Association of obesity and metabolic health status with cerebral small vessel disease in stroke-free individuals

Abstract Background It remains unclear whether obesity itself or metabolic abnormalities coexisting with obesity, are associated with stroke. Purpose We aimed to investigate the association of obesity and metabolic health status with cerebral small vessel disease (SVD) in stroke-free participants from a brain health check-up. Methods We conducted a cross-sectional study of 6088 stroke-free participants who underwent brain magnetic resonance imaging at a brain check-up between 2013 and 2020. Participants were categorised according to sex-specific waist circumference and metabolic health status. A metabolically healthy status was defined as the absence of components of metabolic syndrome other than a large waist circumference, such as high blood pressure, hyperglycaemia, and dyslipidaemia. The total SVD score was derived from four magnetic resonance imaging markers: silent lacunar infarcts, cerebral microbleeds, moderate-to-severe white matter hyperintensities, and enlarged perivascular spaces. Results The mean age of the participants was 55±12 years and 46% were women. The prevalence of metabolically healthy obesity was 650 (11%) and the proportion of metabolically healthy obesity among individuals with obesity was 24%. The prevalence of metabolically unhealthy obesity was 2043 (34%), and the proportion of metabolically unhealthy obesity among individuals with metabolically unhealthy individuals was 58%. The prevalence of moderate-to-severe SVD scores (≥2) was 348 (6%), which was higher in metabolically unhealthy individuals, regardless of obesity status. Compared with the metabolically healthy non-obesity group, the metabolically unhealthy non-obesity (odds ratio 2.22 [95% CI, 1.44–3.42]) and metabolically unhealthy obesity (odds ratio, 2.76 [95% CI, 1.80–4.24]) groups had a significantly higher multivariable-adjusted risk for a total SVD score of ≥2. Further sensitivity analyses using BMI-defined obesity instead of waist circumference-defined obesity yielded similar results. Conclusions Abdominal and general obesity alone are not associated with higher total SVD scores in stroke-free individuals. Unhealthy metabolic components, especially high blood pressure and hyperglycaemia, are important risk factors for SVD.