Cholesterol paradox- High LDL cholesterol level lowers mortality in non-diabetic HF patients

"Non-diabetic HF patients with LDL-c>100 mg/dL were shown to have a 35% reduction in mortality risk versus those with lower values," the researchers reported. "The “cholesterol paradox” in HF also applies to LDL cholesterol in non-DM patients."

Previous studies have shown that low total cholesterol levels are associated with a worse prognosis in patients with established HF. However, evidence is scarce on the impact of LDL cholesterol in heart failure patients. LDL-c is the most atherogenic cholesterol lipoprotein and is an established cardiovascular (CV) risk factor.

To fill this knowledge gap, R. Gouveia and the research team from Portugal sought to evaluate the prognostic effect of LDL-C in patients with HF, both with and without diabetes mellitus (DM).

For this purpose, the researchers retrospectively analyzed outpatients with chronic HF and systolic dysfunction from 2012 to 2018 in an HF clinic. Friedewald's formula was used to calculate the LDL cholesterol. Those without a complete lipid profile were excluded. A total of 522 chronic HF patients were included (mean age 70 years and 66.5% were males) and were followed until January 2021.

The endpoint was all-cause mortality. The prognostic impact of LDL-C was studied using a Cox regression analysis. The LDL cholesterol cut-off used was 100 mg/dL (mean value).

Stratification was done as per the coexistence of diabetes. Multivariate models were built after adjustment for sex, age, coronary artery disease, arterial hypertension, atherosclerotic non-coronary artery disease, statin use, smoking status, creatinine clearance, severity of systolic dysfunction, and evidence-based therapy.

The authors reported the following findings:

• Severe systolic dysfunction was present in 42.7%, 30.5% had coronary heart disease, 60.5% had arterial hypertension, and 41.6% had DM.
• A total of 92.0% were treated with beta-blockers, 87.5% with an ACEi/ARB and 29.1% with an MRA.
• During a median follow-up of 53 months, 45% of patients died.
• Patients with LDL-c ≤100 mg/dL presented an increased multivariate-adjusted risk of all-cause mortality: HR = 1.58.
• When patients were stratified according to DM, LDL-c ≤100 mg/dL was independently associated with increased death risk – HR = 1.55 in patients without DM; in patients with DM, no association was detected – multivariate-adjusted HR = 1.18.

"Lower LDL-c is not associated with survival benefits in HF patients," the researchers wrote. "By the contrary, non-DM HF patients with LDL-c>100 mg/dL have a 34% lower mortality risk when compared with those with lower values".

"The cholesterol paradox in HF also applies to LDL-C in non-diabetic patients," they concluded.

Reference:

Gouveia, R., Madureira, S., Elias, C., Neves, A., Soares, P. R., Soares-Carreira, M., Pereira, J., Ribeiro, A., Amorim, M., Almeida, J., Araújo, J., & Lourenco, P. (2023). Lower low density lipoprotein cholesterol associates to higher mortality in non-diabetic heart failure patients. International Journal of Cardiology Cardiovascular Risk and Prevention, 200197. https://doi.org/10.1016/j.ijcrp.2023.200197