Correspondence
n–3 Fatty Acids and the Risk of Sudden Death
N Engl J Med 2002; 347:531-533August 15, 2002
- Article
To the Editor:
The observations of Albert et al. (April 11 issue)1 on the protective effects of long-chain n–3 fatty acids (largely available in fish) with regard to sudden death may have profound clinical implications. These findings confirm previous observations that suggest that dietary patterns may reduce sudden death without an effect on myocardial infarction.2-4 A major underlying cause of sudden death is myocardial ischemia and infarction, as suggested by the authors' definition of sudden death: “death within one hour after the onset of symptoms.” These symptoms may include chest pain, and therefore some patients who die suddenly have had an ischemic event, most probably an acute myocardial infarction.
In the current study, the selection criteria for enrollment in the control group excluded patients with signs or symptoms of coronary artery disease at follow-up. Therefore, we believe that the authors' conclusions, based on comparison with a population selected for the absence of signs of coronary artery disease, may be appropriate but give only a partial answer to the following question: Do these long-chain n–3 fatty acids protect against sudden death when coronary artery disease is present? The Methods section of the article suggests that the investigators could have selected an additional group of controls who had survived a documented myocardial infarction at the time that they became controls, with an approximately equal follow-up. This comparison would have greatly enhanced the importance of the presented observations.
4 ReferencesJose P.S. Henriques, M.D.
Felix Zijlstra, M.D., Ph.D.
Hospital De Weezenlanden, 8011 JW Zwolle, the Netherlands
f.zijlstra@diagram-zwolle. nl 1
Albert CM ,Campos H ,Stampfer MJ , et al. Blood levels of long-chain n-3 fatty acids and the risk of sudden death. N Engl J Med 2002;346:1113-1118
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GISSI-Prevenzione Investigators
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Albert CM ,Hennekens CH ,O'Donnell CJ , et al. Fish consumption and risk of sudden cardiac death. JAMA 1998;279:23-28
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Billman GE ,Kang JX ,Leaf A . Prevention of sudden cardiac death by dietary pure -3 polyunsaturated fatty acids in dogs. Circulation 1999;99:2452-2457
Web of Science | Medline
To the Editor:
Albert et al. identify predictors of heart disease. However, higher oxidation of n–3 fatty acids or cholesterol in the subjects who died suddenly than in the controls could account for the findings. People in whom cardiovascular disease is likely to develop may have low levels of antioxidants and high levels of cholesterol. They may also eat foods low in essential fats1 and high in processed fats.2 These foods are usually low in antioxidants. During storage and processing, whole blood is more susceptible to oxidation than whole plasma. Oxidation destroys derivatives of linolenic acid (i.e., eicosapentaenoic acid [EPA] and docosahexaenoic acid [DHA]). Whole-blood analysis has substantial variability in the oxidation of essential fats. A fatty-acid profile provides data to determine the extent of oxidation in the sample. The authors should present the distribution of n–3 fatty acids in the subjects who died suddenly and the controls as well as data on the presence of markers of oxidation.
2 ReferencesEdward Siguel, M.D., Ph.D.
501 Crooked Creek Dr., Rockville, MD 20850
coolfoods@hotmail.com 1
Siguel EN ,Lerman RH . Altered fatty acid metabolism in patients with angiographically documented coronary artery disease. Metabolism 1994;43:982-993
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Siguel EN ,Lerman RH . Trans-fatty acid patterns in patients with angiographically documented coronary artery disease. Am J Cardiol 1993;71:916-920
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To the Editor:
Albert et al. report that blood levels of long-chain n–3 fatty acids are negatively correlated with the risk of sudden death in men in the Physicians' Health Study, and they imply that this correlation is due to the consumption of fish. However, this effect may not be related solely to fish consumption. Did the authors adjust for the consumption of nuts? Tree nuts, especially walnuts, contain high levels of n–3 α-linolenic acid, which can be converted into longer-chain n–3 acids in vivo. In addition, as Albert et al. point out, metabolic constraints and the conversion of α-linolenic acid into DHA during the storage of samples may have resulted in falsely lowered α-linolenic acid levels and falsely elevated DHA levels in their subjects.
Nut consumption has been correlated with beneficial lipid profiles1 and a decreased risk of coronary artery disease.2 A previous report indicated that the consumption of nuts is associated with a reduced risk of sudden cardiac death.3 Since nuts are a convenient and widely available source of n–3 fatty acids, it may be that at least some of the protective effects found in the current study were due to consumption of nuts.
3 ReferencesDaniel B. Hrdy, M.D., Ph.D.
University of California, Davis, Medical Center, Sacramento, CA 95817
dbhrdy@citrona.com 1
Sabate J ,Fraser GE ,Burke K ,Knutsen SF ,Bennett H ,Lindsted KD . Effects of walnuts on serum lipid levels and blood pressure in normal men. N Engl J Med 1993;328:603-607
Full Text | Web of Science | Medline2
Hu FB ,Stampfer MJ ,Manson JE , et al. Frequent nut consumption and risk of coronary heart disease in women: prospective cohort study. BMJ 1998;317:1341-1345
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Albert CM ,Willett WC ,Manson JE ,Hennekens CH . Nut consumption and the risk of sudden and total cardiac death in the Physicians Health Study. Circulation 1998;98:Suppl 1:I-582 abstract.
To the Editor:
I am writing as both a physician and an environmentalist in response to the Perspective by Rosenberg,1 who comments on the article by Albert et al. Rosenberg notes the well-known incidence of coronary artery disease in the industrialized world and the American Heart Association's recommendation to consume ocean fish twice a week. I wish to point out that there is not a saltwater fishery on the planet that has not been overfished to the point of depletion. Dr. Rosenberg refers to the New England fishermen of the 19th century but does not mention that their main catch at that time (North Atlantic cod) has since been depleted to such an extent that the cod yield in the North Atlantic is now insubstantial.
We have many excellent means to help lessen the burden of coronary artery disease on patients and society. I argue that consuming fish twice a week to reduce the risk of coronary artery disease is harmful proximally to the balance of life in the sea and ultimately to our species and that it should not be recommended.
1 ReferencesThomas P. Knecht, M.D., Ph.D.
University of Utah School of Medicine, Salt Lake City, UT 84108
tom.knecht@hsc. utah. edu 1
Rosenberg IH . Fish -- food to calm the heart. N Engl J Med 2002;346:1102-1103
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Author/Editor Response
The authors reply:
To the Editor: In our observational study of men who were apparently healthy at base line, we focused our analysis on men in whom sudden death was the first manifestation of cardiovascular disease. There are few prospective data on n–3 fatty acids and the risk of sudden death in this important subgroup of the population, which accounts for 50 percent of all sudden deaths.1 Therefore, as Drs. Henriques and Zijlstra point out, the selection criteria for both the case and control groups excluded those with previous confirmed cardiovascular disease. The specific question they pose — “Do these long-chain n–3 fatty acids protect against sudden death when coronary artery disease is present?” — was addressed in the Gruppo Italiano per lo Studio della Sopravvivenza nell'Infarto Miocardico Prevenzione trial.2 This trial reported a 45 percent reduction in the rate of sudden death among patients who had had a myocardial infarction and who were randomly assigned to receive long-chain n–3 fatty-acid capsules. Moreover, since changes in diet after a diagnosis of coronary disease may confound information on diet and disease, this specific question is best addressed in randomized trials, which are more practical in patients for whom secondary prevention is the goal than in those for whom primary prevention is the goal.
Dr. Siguel raises the concern that the results of our study could be due to greater oxidation of long-chain n–3 fatty acids in the blood samples from the men who died suddenly than in those from the controls. If this were the case, one would expect that levels of fatty acids that are equally susceptible to oxidation, such as the n–6 fatty acids, would also be lower in the men who died suddenly than in the controls. As shown in Table 2 of our article, there were no differences in the levels of other fatty acids, including n–6 fatty acids, between the two groups of men. Analysis of markers of oxidation typically requires fresh samples.3
We agree with Dr. Hrdy's point that nuts and other food sources of α-linolenic acid may have contributed to long-chain n–3 fatty acid levels in this study4 and therefore may have accounted for some of the protective association observed. We did not mean to imply that fish is the only source of these long-chain n–3 fatty acids; however, it is the primary source. Finally, Dr. Knecht reminds us that we need to examine the global impact of any recommendation. To ensure that the benefits of n–3 fatty acids will be available for future generations, we should encourage sustainable fisheries as well as research into terrestrial oils that may have the same benefit.
4 ReferencesChristine M. Albert, M.D., M.P.H.
Meir J. Stampfer, M.D., Dr.P.H.
Jing Ma, M.D., Ph.D.
Brigham and Women's Hospital, Boston, MA 02215-1204
calbert@partners.org 1
Kannel WB ,Schatzkin A . Sudden death: lessons from subsets in population studies. J Am Coll Cardiol 1985;5:Suppl:141B-149B
CrossRef | Web of Science | Medline2
GISSI-Prevenzione Investigators
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Holvoet P ,Mertens A ,Verhamme P , et al. Circulating oxidized LDL is a useful marker for identifying patients with coronary artery disease. Arterioscler Thromb Vasc Biol 2001;21:844-848
CrossRef | Web of Science | Medline4
Kang JX ,Leaf A . Antiarrhythmic effects of polyunsaturated fatty acids: recent studies. Circulation 1996;94:1774-1780
Web of Science | Medline
Author/Editor Response
Dr. Rosenberg replies:
To the Editor: I share Dr. Knecht's lament about the state of marine fisheries, particularly the depleted Georges Bank cod fishery off the New England coast. However, that concern should not trump efforts to increase the consumption of n–3 polyunsaturated fatty acids for health benefits.
As I note in my Perspective, marine fish are not the only source of long-chain n–3 fatty acids, which can be produced by chain elongation (albeit at uncertain efficiency) from plant-derived linolenic acid. In addition, promising plant biotechnology research may provide additional approaches to achieving intake of protective EPA and DHA while, we hope, our marine fisheries make a comeback.
Irwin H. Rosenberg, M.D.
Friedman School of Nutrition Science and Policy at Tufts University, Boston, MA 02111
irosenberg@hnrc.tufts. edu - Citing Articles (1)
Citing Articles
1
Christine M. Albert. (2007) Dietary n-3 fatty acid intake and risk of sudden death and coronary artery disease. Current Treatment Options in Cardiovascular Medicine 9:1, 71-77
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