Moderate fish consumption was associated with lower long-term cardiovascular disease (CVD) risk in high-risk individuals and those with existing vascular disease but not in the general population, according to a large pooled analysis.
In the largely CVD-naïve PURE study cohort, individuals who ate 350 g (or four servings of fish) a week were not better off than peers with little or no fish intake in terms of major CVD events (HR 0.95, 95% CI 0.86-1.04) or total mortality (HR 0.96, 95% CI 0.88-1.05) over a median 9.1 years of follow-up.
By contrast, moderate fish consumption at 175 g (two servings) per week was associated with reduced risk of major CVD (HR 0.84, 95% CI 0.73-0.96) and total mortality (HR 0.82, 95% CI 0.74-0.91) among the smaller ONTARGET, TRANSCEND, and ORIGIN cohorts of people with vascular disease or diabetes. Risk did not sink further with greater fish intake in this group.
The pattern was similar for sudden cardiac death, with significant advantage observed in vascular disease but not general populations without vascular disease, according to Andrew Mente, PhD, of the Population Health Research Institute of Hamilton Health Sciences and McMaster University, Ontario, and colleagues reporting online in JAMA Internal Medicine.
Thus, study findings were consistent with dietary guidelines that recommend fish consumption at least twice a week for CVD prevention.
“The lack of confirmation of a statistically significant lower risk of CVD in the PURE cohort does not alter the large body of prior observational evidence supporting the cardiac benefits of fish intake in general populations,” according to an invited commentary by Dariush Mozaffarian, MD, DrPH, of Tufts University in Boston.
Moreover, Mozaffarian suggested that the composite CVD outcome (including MI, stroke, congestive heart failure, or sudden death) could have hampered the finding of benefit to fish consumption in the non-CVD cohort.
“Prior studies in general populations suggest that the benefits of fish or ω-3 are strongest for coronary events, such as MI and CHD [coronary heart disease] death, rather than composite CVD outcomes that include stroke,” the editorialist noted.
As for the issue of trace mercury and other contaminants in fish, Mozaffarian advised that their presence at current levels are unlikely to offset the cardiac benefits of eating fish. Pregnant woman, however, should avoid some larger mercury-containing species (e.g., swordfish, king mackerel, bluefin tuna) and any fish caught in polluted areas, he said.
In total, the four aforementioned studies included 191,558 individuals (mean age 54.1 years, 47.9% men) from 58 countries. Among them, 51,731 had a known history of vascular disease. Fish consumption was recorded using validated food frequency questionnaires.
Follow-up lasted a median 7.5 years across the four studies.
PURE contributed the most patients to the pooled analysis. Out of its 147,645 participants, 5.3% had a history of CVD.
Only the ORIGIN cohort provided information on type of fish consumed. It appeared that oily fish (e.g., salmon, sardines, tuna, and mackerel) were strongly associated with lower CVD risk (HR 0.94 per 5 g, 95% CI 0.92-0.97), whereas other fish had no effect.
In people with or without vascular disease, higher fish intake was generally linked to lower triglycerides but also higher LDL cholesterol.
“Given that there are associations with CVD risk markers, some of which may be protective and others harmful, and that some fish may contain contaminants, studying the association of fish intake with outcome events is essential to inform recommendations for populations,” the investigators said.
Mente’s group also acknowledged that the pooled analysis was subject to the limitations of self-reported data and potential residual confounding.
“Future research should focus on the many unresolved questions around dose responses, fish preparation methods, background fish consumption, underlying participant risk, and specific clinical outcomes most likely to be affected,” Mozaffarian said.
Mente had no disclosures.
Study authors listed various ties to the drug and food industry.
Mozaffarian reported receiving grants from the Bill & Melinda Gates Foundation, NIH, and The Rockefeller Foundation; receiving personal fees from Acasti Pharma, America’s Test Kitchen, Amarin Corporation, Barilla, Cleveland Clinic Foundation, Danone, GOED, and Motif FoodWorks; serving on the scientific advisory board for Beren Therapeutics, Brightseed, Calibrate, DayTwo, Elysium Health, Filtricine, Foodome Inc, HumanCo, January.ai, Tiny Organics; and receiving royalties from UpToDate.