Differences in risk factors for 3 types of stroke: UK prospective study and meta-analyses

Abstract

Objective: To compare associations of behavioral and related factors for incident subarachnoid hemorrhage and intracerebral hemorrhage and ischemic stroke.

Methods: A total of 712,433 Million Women Study participants without prior stroke, heart disease, or cancer reported behavioral and related factors at baseline (1999-2007) and were followed up by record linkage to national hospital admission and death databases. Cox regression yielded adjusted relative risks (RRs) by type of stroke. Heterogeneity was assessed with χ² tests. When appropriate, meta-analyses were done of published prospective studies.

Results: After 12.9 (SD 2.6) years of follow-up, 8,128 women had an incident ischemic stroke, 2,032 had intracerebral hemorrhage, and 1,536 had subarachnoid hemorrhage. In women with diabetes mellitus, the risk of ischemic stroke was substantially increased (RR 2.01, 95% confidence interval [CI] 1.84-2.20), risk of intracerebral hemorrhage was increased slightly (RR 1.31, 95% CI 1.04-1.65), but risk of subarachnoid hemorrhage was reduced (RR 0.43, 95% CI 0.26-0.69) (heterogeneity by stroke type, p < 0.0001). Stroke incidence was greater in women who rated their health as poor/fair compared to those who rated their health as excellent/good (RR 1.36, 95% CI 1.30-1.42). Among 565,850 women who rated their heath as excellent/good, current smokers were at an increased risk of all 3 stroke types, (although greater for subarachnoid hemorrhage [≥15 cigarettes/d vs never smoker, RR 4.75, 95% CI 4.12-5.47] than for intracerebral hemorrhage [RR 2.30, 95% CI 1.94-2.72] or ischemic stroke [RR 2.50, 95% CI 2.29-2.72]; heterogeneity p < 0.0001). Obesity was associated with an increased risk of ischemic stroke and a decreased risk of hemorrhagic stroke (heterogeneity p < 0.0001). Meta-analyses confirmed the associations and the heterogeneity across the 3 types of stroke.

Conclusion: Classic risk factors for stroke have considerably different effects on the 3 main pathologic types of stroke.

Figure 1. Relative risk of stroke associated with diabetes mellitus and hypertension requiring treatment, reported at baseline

RR^a is the relative risk for diabetes mellitus/hypertension compared to no diabetes mellitus/hypertension stratified by year of birth and calendar year at baseline and adjusted for region of residence, educational attainment, and socioeconomic status. RR^b is the relative risk for diabetes mellitus/hypertension compared to no diabetes mellitus/hypertension, as for RR^a, and additionally adjusted for use of menopausal hormones, smoking, alcohol consumption, body mass index, and physical activity. CI = confidence interval.

Figure 2. Relative risk of hemorrhagic and ischemic stroke associated with classic behavior-related vascular risk factors at baseline in those with excellent/good self-rated health

Relative risk^a is stratified by year of birth and calendar year at baseline and adjusted for region of residence, educational attainment, socioeconomic status, and use of menopausal hormones, and, when appropriate, for smoking, alcohol consumption, body mass index, and physical activity. Test for heterogeneity in the relative risk for current vs never smoking between hemorrhagic and ischemic stroke: p = 0.01. Test for heterogeneity in trend between hemorrhagic and ischemic stroke: alcohol consumption p = 0.02, body mass index p < 0.0001, and physical activity p = 0.59.

Figure 3. Relative risk of subarachnoid and intracerebral hemorrhage associated with classic behavior-related factors at baseline in those with excellent/good self-rated health

Relative risk^a is stratified by year of birth and calendar year at baseline and adjusted for region of residence, educational attainment, socioeconomic status, and use of menopausal hormones, and, when appropriate, for smoking, alcohol consumption, body mass index, and physical activity. Test for heterogeneity in the relative risk for current vs never smoking between subarachnoid hemorrhage and intracerebral hemorrhage: p < 0.0001. Test for heterogeneity in trend between subarachnoid hemorrhage and intracerebral hemorrhage: alcohol consumption p = 0.51, body mass index p = 0.54, and physical activity p = 0.86.

Figure 4. Relative risk of stroke type by amount smoked in current smokers at baseline in those with excellent/good self-rated health

Relative risk^a is the relative risk in current vs never smokers stratified by year of birth and calendar year at baseline and adjusted for region of residence, educational attainment, socioeconomic status, use of menopausal hormones, alcohol consumption, body mass index, and physical activity.

Figure 5. Meta-analysis of prospective studies that reported the risk of the 3 types of stroke

(A) Diabetes mellitus vs no diabetes mellitus (heterogeneity between stroke types p < 0.001) and (B) current vs never smokers (heterogeneity between stroke types p < 0.001 in Asian studies and p < 0.001 in European and North American studies). CI = confidence interval; RR = relative risk.