Stroke Risk Factors: Sex-Specific

Of sex-specific risk factors for stroke, many are hormone-related, according to a systematic review and meta-analysis recently published in JAMA Neurology.

Sex-specific characteristics that influence the risk of stroke were analyzed across 78 studies, most of which had a longitudinal design, published since 1985 through January 2015. Overall, 10,187,540 study participants were included in the analysis. Main outcomes of the study were ischemic stroke, hemorrhagic stroke, any stroke, and stroke mortality.

Primary analysis focused on identifying risk factors for ischemic and hemorrhagic stroke, independently.

Ischemic stroke. The pooled relative risk (RR) of ischemic stroke was higher in women with history of any hypertensive disorder in pregnancy (RR=1.80 [95% confidence interval (CI), 1.49-2.18]) as compared to women without a hypertensive disorder in pregnancy. In men, treatment with androgen deprivation therapy (RR=1.19 [95% CI, 1.05-1.34]) and orchiectomy (RR = 1.21 [95% CI, 1.00-1.46]) increased the relative risk for ischemic stroke.

Hemorrhagic stroke. A history of gestational hypertension was shown to increase the risk of hemorrhagic stroke in women (RR = 5.08 [95% CI, 1.80-14.34]). The risk was also increased in women with menopause at age >55 years (i.e., late menopause) vs 50-54 years (RR = 2.24 [95% CI, 1.19-4.21]). Male-specific risk factors for hemorrhagic stroke could not be pooled from the available data.

Secondary and tertiary analyses focused on risk factors for any type of stroke and stroke mortality, respectively.

Any type of stroke. Women with one of the following risk factors were more likely to have a stroke, regardless of its type: oophorectomy, any hypertensive disorder in pregnancy, preterm delivery, and stillbirth. Having a hysterectomy could be mildly protective against stroke. In men, androgen deprivation therapy and erectile dysfunction increased the pooled relative risk of any type of stroke.

Stroke mortality. The risk of stroke mortality was increased in women with vs without gestational hypertension. Pooled relative risk of stroke mortality in men could not be estimated.

Connection of stroke and hypertensive disorder in pregnancy is not entirely clear but is speculated to stem from common risk factors these conditions share. Alternative theories suggest that hypertensive disorder in pregnancy is either a marker of vascular disease or a source of long-lasting cardiovascular abnormalities ultimately leading to stroke. Exogenous and endogenous hormones are known to be implicated in the risk of stroke in both sexes, however, this connection is far from linear.

While not without limitations, the study has definite strengths, namely, the extensive nature of the literature search, inclusions of factors other than hormonal therapy and contraception in the analysis, and presentation of both pooled and individual findings. The study provides much needed insight into sex-specific risk factors, thus improving the accuracy of individualized stroke risk assessment.

Reference: Poorthuis MHF, et al. Female- and male-specific risk factors for stroke: a systematic review and meta-analysis. JAMA Neurol. November 14, 2016.