Interplay between frailty and cardiometabolic disorders: from pathophysiology to clinical implications
Gaetano Santulli, Giada Sabatelli, Brandon Wang, Marco Savino, Francisco Bruno, Stanislovas S. Jankauskas, Annamaria Massaro, C Peluso, María Vicario, Luigi Savino, Fahimeh Varzideh, Martina D’Onghia, Pasquale Mone
Abstract
Frailty and cardiometabolic disorders are highly prevalent in the aging population and frequently coexist, amplifying each other's adverse effects. Frailty, defined by decreased physiological reserves and heightened vulnerability to stressors, often occurs alongside cardiometabolic conditions such as diabetes, hypertension, and cardiovascular disease. The intersection of these conditions poses substantial clinical challenges, impacting morbidity, mortality, and quality of life. Understanding the shared pathophysiological mechanisms underlying frailty and cardiometabolic disorders is critical for guiding effective prevention and management strategies. This systematic review, registered in PROSPERO (CRD420251164236), documents current knowledge on the definitions, epidemiology, and pathophysiology of frailty in the context of cardiometabolic disorders and highlights the main clinical implications of their coexistence. Additionally, we discuss evidence-based strategies for assessment, prevention, and management, emphasizing the importance of an integrated approach to improve outcomes in older adults. These insights aim to inform about targeted interventions that can mitigate risk, enhance resilience, and optimize patient care.