Assessing the relationship between multimorbidity, NCD configurations, frailty phenotypes, and mortality risk in older adults

Background: Older adults are increasingly susceptible to prolonged illness, multiple chronic diseases, and disabilities, which can lead to the coexistence of multimorbidity and frailty. Multimorbidity may result in various noncommunicable disease (NCD) patterns or configurations that could be associated with frailty and death. Mortality risk may vary depending on the presence of specific chronic diseases configurations or frailty.

Methods: The aim was to examine the impact of NCD configurations on mortality risk among older adults with distinct frailty phenotypes. The population was analyzed from the Costa Rican Longevity and Healthy Aging Study Cohort (CRELES). A total of 2,662 adults aged 60 or older were included and followed for 5 years. Exploratory factor analysis and various clustering techniques were utilized to identify NCD configurations. The frequency of NCD accumulation was also assessed for a multimorbidity definition. Frailty phenotypes were set according to Fried et al. criteria. Kaplan‒Meier survival analyses, mortality rates, and Cox proportional hazards models were estimated.

Results: Four different types of patterns were identified: ‘Neuro-psychiatric’, ‘Metabolic’, ‘Cardiovascular’, and ‘Mixt’ configurations. These configurations showed a higher mortality risk than the mere accumulation of NCDs [Cardiovascular HR:1.65 (1.07–2.57); ‘Mixt’ HR:1.49 (1.00-2.22); ≥3 NCDs HR:1.31 (1.09–1.58)]. Frailty exhibited a high and constant mortality risk, irrespective of the presence of any NCD configuration or multimorbidity definition. However, HRs decreased and lost statistical significance when phenotypes were considered in the Cox models [frailty + ‘Cardiovascular’ HR:1.56 (1.00-2.42); frailty + ‘Mixt’:1.42 (0.95–2.11); and frailty + ≥ 3 NCDs HR:1.23 (1.02–1.49)].

Conclusions: Frailty accompanying multimorbidity emerges as a more crucial indicator of mortality risk than multimorbidity alone. Therefore, studying NCD configurations is worthwhile as they may offer improved risk profiles for mortality as alternatives to straightforward counts.