Apolipoprotein E4 as a genetic biomarker of mortality in patients with dilated cardiomyopathy

Introduction

Dilated cardiomyopathy (DCM) is a leading cause of chronic heart failure and heart transplantation, with persistently high mortality despite therapeutic advances. Novel prognostic markers are needed to improve risk stratification.

The apolipoprotein E ε4 allele (ApoE4) is a known risk factor for Alzheimer’s disease and atherosclerosis, but its role in non-ischemic cardiomyopathy remains unclear.

Purpose

Building on our previous finding that ApoE4 is an independent risk factor for developing DCM, we hypothesized that ApoE4 predicts adverse outcomes in patients with dilated cardiomyopathy. We conducted a longitudinal study to identify independent mortality risk factors and evaluate the prognostic impact of ApoE4 on survival.

Methods

We enrolled 111 Caucasian patients with dilated cardiomyopathy and chronic heart failure (86 men, 25 women; mean age 66 ± 8.7 years). All underwent clinical, biochemical, and echocardiographic assessment. ApoE genotyping was performed using PCR with allele-specific primers. Patients were stratified by the presence of the ApoE4 allele and followed for five years. The primary endpoint was all-cause mortality.

Results

During a mean follow-up of 56.1 ± 14.9 months, 85 patients (76.6%) died, yielding a 5-year survival rate of 23.4%. The ApoE4 allele was present in 52 patients (46.8%). Mortality was higher among carriers (88.5%) than non-carriers (66.1%).

Multivariate Cox analysis identified older age, male sex, diabetes mellitus, increased left atrial dimension, impaired right ventricular function, and ApoE4 carriage as independent predictors of mortality (p < 0.05).

Kaplan–Meier analysis showed significantly reduced survival in ApoE4 carriers (log-rank p < 0.0001). Median survival was 19 months in carriers versus 45 months in non-carriers. ApoE4 carriage was associated with a markedly increased mortality risk (HR 3.36, 95% CI 2.02–5.59; log-rank HR 2.52, 95% CI 1.56–4.08).

Conclusion

This study demonstrates for the first time that ApoE4 is independently associated with significantly poorer long-term survival in patients with dilated cardiomyopathy. Beyond its established role in lipid metabolism and atherosclerosis, ApoE4 may contribute not only to disease susceptibility but also to progression and mortality in DCM. The allele’s association with inflammation, oxidative stress, and impaired myocardial energetics may contribute to adverse remodeling and disease progression. These findings support ApoE4 as a potential biomarker for risk stratification and highlight the feasibility of genotype-guided clinical monitoring in DCM.Prognostic factors in patients with DCMFive-year survival analysis