We have previously demonstrated that HIV infection confers a greater relative risk of ischemic stroke in women compared with men, independent of traditional stroke risk factors. The mechanism underlying this disparity, including the potential role of sex-specific stroke risk factors, is unknown. We investigated whether increased ischemic stroke risk in HIV-infected women persists after adjusting for sex-specific stroke risk factors.
We performed an observational cohort study of 1212 HIV-infected women and 12040 demographics-matched HIV-uninfected women followed from 1996 to 2011 in a large Boston health care system. The primary endpoint was incident ischemic stroke, defined by specific ICD-9-CM codes. Cox proportional hazard modeling was used to evaluate the association of HIV and ischemic stroke and the role of sex-specific risk factors in mediating this association.
Among the HIV-infected women, 38 ischemic strokes occurred, compared with 167 among the HIV-uninfected women. The incidence rate ratio (IRR) for stroke comparing HIV-infected to HIV-uninfected women was 2.34 (95% confidence interval [CI] 1.60-3.34). The relative increase in stroke rates in HIV-infected women was most pronounced among younger women (18-35 years, IRR 4.96, 95% CI 1.58-13.52; 36-45 years, IRR 3.78, 95% CI 1.63-8.10; 46-55 years, IRR 2.60, 95% CI 1.25-5.03). HIV was significantly associated with increased stroke risk in univariate models (hazard ratio [HR] 2.43, 95% CI 1.78-3.61) and in models adjusting for demographics and vascular risk factors (HR 1.81, 95% CI 1.26-2.61). In a multivariable model further adjusted for sex-specific risk factors (menopause/vasomotor symptoms, premature ovarian failure, hormone replacement therapy/oral contraceptive use, pregnancy, pre-eclampsia/eclampsia, migraine, and depression/anxiety), the greater hazard of stroke associated with HIV persisted (HR 2.14, 95% CI 1.45-3.15).
HIV infection was significantly associated with an increased risk of ischemic stroke among women independent of sex-specific stroke risk factors prevalent among HIV-infected women. Investigation of additional factors to explain the differential effect of HIV on vascular risk among women, including evaluation of immunologic factors that differ by sex, will be important to further clarify the mechanism of HIV-associated vascular disease.