Plasma cholesterol and CHD

A number of studies, including several large prospective studies, such as the Framingham Study (Anderson et al, 1987), the Multiple Risk Intervention Trial (Stamler et al, 1986) and the Lipid Research Clinics Program (Pekkanen et al., 1990), as well as the Seven Countries Study (Verschuren et al, 1995) showed a positive correlation between levels of plasma cholesterol and mortality from CHD. However, epidemiological associations cannot prove causality and elevated cholesterol levels could be either a cause, a correlate or a consequence of CHD. 

The early studies on CHD demonstrated that saturated fatty acids and cholesterol increase, whereas polyunsaturated fatty acids decrease plasma cholesterol levels, and that cholesterol levels are associated with CHD risk, led to the diet-heart or lipid hypothesis of CHD. Conversely, it followed that lowering the intake of saturated fatty acids and increasing polyunsaturated fatty acid intake will lower plasma cholesterol levels, which in turn will reduce the risk of CHD. 

The studies that led to the lipid hypothesis measured plasma total cholesterol concentration. Cholesterol is insoluble in aqueous solution and needs to be combined with protein for transport in blood. These plasma lipoproteins are large heterogeneous aggregates that have different physical properties, such as density, chemical composition and metabolic function (Gurr et al., 2002). 

Later epidemiological studies demonstrated that the low-density lipoprotein (LDL)-cholesterol, which is the predominant cholesterol carrier, like total cholesterol, was positively associated with the risk of CHD. On the other hand, HDL-cholesterol was negatively associated with the risk of CHD. Even between individuals having the same LDL-cholesterol level, those with a predominance of small, dense LDL particles have a much higher risk of CHD than individuals with a predominance of large, buoyant LDL particles (Gurr et al., 2002). It is notable that the Ci2 o, Ci4 o and Ci6 o fatty acids that increase total and LDL-cholesterol the most, concomitantly increase the levels of anti-atherogenic HDL-cholesterol, such that there can be a beneficial decrease in the total HDL ratio (Mensink et al., 2003). 

Unfortunately, early studies that measured only levels of total cholesterol are still cited in reviews (e.g., Braunwald, 1997 Schaefer, 2002) to support the contention that restricting saturated fat and cholesterol intake 

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PUFAs are categorized as n-6 PUFAs (mainly derived from linoleic acid) and n-3 PUFAs (mainly present in fatty fish and also derived from alpha-linoleic acid). Clinical trials, in which n-6 PUFAs (containing linoleic acid) were substituted for SFAs showed a greater impact on reduction of both plasma cholesterol and CHD risk, in contrast to trials where low-fat diets were employed. 

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