Elsevier

Atherosclerosis

Volume 181, Issue 2, August 2005, Pages 311-319
Atherosclerosis

High frequency of endothelial vasomotor dysfunction after acute coronary syndromes in non-culprit and angiographically normal coronary arteries: A reversible phenomenon

https://doi.org/10.1016/j.atherosclerosis.2005.01.007Get rights and content

Abstract

This study aimed to assess endothelium-dependent vasomotor function in non-culprit coronary vessels in patients with recent acute coronary syndrome (ACS). Endothelial dysfunction can also concern peripheral vessels during ACS, but the frequency of this phenomenon at coronary circulation level is unknown. Endothelial function was assessed by infusion of graded doses of acetylcholine (ACh) in a non-culprit coronary artery of normal appearance in 43 patients having recently suffered from non-ST ACS, and reassessed 6 months later. Endothelium-dependent vasoreactivity was impaired at baseline in 81% (35/43) of the patients, and only 19% (8/43) of patients showed a normal response to ACh. Among the 35 subjects with initial dysfunction, 77% showed a significant improvement 6 months later. All patients without initial endothelial dysfunction remained normal. C-reactive protein (CRP) level was elevated at month 0, and had declined at follow-up, tending towards normal levels. At that time, apolipoprotein A-I (apoA-I) levels were correlated with vasomotor improvement in univariate (p < 0.02) and multivariate analysis (p < 0.04).

In conclusion, endothelium dysfunction is very frequently observed after recent ACS in non-culprit and angiographically normal coronary arteries, and an improvement occurs within 6 months in most cases. After resolution of the initial inflammation, apoA-I seems to play an important role in endothelial function.

Introduction

Endothelium plays a pivotal role in normal vessel homeostasis by regulating vasomotor tone, barrier permeability and haemostatic processes [1], [2].

All recognized vascular risk factors were previously associated with endothelial dysfunction [3], [4], [5], which has several aspects: decreased nitric oxide bioavaibility [6], increased endothelial permeability and platelet aggregation [7], and enhanced leukocyte adhesion to the endothelium [8]. Among these features, nitric oxide production can be indirectly assessed in humans by vasomotor function studies [6]. Thus, atherosclerosis is recognized as a multifocal disease where endothelial dysfunction plays a crucial role [9]. Recently, inflammation was also shown to play a central role at all steps of the atherosclerotic process, and the global indicator C-reactive protein (CRP) was shown to be increased in acute coronary syndromes and to be predictive of future cardiovascular events [10], [11]. Moreover, it has been suggested that endothelial dysfunction is widespread, as demonstrated by brachial assessment of patients with coronary artery disease [12], [13]. However, the hemodynamics and endothelial characteristics of coronary arteries are known to differ from the systemic characteristics. After unstable angina or acute myocardial infarction, a transient abnormal vasomotor dysfunction has been shown by intra-coronary testing at the location of the culprit lesion [14], [15], [16]. To the best of our knowledge, invasive assessment of endothelial vasomotor function in non-culprit and angiographically normal coronary arteries has never been previously reported after ACS.

Therefore, we investigated the extent to which recent ACS may be associated with abnormal endothelial vasomotor function tested in angiographically non-diseased coronary arteries remote from the culprit lesion, and how the function had evolved 6 months later.

Section snippets

Study population

The protocol was approved by the local Ethics Committee for the protection of human subjects and agreed with the comment: “no individual benefit from the survey for the patient”. Consequently, the study was approved for the duration of 2 years from inclusion to the end of the follow-up. A detailed consent form was signed by each patient. The sample population included 43 patients meeting the required criteria, who underwent an initial assessment of coronary endothelial vasoreactivity and a

Patients’ characteristics and assessment of endothelial function at month 0

The characteristics of the 43 patients satisfying the inclusion criteria are summarized in Table 1. Forty patients had single vessel disease and three had two-vessel disease. Forty-two patients were treated by stent implantation and one had no angioplasty. Endothelial vasomotor function was tested after recent non-ST acute coronary syndrome (5 ± 2 days) in an angiographically “normal” coronary artery (distribution of tested arteries is given in Table 1) before any revascularization procedure.

Discussion

Our study is the first to demonstrate that recent non-ST acute coronary syndromes are very frequently (81%) associated with endothelial dysfunction assessed in non-culprit angiographically normal-appearing coronary arteries. Moreover, reassessment of the patients 6 months later revealed that the initial endothelial dysfunction persisted in only one-fourth of them, demonstrating that reversibility of this phenomenon was the rule.

Conclusions and clinical implications

Our study is the first to demonstrate that, in-patients having recently suffered from ACS, endothelial vasomotor dysfunction is frequently observed in non-culprit and normal-appearing coronary arteries. None of the classic risk factors appear to be correlated with the initial endothelial dysfunction, making it important to identify new factors accounting for this phenomenon. In most cases, the initial endothelial vasomotor dysfunction improved at follow-up, suggesting that the existence of

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