A Genetic risk score for coronary artery disease (CAD) improves the ability of predicting coronary heart disease (CHD). It is unclear whether i) the use of a CAD genetic risk score is superior to the measurement of coronary artery calcification (CAC) for CHD risk assessment and ii) the CHD risk assessment using a CAD genetic risk score differs between men and women. We included 4041 participants (age-range: 45–76 years, 1919 men) of the Heinz Nixdorf Recall study without CHD or stroke at baseline. A standardized weighted CAD genetic risk score was constructed using 70 known genetic variants. The risk score was divided into quintiles (Q1-Q5). We specified low (Q1), intermediate (Q2-Q4) and high (Q5) genetic risk groups. Incident CHD was defined as fatal and non-fatal myocardial infarction, stroke and coronary death. The association between the genetic risk score and genetic risk groups with incident CHD was assessed using Cox models to estimate hazard ratios (HR) and 95%-confidence intervals (CI). The models were adjusted by age and sex (Model1), as well as by established CHD risk factors (RF) and CAC (Model2). The analyses were further stratified by sex and controlled for multiple testing. During a median follow-up time of 11.6 ± 3.7 years, 343 participants experienced CHD events (219 men). Per-standard deviation (SD) increase in the genetic risk score was associated with 18% increased risk for incident CHD (Model1: p = 0.002) which did not change after full adjustment (Model2: HR = 1.18 per-SD (p = 0.003)). In Model2 we observed a 60% increased CHD risk in the high (p = 0.009) compared to the low genetic risk group. Stratifying by sex, only men showed statistically significantly higher risk for CHD (Model2: HR = 1.23 per-SD (p = 0.004); intermediate: HR = 1.52 (p = 0.04) and high: HR = 1.88 (p = 0.008)) with no statistically significant risk observed in women. Our results suggest that the CAD genetic risk score could be useful for CHD risk prediction, at least in men belonging to the higher genetic risk group, but it does not outbalance the value of CT-based quantification of CAC which works independently on both men and women and allows better risk stratification in both the genders.

中文翻译：

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Heinz Nixdorf Recall研究通过遗传风险评分对冠心病的风险预测。

冠状动脉疾病（CAD）的遗传风险评分可提高预测冠心病（CHD）的能力。目前尚不清楚：i）在冠心病风险评估中使用CAD遗传风险评分是否优于冠状动脉钙化（CAC）的测量，以及ii）在男女之间使用CAD遗传风险评分进行冠心病风险评估是否有所不同。我们纳入了4041名Heinz Nixdorf Recall研究的参与者（年龄范围：45-76岁，1919年男性），基线时无冠心病或中风。使用70个已知的遗传变异构建标准化的加权CAD遗传风险评分。风险评分分为五分位数（Q1-Q5）。我们指定了低（Q1），中（Q2-Q4）和高（Q5）遗传风险组。冠心病事件定义为致命和非致命性心肌梗塞，中风和冠心病死亡。使用Cox模型评估遗传风险评分和遗传风险组与发生冠心病的关联，以评估危险比（HR）和95％置信区间（CI）。根据年龄和性别（模型1）以及已建立的冠心病危险因素（RF）和CAC（模型2）调整模型。分析按性别进一步分层，并进行多次测试控制。在中位随访时间11.6±3.7年中，有343名参与者经历了冠心病事件（219名男性）。遗传风险评分的每标准偏差（SD）升高与发生CHD的风险增加18％（模型1：p = 0.002）相关联，但在完全调整后并未改变（模型2：HR = 1.18 per-SD（p = 0.003） ））。在模型2中，与低遗传风险组相比，高（p = 0.009）的冠心病风险增加了60％。按性别分层，只有男性显示出冠心病的风险具有统计学上的显着较高（模型2：HR =每SD 1.23（p = 0.004）；中级：HR = 1.52（p = 0.04）和高：HR = 1.88（p = 0.008）），无统计学意义在女性中观察到的风险。我们的结果表明，CAD遗传风险评分至少对属于较高遗传风险人群的男性而言可用于CHD风险预测，但它并不能抵消基于CT定量CAC的价值，CAC量化对男性和女性均独立起作用妇女，并允许在性别上更好地进行风险分层。