Endothelial Dysfunction and Percutaneous Intervention
Endothelial Dysfunction and Percutaneous Intervention
abstract & commentary
Synopsis: Decreased endothelial integrity with a more intense proliferative response from stenting may be the mechanism that results in more severe arterial injury and less endothelial regrowth in stent patients.
Source: Caramori PR, et al. J Am Coll Cardiol 1999; 34:1675-1679.
It has been long known that coronary angioplasty in humans and in animal models results in abnormal endothelium-dependent vasodilator responses for weeks to months after the procedure. This study sought to ask whether the more severe arterial injury induced by coronary stenting might precipitate a greater degree of endothelial dysfunction than routine angioplasty by inducing an enhanced chronic inflammatory response in the target vessel. Thirty-nine patients who underwent an elective left anterior descending (LAD) angioplasty six months previously were studied. None had clinical or angiographic evidence of restenosis. These subjects underwent conventional angioplasty (PTCA), directional atherectomy (DCA), or stent implantation. Coronary angiography was performed off all medications. Acetylcholine was infused at three concentrations, with angiography repeated immediately after each infusion. All studies were blinded. The target area was a distal long segment of the LAD beyond the intervention site, as well as a segment of a nonintervened circumflex coronary artery in the control angiogram. Of the 39-patient cohort, 15 had PTCA, 12 had DCA, and 12 had coronary stenting. The average time from intervention to the study was 19 ± 2 months. The cohorts were well matched for risk factors. No patient had a significant LAD stenosis, and the average percent diameter reduction of the LAD was 20%. The results indicated that the stented patients had much greater vasoconstrictor responses to the maximal acetylcholine dose than the PTCA or DCA group. Thus, the average vasoconstriction downstream from the stent site was 22% compared to approximately 9% in either the PTCA or the DCA group. Of interest, all 10 stent patients underwent some degree of vasoconstriction of the LAD, whereas the vascular response to acetylcholine in the other two groups were mixed with vasodilation as well as constriction. The circumflex artery demonstrated mild constriction in all groups. By multiple regression analysis, stent placement was the only factor associated with enhanced vasoconstriction to acetylcholine. Caramori and colleagues speculate that decreased endothelial integrity with a more intense proliferative response from stenting may be the mechanism that results in more severe arterial injury and less endothelial regrowth in stent patients. Moreover, they suggest that enhanced inflammatory cell infiltration within the coronary artery may be a factor relating to the more severe endothelial dysfunction in this group. They speculate that long-term effects from stent implantation could result in adverse outcomes, with enhanced atherogenesis and worsened endothelial vasodilator function. An accompanying editorial by Tilton discusses other potential adverse sequelae of endothelial dysfunction, including propensity to coronary thrombosis, as well as decreased coronary flow reserve. Tilton calls for database analyses of large volumes of patients treated with angioplasty and stenting. He emphasizes that stents have resulted in improved outcomes when compared to PTCA in multiple trials, and that these data are provocative but, due to the small number of the cohort, more information is clearly needed to monitor stent patients for long-term complications.
Comment by Jonathan Abrams, MD
These three articles underscore the increasing attention paid to vascular biology in clinical cardiovascular medicine. Each study has pursued a specific area of current interest. The infectious etiology of atherosclerosis and the inflammatory hypothesis have achieved impressive support from a variety of basic science, animal, and human investigations. It may be that in the future, markers of inflammation, be it CRP, IL-6, SAA, adhesion molecules, etc., will become conventional parts of clinical practice. Just as an elevated toponin is now a marker for more adverse outcome in unstable angina and coronary interventions, it is possible that other markers now being investigated will play a role in risk stratification. The association between infectious agents, particularly Chlamydia pneumoniae and CMV, is intriguing. These studies suggest there is a wide variation in host responses to infectious and inflammatory stimuli, which certainly makes considerable sense. This could well contribute to the different conclusions of a variety of studies in the literature. Clearly, it is not yet time for clinicians to worry about measurement of CRP (although a high-quality assay has just been approved by the FDA), IL-6, etc., but measurement of these compounds may turn out to be routine.
Impaired coronary vasodilator responses lasting a long time after percutaneous coronary interventions are not a new observation, but probably not widely recognized. This phenomenon clearly contributes to the difficulty in interpreting stress tests, particularly nuclear imaging, in post-PTCA patients for weeks to months, as the vasoconstrictor response of the intervened upon vessel may well produce a defect when there is no flow-limiting disease or restenosis. Enhanced vasoconstriction to a variety of stimuli is clearly more likely to produce clinical symptoms, even in the absence of clinical restenosis. It is well known that many patients who undergo angioplasty are subjected to a repeat coronary arteriogram in the weeks to months following this procedure because of recurrent chest pain, and the artery looks satisfactory. The small number of patients studied by the Toronto group that had stent employment is of interest. The marked vasoconstrictor response in these patients, significantly greater than DCA or PTCA patients, could implicate stenting as a potential problem. Clinical data are not yet available to support this hypothesis. However, long-term follow-up of stent patients compared to PTCA has not been fully analyzed, although there does not appear to be any clinical experience that would suggest a downside to stenting during late follow-up. This intriguing observation bears watching.
Endothelial injury is greatest with:
a. balloon angioplasty.
b. directional atherectomy.
c. stent placement.
d. intracoronary ultrasound.
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