Anti-Mullerian Hormone Trajectories Are Associated With Cardiovascular Disease in Women Results From the Doetinchem Cohort Study
Anti-Mullerian Hormone Trajectories Are Associated With Cardiovascular Disease in Women Results From the Doetinchem Cohort Study
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DOI：
10.1161/circulationaha.116.025968
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发表时间：
2017-02-07
期刊：
影响因子：
37.8
通讯作者：
van der Schouw, Yvonne T.
中科院分区：
文献类型：
--
作者：
de Kat, Annelien C.;Verschuren, W. Monique;van der Schouw, Yvonne T.
背景：绝经年龄较早被广泛认为与心血管疾病风险增加有关。然而，这种关系的潜在机制仍然不确定。有迹象表明，卵巢储备标志物抗苗勒氏激素(AMH)在生殖系统之外发挥着生理作用。因此，我们调查了纵向AMH下降轨迹是否与心血管疾病(CVD)发生的风险增加相关。方法：这项研究包括3108名年龄在20岁至60岁之间的女性参与者，年龄在以人群为基础的Doetinchem队列的基线。参与者在1987至2010年间完成了连续5次五年期访问中的1次，总跟踪时间为20年。对8507份储存的血浆样品进行了AMH测定。有关总心血管疾病、中风和冠心病的信息是通过医院出院登记链接获得的。通过联合建模，调整年龄、吸烟、口服避孕药、体重指数、绝经状态、绝经后激素治疗、舒张压、总胆固醇、高密度脂蛋白胆固醇和血糖水平，量化AMH轨迹与心血管疾病的关系。结果：在随访结束时，8.2%的女性患有心血管疾病，4.9%患有冠心病，2.6%经历过中风。校正后，AMH水平每降低1 ng/m L，患心血管疾病的风险增加21%(危险比1.21；95%可信区间1.07-1.36)，患冠心病风险增加26%(危险比1.25；95%可信区间1.08-1.46)。(LOG)AMH每多降低一ng/毫升/年，患心血管疾病(危险比为1.46；95%可信区间为1.14-1.87)和冠心病(危险比为1.56；95%可信区间为1.15-2.12)的风险显著增加。未发现AMH与中风之间的关联。结论：这些结果表明，女性AMH的运动轨迹与心血管疾病的风险独立相关。因此，我们推测，循环中AMH水平的下降可能是更年期提前增加心血管风险的病理生理机制的一部分。需要确认这种关联并阐明其潜在机制，才能将这些结果应用于临床。
BACKGROUND: Earlier age at menopause is widely considered to be associated with an increased risk of cardiovascular disease. However, the underlying mechanisms of this relationship remain undetermined. Indications suggest that anti-Mullerian hormone (AMH), an ovarian reserve marker, plays a physiological role outside of the reproductive system. Therefore, we investigated whether longitudinal AMH decline trajectories are associated with an increased risk of cardiovascular disease (CVD) occurrence.METHODS: This study included 3108 female participants between 20 and 60 years of age at baseline of the population-based Doetinchem Cohort. Participants completed >= 1 of 5 consecutive quinquennial visits between 1987 and 2010, resulting in a total follow-up time of 20 years. AMH was measured in 8507 stored plasma samples. Information on total CVD, stroke, and coronary heart disease was obtained through a hospital discharge registry linkage. The association of AMH trajectories with CVD was quantified with joint modeling, with adjustment for age, smoking, oral contraceptive use, body mass index, menopausal status, postmenopausal hormone therapy use, diastolic blood pressure, total cholesterol, high-density lipoprotein cholesterol, and glucose levels.RESULTS: By the end of follow-up, 8.2% of the women had suffered from CVD, 4.9% had suffered from coronary heart disease, and 2.6% had experienced a stroke. After adjustment, each ng/mL lower (log)AMH level was associated with a 21% higher risk of CVD (hazard ratio, 1.21; 95% confidence interval, 1.07-1.36) and a 26% higher risk of coronary heart disease (hazard ratio, 1.25; 95% confidence interval, 1.08-1.46). Each additional ng/mL/year decrease of (log)AMH was associated with a significantly higher risk of CVD (hazard ratio, 1.46; 95% confidence interval, 1.14-1.87) and coronary heart disease (hazard ratio, 1.56; 95% confidence interval, 1.15-2.12). No association between AMH and stroke was found.CONCLUSIONS: These results indicate that AMH trajectories in women are independently associated with CVD risk. Therefore, we postulate that the decline of circulating AMH levels may be part of the pathophysiology of the increased cardiovascular risk of earlier menopause. Confirmation of this association and elucidation of its underlying mechanisms are needed to place these results in a clinical perspective.