Background Many studies have investigated whether single cardiac biomarkers improve cardiovascular risk prediction for primary prevention but whether a combined approach could further improve risk prediction is unclear. We aimed to test a sex-specific, combined cardiac biomarker approach for cardiovascular risk prediction. Methods In the Generation Scotland Scottish Family Health Study, N-terminal pro-B-type natriuretic peptide (NT-proBNP), growth differentiation factor-15 (GDF-15), cardiac troponin I (cTnI), cardiac troponin T (cTnT), and C-reactive protein (CRP) were measured in stored serum using automated immunoassays. Sex-specific Cox models that included SCORE2 risk factors evaluated addition of single and combined biomarkers for prediction of major adverse cardiovascular events (MACE). Combined biomarker models were compared to a baseline model that included SCORE2 risk factors. Results The study population comprised 18 383 individuals (58.9% women, median age of 48 years [25th–75th percentile, 35–58 years]). During the median follow up of 11.6 (25th–75th percentile, 10.8–13.0) years, MACE occurred in 942 (5.1%) individuals. The greatest increase in discrimination with addition of individual biomarkers to the base model was for women GDF-15 and for men NT-proBNP (change in c-index: + 0.010 for women and +0.005 for men). For women, combined biomarker models that included GDF-15 and NT-proBNP (+0.012) or GDF-15 and cTnI (+0.013), but not CRP or cTnT, further improved discrimination. For men, combined biomarker models that included NT-proBNP and GDF-15 (+0.007), NT-proBNP and cTnI (+0.006), or NT-proBNP and CRP (+0.008), but not cTnT, further improved discrimination. Conclusions A combined biomarker approach, particularly the use of GDF-15, NT-proBNP and cTnI, further refined cardiovascular risk estimates.

中文翻译：

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多种心脏生物标志物可改善心血管事件的预测：苏格兰一代苏格兰家庭健康研究的结果

背景 许多研究调查了单一心脏生物标志物是否可以改善一级预防的心血管风险预测，但组合方法是否可以进一步改善风险预测尚不清楚。我们的目的是测试一种用于心血管风险预测的性别特异性组合心脏生物标志物方法。苏格兰一代苏格兰家庭健康研究中的方法，N 末端 B 型利钠肽原 (NT-proBNP)、生长分化因子 15 (GDF-15)、心肌肌钙蛋白 I (cTnI)、心肌肌钙蛋白 T (cTnT)使用自动免疫测定法测量储存血清中的、和 C 反应蛋白 (CRP)。包含 SCORE2 风险因素的性别特异性 Cox 模型评估了单一和组合生物标志物的添加，以预测主要不良心血管事件 (MACE)。将组合生物标志物模型与包含 SCORE2 风险因素的基线模型进行比较。结果 研究人群包括 18 383 人（58.9% 为女性，中位年龄为 48 岁 [第 25-75 个百分位，35-58 岁]）。在中位随访 11.6 年（第 25-75 个百分位，10.8-13.0）年期间，942 人（5.1%）发生 MACE。在基础模型中添加个体生物标志物后，歧视增加最大的是女性 GDF-15 和男性 NT-proBNP（c 指数变化：女性 +0.010，男性 +0.005）。对于女性，包含 GDF-15 和 NT-proBNP (+0.012) 或 GDF-15 和 cTnI (+0.013)（但不包含 CRP 或 cTnT）的组合生物标志物模型进一步改善了辨别能力。对于男性，包含 NT-proBNP 和 GDF-15 (+0.007)、NT-proBNP 和 cTnI (+0.006) 或 NT-proBNP 和 CRP (+0.008)（但不包括 cTnT）的组合生物标志物模型进一步改善了辨别能力。结论 组合生物标志物方法，特别是 GDF-15、NT-proBNP 和 cTnI 的使用，进一步完善了心血管风险评估。