Cardiovascular Risk from Metabolic Dysfunction-Associated Steatotic Liver Disease, Cardiometabolic Risk Factor Count, and Their Longitudinal Changes: A Nationwide Cohort Study

Introduction: Metabolic dysfunction-associated steatotic liver disease (MASLD) is associated with incident cardiovascular disease (CVD). However, CVD risk could vary across and within individuals with MASLD. We investigated the cardiovascular implications of MASLD, cardiometabolic risk factor count, and their longitudinal changes. Methods: From nationwide health screening data, we included adults aged 20-79 without increased/excessive alcohol intake, concomitant liver diseases, and prior CVD at baseline examination in 2009 (N=7,292,497). Participants were classified according to MASLD status; those with MASLD were further categorized by their count of qualifying cardiometabolic risk factors (1-5). Individuals who underwent follow-up examinations in 2011 (N=4,198,672) were additionally classified according to their baseline and follow-up MASLD status; those with persistent MASLD were further categorized by combination of baseline and follow-up cardiometabolic risk factor counts. The risk of incident CVD was assessed using multivariable-adjusted Cox model. Results: Over a median follow-up of 12.3 years, 220,088 new CVD events occurred. The presence of MASLD was associated with higher incidence of CVD. Among participants with MASLD, the risk of CVD increased gradually with higher cardiometabolic risk factor count (per 1-higher; HR, 1.18 [95% CI, 1.18-1.19]). The development of MASLD during follow-up was associated with higher risk of CVD (HR, 1.28 [95% CI, 1.25-1.31]), whereas the regression of MASLD was associated with lower risk of CVD (HR, 0.84 [95% CI, 0.82-0.86]). Among individuals with persistent MASLD, gaining and losing cardiometabolic risk factor count during follow-up were associated with elevated and reduced risk of CVD, respectively. Discussion: MASLD status, cardiometabolic risk factor count, and their longitudinal changes were all associated with the risk of incident CVD. Accurate identification of these markers may facilitate personalized management of MASLD-related CVD risk.