Background:Acute coronary syndrome (ACS) is a clinically significant presentation of coronary heart disease. Genetic information has been proposed to improve prediction beyond well-established clinical risk factors. While polygenic scores (PS) can capture an individual’s genetic risk for ACS, its prediction performance may vary in the context of diverse correlated clinical conditions. Here, we aimed to test whether clinical conditions impact the association between PS and ACS.Methods:We explored the association between 405 clinical conditions diagnosed before baseline and 9080 incident cases of ACS in 387 832 individuals from the UK Biobank. Results were replicated in 6430 incident cases of ACS in 177 876 individuals from FinnGen.Results:We identified 80 conventional (eg, stable angina pectoris and type 2 diabetes) and unconventional (eg, diaphragmatic hernia and inguinal hernia) associations with ACS. The association between PS and ACS was consistent in individuals with and without most clinical conditions. However, a diagnosis of stable angina pectoris yielded a differential association between PS and ACS. PS was associated with a significantly reduced (interaction P=2.87×10⁻⁸) risk for ACS in individuals with stable angina pectoris (hazard ratio, 1.163 [95% CI, 1.082–1.251]) compared with individuals without stable angina pectoris (hazard ratio, 1.531 [95% CI, 1.497–1.565]). These findings were replicated in FinnGen (interaction P=1.38×10⁻⁶).Conclusions:In summary, while most clinical conditions did not impact utility of PS for prediction of ACS, we found that PS was substantially less predictive of ACS in individuals with prevalent stable coronary heart disease. PS may be more appropriate for prediction of ACS in asymptomatic individuals than symptomatic individuals with clinical suspicion for coronary heart disease.

中文翻译：

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临床状况及其对遗传评分预测急性冠状动脉综合征效用的影响

背景：急性冠状动脉综合征（ACS）是冠心病的临床显着表现。已经提出遗传信息来改进超出公认的临床风险因素的预测。虽然多基因评分 (PS) 可以捕捉个体 ACS 的遗传风险，但其预测性能可能会在不同相关临床条件的背景下有所不同。在这里，我们旨在测试临床状况是否会影响 PS 和 ACS 之间的关联。方法：我们探讨了来自 UK Biobank 的 387 832 名个体在基线前诊断的 405 种临床状况与 9080 例 ACS 事件之间的关联。结果在来自 FinnGen 的 177 876 名个体的 6430 例 ACS 病例中重复。结果：我们确定了 80 例常规（例如，稳定型心绞痛和 2 型糖尿病）和非常规（例如，膈疝和腹股沟疝）与 ACS 相关。PS 和 ACS 之间的关联在有和没有大多数临床病症的个体中是一致的。然而，稳定型心绞痛的诊断在 PS 和 ACS 之间产生了不同的关联。PS 与显着降低（交互P =2.87×10 ^-8 ) 与没有稳定型心绞痛的个体（风险比，1.531 [95% CI，1.497 –1.565]）。这些发现在 FinnGen 中得到了复制（相互作用P = 1.38×10 ^-6）。 结论：总之，虽然大多数临床条件不影响 PS 预测 ACS 的效用，但我们发现 PS 对患有 ACS 的个体的预测性显着降低。流行的稳定型冠心病。与临床怀疑有冠心病的有症状个体相比，PS 可能更适合于预测无症状个体的 ACS。