MIDLIFE health profiles defined by clusters of coexisting conditions significantly influence ischemic stroke incidence and severity, according to a large analysis of participants in the Atherosclerosis Risk in Communities (ARIC) study.
Investigators evaluated 15,404 adults without prior stroke, applying a machine-learning clustering approach to midlife clinical risk factors including hypertension, diabetes, coronary heart disease, heart failure, atrial fibrillation, renal dysfunction, and peripheral artery disease. Nine distinct clusters emerged, ranging from relatively healthy individuals to those with multiple cardiovascular and metabolic conditions.
During follow-up from 1987 through 2020, 1,424 incident ischemic strokes were recorded, with 1,104 graded by National Institutes of Health Stroke Scale scores. Stroke severity varied markedly by morbidity cluster. Individuals grouped in the renal dysfunction cluster experienced the highest risk, with a threefold increase in overall ischemic stroke incidence compared with the relatively healthy cluster. Their risk of moderate-to-severe stroke was even greater, with a hazard ratio of 4.78. Elevated risks were also observed for clusters defined by heart failure, atrial fibrillation, and coronary heart disease.
Importantly, most morbidity clusters were linked to strokes occurring before the age of 70 years, emphasizing the role of midlife health in shaping later outcomes. Only the cluster defined by obesity, diabetes, hypertension, and hypertriglyceridemia was associated with increased stroke incidence across all age groups.
These findings underscore the clinical value of considering aggregated morbidity patterns rather than isolated conditions when assessing stroke risk. Early identification of high-risk clusters may improve targeted prevention strategies and guide patient counseling in midlife, a critical period for modifying long-term cerebrovascular outcomes.
Reference: Egle M et al. Role of Morbidity Clusters in Midlife on Ischemic Stroke Incidence and Severity: The ARIC Study. Stroke. 2025. doi: 10.1161/STROKEAHA.124.049496. Online ahead of print.
