High leptin levels are associated with increased risk for fatal cardiovascular (CV) events and worsening heart failure (HF), according to results of a study published in Nutrition, Metabolism & Cardiovascular Diseases.

This analysis pooled data from 2 prospective cohort studies, EUROASPIRE III and IV, which were collected in 2006 to 2007 and 2012 to 2013, respectively, in the Czech Republic. Patients (N=975) aged  younger than 71 years who were hospitalized for coronary artery disease (CAD) were evaluated for demographic and clinical characteristics and serum biomarkers. Risk for all-cause mortality, CV death, nonfatal CV events, and hospitalization for HF at 5 years were evaluated.

The patients are 79.5% men, aged mean 64.3±8.98 years, BMI is 29.4±4.41, leptin levels are 35.6±638.2 ng/mL, 95.3% have a history of coronary revascularization, 62.8% have increased waist circumference, and 40.4% have poor glycemic control.


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At 5 years, all-cause mortality had occurred among 12.3%, CV mortality among 8.4%, and nonfatal CV events among 12.2% of patient and 8.6% were hospitalized for HF.

In the multivariate analysis, leptin levels are related to male gender (β, -0.4086; P <.0001), estimated glomerular filtration rate (β, -0.0032; P <.0001), mean blood pressure (β, -0.0017; P =.020), BMI (β, 0.0181; P <.0001), and waist circumference (β, 0.0114; P <.0001).

Stratified by leptin quartiles, patients with high leptin levels (³18.9 ng/mL; n=244) are older and more are women, have higher BMI, increased waist circumference, diabetes, symptomatic HF, and a lower estimated glomerular filtration rate (all P £.019).

Five-year risk for all-cause mortality is associated with brain natriuretic peptide of 100 or higher ng/mL (adjusted hazard risk ratio [aHRR], 2.78; P <.0001), male gender (aHRR, 2.76; P <.0001), leptin concentration of 18.9 or higher ng/mL (aHRR, 2.10; P =.003), and age (aHRR, 1.08; P <.0001).

Risk for CV mortality is associated with brain natriuretic peptide of 100 or higher ng/mL (aHRR, 3.77; P <.0001), leptin concentration of 18.9 or higher ng/mL (aHRR, 2.65; P =.001), use of renin-angiotensin-aldosterone system blockers (aHRR, 1.37; P =.038), and age (aHRR, 1.09; P <.0001).

Nonfatal CV events are associated with brain natriuretic peptide of 100 or higher ng/mL (aHRR, 1.55; P =.035) and age (aHRR, 0.97; P =.038).

Hospitalization for HF risk is associated with brain natriuretic peptide of 100 or higher ng/mL (aHRR, 4.39; P <.0001), leptin concentration of 18.9 or higher ng/mL (aHRR, 1.95; P =.020), estimated glomerular filtration of less than 60 mL/min (aHRR, 1.69; P =.041), low density lipoprotein of 1.8 or higher mmol/L (aHRR, 0.60; P =.041), and history of coronary revascularization (aHRR, 0.45; P =.036).

Stratified by leptin levels, high levels are associated with poorer all-cause mortality (P =.006), CV death (P =.002), and HF hospitalization (P <.001) survival rates.

The major limitation of this study is that leptin was only evaluated at a single time point.

“High circulating leptin concentrations indicate a poor survival of well-stable CAD patients independent of conventional cardiovascular risk factors and other characteristics,” the study authors wrote. “…further studies of the leptin pathway and related physiology seem to be warranted, namely in the context of possible new treatment targets in heart failure.”

Reference

Mayer O Jr, Bruthans J, Seidlerová J, et al. High leptin status indicates an increased risk of mortality and heart failure in stable coronary artery disease. Nutr Metab Cardiovasc Dis. Published online June 15, 2022. doi:10.1016/j.numecd.2022.06.006