Serum uric acid levels threshold for mortality in diabetic individuals: The URic acid Right for heArt Health (URRAH) project

D’Elia, Lanfranco; Angeli, Fabio; Barbagallo, Carlo M.; Bilancio, Giancarlo; Bombelli, Michele; Bruno, Berardino; Casíglia, Edoardo; Cianci, Rosario; Cicero, A.F.G.; Cirillo, Massimo; Cirillo, Pietro; Desideri, Giovambattista; Ferri, Claudio; Gesualdo, Loreto; Giannattasio, Cristina; Iaccarino, Guido; Lippa, Luciano; Mallamaci, Francesca; Maloberti, Alessandro; Masi, Stefano; Mazza, Alberto; Mengozzi, Alessandro; Muiesan, María Lorenza; Nazzaro, Pietro; Palatini, Paolo; Parati, Gianfranco; Pontremoli, Roberto; Quartı-Trevano, Fosca; Rattazzi, Marcello; Reboldi, Gianpaolo; Rivasi, Giulia; Salvetti, Massimo; Tikhonoff, Valérie; Ungar, Andrea; Verdecchia, Paolo; Viazzi, Francesca; Virdis, Agostino; Volpe, Massimo; Galletti, Ferruccio; Borghi, Claudio

doi:10.1016/j.numecd.2022.01.028

Cited by 19 publications

(20 citation statements)

References 35 publications

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“…First of all, the results of this present analysis confirm that SUA is an independent risk factor for CV events in a long follow-up also after indexing for renal function. This is consistent with a series of studies showing a positive association of incident CV events with SUA as a continuous variable, as well as with being over a well defined prognostic value of SUA [3–8].…”

Section: Discussionsupporting

confidence: 91%

“…The association between serum uric acid (SUA) and cardiovascular (CV) disease has been investigated for almost 50 years [ 1 ] and the role of SUA as a CV risk factor and a metabolic mediator is growing. In the last years, the Uric Acid Right for Heart Health (URRAH) study [ 2 ] found univocal prognostic cut-off values of SUA able to predict incidence of CV events [ 3 ], myocardial infarction [ 4 ], stroke [ 5 ] and heart failure [ 6 ] also in type-2 diabetic patients [ 7 ] and in the aged [ 8 ].…”

Section: Introductionmentioning

confidence: 99%

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

Casíglia¹,

Tikhonoff

Virdis

et al. 2022

Journal of Hypertension

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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.

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Section: Discussionsupporting

confidence: 91%

Section: Introductionmentioning

confidence: 99%

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

Casíglia¹,

Tikhonoff

Virdis

et al. 2022

Journal of Hypertension

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“…In recent years, several papers from our group [ 11 , 23 , 24 , 25 , 26 , 27 , 28 , 40 , 41 , 42 , 43 , 44 ] and others [ 17 , 18 , 19 , 20 ] have reported that SUA might be a relevant tool in the risk-prediction arsenal for assessing individual mortality risk at values lower than the gout-defining ones. However, fewer studies have attempted to determine the potential of SUA as a risk factor for mortality and cardiovascular disease in a population at an early stage of cardiometabolic impairment.…”

Section: Discussionmentioning

confidence: 99%

“…However, these works provide higher and different cut-offs, hindering their adoption in routine clinical care. After having identified two lower and specific cut-offs for ACM and CVM (SUA ≥ 4.7 mg/dL for ACM and SUA ≥ 5.6 mg/dL for CVM) [ 11 ], our group has shown their consistent predictive power in patients with diabetes [ 23 ] and metabolic syndrome [ 24 ]. The present study confirms the findings in cardiometabolic patients without established CV disease and considers the potential simultaneous assessment of hypertriglyceridemia, another neglected potential CV risk factor [ 15 , 16 ].…”

Section: Discussionmentioning

confidence: 99%

“…More importantly, its impact on CV risk starts at a lower level than the traditional threshold for defining hyperuricemia and gout [ 21 , 22 ]. In recent years, the URic acid Right for heArt Health (URRAH) study has identified specific cut-offs for all-cause mortality (ACM) and cardiovascular mortality (CVM) to support its implementation in clinical practice [ 11 , 23 , 24 , 25 , 26 , 27 , 28 ]. Similarly, recent real-world evidence supports the association of TG with CV risk starting from levels defining mild to moderate hypertriglyceridemia (150 mg/dL) [ 29 , 30 ], and Mendelian randomization studies also support a causal role for TG in CV disease [ 31 ].…”

Section: Introductionmentioning

confidence: 99%

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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

et al. 2023

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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.

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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

Maloberti,

Mengozzi,

Russo

et al. 2023

High Blood Press Cardiovasc Prev

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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.

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Serum uric acid levels threshold for mortality in diabetic individuals: The URic acid Right for heArt Health (URRAH) project

Cited by 19 publications

References 35 publications

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

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

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

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

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