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(Circulation. 2003;107:1372.)
© 2003 American Heart Association, Inc.

Clinical Investigation and Reports

Cardiac Benefits of Fish Consumption May Depend on the Type of Fish Meal Consumed

The Cardiovascular Health Study

Dariush Mozaffarian, MD; Rozenn N. Lemaitre, PhD, MPH; Lewis H. Kuller, MD, DrPH; Gregory L. Burke, MD, MS; Russell P. Tracy, PhD; David S. Siscovick, MD, MPH

From the Cardiovascular Health Research Unit, Departments of Medicine (R.L., D.S.) and Epidemiology (D.S.) and Division of Cardiology (D.M.), University of Washington, and the Veterans Affairs Puget Sound Health Care Center (D.M.), Seattle, Wash; the Department of Epidemiology (L.K.), Graduate School of Public Health, University of Pittsburgh, Pittsburgh, Pa; the Department of Public Health Sciences (G.B.), Wake Forest University School of Medicine, Winston-Salem, NC; and the Laboratory for Clinical Biochemistry Research (R.T.), Department of Pathology, University of Vermont, Colchester, Vt.

Correspondence to Dariush Mozaffarian MD, CHRU, 1730 Minor Ave #1360, Seattle, WA 98101. E-mail darymd{at}hotmail.com

	Abstract

Top Abstract Introduction Methods Results Discussion References

 
Background— Few studies have examined associations of fish consumption with ischemic heart disease (IHD) risk among older adults or how different types of fish meals relate to IHD risk.

Methods and Results— In a population-based prospective cohort study, usual fish consumption was ascertained at baseline among 3910 adults aged 65 years and free of known cardiovascular disease in 1989 and 1990. Consumption of tuna and other broiled or baked fish correlated with plasma phospholipid long-chain n-3 fatty acids, whereas consumption of fried fish or fish sandwiches (fish burgers) did not. Over 9.3 years’ mean follow-up, there were 247 IHD deaths (including 148 arrhythmic deaths) and 363 incident nonfatal myocardial infarctions (MIs). After adjustment for potential confounders, consumption of tuna or other broiled or baked fish was associated with lower risk of total IHD death (P for trend=0.001) and arrhythmic IHD death (P=0.001) but not nonfatal MI (P=0.44), with 49% lower risk of total IHD death and 58% lower risk of arrhythmic IHD death among persons consuming tuna/other fish 3 or more times per week compared with less than once per month. In similar analyses, fried fish/fish sandwich consumption was not associated with lower risk of total IHD death, arrhythmic IHD death, or nonfatal MI but rather with trends toward higher risk.

Conclusions— Among adults aged 65 years, modest consumption of tuna or other broiled or baked fish, but not fried fish or fish sandwiches, is associated with lower risk of IHD death, especially arrhythmic IHD death. Cardiac benefits of fish consumption may vary depending on the type of fish meal consumed.

Key Words: diet • fatty acids • coronary disease • arrhythmia

	Introduction

Top Abstract Introduction Methods Results Discussion References

 
Fish consumption is inversely associated with fatal ischemic heart disease (IHD) and arrhythmic death, consistent with prevention of fatal arrhythmias by long-chain n-3 polyunsaturated fatty acids (PUFAs) in fish.^1–7 However, if cardiac effects of fish consumption are primarily related to effects of n-3 PUFAs, then associations may vary depending on the type of fish meal consumed,⁸ as n-3 PUFA content can vary by an order of magnitude comparing fatty fish (eg, salmon) to lean fish (eg, catfish or cod). Additionally, the preparation method (eg, frying) may markedly alter the fatty acid content of a fish meal.⁹ However, little is known about relationships of different types of fish meals with IHD risk.

To investigate the relationships of different types of fish meals with IHD risk, we examined the associations of tuna/other fish consumption and fried fish/fish sandwich consumption with total IHD death, arrhythmic IHD death, and incident nonfatal myocardial infarction (MI) in the Cardiovascular Health Study (CHS), a prospective, population-based cohort study of determinants of cardiovascular events among persons aged 65 years. Few studies have examined relationships of fish consumption with IHD risk specifically among older adults,³ a growing population at particular risk for IHD. Because cardiac effects of fish consumption may be primarily due to antiarrhythmic effects of n-3 PUFAs rather than effects on atherogenesis or plaque stability, our primary hypothesis was that consumption of fish meals higher in n-3 PUFA content would be inversely associated with IHD death but not nonfatal MI, whereas consumption of fish meals lower in n-3 PUFA content would not be associated with IHD death or nonfatal MI.⁸

	Methods

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Design and Population
The design and recruitment experience of CHS have been described.^10,11 Briefly, 5201 men and women aged 65 years were randomly selected and enrolled from Medicare eligibility lists in 4 US communities in 1989 and 1990; an additional 687 black participants enrolled in 1992 were not included in this analysis because a food frequency questionnaire was not administered to these subjects at baseline. Each center’s institutional review committee approved the study, and all subjects gave informed consent. We excluded 1216 participants with known cardiovascular disease at baseline¹² and 75 participants with incomplete data on fish consumption, which resulted in 3910 participants being included in the present analysis. At baseline, participants completed standard questionnaires on health status, medical history, and cardiovascular risk factors and underwent clinic examination, resting ECG, carotid ultrasonography, and laboratory evaluation.^10–13

Dietary Assessment
A picture-sort version of the National Cancer Institute food frequency questionnaire was administered at baseline to assess usual intake of "fried fish or fish sandwich (fish burger)," "tuna fish/tuna salad/tuna casserole," and "other fish (broiled or baked)" with 5 response categories that ranged from <5 times per year to 5 times per week¹⁴; a semiquantitative picture-sort version was validated against 24-hour dietary recalls.^14,15 Summary dietary measures, such as total energy intake, were estimated from the food frequency questionnaire using computer software.¹⁶ Food and nutrient intakes, including fish intake, were adjusted for total energy using regression¹⁷; values are presented for the mean population energy intake (1820 kcal/d). As a biomarker of n-3 PUFA content, we evaluated correlations of fish intake with plasma phospholipid eicosapentaenoic acid (EPA, 20:5n-3) and docosahexaenoic acid (DHA, 22:6n-3) in 56 participants. Combined EPA and DHA levels correlated with tuna intake (Spearman correlation [r]=0.35, P<0.01) and other fish intake (r=0.59, P<0.001) but not fried fish/fish sandwich intake (r=0.04, P=0.78), consistent with lean types of fish typically fried (eg, cod and pollock).

Events
Events were identified during annual examinations and interim 6-month telephone interviews, with review and adjudication by a centralized committee composed of internists using interviews, medical records, death certificates, medical examiner forms, and Health Care Financing Administration hospitalizations.¹⁸ MI was classified using chest pain, cardiac enzymes, and ECGs. Suspected cardiac deaths not meeting all criteria for definite MI were classified as coronary heart disease death if they occurred within 72 hours of chest pain or with an antecedent history of IHD. Mechanisms of fatal cardiac events were also adjudicated using the above records, with mechanisms including primary arrhythmia (within 5 minutes of symptom onset), secondary arrhythmia (preceding subacute ischemic signs or symptoms without chronic heart failure), cardiac procedures, heart failure, and multiple or unknown mechanisms. The sensitivity and specificity of this classification for arrhythmic death were 93% and 95% compared with Hinkle classification. Our primary outcomes were total IHD death (combined fatal MI plus coronary heart disease death) and incident nonfatal MI. To investigate associations of fish consumption with fatal arrhythmia, we also examined the subset of arrhythmic IHD deaths.

Statistical Analysis
Cox proportional hazards models were used to estimate risk, with time from study entry until first event, death, or June 30, 2000. To assess for confounding, prespecified covariates included age, gender, and diabetes. Other characteristics were added, both individually and in groups, based on clinical interest or appreciable change (±5%) in the hazard ratio (HR) associated with fish consumption. Tuna and other fish consumption were correlated (r=0.37, P<0.001), and associations of each with risk were similar to associations of tuna/other fish intake combined. Tuna and other fish consumption were therefore evaluated together (combined correlation with EPA+DHA=0.55, P<0.001). Fried fish/fish sandwich consumption was modestly correlated with tuna/other fish intake (r=0.11, P<0.001) and was evaluated separately. Tuna/other fish and fried fish/fish sandwich consumption were evaluated as categorical variables (<1/mo, 1 to 3/mo, 1/wk, 2/wk, 3/wk). Associations with baseline characteristics were evaluated using regression. Likelihood-ratio testing was used to assess for effect modification. Analyses were performed with Stata 7.0, using the updated CHS database incorporating minor corrections through April 2002. All probability values are 2-tailed.

	Results

Top Abstract Introduction Methods Results Discussion References

 
Mean fried fish/fish sandwich and tuna/other fish consumption were 0.7 and 2.2 servings per week, respectively. Tuna/other fish consumption was associated with younger age, female gender, white race, and higher education, whereas fried fish/fish sandwich consumption was associated with nonwhite race and lower education (Table 1). Tuna/other fish consumption was generally associated with a more favorable cardiovascular risk profile, although both were associated with higher LDL cholesterol. Tuna/other fish consumption was inversely associated with saturated fat and beef/pork intake and positively associated with fruit and vegetable intake; fried fish/fish sandwich consumption was inversely associated with alcohol and fruit intake and positively associated with beef/pork and vegetable intake. Greater tuna/other fish intake, but not fried fish/fish sandwich intake, was associated with higher plasma phospholipid EPA+DHA. Estimated dietary EPA+DHA content of these fish meals is also shown, derived from US commercial landings and Department of Agriculture data.^19,20

View this table: [in this window] [in a new window]   TABLE 1. Baseline Characteristics According to Fish Consumption

During 9.3 years’ mean follow-up, there were 247 IHD deaths (including 48 primary and 100 secondary arrhythmic deaths) and 363 incident nonfatal MIs. After adjustment for age, gender, education, diabetes, and smoking, greater tuna/other fish intake was associated with lower risk of total IHD death (P for trend=0.001) and arrhythmic IHD death (P=0.001) but not nonfatal MI (P=0.44), with 49% lower risk of total IHD death and 58% lower risk of arrhythmic IHD death with consumption 3 times per week compared with less than once per month (Table 2, model 1). Results were similar after adjustment for additional potential confounders or mediators, including body mass index, systolic blood pressure, serum lipids, C-reactive protein, and dietary factors (model 2). In contrast, greater fried fish/fish sandwich intake was not associated with lower risk of total IHD death, arrhythmic IHD death, or nonfatal MI but rather with trends toward higher risk (Table 2).

View this table: [in this window] [in a new window]   TABLE 2. Risk of Total IHD Death, Arrhythmic IHD Death, and Nonfatal MI According to Fish Consumption

Further adjustments had little effect, including for recruitment community, race (white or nonwhite), income (<$25 000 or $25 000 per year), diastolic blood pressure, heart rate, family history of MI, atrial fibrillation, self-perceived health (5 categories), physical activity, exercise intensity, carotid intimal medial thickness; use of aspirin, ß-blockers, lipid-lowering medication, estrogen, and fish oil; fasting glucose and insulin, white blood cell count, fibrinogen, factor VII, and factor VIII; and estimated intake of total fat, polyunsaturated fat, carbohydrates, protein, wine, fried chicken or french fries, thiamine, vitamin A, and vitamin C. There was also little evidence that associations varied according to age, gender, smoking, or presence of diabetes or obesity (P>0.05 for each interaction), although power to detect such effect modification may have been limited.

Given prior literature suggesting potential threshold effects at modest fish/n-3 PUFA intake,^4,21 we also evaluated risks comparing consumption at least once per week to less than once per week. After adjustment for potential confounders (as in model 1), consumption of tuna/other fish at least once per week was associated with lower risk of total IHD death (HR=0.73, 95% CI=0.56 to 0.96) and arrhythmic IHD death (HR=0.66, 95% CI=0.47 to 0.94) but not nonfatal MI (HR=0.92, 95% CI=0.73 to 1.16) compared with less than once per week. In similar analyses, consumption of fried fish/fish sandwich at least once per week was not associated with total IHD death (HR=1.11, 95% CI=0.81 to 1.53), arrhythmic IHD death (HR=1.15, 95% CI=0.76 to 1.72), or nonfatal MI (HR=1.15, 95% CI=0.89 to 1.49) compared with less than once per week.

We also evaluated risks associated with estimated dietary n-3 PUFAs from these fish meals. After adjustment for potential confounders or mediators (as in model 2), each 1 g/d EPA+DHA was associated with lower risk of total IHD death (HR=0.58, 95% CI=0.38 to 0.90) and arrhythmic IHD death (HR=0.45, 95% CI=0.25 to 0.81) but not nonfatal MI (HR=0.89, 95% CI=0.64 to 1.22).

	Discussion

Top Abstract Introduction Methods Results Discussion References

 
In this prospective study, greater consumption of tuna or other broiled or baked fish was associated with lower risk of IHD death, especially arrhythmic IHD death, among older men and women without known cardiovascular disease. There are several potential explanations for these findings. Intake of such fish may be a marker for some other factor that reduces IHD risk; however, the associations persisted after adjustment for a wide variety of demographic, clinical, lifestyle, laboratory, and dietary characteristics. Given correlations of tuna/other fish intake with plasma phospholipid EPA+DHA, as well as the inverse association of estimated dietary EPA+DHA intake with IHD death, it is biologically plausible that the observed relationships are due to cardiovascular effects of n-3 PUFAs.^21–24 Relationships of tuna/other fish consumption and EPA+DHA intake with IHD death persisted after adjustment for blood pressure, serum lipids, and clotting and inflammatory factors, which suggests that baseline differences in these factors did not entirely mediate these associations. Associations appeared strongest for arrhythmic IHD death and weakest for nonfatal MI, even with larger numbers of nonfatal events, consistent with in vitro and in vivo experimental evidence of antiarrhythmic effects of n-3 PUFAs, which decrease myocyte excitability and reduce cytosolic calcium fluctuations via inhibition of Na⁺ and L-type Ca⁺⁺ channels.^21,22 A primary association with fatal arrhythmic events also may explain in part why prior studies did not detect associations of fish/n-3 PUFAs with combined fatal and nonfatal IHD events.^25,26 Consumption of tuna/other fish may also reduce IHD death through some mechanism unrelated to n-3 PUFAs; however, given observational, clinical, and experimental evidence, it is reasonable to assume that n-3 PUFAs may be the active factor or play some role in this association.

We separately examined associations of fried fish/fish sandwich consumption with IHD risk, hypothesizing that intake of such fish (generally lean and not associated with n-3 PUFA levels) would not be associated with lower risk. We observed no associations (and even some trends toward higher risk) with fried fish/fish sandwich consumption. Although this may be due to low n-3 PUFA content of such fish, which are likely mostly lean fish, there are other potential explanations. Modest benefits of low n-3 PUFAs in such fish may be counteracted by ingestion of mercury from contaminated fish, especially lean freshwater fish, which may increase cardiovascular risk.^27,28 Additionally, the preparation method may affect potential benefits: frying can greatly affect a fish meal’s fatty acid composition, often markedly increasing the n-6:n-3 ratio.⁹ Furthermore, trans-fatty acids and lipid oxidation products in fried fats/oils, especially oils used repeatedly for frying, may increase cardiovascular risk.^29–31 To the best of our knowledge, this is the first study evaluating associations of fried fish/fish sandwich consumption with IHD risk in a large population. Our results suggest that consumption of lean fish prepared by frying does not reduce IHD risk; additional investigation is necessary to determine whether this novel finding relates to certain types of fish or to preparation methods.

Few prior studies have examined associations of fish consumption with IHD risk specifically among elderly persons.³ Our findings in this large, population-based cohort of elderly adults (average age 72 years at baseline) suggest that diet may affect cardiovascular risk beyond the earlier development and progression of atherosclerosis in young adulthood and middle age. Modest dietary n-3 PUFA consumption alters myocardial cell membrane fatty acid composition (and arrhythmic potential) within 1 to 2 weeks²¹; if benefits of fish consumption are related to relatively short-term antiarrhythmic effects of n-3 PUFAs, then effects may be gained (or lost) over relatively short periods.

Our analysis has several strengths. The prospective design and exclusion of persons with known cardiovascular disease at baseline reduce potential bias from recall differences or dietary changes due to known disease. The population-based recruitment strategy enhances generalizability. Standardized assessment of a wide variety of participant characteristics increases the capacity to adjust for confounding. Close follow-up, comprehensive review of potential events, and centralized adjudication reduce potential for missed or misclassified outcomes.

There are also potential limitations to our findings. Fish intake was assessed at baseline, and there may have been changes in consumption over time, which would diminish associations and cause underestimation of relationships of fish consumption with IHD risk. Additionally, residual confounding by incompletely measured or unknown factors cannot be excluded. However, given the magnitude of the observed associations, their independence from a wide variety of participant characteristics, and the consistency (for tuna/other fish intake) with results of previous studies, it seems unlikely that residual confounding entirely accounts for our observations.

Our findings suggest that consumption of tuna and other broiled or baked fish reduces risk of total and arrhythmic IHD death among older adults, consistent with prevention of fatal cardiac arrhythmias by dietary n-3 PUFAs and in support of recommendations of fatty fish consumption at least 1 to 2 servings per week. The absence of lower risk with fried fish or fish sandwich consumption suggests that cardiac benefits of a fish meal may vary depending on the n-3 PUFA content or preparation method; consideration should be given to these factors when one considers potential cardiovascular effects, as increasing consumption of all types of fish meals may not be beneficial. Continued investigation is necessary to further elucidate relationships and mechanisms of benefit and risk, with particular focus on different types of fish meals and on the pathogenesis and prevention of cardiac arrhythmias.

	Acknowledgments

 
Salary support for Dr Mozaffarian was provided by a VA Health Services Research and Development fellowship at the VA Puget Sound Health Care Center. The research reported in this article was supported by contracts N01-HC-85079 through N01-HC-85086, N01-HC-35129, and N01 HC-15103 from the National Heart, Lung, and Blood Institute. For a full list of participating CHS investigators and institutions, see "About CHS: Principal Investigators and Study Sites" at http://chs-nhlbi.org.

Received September 30, 2002; revision received December 10, 2002; accepted December 10, 2002.

	References

Top Abstract Introduction Methods Results Discussion References

 
1. Bang HO, Dyerberg J. Lipid metabolism and ischemic heart disease in Greenland Eskimos. In: Draper H, ed. Advances in Nutrition Research. New York, NY: Plenum Press; 1980: 1–22.

2. 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.[Abstract/Free Full Text]

3. Kromhout D, Feskens EJ, Bowles CH. The protective effect of a small amount of fish on coronary heart disease mortality in an elderly population. Int J Epidemiol. 1995; 24: 340–345.[Abstract/Free Full Text]

4. Albert CM, Hennekens CH, O’Donnell CJ, et al. Fish consumption and risk of sudden cardiac death. JAMA. 1998; 279: 23–28.[Abstract/Free Full Text]

5. Hu FB, Bronner L, Willett WC, et al. Fish and omega-3 fatty acid intake and risk of coronary heart disease in women. JAMA. 2002; 287: 1815–1821.[Abstract/Free Full Text]

6. Burr ML, Fehily AM, Gilbert JF, et al. Effects of changes in fat, fish, and fibre intakes on death and myocardial reinfarction: Diet And Reinfarction Trial. Lancet. 1989; 2: 757–761.[Medline] [Order article via Infotrieve]

7. Gruppo Italiano per lo Studio della Sopravvivenza nell’Infarto miocardico. Dietary supplementation with n-3 polyunsaturated fatty acids and vitamin E after myocardial infarction: GISSI-Prevenzione trial. Lancet. 1999; 354: 447–455.[CrossRef][Medline] [Order article via Infotrieve]

8. Siscovick DS, Raghunathan TE, Lemaitre R, et al. Long chain n-3 polyunsaturated fatty acids and out-of-hospital primary cardiac arrest: clinical and public health implications of observational studies and clinical trials. Eur Heart J. 2001; 3: 70S–74S.

9. Candela M, Astiasaran I, Bello J. Deep-fat frying modifies high-fat fish lipid fraction. J Agric Food Chem. 1998; 46: 2793–2796.[CrossRef]

10. Fried LP, Borhani NO, Enright P, et al. The Cardiovascular Health Study: design and rationale. Ann Epidemiol. 1991; 1: 263–276.[Medline] [Order article via Infotrieve]

11. Tell GS, Fried LP, Hermanson B, et al. Recruitment of adults 65 years and older as participants in the Cardiovascular Health Study. Ann Epidemiol. 1993; 3: 358–366.[Medline] [Order article via Infotrieve]

12. Psaty BM, Kuller LH, Bild D, et al. Methods of assessing prevalent cardiovascular disease in the Cardiovascular Health Study. Ann Epidemiol. 1995; 5: 270–277.[CrossRef][Medline] [Order article via Infotrieve]

13. Cushman M, Cornell ES, Howard PR, et al. Laboratory methods and quality assurance in the Cardiovascular Health Study. Clin Chem. 1995; 41: 264–270.[Abstract/Free Full Text]

14. Kumanyika S, Tell GS, Shemanski L, et al. Eating patterns of community-dwelling older adults: the Cardiovascular Health Study. Ann Epidemiol. 1994; 4: 404–415.[Medline] [Order article via Infotrieve]

15. Kumanyika SK, Tell GS, Shemanski L, et al. Dietary assessment using a picture-sort approach. Am J Clin Nutr. 1997; 65: 1123S–1129S.[Medline] [Order article via Infotrieve]

16. Smucker R, Block G, Coyle L, et al. A dietary and risk factor questionnaire and analysis system for personal computers. Am J Epidemiol. 1989; 129: 445–449.[Abstract/Free Full Text]

17. Willett W, Stampfer MJ. Total energy intake: implications for epidemiologic analyses. Am J Epidemiol. 1986; 124: 17–27.[Free Full Text]

18. Ives DG, Fitzpatrick AL, Bild DE, et al. Surveillance and ascertainment of cardiovascular events: The Cardiovascular Health Study. Ann Epidemiol. 1995; 5: 278–285.[CrossRef][Medline] [Order article via Infotrieve]

19. National Marine Fisheries Service. Fisheries of the United States, 2000. Silver Spring, MD: US Dept of Commerce; 2001.

20. US Department of Agriculture, Agricultural Research Service. 2002 USDA National Nutrient Database for Standard Reference, Release 15. Available at: http://www.nal.usda.gov/fnic/foodcomp. Accessed August 1, 2002.

21. McLennan PL. Myocardial membrane fatty acids and the antiarrhythmic actions of dietary fish oil in animal models. Lipids. 2001; 36: 111S–114S.[CrossRef]

22. Kang JX, Leaf A. Prevention of fatal cardiac arrhythmias by polyunsaturated fatty acids. Am J Clin Nutr. 2000; 71: 202S–207S.[Abstract/Free Full Text]

23. Nestel PJ. Fish oil and cardiovascular disease: lipids and arterial function. Am J Clin Nutr. 2000; 71: 228S–231S.[Abstract/Free Full Text]

24. von Schacky C. n-3 fatty acids and the prevention of coronary atherosclerosis. Am J Clin Nutr. 2000; 71: 224S–227S.[Abstract/Free Full Text]

25. Ascherio A, Rimm EB, Stampfer MJ, et al. Dietary intake of marine n-3 omega fatty acids, fish intake, and the risk of coronary disease among men. N Engl J Med. 1995; 332: 977–982.[Abstract/Free Full Text]

26. Morris MC, Manson JE, Rosner B, et al. Fish consumption and cardiovascular disease in the Physicians’ Health Study: a prospective study. Am J Epidemiol. 1995; 142: 166–175.[Abstract/Free Full Text]

27. Salonen JT, Seppanen K, Nyyssonen K, et al. Intake of mercury from fish, lipid peroxidation, and the risk of myocardial infarction and coronary, cardiovascular, and any death in eastern Finnish men. Circulation. 1995; 91: 645–655.[Abstract/Free Full Text]

28. Rissanen T, Voutilainen S, Nyyssonen K, et al. Fish oil-derived fatty acids, docosahexaenoic acid and docosapentaenoic acid, and the risk of acute coronary events: the Kuopio Ischaemic Heart Disease Risk Factor Study. Circulation. 2000; 102: 2677–2679.[Abstract/Free Full Text]

29. Ascherio A, Katan MB, Zock PL, et al. Trans-fatty acids and coronary heart disease. N Engl J Med. 1999; 340: 1994–1998.[Free Full Text]

30. Lemaitre RN, King IB, Raghunathan TE, et al. Cell membrane trans-fatty acids and the risk of primary cardiac arrest. Circulation. 2002; 105: 697–701.[Abstract/Free Full Text]

31. Williams MJ, Sutherland WH, McCormick MP, et al. Impaired endothelial function following a meal rich in used cooking fat. J Am Coll Cardiol. 1999; 33: 1050–1055.[Abstract/Free Full Text]

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				U. J. Jung, C. Torrejon, A. P Tighe, and R. J Deckelbaum n-3 Fatty acids and cardiovascular disease: mechanisms underlying beneficial effects Am. J. Clinical Nutrition, June 1, 2008; 87(6): 2003S - 2009S. [Abstract] [Full Text] [PDF]

				D. J.A. Jenkins, A. R. Josse, P. Dorian, M. L. Burr, R. LaBelle Trangmar, C. W.C. Kendall, and S. C. Cunnane Heterogeneity in Randomized Controlled Trials of Long Chain (Fish) Omega-3 Fatty Acids in Restenosis, Secondary Prevention and Ventricular Arrhythmias J. Am. Coll. Nutr., June 1, 2008; 27(3): 367 - 378. [Abstract] [Full Text] [PDF]

				J. H. O'Keefe, J. H. Lee, R. Marchioli, C. J. Lavie, and W. S. Harris Are All Fish Equally Close to the Heart?-Reply Mayo Clin. Proc., June 1, 2008; 83(6): 724 - 725. [Full Text] [PDF]

				D. Mozaffarian, P. K. Stein, R. J. Prineas, and D. S. Siscovick Dietary Fish and {omega}-3 Fatty Acid Consumption and Heart Rate Variability in US Adults Circulation, March 4, 2008; 117(9): 1130 - 1137. [Abstract] [Full Text] [PDF]

				G. Laurent, G. Moe, X. Hu, B. Holub, H. Leong-Poi, J. Trogadis, K. Connelly, D. Courtman, B. H. Strauss, and P. Dorian Long chain n-3 polyunsaturated fatty acids reduce atrial vulnerability in a novel canine pacing model Cardiovasc Res, January 1, 2008; 77(1): 89 - 97. [Abstract] [Full Text] [PDF]

				B. London, C. Albert, M. E. Anderson, W. R. Giles, D. R. Van Wagoner, E. Balk, G. E. Billman, M. Chung, W. Lands, A. Leaf, et al. Omega-3 Fatty Acids and Cardiac Arrhythmias: Prior Studies and Recommendations for Future Research: A Report from the National Heart, Lung, and Blood Institute and Office of Dietary Supplements Omega-3 Fatty Acids and Their Role in Cardiac Arrhythmogenesis Workshop Circulation, September 4, 2007; 116(10): e320 - e335. [Full Text] [PDF]

				D. Mozaffarian and E. B. Rimm Fish intake, contaminants, and human health: evaluating the risks and the benefits. JAMA, October 18, 2006; 296(15): 1885 - 1899. [Abstract] [Full Text] [PDF]

				D. Mozaffarian, R. J. Prineas, P. K. Stein, and D. S. Siscovick Dietary Fish and n-3 Fatty Acid Intake and Cardiac Electrocardiographic Parameters in Humans J. Am. Coll. Cardiol., August 1, 2006; 48(3): 478 - 484. [Abstract] [Full Text] [PDF]

				C. Wang, W. S Harris, M. Chung, A. H Lichtenstein, E. M Balk, B. Kupelnick, H. S Jordan, and J. Lau n-3 Fatty acids from fish or fish-oil supplements, but not {alpha}-linolenic acid, benefit cardiovascular disease outcomes in primary- and secondary-prevention studies: a systematic review Am. J. Clinical Nutrition, July 1, 2006; 84(1): 5 - 17. [Abstract] [Full Text] [PDF]

				J. L Breslow n-3 Fatty acids and cardiovascular disease Am. J. Clinical Nutrition, June 1, 2006; 83(6): S1477 - 1482S. [Abstract] [Full Text] [PDF]

				American Heart Association, S. S. Gidding, B. A. Dennison, L. L. Birch, S. R. Daniels, M. W. Gilman, A. H. Lichtenstein, K. T. Rattay, J. Steinberger, N. Stettler, et al. Dietary Recommendations for Children and Adolescents: A Guide for Practitioners Pediatrics, February 1, 2006; 117(2): 544 - 559. [Abstract] [Full Text] [PDF]

				T. L. Huang, P. P. Zandi, K. L. Tucker, A. L. Fitzpatrick, L. H. Kuller, L. P. Fried, G. L. Burke, and M. C. Carlson Benefits of fatty fish on dementia risk are stronger for those without APOE {epsilon}4 Neurology, November 8, 2005; 65(9): 1409 - 1414. [Abstract] [Full Text] [PDF]

				A. Leaf, C. M. Albert, M. Josephson, D. Steinhaus, J. Kluger, J. X. Kang, B. Cox, H. Zhang, D. Schoenfeld, and for the Fatty Acid Antiarrhythmia Trial Investigat Prevention of Fatal Arrhythmias in High-Risk Subjects by Fish Oil n-3 Fatty Acid Intake Circulation, November 1, 2005; 112(18): 2762 - 2768. [Abstract] [Full Text] [PDF]

				Endorsed by the American Academy of Pediatrics, S. S. Gidding, B. A. Dennison, L. L. Birch, S. R. Daniels, M. W. Gilman, A. H. Lichtenstein, K. T. Rattay, J. Steinberger, N. Stettler, et al. Dietary Recommendations for Children and Adolescents: A Guide for Practitioners: Consensus Statement From the American Heart Association Circulation, September 27, 2005; 112(13): 2061 - 2075. [Abstract] [Full Text] [PDF]

				D. Mozaffarian, A. Geelen, I. A. Brouwer, J. M. Geleijnse, P. L. Zock, and M. B. Katan Effect of Fish Oil on Heart Rate in Humans: A Meta-Analysis of Randomized Controlled Trials Circulation, September 27, 2005; 112(13): 1945 - 1952. [Abstract] [Full Text] [PDF]

				D. Mozaffarian, C. L. Bryson, R. N. Lemaitre, G. L. Burke, and D. S. Siscovick Fish Intake and Risk of Incident Heart Failure J. Am. Coll. Cardiol., June 21, 2005; 45(12): 2015 - 2021. [Abstract] [Full Text] [PDF]

				L. Calo, L. Bianconi, F. Colivicchi, F. Lamberti, M. L. Loricchio, E. de Ruvo, A. Meo, C. Pandozi, M. Staibano, and M. Santini N-3 Fatty Acids for the Prevention of Atrial Fibrillation After Coronary Artery Bypass Surgery: A Randomized, Controlled Trial J. Am. Coll. Cardiol., May 17, 2005; 45(10): 1723 - 1728. [Abstract] [Full Text] [PDF]

				D. Mozaffarian, W. T. Longstreth Jr, R. N. Lemaitre, T. A. Manolio, L. H. Kuller, G. L. Burke, and D. S. Siscovick Fish Consumption and Stroke Risk in Elderly Individuals: The Cardiovascular Health Study Arch Intern Med, January 24, 2005; 165(2): 200 - 206. [Abstract] [Full Text] [PDF]

				D. Mozaffarian, A. Ascherio, F. B. Hu, M. J. Stampfer, W. C. Willett, D. S. Siscovick, and E. B. Rimm Interplay Between Different Polyunsaturated Fatty Acids and Risk of Coronary Heart Disease in Men Circulation, January 18, 2005; 111(2): 157 - 164. [Abstract] [Full Text] [PDF]

				J. H. Christensen, S. Riahi, E. B. Schmidt, H. Mølgaard, A. K. Pedersen, F. Heath, J. C. Nielsen, and E. Toft n-3 Fatty acids and ventricular arrhythmias in patients with ischaemic heart disease and implantable cardioverter defibrillators Europace, January 1, 2005; 7(4): 338 - 344. [Abstract] [Full Text] [PDF]

				A. T Erkkila, A. H Lichtenstein, D. Mozaffarian, and D. M Herrington Fish intake is associated with a reduced progression of coronary artery atherosclerosis in postmenopausal women with coronary artery disease Am. J. Clinical Nutrition, September 1, 2004; 80(3): 626 - 632. [Abstract] [Full Text] [PDF]

				D. Mozaffarian, B. M. Psaty, E. B. Rimm, R. N. Lemaitre, G. L. Burke, M. F. Lyles, D. Lefkowitz, and D. S. Siscovick Fish Intake and Risk of Incident Atrial Fibrillation Circulation, July 27, 2004; 110(4): 368 - 373. [Abstract] [Full Text] [PDF]

				K. He, Y. Song, M. L. Daviglus, K. Liu, L. Van Horn, A. R. Dyer, and P. Greenland Accumulated Evidence on Fish Consumption and Coronary Heart Disease Mortality: A Meta-Analysis of Cohort Studies Circulation, June 8, 2004; 109(22): 2705 - 2711. [Abstract] [Full Text] [PDF]

				D. S. Siscovick, R. N. Lemaitre, and D. Mozaffarian The Fish Story: A Diet-Heart Hypothesis With Clinical Implications: n-3 Polyunsaturated Fatty Acids, Myocardial Vulnerability, and Sudden Death Circulation, June 3, 2003; 107(21): 2632 - 2634. [Full Text] [PDF]

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