Differential and sex- and age-specific risks of cardiometabolic diseases with unrelated metabolic syndrome dimensions

Abstract

Objective: This study aimed to investigate whether independent dimensions of metabolic syndrome (MetS) components are associated differentially with incident cardiometabolic diseases. Methods: Principal components analysis was performed using the five MetS components from 153,073 unrelated European-ancestry participants (55% women) from the UK Biobank. The associations of the principal components (PCs) with incident type 2 diabetes mellitus (T2D), coronary artery disease (CAD), and (ischemic) stroke were analyzed using multivariable-adjusted Cox proportional hazards models in groups stratified by sex and baseline age. Results: PC1 (40.5% explained variance; increased waist circumference with dyslipidemia) and PC2 (22.7% explained variance; hyperglycemia) were both associated with incident cardiometabolic disease. Hazard ratios for CAD and T2D were higher for PC1 than for PC2 (1.27 [95% CI: 1.25–1.29] vs. 1.06 [95% CI: 1.03–1.08] and 2.09 [95% CI: 2.03–2.16] vs. 1.39 [95% CI: 1.34–1.44], respectively). Furthermore, the association of PC1 with T2D was slightly higher for women than for men, and especially the HRs of PC1 with CAD and T2D attenuated with increasing age (p values for heterogeneity test among subgroups < 0.05). Conclusions: MetS can be dissected into two distinct presentations characterized by differential sex- and age-associated cardiometabolic disease risk, confirming the loss of information using the dichotomous MetS.