No effect of n3 fatty acids supplementation on NT proBNP after myocardial infarction: The Alpha Omega Trial

Background: heart failure is a major risk factor for cardiovascular mortality, for which n 3 fatty acids may have beneficial effects. We examined the effect of marine eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), and plant derived alpha linolenic acid (ALA) on N Terminal pro Brain Natriuretic Peptide (NT proBNP), a biomarker of heart failure. Methods: we randomly assigned 4837 post myocardial infarction patients, aged 60 to 80 years (82 per cent men), to margarines supplemented with a targeted additional intake of 400 mg per day EPA and DHA, 2 g per day ALA, EPA DHA plus ALA, or placebo for 40 months. In a random selection of 639 patients, NT minus proBNP was determined both at baseline and at the end of follow up. NT proBNP was loge transformed and analysed by type of treatment using analysis of covariance adjusting for baseline NT proNBP. Results: patients consumed on average 19.8 g margarine per day, providing an additional amount of 238 mg per day EPA with 158 mg per day DHA, 1.98 g per day ALA, or both, in the active treatment groups. In the placebo group, the geometric mean level NT proBNP increased from 245 ng per l  after 40 months. NT proBNP levels were not affected by ALA , EPA DHA , nor EPA DHA plus ALA (9 percent versus placebo treatment. Conclusions: supplementation with modest amounts of EPA DHA, with or without ALA, did not have a significant effect on NT proBNP levels in patients with a history of myocardial infarction. (Authors abstract)

Epidemiological studies have demonstrated an inverse association between consumption of fish and risk of heart failure (HF). In the Alpha Omega Trial, totalling 4837 patients, the authors showed that low dose n 3 fatty acids did not significantly reduce the rate of major cardiovascular events in post myocardial infarction (MI) patients.  In an ancillary study of the Alpha Omega Trial the authors examined the effect on NT pro BNP of long term supplementation of marine n 3 fatty acids EPA and DHA, and of alpha linolenic acid (ALA) among post MI patients, because they are at increased risk of HF.   An increased level of the stable biomarker NT pro BNP is an indicator of myocardial ischaemia and left ventricular dysfunction, and therefore a good proxy of HF with independent prognostic value of mortality. An additional daily intake of 396 mg EPA DHA with or without 2 g ALA over 40 months did not have a beneficial effect in addition to cardiovascular drug treatment on the level of NT proBNP in patients with a history of MI. In the placebo group there was a 20 per cent  increment of NT proBNP levels after 40 months.

In the Alpha Omega trial the majority of patients were on statin treatment. It has been shown that low dose n 3 fatty acids in addition to statin therapy do not have a beneficial effect on inflammation as reflected by the level of high sensitivity C reactive protein. The present study was too small to merit subgroup analysis in non statin users to explore the effect on NT proBNP level. This issue should be studied in a larger population of non statin users.  Although NT proBNP is an established marker for HF, non cardiac factors may also affect level of serum NT proBNP: levels are higher in women compared to men, increase with ageing, and are lower in people with obesity compared to those with a normal body mass index.  Differences in underlying causes of HF, more severe HF and the higher daily doses of EPA DHA and ALA may explain the lack of effect in this study compared to other trials. This study has several limitations. At baseline there were differences between the four groups with regard to current smoking and kidney function.
Future intervention studies should explore the effects of higher doses of n 3
fatty acids supplementation on NT proBNP in larger numbers of subjects. (Editors comments)