O'keefe JH Jr, Abuissa H, Sastre A, et al. Effects of Omega-3 Fatty Acids on Resting Heart Rate, Heart Rate Recovery After Exercise, and Heart Rate Variability in Men With Healed Myocardial Infarctions and Depressed Ejection Fractions. Am J Cardiol,

We explored possible mechanisms by which recommended intakes of omega-3 fatty acids may decrease the risk for sudden cardiac death in patients with documented coronary heart disease.

The cardioprotective effects of omega-3 fatty acids have been documented in epidemiologic and randomized controlled trials. These fatty acids are presumed to decrease susceptibility to fatal arrhythmias, but whether this is mediated by classic risk factors or direct cardiac mechanisms is not known.

Eighteen white men with a history of myocardial infarction and ejection fractions <40% were randomized to placebo or omega-3 fatty acids (585 mg of docosahexaenoic acid and 225 mg of eicosapentaenoic acid) for two 4-month periods in a crossover design.

At the end of each period, heart rate (HR), HR variability, and rate of HR recovery after exercise were determined, as were effects on arterial compliance, blood pressure, cardiac function, and fasting serum levels of lipids and inflammatory markers.

Omega-3 fatty acids decreased HR at rest from 73 +/- 13 to 68 +/- 13 beats/min (p <0.0001) and improved 1-minute HR recovery after exercise (-27 +/- 10 to -32 +/- 12 beats/min, p <0.01). HR variability in the high-frequency band increased (p <0.02), but no change was noted in overall HR variability.

There were no significant effects on blood pressure, arterial compliance, lipids, or inflammatory markers. These changes are consistent with an increase in vagal activity and may in part explain the observed decrease in risk for sudden cardiac death seen with omega-3 fatty acid supplementation.

PMID: 16616012

Leaf A, Albert CM, Josephson M, et al. Prevention of Fatal Arrhythmias in High-Risk Subjects by Fish Oil n-3 Fatty Acid Intake. Circulation. 2005;112:2762-2768.

Background: The long-chain n-3 fatty acids in fish have been demonstrated to have antiarrhythmic properties in experimental models and to prevent sudden cardiac death in a randomized trial of post?myocardial infarction patients.

Therefore, we hypothesized that these n-3 fatty acids might prevent potentially fatal ventricular arrhythmias in high-risk patients.

Methods and Results: Four hundred two patients with implanted cardioverter/defibrillators (ICDs) were randomly assigned to double-blind treatment with either a fish oil or an olive oil daily supplement for 12 months.

The primary end point, time to first ICD event for ventricular tachycardia or fibrillation (VT or VF) confirmed by stored electrograms or death from any cause, was analyzed by intention to treat.

Secondary analyses were performed for "probable" ventricular arrhythmias, "on-treatment" analyses for all subjects who had taken any of their oil supplements, and "on-treatment" analyses only of those subjects who were on treatment for at least 11 months.

Compliance with double-blind treatment was similar in the 2 groups; however, the noncompliance rate was high (35% of all enrollees).

In the primary analysis, assignment to treatment with the fish oil supplement showed a trend toward a prolonged time to the first ICD event (VT or VF) or of death from any cause (risk reduction of 28%; P=0.057).

When therapies for probable episodes of VT or VF were included, the risk reduction became significant at 31%; P=0.033.

For those who stayed on protocol for at least 11 months, the antiarrhythmic benefit of fish oil was improved for those with confirmed events (risk reduction of 38%; P=0.034).

Conclusions: Although significance was not achieved for the primary end point, this study provides evidence that for individuals at high risk of fatal ventricular arrhythmias, regular daily ingestion of fish oil fatty acids may significantly reduce potentially fatal ventricular arrhythmias.

Jouven X, Charles M, Desnos M, et al. Circulating Nonesterified Fatty Acid Level as a Predictive Risk Factor for Sudden Death in the Population. Circulation 2001;104:756-761.

Background In ischemic conditions, concentration of circulating nonesterified fatty acids (NEFA) is increased and has a proarrhythmic effect that is responsible for ventricular tachyarrhythmias. In nonischemic patients, high NEFA plasma concentration has been shown to be associated with frequent premature ventricular complexes and increased familial risk of cardiovascular disease, but its relation to sudden death has not been studied. We assessed the role of circulating NEFA in sudden death in asymptomatic men in a long-term cohort study.

Methods and Results A total of 5250 men employed by the city of Paris, aged 42 to 53 in 1967 to 1972, free of known ischemic cardiac disease, and included in the Paris Prospective Study I, completed a second annual examination and had fasting plasma circulating NEFA measured. Each subject underwent a physical examination and ECG, provided blood for laboratory tests, and answered questionnaires administered by trained interviewers. Vital status was obtained for each subject from specific inquiries until he retired; after retirement, it was obtained from death certificates. Body mass index, systolic and diastolic blood pressures, tobacco consumption, parental history of sudden death, fasting cholesterol level, and circulating NEFA concentration were independent factors associated with sudden death during follow up (average, 22 years). When adjusted for confounding factors, circulating NEFA concentration remained an independent risk factor for sudden death (relative risk, 1.70; 95% confidence interval, 1.21 to 2.13) but not for fatal myocardial infarction.

Conclusions Circulating NEFA concentration is an independent risk factor for sudden death in middle-aged men. Some form of primary prevention could be envisaged in subjects at high risk of sudden death.

Mozaffarian D, Psaty BM, Rimm EB, et al. Fish Intake and Risk of Incident Atrial Fibrillation Circulation, 2004;110:368-373.

Background Atrial fibrillation (AF) is the most common arrhythmia in clinical practice and is particularly common in the elderly.

Although effects of fish intake, including potential antiarrhythmic effects, may favorably influence risk of AF, relationships between fish intake and AF incidence have not been evaluated.

Methods and Results In a prospective, population-based cohort of 4815 adults age 65 years, usual dietary intake was assessed at baseline 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.
AF incidence was prospectively ascertained on the basis of hospital discharge records and annual electrocardiograms.

During 12 years follow-up, 980 cases of incident AF were diagnosed. In multivariate analyses, consumption of tuna or other broiled or baked fish was inversely associated with incidence of AF, with 28% lower risk with intake 1 to 4 times per week (HR=0.72, 95% CI=0.58 to 0.91, P=0.005), and 31% lower risk with intake 5 times per week (HR=0.69, 95% CI=0.52 to 0.91, P=0.008), compared with <1 time per month (P trend=0.004).

Results were not materially different after adjustment for preceding myocardial infarction or congestive heart failure. In similar analyses, fried fish/fish sandwich consumption was not associated with lower risk of AF.

Conclusions Among elderly adults, consumption of tuna or other broiled or baked fish, but not fried fish or fish sandwiches, is associated with lower incidence of AF. Fish intake may influence risk of this common

Marchioli R, Barzi F, et al. Early protection against sudden death by n-3 polyunsaturated fatty acids after myocardial infarction: time-course analysis of the results [ ]. Circulation, 2002;105:1897-1903.

BACKGROUND: Our purpose was to assess the time course of the benefit of n-3 polyunsaturated fatty acids (PUFAs) on mortality documented by the GISSI-Prevenzione trial in patients surviving a recent (<3 months) myocardial infarction.

METHODS AND RESULTS: In this study, 11,323 patients were randomly assigned to supplements of n-3 PUFAs, vitamin E (300 mg/d), both, or no treatment (control) on top of optimal pharmacological treatment and lifestyle advice. Intention-to-treat analysis adjusted for interaction between treatments was carried out. Early efficacy of n-3 PUFA treatment for total, cardiovascular, cardiac, coronary, and sudden death; nonfatal myocardial infarction; total coronary heart disease; and cerebrovascular events was assessed by right-censoring follow-up data 12 times from the first month after randomization up to 12 months. Survival curves for n-3 PUFA treatment diverged early after randomization, and total mortality was significantly lowered after 3 months of treatment (relative risk [RR] 0.59; 95% CI 0.36 to 0.97; P=0.037). The reduction in risk of sudden death was specifically relevant and statistically significant already at 4 months (RR 0.47; 95% CI 0.219 to 0.995; P=0.048). A similarly significant, although delayed, pattern after 6 to 8 months of treatment was observed for cardiovascular, cardiac, and coronary deaths.

CONCLUSIONS: The early effect of low-dose (1 g/d) n-3 PUFAs on total mortality and sudden death supports the hypothesis of an antiarrhythmic effect of this drug. Such a result is consistent with the wealth of evidence coming from laboratory experiments on isolated myocytes, animal models, and epidemiological and clinical studies.

Franzosi MG, Brunetti M, et al. Cost-effectiveness analysis of n-3 polyunsaturated fatty acids (PUFA) after myocardial infarction: results from Gruppo Italiano per lo Studio della Sopravvivenza nell'Infarto (GISSI)-Prevenzione Trial. Pharmacoeconomics

OBJECTIVE: To estimate the cost effectiveness of treatment with n-3 polyunsaturated fatty acids (PUFA) for secondary prevention after myocardial infarction (MI).

DESIGN AND SETTING: The cost-effectiveness analysis of n-3 PUFA treatment after MI was based on morbidity and mortality data and the use of resources obtained prospectively during the 3.5 year follow-up period of the Gruppo Italiano per lo Studio della Sopravvivenza nell'Infarto (GISSI)-Prevenzione study. The cost-effectiveness analysis took into account the incremental number of life-years gained and the incremental costs for hospital admissions, diagnostic tests and drugs, applying a 5% discount rate. The value for money of n-3 PUFA treatment was assessed using the cost-effectiveness ratio and the number needed to treat (NNT) approach.

PERSPECTIVE: Third-party payer.

MAIN OUTCOME MEASURES AND RESULTS: The incremental cost-effectiveness ratio for n-3 PUFA in the basecase scenario was 24,603 euro (EUR, 1999 values) per life-year gained (95% confidence interval: 22,646 to 26,930). Sensitivity analysis included the analysis of extremes, producing estimates varying from EUR15,721 to EUR52,524 per life-year gained. 172 patients would need to be treated per year with n-3 PUFA, at an annual cost of EUR68,000, in order to save 1 patient. This is comparable with the NNT value, and associated annual cost for simvastatin, but less costly than that for pravastatin.

CONCLUSIONS: The cost effectiveness of long term treatment with n-3 PUFA is comparable with other drugs recently introduced in the routine care of secondary prevention after MI. Since the clinical benefit provided by n-3 PUFA is additive, this therapy should be added to the established routine practice, with additive costs.

Marchioli R, Schweiger C, et al. Efficacy of n-3 polyunsaturated fatty acids after myocardial infarction: results of GISSI-Prevenzione trial. Lipids, 2001;36:S119-126.

Gruppo Italiano per lo Studio della Sopravvivenza nell'Infarto Miocardio (GISSI)-Prevenzione was conceived as a population, pragmatic trial on patients with recent myocardial infarctions conducted in the framework of the Italian public health system. In GISSI-Prevenzione, patients were invited to follow Mediterranean dietary habits, and were treated with up-to-date preventive pharmacological interventions. Long-term n-3 PUFA (1 g daily) but not vitamin E (300 mg daily) was beneficial for death and for combined death, nonfatal myocardial infarction, and stroke. All the benefit, however, was attributable to the decrease in risk for overall, cardiovascular, cardiac, coronary, and sudden death. At variance with the orientation of a scientific scenario largely dominated by the "cholesterol-heart hypothesis," GISSI-Prevenzione results indicate n-3 PUFA (virtually devoid of any cholesterol-lowering effect) as a relevant pharmacological treatment for secondary prevention after myocardial infarction. As to the relevance and comparability of GISSI-Prevenzione results, up to 5.7 lives could be saved every 1000 patients with previous myocardial infarction treated with n-3 PUFA (1 g daily) per year. Such a result is comparable to that observed in the Long-Term Intervention with Pravastatin in Ischaemic Disease (LIPID) trial, where 5.2 lives could be saved per 1000 hypercholesterolemic, coronary heart disease patients treated with pravastatin for 1 yr. The choice of a relatively low-dose regimen (1-g capsule daily) more acceptable for long-term treatment in a population of patients following Mediterranean dietary habits, and the pattern of effects seen in GISSI-Prevenzione (namely, reduction of overall mortality with no decrease in the rate of nonfatal myocardial infarction) all strongly suggest that n-3 PUFA treatment should be considered a recommended new component of secondary prevention. The importance of this combined/additive effect is further suggested by the analyses of the interplay between diet and n-3 PUFA: There is an interesting direct correlation between size of the effect and "correctness" of background diets. It can be anticipated that a conceptual barrier must be overcome: A "dietary drug" should be added to "dietary advice," which remains fundamental to allow this statement to become true in clinical practice.

Calo L, Bianconi L, et al. N-3 Fatty acids for the prevention of atrial fibrillation after coronary artery bypass surgery: a randomized, controlled trial. J Am Coll Cardiol, 2005;45(10) :1723-1728.

OBJECTIVES: The aim of this study was to assess the efficacy of preoperative and postoperative treatment with n-3 polyunsaturated fatty acids (PUFAs) in preventing the occurrence of atrial fibrillation (AF) after coronary artery bypass graft surgery (CABG).

BACKGROUND: Postoperative AF is a common complication of CABG. There is growing clinical evidence that PUFAs have cardiac antiarrhythmic effects.

METHODS: A total of 160 patients were prospectively randomized to a control group (81 patients, 13 female, 64.9 +/- 9.1 years) or PUFAs 2 g/day (79 patients, 11 female, 66.2 +/- 8.0 years) for at least 5 days before elective CABG and until the day of discharge from the hospital. The primary end point was the development of AF in the postoperative period. The secondary end point was the hospital length of stay after surgery. All end points were independently adjudicated by two cardiologists blinded to treatment assignment.

RESULTS: The clinical and surgical characteristics of the patients in the two groups were similar. Postoperative AF developed in 27 patients of the control group (33.3%) and in 12 patients of the PUFA group (15.2%) (p = 0.013). There was no significant difference in the incidence of nonfatal postoperative complications, and postoperative mortality was similar in the PUFA-treated patients (1.3%) versus controls (2.5%). After CABG, the PUFA patients were hospitalized for significantly fewer days than controls (7.3 +/- 2.1 days vs. 8.2 +/- 2.6 days, p = 0.017).

CONCLUSIONS: This study first demonstrates that PUFA administration during hospitalization in patients undergoing CABG substantially reduced the incidence of postoperative AF (54.4%) and was associated with a shorter hospital stay.

Hu FB, Bronner L, et al. Fish and Omega-3 Fatty Acid Intake and Risk of Coronary Heart Disease in Women. JAMA. 2002;287(14):1815-1821.

CONTEXT: Higher consumption of fish and omega-3 fatty acids has been associated with a lower risk of coronary heart disease (CHD) in men, but limited data are available regarding women.

OBJECTIVE: To examine the association between fish and long-chain omega-3 fatty acid consumption and risk of CHD in women.

DESIGN, SETTING, AND PARTICIPANTS: Dietary consumption and follow-up data from 84,688 female nurses enrolled in the Nurses' Health Study, aged 34 to 59 years and free from cardiovascular disease and cancer at baseline in 1980, were compared from validated questionnaires completed in 1980, 1984, 1986, 1990, and 1994. MAIN

OUTCOME MEASURES: Incident nonfatal myocardial infarction and CHD deaths.

RESULTS: During 16 years of follow-up, there were 1513 incident cases of CHD (484 CHD deaths and 1029 nonfatal myocardial infarctions). Compared with women who rarely ate fish (<1 per month), those with a higher intake of fish had a lower risk of CHD. After adjustment for age, smoking, and other cardiovascular risk factors, the multivariable relative risks (RRs) of CHD were 0.79 (95% confidence interval [CI], 0.64-0.97) for fish consumption 1 to 3 times per month, 0.71 (95% CI, 0.58-0.87) for once per week, 0.69 (95% CI, 0.55-0.88) for 2 to 4 times per week, and 0.66 (95% CI, 0.50-0.89) for 5 or more times per week (P for trend =.001). Similarly, women with a higher intake of omega-3 fatty acids had a lower risk of CHD, with multivariable RRs of 1.0, 0.93, 0.78, 0.68, and 0.67 (P<.001 for trend) across quintiles of intake. For fish intake and omega-3 fatty acids, the inverse association appeared to be stronger for CHD deaths (multivariate RR for fish consumption 5 times per week, 0.55 [95% CI, 0.33-0.90] for CHD deaths vs 0.73 [0.51-1.04]) than for nonfatal myocardial infarction.

CONCLUSION: Among women, higher consumption of fish and omega-3 fatty acids is associated with a lower risk of CHD, particularly CHD deaths.

Raitt MH, Connor WE, Morris C, et al. Fish Oil Supplementation and Risk of Ventricular Tachycardia and Ventricular Fibrillation in Patients With Implantable Defibrillators: A Randomized Controlled Trial. JAMA. 2005;293:2884-2891.

Context: Clinical studies of omega-3 polyunsaturated fatty acids (PUFAs) have shown a reduction in sudden cardiac death, suggesting that omega-3 PUFAs may have antiarrhythmic effects.

Objective: To determine whether omega-3 PUFAs have beneficial antiarrhythmic effects in patients with a history of sustained ventricular tachycardia (VT) or ventricular fibrillation (VF).

Design and Setting: Randomized, double-blind, placebo-controlled trial performed at 6 US medical centers with enrollment from February 1999 until January 2003.

Patients: Two hundred patients with an implantable cardioverter defibrillator (ICD) and a recent episode of sustained VT or VF.

Intervention: Patients were randomly assigned to receive fish oil, 1.8 g/d, 72% omega-3 PUFAs, or placebo and were followed up for a median of 718 days (range, 20-828 days).

Main Outcome Measures: Time to first episode of ICD treatment for VT/VF, changes in red blood cell concentrations of omega-3 PUFAs, frequency of recurrent VT/VF events, and predetermined subgroup analyses.

Results: Patients randomized to receive fish oil had an increase in the mean percentage of omega-3 PUFAs in red blood cell membranes from 4.7% to 8.3% (P<.001), with no change observed in patients receiving placebo.
At 6, 12, and 24 months, 46% (SE, 5%), 51% (5%), and 65% (5%) of patients randomized to receive fish oil had ICD therapy for VT/VF compared with 36% (5%), 41% (5%), and 59% (5%) for patients randomized to receive placebo (P = .19).

In the subset of 133 patients whose qualifying arrhythmia was VT, 61% (SE, 6%), 66% (6%), and 79% (6%) of patients in the fish oil group had VT/VF at 6, 12, and 24 months compared with 37% (6%), 43% (6%), and 65% (6%) of patients in the control group (P = .007). Recurrent VT/VF events were more common in patients randomized to receive fish oil (P<.001).

Conclusion: Among patients with a recent episode of sustained ventricular arrhythmia and an ICD, fish oil supplementation does not reduce the risk of VT/VF and may be proarrhythmic in some patients.

Hoang A, Canada T. Omega-3 Fatty Acids for the Prevention of Atrial Fibrillation After Coronary Artery Bypass Surgery: A Randomized, Controlled Trial. Nutrition in Clinical Practice 2006:21;2:189-190.

Objectives:
The aim of this study was to assess the efficacy of preoperative and postoperative treatment with omega-3 polyunsaturated fatty acids (PUFAs) in preventing the occurrence of atrial fibrillation (AF) after coronary artery bypass graft surgery (CABG).

Background:
Postoperative AF is a common complication of CABG. There is growing clinical evidence that PUFAs have cardiac antiarrhythmic effects.

Methods:
A total of 160 patients were prospectively randomized to a control group (81 patients, 13 female, 64.9 ± 9.1 years) or PUFAs 2 g/day (79 patients, 11 female, 66.2 ± 8.0 years) for at least 5 days before elective CABG and until the day of discharge from the hospital.

The primary end point was the development of AF in the postoperative period. The secondary end point was the hospital length of stay after surgery. All end points were independentlyadjudicated by 2 cardiologists blinded to treatment assignment.

Results:
The clinical and surgical characteristics of the patients in the 2 groups were similar. Postoperative AF developed in 27 patients of the control group (33.3%) and in 12 patients of the PUFAs group (15.2%) (p = .013). There was no significant difference in the incidence of nonfatal postoperative complications, and postoperative mortality was similar in the PUFAs-treated patients (1.3%) vs controls (2.5%). After CABG, the PUFAs patients were hospitalized for significantly fewer days than controls (7.3 ± 2.1 days vs 8.2 ± 2.6 days, p = .017).

Conclusions:
This study first demonstrates that PUFA administration during hospitalization in patients undergoing CABG substantially reduced the incidence of postoperative AF (54.4%) and was associated with a shorter hospital stay.

Albert CM, Campos H, et al. Blood levels of long-chain n-3 fatty acids and the risk of sudden death. N Eng J. Med 2002. Apr 11; 346(15):1113-1118.

BACKGROUND: Experimental data suggest that long-chain n-3 polyunsaturated fatty acids found in fish have antiarrhythmic properties, and a randomized trial suggested that dietary supplements of n-3 fatty acids may reduce the risk of sudden death among survivors of myocardial infarction. Whether long-chain n-3 fatty acids are also associated with the risk of sudden death in those without a history of cardiovascular disease is unknown.

METHODS: We conducted a prospective, nested case-control analysis among apparently healthy men who were followed for up to 17 years in the Physicians' Health Study. The fatty-acid composition of previously collected blood was analyzed by gas-liquid chromatography for 94 men in whom sudden death occurred as the first manifestation of cardiovascular disease and for 184 controls

RESULTS: Base-line blood levels of long-chain n-3 fatty acids were inversely related to the risk of sudden death both before adjustment for potential confounders (P for trend = 0.004) and after such adjustment (P for trend = 0.007). As compared with men whose blood levels of long-chain n-3 fatty acids were in the lowest quartile, the relative risk of sudden death was significantly lower among men with levels in the third quartile (adjusted relative risk, 0.28; 95 percent confidence interval, 0.09 to 0.87) and the fourth quartile (adjusted relative risk, 0.19; 95 percent confidence interval, 0.05 to 0.71).

CONCLUSIONS: The n-3 fatty acids found in fish are strongly associated with a reduced risk of sudden death among men without evidence of prior cardiovascular disease.

DALLAS, May 27 Eating oily fish like salmon, tuna or bluefish at least twice a week can prevent sudden cardiac death because fatty acids in the fish block dangerous irregular heart rhythms, experts say in a review article in todays issue of Circulation: Journal of the American Heart Association.

Epidemiologists have known for years that eating fish was associated with reduced risk of cardiovascular disease, but only recently have researchers had laboratory evidence to explain this effect, says review author Alexander Leaf, M.D., Jackson Professor of Clinical Medicine Emeritus, Harvard Medical School, Boston. Leaf and colleagues present a detailed explanation of how omega-3 (n-3) fish oils benefit the heart.

Animal experiments show that fatty acids from n-3 fish oils are stored in the cell membranes of heart cells and can prevent sudden cardiac death or fatal arrhythmias, Leaf says.

Arrhythmias are irregular heart rhythms. Leaf says that studies of individual heart cells demonstrated that the omega-3 essential polyunsaturated fatty acids (n-3 PUFAs) specifically block excessive sodium and calcium currents in the heart. Those excessive electrical discharges cause dangerous and erratic changes in heart rhythm.

The first clinical suggestion that n-3 PUFAs significantly benefited the heart came from a 1989 study in which 2,033 men with heart disease were given dietary advice on fat, fiber or fish. After two years the men who were told to eat fish at least twice a week had a 29 percent reduction in death. There was no benefit in either the fiber or fat groups.

Since about 50 percent to 60 percent of deaths in the setting of coronary heart disease are sudden cardiac death [deaths within one hour of symptoms of a heart attack] attributed to sustained ventricular arrhythmias the authors write, the reduction in deaths reported in this early study is probably evidence of fewer fatal arrhythmias.

This initial study was followed by a series of observational studies and controlled clinical trials. All arrived at the same conclusion: A diet rich in fatty fish reduced fatal heart attacks. But Leaf says that this protection was still not completely understood.

In early animal experiments, researchers demonstrated that animals fed a diet in which 12 percent of the calories came from saturated fat died of sustained ventricular fibrillation, but animals that were also fed n-3 PUFAs did not develop these dangerous arrhythmias when their coronary arteries were tied off.

But then Leaf and other researchers still needed to find out if there were any plausible biochemical or physiological effects of these n-3 fatty acids which could explain their antiarrhythmic action. To do so, they cultured neonatal heart cells from rats and observed them under the microscope. The cells clump together and the clump beats spontaneously, rhythmically and simultaneously just like the whole heart.

Using a video camera, Leaf and his colleagues taped the action of the cells and the effect of different toxic agents on the cells. They discovered that adding n-3 PUFA prevented arrhythmias induced in the cells.

Leaf and his colleagues conclude that n-3 fatty acids have been part of the human diet for some 2-4 million years during which our genes were adapting to our environment, including our diets. They are safe and have been listed on the GRAS list (generally regarded as safe) according to the FDA.

Leaf says that fresh or frozen fish are the best choices but canned tuna can be used if it is packed in water. Tuna packed in oil is not a good choice because the extra oil will extract the beneficial n-3 oil from the fish, he says.

According to a recent American Heart Association scientific statement a dietary approach to increasing omega-3 fatty acid intake is preferable. Still, for patients with coronary artery disease, the dose of omega-3 (about one gram per day) may be greater than what can readily be achieved through diet alone. These individuals, in consultation with their physician, could consider supplements for CHD risk reduction.

The association recommends that individuals with certain cardiovascular conditions consult with their physician about fish oil supplements.

In an accompanying editorial, authors David S. Siscovick, M.D., Rozenn N. Lemaitre, Ph.D., and Dariush Mozaffarian, M.D. say the messages from Leaf and colleagues are clear.

?For clinicians, it is time to implement the current American Heart Association dietary guidelines . . . For policymakers, there is a need to consider a new indication for treatment with low-dose n-3 PUFA supplements the prevention of sudden cardiac death in patients with a prior [heart attack]. For researchers, there is a need to continue both clinical studies and studies that explore the mechanism through which n-3 PUFAS influence the risk of sudden cardiac death, they write. The American Heart Association estimates that sudden cardiac death causes 250,000 deaths in the United States each year.

Co-authors are Jing X. Kang, M.D., Ph.D.; Yong-Fu Xiao, M.D., Ph.D.; and George E. Billman, Ph.D. The study was partly funded by the National Institutes of Health and the American Heart Association.

Source: http://www.americanheart.org/presenter.jhtml?identifier=3012101

Leaf A. J. Diet and Sudden Cardiac Health. Nutr Health Aging 2001; 5(3):173-178.

The purpose of this paper is to review the evidence that dietary factors, namely the ingestion of the n-3 (or w-3) polyunsaturated fatty acids of fish oils can prevent fatal cardiac arrhythmias (so-called sudden cardiac death) in experimental animals, and probably in humans as well. The mechanism for this striking effect results from the ability of these fatty acids to directly stabilize electrically every contractile myocyte in the heart. This is accomplished by modulation by the free n-3 fatty acids of the ionic currents in heart cells; particularly the voltage-dependent sodium currents which initiate action potentials and the L-type calcium currents, which initiate release of sarcoplasmic reticulum stores of calcium into the cytosol of heart cells. The resultant rise in cytosolic calcium concentration initiates contraction of the heart cells and the beating rate of the heart. The gradually accumulating clinical evidence that these fish oil fatty acids are potent preventors of cardiac sudden death in humans will be reviewed. With some 250,000 deaths occurring within one hour of the onset of acute myocardial infarctions annually in the USA alone and millions more in the whole world, the potential large public health benefit from this understanding is evident.

Singer P, Wirth M. Can n-3 PUFA reduce cardiac arrhythmias? Results of a clinical trial. Prostaglandins Leukot Essent Fatty Acids, 2004; 71(3): 153-159

Dietary n-3 polyunsaturated fatty acids (PUFA) derived from fatty fish or fish oil may reduce the incidence of lethal myocardial infarction and sudden cardiac death..

This might be due to a prevention of fatal cardiac arrhythmias. So far, however, only few clinical data are available being adequate to define indications for an antiarrhythmic treatment with n-3 PUFA.

In a randomized, double-blind, placebo-controlled study 65 patients with cardiac arrhythmias without coronary heart disease or heart failure were subdivided into 2 groups.

One group (n = 33) was supplemented with encapsulated fish oil (3g/day, equivalent to 1g/day of n-3 PUFA) over 6 months.
The other group (n = 32) was given 3g/day of olive oil as placebo.

In the fish oil group a decrease of serum triglycerides, total cholesterol, LDL cholesterol, plasma free fatty acids and thromboxane B2 as well as an increase of HDL cholesterol were observed.

Moreover, a reduced incidence of atrial and ventricular premature complexes, couplets and triplets were documented.

Accordingly, higher grades of Lown's classification switched to lower grades at the end of the dietary period.

No changes were seen in the placebo group.

The data indicate an antiarrhythmic action of n-3 PUFA under conditions of clinical practice which might help to explain the reduced incidence of fatal myocardial infarction and sudden cardiac death in cohorts on a fish-rich diet or supplemented with n-3 PUFA.

Further studies elucidating the possible link between the reduced incidence of cardiac arrhythmias and sudden cardiac death by dietary intake of n-3 PUFA are warranted.