Coronory Heart Disease

Timothy J. Key and Paul N. Appleby

CONTENTS

I. Introduction 34

II. Vegetarianism and Coronary Risk Factors 35

A. Established Risk Factors 35

1. Lipids and Lipoproteins 35

2. Hypertension 37

3. Hemostatic Factors 38

4. Glucose Intolerance and Insulin Resistance 38

5. Obesity 39

6. Smoking 40

7. Alcohol 40

8. Exercise 41

B. Possible Risk Factors 41

1. Homocysteine 41

2. Antioxidants 42

III. Vegetarianism and Coronary Heart Disease 43

A. Observational Studies 43

0-8493-8508-3/01/$0.00+$.50 © 2001 by CRC Press LLC

B. Intervention Trial of a Low-Fat Vegetarian Diet 45

C. Foods, Nutrients, Vegetarianism and Coronary Heart Disease 45

IV. Topics Requiring More Research 46

A. Coronary Heart Disease in Vegans 46

B. Coronary Heart Disease in Vegetarian South Asians 47

C. Vitamin B12 and Homocysteine 47

D. n-3 Fatty Acids 47

V. Conclusion 48

References 48

I. INTRODUCTION

Coronary heart disease (CHD) is the major cause of death in most Western countries, and is rapidly becoming a major cause of death in developing countries too. Lopez and Murray1 predicted that, by the year 2020, CHD will be the leading cause of disease worldwide. Differences in the diets consumed by different populations account for much of the observed variation in CHD mortality rates, and the effect of vegetarian diets on CHD is a topic of great interest.

Vegetarian diets are defined by what they do not include and can vary enormously in terms of both foods and nutrients. The diets of affluent Western vegetarians are very different from those of poor vegetarians in developing countries. Even within Western countries, vegetarian diets vary substantially according to the degree of exclusion of animal foods and according to whether the diet is followed predominately for ethical or health reasons. In view of this, any discussion of the health effects of a vegetarian diet must take into account the type of vegetarian diet studied and, equally important, the type of diet of the non-vegetarian comparison group. In this chapter, we concentrate on studies that compare vegetarians with non-vegetarians from a similar background. Unless otherwise specified, reference to vegetarians means lacto-ovovegetarians, because relatively few data are available for vegans.

In section II, we review the established and possible risk factors for CHD and comment on their relationships with vegetarian diets. Behavioral risk factors such as smoking should be considered as potential confounding factors that are not due to diet but that could cause differences in CHD rates between vegetarians and non-vegetarians; it is important that statistical analyses adjust for such factors. In contrast, factors such as fruit and vegetable consumption and body mass index are either components of the vegetarian diet or are strongly determined by diet; such factors are not confounders and, in general, it is not appropriate to adjust for these factors in statistical analyses.

In section III, we review epidemiological studies of CHD in vegetarians and the use of a low-fat vegetarian diet in the secondary prevention of CHD. Topics requiring further research are considered in section IV and our conclusions are presented in section V.

II. VEGETARIANISM AND CORONARY RISK FACTORS A. Established Risk Factors 1. Lipids and Lipoproteins

Serum total cholesterol concentration is the most important biochemical risk factor for CHD. There is an approximately linear relationship between serum total cholesterol and the risk of death from CHD. Most studies have underestimated the strength of this relationship because they have categorized individuals on the basis of a single measurement of serum cholesterol, which is only imperfectly correlated with the usual long-term cholesterol level of an individual. Correction for this underestimation, due to the "regression dilution bias," increases the strength of the relationship between serum cholesterol and CHD. Law et al.2 estimated that a 0.6 mmol/l reduction in serum total cholesterol causes a 24% reduction in mortality from CHD in middle-aged men. The effect is greater at younger ages; a reduction of total serum cholesterol of 0.6 mmol/l is estimated to reduce the incidence of CHD by 54% at age 40, 39% at age 50, 27% at age 60, 20% at age 70 and 19% at age 80.3 Importantly, the relationship between serum cholesterol concentration and CHD is observed not only in Western populations with high average serum cholesterol concentrations, but also within populations with relatively low cholesterol levels by Western standards, suggesting that reductions in cholesterol would reduce CHD rates in most populations.4

The association between serum total cholesterol and CHD mortality is largely due to low-density lipoprotein (LDL) cholesterol, which in Western countries typically comprises about four-fifths of total serum cholesterol. The relationship between LDL cholesterol and CHD mortality is stronger than that for total cholesterol — Law et al. estimated that a 0.6 mmol/l reduction in LDL cholesterol causes a 27% reduction in mortality from CHD.2

The other major component of total cholesterol is high-density lipo-protein (HDL) cholesterol that is inversely related to the risk of CHD.5 Therefore, it is important to consider both LDL cholesterol and HDL cholesterol when discussing the effects of vegetarian diets on serum lipids and CHD risk.

Since the pioneering work of Hardinge and Stare,6 numerous studies have established that vegetarians have lower total serum cholesterol con-

Table 3.1 Plasma Lipid Concentrations in Vegetarians and Non-Vegetarians, Adjusted for Age and Sexa

Total Cholesterol

LDL-Cholesterol

HDL-Cholesterol

(mmol l-')

(mmol l-')

(mmol l-')

Diet

N

Mean

SE

Mean

SE

Mean

SE

Meat-eater

1198

5.31

0.101

3.17

0.091

1.49

0.035

Vegetarian

1550

4.88

0.100

2.74

0.090

1.50

0.035

Vegan

114

4.29

0.140

2.28

0.126

1.49

0.048

aFrom Thorogood et al.7

aFrom Thorogood et al.7

centrations than comparable non-vegetarians. In Britain, data on 3277 participants in the Oxford Vegetarian Study showed that total cholesterol was, on average, 0.43 mmol/l lower in vegetarians than in meat-eaters.7 This difference was entirely due to differences in LDL cholesterol, which was also 0.43 mmol/l lower in the vegetarians (Table 3.1). Among vegans, total cholesterol was 1.02 mmol/l lower than in meat-eaters, largely due to a difference of 0.89 mmol/l in LDL cholesterol. The principal dietary determinant of total cholesterol in this population was fat intake, as summarized by the Keys score8 calculated from the intake of saturated fatty acids, polyunsaturated fatty acids, and cholesterol.9

The relatively low serum total cholesterol of vegetarians has been observed in diverse populations, including white American Seventh-Day Adventists,10,11 American commune-dwelling vegans,12 American macrobiotic vegetarians,13 British vegetarians,14,15 elderly Chinese vegetarians,16 Slovakian vegetarians,17 West African Seventh-Day Adventists,18 Siberian vegans,19 German vegetarians,20 and many others.21 Furthermore, intervention trials have demonstrated that changing to a vegetarian diet can reduce serum cholesterol concentrations.21,22 However, a vegetarian diet was not significantly related to plasma cholesterol concentrations among Asians from the Indian subcontinent living in London23 or among Asian Indian physicians living in the USA.24

The effects of a vegetarian diet on HDL cholesterol levels are less clear. The Oxford Vegetarian Study found that HDL levels were the same in vegans, vegetarians, and meat-eaters (Table 3.1), and that the principal dietary determinant of HDL cholesterol in this population was alcohol intake.9,25 In contrast, Fraser11 reported that HDL cholesterol was lower in largely vegetarian Seventh-Day Adventists than in their neighbors, with the result that the ratio of total to HDL cholesterol was almost identical in the two groups. Replacement of total fat by complex carbohydrate lowers HDL cholesterol26 and it is likely that the British vegetarians did not have lower HDL cholesterol than non-vegetarians because they did not have a low total fat intake.9 The relatively low level of HDL cholesterol in Seventh-Day Adventists may be due to their abstinence from alcohol, because alcohol raises HDL cholesterol.11

In terms of coronary risk, the data on lipid levels in vegetarians imply that they are definitely at lower risk in terms of their levels of total and LDL cholesterol, but that, within some populations, part of this benefi t might be offset by an accompanying reduction in HDL cholesterol levels.

The role of triacylglycerol as an independent risk factor for CHD has been uncertain, because adjustment for HDL cholesterol has tended to reduce or eliminate the association. However, a recent meta-analysis of prospective studies has shown that triacylglycerol is an independent risk factor for CHD; Austin et al.27 found that, after adjustment for HDL cholesterol, a 1 mmol/l increase in triacylglycerol was associated with increases in cardiovascular disease risk of 14% and 37% in men and women, respectively. Some small studies have reported that vegetarians have lower plasma triacylglycerol concentrations than meat-eaters,13,18 but other studies have not observed any difference between vegetarians and non-vegetarians.16

2. Hypertension

CHD is linearly related to increasing levels of systolic and diastolic blood pressure.28 As with serum cholesterol, most epidemiological studies have underestimated the size of the effect because they used a single measurement of blood pressure for each individual. After correction for this regression dilution bias, a reduction in diastolic blood pressure of 10 mmHg was associated with a 37% reduction in the risk of CHD (and a 56% reduction in the risk of stroke).29

The principal diet-related determinants of high blood pressure are obesity, high alcohol intake, high sodium intake, and low potassium intake.30,31 Most comparative studies have found that vegetarians are thinner and have a lower alcohol intake than non-vegetarians, and that they have a higher potassium intake, but there is no consistent evidence that vegetarians have a low sodium intake; some vegetarian foods are high in sodium. A number of studies have examined the association of vegetarian diets with blood pressure. Some studies comparing groups of vegetarians and non-vegetarians found lower blood pressure in the vegetarians, but other studies found no difference.32 Randomized trials of the effects of vegetarian diets on blood pressure have shown reductions in blood pressure of around 5 mmHg that were not due to changes in sodium intake and did not appear to be explicable by changes in other relevant nutrients such as potassium.32 Subsequent trials have attempted to establish whether the apparent hypotensive effect of a vegetarian diet could be explained by changes in nutrients such as fat and dietary fiber, but the results have been inconclusive.32

Some populations in rural Japan and China have semi-vegetarian diets, with a low intake of meat and dairy products and a heavy reliance on staple plant foods. These populations have a high prevalence of hypertension and high rates of stroke, but also have low cholesterol levels and low rates of CHD. The high prevalence of hypertension may be largely due to a high salt intake, but this observation demonstrates that a semi-vegetarian diet does not have a strong protective effect against hypertension. Indeed, there is some evidence from Japan that within this population, a low intake of animal protein might increase the risk for hypertension.33

Vegetarian diets, per se, do not strongly protect against the development of hypertension. To reduce the risk of developing hypertension, all diets should be low in sodium and high in potassium, alcohol intake should be low, and obesity should be avoided.

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