Frailty Attenuates the Prognostic Value of Multimorbidity in Heart Failure - Insights From the Largest Tertiary Center in the Middle East.
TL;DR
Frailty fundamentally attenuates risk in HF, while multimorbidity stratifies prognosis only when physiological reserve is preserved, while multimorbidity stratifies prognosis only when physiological reserve is preserved.
Abstract
Objective
To evaluate whether frailty modifies the association of multimorbidity in HF.
Methods
A retrospective cohort study of HF patients. Multimorbidity was quantified using 26 conditions and categorized as low (≤4), intermediate (5-7), or high (>8). Frailty was defined using a multimodal construct integrating functional, nutritional, and biochemical domains. All-cause mortality was assessed using cox models with frailty-multimorbidity interaction testing. Charlson Comorbidity Index (CCI) was used for validation.
Results
Among 18,058 patients (median age 74 years; 62% male; 64% frail), 57% died over a median follow-up of 4.0 years (IQR 1.3-7.7). Multimorbidity burden comprised 30.5% low, 48% intermediate, and 21.5% high. Frailty was associated with a 91% higher mortality risk (adjusted HR 1.91; 95% CI 1.85-2.00). Compared with low multimorbidity, intermediate and high burden were associated with an independent 8% and 20% higher mortality risks, respectively (95% CI 1.02-1.14 and 1.13-1.27; both p<.001). However, the association of multimorbidity differed by frailty such that among non-frail patients, intermediate and high multimorbidity increased mortality by 18% and 42% whereas in frail patients, the association was attenuated, with no excess risk for intermediate burden and only 13% increase for high burden (p-for-interaction <.001). CCI analyses was consistent, though differed among females and HFpEF.
Conclusion
Frailty fundamentally attenuates risk in HF, while multimorbidity stratifies prognosis only when physiological reserve is preserved.