Cardiovascular disease (CVD)

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Chapter 10 Cardiovascular disease (CVD)

Reducing risk factors

In the management of all of these risk factors an integrated approach to the treatment of CVD is required, which includes mind–body medicine, nutrition, supplements and exercise.

For treatment and prevention of hyperlipidaemia see Chapter 18.

For treatment and prevention of hypertension see Chapter 19.

Obesity

A distinct relationship between body weight, blood pressure and CVD have been well documented, and the relative risk of developing hypertension, a risk factor for CVD, increases as body mass index (BMI) increases.4 Modest weight loss of approximately 10% of body weight can normalise blood pressure. A recent review of the Trials Of Hypertension Prevention (TOHP) phase II revealed that a weight loss of approximately 5 kg can result in a significant reduction in blood pressure.5 Advice about weight loss is essential. Maintaining weight loss is the greatest difficulty faced by patients. A healthy diet and regular exercise are essential for maintaining ideal BMI.

Recently it has been reported that people lose weight by just eating fewer calories, regardless of where those calories come from.6, 7 In this US study it was reported that after 2 years, 811 overweight adults randomised to 1 of 4 heart-healthy diets, each emphasising different levels of fat, protein, and carbohydrates, showed similar degrees of weight loss. On average, participants in the study lost 6 kg in 6 months, but gradually began to regain weight after 12 months, regardless of diet group. Briefly, the diets tested in the study included the same types of foods, but in different proportions, and were tailored to patients such that overall calorie consumption was reduced by approximately 750 calories per day, with each diet including a different macronutrient composition:

Prevention

The public and health professionals must implement comprehensive preventative programs that address lifestyle and nutritional issues if it is to achieve a significant reversal of the increasing incidence of CVD worldwide.1 The major focus is currently on treatment of CVD, however, there is increasing interest in dealing with the factors responsible for this disease, but more needs to be done. More is known about the factors responsible for CVD than most other diseases and hence it lends itself well to interventions with primary and secondary prevention.

The Australian Heart Foundation website provides extensive public and health professional information on risk factors, prevention and lifestyle strategies for hypertension and CVD.8

Lifestyle

Many studies consistently demonstrate greater reduction of cardiac risk factors by implementing positive lifestyle behavioural changes such as avoiding smoking, stress management, dietary changes, and physical activity.9, 10

Combining a low-risk diet and healthy lifestyle behaviour, such as moderate amounts of alcohol, being physically active, not smoking, and maintaining a healthy weight, can significantly reduce the risk of myocardial infarction according to a population-based prospective study of 24 444 post-menopausal women diagnosed with cancer, CVD and diabetes mellitus.11 Specifically the protective lifestyle factors included: not smoking, waist-hip ratio less than the 75th percentile (< 0.85), being physically active (at least 40 minutes of daily walking or bicycling and 1 hour of weekly exercise) and a dietary pattern characterised by a high intake of vegetables, fruit, wholegrains, fish, and legumes, in combination with moderate alcohol consumption (no more than 5 g of alcohol per day; a standard glass of wine contains 11g of alcohol). The authors concluded that most myocardial infarctions are preventable through lifestyle changes.

The Ornish program has shown that it is possible to reverse CVD in selected patients using a program that incorporates aspects to do with the causes of this disease, namely, psychological factors, nutritional factors and exercise.12 The Ornish program includes a very low fat, whole food, vegetarian diet rich in complex carbohydrates and low in simple sugars (supplemented with vitamin B12) along with regular walking, smoking cessation and stress management techniques. This program produced a 91% reduction in the frequency of angina and there was regression of coronary atherosclerosis after only 1 year and even more regression after 5 years in select patients.3 The control group had increased coronary atherosclerosis and increased angina after 1 year and even more stenosis after 5 years. This program has been criticised because patients can have difficulty in maintaining such a low-fat diet, plus tended to have increased serum triglycerides and decreased high density lipoprotein (HDL). Dietary fish or fish oil supplementation can be used to normalise triglycerides and have been demonstrated to improve survival in patients with coronary artery disease and hypercholoesterolaemia.13, 14

Despite an increasing interest by various public health authorities to recommend lifestyle and dietary changes to population groups, the general health of those groups is deteriorating as reflected by a decrease in physical activity and a massive increase in the problem of overweight and obesity.2

In recent reviews it has been shown that people in developed countries just do not consume the recommended daily allowance of 6–8 helpings of fruit and vegetables.15, 16 Hence the recommendations have included supplementation with good multivitamin and mineral preparations.5 In an article in the Heart Lung journal, Lewis encourages doctors to utilise nutritional supplements to assist in the management of patients with CVD.17 In his article he cites the benefits that are to be gained from patients adopting lifestyle–nutritional changes that can easily be annexed to traditional treatment options, and explains why it is necessary. A unique part of this article is how he describes the 3 distinct morphological processes of CVD and explains the difference between primary and secondary prevention. The 3 distinct pathological processes are plaque growth, which begins in adolescence and involves oxidation of low-density lipoprotein (LDL) cholesterol, plaque rupture, and clot formation which leads to immediate coronary artery occlusion and arrhythmias which result from myocardial ischemia. Understanding the timing of the distinct pathological processes allows for the most appropriate use of certain nutritional supplements.

Certainly the inappropriate timing of nutritional supplement use could explain why supplements may not be effective in some CVD studies. Despite this there is increasing evidence that supplements such as vitamins, minerals and omega-3 fats are useful in the prevention and management of CVD.

Family lifestyle intervention for children

Obesity in children and adolescence is a growing problem in virtually every developed country and the prevalence is rising. Extrapolation from current US data found adolescent overweight is projected to increase the prevalence of obesity in adulthood (35-year-olds) in 2020 to 30–37% in men and 34–44% in women, which will consequently increase the incidence and risk of coronary heart disease (CHD), cardiac events and deaths in young adults and the middle aged.18 Management of the child to lose weight needs to focus on lifestyle interventions such as modifying diet, physical activity and behavioural therapies within the whole family. A recent Cochrane review evaluated the efficacy of lifestyle, drug, and surgical interventions to treat obesity in childhood.19 A total of 12 studies were directed at lifestyle interventions (physical activity and sedentary behaviour), 6 studies addressed diet and 36 evaluated behaviourally oriented treatment programs. This review concluded that family-based lifestyle interventions that modify diet and physical activity and include behavioural therapy can significantly help obese children lose weight and maintain that loss for at least 6 months compared to standard care or self-help alone.

Breast-feeding

A recent study investigated the relationship between duration of lactation and maternal incident myocardial infarction.20 It was reported that compared with parous women who had never breastfed, women who had breastfed for a lifetime total of 2 years or longer had 37% lower risk of CHD, adjusting for age, parity, and stillbirth history.

Mind–body medicine

Participants of a large prospective population-based cohort study of 6025 adults without CHD followed for a mean of 15 years demonstrated a dose-response relationship between emotional vitality (defined as a positive state associated with feelings of enthusiasm, energy, and interest) and reduced risk of CHD.21 The authors concluded: emotional vitality may protect against risk of CHD in men and women.

Depression and social isolation

Depression and social isolation are strongly associated with CVD and can have a major influence on prognosis.22 The impact of depression and social isolation is of a similar order to conventional risk factors such as smoking. A study of up to 500 patients hospitalised for acute coronary syndrome found that the onset of depression immediately following an acute cardiac event significantly influenced the long-term survival and illness severity of the patient.23

The Heart and Soul Study is a prospective cohort study of 1017 outpatients with stable CHD followed for an average period of 4.8 years.24 After adjustment for co-morbid conditions and disease severity, depressive symptoms were associated with a significant 31% higher rate of cardiovascular events compared with those with no depression, which was largely explained by negative behaviour patterns such as physical inactivity.

Worrying and mental stress are also a risk factor for cardiac events, CHD and accelerates atherosclerosis according to studies.25, 26

Social isolation is a difficult problem to deal with and requires taking an extensive family history about family and friends and usually assistance and support from other health professionals and support groups.

A cohort of 13 000 women and men demonstrated a doubling of the coronary risk factor with social deprivation over a 10-year period.27 Having a close friend for regular support when needed can reduce the risk of subsequent myocardial infarction by 50%.28

An expert working group for the National Heart Foundation of Australia did a systematic review of the literature and found strong and consistent evidence to indicate depression, social isolation and lack of quality social support is associated with the causes and prognosis of CHD.29

Owning a pet may help pet owners survive longer after a heart attack and reduces heart rate variability according to a US study of 100 patients following a myocardial infarction when compared with non-pet owners.30

Social support

The Framingham Heart Study social network followed up 4739 individuals over a 10-year period and found that people’s degree of happiness was determined by the happiness of others whom they are connected with, being surrounded by happy people and geographical proximity in close range.31 For example, a happy friend who lives within 1.6 km increases the probability that a person is happy by 25%. Similar effects were seen with partners, siblings who live close and next door neighbours, but not seen between co-workers. Effects are not seen between co-workers and happiness declined with time and geographical separation.

Unhappy marriage

An interesting 5-year follow-up study found that women with CHD had a 3-times higher chance of major cardiac events and death over the 5 years if they had a stressful marital or cohabiting relationship.32 Negative relationships can increase the likelihood of cardiac events and in 1 study this risk was estimated to be as high as 34% compared with low level negativity.33, 34 A good marriage also improved survival in women with heart failure.35

Stress

Stress has been identified as a causative factor in hypertension.37 Stress is also known to precipitate cardiac events and is considered a more important marker of myocardial infarction than hypertension and diabetes. For example, viewing a stressful soccer match doubles the risk of an acute cardiovascular event such as risk of angina, myocardial infarction or arrhythmia.38 A sudden emotional shock such as the loss of a loved one can cause symptoms of myocardial infarction even in patients with no clinically significant coronary disease39, including in young people by triggering coronary vasospasm.40

A review of the literature has found stress impacts adversely on health and on longevity and can increase the risk of stroke.41, 42 A study found that for women who are content with their lives at home and at work, atherosclerosis can actually regress, but progresses in those experiencing ongoing stress, independent of other CVD risk factors such as age, smoking, hypertension and HDL levels at baseline.43 A Lancet review found a strong and consistent association between stress and CVD.44

Work stress

A prospective cohort of almost 1000 middle-aged patients following a myocardial infarction demonstrated chronic work stress was associated with a twofold increased risk of CVD 2–6 years after returning to work compared with low job stress.45 In another study of London civil servants, being in a ‘just’ or fair workplace reduced the risk of CHD by 35% compared to employees who described their work as being ‘unjust’.46 Also, a sense of ‘lack of control’ at work can increase the risk of CHD.47

Sleep

Siesta (afternoon nap)

Greek researchers demonstrated a daily siesta is protective towards CVD and coronary mortality according to a large scale cohort study of 23 681 individuals.54 After excluding confounders, occasional napping reduced risk of coronary mortality by 12%, and systematic napping by up to 37%, particularly in working men, compared with non-nappers. However, a recent report warns that excessive daytime sleepiness is an independent risk factor for total and cardiovascular-related mortality in elderly individuals.55

Sleep deprivation

Lack of sleep is being identified as a new risk factor for coronary artery disease, including calcification of the arteries. A US study of 500 healthy middle-aged men and women found that just 1 hour of extra sleep per night reduced the risk of calcification of the arteries (coronary artery calcification was measured by computed tomography) by an average of 33%.56 This association was more pronounced in women. The study adjusted for all other risk factors such as age, sex and BMI. The researchers postulated that blood pressure drops during sleep, so insufficient or poor quality sleep may interfere with the decline in blood pressure, increasing the risk of CVD.

A Japanese study of hypertensive patients also found after adjusting for confounders, short sleep duration significantly increases the risk of CVD compared with normal sleep duration.57 The researchers’ conclude that lack of sleep is an independent predictor of cardiovascular events.

Snoring and obstructive sleep apnoea (OSA)

OSA is a well-recognised risk factor for CVD and mortality, including nocturnal sudden cardiac death.58, 59 Sleep units are now well established in a number of hospitals, especially in developed countries, to help identify this problem and provide nocturnal oxygen inhalation therapy for those with confirmed sleep apnoea. Researchers found that sudden cardiac death occurred overnight significantly more in subjects with severe OSA (46%) than those without OSA (21%) or compared with sudden cardiac death victims in the general population (16%).60 An observational cohort study of 110 subjects who underwent bilateral carotid and femoral artery ultrasounds to quantify atherosclerosis, demonstrated snoring is a significant independent risk factor for carotid (not femoral) artery atherosclerosis; the risk factor increasing with degree of severity of snoring.61

Sunshine and vitamin D

Sunshine exposure, specifically solar ultraviolet B, is the major source for vitamin D production by the human body. Epidemiological studies indicate lack of ultraviolet light exposure may contribute to geographic and racial blood pressure differences, CVD and CVD mortality. 6266 Deaths due to CVD are more common in the winter and at higher or lower latitudes.67 Vitamin D deficiency is common worldwide and epidemiological evidence is associated with increased risk of CVD, hypertension, metabolic syndrome, heart disease, congestive heart failure, myopathy, chronic vascular inflammation, peripheral artery disease, hyperparathyroidism, autoimmune diseases, diabetes, cancer and all-cause mortality as well as many other diseases (see also Chapter 30, osteoporosis).6876 The proposed mechanisms include an increase in parathyroid hormone and activation of the rennin-angiotensin-aldosterone system. The hormone 1,25 hydroxy-vitamin D is involved in the production of renin which regulates blood pressure.

In a large prospective study the researchers demonstrated that deficiency in either 25-hydroxyvitamin D and 1,25-hydroxyvitamin D were equally associated with increase in all-cause mortality and CVD mortality.77 Serum parathyroid (PTH) levels increase when vitamin D levels fall below 75mmol/L. Slightly enhanced PTH levels are associated with CVD morbidity and mortality, as seen in renal patients and peripheral artery disease.7880

Also, studies demonstrate vitamin D deficiency is linked with elevated C-reactive protein levels which are associated with increased cardiovascular events.81 Whilst an observation study did not demonstrate an association of CVD and low levels of 1,25 hydroxy-vitamin D in patients with myocardial infarction,82 community-based studies have shown a strongly positive correlation with low vitamin D contributing to the pathogenesis of congestive cardiac failure and myocardial infarction.83, 84 A recent study of over 3200 patients referred for coronary angiogram and assessed over an 8-year period, found a strong independent correlation with low serum 25(OH)vitamin D (7.6–13.3ng/ml) and double risk of cardiovascular mortality.85 Overall the weight of evidence points strongly towards an association of CVD and lack of sunshine and vitamin D deficiency. Due to its widespread benefit in many areas of health, safe sunshine exposure of at least 30 minutes daily, with walking, would appear to be of great benefit to anyone to ensure normal vitamin D levels and for the prevention and management of CVD.

Environment

Physical activity

Yoga

Yoga has been recommended as efficacious in the primary and secondary prevention of ischaemic heart disease and post-myocardial infarction patient rehabilitation.99 There are several studies that demonstrate yoga can reduce cardiovascular reactivity to stress, a factor that is strongly associated with cardiovascular risk.100 Controlled studies have demonstrated that yoga can reduce blood pressure (see also Chapter 19, hypertension) and hence cardiovascular risk.101105

Qigong

Several randomised controlled trials have evaluated qigong interventions from multiple perspectives, specifically targeting older adults.101 In adults, particularly the aged, this form of physical activity can lead to significant improvements in physical functioning, mood, weight, and in the reduction of cardiovascular risk factors.101 Improvements in cardiovascular factors such as systolic and diastolic blood pressure, increased pre-ejection fraction and heart rate variability have been documented.108111

Physical therapies

Musculoskeletal therapy

Some complementary and alternative physical therapies show promise in cardiac rehabilitation.112 A recent study with stroke patients reported that single-modality exercises targeted at existing impairments do not optimally address the functional deficits of walking but did ameliorate the underlying impairments.113 Also the study reported that the underlying cardiovascular and musculoskeletal impairments were significantly modifiable years after stroke with targeted robust exercise. In another recent study it was reported that regular arm aerobic exercise lead to a marked reduction in systolic and diastolic blood pressures and an improvement in small artery compliance.114 The study further concluded that arm-cycling was a logical option for hypertensive patients who choose to support blood pressure control by sports despite having coxarthrosis, gonarthrosis, or intermittent claudication.

Acupuncture

An early report concluded that there were sufficient clinical studies in humans that demonstrate acupuncture can exert significant effects on the cardiovascular system and provide effective therapy for a variety of cardiovascular ailments.115 In a recent study of acupuncture and cardiac arrhythmias; the 8 eligible studies reviewed demonstrated that 87–100% of participants converted to normal sinus rhythm after acupuncture. Hence it was concluded that acupuncture seemed to be effective in treating several cardiac arrhythmias, but limited methodological quality of the studies necessitates better-controlled clinical trials to be performed.116

Nutritional influences

Worldwide dietary patterns

Diet is a modifiable risk factor for CVD. The INTERHEART study involving 52 countries identified 3 major dietary patterns: Oriental (high intake of tofu, soy and other sauces), Western (high in fried foods, salty snacks, eggs, and meat), and prudent (high in fruit and vegetables).118 The study demonstrated an inverse association between the prudent pattern and acute myocardial infarction (AMI); the Western pattern showed a U–shaped association with AMI; the Oriental pattern demonstrated no relationship with AMI. The researchers concluded that the unhealthy dietary intake increases the risk of AMI globally and accounts for about 30% of the population-attributable risk.

The INTERGENE population study of 3452 participants (aged 25–74 years) identified dietary patterns associated with CVD risk factors, obesity and metabolic syndrome.119 Unhealthy food patterns were characterised by high consumption of energy-dense drinks and white bread, and low consumption of fruit and vegetables. Healthy food patterns was distinguished by more frequent consumption of high-fibre and low–fat foods and lower consumption of products rich in fat and sugar.

A recent Cochrane review of the literature also demonstrates dietary advice lowers prevalence and incidence of CVD.120

The Seven Countries study demonstrated that population-related factors significantly affect the risk of CVD and that diet was directly related to the risk of developing coronary artery thrombosis that lead to heart attacks.120 Dietary factors were far more significant than other risk factors, as variations in cholesterol and incidence of smoking in men from one country to another did not account for the differences seen in CVD. This study also demonstrated lower levels of many cancers, dementia and all-cause mortality in people who adhered closely to their traditional Mediterranean or Japanese diets.

Olive oil

A study of patients with stable CHD aimed to identify the effects of olive oil on cardiac risk factor blood parameters.127 The placebo-controlled, cross-over, trial randomised patients with either raw daily dose of 50ml of virgin olive oil or refined olive oil over a total 6-week period and found reduction in the inflammatory markers interleukin-6 and C-reactive protein with virgin olive oil intervention compared with refined olive oil group, but no changes observed with glucose and lipid profile.

The polymeal

The polymeal, as opposed to the polypill, are the foods identified to be cardio-protective. The polymeal is far safer and more natural and can reduce the risk of CVD by more than 75% (see Table 10.1).128 Taking the polymeal daily significantly increased total life expectancy far greater in men than in women.

Table 10.1 Effect of ingredients of polymeal in reducing risk of CVD

Ingredients Average percentage reduction (95% CI) in risk of CVD source NHMRC level of evidenceMA = meta-analysis; RCT = randomised controlled trial
Wine (150ml/day) 32 % MA
Fish (114g x 4 times/week) 14% MA
Dark chocolate (100g/day) 21% RCT
Fruit and vegetables (400g/day) 21% RCT
Garlic (2.7g/day) 25% MA
Almonds (68g/day) 12.5% RCTs
Combined effect 76% (63 to 84%)  

(Source: adapted from Franco et al. 2005)128

A recent meta-analysis of 12 prospective cohort studies of over 1.5 million participants over a 3–18 year period affirms the health benefits of the Mediterranean diet.129 Stricter adherence to the diet conferred significant cardiac protection, and led to further reductions in risk of all cause-mortality, death from CVD, as well as cancer and degenerative diseases compared with low adherence. Adherence to the Mediterranean diet can also significantly reduce the risk for type 2 diabetes.130

High fibre diet

Total dietary fibre (cereal, fruit, and vegetable) is associated with a 14% reduction in the risk of all coronary events and a 27% decrease in the risk of coronary death.134 Further research confirms its protective role towards CVD according to analysis of the Physicians Health Study I, that demonstrated consumption of wholegrain cereal at breakfast and high dietary fibre are associated with less prevalence of hypertension, lower risk of heart failure and reduced incidence of myocardial infarction.135 Intakes of wholegrain fibre are inversely associated with progression of atherosclerosis, according to a study on post-menopausal women with coronary artery disease.136 Oatmeal for breakfast also reduces the risk of CHD.137

Dietary fibre also improves glycaemic control in diabetics, as well as lowering cholesterol/low-density lipoprotein LDL.

Vegetarian diet

A vegetarian diet has been reviewed for its beneficial and adverse effects in various medical conditions.139 It was concluded in that study that the beneficial effects may be due to the diet (consisting of monounsaturated and polyunsaturated fatty acids, minerals, fibre, complex carbohydrates, antioxidant vitamins, flavanoids, folic acid and phytoestrogens) as well as the associated healthy lifestyle that vegetarians pursue. There were few adverse effects reported and these consisted of increased intestinal gas production and a small risk of vitamin B12 deficiency.

A more recent report conducted over a mean of 8.1 years suggested a dietary intervention that reduced total fat intake and increased intakes of vegetables, fruits and grains did not significantly reduce the risk of CHD, stroke, or CVD in post-menopausal women and achieved only modest effects on CVD risk factors, suggesting that more focused dietary and lifestyle interventions may be needed to improve risk factors and reduce CVD risk.140

Fish and omega–3 polyunsaturated fatty acids

The benefits of eating just 1–2 servings of fish weekly can significantly reduce the risk of coronary death, which outweighs harm from contaminant exposure from mercury and dioxins from fish intake.141 Modest intake of fish consumption compared with eating fish only once weekly substantially reduced the risk of CHD amongst middle-aged persons.142 This prospective study of nearly 42 000 Japanese people demonstrated the more fish intake the lower the risk of CVD. The group with the highest fish intake, equivalent to 180g daily, reduced the CVD risk by 40%.

A number of cohort studies demonstrate that regular consumption of fish, even just 1–2 servings weekly, is associated with reduced risk of sudden death, cardiac arrest, heart failure and atrial fibrillation, compared with those who only eat fish once monthly.143, 144, 145

Salt/sodium restriction

Data from 2 randomised trials, TOHP I and TOHP II, involved a total of 3126 participants assessed over a 10–15 year period who were randomised to a sodium reduction intervention or control for 18 months (TOHP I) or 36-48 months (TOHP II).155 The researchers found a significant reduction in risk of a cardiovascular event by up to 30% among those in the low-sodium diet intervention group compared with control group. The researchers concluded: ‘Sodium reduction, previously shown to lower blood pressure, may also reduce long-term risk of cardiovascular events’. 154

A low-salt diet is also cardio-protective in normotensive patients, as well as effectively lowering blood pressure in hypertensives. A recent study of normotensive overweight and obese adults were randomised to low or standard diet groups.155 Within 2 weeks the low-salt diet group (50nmol sodium per day) demonstrated 30% less brachial artery flow-mediated dilatation, lower systolic blood pressure and reduced 24 hour sodium excretion compared with the standard diet group. This study highlights the need to remove salt from many prepared foods and in the diet to prevent the onset of hypertension.

Cocoa and/or dark chocolate

Several studies have shown that cocoa can decrease blood pressure to a similar extent to that of pharmaceuticals.156 New research suggests 1 serving of dark chocolate (20g; not milk chocolate) every 3 days significantly reduces the levels of the inflammatory marker C-reactive protein which may help to reduce inflammation, a known risk factor for many diseases, including CVD and cancer.157 A 30-day trial demonstrated drinking a cup of cocoa daily can improve flow-mediated dilation and combat blood vessel dysfunction linked to diabetes.158 Daily consumption of 46g of dark chocolate increased blood levels of flavonoid epicatechin and significantly improved arterial function in a group of healthy volunteers.159

Alcohol

Whilst the cardio-protective properties of moderate alcohol consumption, compared with abstinence or heavy drinking, are widely recognised, this interesting study, a longitudinal-based cohort study, aimed to identify whether the benefits are experienced equally by all moderate drinkers.160 The study found a significant benefit of moderate drinking was identified amongst those with poor health behaviours (little exercise, poor diet and smokers) compared with abstinence or heavy drinking. There was no additional benefit from alcohol amongst those with the healthiest behaviour profile (>3 hours vigorous exercise per week, daily fruit or vegetable consumption and non-smokers). The authors concluded the cardio-protective benefit from moderate alcohol drinking ‘does not apply equally to all drinkers, and this variability should be emphasised in public health messages’.160 However, another large-scale US study of a cohort of 8867 men over 16 years found after adjusting for confounders, moderate levels of alcohol (5–30g per day) reduced the risk of myocardial infarction by up to 50%.161

Nutritional supplements

Antioxidants

A US cross-sectional study assessed users of a broad range of daily nutritional, herbal and dietary supplements.172 After adjustment for age, gender, income, education and BMI, supplement use was associated with optimal levels of chronic disease biomarkers (serum homocysteine, C-reactive protein) and high-density lipoprotein cholesterol and triglycerides, less likely to have sub-optimal blood nutrient levels, elevated blood pressure, high BMI and diabetes compared with non-users or multivitamin/mineral users alone.

A trial of 13 017 French adults (7876 women aged 35–60 years and 5141 men aged 45–60 years) randomised to either a single daily capsule of antioxidants (120mg of ascorbic acid, 30mg of vitamin E, 6mg of beta-carotene, 100mcg of selenium and 20mg of zinc) or a placebo over a 7.5 year period. The study found the antioxidant supplement reduced the risk of cancer and all-cause mortality in men, but not in women.173 The researchers postulated that men are more likely to have lower baseline status of certain antioxidants, especially of beta-carotene.

Vitamins E and C

There is increasing biological plausibility for the use of vitamin supplements for the prevention of CVD. Oxidised LDL cholesterol attracts and interacts with monocytes, macrophages and platelets to promote atherogenesis and also causes endothelial necrosis plus interferes with vaso-relaxation. vitamins E and C have been shown to inhibit LDL oxidation and vitamin E reduces endothelial monocyte adhesion, as well as inhibiting platelet activation.174176 Angiographic and ultrasonographic studies in humans suggest that vitamin E also inhibits the progression of atherosclerosis.8, 9, 177 Often researchers do not distinguish between the synthetic and natural forms of vitamin E which have different structures and functions. Studies in general that utilise natural vitamin E and at doses of 500IU or above have shown a benefit.178 Whereas, studies that employed a lower dose or the synthetic form of the vitamin were found to be ineffective.11 There is a known synergy between vitamin E and vitamin C plus selenium that allows for a maximum benefit.

Vitamin E is synergistic also with aspirin as they are both cyclooxygenase inhibitors which significantly increases the efficacy of aspirin therapy.179 Unfortunately, there are no primary prevention studies that have evaluated the role of natural vitamin E. Vitamin C, in addition to regenerating the antioxidant properties of vitamin E, has an anti-inflammatory action which is thought to be important in the prevention of arterial disease.180

According to the Physician’s Health Study II, a double-blind, placebo-controlled trial of high doses of synthetic vitamin E (400IU 2nd daily) with vitamin C (500mg daily), or provided alone, compared with placebo over an 8-year period was not cardio-protective and did not reduce total mortality.181 It was also concerning that the vitamin E treatment group had a marginally significant increased risk of hemorrhagic stroke, which is plausible as vitamin E is known to prolong bleeding times. It is likely the benefits of vitamin E witnessed in other trials are found with the natural forms (not synthetic).

Findings from the Women’s Antioxidant Cardiovascular study of 1450 women also demonstrated no overall benefit of either ascorbic acid (500mg/d), vitamin E (600IU every other day) and beta-carotene (50mg every other day) for CVD, although there was a marginally significant reduction in the vitamin E group in women with prior history of CVD and those randomised to both active ascorbic acid and vitamin E experienced fewer strokes.182 There are concerns with the use of synthetic vitamin E.

Vitamin B

Nicotinic acid (Niacin)

Niacin lowers LDL cholesterol as well as triglycerides plus raising HDL and lowering total cholesterol. The major drawback is that it causes flushing at high doses and can cause liver toxicity.183 A slowly released form of niacin is generally better tolerated. Further, a meta-analysis of niacin has shown that it is a safe and an effective option for dyslipidemia.184

Folate, vitamin B12, vitamin B6 and Homoceysteine

Previously only very high levels of homocystine were thought to be related to coronary artery disease. More recent data suggests that levels as low as 12mol/L may increase the risk of vascular disease.185 There is a relationship between homocysteine levels and vascular disease that is supported by epidemiological data. However, there are also negative studies. Homocysteine is an amino acid product of normal protein metabolism. Folate, vitamin B12 and vitamin B6 are all involved in the metabolism of homocysteine. Deficiencies of 1 or more of these vitamins can lead to hyperhomocysteinemia.15, 186 Folic acid in combination with vitamin B12 and vitamin B6 have emerged as potentially valuable nutrients for the prevention and treatment of atherosclerosis.16

Since the voluntary fortification of foods in Australia with folate, serum folate levels have risen and there has been a corresponding reduction of homocysteine levels in a group of 468 adults in Western Australia over a 4-year period.187

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