Nearly 20 years ago, Bang and coworkers[1] first suggested that the low mortality rate from coronary heart disease among Greenland Eskimos compared with Danes may be due to their high consumption of seafood. Five years later, in a prospective cohort study, Kromhout et al[2] showed that consumption of fish once or twice a week was associated with a 50% reduction in coronary heart disease mortality. Since that time, the majority (but not all) of 14 additional cohort studies that have been published have shown a protective effect from the consumption of a small amount of fish.[3] The controversy surrounding the association between fish consumption and coronary heart disease was enhanced by the publication of negative results from 2 large cohort studies from the United States[4,5] and the inconsistent findings from 3 other studies.[6-8]
The hypothesis that fish consumption may be protective in relation to sudden cardiac death is derived from the Diet and Reinfarction Trial.[9] This secondary prevention trial showed a significant reduction in all-cause mortality (by 29%) and cardiac mortality (by 33%) in patients with cardiac disease who consumed at least 2 portions of fatty fish per week. The authors suggested that the protective effect of fish may be due to preventing ventricular fibrillation during acute ischemia, although no benefit was observed on the incidence of nonfatal myocardial infarction.
In this issue of THE JOURNAL, Albert and colleagues[8] use data from the Physicians' Health Study to test the hypotheses that fish has antiarrhythmic properties and may prevent sudden cardiac death. More than 20,000 male physicians who were aged 40 to 84 years and who were free of cardiovascular disease and cancer at baseline were followed up for 11 years. Men who consumed fish at least once per month had a 52% lower risk of sudden cardiac death compared with those who consumed fish less than once per month. Dietary intake of n-3 polyunsaturated fatty acid was not significantly associated with a reduced risk of sudden cardiac death. Fish consumption was not related to nonsudden cardiac death or coronary heart disease death.
However, this cohort study does not provide clear-cut answers. The results are consistent with the hypothesis that a small amount of fish is protective in relation to sudden cardiac death, yet a protective effect on nonsudden cardiac death and coronary heart disease mortality was not observed. As the authors acknowledge, their results differ from those obtained from the Western Electric study.[7] In that cohort study of approximately 2000 middle-aged men with 30 years of follow-up, there was a significant inverse association between fish consumption and coronary heart disease mortality and nonsudden cardiac death, but not with sudden cardiac death. In the Western Electric study, death certificate data were the only source of information available to determine the specific type of coronary death; sudden cardiac death was defined as death occurring no more than 12 hours after the onset of the terminal acute illness. In the Physicians' Health Study, detailed information was available from next of kin, medical records, and autopsy reports; sudden death was defined as death within 1 hour of onset of symptoms. In the Western Electric study, 164 (16%) of 1042 deaths were sudden, whereas in the Physicians' Health Study, 133 (8%) of 1652 deaths were classified as sudden. The difference in sudden death definition may explain the different results obtained in the 2 studies.
The population in the Physicians' Health Study was characterized by a high fish intake. Only 3% of men consumed fish less than once per month, and 6% between once and 3 times per month. More than 90% of the men consumed fish at least once per week, and more than 10% consumed fish at least 5 times per week. This level of fish intake raises the question of selection in relation to men who consumed fish less than once per week and especially to the 3% who consumed fish less than once per month and who formed the reference group in the analyses. These men also had increased risk factors associated with an elevated risk of (sudden) cardiac death. They smoked more, drank less alcohol, and exercised less than the men with a higher fish intake. Although the authors adjusted for these risk factors in their analyses, residual confounding because of a less healthy lifestyle in this small reference group cannot be excluded.
The main hypotheses of Albert et al in explaining the protective effect of fish consumption on sudden cardiac death is the antiarrhythmic effect of n-3 polyunsaturated fatty acids. However, in their study, the association between fish consumption and sudden cardiac death was stronger than that between n-3 polyunsaturated fatty acid intake and sudden cardiac death. This finding does not rule out the possibility that constituents present in fish other than n-3 polyunsaturated fatty acids may be responsible for the protective effect.[2] Another explanation may be that measurement error in the quantification of the fish intake was responsible for failure to show a dose-response relationship. In a case-control study on fish consumption and cardiac arrest, Siscovick et al[6] quantified n-3 polyunsaturated fatty acids in diet and in red blood cell membranes and documented a dose-response relationship.
The question of a dose-response relationship is of particular interest. Two reports from Finland suggest that a high intake of fish and n-3 polyunsaturated fatty acids is associated with an increased risk for coronary death.[10,11] Moreover, in 1 study,[10] a high intake of local lean fish was associated with a high intake of mercury, and the authors speculate that mercury promotes lipid peroxidation. These results suggest that a high intake of fish is not necessarily better than a low intake and may even result in a detrimental health effect.
Based on current knowledge of the association between fish consumption and coronary heart disease, what should clinicians advise in relation to primary and secondary prevention? Cohort studies have convincingly shown that men who consume fish once a week have a lower mortality rate from coronary heart disease than men who do not eat fish, but also show no association between fish consumption and the incidence of nonfatal coronary heart disease. There is now evidence from an intervention trial,[9] a case-control study,[6] and the Physicians' Health Study[8] that intake of fatty fish may reduce the occurrence of cardiac arrest. The existing evidence suggests that consumption of fish once a week will help prevent coronary heart disease and therefore should be a component of a healthy diet. It also appears justified to advise patients with cardiac disease to consume 2 fish servings per week. These levels of fish consumption not only may help reduce coronary heart disease mortality, but also may favorably influence all-cause mortality.
Daan Kromhout, PhD, MPH
From the Division of Public Health Research, National Institute of Public Health and the Environment, Bilthoven, the Netherlands.
Reprints: Daan Kromhout, PhD, MPH, Division of Public Health Research, National Institute of Public Health and the Environment, PO Box 1, 3720 BA Bilthoven, the Netherlands.
Editorials represent the opinions of the authors and THE JOURNAL and not those of the American Medical Association.
References
1. Bang HO, Dyerberg J, Sinclair HM. The composition of the Eskimo food in north western Greenland. Am J Clin Nutr. 1980;33:2657-2661.
2. Kromhout D, Bosschieter EB, De Lezenne Coulander C. The inverse relation between fish consumption and 20-year mortality from coronary heart disease. N Engl J Med. 1985;312:1205-1209.
3. Shekelle RB, Stamler J. Fish and coronary heart disease: the epidemiologic evidence. Nutr Metab Cardiovasc Dis. 1993;4:46-51.
4. Ascherio A, Rimm EB, Stampfer MJ, Giovannucci EL, Willett WC. Dietary intake of marine n-3 fatty acids, fish intake, and the risk of coronary disease among men. N Engl J Med. 1995;332:978-982.
5. Morris MC, Manson JE, Rosner B, Buring JE, Willett WC, Hennekens CH. Fish consumption and cardiovascular disease in the Physicians' Health Study: a prospective study. Am J Epidemiol. 1995;142:166-175.
6. Siscovick DS, Raghunathan TE, King I, et al. Dietary intake and cell membrane levels of long-chain n-3 polyunsaturated fatty acids and the risk of primary cardiac arrest. JAMA. 1995;274:1363-1367.
7. Daviglus ML, Stamler J, Orencia AJ, et al. Fish consumption and the 30-year risk of fatal myocardial infarction. N Engl J Med. 1997;336:1046-1053.
8. Albert CM, Hennekens CH, O'Donnell CJ, et al. Fish consumption and risk of sudden cardiac death. JAMA. 1998;279:23-28.
9. Burr ML, Fehily AM, Gilbert JF, et al. Effects of changes in fat, fish, and fibre intakes on death and myocardial infarction: Diet and Reinfarction Trial (DART). Lancet. 1989;2:757-761.
10. Salonen JT, Seppaenen K, Nyyssoenen K, et al. Intake of mercury from fish, l ipid peroxidation and the risk of myocardial infarction and coronary, cardiovascular, and any death in Eastern Finnish men. Circulation. 1995;91:645655.
11. Pietinen P, Ascherio A, Krohonen P, et al. Intake of fatty acids and risk of coronary heart disease in a cohort of Finnish men. Am J Epidemiol. 1997;145:876887.
Material presented on this home page constitutes opinion of the author.
Copyright © 1997 Steven J. Milloy. All rights reserved. Site developed and hosted by WestLake Solutions, Inc.