Background Premature coronary heart disease (CHD) is a major cause of death in women. We aimed to characterize biomarker profiles of women who developed CHD before and after age 65 years. Methods In the Women’s Health Study (median follow-up 21.5 years), women were grouped by age and timing of incident CHD: baseline age <65 years with premature CHD by age 65 years (25 042 women; 447 events) and baseline age ≥65 years with nonpremature CHD (2982 women; 351 events). Associations of 44 baseline plasma biomarkers measured using standard assays and a nuclear magnetic resonance (NMR)-metabolomics assay were analyzed using Cox models adjusted for clinical risk factors. Results Twelve biomarkers showed associations only with premature CHD and included lipoprotein(a), which was associated with premature CHD [adjusted hazard ratio (HR) per SD: 1.29 (95% CI 1.17–1.42)] but not with nonpremature CHD [1.09(0.98–1.22)](Pinteraction = 0.02). NMR-measured lipoprotein insulin resistance was associated with the highest risk of premature CHD [1.92 (1.52–2.42)] but was not associated with nonpremature CHD (Pinteraction <0.001). Eleven biomarkers showed stronger associations with premature vs nonpremature CHD, including apolipoprotein B. Nine NMR biomarkers showed no association with premature or nonpremature CHD, whereas 12 biomarkers showed similar significant associations with premature and nonpremature CHD, respectively, including low-density lipoprotein (LDL) cholesterol [1.30(1.20–1.45) and 1.22(1.10–1.35)] and C-reactive protein [1.34(1.19–1.50) and 1.25(1.08–1.44)]. Conclusions In women, a profile of 12 biomarkers was selectively associated with premature CHD, driven by lipoprotein(a) and insulin-resistant atherogenic dyslipoproteinemia. This has implications for the development of biomarker panels to screen for premature CHD.

中文翻译：

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女性早产和非早产冠心病的血浆生物标志物谱

背景 过早冠心病（CHD）是女性死亡的主要原因。我们的目的是描述 65 岁之前和之后患 CHD 的女性的生物标志物特征。方法 在女性健康研究中（中位随访时间 21.5 年），按照年龄和 CHD 发生时间对女性进行分组：基线年龄 <65 岁，早发 CHD 按 65 岁分组（25 042 名女性；447 例事件）和基线年龄≥65 岁患有非早产性 CHD（2982 名女性；351 起事件）。使用根据临床风险因素调整的 Cox 模型，对使用标准测定和核磁共振 (NMR) 代谢组学测定测量的 44 种基线血浆生物标志物的关联进行分析。结果 12 种生物标志物仅与早发 CHD 相关，其中包括脂蛋白 (a)，脂蛋白 (a) 与早发 CHD 相关[调整后的风险比 (HR)/SD：1.29 (95% CI 1.17–1.42)]，但与非早发 CHD 无关[1.09( 0.98–1.22)](交互作用 = 0.02)。NMR 测量的脂蛋白胰岛素抵抗与早发 CHD 的最高风险相关 [1.92 (1.52–2.42)]，但与非早发 CHD 无关（Pinteraction <0.001）。11 种生物标志物显示与早产儿和非早产儿 CHD 的关联性更强，包括载脂蛋白 B。9 种 NMR 生物标志物显示与早产儿或非早产儿 CHD 没有关联，而 12 种生物标志物分别与早产儿和非早产儿 CHD 表现出类似的显着关联，包括低密度脂蛋白 (LDL)胆固醇[1.30(1.20–1.45)和1.22(1.10–1.35)]和C反应蛋白[1.34(1.19–1.50)和1.25(1.08–1.44)]。结论 在女性中，12 种生物标志物选择性地与早发冠心病相关，由脂蛋白 (a) 和胰岛素抵抗性动脉粥样硬化性异常脂蛋白血症驱动。这对于开发用于筛查过早冠心病的生物标志物组合具有重要意义。