Different association of HDL-C, apoA-I, and HDL-C/apoA-I with multiple outcomes in HFrEF patients.

Background: High-density lipoprotein-cholesterol (HDL-C) has been considered a cardioprotective factor for several decades. However, its association with outcomes in patients with heart failure with reduced ejection fraction (HFrEF) remains controversial. We aimed to investigate the association of HDL-C, apolipoprotein A-I (apoA-I), and the HDL-C/apoA-I ratio with multiple outcomes of HFrEF patients and establish prognostic models using machine learning methods.

Methods And Results: This was a retrospective, single-center study. The associations between lipid levels and multiple outcomes were examined using logistic regression analysis. Prognostic models for multiple outcomes were further established using four machine learning methods. A total of 352 HFrEF patients were visited successfully. In the multivariable-adjusted logistic regression analysis, HDL-C did not show a significant association with any of the studied outcomes; apoA-I was marginally unassociated with all-cause rehospitalization (adjusted odds ratio [aOR] = 0.62, p = 0.063) but was significantly negatively associated with all-cause death (aOR = 0.53, p = 0.038), rehospitalization for cardiovascular or cerebrovascular disease (aOR = 0.43, p < 0.001), and rehospitalization for heart failure (aOR = 0.55, p = 0.024); apoA-I was also significantly positively associated with left ventricular ejection fraction (LVEF) improvement (aOR = 2.00, p = 0.039). Although several p-values were not statistically significant, both the first and third HDL-C/apoA-I groups showed an increased incidence rate for all adverse outcomes compared with the middle group and a decreased incidence rate for LVEF improvement. In the machine learning analysis, the support vector machine and extreme gradient boosting models demonstrated better predictive performance. For each outcome prognosis, apoA-I and logarithmic N-terminal pro-B-type natriuretic peptide were automatically selected.

Conclusion: Among HFrEF patients, apoA-I may be a better marker for predicting outcomes than HDL-C. Both low and high levels of HDL-C/apoA-I may indicate a poor prognosis of HFrEF patients.