Association of Vascular Risk With Severe vs Non-Severe Stroke: An Analysis of the INTERSTROKE Study

BACKGROUND AND OBJECTIVES: Acute stroke is associated with a spectrum of functional deficits. The objective of this analysis was to explore whether the importance of individual risk factors differ by stroke severity, which may be of relevance to public health strategies to reduce disability. METHODS: INTERSTROKE is an international case-control study of risk factors of first acute stroke (recruitment 2007-August 2015) in 32 countries. Stroke severity was measured using the modified Rankin Scale (mRS) score within 72 hours of admission to hospital. Severe stroke is defined as mRS scores of 4-6 (and non-severe stroke, score of 0-3). We used multinomial logistic regression to estimate comparative odds ratios (ORs; 95% CIs) for severe and non-severe stroke and tested for heterogeneity (pheterogeneity). We also conducted a matched case-case analysis (matched for age, sex, country, and primary stroke subtype) to determine whether the prevalence of risk factors differed significantly between severe and non-severe stroke. A significant difference in the association of a risk factor of severe stroke compared with non-severe stroke was defined as p < 0.05 for both pheterogeneity and pcase-case. RESULTS: Of patients with acute stroke (n = 13,460), 64.0% (n = 8,612) were reported to have mRS scores of 0-3 and 36.0% (n = 4,848) scores of 4-6. The mean age was 61.7 years for patients with non-severe stroke and 62.9 years for patients with severe stroke (p = 0.72). 38.1% (n = 3,278) of patients with non-severe stroke and 44.6% (n = 2,162) of patients with severe stroke were female. Hypertension (OR 3.21; 95% CI 2.97-3.47 for severe stroke, OR 2.87; 95% CI 2.69-3.05 for non-severe stroke; pheterogeneity = 0.03; pcase-case < 0.001), atrial fibrillation (OR 4.70; 95% CI 4.05-5.45 for severe stroke, OR 3.61; 95% CI 3.16-4.13 for non-severe stroke; pheterogeneity = 0.009; pcase-case < 0.001), and smoking (OR 1.87; 95% CI 1.72-2.03 for severe stroke, OR 1.65; 95% CI 1.54-1.77 for non-severe stroke; pheterogeneity = 0.02; pcase-case < 0.001) had a stronger association with severe stroke, compared with non-severe stroke. The waist-to-hip ratio had a stronger association with non-severe stroke compared with severe stroke (pheterogeneity < 0.001; pcase-case < 0.001). DISCUSSION: Hypertension, atrial fibrillation, and smoking had a stronger magnitude of association with severe stroke (compared with non-severe stroke) while the increased waist-to-hip ratio had a stronger magnitude of association with non-severe stroke.