美国心脏学会（AHA）2012科学年会上公布的一项丹麦研究显示，妊娠失败与此后15年发生3种不同动脉粥硬化疾病的风险增加强烈相关。

Mattis F. Ranthe博士

　　哥本哈根Statens血清研究所的Mattis F. Ranthe博士及其同事从丹麦全国出生至死亡保健注册库中选取1,031,279例1977~1988年妊娠时无心血管病史的丹麦女性，探讨了妊娠失败后动脉粥样硬化疾病的发生情况。这是迄今最大规模的同类研究。

　　共8,191例女性有≥1次死产。151,808例女性有1次流产，28,398例有2次流产，5,979例有3次流产，2,406例有≥4次流产。

　　该研究评价的3种动脉粥样硬化疾病为急性心肌梗死(MI)、脑梗死和肾血管性高血压。在超过150万人-年的随访期间，观察到2,798例MI、4,053脑梗死和1,269例肾血管性高血压。

　　校正年龄、活产次数和日历年后发现，单次死产史与此后的MI发生率比(incidence rate ratio)增加1.69倍、脑梗死发生率比增加0.74倍和肾血管性高血压发生率比增加1.42倍相关。

　　流产次数与动脉粥样硬化疾病风险呈强烈量效关系。随访期间单次流产女性的校正后MI、脑梗死和肾血管性高血压风险分别是无流产史女性的1.11倍、1.13倍和1.15倍。鉴于样本量巨大，上述11%~15%的相对风险增幅均具有强烈显著性。

　　流产2次女性发生MI、脑梗死和肾血管性高血压的风险分别是无流产史女性的1.18倍、1.22倍和1.12倍。流产3次女性发生MI、脑梗死和肾血管性高血压的风险分别是无流产史女性的0.85倍、1.43倍和1.78.倍。流产≥4次女性发生MI、脑梗死和肾血管性高血压的风险分别是无流产史女性的2.08倍、1.89倍和3.78倍。进一步校正188bet在线平台网址 、吸烟状况、血栓形成倾向和多囊卵巢综合征后，这些估计值仍未改变。

　　流产每增加1次，3种动脉粥样硬化疾病的风险就分别增加10%~20%。然而，这些风险在不同年龄组中并非平均分布。在流产的最年轻女性中观察到的此后15年内发生动脉粥样硬化疾病的风险最高。在育龄期后期流产的女性中观察到的风险较小。

　　一位与会者表示，对于较早就患有心肌梗死的年龄较小的育龄期女性，医生往往会认为其为动脉粥样硬化疾病，但实际上还可能是结缔组织疾病等其他原因引起。因此，并非所有的病理生理均可用动脉粥样硬化疾病来解释。Ranthe博士对此表示赞同。

　　该研究获丹麦心脏基金会资助，Ranthe博士声明无与该研究相关的经济利益冲突。

　　By: BRUCE JANCIN, Cardiology News Digital Network

　　LOS ANGELES – Pregnancy loss is strongly associated with increased risks of three different clinical forms of atherosclerotic disease over the subsequent 15 years, a study of more than 1 million Danish pregnant women has shown.

　　"This is the largest-ever study on the occurrence of atherosclerotic disease after pregnancy loss. This study, taken together with previous studies, implies a possible common underlying pathology linking pregnancy losses and atherosclerosis," said Dr. Mattis F. Ranthe of the Statens Serum Institute, Copenhagen.

The study used Denmark’s comprehensive national cradle-to-the-grave health care registry to track all 1,031,279 Danes who were free of a history of cardiovascular disease at the time they became pregnant during 1977-1988. A total of 8,191 women had one or more stillbirths. There were 151,808 women with one miscarriage, 28,398 with two miscarriages, 5,979 with three, and 2,406 women with four or more miscarriages.

　　The three expressions of atherosclerosis under study were acute MI, cerebral infarction, and renovascular hypertension. During more than 15 million person-years of follow-up through the registry, there were 2,798 cases of MI, 4,053 cerebral infarcts, and 1,269 diagnoses of renovascular hypertension, Dr. Ranthe reported at the annual scientific sessions of the American Heart Association.

　　A history of even a single stillbirth was associated with a 2.69-fold increased incidence rate ratio for subsequent MI, a 1.74-fold increase in cerebral infarction, and a 2.42-fold increase in renovascular hypertension after adjustment for age, number of live births, and calendar year.

　　A robust dose-response relationship was evident between the number of miscarriages and atherosclerotic disease risk. Women with a history of a single miscarriage had an adjusted 1.11-fold increased risk of MI, a 1.13-fold increase in cerebral infarction, and a 1.15-fold greater risk of developing renovascular hypertension during follow-up than did women with no miscarriages. These 11%-15% increases in relative risk were all strongly significant, given the large numbers.

　　With two miscarriages, the risks of MI, cerebral infarct, and renovascular hypertension were increased 1.18-fold, 1.22-fold, and 1.12-fold, respectively. With a history of three miscarriages, the risks were 0.85, 1.43, and 1.78. And with 4 or more miscarriages, the incidence rate ratio for MI was increased 2.08-fold, that for cerebral infarct was 1.89-fold, and for renovascular hypertension it was 3.78-fold greater than in women with no miscarriages.

　　Further adjustment for diabetes, smoking, thrombophilia, and polycystic ovarian syndrome left these estimates unchanged.

　　The risk of each of the three forms of atherosclerosis climbed by 10%-20% with each additional miscarriage. However, the risk wasn’t evenly spread across all age groups. Rather, the risk of developing atherosclerotic disease within the next 15 years was greatest in the youngest women who miscarried. The risk associated with miscarriage late in the period of childbearing potential was far less, the physician noted.

　　That observation raised a red flag for one audience member.

　　"If you have younger women of childbearing years having myocardial infarctions earlier on, one tends to think that mechanistically it may be atherosclerosis, but it may actually be due to other issues involving connective tissue diseases. I’d be cautious in using atherosclerosis as a broad pathophysiologic explanation," she said.

　　Dr. Ranthe agreed.

　　He reported having no financial conflicts related to this study, which was funded by the Danish Heart Foundation.