Aims The aim of this study was to explore the association of pregnancy loss (PL) with the incidence of cardiovascular disease (CVD) and examine the extent to which this relation is mediated by subsequent metabolic disorders. Methods and results We followed 95 465 ever-gravid women participating in the Nurses’ Health Study II between 1993 and 2017. Cox proportional hazards models were used to estimate the hazard ratios (HRs) of CVD, including coronary heart disease (CHD), and stroke, according to the occurrence of PL. A mediation analysis was conducted to explore the intermediating effect of subsequent type 2 diabetes, hypertension, or hypercholesterolaemia. During 2 205 392 person-years of follow-up (mean 23.10 years), 2225 (2.3%) incident CVD cases were documented. After adjusting for confounding factors, PL was associated with an HR of 1.21 [95% confidence interval (CI) 1.10–1.33] for CVD during follow-up. A similar association was observed for CHD (HR 1.20; 95% CI 1.07–1.35) and stroke (HR 1.23; 95% CI 1.04–1.44). The risk of CVD increased with the number of PLs [HR 1.18 (95% CI 1.06–1.31) for 1 and 1.34 (95% CI 1.13–1.59) for ≥2 times] and was greater for PL occurring early in reproductive lifespan [HR 1.40 (95% CI 1.21–1.62) for age ≤23 years, 1.25 (95% CI 1.09–1.43) for age 24–29 years, and 1.03 (95% CI 0.88–1.19) for age ≥30 years]. Hypertension, hypercholesterolaemia, and type 2 diabetes all explained <1.80% of the association between PL and CVD. Conclusion PL was associated with a greater CVD risk, independently of subsequent development of metabolic disorders.

中文翻译：

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妊娠失败和心血管疾病的风险：护士健康研究 II

目的 本研究的目的是探讨妊娠丢失 (PL) 与心血管疾病 (CVD) 发病率的关系，并检查随后的代谢紊乱介导这种关系的程度。方法和结果 我们对 1993 年至 2017 年间参加护士健康研究 II 的 95 465 名曾经怀孕过的女性进行了追踪。Cox 比例风险模型用于估计 CVD 的风险比 (HR)，包括冠心病 (CHD) 和中风，根据 PL 的发生情况。进行中介分析以探讨随后的 2 型糖尿病、高血压或高胆固醇血症的中介效应。在 2 205 392 人年的随访期间（平均 23.10 年），记录了 2225 例 (2.3%) CVD 病例。调整混杂因素后，随访期间 PL 与 CVD 的 HR 为 1.21 [95% 置信区间 (CI) 1.10–1.33] 相关。CHD（HR 1.20；95% CI 1.07–1.35）和卒中（HR 1.23；95% CI 1.04–1.44）也观察到类似的关联。CVD 风险随着 PL 数量的增加而增加 [1 次的 HR 为 1.18 (95% CI 1.06–1.31)，≥2 次的 HR 为 1.34 (95% CI 1.13–1.59)]，且发生在生殖寿命早期的 PL 的风险更大 [HR年龄≤23岁为1.40（95% CI 1.21-1.62），24-29岁为1.25（95% CI 1.09-1.43），年龄≥30岁为1.03（95% CI 0.88-1.19）]。高血压、高胆固醇血症和2型糖尿病都解释了PL和CVD之间的相关性的<1.80%。结论 PL 与较高的 CVD 风险相关，与代谢紊乱的后续发展无关。