The Role of Omega-3-Fatty Acids in the Prevention of Cardiac Events

Abstract

Cardiac disease continues to be a major cause of death in the Western world. Several preventive measures can be implemented to reduce the risk of a cardiac event. One of these measures is diet. A diet that is rich in fatty fish provides a considerable quantity of omega-3-fatty acids. These fatty acids have been shown to reduce the risk of cardiac events such as arrhythmias, stroke and thrombosis. The nurse has a key health education role to play in the promotion of healthy eating in order to reduce the incidence of cardiac events in patients with existing cardiac disease.

Key words: * Cardiovascular system and disorders * Nutrition and diet

Cardiac disease continues to be a major cause of death in the UK accounting for 238000 deaths in 2002 (British Heart Foundation, 2004). Cardiovascular disease is one of the most common forms of premature death (before the age of 75 years) in the UK. It contributes to more than 35% of the premature deaths in males and 27% of premature deaths in females (British Heart Foundation, 2004). Government initiatives, such as the National Service Framework in Coronary Heart Disease, aim to inform practitioners of the measures that can be undertaken to reduce the incidence of cardiovascular disease within the population of the UK (Department of Health (DoH), 2000).

Measures to lower the risk of cardiovascular disease through dietary modification and health education, including exercise, are thought to be beneficial in reducing cholesterol and improving cardiac status (American Heart Association (AHA), 2000). Health educators have a key role to play in the education of patients on diet and its related benefits of healthy eating. This article aims to present some evidence to support the role and benefits of omega- 3-fatty acids and their impact on existing cardiovascular disease.

Figure 1. Structure of the omega-3-fatty adds EPA and DHA.

It is well established that a diet that is rich in unsaturated and polyunsaturated fatty acids, such as fish, sea food, vegetable oils, and olive oil, lower cholesterol, whereas a diet that is rich in saturated-fatty acids, that can be found in full-fat dairy produce, such as butter, cream and full-fat cheese, can increase cholesterol levels (Crombie, 1999).

Omega-3-fatty acids are not produced by the body and therefore have to be provided by diet. Rich sources of omega-3-fatty acids are found in cold water fish such as sardines, salmon, herring, trout and mackerel (Daniels, 2004).These essential oils are also found in tofu, almonds, walnuts, canola, soyabeans and flaxseed oil (American Heart Association (AHA), 2000). Omega3-fatty acids contain two acids: eicosapentaenoic acid (EPA) and docasahexaenoic acid (DHA). EPA is the major omega-3-fatty acid and is converted to DHA. Subsequently, DHA is metabolized to a range of metabolically active molecules commonly referred to as eicosanoids (AHA, 2000). These are locally produced compounds that possess inflammatory characteristics and include prostaglandins and leukotrienes (Figure 1).

In fish, omega-3-fatty acids are contained in lipid stores located within the liver, peritoneal lining, underneath the skin and in muscle tissue (Fish Foundation, 2000). Recommendations for omega- 3-fatty acids 0.3-0.5 g/day EPA and DHA are advised by the Institute of Medicine (2002). This requirement can be met by consuming two fish meals per week with emphasis on eating at least one meal containing fatty fish such as mackerel, salmon, herrings, pilchards or sardines (Institute of Medicine, 2002). Commerically prepared fried fish should be avoided as this tends to be low in omega-3- fatty acids and high in trans-fatty acids. Trans-fatty acids are athrogenic (capable of forming lipid-filled plaques in coronary and cerebral arteries) and should be avoided (AHA, 2000) (Figure 2).

It is true to say that eating a diet rich in omega-3-fatty acids is beneficial to cardiac health (Daniels, 2004). Patients with coronary heart disease or hypercholesterolaeniia should be encouraged to increase the consumption of omega-3-fatty acids to 1 g/ day through diet and supplementation with EPA and DHA (Kris- Etherton et al, 2002).The requisite amount offish may be difficult to sustain over the long term; therefore, the use of supplementary EPA and DHA may be required, with estimates of 3 x 1 g fish oil capsules producing 1 g/day of omega-3-fatty acids required (Kris- Etherton et al, 2002). Fish oil capsules are generally free of sideeffects, but they may cause a ‘fishy’ aftertaste. Nurse educators need to educate patients on the role of omega-3-fatty acids in the diet. Diets that are high in unsaturated and polyunsaturated fats lower ‘bad’ cholesterol; in contrast, saturated fats increase ‘bad’ cholesterol. The ideal diet is high in monosaturated and polyunsaturated fatty acids (AHA, 2000) (Figure J).There should be a higher polyunsaturated to saturated fatty-acid ratio and high-fibre content. This balance can induce numerous favourable changes in coronary artery disease risk factors in hypercholesterolaemic men (Beuschesne-Rondeau et al, 2003).

Figure 2. Trans-fatty adds -formed when the ‘kink’ in a fatty add is lost as a result of rotation about the double bond.

EPA and DHA are postulated to be beneficial to patients with pre- existing cardiovascular disease (AHA, 2002). EPA and DHA are beneficial for healthy eating and for cardiac function (Table 1).

Fish consumption

Evidence to support a role for eating fish has been provided through numerous studies that illustrate the cardiac benefits of eating fish and the quantities needed to improve existing cardiac conditions (Howe, 1997; Belch, 2000; Kris-Etherton et al, 2002). There is no consistent estimate of the quantities offish that should be consumed. Iso et al (2001) suggest that an individual should eat at least one portion of fish per week to reduce the risk of stroke. Stone (1996) found that men who ate more than 35 g of fish had a reduced risk of coronary heart disease and sudden death by myocardial infarction. However, Burr et al (1989), in their studies of males with a history of myocardial infarction, found the consumption of 200-40Og of fatty fish per week provided 500-800 mg/ day of omega-3-fatty acids. This enriched quantity of omega-3-fatty acids helped to reduce the symptoms of angina in patients with fatal myocardial infarction. Findings from this study led to the hypothesis that omega-3-fatty acids might protect the myocardium against the adverse sequela of acute ischaemic stress. Landmark et al (1998a,b) suggest that an intake of 200-40Og of fatty fish per week -would be suggestive of a chronic intake of fish. Such an intake has been associated with a reduction in infarct size, estimated by peak creatine kinase and lactate dehydrogenase activities post-myocardial infarction and the frequency of Q-wave infarcts (Landmark et al, 1998a,b).

The perceived cardiac benefits of consuming fatty fish, in particular herring, mackerel and sardines, are thought to be a lowering of coronary heart disease mortality (ShekeUe et al, 1985; Kromhout et al, 1995; Oomen et al, 2000) and a reduction in cardiac risk factors (Mizushima et al, 1997). In their study, Mizushima et al (1997) reported a dose response relationship between frequency of weekly fish intake and reduced incidence of cardiovascular risk factors which included: obesity; hypertension; glycol-haemoglobin; ST-T segment; and change in the electrocardiograph. Siscovick et al (1995) also suggest that consumption of two fatty fish meals per week equated to a 50% reduction in primary cardiac arrest. In their study, they found an inverse relationship between blood levels of omega-3-fatty acids and risk of sudden death in men with a history of coronary vascular disease. Cholesterol metabolism can also be affected by fish consumption. Sanchez-Muniz et al (2003) found that whole sardines fried in olive oil normalized cholesterol metabolism in hypercholesterolemic rats quicker than consumption of extracted fat. The clinical benefit of this study, although potentially worthwhile, is limited, as equivalent studies have not been undertaken in man.

Figure 3. Cholesterol metabolism and transport. Cholesterol is transported from the liner to the blood and the tissues by VLDL and LDL (‘bad cholesterol’). LDL is associated with atherosclerosis. Bad cholesterol is increased by saturated fats in the diet. Cholesterol is returned to the liver by HDL (‘good cholesterol’). Good cholesterol is increased by monosaturated and polyunsaturated fats in the diet (which therefore decreases bad cholesterol).

Table I. Potential benefits of eicosapentaenoic acid (EPA) and docasahexaenoic acid (DHA)

Not all studies on the cardiac benefits of fish consumption have been so convincing. Marckmann and Gronbaek (1999) suggest that the protective effect of fish consumption relates to the coronary heart disease risk status of the population being studied and may relate to the type offish consumed. Oomen et al (2000) concur with this and suggest that the consumption of fatty fish, but not lean fish, reportedly lowers coronary heart disease mortality in populations. However, there are some contrasting studies that suggest no association exists between fish consumption and reduced risk of myocardial infarction, nonsudden cardiac death or total cardiovascular mortality (Ascherio et al, 1995; Albert et al,1998; Hu et al, 2002) or coronary heart disease incidence and mortality (Kromhout et al, 1996). Several reasons may account for the perceived lack of association between fish consumption and reduced risk of myocardial infarction or coronary mortality.These include; the small scale of the studies involved; how fish consumption was estimated; and the study population (Albert et al, 1998; Sheard, 1998).

Interestingly, the EURAMIC (European Community Study on Antioxidants, Myocardial Infarction and Breast Cancer) study (Guallar et al, 1999) was an international case-control study that showed no evidence of a protective effect of adipose fatty acids (a marker of long-term consumption of DHA) on the risk of developing a myocardial infarction (Guallar et al, 1999). In addressing the data generated from the EURAMIC study,Johansen et al (1999) propose that differences in findings may be owing to variability in the end- point studied (i.e. the patient outcomes – sudden death as opposed to development of a myocardial infarction and its manifestations). This may include definitions of sudden death, experimental design, different study populations, how fish intake is measured, and estimated and confounding effect of an increase in haemorrhagic stroke (Sheard, 1998).

Supplementation with EPA and DHA has also been found to have beneficial cardiac effects. Singh et al (1997) found that patients with acute myocardial infarction who consumed fish oil capsules (1.8 g/day EPA and DHA) had 25% less cardiac effects than the control group who did not receive fish oil capsules. More recently, Belch (2000) explored the role of essential fatty acids in the development of heart disease. Several vascular substances were assessed to explore the impact of essential fatty acids on the vascular system. Several vascular proteins were assessed in patients receiving dietary supplementation of essential fatty acids; these included: the vascular damage marker thromobomodulin, nitric oxide (a substance produced by platelets that vasodilates blood vessels), and plasma endothelin (a protein that has a vasoconstricting effect on blood vessels). Findings indicate that dietary supplementation with essential fatty acids improved vascular tone and reduced vascular damage to blood vessels. These findings confirmed the premise that individuals should consume three or four portions of fish per week in order to prevent heart disease (Belch, 2000).

Nurses as health educators can play a key role in the identification of potential risk factors and the provision of dietary advice in relation to the need for individuals to acknowledge the benefits of a weekly consumption of fatty fish.

Triglycerides

Grimsgaard et al (1998) suggest that omega-3-fatty acids such as EPA and DHA may possess triglyceride-lowering properties and offer cardioprotective effects in patients consuming 1 g/day. EPA and DHA are sensitive to post-prandial triglyceride levels. Fish oil can have a therapeutic role in the treatment of patients with marked hypertriglyceridaemia (AHA, 2000). However, patients who administer more than 3 g/day of supplemental EPA and DHA should do so under the care of a physician owing to the potential risk of bleeding (British National Formulary, 2005).

Stroke

The role of fish and omega-3-fatty acid supplementation has provided contrasting views. Iso et al (2001) postulate that fish consumption may offer some protection against stroke. This is supported by Gillum et al (1996) who reported that the ageadjusted stroke incidence was reduced by half in women with pre-existing cardiac disease who consumed fish compared to women who did not consume fish. Similarly, consumption of fish oil capsules containing 900 mg/day of EPA and DHA have been shown to offer some protection against the development of strokes (Albert et al, 1998). Oomen et al (2000) conducted a large population study over 3.5 years; 324 patients from Italy, Finland and the Netherlands with pre-existing coronary heart disease were randomized to either take omega-3-fatty acids or not (the control). The researchers reported that the group randomized to omega-3-fatty acids experienced a 15% reduction in non- fatal myocardial infarction, or non-fatal stroke, compared to the control group who were not having omega-3-fatty acids. However, larger more recent trials do not support this conclusion (Morris et al, 1995; Orencia et al, 1996;Johansen et al, 1999).

Blood pressure

Omega-3-fatty acids have a small, dose-dependent, hypotensive effect which appears to be dependent on the degree of hypertension (Howe, 1997). However, Morris et al (1993) found that omega-3-fatty acids had a marginal role in the management of blood pressure most likely owing to the high doses of EPA and DHA required to induce a superficial effect on blood pressure in hypertensive patients. This is in agreement with the AHA (2002) who suggests that owing to the high doses of EPA and DHA required to lower blood pressure, omega-3- fatty acids have a limited role in the management of hypertension.

Arrhythmias

The omega-3-fatty acids DHA and EPA appear to elicit multiple effects on the myocardium and the development of cardiac arrhythmias (Pepe and McLennan, 1996). The antiarrhythmic effects include effects on haemodynamics, cardiac mechanics, arterial endothelial function and reductions in the incidence of sudden cardiac death based on evidence from a prospective cohort study (Albert et al, 1998), a case control study (Siscovick et al, 1995), and four prospective dietary interaction trials (Burr et al, 1989; Smgh et al, 1997).

Figure 4. Parasympathetic nerve ending, where acetylcholine and nitric oxide affect vascular tone and vasodilation; DHA = docasahexaenoic acid; EPA – eicosapentaenoic add.

Similarly, Lee and Lip (2003) found that omega-3-fatty acids possessed some degree of cardioprotective activity by their ability to electrogenically stabilize the myocardium resulting in reduced susceptibility to ventricular arrhythmias, thereby reducing the risk of sudden death. EPA and DHA also reduced the resting heart rate and increased the left ventricular filling capacity (Grimsgaard et al, 1998), reduced damage to cardiac tissue and forestalled the development of ventricular arrhythmias when heart attacks were reduced (Pepe and McLennan, 1996; Billman et al, 1997). Omega3- fatty acids also influence the exchange of essential ions that play a role in cardiac automaticity and arrhythmia prevention. For example, the prevention of calcium overload by maintaining the activity of L-type calcium channels during periods of stress (Hallaq et al, 1992) and the potent inhibition of voltage-gated sodium channels (Kang and Leaf, 1996).

Thrombosis and blood vessel tone

Vascular tone is partially controlled by the parasympathetic nervous system and the neurotransmitter acetylcholine (Burke et al, 2003). Acetylcholine is released locally and can promote the relaxation of small arteries. Goode et al (1997) reported that acetylcholine-induced relaxation of small arteries was much improved in hypercholesterolaemic patients that had received supplementation with 3 g/day of DHA and EPA for a period of 3 months. Blood vessel tone can also be influenced by the release of nitric oxide. This substance can cause vasodilation of the blood vessel wall. Harris (1997) found that nitric oxide production was enhanced and endothelial function and arterial compliance improved by supplementation with fish oil. Supplementation of omega-3-fatty acids 5.1g/day for 6 months in coronary patients can also increase the soluble forms of e-selection (a vascular adhesion molecule that is involved in the transport of molecules across blood vessel walls) and vascular cell adhesion molecule (VCAM-1), both of which are important in transport across the blood vessel wall (Figure 4).

A small reduction in myocardial infarction was reported in patients receiving the equivalent of two fish meals per week (Bandolier, 2004). In contrast, Nilsen et al (2001) found that 3.5g/ day of EPA and DHA failed to influence cardiac events post- myocardial infarction. The lack of effect may be owing to the high habitual fish intake in residents of northern Norway which could have afforded maximal protection beyond which no additional effects would be expected (Nilson et al, 2001).

Fish oils may also have an affect on the coagulation of blood. Eritsland et al (1996) reported that 610 patients undergoing coronary artery bypass grafting and administering omega-3-fatty acids had a 6% reduction in vein graft occlusion rate reductions from 33% to 27%. In contrast, coronary artery risk development in young adults was explored in the CARDIA (Coronary Artery Risk Development in Young Adults) study (Knapp, 1997), but no significant association between consumption offish and clotting coagulation factors was found.

Figure 5. The effect of omega-3-fatty acids on TNF (tumour necrosis factor) and interleukin production, and on the arachidonic acid cascade.

Fish oil also affects the metabolism of the inflammatory mediators interleukin and tumour necrosis factor (Endres and von Schacky, 1996), both of which are believed to play a role in athrogenesis (the development of lipid-laden plaques in coronary and cerebral arteries) and plaque stability (Lee and Libby, 1997). It is thought that omega-3-fatty acids interfere with the arachidonic acid cascade and the production of eicosanoids (Uauy et al, 1999). EPA can replace arachidonic acid in phospholipids bilayers and competitively inhibit cyclooxygenase reducing the production of prostaglandins, particularly prostacyclin, thromboxane A2 and leukotrienes.The net effect is one where omega-3-fatty acids reduce inflammatory processes, vasoconstriction, platelet aggregation and promote anti-arthrogenic activity, i.e. the development of processes that are involved in the development of lipid-laden plaques in coronary and cerebral arteries (AHA, 2002) (Figur\e 5).

Conclusion

EPA and DHA are components of omega-3-fatty acids commonly found in sea food and fatty fish. Numerous studies have highlighted the benefits of the consumption of three fish meals per week with emphasis on at least one fatty fish meal per week, such as mackerel, salmon, herring, or trout. Dietary supplementation with EPA and DHA are both thought to be beneficial to the cardiovascular system and assist the reduction of cardiovascular risk. As health educators, the benefits of providing appropriate dietary advice to patients cannot be over estimated. Nurses have a health education role to play and should be confident in their ability to express the benefits and the cardioprotective effects of omega-3-fatty acids and the need for dietary modification in order to sustain a healthy heart.

KEY POINTS

* Omega-3-fatty acids are lipid molecules that are thought to be beneficial to health by reducing the risk of cardiac events such as arrhythmias and sudden cardiac death.

* A diet that is rich in essential oils can be found in seafood, walnuts, almonds and soyabeans.

* Supplementation of the diet with the consumption of omega-3- fatty acids is thought to be beneficial to the cardiovascular system.

* Cardiac conditions such as cardiovascular disease and coronary heart disease are one of the main causes of death in the UK.

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Maggi Banning is Research Fellow, The School of Health and Social Sciences, Middlesex University, Archway Campus, London

Accepted for publication: March 2005

Copyright Mark Allen Publishing Ltd. May 12-May 25, 2005