Free fatty acids: independent predictors of long-term adverse cardiovascular outcomes in heart failure patients

Abstract

Abstract Background The association between plasma free fatty acid (FFA) and the outcomes in the heart failure (HF) patients remains unclear. Methods A cohort study among HF patients was performed. Plasma FFA was analyzed as both a continuous and a categorical variable (grouped by tertiles) to assess its association with composite cardiovascular (CV) death and HF hospitalization (CV death & HHP), CV death alone, and all-cause mortality (ACM) using Cox regression models. Subgroup analyses of HF patients with preserved ejection fraction (HFpEF) and mildly reduced/reduced ejection fraction (HFmrEF/HFrEF) were performed. This work also assessed the effectiveness of combining FFA and NT-pro BNP biomarkers for risk stratification by calculating the concordance index (C-index). Results Among the 4,109 HF patients, FFA levels exceeding 0.4–0.42 mmol/L were associated with increased risks of the three outcomes. Patients in the highest FFA tertile faced greater risks than those in the lowest tertile. Adjusted hazard ratios were 1.32 (95% CI: 1.11–1.58) for CV death & HHP, 1.45 (95% CI: 1.16–1.82) for CV death, and 1.39 (95% CI: 1.15–1.68) for ACM, with a maximum follow-up of 8 years (median: 25 months). Subgroup analyses revealed that elevated FFA levels consistently predicted worse outcomes in both HFmrEF/HFrEF and HFpEF patients. The C-index for predicting outcomes was significantly greater when NT-pro BNP and FFA were combined than when NT-pro BNP was used alone (P < 0.01). Conclusion Increased plasma FFA concentrations were independently associated with greater risks of CV death & HHP, CV death, and ACM among HF patients, irrespective of the ejection fraction. The combination of FFA and NT-pro BNP biomarkers significantly improved risk stratification in HF patients.

Keywords

• Free fatty acids
• Heart failure
• Long-term follow-up
• Adverse cardiovascular outcomes
• All-cause mortality