Serum n-3 and n-6 polyunsaturated fatty acid profile as an independent predictor of cardiovascular events in hemodialysis patients

Abstract

Background: Unlike the n-6 polyunsaturated fatty acid (PUFA) arachidonic acid (AA), n-3-PUFAs such as eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) appear to have beneficial effects on inflammation, thrombosis, and cardiovascular disease (CVD). We examined possible alterations in serum PUFA profiles in patients on maintenance hemodialysis therapy and its association with CVD risk.

Study design: An observational study including cross-sectional and longitudinal analyses.

Setting & participants: Single-center study of 517 maintenance hemodialysis patients in an urban area in Japan.

Predictors: Serum EPA, DHA, and AA concentrations and EPA:AA, DHA:AA, and (EPA+DHA):AA ratios.

Outcomes: CVD events, including ischemic heart disease, stroke, peripheral artery disease, pulmonary edema, and valve disease.

Results: Hemodialysis patients showed lower (EPA+DHA):AA, EPA:AA, and DHA:AA ratios than 122 controls similar in age and sex. During follow-up, 190 CVD events were recorded. (EPA+DHA):AA ratio was not associated significantly with CVD in unadjusted analysis, but was associated significantly and inversely with CVD in Cox models adjusted for age and other confounding variables, with HRs in the range of 1.71-1.99 in the lowest versus highest quartile of (EPA+DHA):AA ratios. Similarly, EPA:AA and DHA:AA ratios showed inverse associations with CVD, whereas serum EPA, DHA, and AA concentrations were not predictive of CVD.

Limitations: No information for dietary intake, use of dietary supplements, or cell membrane PUFA content.

Conclusions: In hemodialysis patients, serum PUFA profile is unfavorably altered, and the low n-3-PUFA:AA ratios are independent predictors of CVD.

Keywords: arachidonic acid (AA); cardiovascular disease; docosahexaenoic acid (DHA); eicosapentaenoic acid (EPA); hemodialysis; n-3-polyunsaturated fatty acid (PUFA).