U-shaped relationship between LDL cholesterol and clinical outcomes in lipid-lowering therapy-naive patients with nonischemic heart failure with reduced ejection fraction
S A Bae, K H Chun, S W Kim, S M Lim, M K Kim, I H JungAbstract
Background and Aims
The relationship between low-density lipoprotein cholesterol (LDL-C) and clinical outcomes in patients with heart failure (HF) remains controversial. We investigated this relationship in patients with nonischaemic HF with reduced ejection fraction (HFrEF).
Methods
Using the Korean National Health Insurance Service database (2009–2017), we identified lipid-lowering therapy-naïve patients hospitalised for nonischaemic HFrEF (left ventricular ejection fraction ≤45%, no significant coronary artery disease). Patients were stratified by baseline LDL-C level as follows: Group 1 (< 70 mg/dL), Group 2 (70–100 mg/dL), Group 3 (100–130 mg/dL), and Group 4 (> 130 mg/dL). Cox regression and restricted cubic spline analyses were used to evaluate the associations with all-cause mortality, cardiovascular death, major adverse cardiovascular events, and HF-related rehospitalisation.
Results
Among 30 757 patients (mean age, 68.1 years; 51.6% men), 11 485 deaths occurred during the 5-year follow-up. Group 3 showed the lowest mortality rate (34.7%). After adjustment, compared with Group 3, the hazard ratios for all-cause mortality were 1.08 (95% confidence interval, 0.99–1.16), 1.08 (1.03–1.13), and 1.09 (1.03–1.15) for Groups 1, 2, and 4, respectively. Cubic spline analysis revealed a U-shaped relationship, with a nadir of approximately 110 mg/dL. Similar patterns were observed for cardiovascular death, major adverse cardiovascular events, and HF-related rehospitalisation.
Conclusions
This large population-based study revealed a novel U-shaped relationship between LDL-C levels and clinical outcomes in patients with nonischaemic HFrEF. These findings challenge the current guidelines advocating LDL-C lowering in high-risk patients, underscoring the necessity for dedicated research of HF-specific lipid management strategies.Graphical abstractFor image description, please refer to the figure legend and surrounding text.Spline curve of adjusted HR for outcomesFor image description, please refer to the figure legend and surrounding text.