Early cardiometabolic dysfunction: subclinical indicators and sex-specific considerations

Cardiometabolic disease develops over decades, yet most research emphasizes markers of disease risk in those with established disease or focuses primarily on traditional risk factors (e.g., low-density lipoprotein, fasted blood glucose). Meanwhile, indicators of early cardiometabolic dysfunction in young adults are not well-characterized but are crucial for advancing early detection and prevention efforts. The present review addresses this gap in the literature by providing a synthesis of subclinical indicators of early cardiometabolic dysfunction in young adults, including pathophysiologic vascular/endothelial, metabolic, inflammatory, and neuroendocrine indicators, as well as newly emerging targets. Importantly, it is well-established that cardiometabolic risk and disease differ by biological sex. This review also incorporates sex-specific considerations where possible to address this difference. This review summarizes the available literature regarding subclinical indicators of early cardiometabolic dysfunction, aiming to improve the mechanistic understanding of cardiometabolic disease pathogenesis and offer a novel conceptual framework to advance how researchers and clinicians approach early detection and prevention of cardiometabolic dysfunction and disease.