OBJECTIVE The recent availability of cardiovascular risk-reducing type 2 diabetes (T2D) therapies makes it imperative to optimally identify individuals who could derive benefit. Current clinical risk prediction may misclassify individuals as low risk and could be improved. Our aim was to determine the incremental prognostic value of a coronary heart disease (CHD) genome-wide polygenic risk score (PRS) to a clinical risk score in prediction of major adverse cardiovascular events (MACE) in patients with T2D. RESEARCH DESIGN AND METHODS We evaluated 10,556 individuals with T2D aged 40–79 without a prior cardiovascular hospitalization. We calculated 10-year clinical cardiovascular risk at the date of recruitment using the Pooled Cohort Equation (PCE Risk) and constructed a CHD PRS. The primary outcome was time to first MACE incidence, and we assessed the additional incremental predictive value of the CHD PRS to the PCE risk. RESULTS At 10 years, there were 1,477 MACE. After adjustment for clinical risk, the CHD PRS was significantly associated with MACE (hazard ratio [HR] 1.69 per SD increase, 95% CI 1.60–1.79). Individuals with PCE Risk <7.5% but in the top quintile of CHD PRS had a significantly increased likelihood of MACE (HR 10.69, 95% CI 5.07–22.55) compared with those in the lowest. The addition of the PRS to the clinical risk score led to significant improvements in risk prediction, particularly in those at low clinical risk. CONCLUSIONS The addition of a CHD PRS to clinical assessment improved MACE prediction in T2D individuals without prior cardiovascular disease, particularly in those at low clinical risk.

中文翻译：

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冠心病多基因风险评分在 2 型糖尿病中的增量预后价值


目的 最近可用的降低心血管风险的 2 型糖尿病 （T2D） 疗法使得必须以最佳方式识别可能受益的个体。当前的临床风险预测可能会将个体错误地归类为低风险，并且可以改进。我们的目标是确定冠心病 （CHD） 全基因组多基因风险评分 （PRS） 对临床风险评分在预测 T2D 患者主要不良心血管事件 （MACE） 中的增量预后价值。研究设计和方法 我们评估了 10,556 名年龄在 40-79 岁之间且既往没有心血管住院治疗的 T2D 患者。我们使用汇总队列方程 （PCE Risk） 计算了招募之日的 10 年临床心血管风险，并构建了 CHD PRS。主要结局是首次发生 MACE 的时间，我们评估了 CHD PRS 对 PCE 风险的额外增量预测价值。结果 10 岁时，有 1,477 只 MACE。调整临床风险后，CHD PRS 与 MACE 显著相关 （风险比 [HR] 每增加 SD 1.69,95% CI 1.60-1.79）。与最低人群相比，PCE 风险 <7.5% 但在 CHD 前五分之一的个体 PRS 发生 MACE 的可能性显著增加 （HR 10.69,95% CI 5.07-22.55）。将 PRS 添加到临床风险评分中导致风险预测的显着改善，尤其是在临床风险较低的患者中。结论 在临床评估中加入 CHD PRS 改善了既往无心血管疾病的 T2D 个体的 MACE 预测，尤其是在临床风险低的患者中。