Sex-specific cardiometabolic multimorbidity, metabolic syndrome and left ventricular function in heart failure with preserved ejection fraction in the UK Biobank.

BACKGROUND: Cardiometabolic disturbances play a central role in the pathogenesis of heart failure with preserved ejection fraction (HFpEF). Due to its complexity, HFpEF is a challenging condition to treat, making phenotype-specific disease management a promising approach. However, HFpEF phenotypes are heterogenous and there is a lack of detailed evidence on the different, sex-specific profiles of cardiometabolic multimorbidity and metabolic syndrome present in HFpEF. METHODS: We performed a retrospective, modified cross-sectional study examining a subset of participants in the UK Biobank, an ongoing multi-centre prospective cohort study in the United Kingdom. We defined HFpEF as a record of a heart failure diagnosis using ICD-10 code I50, coupled with a left ventricular ejection fraction (LVEF) ≥ 50% derived from cardiac magnetic resonance (CMR) imaging. We examined sex-specific differences in cardiometabolic comorbidity burden and metabolic syndrome, performed latent class analysis (LCA) to identify distinct clusters of patients based on their cardiometabolic profile, and compared CMR imaging-derived parameters of left ventricular function at rest in the different clusters identified to reflect possible differences in adverse cardiac remodelling. RESULTS: We ascertained HFpEF in 445 participants, of which 299 (67%) were men and 146 (33%) women. The median age was 70 years old (interquartile range: [66.0-74.0]). A combination of hypertension and obesity was the most prevalent cardiometabolic pattern both in men and women with HFpEF. Most men had 2-3 clinical cardiometabolic comorbidities while most women had 1-2, despite a similar metabolic syndrome profile (p = 0.05). LCA revealed three distinct, clinically relevant phenogroups, namely (1) a most male and multimorbid group (n = 117); (2) a group with a high prevalence of severe obesity, abnormal waist circumference and with the highest relative proportion of females (n = 116); and finally (3) a group with an apparently lower comorbidity burden aside from hypertension (n = 212). There were significant differences in clinical measurements and medication across the three phenogroups identified. Cardiac output at rest was significantly higher in group 2 vs. group 3 (males: median 5.6 L/min vs. 5.2 L/min, p