Uric Acid and Cardiovascular Events: A Mendelian Randomization Study
Uric Acid and Cardiovascular Events: A Mendelian Randomization Study
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DOI：
10.1681/asn.2014070660
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发表时间：
2015-11-01
影响因子：
13.6
通讯作者：
Maerz, Winfried
中科院分区：
文献类型：
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作者：
Kleber, Marcus E.;La Delgado, Gracie;Maerz, Winfried
肥胖和富含尿酸升高成分的饮食似乎是西化人群中高尿酸血症患病率增加的原因。高血压、糖尿病、慢性肾脏病和心血管疾病的患病率也在增加。我们采用孟德尔随机化方法来检验尿酸是否是一个独立的心血管危险因素。在路德维希港风险和心脏血管健康研究的3315例患者中测定了血清尿酸。我们根据8个尿酸调节单核苷酸多态性计算了尿酸浓度的加权遗传风险评分（GRS）。使用两阶段回归估计计算因果比值比和因果风险比（HR），以GRS作为工具变量，分别通过logistic回归和考克斯回归检查与心脏代谢表型（横断面）和死亡率（前瞻性）的相关性。我们的GRS与除尿酸外的任何生化标志物均不一致，这与多效性有关。尿酸与一系列流行疾病有关，包括冠状动脉疾病。尿酸和GRS均与心血管死亡和心源性猝死相关。在一个多变量模型中，调整了包括药物在内的因素，对应于遗传预测尿酸浓度每增加1 mg/dl的因果HR对于心血管死亡（HR，1.77; 95%置信区间，1.12至2.81）和心源性猝死（HR，2.41; 95%置信区间，1.16至5.00）具有显著性。这些结果表明，高尿酸与不良心血管结局，特别是心源性猝死有因果关系。
Obesity and diets rich in uric acid raising components appear to account for the increased prevalence of hyperuricemia in Westernized populations. Prevalence rates of hypertension, diabetes mellitus, CKD, and cardiovascular disease are also increasing. We used Mendelian randomization to examine whether uric acid is an independent and causal cardiovascular risk factor. Serum uric acid was measured in 3315 patients of the Ludwigshafen Risk and Cardiov.ascular Health Study. We calculated a weighted genetic risk score (GRS) for uric acid concentration based on eight uric acid regulating single nucleotide polymorphisms. Causal odds ratios and causal hazard ratios (HRs) were calculated using a two-stage regression estimate with the GRS as the instrumental variable to examine associations with cardiometabolic phenotypes (cross-sectional) and mortality (prospectively) by logistic regression and Cox regression, respectively. Our GRS was not consistently associated with any biochemical marker except for uric acid, arguing against pleiotropy. Uric acid was associated with a range of prevalent diseases, including coronary artery disease. Uric acid and the GRS were both associated with cardiovascular death and sudden cardiac death. In a multivariate model adjusted for factors including medication, causal HRs corresponding to each 1-mg/dl increase in genetically predicted uric acid concentration were significant for cardiovascular death (HR, 1.77; 95% confidence interval, 1.12 to 2.81) and sudden cardiac death (HR, 2.41; 95% confidence interval, 1.16 to 5.00). These results suggest that high uric acid is causally related to adverse cardiovascular outcomes, especially sudden cardiac death.