Cholesterol, coronary heart disease and stroke: a review of published evidence from observational studies and randomized controlled trials.

In observational epidemiologic studies, lower blood cholesterol is associated with a reduced risk from coronary heart disease (CHD) throughout the normal range of cholesterol values observed in most Western populations. There is a continuous positive relationship between CHD risk and blood cholesterol down to at least 3 to 4 mmol/l, with no threshold below which a lower cholesterol is not associated with a lower risk. Observational studies suggest that a prolonged difference in total cholesterol of about 1 mmol/l is associated with one-third less CHD deaths in middle age. Evidence from large-scale cholesterol lowering trials in patients at high-risk of CHD have demonstrated that much of the epidemiologically predicted difference in CHD risk associated with differences in cholesterol was achieved within a few years of treatment. Moreover, these trials have demonstrated that such therapy was not associated with increased non-CHD mortality. Total cholesterol is transported in blood as low-density lipoprotein cholesterol or LDL cholesterol (about 70%) and as high density lipoprotein cholesterol or HDL cholesterol (about 30%). Since these two cholesterol fractions have opposing effects on vascular risk, a 1 mmol/l reduction in LDL cholesterol is likely to be associated with 40 to 50% lower CHD risk. The size of the absolute reduction in CHD produced by lowering total and LDL cholesterol is determined by an individual's overall risk rather than their initial cholesterol level. Consequently, the benefits of drug treatment to lower LDL cholesterol are greater in those at higher absolute risk of CHD rather than at high cholesterol levels. Dietary saturated fat is the chief determinant of total and LDL cholesterol levels. Replacing 60% of the intake of saturated fat by other fats and reducing the intake of dietary cholesterol could reduce blood total cholesterol levels by about 0.8 mmol/l (that is by 10 to 15%), with four fifths of this reduction being in LDL cholesterol.