Department of Medicine, Northwestern University Feinberg School of Medicine, Chicago, Illinois.
Department of Preventive Medicine, Northwestern University Feinberg School of Medicine, Chicago, Illinois.
JAMA. 2023 May 23;329(20):1768-1777. doi: 10.1001/jama.2023.7575.
Coronary artery calcium score and polygenic risk score have each separately been proposed as novel markers to identify risk of coronary heart disease (CHD), but no prior studies have directly compared these markers in the same cohorts.
To evaluate change in CHD risk prediction when a coronary artery calcium score, a polygenic risk score, or both are added to a traditional risk factor-based model.
DESIGN, SETTING, AND PARTICIPANTS: Two observational population-based studies involving individuals aged 45 years through 79 years of European ancestry and free of clinical CHD at baseline: the Multi-Ethnic Study of Atherosclerosis (MESA) study involved 1991 participants at 6 US centers and the Rotterdam Study (RS) involved 1217 in Rotterdam, the Netherlands.
Traditional risk factors were used to calculate CHD risk (eg, pooled cohort equations [PCEs]), computed tomography for the coronary artery calcium score, and genotyped samples for a validated polygenic risk score.
Model discrimination, calibration, and net reclassification improvement (at the recommended risk threshold of 7.5%) for prediction of incident CHD events were assessed.
The median age was 61 years in MESA and 67 years in RS. Both log (coronary artery calcium+1) and polygenic risk score were significantly associated with 10-year risk of incident CHD (hazards ratio per SD, 2.60; 95% CI, 2.08-3.26 and 1.43; 95% CI, 1.20-1.71, respectively), in MESA. The C statistic for the coronary artery calcium score was 0.76 (95% CI, 0.71-0.79) and for the polygenic risk score, 0.69 (95% CI, 0.63-0.71). The change in the C statistic when each was added to the PCEs was 0.09 (95% CI, 0.06-0.13) for the coronary artery calcium score, 0.02 (95% CI, 0.00-0.04) for the polygenic risk score, and 0.10 (95% CI, 0.07-0.14) for both. Overall categorical net reclassification improvement was significant when the coronary artery calcium score (0.19; 95% CI, 0.06-0.28) but was not significant when the polygenic risk score (0.04; 95% CI, -0.05 to 0.10) was added to the PCEs. Calibration of the PCEs and models with coronary artery calcium and/or polygenic risk scores was adequate (all χ2<20). Subgroup analysis stratified by the median age demonstrated similar findings. Similar findings were observed for 10-year risk in RS and in longer-term follow-up in MESA (median, 16.0 years).
In 2 cohorts of middle-aged to older adults from the US and the Netherlands, the coronary artery calcium score had better discrimination than the polygenic risk score for risk prediction of CHD. In addition, the coronary artery calcium score but not the polygenic risk score significantly improved risk discrimination and risk reclassification for CHD when added to traditional risk factors.
冠状动脉钙评分和多基因风险评分已分别被提议作为识别冠心病 (CHD) 风险的新标志物，但以前没有研究在同一队列中直接比较这些标志物。
评估当在传统基于风险因素的模型中添加冠状动脉钙评分、多基因风险评分或两者时，CHD 风险预测的变化。
设计、地点和参与者：涉及欧洲血统、基线时无临床 CHD 的 45 岁至 79 岁个体的两项观察性基于人群的研究：多民族动脉粥样硬化研究 (MESA) 研究涉及 6 个美国中心的 1991 名参与者和荷兰鹿特丹的 1217 名参与者的 Rotterdam 研究（RS）。
使用传统风险因素计算 CHD 风险（例如，汇总队列方程 [PCE]），使用计算机断层扫描进行冠状动脉钙评分，使用经验证的多基因风险评分进行基因分型样本。
评估预测 CHD 事件发生的模型区分度、校准和净重新分类改善（在推荐的 7.5%风险阈值下）。
MESA 的中位年龄为 61 岁，RS 为 67 岁。在 MESA 中，log（冠状动脉钙+1）和多基因风险评分均与 10 年 CHD 风险发生显著相关（每标准差的危险比分别为 2.60；95%CI，2.08-3.26 和 1.43；95%CI，1.20-1.71）。冠状动脉钙评分的 C 统计量为 0.76（95%CI，0.71-0.79），多基因风险评分的 C 统计量为 0.69（95%CI，0.63-0.71）。当将每个评分添加到 PCEs 中时，冠状动脉钙评分的 C 统计量变化为 0.09（95%CI，0.06-0.13），多基因风险评分的 C 统计量变化为 0.02（95%CI，0.00-0.04），两者均为 0.10（95%CI，0.07-0.14）。当冠状动脉钙评分（0.19；95%CI，0.06-0.28）添加到 PCEs 时，整体分类净重新分类改善具有统计学意义，但当多基因风险评分（0.04；95%CI，-0.05 至 0.10）添加到 PCEs 时，无统计学意义。PCEs 和包含冠状动脉钙和/或多基因风险评分的模型的校准是充分的（所有 χ2<20）。按中位年龄分层的亚组分析显示出类似的发现。在 RS 中观察到 10 年风险和 MESA 中的更长随访时间（中位数为 16.0 年）中也观察到了类似的发现。
在美国和荷兰的 2 个中年至老年人群队列中，冠状动脉钙评分在 CHD 风险预测方面的区分度优于多基因风险评分。此外，当在传统风险因素中添加冠状动脉钙评分而不是多基因风险评分时，CHD 的风险区分度和风险再分类显著改善。
