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Background and Aims: Hyperuricemia is independently associated with cardiovascular disease (CVD) and is considered to be one of the major risk factors for CVD. However, the impact of inter-visit uric acid (UA) variability on cardiovascular risk remains undetermined., Methods: We enrolled 3202 patients with coronary artery disease (CAD), who received successful coronary intervention, in a cohort from Taipei Veterans General Hospital from 2006 to 2015. All post-baseline visits UA measurements using standard deviation (SD) were analyzed to correlate with long-term outcome. The primary outcome was the composite of cardiac death, nonfatal MI, nonfatal stroke (MACE). The secondary event was MACE and hospitalization for heart failure., Results: During an average 65.06 ± 32.1-month follow-up, there were 66 cardiovascular deaths, 175 nonfatal myocardial infarctions, 64 nonfatal strokes, 287 hospitalizations for heart failure, and 683 revascularization procedures. There was a linear association between high UA SD and future adverse events. Compared to the lowest quartile SD, subjects in the highest quartile SD had a higher risk of MACE (HR: 2.53, 95% CI: 1.78-3.59), myocardial infarction (HR: 2.43, 95% CI: 1.53-3.86), cardiovascular death (HR: 6.45, 95% CI: 2.52-16.55), heart failure-related hospitalization (HR: 3.43, 95% CI: 2.32-5.05), and total major CV events (HR: 2.72, 95% CI: 2.09-3.56). Furthermore, compared to the average achieved on-treatment UA value, increasing UA SD had a stronger association of higher risk of developing MACE (HR: 1.51, 95% CI: 1.36-1.68), myocardial infarction (HR: 1.37, 95% CI: 1.38-1.68), ischemic stroke (HR: 1.43, 95% CI: 1.13-1.82), CV death (HR: 1.77, 95% CI: 1.50-2.11), HF (HR: 1.43, 95% CI: 1.29-1.58), and total major CV events (HR: 1.46, 95% CI: 1.34-1.58)., Conclusions: High UA variability is associated with a higher risk of developing future cardiovascular events, suggesting the importance of maintaining stable serum UA levels and avoiding large fluctuations in CAD patients after percutaneous coronary intervention (PCI)., Competing Interests: Declaration of competing interest The authors declared they do not have anything to disclose regarding conflict of interest with respect to this manuscript., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Background and Aims: Evidence links uric acid (UA) with the promotion of cardiovascular disease. We assessed the prognostic value of UA on long-term major adverse outcomes (MACE) in patients with acute coronary syndrome (ACS), undergoing percutaneous coronary intervention (PCI)., Methods: As primary endpoint, we assessed the association of UA (continuous and dichotomized) with MACE, including cardiovascular death, myocardial infarction (MI) and stroke, using Cox regression and propensity matching. As secondary endpoints, the influence of hyperuricemia (defined as UA levels > 6.0 mg/dl in women, and >7.0 mg/dl in men) was analysed separately for cardiovascular death, MI, and stroke. The incremental prognostic value of UA was tested using the net reclassification improvement (NRI), and the integrated discrimination improvement (IDI)., Results: We included 1215 patients. Hyperuricemia was present in 356 (29.3%) patients. Mean follow-up was 5.5 years. UA (HR 1.091 [1.035-1.150]; p = 0.001) and hyperuricemia (HR 1.750 [1.388-2.207]; p < 0.001) were significantly associated with MACE. Results were consistent between Cox regression and propensity matched analysis. Patients with hyperuricemia had a 1.6-fold increased relative risk for cardiovascular death (p = 0.005) and a 1.5-fold increased risk for MI (p = 0.032). For stroke, hyperuricemia only constituted a confounder (HR 1.104; p = 0.970). The prognostic accuracy of an established risk prediction model was significantly increased by adding UA (continuous NRI p = 0.004; categorical NRI p = 0.029; IDI p = 0.002)., Conclusions: Our data suggest an independent association of elevated UA with long-term MACE in ACS patients undergoing PCI. Whether lowering UA might be beneficial remains to be elucidated in large clinical trials., (Copyright © 2018 Elsevier B.V. All rights reserved.)

Background and Aims: Many studies have reported the independent association between uric acid and cardiovascular disease, its role as a risk predictor for outcomes in people with acute coronary syndrome remains controversial. This study aims to assess the association between hyperuricemia and medium/long-term clinical outcomes in people with acute coronary syndrome and determine whether adding hyperuricemia to the GRACE score improves its predictive capability., Methods: This cohort study included patients admitted for acute coronary syndrome between 2008 and 2013. Outcomes were cardiovascular and total mortality, and major cardiovascular events. We used a multivariate model to adjust for potential confounding covariates and presented event rates with Kaplan-Meier curves. After adding hyperuricemia to the GRACE score, we compared scores from the reclassification table and the net reclassification improvement., Results: 1119 participants were included and followed-up for a mean of 36 months. Multivariate models showed hyperuricemia was independently associated with higher cardiovascular mortality (HR:1.91; 95% CI:1.32-2.76; p < 0.01), higher all-cause mortality (HR:1.59; 95% CI:1.18-2.15; p < 0.01) and higher major cardiovascular event rates (HR:1.36; 95% CI:1.11-1.67; p < 0.01). The hyperuricemia addition to GRACE score led to reclassifying 26% of the participants, and net reclassification improvement was 34%. However, the area under the curve increase was 0.009 and not statistically significant (p > 0.05)., Conclusions: Hyperuricemia is associated with higher medium/long-term mortality and major cardiovascular event rates in patients following acute coronary syndrome. The addition of hyperuricemia to the GRACE score seems to improve risk classification but the discrimination of the new predictive model did not change. Hyperuricemic patients had higher all-cause mortality in medium and high-risk score categories., (Copyright © 2018 Elsevier B.V. All rights reserved.)

Objective: Serum uric acid (SUA) levels have been associated with cardiovascular and all-cause mortality. It remains unclear whether these associations differ by gender, menopausal status and hormone replacement therapy (HRT) and whether they persist after adjustment for known cardiovascular risk factors., Methods: We determined the associations between fasting SUA level and death certificate-based mortality among 5856 participants of the third US National Health and Nutrition Examination Survey aged ≥20 years recruited between 1988 and 1994 and followed for mortality until December 2006 (mean follow-up: 13.5 years; maximum follow-up: 18 years). Cox proportional hazards regression analysis was used to adjust for demographic characteristics, cardiovascular risk factors and other variables potentially associated with SUA levels., Results: Among women, SUA level was associated with all-cause and cardiovascular mortality (adjusted hazard ratio [AHR] 1.17, 95% CI 1.03-1.32 and AHR 1.23 (1.01-1.51) respectively per unit increase in SUA. These associations persisted among postmenopausal but not premenopausal women. Furthermore, among postmenopausal women, significant associations were identified between SUA and all-cause (AHR 1.30 [1.11-1.51]) or cardiovascular (AHR 1.61 [1.33-1.94]) mortality only among women not taking HRT, but not among women on HRT. We did not identify associations between SUA levels and all-cause or cardiovascular mortality in men, either under or over 51 years of age, in unadjusted or adjusted analyses., Conclusions: SUA level predicts cardiovascular and all-cause mortality independently of major predictors and risk factors in postmenopausal women not taking HRT but not in premenopausal women, postmenopausal women on HRT, or men., (Published by Elsevier Ireland Ltd.)

Objective: Although some studies have suggested that uric acid is a risk factor for mortality, this relationship is still uncertain in people with type 2 diabetes., Methods: The study base was the population-based cohort of 1540 diabetic subjects (median age 68.9 years) of the Casale Monferrato Study. The role of serum uric acid on 15-years all-cause, cardiovascular and non-cardiovascular mortality was assessed by multivariate Cox proportional hazards modeling., Results: Baseline levels of serum uric acid were negatively correlated with HbA1c, were higher in men and in the elderly and were independently associated with components of the metabolic syndrome. Out of 14,179 person-years, 1000 deaths (514 due to cardiovascular diseases) were observed. Compared to the lower quartile of uric acid, HRs (95% CI) in the upper quartile were 1.47 (1.22-1.76) for all-cause mortality; 1.40 (1.09-1.80) for cardiovascular mortality and 1.50 (1.15-1.96) for non-cardiovascular mortality. In multiple adjusted models, however, HRs were 1.30 (1.06-1.60) for all-cause mortality, 1.13 (0.85-1.50) for cardiovascular mortality and 1.50 (1.11-2.02) for non-cardiovascular mortality (men 1.87, 1.19-2.95; women 1.20, 0.80-1.80); the latter appeared to be due to neoplastic diseases (HR in all combined quartiles vs. lower quartile: both sexes 1.59, 1.05-2.40; men 1.54, 0.83-2.84, women 1.68, 0.95-2.92)., Conclusions: In diabetic people, uric acid is associated with components of the metabolic syndrome but it may not be accounted as an independent risk factor for cardiovascular mortality. The increased all-cause mortality risk with higher levels of uric acid might be due to increased neoplastic mortality and deserves future studies., (Copyright © 2012. Published by Elsevier Ireland Ltd.)