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Abstract：
Background Premature and early menopause are independently associated with greater risk of cardiovascular disease (CVD). However, mechanisms linking age of menopause with CVD remain poorly characterized. Methods and Results We measured 71 circulating CVD protein biomarkers in 1565 postmenopausal women enrolled in the FHS (Framingham Heart Study). We examined the association of early menopause with biomarkers and tested whether early menopause modified the association of biomarkers with incident cardiovascular outcomes (heart failure, major CVD, and all-cause death) using multivariable-adjusted linear regression and Cox models, respectively. Among 1565 postmenopausal women included (mean age 62 years), 395 (25%) had a history of early menopause. Of 71 biomarkers examined, we identified 7 biomarkers that were significantly associated with early menopause, of which 5 were higher in women with early menopause including adrenomedullin and resistin, and 2 were higher in women without early menopause including insulin growth factor-1 and CNTN1 (contactin-1) (Benjamini-Hochberg adjusted P<0.1 for all). Early menopause also modified the association of specific biomarkers with incident cardiovascular outcomes including adrenomedullin (Pint<0.05). Conclusions Early menopause is associated with circulating levels of CVD protein biomarkers and appears to modify the association between select biomarkers with incident cardiovascular outcomes. Identified biomarkers reflect several distinct biological pathways, including inflammation, adiposity, and neurohormonal regulation. Further investigation of these pathways may provide mechanistic insights into the pathogenesis, prevention, and treatment of early menopause-associated CVD.
摘要：
背景：过早和过早绝经与心血管疾病（CVD）的更大风险独立相关。然而,绝经年龄与CVD之间的联系机制尚不明确。方法和结果我们在参加FHS（Framingham心脏研究）的1565名绝经后妇女中测量了71种循环CVD蛋白生物标志物。我们检查了早期绝经与生物标志物的关联，并测试了早期绝经是否改变了生物标志物与心血管事件的关联（心力衰竭，主要CVD,和全因死亡)使用多变量调整线性回归和Cox模型，分别。在1565名绝经后妇女中（平均年龄62岁），395人(25%)有早期绝经史。在检查的71种生物标志物中，我们确定了7个与绝经早期显著相关的生物标志物，其中5在绝经早期女性中更高，包括肾上腺髓质素和抵抗素，2在没有早期绝经的女性中更高，包括胰岛素生长因子-1和CNTN1（contactin-1）（Benjamini-Hochberg校正P<0.1）。早期绝经还改变了特定生物标志物与心血管事件的关联，包括肾上腺髓质素（Pint<0.05）。结论绝经早期与循环中的CVD蛋白生物标志物水平相关，并且似乎改变了选择的生物标志物与心血管事件之间的关系。鉴定的生物标志物反映了几种不同的生物学途径，包括炎症,肥胖,和神经激素调节。对这些途径的进一步研究可能会提供对发病机理的机械见解，预防,和早期绝经相关CVD的治疗。
