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ω-3 Fatty acids, atherosclerosis progression and cardiovascular outcomes in recent trials: new pieces in a complex puzzle
  1. Jason H Y Wu1,
  2. Dariush Mozaffarian1,2,3
  1. 1Department of Epidemiology, Harvard School of Public Health, Boston, MA
  2. 2Department of Nutrition, Harvard School of Public Health, Boston, Massachusetts, USA
  3. 3Division of Cardiovascular Medicine and Channing Division of Network Medicine, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts, USA
  1. Correspondence to Dr Jason H Y Wu, 665 Huntington Ave, Kresge Building-913, Boston, MA, 02115, USA; jasonwu{at}

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The cardiovascular effects of seafood-derived n-3 polyunsaturated fatty acids (n-3 PUFA) have been examined in a diverse and continually expanding array of studies ranging from in vitro molecular experiments to large randomised controlled trials. In contrast to earlier trials, recent clinical trials have not observed significant effects of n-3 PUFA supplementation on cardiovascular disease (CVD) events.1 ,2 These mixed findings have stimulated renewed debate and interest about the role of n-3 PUFA for CVD prevention and treatment.

Sekikawa and colleagues investigated whether circulating n-3 PUFA levels were associated with differences in new-onset of coronary artery calcification (CAC) between middle-aged men in Japan and the USA.3 Measurement of CAC by electron beam CT provides an estimate of overall coronary atherosclerotic burden. While CAC does not necessarily identify with plaque morphology or propensity for rupture, overall CAC burden does predict future risk of clinical CVD events. In this case, investigating the association of circulating n-3 PUFA with serial measures of CAC addresses the interesting hypothesis that these fats might slow atherosclerosis progression, providing mechanistic insight that would be complimentary to studies of clinical endpoints. In this investigation, Japanese men had substantially (∼150%) higher circulating n-3 PUFA than did US men, consistent with much higher levels of seafood consumption in Japan. Japanese men also had a substantially lower incidence of new CAC (rate ratio=0.26, 95%CI=0.09 to 0.73), compared with US men, which was not explained by adjustment for conventional CVD risk factors including age, systolic blood pressure, cholesterol, triglycerides, BMI, diabetes, smoking and hypertension medication. In contrast, the association between country (Japan vs USA) and incident CAC was attenuated following adjustment for serum n-3 PUFA. The authors concluded that n-3 PUFA may have antiatherosclerotic effects at levels observed in Japan.

While this analysis has several strengths, including use of objective …

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  • Contributors JW wrote paper. JW and DM had primary responsibility for final content and critical revision of the manuscript for important intellectual content. Both authors read and approved the final manuscript.

  • Funding This work was funded by the NIH Heart, Lung and Blood Institute the grant number is NHLBI 2R01 HL085710.

  • Provenance and peer review Commissioned; internally peer reviewed.

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