LETTER TO THE EDITOR
Heterogeneity of response to lipid-lowering therapy: Reply
William F. Penny, MD, FACCa and
Kirk L. Peterson, MD, FACCa
a Division of Cardiology, VA San Diego Healthcare System, University of California, San Diego, 3350 La Jolla Village Drive, San Diego, California 92161 USA
We appreciate Dr. Bach’s interesting comments regarding our study of the changes in coronary endothelial dysfunction occurring after lipid lowering (1). We certainly agree that the segmental heterogeneity of these changes in response to acetlycholine suggests a level of complexity that has been previously underemphasized.
The reduction in clinical events in groups of patients on lipid-lowering therapy is irrefutable. Our work confirms previous reports that this therapy can also improve endothelial function in a group of patients. However, as in all therapies, not all patients respond equally, and the inclusion of all analyzable coronary segments in our study expands on the original observation of El-Tamimi et al. (2) that not all areas of the artery respond equally.
As pointed out in our current study (1) as well as in our earlier work (3), it is difficult to separate true physiologic heterogeneity from methodologic variablity inherent in all analytic techniques. We reiterate that the phenomenon of regression to the mean may well account for some of the findings of most constricted and most dilated segmental responses being moderated on follow-up. However, the conclusion that some responses are actually adversely affected by lipid reduction cannot be made by our study given the lack of a comparative placebo group—a more abnormal response might be expected at follow-up given the natural history of atherosclerotic coronary disease, and some of these "worsened" responses could have been an improvement over that seen in the absence of lipid reduction.
We agree that the pattern of vasomotor response and the correlation with oxidized low-density lipoprotein may possibly reflect a given patient’s clinical response to lipid-lowering therapy. This observation deserves further study.
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References
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1. Penny WF, Ben-Yehuda O, Kuroe K, et al. Improvement of coronary artery endothelial dysfunction with lipid-lowering therapy: heterogeneity of segmental response and correlation with plasma-oxidized low density lipoprotein. J Am Coll Cardiol. 2001;37:766–774[Abstract/Free Full Text]
2. El-Tamimi H, Mansour M, Wargovich TJ, et al. Constrictor and dilator responses to intracoronary acetylcholine in adjacent segments of the same coronary artery in patients with coronary artery disease: endothelial function revisited. Circulation. 1994;89:45–51[Abstract/Free Full Text]
3. Penny WF, Rockman H, Long J, et al. Heterogeneity of vasomotor response to acetylcholine along the human coronary artery. J Am Coll Cardiol. 1995;25:1046–1055[Abstract]
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