Lower low density lipoprotein cholesterol associates to higher mortality in non-diabetic heart failure patients

In patients with established heart failure (HF) low total cholesterol levels associate with worse prognosis. Evidence concerning the impact of Low-density lipoprotein cholesterol (LDL-c) in HF is scarce. We aimed to evaluate the prognostic impact of LDL-c in patients with HF, both with and without diabetes mellitus (DM).

We retrospectively analyzed outpatients with chronic HF with systolic dysfunction followed in our HF clinic from January/2012 to May/2018. LDL-c was calculated using the Friedewald's formula. Patients without a complete lipid profile were excluded. The endpoint under analysis was all-cause mortality. Patients were followed until January/2021. A Cox-regression analysis was used to study the prognostic impact of LDL-c. The LDL-c cut-off used was 100 mg/dL (mean value). Analysis was stratified according to the coexistence of DM. Multivariate models were built adjusting for age, sex, coronary artery disease, atherosclerotic non-coronary artery disease, arterial hypertension, smoking status, statin use, severity of systolic dysfunction, creatinine clearance and evidence-based therapy.

We studied 522 chronic HF patients, mean age was 70 years, 66.5% males. Severe systolic dysfunction was present in 42.7%, 30.5% had coronary heart disease, 60.5% had arterial hypertension, 41.6% had DM. A total of 92.0% were treated with beta blocker, 87.5% with an ACEi/ARB and 29.1% with a MRA. During a median follow-up of 53 (interquartile range 33-73) months, 235 (45%) patients died. Patients with LDL-c ≤100 mg/dL presented increased multivariate-adjusted risk of all-cause mortality: HR = 1.58 (95% CI: 1.08-2.30), p = 0.02. When patients were stratified according to DM, LDL-c ≤100 mg/dL was independently associated with increased death risk - HR = 1.55 (95% CI:1.05-2.30), p = 0.03 in patients without DM; in patients with DM no association was detected - multivariate-adjusted HR = 1.18 (95% CI: 0.77-1.80), p = 0.44.

Non-DM HF patients with LDL-c>100 mg/dL have a 35% reduction in the mortality risk when compared with those with lower values. The "cholesterol paradox" in HF also applies to LDL-c in non-DM patients.