Sex differences in heart failure and cardiometabolic disease: risk, mechanisms, and therapeutic responses

Sex and gender are increasingly recognized as critical determinants in the pathogenesis, clinical courses, and therapeutic responses of both heart failure and cardiometabolic diseases. Heart failure with preserved ejection fraction (HFpEF) is now understood as a predominantly sex-biased syndrome, with its prevalence, inflammatory pathways, fibrotic remodeling, and associations with obesity and diabetes differing markedly between women and men. The interaction between sex hormones, immune function, and metabolic derangements shapes not only HFpEF development but also responses to emerging therapies.Cardiometabolic risk trajectories—including patterns of dyslipidemia, insulin resistance, and visceral adiposity—are shaped by inherent sex differences, leading to disparities in the incidence and progression of cardiovascular disease across the lifespan. Furthermore, recent clinical evidence highlights important sex-based differences in the effectiveness and adverse effect profiles of novel therapeutic agents, such as SGLT2 inhibitors and GLP-1 receptor agonists, especially when examined in real-world populations.This Research Topic aims to advance understanding of how sex and gender influence cardiometabolic risk, heart failure pathophysiology, and responses to established and novel drug classes. We welcome laboratory-based, translational, clinical, or real-world evidence studies and reviews that address, but are not limited to, the following themes:o Pathobiology and mechanisms of HFpEF as a sex-biased syndrome, including the roles of inflammation, fibrosis, and metabolic dysregulationo Sex-based differences in trajectories of dyslipidemia, insulin resistance, and adiposity, and their impact on cardiometabolic and cardiovascular disease risko Sex- and gender-specific responses to SGLT2 inhibitors, GLP-1RAs, and other cardiometabolic therapeutics, including effectiveness and adverse events in real-world settingso The influence of hormonal, genetic, and environmental factors on cardiometabolic and cardiac outcomes in men and womeno Strategies to personalize preventive and therapeutic approaches in heart failure and cardiometabolic disease by incorporating sex and gender perspectivesThrough this collection, we aim to foster new insights into sex- and gender-specific cardiovascular medicine, promote mechanistic discoveries, and inform improved, evidence-based approaches for prevention and treatment in cardiometabolic disease and heart failure. Topic editors: Alexandra Kautzky-Willer, Ilaria Campesi, Fabiana Isabella Gambarin Source: https://www.frontiersin.org/research-topics/81172/sex-differences-in-heart-failure-and-cardiometabolic-disease-risk-mechanisms-and-therapeutic-responses