Beyond lipids: The role of omega-3 fatty acids from fish oil in the prevention of coronary heart disease

Omega-3 fatty acid therapy shows great promise in the secondary prevention of coronary artery disease. A meta-analysis of recent omega-3 trials shows reductions of coronary heart disease mortality of 36% (95% Cl, 20%–50%; P < 0.001) and total mortality of 17% (95% Cl, 0%–32%; P = 0.046). Some of the potential mechanisms for cardiovascular protection include a reduction in cardiac arrhythmias and plaque stabilization. Since the publication of the landmark GISSI-Prevenzione trial, there have been three major intermediate cardiovascular endpoint studies in patients with implantable cardioverter defibrillators (ICDs) and one large trial, the Japan EPA Lipid Interventional Study (JELIS) trial, which involved 18,645 Japanese patients in primary and secondary prevention. The three studies with ICD patients have been mixed, with favorable trends toward reduction in the incidence of ventricular arrhythmias in some but not all of the studies. Results of the recent JELIS trial in a Japanese population already consuming a high intake of omega-3 fatty acids showed a 19% risk reduction in major coronary events. Most of the reductions were in unstable angina and nonfatal coronary events, but not in sudden death and cardiovascular mortality. The totality of evidence suggests greater benefits with omega-3 fatty acids in secondary prevention than primary prevention and in populations consuming low amounts of omega-3 fatty acids.     

The fats of life: the role of omega-3 fatty acids in the prevention of coronary heart disease

Epidemiological and clinical trial evidence suggests that omega-3 polyunsaturated fatty acids (PUFAs) might have a significant role in the prevention of coronary heart disease. Dietary sources of omega-3 PUFA include fish oils rich in eicosapentaenoic acid and docosahexaenoic acid along with plants rich in alpha-linolenic acid. Randomized clinical trials with fish oils (eicosapentaenoic acid and docosahexaenoic acid) and alpha-linolenic acid have demonstrated reductions in risk that compare favorably with those seen in landmark secondary prevention trials with lipid-lowering drugs. Several mechanisms explaining the cardioprotective effect of omega-3 PUFAs have been suggested, including antiarrhythmic, hypolipidemic, and antithrombotic roles. Although official US guidelines for the dietary intake of omega-3 PUFAs are not available, several international guidelines have been published. Fish is an important source of omega-3 PUFAs in the US diet; however, vegetable sources, including grains and oils, offer an alternative source for those who are unable to regularly consume fish.     

Usefulness of omega-3 fatty acids and the prevention of coronary heart disease

Clinical trial evidence exists that supports a role for the omega-3 polyunsaturated fatty acids in coronary heart disease prevention. However, the results from these clinical trials have varied and were conducted in diverse population groups using several different types of omega-3 polyunsaturated fatty acids, including eicosapentaenoic acid, docosahexaenoic acid, and alpha-linolenic acid (ALA). Thus, we systematically reviewed previously published reports assessing the different types of omega-3 polyunsaturated fatty acid interventions and cardiovascular outcomes. Fourteen randomized clinical trials were included in the review. Six trials were included with fish oil, with 1 large trial (10,000 patients) dominating the analysis. In aggregate, the fish oil trials demonstrated a reduction in total mortality and sudden death without a clinically significant reduction in nonfatal myocardial infarction. The 6 trials with ALA supplements or an ALA-enriched diet were of poorer design than the fish oil trials and had limited power. Many of the trials with ALA involved other changes in dietary components. In aggregate, the ALA trials demonstrated possible benefits in reducing sudden death and nonfatal myocardial infarction, but with wider confidence intervals than in the fish oil trials. In conclusion, the evidence suggests a role for fish oil (eicosapentaenoic acid, docosahexaenoic acid) or fish in secondary prevention because recent clinical trial data have demonstrated a significant reduction in total mortality, coronary heart disease death, and sudden death. The data on ALA have been limited by studies of smaller sample size and limited quality.     

Mediterranean diet and prevention of coronary heart disease in the elderly

There are now several scientific studies that relate this traditional dietary pattern with the incidence of coronary heart disease, various types of cancer, and other diseases. The past years have several observational and clinical studies suggested the mechanisms by which this traditional diet may affect coronary risk. This review underlines the importance of the Mediterranean dietary patterns in the prevention of coronary heart disease.     

Hypertriglyceridemia and omega-3 fatty acids: Their often overlooked role in cardiovascular disease prevention

Aims

This review aims to describe the pathogenic role of triglycerides in cardiometabolic risk, and the potential role of omega-3 fatty acids in the management of hypertriglyceridemia and cardiovascular disease.

Lipid-lowering drugs and essential omega-6 and omega-3 fatty acids in patients with coronary heart disease

BACKGROUND AND AIM: There are only little data about the effects of lipid-lowering drugs (LLDs) on the metabolism of essential n-6 and n-3 fatty acids in patients with established coronary heart disease (CHD). METHODS AND RESULTS: Male patients with CHD and high cholesterol levels (>6.2 mmol/L) were randomized (double-blind protocol) to receive either simvastatin 20mg (S) or fenofibrate 200mg daily (F) for 3 months. Dietary habits and plasma fatty acids were not different in the two groups at baseline. After treatment, there were significant changes in both the groups for the main n-6 fatty acids, with an increase in arachidonate (from 6.5+/-1.7% of total fatty acids to 7.5+/-2.1, p<0.001 in S and from 6.2+/-1.4 to 6.8+/-1.4, p<0.005 in F) and a decrease in linoleate (from 26.9+/-3.9 to 24.2+/-3.6, p<0.001, and from 27.8+/-3.4 to 26.1+/-4.2, p<0.05, in S and F, respectively). In addition, there was a decrease in two major n-3 fatty acids (alpha-linolenate and docosahexanoate, both p<0.05), but only in F. CONCLUSIONS: For the first time in a double-blind randomized study in CHD patients, we report that LLDs significantly alter the metabolism of essential fatty acids that are critically important for the pathogenesis and prevention of CHD. Further studies are urgently needed to examine the effects of higher dosages of statins (as currently proposed to reduce more cholesterol) on these essential fatty acids in the clinical setting and the crucial questions of whether specific dietary intervention (combining low intake of n-6 fatty acids and high intake of n-3 fatty acids) may improve the effectiveness of these drugs.     

The role of omega-3 fatty acids in cardiovascular disease

Plant-derived alpha-linolenic acid has been studied in a limited number of investigations. So far, some epidemiologic and a few mechanistic studies suggest a potential of protection from cardiovascular disease, but this potential remains to be proven in intervention studies. In contrast, eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), which are prevalent in fish and fish oils, have been studied in thousands of investigations. A consistent body of evidence has been elaborated in various types of investigations, ultimately demonstrating reduction in total mortality, cardiovascular mortality, and morbidity by ingestion of roughly I g/d of EPA plus DHA. Current guidelines, however, do not discern between the omega-3 fatty acids mentioned; in fact, most even do not differentiate polyunsaturated fatty acids at all. Unfortunately, this complicates efficient implementation of an effective means of prophylaxis of atherosclerosis.     

Mediterranean diet and survival among patients with coronary heart disease in Greece

BACKGROUND: The Mediterranean diet has been hypothesized to reduce fatality among patients with coronary heart disease. METHODS: We examined the association between the degree of adherence to the traditional Mediterranean diet and survival of persons with diagnosed coronary heart disease at enrollment, in a population-based prospective investigation of 1302 Greek men and women, who were followed up for an average of 3.78 years (the European Prospective Investigation Into Cancer and Nutrition cohort). Information on usual dietary intakes during the year preceding enrollment was recorded through a validated food frequency questionnaire. Adherence to the Mediterranean diet was assessed by a 10-unit Mediterranean diet score that incorporates the salient characteristics of this diet. Proportional hazards regression was used to assess the relation of overall degree of adherence to the Mediterranean diet with mortality overall or by cause (cardiac vs noncardiac). RESULTS: Higher adherence to the Mediterranean diet by 2 units was associated with a 27% lower mortality rate among persons with prevalent coronary heart disease at enrollment (total deaths, 131; adjusted mortality ratio, 0.73; 95% confidence interval, 0.58-0.93). The reduced mortality was more evident and amounted to 31% (total deaths, 85; adjusted mortality ratio, 0.69; 95% confidence interval, 0.52-0.93) when only cardiac deaths were considered as the relevant outcome. Associations between individual food groups contributing to the Mediterranean diet score and mortality were generally not significant. CONCLUSION: Greater adherence to the traditional Mediterranean diet is associated with a significant reduction in mortality among individuals diagnosed as having coronary heart disease.     

Relation of omega-3 Fatty Acid intake to other dietary factors known to reduce coronary heart disease risk

Data supporting the inverse correlation of fish or long-chain omega-3 fatty acid (FA) (eicosapentaenoic acid plus docosahexaenoic acid) supplement consumption and coronary heart disease are inconclusive and may be confounded by other dietary and lifestyle factors. Using the Diabetic Control and Complications Trial (DCCT) database (n = 1,441), correlations between consumption of omega-3 FAs and saturated FAs to dietary variables (kilocalories, macronutrients, sodium, and cholesterol) and to age, gender, exercise level, and tobacco use were tested using Pearson correlation coefficients. Long-chain omega-3 FA intake inversely correlated with consumption of calories (r = -0.16, p <0.0001), percent calories from total fat (r = -0.14, p <0.0001), and percent calories from saturated FAs (r = -0.21, p <0.0001) and directly with dietary fiber intake (grams per 1,000 kcal, r = 0.20, p <0.0001). In the DCCT database, long-chain omega-3 FAs (i.e., fish consumption) inversely correlated with an overall low risk nutritional profile for coronary heart disease. In conclusion, these findings provide evidence that associations observed in studies suggesting a benefit of fish or long-chain omega-3 FAs may be due to a convergence of greater fish intakes with an overall healthier dietary pattern rather than with a specific effect of long-chain omega-3 FAs.     

Diet and prevention of coronary heart disease: the potential role of phytochemicals

Epidemiological studies, and some clinical trials, demonstrate that a proper diet reduces the rate of occurrence of cardiovascular disorders. Several in vitro studies suggest that some components of plant foods, most of which sharing a phenolic structure, are endowed with interesting 'pharmacological activities'. This article reviews the evidence that links a high dietary intake of phytochemicals from various sources with a reduced incidence of coronary heart disease.     

The role of lipid metabolism in the prevention of coronary heart disease

Prevention of cardiovascular disease should be considered as a continuum from low to high risk: those at the highest risk are patients with clinically manifest cardiovascular disease, followed by subjects without known cardiovascular disease at different levels of risk from high to low. Today there is clear evidence that an independent relationship exists between plasma LDL cholesterol levels and the risk for coronary heart disease. The relationship between other plasma lipoproteins and atherosclerosis is more complex. The threshold for individuals requiring LDL cholesterol reduction is determined by epidemiological data, randomized controlled trials, and economic considerations. Patients with familial dyslipidemia suffer early coronary morbidity and mortality. For these patients, consequent lowering of LDL cholesterol should be the primary objective. For patients with established coronary heart disease or other atherosclerotic disease and for those with diabetes, there is significant evidence that reducing LDL cholesterol, irrespective of the initial values, reduces the risk of further coronary events, stroke, and total mortality. For asymptomatic individuals, the treatment of plasma lipids should be based on their absolute coronary risk, including other cardiovascular risk factors. The goals for plasma LDL cholesterol have been set in national and international recommendations. The goals for LDL cholesterol in patients with low, moderate and high coronary risk are <160, <130 and 100 mg/dl, respectively. In some very high risk patients LDL level markedly below 100 mg/dl should be aimed at. HDL cholesterol and triglyceride measurements should be used to identify individuals at high multifactorial risk of cardiovascular disease and used as additional considerations in the selection of lifestyle and drug interventions.     

Can supplementation of diet with omega-3 polyunsaturated fatty acids reduce coronary angioplasty restenosis rate?

The objective of this blinded, randomized, prospective study was to assess whether supplementation of normal diet with omega-3 polyunsaturated fatty acids can reduce angiographically defined restenosis following coronary angioplasty. The study included all patients undergoing coronary angioplasty in this institution between January 1988 and January 1989. One hundred and twenty patients enrolled, 60 in each treatment group. All were randomized to either supplementation of normal diet with 3 g of omega-3 polyunsaturated fatty acids per day started 1-2 days prior to angioplasty and continued for 6 months (treatment group), or to receive standard therapy only (control group). Quantitative angiographically defined restenosis was assessed at 6 months post angioplasty. Restenosis occurred in 27.8% (95% CI 18.0-37.7%) of lesions in the treatment group and in 28.3% (CI 16.9-39.7%) of lesions in the control group, but the difference was not statistically significant. The study showed that diet supplemented with 3 g of omega-3 polyunsaturated fatty acids started 1-2 days preceding angioplasty does not reduce angiographically defined restenosis rate.