Sex-specific multimorbidity clusters and all-cause mortality among community-dwelling older adults: findings from the ASPREE cohort

Abstract Background Multimorbidity is common in older adults, but sex differences in chronic condition clustering remain unclear. This study explored multimorbidity clusters and their associations with all-cause mortality among community-dwelling adults aged 70 years and over. Methods This was a secondary analysis of data from 16,095 Australian ASPREE participants aged ≥70 years without prior dementia or cardiovascular disease. Fifteen baseline chronic conditions were grouped using latent class analysis (LCA). Observed-to-expected (O/E) ratios characterized conditions over-represented within clusters, and Cox proportional hazards models assessed associations with all-cause mortality. Results Among 16,095 participants (mean age 75.3 years), 88.3% had multimorbidity at baseline; 4,217 deaths occurred over a median follow-up of 10.85 years. Five clusters were identified overall: hypertension & dyslipidemia (52.1%), gout & metabolic (14.4%), depressive symptoms, osteoporosis & frailty (10.0%), anemia & kidney disease (10.2%), and hypotension, thyroid disorder & past cancer (13.3%). Sex-stratified analyses revealed three clusters in males and four in females. The frailty, depressive symptoms & osteoporosis cluster was associated with higher mortality in both sexes (aHR 1.56 [95% CI 1.40–1.73] in males; 1.68 [1.49–1.89] in females). Higher mortality was also observed for the metabolic, gout & kidney disease cluster in males (aHR 1.63 [1.47–1.81]) and the gout, anemia & kidney disease cluster in females (aHR 1.96 [1.74–2.21]). Conclusions Distinct multimorbidity clusters were identified overall and in sex-stratified analyses. These hypothesis-generating findings suggest the potential clinical utility of multimorbidity clusters to identify individuals at increased risk of death, but further research is needed.