Reproductive Risk Factors and Coronary Heart Disease in the Women's Health Initiative Observational Study.
Reproductive Risk Factors and Coronary Heart Disease in the Women's Health Initiative Observational Study.
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DOI：
10.1161/circulationaha.115.017854
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发表时间：
2016-05-31
期刊：
影响因子：
37.8
通讯作者：
Howard BV
中科院分区：
文献类型：
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作者：
Parikh NI;Jeppson RP;Berger JS;Eaton CB;Kroenke CH;LeBlanc ES;Lewis CE;Loucks EB;Parker DR;Rillamas-Sun E;Ryckman KK;Waring ME;Schenken RS;Johnson KC;Edstedt-Bonamy AK;Allison MA;Howard BV
生殖因素为了解女性冠心病 (CHD) 风险提供了一个早期窗口，但它们对 CHD 风险分层的贡献尚不确定。在妇女健康倡议观察研究中，我们构建了冠心病的Cox比例风险模型，包括年龄、妊娠状况、活产数量、初潮年龄、月经不调、初产年龄、死产、流产、不孕≥1年、不孕原因和母乳喂养。接下来，我们将每个候选生殖因素添加到已建立的冠心病风险因素模型中。然后构建了最终模型，在已确定的冠心病危险因素中添加了重要的生殖因素。评估了 C 统计、净重分类指数（或风险类别 <5%、5-<10% 和 ≥10% 10% 冠心病风险的 NRI）和综合歧视指数 (IDI) 的改善。在 72,982 名女性中 [n=4607 例 CHD 事件，中位随访时间=12.0 (IQR=8.3–13.7) 年，平均 (SD) 年龄 63.2 (7.2) 岁]，年龄调整的生殖危险因素模型的 CHD 统计值为 0.675。在针对已确定的冠心病危险因素进行调整的模型中，首胎出生年龄较小、死产数量、流产数量和缺乏母乳喂养与冠心病呈正相关。生殖因素适度改善了模型辨别力（C 统计量从 0.726 增加到 0.730；IDI=0.0013，p 值 < 0.0001）。发生事件的女性的净重新分类没有改善（NRI 事件=0.007，p 值=0.18）；对于没有事件的女性，略有改善（NRI 非事件 = 0.002，p 值 = 0.04）关键生殖因素与 CHD 相关，独立于已确定的 CHD 危险因素，非常适度地改善模型辨别力，并且不会实质性地改善净重新分类。
Reproductive factors provide an early window into a woman’s coronary heart disease (CHD) risk, however their contribution to CHD risk stratification is uncertain. In the Women’s Health Initiative Observational Study, we constructed Cox proportional hazards models for CHD including age, pregnancy status, number of live births, age at menarche, menstrual irregularity, age at first birth, stillbirths, miscarriages, infertility ≥ 1 year, infertility cause, and breastfeeding. We next added each candidate reproductive factor to an established CHD risk factor model. A final model was then constructed with significant reproductive factors added to established CHD risk factors. Improvement in C-statistic, net reclassification index (or NRI with risk categories of <5%, 5–<10%, and ≥10% 10-year risk of CHD) and integrated discriminatory index (IDI) were assessed. Among 72,982 women [n=4607 CHD events, median follow-up=12.0 (IQR=8.3–13.7) years, mean (SD) age 63.2 (7.2) years], an age-adjusted reproductive risk factor model had a C-statistic of 0.675 for CHD. In a model adjusted for established CHD risk factors, younger age at first birth, number of still births, number of miscarriages and lack of breastfeeding were positively associated with CHD. Reproductive factors modestly improved model discrimination (C-statistic increased from 0.726 to 0.730; IDI=0.0013, p-value < 0.0001). Net reclassification for women with events was not improved (NRI events=0.007, p-value=0.18); and for women without events was marginally improved (NRI non-events=0.002, p-value=0.04) Key reproductive factors are associated with CHD independently of established CHD risk factors, very modestly improve model discrimination and do not materially improve net reclassification.