Role of Morbidity Clusters in Midlife on Ischemic Stroke Incidence and Severity: The ARIC Study
Year: 2025
Type: article
Abstract: BACKGROUND: There is a strong association between vascular risk factors, particularly in midlife, and stroke risk; therefore, the co-occurrence of multiple risk factors may be especially informative. This study used a machine-learning-based cluster analysis to group individuals into clusters based on similar clinical profiles in midlife and assessed the clusters' associations with stroke risk and severity. METHODS: Participants (N=15 404) without prevalent stroke from the ARIC study (Atherosclerosis Risk in Communities) were included. An unsupervised agglomerative hierarchical clustering approach was used to allocate participants into clusters based on the presence of clinical risk factors in midlife: hypertension, diabetes, coronary heart disease, heart failure, atrial fibrillation, renal dysfunction, and peripheral artery disease. Clusters were then characterized by their defining features. In Cox proportional hazard models, the association of the clusters with overall stroke incidence (and with ischemic stroke incidence stratified by stroke severity) was tested. Multinomial logistic regression models were used to examine the association of morbidity clusters with outcomes of no stroke, stroke before the age of 70 years, and stroke at age of ≥70 years. RESULTS: Of 1424 incident ischemic strokes diagnosed from baseline (1987-1989) to December 31, 2020, 1104 included National Institutes of Health Stroke Scale (NIHSS) grading (minor-mild stroke: NIHSS score ≤5 [n=687]; moderate-severe stroke: NIHSS score >5 [n=417]). The cluster analysis identified 9 distinct clusters in the population with defining features: cluster 1 (relatively healthy); cluster 2 (smoking); cluster 3 (cancer); cluster 4 (peripheral artery disease); cluster 5 (obesity, diabetes, hypertension, and hypertriglyceridemia); cluster 6 (coronary heart disease); cluster 7 (atrial fibrillation); cluster 8 (heart failure); and cluster 9 (renal dysfunction). Compared with cluster 1, clusters 2 to 9 were each associated with a greater stroke risk, with the largest effect estimate for cluster 9 (hazard ratio, 3.00 [95% CI, 2.00-4.50]). The association with moderate-severe stroke incidence (versus no stroke) was also strongest for cluster 9 (hazard ratio, 4.78 [95% CI, 2.62-8.74]). Except for cluster 5 (which was associated with stroke at any age), all midlife morbidity clusters were associated with greater stroke risk before the age of 70 years but not after the age of 70 years. CONCLUSIONS: The findings emphasize the importance of morbidity clusters in midlife for stroke incidence and severity.
Source: Stroke
Language: English
Subfield: Epidemiology
Field: Medicine
Domain: Health Sciences
Open Access status: hybrid
Funders: Autism Speaks, U.S. Department of Agriculture, U.S. Department of Veterans Affairs, Gordon and Betty Moore Foundation, American Heart Association, GAVI Alliance, World Bank Group, American Surgical Association Foundation, Natural Science Foundation of Shanghai, Wellcome Trust, Royal University Hospital Foundation, British Heart Foundation, European Commission, Deutsche Forschungsgemeinschaft, Agence Nationale de la Recherche, National Natural Science Foundation of China, Chung-Ang University, Nederlandse Organisatie voor Wetenschappelijk Onderzoek, Natural Science Foundation of Guangdong Province, University of Toronto, King Abdulaziz University, Khalifa University of Science, Technology and Research, Narodowe Centrum Nauki, Vetenskapsrådet, Ministerstwo Edukacji i Nauki, Natural Science Foundation of Jiangsu Province, Department of Science and Technology of Sichuan Province, Ministerio de Ciencia e Innovación, Food and Health Bureau, Sydäntutkimussäätiö, Emberi Eroforrások Minisztériuma, China Academy of Chinese Medical Sciences, Deutsche Krebshilfe, Fundo para o Desenvolvimento das Ciências e da Tecnologia, Natural Science Foundation of Shandong Province, Nanjing University of Chinese Medicine, Hersenstichting, Inner Mongolia University of Technology, Universität Konstanz, Alzheimer Nederland, National Center for Genetic Engineering and Biotechnology, ShanghaiTech University, Hellenic Foundation for Research and Innovation, Uniwersytet im. Adama Mickiewicza w Poznaniu, Macau University of Science and Technology, Shenzhen Municipal Science and Technology Innovation Council, UK Regenerative Medicine Platform, National Institutes of Health, Canadian Institutes of Health Research, Natural Sciences and Engineering Research Council of Canada, Engineering and Physical Sciences Research Council, Biotechnology and Biological Sciences Research Council, National Health and Medical Research Council, Japan Society for the Promotion of Science, Agencia Estatal de Investigación, National Key Research and Development Program of China, Fundamental Research Funds for the Central Universities, Shengjing Hospital, Basic and Applied Basic Research Foundation of Guangdong Province, National Institute on Aging, National Heart, Lung, and Blood Institute, National Institute of General Medical Sciences, Eunice Kennedy Shriver National Institute of Child Health and Human Development, JST-Mirai Program, Congressionally Directed Medical Research Programs, H2020 European Research Council, Northwest Fisheries Science Center, HORIZON EUROPE Reforming and enhancing the European Research and Innovation system, Natural Science Foundation of Zhejiang Province, Laboratoires Théa
OpenAlex ID: W4413993451