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 xxxx
Keywords:
Atherosclerosis
Cholesterol
Plasma lipids
Exposure-response

Recently Tenenbaum et al. reported that long-termchanges in serum cholesterol did not correlate with the progression ofcoronary calcium measured by computerized tomography (1). Theirfinding shows that the benefit of various cholesterol-loweringtreat-ments obtained in many angiographic trials must be caused by otherand un-known factors. The authors argued that one of the reasons to thelack of exposure/response may be that calcific plaques are resistant toundergoing changes in size in response to systemic anti-atherosclerotictherapy. However, other studies using different techniques and other kindsof outcome have also shown lack of exposure/response. In a pre-viousreview of the angiographic cholesterol-lowering trials I identifiedsixteen trials in which the authors had calculated exposure/responsebetween changes in low-density and/or total cholesterol, and degree ofathero-sclerotic progress measured either as change of minimum lumendiameter or percent stenosis (2). In these trials almost all kinds ofcholesterol lowering were used, including LDL-apheresis, multiple riskfactor reduction, low-fat diet and exercise, as well as drug treatmentwith chole-styramine, colestipol, niacin, fenofibrate, probucol, bezafibrate, lovastatin, prava-statin andsimvastatin. With one exception no expo-sure/response was recorded in anyof these trials. The exception was a trial where the only treatment usedwas physical exercise. In 12 of the trials exposure/response wasalsocalculated for HDL-cholesterol, in ten for tri-glycerides, in six for

apolipoprotein B, in three forapolipoprotein A1, in three for VLDL-cholesterol andin one for small, dense LDL-cholesterol; in all of them the result was thesame: no exposure-response.
The findings of Tenenbaum et al. are in agree-mentwith the previous study by Hecht and Harman (3), who found no associationbetween the degree of LDL-cholesterol lowering and calcified plaqueprogression, using electron beam tomography. Exposure-response has alsobeen absent (4-6) and even inverse (7) in observationalangiographic studies.
Obviously the benefit achieved by the variouscholesterol-lowering treatments is caused by factors other than loweringof the blood lipids. Presence of exposure/response is not necessarilyproof of causa-lity, but its absence definitely disproves it. There-fore,the findings of Tenenbaum et al. cast doubt on the current view about thecausation of athero-sclerosis by plasma lipoproteins.References

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[3] Hecht HS, Harman SM. Relationof aggressiveness of lipid-lowering treatment to changes in calcifiedplaque burden by electron beam tomography. Am J Cardiol 2003;92:334-6.
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[5] Bissett JK, Wyeth RP, Matts JP, Johnson JW. Plasma lipidconcentrations and subsequent coronary occlusion after a first myocardialinfarction. The POSCH group. Am J Med Sci 1993; 305:139-44.
[6] Bemis CE, Gorlin R, Kemp HG, Herman MV. Progress-ion of coronaryartery disease: a clinical arteriographic study. Circulation1973;47:455-64.
[7] Shub C, Vlietstra RE, Smith HC, Fulton RE, Elveback LR. Theunpredictable progression of symptomatic coronary artery disease: a serialclinical-angiographic analysis. Mayo Clin Proc 1981;56:15560.

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