Abstract 11825: The Association Between Frailty and Vascular Endothelial Growth Factor Families in Patients With Heart Failure: The PREHOSP-CHF Study

Background: Frailty is a complex clinical syndrome associated with ageing and chronic illness, and is common in heart failure (HF). Vascular endothelial dysfunction including maladaptive angiogenesis and lymphangiogenesis is involved in the pathogenesis of HF, and is also considered to be the causes of frailty. We investigated the association of vascular endothelial growth factor (VEGF) families, central regulators of angiogenesis and lymphangiogenesis, with frailty, and prognostic role of these cytokines in frail HF patients. Methods: We performed a multicenter prospective cohort study to determine the predictive value of VEGF families for prognosis among patients with HF. A total of 1,024 patients (mean age, 75.5 years, 58.7% male) were included in the analyses. Serum levels of VEGF, VEGF-C, VEGF-D, and soluble VEGF receptor-2 (sVEGFR-2) were measured. Frailty was assessed by Canadian Study of Health and Aging Clinical Frailty Scale (CFS). Results: A total of 256 (25.1%) patients had frailty (CFS≥5) at baseline. Frail patients were older, more likely female, and had lower body mass index, higher NYHA class, and higher rates of prior hospitalization for HF, HF with preserved ejection fraction, anemia, cerebrovascular disease, and dementia. N-terminal pro brain natriuretic peptide, high sensitivity troponin I, and high sensitivity C-reactive protein levels were higher in frail patients. During the 2-year follow-up, 211 all cause death occurred. In Kaplan-Maier analysis, frail patients showed significantly higher incidence of all-cause (hazard ratio [HR], 4.12; 95% confidence interval [CI], 3.14-5.42). Regarding VEGF families, frail patients had significantly lower levels of sVEGFR-2 and VEGF-C, and higher levels of VEGF-D. Multiple regression analysis revealed that VEGF-C had inverse correlation with CFS (P, 0.03). After adjusting for clinical confounders, a low VEGF-C level was independently associated with all-cause death in frail patients (HR, 0.74; 95%CI, 0.58-0.94 for 1-SD increase), but was not in non-frail patients (HR, 0.87; 95%CI, 0.64-1.14 for 1-SD increase) (P for interaction, 0.09). Conclusions: In HF patients, a low VEGF-C value was associated with frailty and was independent risk for all-cause death in frail patients.