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Sex-specific multimorbidity clusters and all-cause mortality in relatively healthy older adults: findings from the ASPREE cohort
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Sex-specific multimorbidity clusters and all-cause mortality in relatively healthy older adults: findings from the ASPREE cohort

Rong Du, Swarna Vishwanath, Zimu Wu, Aung Zaw Zaw Phyo, Suzanne G Orchard, Kerry Sheets, Michael E Ernst and Joanne Ryan
medRxiv : the preprint server for health sciences
Cold Spring Harbor Laboratory
06/22/2026
DOI: 10.64898/2026.06.18.26355909
PMID: 42396311
url
https://doi.org/10.64898/2026.06.18.26355909View
Preprint (Author's original) This preprint has not been evaluated by subject experts through peer review. Preprints may undergo extensive changes and/or become peer-reviewed journal articles. Open Access

Abstract

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. 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 characterised conditions over-represented within clusters, and Cox proportional hazards models assessed associations with all-cause mortality. Among 16,095 participants (mean age 74 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%), anaemia & 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, anaemia & kidney disease cluster in females (aHR 1.96 [1.74-2.21]). Distinct multimorbidity clusters differed by sex and were associated with increased all-cause mortality. These findings may support risk stratification, targeted screening, and more person-centred management of older adults with multimorbidity.

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