Age-Dependent Sex Differences in the Prevalence and Prognosis of Multimorbid Conditions in Individuals with Heart Failure in Japan

Background Multimorbidity is common among patients with heart failure (HF) and contributes to poor prognosis; however, the influence of age group and sex differences on the prevalence and outcomes of multimorbidity remains unclear. Methods This multicenter retrospective study included 3,004 hospitalized patients with HF. Multimorbidity was defined as the presence of two or more comorbidities and was quantified for stratification of comorbidity burden using the age-adjusted Charlson Comorbidity Index (CCI). Patients were dichotomized into high-and low-CCI groups based on the median CCI and were evaluated for prognosis using a composite endpoint of all-cause death or HF readmission. Results Multimorbidity increased with age but declined slightly in individuals aged > 85 years. And sex differences were observed, with males demonstrating a steeper increase in multimorbidity prevalence than females. Event-free survival rates were lower in the high-CCI group (hazard ratio [HR], 1.786; 95% confidence interval [CI], 1.483–2.151), consistent across sexes (males: HR, 1.927; 95% CI, 1.520–2.443; females: HR, 1.581; 95% CI, 1.171–2.135). Among individuals aged ≥75 years with a high CCI, males had a stronger association with events than females (HR, 1.334; 95% CI, 1.031–1.727). Conclusions In individuals with HF, sex differences were evident in the prevalence of multimorbidity by age group and were associated with prognosis in older populations with a high comorbidity burden. Recognizing these differences is essential for tailoring HF management strategies to improve outcomes in individuals with multimorbid HF. Clinical trial registration URL: https://www.umin.ac.jp/ctr ; unique identifier: UMIN000054854 Clinical perspective What Is New? This multicenter study demonstrated that age-dependent sex differences exist in both the prevalence and prognostic impact of multimorbidity among Japanese individuals with heart failure. A three-way interaction analysis (age × sex × comorbidity burden) utilizing restricted cubic splines revealed that, among individuals with a high comorbidity burden, sex-related prognostic differences became increasingly pronounced with age, with older males exhibiting a higher risk than females. What Are the Clinical Implications? Incorporating age-and sex-specific risk assessments based on comorbidity burden may enhance individualized management strategies and improve clinical outcomes in individuals with heart failure, particularly in older adults with multiple comorbidities.