Raised serum cholesterol does not adequately explain the increased risk of CHD within populations or the relationship between diet and CHD. Nevertheless, the principal transport vehicle of cholesterol in the circulation, LDL, must still be regarded as the most atherogenic lipoprotein species, but not because of its contribution to serum cholesterol. The atherogenic potential of LDL in the majority of individuals arises from an increase in the number of small dense LDL particles and not from its cholesterol content per se. There is now a wealth of evidence from cross-sectional and prospective studies to show that LDL particle size is significantly associated with CHD and predictive of increased coronary risk. Moreover, there are a number of credible mechanisms to link small dense LDL with the atherogenic process. The rate of influx of serum lipoproteins into the arterial wall is a function of particle size, and will thus be more rapid for small dense LDL. Components of the extracellular tissue matrix in the intima, most notably proteoglycans, selectively bind small dense LDL with high affinity, sequestering this lipoprotein in a pro-oxidative environment. The oxidation of LDL promotes the final deposition of cholesterol in the arterial wall, and numerous studies have shown small dense LDL to be more susceptible to oxidative modification than its larger and lighter counterparts. An increase in the number of small dense LDL particles may originate from a defect in the metabolism of triacylglycerol-rich lipoproteins. One mechanism may involve the overproduction and increased residence time of large triacylglycerol-rich VLDL in the postprandial phase, a situation thought to arise through pathways of insulin resistance.

CHD is a multifactorial disease that is associated with non-modifiable risk factors, such as age, gender and genetic background, and with modifiable risk factors, including elevated total cholesterol and LDL-cholesterol levels. Lifestyle modification should be the primary treatment for lowering cholesterol values. The modifications recommended include dietary changes, regular aerobic exercise, and normalization of body weight. The recommended dietary changes include restriction in the amount of total fat, saturated fat and cholesterol together with an increase in the consumption of complex carbohydrate and dietary fibre, especially water-soluble fibre. However, nutrition scientists continue to question the value of these universal concepts and the public health benefits of low-fat diets, and an intense debate has been conducted in the literature on whether to focus on reduction of total fat or to aim efforts primarily towards reducing the consumption of saturated and trans fats. Moreover, it is well known that there is a striking variability between subjects in the response of serum cholesterol to diet. Multiple studies have examined the genediet interactions in the response of plasma lipid concentrations to changes in dietary fat and/or cholesterol. These studies have focused on candidate genes known to play key roles in lipoprotein metabolism. Among the gene loci examined, APOE has been the most studied, and the current evidence suggests that this locus might be responsible for some of the inter-individual variability in dietary response. Other loci, including APOA4, APOA1, APOB, APOC3, LPL and CETP have also been found to account for some of the variability in the fasting and fed states.

Quantitative dietary guidelines for fats were first issued in 1977 in the USA and these guidelines have changed little since then. In the UK only 14 % of the population achieve the dietary goal for fat (33 % energy) and only 3 % achieve the target (10 % energy) from saturated fatty acids. Analysis of the Dietary and Nutritional Survey of British Adults reveals that across quartiles of decreasing total fat intake, the actual fatty acid composition of this fat does not alter; i.e. when total fat is lowered, all fatty acid categories are equally lowered. This arises because 85 % of total fat and of each of the categories of fatty acids are provided by just five foods (milk, meat, cereals, spreads and vegetables). When total fat in the UK is lowered, the intake of polyunsaturated fatty acids is lowered. The problem is that if the intake of polyunsaturated fatty acids falls below a threshold of about 5 % energy, the cholesterol-raising properties of certain saturated fatty acids, e.g. myristic acid, are greatly augmented. In order to alter the balance of dietary fatty acids, more data are needed on food choices of those in the population achieving particular targets. These targets cannot be based on existing dietary goals, since so few people attain them. A new set of‘interim attainable dietary guidelines’, based on prevailing dietary intakes, must be the basis for establishing sensible food-based dietary guidelines.

CHD is a major cause of morbidity and mortality in women. The incidence of CHD in premenopausal women is low but increases substantially after the menopause, and this difference suggests that endogenous oestrogens are cardioprotective. Observational prospective studies have consistently shown that exogenous oestrogens also lower CHD risk. The biological mechanisms by which endogenous and exogenous oestrogens exert their protective effect are multifactorial, affecting lipids, carbohydrate metabolism, body fat distribution and blood pressure. The prevention of CHD with oestrogen therapy is therefore aimed both at correction of the traditional risk factors and at direct control of vessel structure and function. The wide international variation in rates of CHD together with the lower mortality in sub-groups of the population suggests that a considerable proportion of CHD may be prevented by dietary modification. Since phyto-oestrogens are structually similar to oestrogen, they have the potential to mimic its effects in vivo. The hypocholesterolaemic effects of soyabean protein (rich in phyto-oestrogen precursors) are well established, but the underlying mechanism and atherogenic potential of these changes are unknown. One isoflavone, genistein, has been shown in vitro to exert effects which may slow the development of atherosclerotic disease. However, further studies are required to determine the dose-related changes induced by phyto-oestrogens on serum lipoproteins, haemostasis and vascular function.

There is a growing body of scientific evidence which demonstrates that plasma triacylglycerol (TAG) concentration, especially in the postprandial state, is an important risk factor in relation to the development of CHD. Postprandial hypertriacylglycerolaemia is associated with a number of adverse metabolic risk factors, including the preponderance of small dense LDL, low HDL-cholesterol concentrations and elevated factor VII activity. Traditionally, a low-fat high-carbohydrate diet was used to prevent CHD because it effectively reduces plasma cholesterol concentrations, but this dietary regimen increases plasma TAG concentrations and reduces HDL-cholesterol concentrations. There is substantial epidemiological evidence which demonstrates that high plasma TAG and low plasma HDL concentrations are associated with an increased risk of CHD. Thus, there is reason for concern that the adverse effects of low-fat high-carbohydrate diets on TAG and HDL may counteract or negate the beneficial effect of reducing LDL-cholesterol concentrations. Although there have been no prospective studies to investigate whether reduced fat intake has an adverse effect on CHD, there is strong epidemiological evidence that reducing total fat intake is not protective against CHD. On the other hand, high-fat diets predispose to obesity, and central obesity adversely affects TAG metabolism. There is substantial evidence that in free-living situations low-fat high-carbohydrate diets lead to weight loss, which in turn will correct insulin resistance and plasma TAG metabolism. Clearly there is a need for prospective studies to resolve the issue as to whether low-fat high-carbohydrate diets play an adverse or beneficial role in relation to the development of CHD.