International Journal of Cardiology

Letter to the Editor

The doubtful association between blood lipid changes and progression
of atherosclerosis

Uffe Ravnskov

Magle Stora Kyrkogata 9, 22350 Lund, Sweden

a r t i c l e  i n f o

Article history:

Received 20 August 2011
Accepted 26 August 2011
Available online xxxx
Keywords:
Atherosclerosis
Cholesterol
Plasma lipids
Exposure-response

Recently Tenenbaum et al. reported that long-term changes in serum cholesterol did not correlate with the progression of coronary calcium measured by computerized tomography (1). Their  finding shows that the benefit of various cholesterol-lowering treat-ments obtained in many angiographic trials must be caused by other and un-known factors. The authors argued that one of the reasons to the lack of exposure/response may be that calcific plaques are resistant to undergoing changes in size in response to systemic anti-atherosclerotic therapy. However, other studies using different techniques and other kinds of outcome have also shown lack of exposure/response. In a pre-vious review of the angiographic cholesterol-lowering trials I identified sixteen trials in which the authors had calculated exposure/response between changes in low-density and/or total cholesterol, and degree of athero-sclerotic progress measured either as change of minimum lumen diameter or percent stenosis (2). In these trials almost all kinds of cholesterol lowering were used, including LDL-apheresis, multiple risk factor reduction, low-fat diet and exercise, as well as drug treatment with chole-styramine, colestipol, niacin, fenofibrate, probucol, bezafibrate, lovastatin, prava-statin and simvastatin. With one exception no expo-sure/response was recorded in any of these trials. The exception was a trial where the only treatment used was physical exercise. In 12 of the trials exposure/response was alsocalculated for HDL-cholesterol, in ten for tri-glycerides, in six for

apolipoprotein B, in three forapolipoprotein A1, in three for VLDL-cholesterol and in one for small, dense LDL-cholesterol; in all of them the result was the same: no exposure-response.     
     The findings of Tenenbaum et al. are in agree-ment with the previous study by Hecht and Harman (3), who found no association between the degree of LDL-cholesterol lowering and calcified plaque progression, using electron beam tomography. Exposure-response has also been absent (4-6) and even inverse (7) in observational angiographic studies.
     Obviously the benefit achieved by the various cholesterol-lowering treatments is caused by factors other than lowering of the blood lipids. Presence of exposure/response is not necessarily proof of causa-lity, but its absence definitely disproves it. There-fore, the findings of Tenenbaum et al. cast doubt on the current view about the causation of athero-sclerosis by plasma lipoproteins. 

References

[1] Tenenbaum A, Shemesh J, Koren-Morag, Fisman EZ, Adler Y, Goldenberg I, et al. Long-term changes in serum cholesterol level does not influence the progression of coronary calci-fication. Int J Cardiol 2011;150:130-4.
[2] Ravnskov U. High cholesterol may protect against infections and atherosclerosis. QJ Med 2003;96:927-34
[3] Hecht HS, Harman SM. Relation of aggressiveness of lipid-lowering treatment to changes in calcified plaque burden by electron beam tomography. Am J Cardiol 2003;92:334-6.
[4] Bruschke AV, Kramer JR Jr, Bal ET, Haque IU, Detrano RC, Goomastic M. The dynamics of progression of coronary athe-rosclerosis studied in 168 medically treated patients who underwent coronary arteriography three times. Am Heart J 1989;117:296–305.
[5] Bissett JK, Wyeth RP, Matts JP, Johnson JW. Plasma lipid concentrations and subsequent coronary occlusion after a first myocardial infarction. The POSCH group. Am J Med Sci 1993; 305:139-44.
[6] Bemis CE, Gorlin R, Kemp HG, Herman MV. Progress-ion of coronary artery disease: a clinical arteriographic study. Circulation 1973;47:455-64.
[7] Shub C, Vlietstra RE, Smith HC, Fulton RE, Elveback LR. The unpredictable progression of symptomatic coronary artery disease: a serial clinical-angiographic analysis. Mayo Clin Proc 1981;56:155–60.

 
Please cite this article as: Ravnskov U, The doubtful association between blood lipid changes and progression of atherosclerosis, Int J Cardiol (2011), doi:10.1016/j.ijcard.2011.08.846