Frailty determinants in heart failure: Inflammatory markers, cognitive impairment and psychosocial interaction

This study aimed to identify factors associated with frailty in heart failure (HF) patients, focusing on demographic, biochemical and health-related variables. It also explored the correlation between frailty and comorbidities such as malnutrition, cognitive impairment and depression, assessing how these factors interact to influence frailty risk.

A total of 250 HF patients (mean age 73.5 ± 7.2 years; 45.6% female) hospitalized for acute decompensated HF were included. Frailty was assessed using Fried phenotype criteria. Cognitive function, depression and nutritional status were evaluated using validated instruments [Mini-Mental State Examination (MMSE), Patient Health Questionnaire-9 (PHQ-9) and Mini Nutritional Assessment (MNA)]. Biochemical markers included C-reactive protein (CRP), N-terminal prohormone of brain natriuretic peptide (NT-proBNP), haemoglobin, estimated glomerular filtration rate (eGFR) and systolic blood pressure (SBP). Statistical analyses, including logistic regression, were performed to assess associations and odds ratios (ORs) for frailty, adjusted for inflammation and HF type.

Frailty was present in 60.4% of patients. Frail individuals exhibited significantly higher CRP (median 4.60 vs. 2.54 mg/L, P < 0.001) and NT-proBNP (median 2558.8 vs. 1102.6 pg/mL, P = 0.001) and lower haemoglobin (13.7 vs. 14.3 g/dL, P = 0.012), eGFR (62 vs. 71 mL/min/1.73 m², P = 0.025) and SBP (130 vs. 134 mmHg, P = 0.026). Each 10% increase in CRP was associated with a 5.5% increase in frailty odds (P < 0.001). Frailty was linked to cognitive impairment (OR 2.1, P = 0.018), malnutrition (OR 3.0, P < 0.001) and depression (OR 3.1, P < 0.001), while high adherence to treatment reduced frailty risk by 78.9% (P = 0.027). Interactions were observed between cognitive impairment and body mass index (BMI) (P = 0.020), where higher BMI mitigated the frailty odds difference between cognitively impaired and unimpaired patients. Depression's association with frailty odds varied by adherence levels (P = 0.034) and central obesity (P = 0.047), with the absence of depression offering protection against frailty in patients with central obesity. These interactions remained significant after adjustment for HF type and left ventricular ejection fraction (LVEF) and were consistent across stratifications by these factors.

Frailty in HF is influenced by inflammatory markers, cognitive impairment and psychosocial factors. Elevated CRP and NT-proBNP were strong predictors of frailty. Cognitive impairment and depression were key modifiable factors, interacting with BMI, adherence and obesity. Targeting these factors with early interventions could mitigate frailty risk, improving outcomes and quality of life in HF patients.