Division of Nephrology, Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, MD
Department of Medicine, Kidney Research Institute, University of Washington, Seattle, WA.
J Am Heart Assoc. 2017 Dec 21;6(12):e007199. doi: 10.1161/JAHA.117.007199.
genetic variants confer an increased risk for kidney disease. Their associations with cardiovascular disease (CVD) are less certain. We aimed to compare the prevalence of subclinical CVD and incidence of atherosclerotic CVD and heart failure by genotypes among self-identified black participants of MESA (Multi-Ethnic Study of Atherosclerosis).
Cross-sectional associations of genotypes (high-risk=2 alleles; low-risk=0 or 1 allele) with coronary artery calcification, carotid-intimal media thickness, and left ventricular mass were evaluated using logistic and linear regression. Longitudinal associations of genotypes with incident myocardial infarction, stroke, coronary heart disease, and congestive heart failure were examined using Cox regression. We adjusted for African ancestry, age, and sex. We also evaluated whether hypertension or kidney function markers explained the observed associations. Among 1746 participants with genotyping (mean age 62 years, 55% women, mean cystatin C-based estimated glomerular filtration rate 89 mL/min per 1.73 m, 12% with albuminuria), 12% had the high-risk genotypes. We found no difference in prevalence or severity of coronary artery calcification, carotid-intimal media thickness, or left ventricular mass by genotypes. The high-risk group was 82% more likely to develop incident heart failure compared with the low-risk group (95% confidence interval, 1.01-3.28). Adjusting for hypertension (hazard ratio, 1.80; 95% confidence interval, 1.00-3.24) but not markers of kidney function (hazard ratio, 1.86; 95% confidence interval, 1.03-3.35) slightly attenuated this association. The high-risk genotypes were not significantly associated with other clinical CVD outcomes.
Among blacks without baseline CVD, the high-risk variants may be associated with increased risk for incident heart failure but not subclinical CVD or incident clinical atherosclerotic CVD.
遗传变异会增加患肾病的风险。它们与心血管疾病（CVD）的关联尚不确定。我们旨在比较 MESA（动脉粥样硬化多民族研究）中自我认同的黑人参与者的基因型与亚临床 CVD 和动脉粥样硬化性 CVD 及心力衰竭的发病率。
使用逻辑回归和线性回归评估基因型（高危=2 个等位基因；低危=0 或 1 个等位基因）与冠状动脉钙化、颈动脉内膜中层厚度和左心室质量的横断面关联。使用 Cox 回归检验基因型与新发心肌梗死、中风、冠心病和充血性心力衰竭的纵向关联。我们调整了非洲血统、年龄和性别。我们还评估了高血压或肾功能标志物是否解释了观察到的关联。在有基因型的 1746 名参与者中（平均年龄 62 岁，55%为女性，基于胱抑素 C 的估算肾小球滤过率为 89 mL/min/1.73 m，12%有白蛋白尿），12%携带高危基因型。我们没有发现基因型与冠状动脉钙化、颈动脉内膜中层厚度或左心室质量的患病率或严重程度存在差异。与低危组相比，高危组发生新发心力衰竭的风险高 82%（95%置信区间，1.01-3.28）。调整高血压（危险比，1.80；95%置信区间，1.00-3.24）但不调整肾功能标志物（危险比，1.86；95%置信区间，1.03-3.35）后，这种关联略有减弱。高危基因型与其他临床 CVD 结局无显著相关性。
在没有基线 CVD 的黑人中，高危变异可能与新发心力衰竭的风险增加相关，但与亚临床 CVD 或新发临床动脉粥样硬化性 CVD 无关。
