(Circulation. 1999;99:1922-1926.)
© 1999 American Heart Association, Inc.
Correspondence |
Hypercholesterolemia, Abnormal Coronary Vasomotion, and Calcium Antagonists
Clinical Professor of Medicine, UCLA School of Medicine, Los Angeles, Calif
To the Editor:
I was fascinated by the recent article by Kaufmann et al1 on the reversal by calcium antagonists of the abnormal coronary vasomotion associated with hypercholesterolemia. Teleologically, this observation is quite logical, and it also explains some of the clinical observations made about coronary artery disease. Let me explain.
Studies in experimental animals have shown that the entry of cholesterol into the endothelial lining of the aorta is dependent on the concentration of cholesterol in the perfusing solution, the pulse pressure, and the number of pulses per minute.2 These very early abnormalities are noted at the ultrastructural level well before there is any grossly visible modification of the vessel wall (such as the fatty streak). Because the initial injury that starts the long process of formation of the atherosclerotic plaque is very dependent on cholesterol entry into the endothelial cells, it is teleologically reasonable that the greater the level of serum cholesterol, the more the normal increase in pulse pressure with exercise should be constrained.
Also, it is now well accepted that the higher the serum cholesterol level, the greater the development of soft plaques that are more easily ruptured or fissured. Thus, it makes sense that with the higher serum cholesterol, the greater decrease in pulse pressure with exercise would in part protect against such sudden acute events in hypercholesterolemic patients.
There has been a great controversy brewing with regard to the effect of calcium channel blockers on the progression of coronary artery disease. This has especially been noted in the long-term treatment of hypertensives. Some of this has been attributed to the rebound vasoconstriction that occurs with the shorter-acting calcium channel blockers. However, the observation by Kaufmann et al that calcium channel blockers will dilate the coronary arteries with exercise irrespective of the level of serum cholesterol may be another explanation for the greater progression of coronary artery disease in patients on long-term therapy with calcium channel blockers. Thus, this observation by Kaufmann et al would predict that even long-acting calcium channel blockers would have an adverse effect on the development and progression of coronary artery disease in hypertensives, although not as great as the effect of short-acting calcium channel blockers.
It may be that calcium channel blockers should not be used in hypertensives who are free of coronary artery disease unless their cholesterol levels are first lowered to the levels suggested by the American Heart Association. Also, calcium channel blockers should probably be used in patients with well-documented coronary artery disease only after their LDL cholesterol level has been decreased to below 100 mm Hg.
References
1.
Kaufmann PA, Frielingsdorf J, Mandinov L, Seiler C,
Hug R, Hess OM. Reversal of abnormal coronary vasomotion by
calcium antagonists in patients with
hypercholesterolemia.
Circulation. 1998;97:1348–1354.
2. Simionescu N. Prelesional changes of arterial endothelium in hyperlipoproteinemic atherogenesis. In: Simionescu N, Simionescu M. Endothelial Cell Biology in Health and Disease. New York, NY: Plenum Press; 1988:385–429.
Response
Zurich, Switzerland
Professor of Cardiology Bern, Switzerland
We appreciate Dr David's interest in our article1 and his thoughts on clinical observations and the possible effects of calcium channel blockers on the progression of coronary artery disease, with special emphasis on hypertensive patients. However, for the following reasons we do not believe that our results can entirely be extrapolated to Dr David's conclusions. First, we found beneficial effects of calcium channel blockers on the abnormal coronary vasomotion in patients with hypercholesterolemia in our acute intervention study, but we have not studied long-term effects, precluding any statement in this regard. However, we would expect the pulse pressure to decrease after calcium channel blocker–induced coronary dilation, and according to Dr David, this is thought to protect against sudden acute events rather than being unfavorable. Second, we did not address the issue of the effect of calcium channel blockers on progression or regression of coronary lesions or on morbidity and mortality. Third, hypertensive patients were excluded from the study because hypertension has been shown to be an important determinant of coronary vasomotion,2 as we stressed in the Methods section. However, we previously reported on the beneficial effects of calcium channel blockers in patients with hypertension,3 challenging Dr David's conclusion about adverse effects in this important group of patients.
In summary, we were very cautious to restrict our statements on conclusions based on findings of the study, although we appreciate that many of our findings might stimulate further thoughts and personal interpretation.
References
1. Kaufmann PA, Frielingsdorf J, Mandinov L, Seiler C, Hug R, Hess OM. Reversal of abnormal coronary vasomotion by calcium antagonists in patients with hypercholesterolemia. Circulation. 1998;97:1348–1354.
2. Frielingsdorf J, Kaufmann P, Seiler C, Vassalli G, Suter T, Hess OM. Abnormal coronary vasomotion in hypertension: role of coronary artery disease. J Am Coll Cardiol. 1996;28:935–941.[Abstract]
3.
Frielingsdorf J, Seiler C, Kaufmann P, Vassalli
G, Suter T, Hess OM. Normalization of abnormal coronary
vasomotion by calcium antagonists in patients with
hypertension. Circulation. 1996;93:1380–1387.
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