Phenotypes of vulnerability and mortality risk in older adults with cardiovascular disease
C Fumagalli, G Vetere, R Presta, A Argiro', S Baldasseroni, G Sergi, G Limongelli, B Musumeci, C Sardu, L Guasti, M Bo, R Marfella, A Ungar, N MarchionniAbstract
Background
In older adults with cardiovascular disease (CVD) and heart failure (HF), prognosis is strongly influenced by global functional reserve rather than cardiac disease severity alone. However, functional disability, malnutrition, and physical performance are rarely integrated into routine cardiovascular risk stratification.
Purpose
To identify hierarchical phenotypes of vulnerability based on key geriatric domains and to evaluate their association with mortality across different cardiovascular conditions: participants included patients referred for transcatheter aortic valve implantation (TAVI), transthyretin cardiac amyloidosis (ATTR-CA), or chronic HF.
Methods
We prospectively studied 956 consecutive patients aged ≥75 years undergoing comprehensive geriatric assessment across seven tertiary centres. Patients were evaluated for functional disability (Basic Activities of Daily Living, BADL), nutritional status (Mini Nutritional Assessment–Short Form, MNA-SF), and physical performance (Short Physical Performance Battery, SPPB). A hierarchical modelling approach identified vulnerability phenotypes based on the sequential prognostic weight of geriatric domains. Two-year all-cause mortality was assessed using Cox regression and Kaplan–Meier analysis. Incremental prognostic discrimination was evaluated using Uno’s time-dependent C-statistic.
Results
The cohort had a median age of 83 years (IQR 80–86), and 55% were male. Over 2 years, 133 patients (13.9%) died. Functional disability (BADL ≤3) was the strongest independent predictor of mortality (HR 3.78, 95% CI 2.46–5.99; p<0.001). Among non-disabled patients, malnutrition risk (MNA-SF ≤11) remained independently associated with mortality (HR 2.09, 95% CI 1.22–3.42; p<0.001). In patients free from both disability and malnutrition, preserved physical performance (SPPB >6) was protective (HR 0.53, 95% CI 0.27–0.91; p=0.038). Patients with ATTR-CA had overall a worse prognosis than TAVI patients. Five hierarchical vulnerability phenotypes were identified (Figure), showing a stepwise decline in both 1- and 2-year survival. Two-year survival ranged from 92.3% in fully preserved patients to 59.7% in those with combined disability and malnutrition. Sequential inclusion of geriatric domains significantly improved prognostic discrimination beyond age, sex, NYHA class, and clinical context (TAVI vs ATTR-CA vs HF).
Conclusions
A simple hierarchical assessment of disability, nutrition, and physical performance identifies distinct vulnerability phenotypes with markedly different prognoses in older adults with CVD, irrespective of cardiac diagnosis. Integrating multidomain geriatric assessment into cardiovascular care may substantially improve risk stratification and clinical decision-making in this growing population, reducing ageism and futility.Phenotypes of Vulnerability and SurvivalFor image description, please refer to the figure legend and surrounding text.