Sex differences in the association between major risk factors and the risk of stroke in the UK Biobank cohort study

Abstract

Objective: To determine whether there are sex differences in the association between risk factors and incident stroke, including stroke subtypes.

Methods: A total of 471,971 (56% women) UK Biobank participants without a history of cardiovascular disease were included. During 9 years of follow-up, 4,662 (44% women) cases of stroke were recorded. Cox models yielded adjusted hazard ratios (HRs) and women-to-men ratios of HRs (RHRs) for stroke associated with 7 risk factors.

Results: The incidence rate per 10,000 person-years was 8.66 (8.29-9.04) in women and 13.96 (13.44-14.50) in men for any stroke, 6.06 (5.75-6.38) in women and 11.35 (10.88; 11.84) in men for ischemic stroke, and 1.56 (1.41-1.73) in women and 2.23 (2.02-2.45) in men for hemorrhagic stroke. The association between increases in blood pressure, body anthropometry, and lipids, diabetes, and atrial fibrillation and any stroke was similar between men and women. Hypertension, smoking, and a low socioeconomic status were associated with a greater HR of any stroke in women than men; the RHRs were 1.36 (1.26-1.47), 1.18 (1.02-1.36), and 1.17 (1.03-1.33), respectively. Diabetes was associated with a higher HR of ischemic stroke in women than men (RHR 1.25 [1.00-1.56]). Atrial fibrillation was associated with a higher HR of hemorrhagic stroke in women than men (RHR 2.80 [1.07-7.36]).

Conclusion: Several risk factors are more strongly associated with the risk of any stroke or stroke subtypes in women compared with men. Despite this, the incidence of stroke remains higher among men than women.

Figure 1. Adjusted HRs for incident ischemic stroke associated with risk factors, by sex

Horizontal lines indicate the corresponding 95% confidence intervals (CIs) around the hazard ratios (HRs). AF = atrial fibrillation; BMI = body mass index; BP = blood pressure; HDL = high-density lipoprotein; LDL = low-density lipoprotein; SES = socioeconomic status.

Figure 2. Adjusted HRs for incident hemorrhagic stroke associated with risk factors, by sex

Horizontal lines indicate the corresponding 95% confidence intervals (CIs) around the hazard ratios (HRs). AF = atrial fibrillation; BMI = body mass index; BP = blood pressure; HDL = high-density lipoprotein; LDL = low-density lipoprotein; SES = socioeconomic status.

Figure 3. Adjusted women-to-men RHRs for ischemic and hemorrhagic stroke associated with risk factors

Horizontal lines indicate the corresponding 95% confidence intervals (CIs) around the ratio of hazard ratios (RHRs). AF = atrial fibrillation; BMI = body mass index; BP = blood pressure; HDL = high-density lipoprotein; LDL = low-density lipoprotein; SES = socioeconomic status.