Abstract

Background: Intake of n-3 polyunsaturated fatty acids (n-3 PUFA), including eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), lowers risk of atherosclerotic cardiovascular events, particularly ischemic heart disease. In addition, a ratio of EPA/arachidonic acid (AA) is recently recognized as a risk marker of ischemic heart disease. In contrast, prognostic impact of the EPA, DHA and EPA/AA ratio on patients with heart failure (HF) still remains unclear. Methods and Results: Consecutive 577 patients admitted for HF were divided into 2 groups based on median levels of EPA/AA ratio: low EPA/AA (EPA/AA ≤ 0.32 mg/dl, n=291) and high EPA/AA (0.32 < EPA/AA, n=286) groups. We compared laboratory data, echocardiographic findings and cardio-pulmonary exercise test results, and prospectively followed cardiac and all-cause mortality. The low EPA/AA group, as compared to the high EPA/AA group, had lower levels of EPA and DHA (EPA: 33.9 vs. 86.8 μg/ml, P<0.003; DHA: 107.0 vs. 150.5 μg/ml, P<0.001), and higher levels of AA and dihomosexual linolenic acid (AA: 174.0 vs. 156.5 μg/ml, P<0.001; dihomosexual linolenic acid: 32.4 vs. 29.5 μg/ml, P=0.010). In contrast, body mass index, blood pressure, B-type natriuretic peptide, hemoglobin, estimated GFR, total protein, albumin, sodium, C-reactive protein, left ventricular ejection fraction, peak VO 2 and VE/VCO 2 slope were similar between the two groups. Cardiac mortality (log-rank P=0.004) and all-cause mortality (P<0.001) were higher in the low EPA/AA group than in the high EPA/AA group. In the multivariable Cox proportional hazard analyses, the EPA/AA ratio was an independent predictor of cardiac mortality (HR 0.087, P=0.003) and all-cause mortality (HR 0.233, P=0.009) in HF patients. Conclusions: The EPA/AA ratio was an independent predictor of cardiac and all-cause mortality in HF patients. Thus, taking appropriate management to control EPA/AA balance may improve the prognosis of HF patients.

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