High Low-Density Lipoprotein Cholesterol Associated With Improved Survival in Acutely Decompensated Heart Failure

In a population of patients admitted for acutely decompensated heart failure (HF), higher levels of low-density lipoprotein cholesterol (LDL-C) were independently associated with improved survival outcomes, according to study results published in the Portuguese Journal of Cardiology.¹

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Determining new biomarkers that can indicate the potential development or severity of HF remains essential given the immense health burden on patients across the globe. Existing literature on the potential association between cholesterol levels and HF morbidity and mortality suggests varying conclusions.^1-4

Some clinical trials reported a major reduction in cardiovascular (CV) events with LDL-C levels below previously established targets, although the current authors note that only a minority of patients enrolled in those trials had co-existing HF. Studies conducted previously have observed an independent association between low cholesterol levels and adverse outcomes and mortality in patients with chronic HF. Most pertinent for this current investigation, a similar association was found by Horwich et al in patients admitted for acutely decompensated HF. In that investigation, total cholesterol was inversely related to length of stay, symptoms at discharge, and in-hospital mortality.^2-4

With this literature in consideration, the current authors aimed to better elucidate the association between LDL-C levels and prognosis in patients admitted for acutely decompensated HF. They sought to establish the lowest LDL-C value associated with worse prognosis in this population and contribute to more accurately recommended CV risk-based LDL-C targets in the general population.¹

A single-center, observational, retrospective study was designed to analyze consecutive patients admitted for acute HF from January 2016 to December 2018 with a lipid panel performed on hospital admission. The primary end point was all-cause mortality at 1-year follow-up, with secondary end points including HF hospitalizations, major thrombotic events, and net clinical benefit, defined by the composite of the previous factors, the investigators wrote.¹

In total, 167 patients fulfilled inclusion criteria for the trial. The median LDL-C level across the patient population was 82 mg per dL, and 45.5% of the patients presented with LDL-C levels below the target proposed for their estimated CV risk, per the ESC Dyslipidemia and Cardiovascular Prevention Guidelines.¹

Regarding the primary outcome, 24 (14.4%) patients died during the follow-up period. Furthermore, serum LDL-C, hemoglobin, and body mass index (BMI) with female gender were significantly associated with mortality. Upon adjusting for clinically relevant factors in a multivariate analysis, higher LDL-C and BMI were determined to be independent protective factors for mortality, with a 4-fold increase in survival probability for each 1 mg/dL increase in serum LDL-C, according to the investigators.¹

When only considering patients at high and very-high CV risk, a higher LDL-C level remained a protective factor for 1-year mortality on multivariate analysis. In addition, when only considering individual CV risk, patients with an LDL-C level below the recommended target presented a heightened risk of mortality. In a critical finding, the minimum value of LDL-C not associated with increased risk of 1-year mortality was 88 mg/dL, whereas in patients with a high and very-high CV risk, the cut-off was 84 mg/dL. At the same time, an LDL-C level below 88 mg/dL was linked to a meaningful increase in mortality risk.¹

In their discussion, the investigators noted that the cut-off they determined in this study is lower than the suggested targets for moderate- and low-CV risk patients and is significantly higher than the proposed targets for high- and very-high-risk patients. They also acknowledge that recommending more liberal LDL-C control in patients with HF could lead to more thrombotic events being reported but ultimately believe the trade-off would be beneficial for patients in this population.¹

“These findings challenge the current guidelines and raise questions about the application of standard LDL-C targets to patients with established HF,” the investigators wrote in their conclusion. “Nevertheless, these results should be externally validated, and further research is warranted to better understand the role of LDL-C in HF prognosis as well as to refine guidelines for lipid management in this specific patient population.”¹

REFERENCES

1. Brito J, Rin J, Duarte C, et al. Association of LDL-cholesterol with prognosis in patients admitted for acutely decompensated heart failure. Portuguese Journal of Cardiology. 2025. doi:10.1016/j.repc.2024.09.004

2. Schwartz GC, Steg G, Szarek M, et al. Alirocumab and cardiovascular outcomes after acute coronary syndrome. N Engl J Med. 2018;379(2):2097-2107. doi:10.1056/NEJMoa1801174

3. Rauchhaus M, Clark AL, Doehner W, et al. The relationship between cholesterol and survival in patients with chronic heart failure. Journ Amer College Cardio. 2003;42(11):1933-1940. doi:10.1016/j.jacc.2003.07.016

4. Horwich TB, Hernandez AF, Dai D, et al. Cholesterol levels and in-hospital mortality in patients with acute decompensated heart failure. American Heart Journal. 2008;156(6):1170-1176. doi:10.1016/j.ahj.2008.07.004