Desideri, Arrigo F G Cicero, Tikhonoff, Valérie, Casiglia, Edoardo, Spinella, Paolo, Barbagallo, Carlo M., Bombelli, Michele, Cicero, Arrigo F. G., Cirillo, Massimo, Cirillo, Pietro, Desideri, Giovambattista, D’Elia, Lanfranco, Ferri, Claudio, Galletti, Ferruccio, Gesualdo, Loreto, Giannattasio, Cristina, Iaccarino, Guido, Mallamaci, Francesca, Maloberti, Alessandro, Masi, Stefano, Mazza, Alberto, Muiesan, Maria Lorenza, Nazzaro, Pietro, Palatini, Paolo, Parati, Gianfranco, Pontremoli, Roberto, Quarti-Trevano, Fosca, Rattazzi, Marcello, Rivasi, Giulia, Salvetti, Massimo, Tocci, Giuliano, Ungar, Andrea, Verdecchia, Paolo, Viazzi, Francesca, Virdis, Agostino, Volpe, Massimo, Grassi, Guido, Borghi, Claudio, Tikhonoff, V, Casiglia, E, Spinella, P, Barbagallo, C, Bombelli, M, Cicero, A, Cirillo, M, Cirillo, P, Desideri, G, D'Elia, L, Ferri, C, Galletti, F, Gesualdo, L, Giannattasio, C, Iaccarino, G, Mallamaci, F, Maloberti, A, Masi, S, Mazza, A, Muiesan, M, Nazzaro, P, Palatini, P, Parati, G, Pontremoli, R, Quarti-Trevano, F, Rattazzi, M, Rivasi, G, Salvetti, M, Tocci, G, Ungar, A, Verdecchia, P, Viazzi, F, Virdis, A, Volpe, M, Grassi, G, Borghi, C, and Tikhonoff V, Casiglia E, Spinella P, Barbagallo CM, Bombelli M, Cicero AFG, Cirillo M, Cirillo P, Desideri G, D'elia L, Ferri C, Galletti F, Gesualdo L, Giannattasio C, Iaccarino G, Mallamaci F, Maloberti A, Masi S, Mazza A, Muiesan ML, Nazzaro P, Palatini P, Parati G, Pontremoli R, Quarti-Trevano F, Rattazzi M, Rivasi G, Salvetti M, Tocci G, Ungar A, Verdecchia P, Viazzi F, Virdis A, Volpe M, Grassi G, Borghi C

Subjects
medicine.medical_specialty, Settore MED/09 - Medicina Interna, uric acid, cardiovascular risk, serum uric acid, stroke, hypertension, cardiovascular prevention, cardiovascular disease, chemistry.chemical_compound, Risk Factors, Internal medicine, Diabetes mellitus, Internal Medicine, medicine, Humans, Stroke, uric acid, hypertension, business.industry, Confounding, Prognosis, medicine.disease, Confidence interval, Uric Acid, chemistry, Hypertension, Uric acid, business, Body mass index, Cohort study, Kidney disease
Abstract

The Working Group on Uric Acid and Cardiovascular Risk of the Italian Society of Hypertension conceived and designed an ad hoc study aimed at searching for prognostic cut-off values of serum uric acid (SUA) in predicting combined (fatal and non-fatal) cerebrovascular (CBV) events in the whole database. The URic acid Right for heArt Health study is a nationwide, multicenter, observational cohort study involving data on subjects aged 18-95 years recruited on a regional community basis from all the territory of Italy under the patronage of the Italian Society of Hypertension with a mean follow-up period of 120.7 ± 61.8 months. A total of 14,588 subjects were included in the analysis. A prognostic cut-off value of SUA able to discriminate combined CBV events (>4.79 mg/dL or >284.91 µmol/L) was identified by means of receiver operating characteristic curve in the whole database. Multivariate Cox regression analysis adjusted for confounders (age, sex, arterial hypertension, diabetes, chronic kidney disease, smoking habit, ethanol intake, body mass index, low-density lipoprotein cholesterol, and use of diuretics) identified an independent association between SUA and combined CBV events in the whole database (HR 1.249, 95% confidence interval, 1.041-1.497, p = 0.016). The results of the present study confirm that SUA is an independent risk marker for CBV events after adjusting for potential confounding variables, including arterial hypertension, and demonstrate that >4.79 mg/dL is a valid prognostic cut-off value.

Published
2021

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

Author

Massimo Volpe, Luciano Lippa, Andrea Ungar, Francesca Viazzi, Agostino Virdis, Maria Lorenza Muiesan, Georgios Georgiopoulos, Berardino Bruno, Cristina Giannattasio, Loreto Gesualdo, Pietro Nazzaro, Paolo Palatini, Alberto Mazza, Guido Grassi, Massimo Salvetti, Carlo M. Barbagallo, Claudio Borghi, Lanfranco D'Elia, Marcello Rattazzi, Francesca Mallamaci, Arrigo F G Cicero, Ferruccio Galletti, Gianfranco Parati, Alessandro Maloberti, Raffaella Dell'Oro, Alessandro Mengozzi, Giuliano Tocci, Stefano Masi, Giovambattista Desideri, Pietro Cirillo, Valérie Tikhonoff, Michele Bombelli, Gianpaolo Reboldi, Massimo Cirillo, Roberto Pontremoli, Claudio Ferri, Paolo Verdecchia, Edoardo Casiglia, Guido Iaccarino, Fabio Angeli, Giulia Rivasi, 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 P, Parati G, Virdis A, Reboldi G, Masi S, Mengozzi A, Casiglia E, Tikhonoff V, Cicero AFG, Ungar A, Rivasi G, Salvetti M, Barbagallo CM, Bombelli M, Dell'Oro R, Bruno B, Lippa L, D'Elia L, Verdecchia P, 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 ML, 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, Georgio, Iaccarino, Guido, Nazzaro, Pietro, Galletti, Ferruccio, Ferri, Claudio, Desideri, Giovambattista, Viazzi, Francesca, Pontremoli, Roberto, Muiesan, Maria Lorenza, Grassi, Guido, and Borghi, Claudio

Subjects
medicine.medical_specialty, Sympathetic nervous system, Longitudinal study, Epidemiology, Heart rate, 030204 cardiovascular system & hematology, Cardiovascular, 03 medical and health sciences, chemistry.chemical_compound, 0302 clinical medicine, Internal medicine, Sympathetic activity, Medicine, 030212 general & internal medicine, Risk factor, Mortality, Proportional hazards model, business.industry, Hazard ratio, Confidence interval, medicine.anatomical_structure, chemistry, Cardiology, Uric acid, Cardiology and Cardiovascular Medicine, business
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 Conclusion This data suggest that the contribution of UA to determining CVM is modulated by the level of HR supporting the hypothesis that activation of the sympathetic nervous system facilitates the action of UA as a cardiovascular risk factor.

Published
2020

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

Author

Marcello Rattazzi, Francesca Viazzi, Maria Lorenza Muiesan, Pietro Cirillo, Pietro Nazzaro, Paolo Verdecchia, Andrea Ungar, Georgios Georgiopoulos, Giulia Rivasi, Berardino Bruno, Alberto Mazza, Claudio Borghi, Agostino Virdis, Massimo Volpe, Loreto Gesualdo, Alessandro Maloberti, Giovambattista Desideri, Giuliano Tocci, Valérie Tikhonoff, Michele Bombelli, Cristina Giannattasio, Roberto Pontremoli, Paolo Palatini, Carlo M. Barbagallo, Raffaella Dell'Oro, Lanfranco D'Elia, Massimo Cirillo, Ferruccio Galletti, Gianfranco Parati, Luciano Lippa, Stefano Masi, Guido Grassi, Francesca Mallamaci, Massimo Salvetti, Claudio Ferri, Edoardo Casiglia, Guido Iaccarino, Arrigo F G Cicero, Virdis, A, Masi, S, Casiglia, E, Tikhonoff, V, Cicero, A, Ungar, A, Rivasi, G, Salvetti, M, Barbagallo, C, Bombelli, M, Dell'Oro, R, Bruno, B, Lippa, L, D'Elia, L, Verdecchia, P, Mallamaci, F, Cirillo, M, Rattazzi, M, Cirillo, P, Gesualdo, L, Mazza, A, Giannattasio, C, Maloberti, A, Volpe, M, Tocci, G, Georgiopoulos, G, Iaccarino, G, Nazzaro, P, Parati, G, Palatini, P, Galletti, F, Ferri, C, Desideri, G, Viazzi, F, Pontremoli, R, Muiesan, M, Grassi, G, Borghi, C, Virdis, A., Masi, S., Casiglia, E., Tikhonoff, V., Cicero, A. F. G., Ungar, A., Rivasi, G., Salvetti, M., Barbagallo, C. M., Bombelli, M., Dell'Oro, R., Bruno, B., Lippa, L., D'Elia, L., Verdecchia, P., Mallamaci, F., Cirillo, M., Rattazzi, M., Cirillo, P., Gesualdo, L., Mazza, A., Giannattasio, C., Maloberti, A., Volpe, M., Tocci, G., Georgiopoulos, G., Iaccarino, G., Nazzaro, P., Parati, G., Palatini, P., Galletti, F., Ferri, C., Desideri, G., Viazzi, F., Pontremoli, R., Muiesan, M. L., Grassi, G., Borghi, C., Virdis A, Masi S, Casiglia E, Tikhonoff V, Cicero AFG, Ungar A, Rivasi G, Salvetti M, Barbagallo CM, Bombelli M, Dell'Oro R, Bruno B, Lippa L, D'Elia L, Verdecchia P, Mallamaci F, Cirillo M, Rattazzi M, Cirillo P, Gesualdo L, Mazza A, Giannattasio C, Maloberti A, Volpe M, Tocci G, Georgiopoulos G, Iaccarino G, Nazzaro P, Parati G, Palatini P, Galletti F, Ferri C, Desideri G, Viazzi F, Pontremoli R, Muiesan ML, Grassi G, Borghi C, Virdis A., Masi S., Casiglia E., Tikhonoff V., Cicero A.F.G., Ungar A., Rivasi G., Salvetti M., Barbagallo C.M., Bombelli M., Dell'Oro R., Bruno B., Lippa L., D'Elia L., Verdecchia P., Mallamaci F., Cirillo M., Rattazzi M., Cirillo P., Gesualdo L., Mazza A., Giannattasio C., Maloberti A., Volpe M., Tocci G., Georgiopoulos G., Iaccarino G., Nazzaro P., Parati G., Palatini P., Galletti F., Ferri C., Desideri G., Viazzi F., Pontremoli R., Muiesan M.L., Grassi G., and Borghi C.

Subjects
Male, medicine.medical_specialty, Settore MED/09 - Medicina Interna, epidemiology, heart failure, humans, risk, uric acid, Cause of Death, Female, Humans, Italy, Middle Aged, Mortality, Practice Patterns, Physicians', Quality Improvement, Risk Assessment, Risk Factors, Uric Acid, Cardiovascular Diseases, Hypertension, Hyperuricemia, Practice Patterns, 030204 cardiovascular system & hematology, Sudden cardiac death, 03 medical and health sciences, 0302 clinical medicine, Internal medicine, Epidemiology, Internal Medicine, Medicine, 030212 general & internal medicine, Myocardial infarction, human, Stroke, Epidemiology, heart failure, humans, risk, uric acid, Physicians', business.industry, Proportional hazards model, Hazard ratio, Uric acid, cardiovascular mortality, epidemiology, medicine.disease, Heart failure, business
Abstract

Serum uric acid (SUA) levels discriminating across the different strata of cardiovascular risk is still unknown. By utilizing a large population-based database, we assessed the threshold of SUA that increases the risk of total mortality and cardiovascular mortality (CVM). The URRAH study (Uric Acid Right for Heart Health) is a multicentre retrospective, observational study, which collected data from several large population-based longitudinal studies in Italy and subjects recruited in the hypertension clinics of the Italian Society of Hypertension. Total mortality was defined as mortality for any cause, CVM as death due to fatal myocardial infarction, stroke, sudden cardiac death, or heart failure. A total of 22 714 subjects were included in the analysis. Multivariate Cox regression analyses identified an independent association between SUA and total mortality (hazard ratio, 1.53 [95% CI, 1.21–1.93]) or CVM (hazard ratio, 2.08 [95% CI, 1.146–2.97]; P P

Published
2020

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

Author

Luciano Lippa, Raffaella Dell'Oro, M.L. Muiesan, Guido Grassi, Stefano Masi, Andrea Ungar, Ferruccio Galletti, P. Verdecchia, Enrico Agabiti Rosei, Agostino Virdis, Loreto Gesualdo, Massimo Cirillo, Francesca Mallamaci, Massimo Salvetti, Giulia Rivasi, B Bernardino, Massimo Volpe, Cristina Giannattasio, Paolo Palatini, Rita Facchetti, Carlo M. Barbagallo, Paolo Pauletto, Lanfranco D'Elia, Francesca Viazzi, Roberto Pontremoli, Arrigo Fg Cicero, Pietro Nazzaro, Claudio Ferri, Alessandro Maloberti, Giuliano Tocci, Gianfranco Parati, Valérie Tikhonoff, Michele Bombelli, Guido Iaccarino, Marcello Rattazzi, Edoardo Casiglia, Alberto Mazza, Claudio Borghi, Giovambattista Desideri, Pietro Cirillo, Fosca Quarti-Trevano, Maloberti, A, Giannattasio, C, Bombelli, M, Desideri, G, Cicero, Afg, Muiesan, Ml, Rosei, Ea, Salvetti, M, Ungar, A, Rivasi, G, Pontremoli, R, Viazzi, F, Facchetti, R, Ferri, C, Bernardino, B, Galletti, F, D’Elia, L, Palatini, P, Casiglia, E, Tikhonoff, V, Barbagallo, Cm, Verdecchia, P, Masi, S, Mallamaci, F, Cirillo, M, Rattazzi, M, Pauletto, P, Cirillo, P, Gesualdo, L, Mazza, A, Volpe, M, Tocci, G, Iaccarino, G, Nazzaro, P, Lippa, L, Parati, G, Dell’Oro, R, Quarti‑trevano, F, Grassi, G, Virdis, A, Borghi, C., Maloberti A, Giannattasio C, Bombelli M, Desideri G, Cicero AF, Muiesan ML, Rosei EA, Salvetti M, Ungar A, Rivasi G, Pontremoli R, Viazzi F, Facchetti R, Ferri C, Bernardino B, Galletti F, D'Elia L, Palatini P, Casiglia E, Tikhonoff V, Barbagallo CM, Verdecchia P, Masi S, Mallamaci F, Cirillo M, Rattazzi M, Pauletto P, Cirillo P, Gesualdo L, Mazza A, Volpe M, Tocci G, Iaccarino G, Nazzaro P, Lippa L, Parati G, Dell'Oro R, Quarti-Trevano F, Grassi G, Virdis A, Borghi C, Cicero, A, Muiesan, M, Rosei, E, D'Elia, L, Barbagallo, C, Dell'Oro, R, Quarti-Trevano, F, Borghi, C, and Maloberti A, Giannattasio C, Bombelli M, Desideri G, Cicero AFG, Muiesan ML, Rosei EA, Salvetti M, Ungar A, Rivasi G, Pontremoli R, Viazzi F, Facchetti R, Ferri C, Bernardino B, Galletti F, D'Elia L, Palatini P, Casiglia E, Tikhonoff V, Barbagallo CM, Verdecchia P, Masi S, Mallamaci F, Cirillo M, Rattazzi M, Pauletto P, Cirillo P, Gesualdo L, Mazza A, Volpe M, Tocci G, Iaccarino G, Nazzaro P, Lippa L, Parati G, Dell'Oro R, Quarti-Trevano F, Grassi G, Virdis A, Borghi C

Subjects
0301 basic medicine, Male, Time Factors, Disease, Uric acid, chemistry.chemical_compound, 0302 clinical medicine, Risk Factors, Uric Acid, Cardiovascular events, epidemiology, Epidemiology, Multicenter Studies as Topic, Hyperuricemia, Stroke, Cardiovascular events, Cardiovascular mortality, URRAH, Middle Aged, Prognosis, Observational Studies as Topic, Italy, Cardiovascular Diseases, Research Design, Female, Cardiology and Cardiovascular Medicine, Adult, medicine.medical_specialty, Uric acid · Cardiovascular mortality · Cardiovascular events · URRAH, Context (language use), Cardiovascular event, Risk Assessment, 03 medical and health sciences, cardiovascular events, cardiovascular mortality, urrah, uric acid, Pharmacotherapy, Internal medicine, Internal Medicine, medicine, Humans, Aged, Retrospective Studies, business.industry, medicine.disease, 030104 developmental biology, chemistry, Heart failure, business, 030217 neurology & neurosurgery, Biomarkers, Uric Acid
Abstract

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

Published
2020

13. Evaluation of Unattended Automated Office, Conventional Office and Ambulatory Blood Pressure Measurements and Their Correlation with Target Organ Damage in an Outpatient Population of Hypertensives: Study Design and Methodological Aspects

Author

Grazia Canciello, Gianfranco Parati, Martina Rosticci, Giulia Rivasi, Martina De Feo, Maria Virginia Manzi, Giulio Geraci, Rosa Maria Bruno, Rita Del Pinto, Francesca Saladini, Martino F. Pengo, Fabio Bertacchini, Valeria Bisogni, Alessandro Maloberti, Costantino Mancusi, Giacomo Pucci, Silvia Monticone, Mancusi, C, Saladini, F, Pucci, G, Bertacchini, F, Bisogni, V, Bruno, R, Rivasi, G, Maloberti, A, Manzi, M, Rosticci, M, Monticone, S, de Feo, M, Del Pinto, R, Geraci, G, Canciello, G, Pengo, M, Parati, G, Mancusi, C., Saladini, F., Pucci, G., Bertacchini, F., Bisogni, V., Bruno, R. M., Rivasi, G., Maloberti, A., Manzi, M. V., Rosticci, M., Monticone, S., de Feo, M., Del Pinto, R., Geraci, G., Canciello, G., Pengo, M., and Parati, G.

Subjects
0301 basic medicine, Office Visits, Predictive Value of Test, Blood Pressure, Left ventricular hypertrophy, 0302 clinical medicine, Blood Pressure Monitoring, Risk Factors, Ambulatory Care, education.field_of_study, Blood Pressure Monitoring, Ambulatory, Prognosis, Target organ damage, Left Ventricular, Italy, Echocardiography, Research Design, Hypertension, Hypertrophy, Left Ventricular, Cardiology and Cardiovascular Medicine, White coat effect, White Coat Hypertension, Human, medicine.medical_specialty, Ambulatory blood pressure, Prognosi, Population, Reproducibility of Result, 03 medical and health sciences, Peripheral Arterial Disease, Left atrial dilatation, Predictive Value of Tests, Ambulatory, Internal Medicine, medicine, Humans, Ankle brachial index, education, Cross-Sectional Studie, business.industry, Risk Factor, Reproducibility of Results, Blood Pressure Determination, Hypertrophy, medicine.disease, 030104 developmental biology, Blood pressure, Cross-Sectional Studies, Emergency medicine, Observational study, business, 030217 neurology & neurosurgery
Abstract

Accurate measurement of blood pressure (BP) has a pivotal role in the management of patients with arterial hypertension. Recently, introduction of unattended office BP measurement has been proposed as a method allowing more accurate management of hypertensive patients and prediction of hypertension-mediated target organ damage (HMOD). This approach to BP measurement has been in particular proposed to avoid the white coat effect (WCE), which can be easily assessed once both attended and unattended BP measurements are obtained. In spite of its interest, the role of WCE in predicting HMOD remains largely unexplored. To fill this gap the Young Investigator Group of the Italian Hypertension Society (SIIA) conceived the study “Evaluation of unattended automated office, conventional office and ambulatory blood pressure measurements and their correlation with target organ damage in an outpatient population of hypertensives”. This is a no-profit multicenter observational study aiming to correlate attended and unattended BP measurements for quantification of WCE and to correlate WCE with markers of HMOD, such us left ventricular hypertrophy, left atrial dilatation, and peripheral atherosclerosis. The Ethical committee of the Federico II University hospital has approved the study.

Published
2019

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

Author

Davide Soranna, Artur Fedorowski, Raffaello Furlan, Satish R. Raj, Michele Brignole, A Zambon, Andrea Ungar, Carlos A. Morillo, Viktor Hamrefors, Richard Sutton, Gert van Dijk, Giulia Rivasi, Mohamed H. Hamdan, Robert S. Sheldon, Rose Anne Kenny, Chloe Park, Gianfranco Parati, Gunnar Engström, Brignole, M, Rivasi, G, Sutton, R, Kenny, R, Morillo, C, Sheldon, R, Raj, S, Ungar, A, Furlan, R, van Dijk, G, Hamdan, M, Hamrefors, V, Engstrom, G, Park, C, Soranna, D, Zambon, A, Parati, G, and Fedorowski, A

Subjects
Adult, Male, medicine.medical_specialty, Physiology, Population, Hemodynamics, population, 030204 cardiovascular system & hematology, hemodynamics, Syncope, 03 medical and health sciences, 0302 clinical medicine, hemodynamic, Internal medicine, Heart rate, Reflex, Internal Medicine, heart rate, Medicine, Humans, 030212 general & internal medicine, education, 1102 Cardiorespiratory Medicine and Haematology, MED/01 - STATISTICA MEDICA, reflex syncope, education.field_of_study, Vagovagal reflex, business.industry, autonomic nervous system, blood pressure, 1103 Clinical Sciences, Stroke volume, Cardiovascular physiology, Pulse pressure, ORIGINAL PAPERS: Diagnostic aspects, Blood pressure, Cross-Sectional Studies, Phenotype, Cardiovascular System & Hematology, 1116 Medical Physiology, Cardiology, Female, Cardiology and Cardiovascular Medicine, business, circulatory and respiratory physiology
Abstract

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

Published
2021

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

Author

Martina Rafanelli, Martino F. Pengo, Andrea Ungar, Michele Brignole, Giulia Rivasi, Grzegorz Bilo, Gianfranco Parati, Rivasi, G, Brignole, M, Rafanelli, M, Bilo, G, Pengo, M, Ungar, A, and Parati, G

Subjects
medicine.medical_specialty, Physiology, Multidimensional assessment, 030204 cardiovascular system & hematology, Syncope, older adult, 03 medical and health sciences, 0302 clinical medicine, Risk Factors, Internal Medicine, medicine, Humans, In patient, 030212 general & internal medicine, Antihypertensive Agents, Balance (ability), Blood pressure management, biology, business.industry, Intensive treatment, Syncope (genus), biology.organism_classification, Blood pressure, Cardiovascular Diseases, Heart Disease Risk Factors, Hypertension, Emergency medicine, Functional status, Hypotension, Cardiology and Cardiovascular Medicine, business, Algorithms
Abstract

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

Published
2020
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16. Increasing Prevalence of Orthostatic Hypotension as a Cause of Syncope With Advancing Age and Multimorbidity

Author

Pasquale Abete, Giulia Rivasi, Mario Bo, Martina Rafanelli, Enrico Mossello, Chiara Mussi, Anna Maria Martone, Alice Ceccofiglio, Andrea Ungar, Ceccofiglio, A., Mussi, C., Rafanelli, M., Rivasi, G., Bo, M., Mossello, E., Martone, A. M., Abete, P., and Ungar, A.

Subjects
medicine.medical_specialty, Drug-Related Side Effects and Adverse Reactions, Blood Pressure, Syncope, Orthostatic vital signs, Hypotension, Orthostatic, Internal medicine, medicine, Prevalence, Dementia, Humans, Multicenter Studies as Topic, General Nursing, Aged, Aged, 80 and over, biology, business.industry, Health Policy, Syncope (genus), Multimorbidity, General Medicine, biology.organism_classification, medicine.disease, Cardiology, Geriatrics and Gerontology, business
Published
2019

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