The doubtful association between blood lipid changes and progression

International Journal of Cardiology

Letter to the Editor

The doubtful association between blood lipid changesand progression
of atherosclerosis

Uffe Ravnskov

Magle StoraKyrkogata 9, 22350 Lund, Sweden

a r t i c l ei n f o

Article history:

Received 20 August 2011
Accepted 26 August 2011
Available online
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 treatments obtained in many angiographic trials must be caused by other and unknown 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-atherosclerotict herapy. However, other studies using different techniques and other kinds of outcome have also shown lack of exposure/response. In a previous 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 riskfactor reduction, low-fat diet and exercise, as well as drug treatment with cholestyramine, colestipol, niacin, fenofibrate, probucol, bezafibrate, lovastatin, pravastatin and simvastatin. With one exception no exposure/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 also calculated for HDL-cholesterol, in ten for tri-glycerides, in six for

apolipoprotein B, in three for apolipoprotein 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 agreement 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 causality, but its absence definitely disproves it. Therefore, the findings of Tenenbaum et al. cast doubt on the current view about the causation of atherosclerosis 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 calcification. 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 atherosclerosis studied in 168 medically treated patients who underwent coronary arteriography three times. Am Heart J 1989;117:296305.
[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. Progression 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;56:15560.

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
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