The omega-3 index in patients with heart failure: A prospective cohort study

https://doi.org/10.1016/j.plefa.2018.11.012Get rights and content

Highlights

  • In patients hospitalized for decompensated heart failure, marked depletion of omega-3 fatty acids was detected.

  • Although the Omega-3 index was associated with established risk markers in heart failure, it did not predict mortality risk.

  • The lack of predictive power of the omega-3 index might be due to a very homogeneous distribution in this cohort.

Abstract

Background

Epidemiologic studies on the omega-3 fatty acids eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) in heart failure are scarce, while one large intervention trial demonstrated a modest benefit.

Methods

This is a secondary analysis from the Interdisciplinary Network Heart Failure (INH) program. Patients hospitalized for systolic heart failure were enrolled and followed for 36 months. At baseline, whole blood samples from 899 patients were analyzed for fatty acid composition using a standardized analytical procedure (HS-Omega-3 Index®, O3-I). Associations of the O3-I with markers of heart failure severity, clinical characteristics, biomarkers, and mortality were analyzed.

Results

The mean O3-I was 3.7 ± 1.0%. Patient mean age was 68 ± 12 years (72% male, 43% in New York Heart Association (NYHA) class III or IV, mean LVEF 30 ± 8%). During follow-up 258 patients (28.7%) died. After adjustment for potential confounders, the O3-I showed weak associations with uncured malignancy, end-systolic diameter of the left atrium, left ventricular end-diastolic and end-systolic diameters, and blood lipids and other laboratory parameters (all p < 0.05), but not with NYHA class, left ventricular ejection fraction, and the underlying cause of heart failure. The O3-I did not predict the 3-year mortality risk.

Conclusions

Our results show a marked depletion of omega-3 fatty acids in patients hospitalized for decompensated heart failure (suggested target range 8–11%). Although the O3-I was associated with a panel of established risk indicators in heart failure, it did not predict mortality risk.

Clinical Trial Registration

www.controlled-trials.com; ISRCTN23325295

Introduction

In congestive heart failure (HF), 1 g/day of two omega-3 fatty acids, eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), reduced the 3.9 year total mortality from 29.1 to 27.3% – an absolute difference of 1.8% (GISSI-Heart Failure; GISSI-HF) [1]. Therefore, in a recent scientific advisory the American Heart Association endorsed the use of EPA + DHA supplements in HF with a class IIa recommendation [2]. The beneficial physiologic effects of omega-3 fatty acids on inflammation, lipid profile, myocardial function, and arrhythmias in various diseases have recently been summarized in a State of the Art article [3]. Importantly, in GISSI-HF, patients in the low tertile of plasma baseline levels of marine omega-3 fatty acids had a total mortality of 32.3%, contrasting with 24.2% mortality of patients in the high tertile, i.e. an absolute difference of 8.1% [4]. In patients with HF and depression higher levels of omega-3 fatty acids were also associated with lower mortality [5]. Thus, the relation of levels of omega-3 fatty acids with mortality risk was more pronounced than the effect of supplementation observed, thus, indicating an unrealized therapeutic potential of EPA + DHA.

In contrast to most predictors of mortality risk in HF [6], levels of omega-3 fatty acids can be modified easily, e.g. via increasing intake of omega-3 fatty acids. However, problems of bioavailability exist, and a large inter-individual variability of levels in response to increased intake of omega-3 fatty acids has also been observed [7]. Levels of EPA and DHA in plasma have a high biological variability, and no standardized analytical method exists [8]. This impedes cross-study comparability and the generation of a unified database. In contrast, levels of EPA and DHA in erythrocytes have a low biological variability, and a standardized analytical method has been suggested (“HS-Omega-3 Index®”, O3-I)[9]. For this analytical approach a large number of publications has been accrued that may facilitate paving the way towards transfer of research results into clinical routine [10].

We therefore aimed to characterize in a large and well-characterized prospective cohort of patients hospitalized for systolic HF the associations of the O3-I with clinical characteristics and biomarkers, and to determine its prognostic utility.

Section snippets

Study design and patients

The present study is a secondary analysis of the Interdisciplinary Network Heart Failure (INH) study (www.controlled-trials.com; ISRCTN23325295), a randomized multi-center trial investigating the effects of a disease management program on morbidity, mortality and quality of life for patients with HF. The INH study was carried out by the German Competence Network Heart Failure, a national research alliance, which mandates harmonized standard operating procedures in all its clinical studies to

Results

The mean age of the 899 patients was 68 ± 12 years; 72% of all patients were male, and 43% were in NYHA classes III or IV at baseline. The most frequent underlying cause of HF was coronary heart disease (50%). Detailed baseline patient characteristics are shown in Table 1. During the 36-month follow-up period 258 patients (28.7%) had died.

Values of the mean O3-I were approximately normally distributed (Fig. 1), with a mean value of 3.7 ± 1.0% (median 3.6%, quartiles 3.0%; 4.4%). An overview of

Discussion

The mean O3-I in our study population was 3.7 ± 1.0%, a very low value compared to the suggested optimal range between 8–11% [9]. The O3-I was independent of left ventricular ejection fraction and NYHA functional class but associated with a less conventional panel of factors currently under study as predictors of mortality in patients with HF. In contrast to our hypothesis, the O3-I was not associated with prognosis.

A mean O3-I of 3.7% is substantially lower than observed in unselected German

Conclusion

In patients after an acute decompensation for systolic HF, the O3-I was 3.7 ± 1.0%, i.e. considerably lower than the suggested therapeutic target range of 8–11%. The O3-I was associated with a variety of established indicators of mortality risk in HF. However, during the observation period of three years, the O3-I had no impact on prognosis, which was probably due to the homogenously low levels observed.

Funding

The study was supported by the German Ministry of Education and Research (BMBF, Berlin, Germany, #01GL0304), the German Competence Network Heart Failure (BMBF #01GI0205) and the Comprehensive Heart Failure Center Würzburg (BMBF #01EO1004 & #01EO1504). Omegametrix performed the O3-I measurements in a blinded fashion. None of the funding institutions influenced the study design, conduct, data analysis, or reporting and interpreting of results.

Disclosures

C.v.S. operates Omegametrix, a laboratory for fatty acid analysis, consults for Huntsworth Medical, Marine Ingredients and BASFand received speaker's honoraria from DSM and Santis. RK is employee of Omegametrix. All other authors: none.

Acknowledgments

none

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