经历过中风或短暂性脑缺血发作的人未来发生心血管事件的风险更高。识别后续心血管结局的遗传和分子危险因素可能会确定有效的治疗靶点，以改善中风后的预后。我们对后续主要不良心血管事件进行了全基因组关联研究（MACE；ncases=51 929；ncontrols=39 980）百万退伍军人计划和英国生物库中首次中风后发生的动脉缺血性中风（AIS；ncases=45 120；ncontrols=46 789）。然后，我们使用与蛋白质（蛋白质数量性状位点）相关的遗传变异，使用孟德尔随机化确定 1463 个血浆蛋白丰度对随后 MACE 的影响。两个变异与随后的心血管事件显着相关：基因 RNF220 附近的 rs76472767（比值比，0.75 [ 95% CI, 0.64-0.85]；P=3.69×10-8) 以及随后的 AIS 和基因 LINC01492 附近的 rs13294166（比值比，1.52 [95% CI, 1.37-1.67]；P=3.77×10-8）锤。使用孟德尔随机化，我们确定了 2 种对中风后后续 MACE 产生影响的蛋白质：CCL27（[C-C 基序趋化因子 27]，效应比值比，0.77 [95% CI，0.66-0.88]；调整后的 P=0.05）和 TNFRSF14（ [肿瘤坏死因子受体超家族成员 14]，效应比值比，1.42 [95% CI，1.24-1.60]；调整后的 P=0.006）。这些蛋白质与突发 AIS 无关，并且与炎症有关。我们发现有证据表明，对突发中风影响不大的 2 种蛋白质似乎会影响突发 AIS 后的后续 MACE。这些关联表明炎症是 AIS 事件后后续 MACE 结局的一个影响因素，并突出了潜在的新靶标。

Individuals who have experienced a stroke, or transient ischemic attack, face a heightened risk of future cardiovascular events. Identification of genetic and molecular risk factors for subsequent cardiovascular outcomes may identify effective therapeutic targets to improve prognosis after an incident stroke.We performed genome-wide association studies for subsequent major adverse cardiovascular events (MACE; ncases=51 929; ncontrols=39 980) and subsequent arterial ischemic stroke (AIS; ncases=45 120; ncontrols=46 789) after the first incident stroke within the Million Veteran Program and UK Biobank. We then used genetic variants associated with proteins (protein quantitative trait loci) to determine the effect of 1463 plasma protein abundances on subsequent MACE using Mendelian randomization.Two variants were significantly associated with subsequent cardiovascular events: rs76472767 near gene RNF220 (odds ratio, 0.75 [95% CI, 0.64-0.85]; P=3.69×10-8) with subsequent AIS and rs13294166 near gene LINC01492 (odds ratio, 1.52 [95% CI, 1.37-1.67]; P=3.77×10-8) with subsequent MACE. Using Mendelian randomization, we identified 2 proteins with an effect on subsequent MACE after a stroke: CCL27 ([C-C motif chemokine 27], effect odds ratio, 0.77 [95% CI, 0.66-0.88]; adjusted P=0.05) and TNFRSF14 ([tumor necrosis factor receptor superfamily member 14], effect odds ratio, 1.42 [95% CI, 1.24-1.60]; adjusted P=0.006). These proteins are not associated with incident AIS and are implicated to have a role in inflammation.We found evidence that 2 proteins with little effect on incident stroke appear to influence subsequent MACE after incident AIS. These associations suggest that inflammation is a contributing factor to subsequent MACE outcomes after incident AIS and highlights potential novel targets.