Abstract
BACKGROUND AND AIMS: Little is known about the relationships between lipoprotein subclasses and the risk of cardiovascular disease (CVD) in individuals with metabolic dysfunction-associated steatotic liver disease (MASLD). We sought to elucidate the associations of lipoprotein subclasses with the risk of CVD in individuals with MASLD.
METHODS AND RESULTS: This study included 51,472 individuals with MASLD from the UK biobank. Concentrations of lipoprotein subclasses were quantified by nuclear magnetic resonance. Multivariable-adjusted Cox proportional hazards model was used to evaluate the associations between lipoprotein subclasses and the incidence/mortality of CVD. During median follow-ups of 13.3-13.5 years, 6208 incident CVD cases, 5206 coronary heart disease cases, 1270 stroke cases, and 559 CVD-related deaths were documented. Most very-low-density lipoprotein (VLDL) [hazard ratio (HR) range: 1.03-1.13; P <0.05], intermediate-density lipoprotein (HR range: 1.08-1.11; P <0.05), low-density lipoprotein (HR range: 1.05-1.11; P <0.05), very large high-density lipoprotein (HDL) particles and triglycerides in small HDL subclasses (HR range: 1.04-1.16; P <0.05) were positively associated with the risk of incident CVD, whereas other HDL particles and their subclasses were related to reduced risks of incident CVD (HR range: 0.86-0.95; P <0.05). Moreover, the association of VLDL particles with CVD strengthened as the diameter of VLDL decreased.
CONCLUSION: These findings suggest that associations between lipoprotein subclasses and the risk of CVD differed by particle diameter in individuals with MASLD. Integrating lipoprotein subclass assessment into clinical management and promoting subclass-targeted lipid-lowering strategies may strengthen CVD prevention in MASLD.