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
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