Associations of Behaviors, Biological Phenotypes and Cardiovascular Health With Risks of Stroke and Stroke Subtypes: A Prospective UK Biobank Cohort

Background: Although many cardiovascular risk factors for stroke have been reported before, it has not been investigated comprehensively for all major stroke types in large datasets. This study aimed to evaluate the associations of healthy behaviors, biological phenotypes and cardiovascular health (CVH) with long-term risks of strokes events, overall and stroke subtypes (ischemic stroke [IS], intracerebral hemorrhage [ICH], subarachnoid hemorrhage [SAH], and unspecified stroke). Methods: Between 2006 and 2010, a total of 354,976 participants (age 40-70 years) in the UK Biobank free of stroke and coronary heart disease were examined and thereafter followed up to 2020. According to American Heart Association guideline, the global CVH included four behavioral (smoking, diet, physical activity, body mass index) and three biological (blood glucose, blood cholesterol, blood pressure) metrics, coded on a three-point scale (0, 1, 2). The behavioral, biological and global CVH score was the sum of four, three, and seven metrics, respectively, and then was categorized into poor, intermediate and ideal group. Cox proportional hazard models were used to estimate the hazard ratios (HRs) and 95% confidence intervals (CIs) of stroke events. Finding: A total of 5804 incident stroke cases, including 3664 IS, 714 ICH and 453 SAH, were documented over a median follow-up of 11 years. The risk of stroke decreased significantly and linearly with both increasing behavioral CVH score (HR=0.90, 95% CI: 0.88-0.91 per 1-point increment) and biological CVH score (HR=0.82, 95% CI: 0.80-0.84 per 1-point increment). Ideal behavioral CVH group was significantly associated with lower risks of all stroke subtypes, biological CVH was related to stroke events except for SAH. There was no interaction between biological and behavioral CVH on risk of stroke (P for interaction = 0.95). Additionally, the 1-point increment in global CVH score was associated with 11% (HR=0.89, 95% CI: 0.88-0.90), 13% (HR=0.87, 95% CI: 0.86-0.89), 8% (HR=0.92, 95% CI: 0.89-0.95) and 13% (HR=0.87, 95% CI: 0.83-0.91) lower risks of stroke, IS, ICH and unspecified stroke, however, there was no significant dose-dependent association between global CVH and SAH (HR=0.97, 95% CI: 0.93-1.02). Interpretation: Our findings demonstrated inverse linear associations of behavioral, biological and global CVH with long-term risks of stroke and stroke subtypes, except for SAH, highlighting the benefits of maintaining better CVH status as a primordial prevention strategy of stroke. Funding Statement: The National Natural Science Foundation of China (91746205, 71910107004, 71673199). Declaration of Interests: The authors declare that they have no conflicts of interests.