LDL-receptor hypothesis questioned
Editor-The lack of an association between blood cholesterol and degree of coronary atherosclerosis was shown for the first time in 1936 by Landé and Sperry (1). Since then it has been confirmed again and again in autopsy and angiographic studies (2). Some of the latter have found a weak correlation coefficient (0.35 at most) but angiographic studies are biased as they include more individuals with familial hypercholesterolemia than in the general population. The lack of an association in normal people found by Hecht and Superko (3), is therefore most interesting. If elevated LDL-cholesterol is a major cause of coronary heart disease (CHD), as stated recently in the new cholesterol guidelines, why isn’t it correlated with degree of coronary calcification in normal people? As the coronary plaque burden identified by electron beam tomography is closely associated with total plaque volume, obstructive CHD and future coronary events (3), the only explanation is that the LDL-cholesterol receptor hypothesis (4) may possibly be valid for individuals with familial hypercholesterolemia, but not for the rest of us. The reason why LDL cholesterol is associated with future CHD may be that it is secondary to other, more important factors, such as lack of exercise, overweight, hypertension, smoking and mental stress, all of which are known to raise LDL cholesterol, but which may stimulate to atherosclerosis and CHD by other mechanisms (5). Uffe Ravnskov, MD,PhD
letter was rejected. Here is the editor's answer:
"Because of space limitations we are able to publish only a few letters addressing controversial issues"
Journal of the American College of Cardiology
Sperry WM. Human atherosclerosis in relation to the cholesterol content of
the blood serum. Arch Pathol 1936;22,301-12.
The Cholesterol Myths. Washington DC: New Trends Publishing:2000:113-33
Superko R. Electron beam tomography and National Cholesterol Education
program guidelines in asymptomatic women. JACC 2001;37:1506-11.
4. Brown MS, Goldstein JL. How LDL receptors influence cholesterol and atherosclerosis. Sci Am 1984:251:58-66
The Cholesterol Myths. Washington DC: New Trends Publishing:2000:61-4.