Cardiometabolic stress can lead to reduces longevity and poorer cardiovascular outcomes. Metabolite profiling is proven to provide a specific measure of global metabolic function to examine specific metabolic mechanisms. This study aims to determine a molecular basis for cardiometabolic stress, along with how it’s associated with cardiovascular prognosis.

This prospective observational cohort study included a total of 668 participants with metabolite profiling who were a part of long-term follow-up for cardiovascular outcomes and mortality. Metabolite profiles across the cohorts were the primary exposure in the study. The main endpoints of the study were the associations with multisystem cardiometabolic stress and all-cause mortality, and incident coronary disease.

Multisystem cardiometabolic stress in the participants was defined as a multidimensional composite of hypothalamic-adrenal axis activity, blood pressure, sympathetic activation, insulin resistance, proatherogenic dyslipidemia, inflammation, and visceral adiposity. The researchers identified a total of 260 metabolites associated with cardiometabolic stress, involving novel and known cardiometabolic disease pathways. A parsimonious metabolite-based score was also created and applied to shared metabolites.

The researchers found that metabolites associated with cardiometabolic stress were associated with a higher risk of coronary heart disease. These results underline the shared molecular pathophysiology of cardiovascular disease and metabolic dysfunction.