Liang C et al.BMJ. 2022 Jun 22;377:e070603. 

全球范围内，中风是导致女性死亡和残疾的主要原因之一。2019年，约有300万女性死于中风，女性因中风致残而失去1000多万年的健康生命。本项研究旨在分析不孕、复发性流产与首次非致命性和致命性中风风险的关系，并进一步按中风亚型进行分层。

研究纳入618851例患者，不孕与非致命性中风风险增加相关(OR 1.14,95%CI 1.08 - 1.20)。反复流产(至少3次)与非致命性和致命性中风的高风险相关(OR 1.35,95%C1.27 - 1.44和1.82,1.58 - 2.10)。流产妇女发生非致命性中风的风险高31%(1.31,1.10 - 1.57)，复发性流产妇女发生致命性中风的风险高26%(1.26,1.15 - 1.39)。

数据结果证实，复发性流产史和产前或产中死亡或流产可被认为是女性特有的卒中危险因素，不同卒中亚型的风险存在差异。这些发现可能有助于改善有此类病史的女性的中风监测和预防。

Abstract

Objective: To examine the associations of infertility, recurrent miscarriage, and stillbirth with the risk of first non-fatal and fatal stroke, further stratified by stroke subtypes.

Design: Individual participant pooled analysis of eight prospective cohort studies.

Setting: Cohort studies across seven countries (Australia, China, Japan, Netherlands, Sweden, the United Kingdom, and the United States) participating in the InterLACE (International Collaboration for a Life Course Approach to Reproductive Health and Chronic Disease Events) consortium, which was established in June 2012.

Participants: 618 851 women aged 32.0-73.0 years at baseline with data on infertility, miscarriage, or stillbirth, at least one outcome event (non-fatal or fatal stroke), and information on covariates were included; 93 119 women were excluded. Of the participants, 275 863 had data on non-fatal and fatal stroke, 54 716 only had data on non-fatal stroke, and 288 272 only had data on fatal stroke.

Main outcome and measures: Non-fatal strokes were identified through self-reported questionnaires, linked hospital data, or national patient registers. Fatal strokes were identified through death registry data.

Results: The median follow-up for non-fatal stroke and fatal stroke was 13.0 years (interquartile range 12.0-14.0) and 9.4 years (7.6-13.0), respectively. A first non-fatal stroke was experienced by 9265 (2.8%) women and 4003 (0.7%) experienced a fatal stroke. Hazard ratios for non-fatal or fatal stroke were stratified by hypertension and adjusted for race or ethnicity, body mass index, smoking status, education level, and study. Infertility was associated with an increased risk of non-fatal stroke (hazard ratio 1.14, 95% confidence interval 1.08 to 1.20). Recurrent miscarriage (at least three) was associated with higher risk of non-fatal and fatal stroke (1.35, 1.27 to 1.44, and 1.82, 1.58 to 2.10, respectively). Women with stillbirth were at 31% higher risk of non-fatal stroke (1.31, 1.10 to 1.57) and women with recurrent stillbirth were at 26% higher risk of fatal stroke (1.26, 1.15 to 1.39). The increased risk of stroke (non-fatal or fatal) associated with infertility or recurrent stillbirths was mainly driven by a single stroke subtype (non-fatal ischaemic stroke and fatal haemorrhagic stroke), while the increased risk of stroke (non-fatal or fatal) associated with recurrent miscarriages was driven by both subtypes.

Conclusion: A history of recurrent miscarriages and death or loss of a baby before or during birth could be considered a female specific risk factor for stroke, with differences in risk according to stroke subtypes. These findings could contribute to improved monitoring and stroke prevention for women with such a history.

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