A provocative article in the World Journal of Cardiology challenges some simplistic assumptions.
Below are a few of the points made in the article.
Total cholesterol is a poor predictor of risk
This has been known for decades. The authors cite findings from the Framingham study in which total cholesterol levels in patients with coronary disease overlap highly with levels in patients free of coronary disease. That is illustrated in this figure. But to say these findings negate the cholesterol hypothesis ignores the distinction between population attributable risk and relative risk. The findings, despite a well documented correlation between cholesterol levels and coronary disease risk, are explained by the multitude of other factors, in addition to cholesterol levels, that contribute to risk. Other factors must be taken into account and in the Framingham study the ratio of total cholesterol to HDL was a strong predictor.
In multiple clinical trials dietary interventions aimed primarily at reducing cholesterol levels failed to impact coronary disease outcomes
Diet trials may have been confounded by increased carbohydrate intake which activated the metabolic syndrome phenotype in many patients. On the other hand, cholesterol lowering drug trials have shown reductions in events. This is not just due to pleiotropic effects of statins, as there is evidence from non statin cholesterol lowering drug trials of event reduction.
Interventions to reduce risk need to be viewed in perspective
For example: cholesterol lowering diets have not been proven to reduce events; statins achieve a relative risk reduction of about 30%; the Mediterranean has been reported to achieve a 70% relative risk reduction.
Though a risk factor, a singular focus on cholesterol reduction is misguided