Cardiometabolic Multimorbidity: Clustering Phenotypes, Shared Pathways, and Integrated Management Strategies

Abstract

Cardiometabolic multimorbidity (CMM), defined as the co-occurrence of hypertension, type 2 diabetes mellitus, dyslipidemia, obesity and related disorders in the same individual, has become an increasingly severe global public health challenge in the era of multimorbidity. Recent large-scale cohort studies have gone beyond simple counting of disease counts and identified heterogeneous phenotypic clusters, such as metabolically healthy obesity (MHO) and metabolically unhealthy normal weight (MUNW), which show significantly different risks of progressing to overt cardiometabolic multimorbidity. This review compares mainstream clustering analysis methods, explores the common pathophysiological mechanisms underlying these phenotypes, including insulin resistance, chronic low-grade inflammation and neuroendocrine disorders, and summarizes evidence-based integrated management strategies tailored to different comorbidity clusters. By integrating phenotype-specific characteristics with multi-target lifestyle interventions, pharmacotherapy and digital health interventions, this framework promotes a shift from fragmented specialty-based management to precision collaborative management, which is expected to reduce cardiovascular events, renal function decline and premature mortality.