Associations of Metabolic Vulnerability Index with Cardiometabolic Diseases, Multimorbidity, and All-cause Mortality

Abstract Background Metabolic vulnerability index (MVX), a novel biomarker of systemic inflammation and metabolic malnutrition, is associated with mortality in patients with cardiovascular diseases. Nevertheless, little is known about its association with cardiometabolic diseases (CMDs) and multimorbidity (CMM). We aimed to examine the associations of MVX with the risk of individual CMDs, their progression to CMM, and all-cause mortality in the general population. Methods In a prospective cohort of 218,635 UK Biobank participants free of CMDs, MVX was calculated based on plasma metabolomics data. CMM was defined as coexistence of two or more CMDs, including coronary heart disease (CHD), stroke, and type 2 diabetes mellitus (T2DM). Cox proportional hazard and multi-state models were employed to evaluate the associations of MVX with the risks of individual CMDs, CMM, and all-cause mortality. Results During a median follow-up of 14.4 years, 27,805 (12.7%) participants developed at least one CMD, 3,006 (1.4%) progressed to CMM, and 14,211 (6.5%) died. Each standard deviation increase of MVX score was associated with 9% (95% confidence interval: 8%-10%), 11% (7%-15%), and 12% (10%-14%) higher risks of developing CMDs, CMM, and mortality, respectively. The MVX-CMM associations were more prominent in females and in the sequential onset pattern of T2DM followed by CHD or stroke. Multi-state model analysis further uncovered consistent associations between higher scores of MVX and higher risks of transitions from CMDs free to CMD, subsequently to CMM, and to death. Conclusions Higher MVX scores were significantly associated with higher risks of incident CMDs, their progressions to CMM, and all-cause mortality. These results underscored the potential of MVX in the primary prevention and management of CMDs and CMM.