Different blood lipid profiles and their role in cardiometabolic disease progression: A comparative study between an East Asian and European Large Prospective Cohorts

Abstract Cardiometabolic multimorbidity (CMM), the coexistence of two or more cardiometabolic diseases (CMDs), poses a significant global health burden. However, the role of individual lipid parameters in cardiometabolic disease progression remains insufficiently understood. We analyzed 95,711 Kailuan study participants and 388,317 UK Biobank participants. CMM comprised two or three prespecified CMDs: coronary heart disease (CHD), stroke, and type 2 diabetes (T2D). Associations of low‐density lipoprotein cholesterol (LDL‐C), triglycerides (TG), total cholesterol (TC), high‐density lipoprotein cholesterol (HDL‐C), and non‐high‐density lipoprotein cholesterol (non‐HDL‐C) with transitions from a CMD‐free state to individual CMDs and subsequently to CMM were assessed using multi‐state models. Lipid parameters were associated with CHD or T2D but showed limited associations with overall stroke risk. Associations with CMM progression varied across lipids and populations. In Kailuan study, higher TG and TC were associated with CMM following CHD (TG: HR, 1.21; 95% CI, 1.01–1.44; TC: HR, 1.13; 95% CI, 1.04–1.23), while higher TG was associated with CMM following T2D (HR, 1.05; 95% CI, 1.00–1.11). In UK Biobank, higher LDL‐C was associated with CMM following T2D (HR, 1.27; 95% CI, 1.03–1.57), while higher TG and non‐HDL‐C were associated with increased risk of CMM following CHD (TG: HR, 1.10; 95% CI, 1.07–1.14; non‐HDL‐C: HR, 1.33; 95% CI, 1.15–1.54). HDL‐C was inversely associated with CMM following CHD (HR, 0.90; 95% CI, 0.86–0.95). Individual lipid parameters showed distinct, transition‐specific associations with cardiometabolic disease progression, with heterogeneous patterns between cohorts. Multiple lipid parameters and disease stages must be considered when assessing cardiometabolic risk.