Serum uric acid and eGFR_CKDEPI differently predict long-term cardiovascular events and all causes of deaths in a residential cohort Paolo Emilio Puddu a, ⁎, Giancarlo Bilancio b , Oscar Terradura Vagnarelli c , Cinzia Lombardi b , Mario Mancini d , Alberto Zanchetti e,f , Alessandro Menotti g a Department of Cardiovascular, Respiratory, Nephrological, Anesthesiological and Geriatric Sciences, Sapienza University of Rome, Viale del Policlinico 155, I-00161 Rome, Italy b Department of Medicine and Surgery, University of Salerno, Via Salvador Allende 43, 84081 Baronissi (SA), Italy c Centre of Preventive Medicine, Gubbio, Italy d Department of Clinical Medicine and Surgery, Federico II University, Naples, Italy e Istituto Auxologico Italiano, Milan, Italy f University of Milan, Milan, Italy g Associazione per la Ricerca Cardiologica, Via Latina 49, 00179 Roma, Italy abstract article info Article history: Received 8 August 2013 Received in revised form 4 November 2013 Accepted 14 December 2013 Available online 22 December 2013 Keywords: Serum uric acid Glomerular filtration rate CVD risk Prediction Residential cohort Gubbio study Objectives: Serum uric acid (SUA) and estimated glomerular filtration rate (eGFR) were separately assessed as risk factors for incident coronary hard (CHDH), cardiovascular disease (CVDH) or all-cause (ALL) deaths but never concomitantly in a residential cohort. Material and methods: Men and women aged 35–74 years, totaling 2888 subjects were followed 13.5–19.5 years for incident CVDH, CHDH and ALL deaths. Systematic comparisons among different end-points were based on: age, gender, systolic blood pressure (SBP), total and HDL cholesterol, cigarette consumption, body mass index, blood glucose, SUA, eGFR from the Chronic Kidney Disease Prognosis Consortium (eGFR_CKDEPI) and (eGFR_CKDEPI) 2 . Results: Significant (p b 0.00001) differences in SUA quintiles were seen for SBP, total and HDL cholesterol, body mass index and eGFR_CKDEPI whereas cigarettes and blood glucose were not statistically different. There were increasingly larger proportions of all events in SUA quintiles (0.05 N p b 0.0001). Among 4 major continuous var- iables, SUA was largely accurate (ROC N 0.610) to predict all end-points whereas eGFR_CKDEPI was the worse uni- variate predictor. Multivariately, age, gender, SBP and cigarettes were significant predictors for all end-points. Total cholesterol was a significant predictor only for CHDH events. Blood glucose and SUA were contributors for CVDH events (RR, for 1 mg/dl of SUA, 1.09, 95%CI 1.01–1.17), CVD deaths (RR 1.11, 95%CI 1.03–1.20) and ALL deaths (RR 1.08, 95%CI 1.03–1.14) whereas (eGFR_CKDEPI) 2 was for ALL deaths only (RR 1.02, 95%CI 1.00–1.04). Conclusion: SUA is a predictor of long-term incidence of cardiovascular events and deaths and all-cause mortality and should be considered for risk predictive purposes and instruments whereas eGFR_CKDEPI only predicts all- cause mortality by a U-shaped relation. © 2013 Elsevier Ireland Ltd. All rights reserved. 1. Introduction Serum uric acid (SUA), the end product of purine metabolism via an enzymatic reaction involving xanthine oxidoreductase, may represent a double-edge sword: it was considered for several years a major antiox- idant in human plasma with possible beneficial anti-atherosclerotic ef- fects and could stimulate oxidative stress, endothelial dysfunction, inflammation and vasoconstriction [1]. Epidemiological studies found that SUA independently predicts the development of hypertension, stroke and heart failure [2–4] and emerging roles were reported in the pathogenesis of metabolic syndrome, obesity and diabetes [5–7] also starting from early adolescence [8–12]. The role of SUA as a risk factor for the incidence of cardiovascular disease (CVD) events was clearly shown by recent meta-analyses [13,14]: when adjusted for potential confounders, the pooled risk ratio (RR) was 1.09 for coronary heart dis- ease (CHD) incidence and 1.16 for mortality. For each 1 mg/dl SUA in- crease [14], the pooled multivariate RR for CHD mortality was 1.12 (95% CI: 1.05–1.19). At variance with dated results from Framingham [15], although in men who physiologically present with higher SUA levels [16,17] no significant association between SUA and CHD inci- dence/mortality was observed, women had an increased risk for CHD mortality with RR 1.67 (95% CI: 1.30–2.04) [14]. International Journal of Cardiology 171 (2014) 361–367 ⁎ Corresponding author at: Laboratory of Biotechnologies Applied to Cardiovascular Medicine, Department of Cardiovascular, Respiratory, Nephrological, Anesthesiological and Geriatric Sciences, Sapienza University of Rome, Viale del Policlinico, 155, Roma 00161, Italy. Tel.: +39 06 49972659; fax: +39 06 4453891. E-mail addresses: paoloemilio.puddu@uniroma1.it (P.E. Puddu), giancarlo.bilancio@gmail.com (G. Bilancio), oscar.terradura@gmail.com (O. Terradura Vagnarelli), cinlomb@inwind.it (C. Lombardi), mariomancini30@virgilio.it (M. Mancini), alberto.zanchetti@unimi.it (A. Zanchetti), menottia@tin.it (A. Menotti). 0167-5273/$ – see front matter © 2013 Elsevier Ireland Ltd. All rights reserved. http://dx.doi.org/10.1016/j.ijcard.2013.12.029 Contents lists available at ScienceDirect International Journal of Cardiology journal homepage: www.elsevier.com/locate/ijcard