Cardiovascular events in hyperuricemia population and a cardiovascular benefit-risk assessment of urate-lowering therapies: a systematic review and meta-analysis

Abstract

Background Hyperuricemia and gout have become public health concerns; many important guidelines have recommended xanthine oxidase inhibitors (XOIs) as the first-line urate-lowering therapies (ULTs) to treat chronic gout with hyperuricemia. However, whether treating hyperuricemia and gout with ULTs modifies cardiovascular risks remains controversial. The aim of this study was to assess the incident risk of cardiovascular (CV) events (CVE) in hyperuricemia population, assess the cardiovascular benefit-risk of ULTs in hyperuricemia patients with or without gout in diverse cardiovascular risk sub-groups, and specify the safety of different ULTs. Methods We searched PubMed, Embase, the Cochrane Library, Wanfang, Chongqing VIP (CQVIP, en.cqvip.com), and China National Knowledge Infrastructure Database for prospective cohort studies and randomized controlled trials (RCTs) in English and Chinese. Potential medications included XOIs, and uricosurics. RCTs were divided into sub-groups analysis based on blinding status and patients’ history of CV diseases. Risk ratios (RRs) were calculated and were reported with corresponding 95% confidence intervals (CIs) by fixed-effects or random-effects model. Results Seven prospective cohort studies and 17 RCT studies were included. The risks of both major adverse cardiovascular events (MACE) (RR = 1.72, 95% CI 1.28–2.33) and CVE (RR = 1.35, 95% CI 1.12–1.62) were higher in the hyperuricemia population than non-hyperuricemia one. In seven RCT studies where XOIs were compared with no-treatment or placebo, the results of five low CV risk studies showed that XOIs lowered the risks of both MACE (RR = 0.35, 95% CI 0.20–0.62) and CVE (RR = 0.61, 95% CI 0.44–0.85); whereas two high CV risk studies showed that XOIs lowered the risk of CVE (RR = 0.69, 95% CI 0.54–0.88) rather than MACE (RR = 0.62, 95% CI 0.29–1.35). In nine RCT studies where the cardiovascular safety between febuxostat and allopurinol were compared, no statistical difference was found in the risk of MACE or CVE. Conclusions The hyperuricemia population does have a higher incidence of CVE, and the results suggested that XOIs might reduce the incidence of MACE and total CVE. In addition, from the perspective of cardiovascular safety, febuxostat equaled allopurinol in our meta-analysis.

Clinical Effect of the Guizhi Shaoyao Zhimu Decoction in the Treatment of Hyperuricemia

“…The SPSS V27.0 [ 29 – 31 ] statistical software was employed for statistical analysis and measurement. The data were expressed as mean ± standard deviation ( ) ( n , %), and a t -test was used for statistical analysis.…”

Cerebrovascular Disease and Cognition in Chronic Kidney Disease Patients

“…The study supports the joint roles of hyperuricemia and hypertension severity with increasing ischemic stroke risk. A recent meta-analysis demonstrates that hyperuricemia-related cardiovascular risk (including stroke) can be modified by treating hyperuricemia and gout with xanthine oxidase inhibitors (111). In Febuxostat for Cerebral and CaRdiorenovascular Events PrEvEntion StuDy cerebral, cardiovascular, renal events and all deaths were significantly reduced in the febuxostat group compared with non-febuxostat treatment [hazard ratio (HR) 0.750, 95% CI 0.592-0.950; P = 0.017] (112).…”

Association Between Uric Acid and Worsening Peripheral Microangiopathy in Systemic Sclerosis

“…On the other hand, the relationship between high UA and various markers of microvascular dysfunction in different vascular beds namely retinal arteriolar narrowing (24), microalbuminuria (25) and coronary flow reserve (26) has been described in previous studies especially in patients with higher cardiovascular risk profile. Considering the increased rate of cardiovascular events such as stoke and myocardial infarction among SSc patients (27) and the well-established contribution of hyperuricemia to the occurrence and development of cardiovascular disease in both rheumatic diseases and general population (28)(29)(30), the results of our study provide further insights in the complex association between micro-and macro vascular involvement in SSc. A growing amount of evidence point toward significant correlations between higher grades of SSc microangiopathy and indices of cardiovascular disease such as arterial stiffness (31) and cardiomyopathy (13,32).…”