Boston VA Healthcare System, MA (A.G.B., J.E.H., J.H., L.H., D.K., K.C., J.M.G., C.J.O.).
Massachusetts General Hospital, Boston (A.G.B., D.K., P.N., S.K.).
Circulation. 2019 Sep 17;140(12):1031-1040. doi: 10.1161/CIRCULATIONAHA.118.036589. Epub 2019 Jul 24.
Approximately 13% of black individuals carry 2 copies of the apolipoprotein L1 () risk alleles G1 or G2, which are associated with 1.5- to 2.5-fold increased risk of chronic kidney disease. There have been conflicting reports as to whether an association exists between risk alleles and cardiovascular disease (CVD) that is independent of the effects of on kidney disease. We sought to test the association of G1/G2 alleles with coronary artery disease, peripheral artery disease, and stroke among black individuals in the Million Veteran Program.
We performed a time-to-event analysis of retrospective electronic health record data using Cox proportional hazard and competing-risks Fine and Gray subdistribution hazard models. The primary exposure was risk allele status. The primary outcome was incident coronary artery disease among individuals without chronic kidney disease during the 12.5-year follow-up period. We separately analyzed the cross-sectional association of risk allele status with lipid traits and 115 cardiovascular diseases using phenome-wide association.
Among 30 903 black Million Veteran Program participants, 3941 (13%) carried the 2 risk allele high-risk genotype. Individuals with normal kidney function at baseline with 2 risk alleles had slightly higher risk of developing coronary artery disease compared with those with no risk alleles (hazard ratio, 1.11 [95% CI, 1.01-1.21]; =0.039). Similarly, modest associations were identified with incident stroke (hazard ratio, 1.20 [95% CI, 1.05-1.36; =0.007) and peripheral artery disease (hazard ratio, 1.15 [95% CI, 1.01-1.29l; =0.031). When both cardiovascular and renal outcomes were modeled, was strongly associated with incident renal disease, whereas no significant association with the CVD end points could be detected. Cardiovascular phenome-wide association analyses did not identify additional significant associations with CVD subsets.
risk variants display a modest association with CVD, and this association is likely mediated by the known association with chronic kidney disease.
约 13%的黑人个体携带载脂蛋白 L1()风险等位基因 G1 或 G2 的两份副本，这与慢性肾脏病的风险增加 1.5 至 2.5 倍相关。关于载脂蛋白 L1()风险等位基因与心血管疾病（CVD）之间是否存在独立于对肾脏疾病影响的关联，一直存在相互矛盾的报告。我们试图在百万退伍军人计划中的黑人个体中检验载脂蛋白 L1()G1/G2 等位基因与冠状动脉疾病、外周动脉疾病和中风之间的关联。
我们使用 Cox 比例风险和竞争风险 Fine 和 Gray 亚分布风险模型对回顾性电子健康记录数据进行了时间事件分析。主要暴露是载脂蛋白 L1()风险等位基因状态。主要结局是在 12.5 年随访期间无慢性肾脏病的个体中发生的冠状动脉疾病。我们分别使用表型全基因组关联分析来分析载脂蛋白 L1()风险等位基因状态与脂质特征和 115 种心血管疾病的横断面关联。
在 30903 名黑人百万退伍军人计划参与者中，有 3941 人（13%）携带 2 份风险等位基因的高危基因型。与无风险等位基因的个体相比，基线时肾功能正常且携带 2 个风险等位基因的个体发生冠状动脉疾病的风险略高（风险比，1.11[95%CI，1.01-1.21]；=0.039）。同样，也发现与中风（风险比，1.20[95%CI，1.05-1.36]；=0.007）和外周动脉疾病（风险比，1.15[95%CI，1.01-1.29]；=0.031）的发病存在适度关联。当同时对心血管和肾脏结局进行建模时，载脂蛋白 L1()与肾脏疾病的发病强烈相关，而与心血管疾病终点没有发现显著关联。心血管表型全基因组关联分析未发现与心血管疾病亚组的其他显著关联。
载脂蛋白 L1()风险变异与 CVD 存在适度关联，这种关联可能是由其与慢性肾脏病的已知关联介导的。
