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Q J Med 2002; 95: 397-403
© 2002 Association of Physicians

Commentaries

Is atherosclerosis caused by high cholesterol?

U. Ravnskov

Introduction

According to the low-density-lipoprotein (LDL) receptor hypothesis, development of atherosclerosis is caused by a high concentration of LDL-cholesterol in the blood, and lowering LDL-cholesterol reverses, or at least retards, atherosclerosis, thus preventing cardiovascular disease.1 As a scientific hypothesis, it is open to falsification: if the concentration of LDL-cholesterol or total cholesterol and the degree of atherosclerosis do not correlate, or if there is no exposure-response, e.g. if there is no association between the cholesterol changes ({Delta}LDL-cholesterol or {Delta}total cholesterol) and atherosclerosis progression.

The successful statin trials, with their substantial reduction of LDL-cholesterol seemed to confirm the LDL receptor hypothesis, but their outcome was independent of the initial cholesterol concentration and the degree of its lowering. For instance, the p values for the relationships between the outcome, and the percentage or the absolute change in LDL cholesterol, as calculated in one of the trial reports,2 were 0.76 and 0.97, respectively. . . . [Full Text of this Article]

Cholesterol does not predict degree of atherosclerosis at autopsy

Cholesterol does not correlate with degree of coronary atherosclerosis on angiography

Cholesterol does not correlate with degree of coronary calcification

Cholesterol does not correlate with degree of peripheral atherosclerosis

No exposure-response

Objections

Why does a high cholesterol predict cardiovascular disease?

Conclusion

Notes

References


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