Lowering heart disease risk with cholesterol reduction: evidence from observational studies and clinical trials

In considering any food or drug that lowers serum lipid levels, the questio n arises as to the expected reduction in heart disease mortality given the reduction in serum total or low-density lipoprotein (LDL) cholesterol. Such quantitative assessment of the relationship between heart disease and its risk factors is best done by analysing observational and trial data in tand em, since the two are complementary in strengths and weaknesses. Estimates based on trials alone are imprecise and short term. Observational data from cohort studies show that, in absolute units, the effect of a given cholest erol difference on heart disease risk is similar whether based on LDL or to tal serum cholesterol levels. The relationship between heart mortality ton a logarithmic scale) and serum cholesterol tin absolute units) fits a linea r model extremely well, indicating that a constant absolute decrease in cho lesterol from any point on the distribution in Western countries is associa ted with a constant proportionate decrease in heart disease mortality. The strength of the relationship varies with age, being proportionately stronge r in younger age groups. In the age group 55-64 years, trial data show litt le reduction in heart disease risk in the first 2 years, but a reduction fr om the third year onwards that is remarkably close to the cohort study esti mate of 27% for a 0.6 mmol.1(-1) cholesterol reduction. This result is impo rtant, showing that risk is reversed relatively quickly (after 2 years), an d reinforcing the cohort study estimate of the size of the long-term effect . Therefore, a population dietary intervention that lowered serum cholester ol by 0.6 mmol. 1(-1) (10%) would reduce heart disease mortality after 2 ye ars by about a quarter. Margarines containing plant sterol/stanol esters ha ve been shown to reduce cholesterol by about this much. Such an effect is p articularly important in Britain, where the population average serum choles terol level has not changed significantly over many years. Although it migh t be considered preferable to direct dietary intervention to those with the highest cholesterol levels in a community, the large number of persons wit h cholesterol levels close to the average gives rise to many more heart dis ease deaths than the smaller number with relatively high levels, and reinfo rces the importance of a population-wide intervention.