Original article
Endothelial Dysfunction After ST-segment Elevation Myocardial Infarction and Long-term Outcome: A Study With Reactive Hyperemia Peripheral Artery TonometryDisfunción endotelial tras infarto de miocardio con elevación del segmento ST y evolución a largo plazo: un estudio con tonometría arterial periférica e hiperemia reactiva

https://doi.org/10.1016/j.rec.2015.12.020Get rights and content

Abstract

Introduction and objectives

Long-term data on the relationship between endothelial dysfunction after ST-segment elevation myocardial infarction and future adverse clinical events are scarce. The aim of this study was to noninvasively assess whether endothelial dysfunction 4 weeks to 6 weeks after primary percutaneous coronary intervention for acute ST-segment elevation myocardial infarction predicts future clinical events.

Methods

This prospective cohort study was performed in 70 patients of the RESPONSE randomized trial, who underwent noninvasive assessment of endothelial function 4 weeks to 6 weeks after primary percutaneous coronary intervention. Endothelial function was measured by the reactive hyperemia peripheral artery tonometry method; an index < 1.67 identified endothelial dysfunction.

Results

The reactive hyperemia peripheral artery tonometry index measured on average 1.90 ± 0.58. A total of 35 (50%) patients had endothelial dysfunction and 35 (50%) patients had normal endothelial function. Periprocedural “complications” (eg, cardiogenic shock, total atrioventricular block) were more common in patients with endothelial dysfunction than in those without (25.7% vs 2.9%; P < .01). During 4.0 ± 1.7 years of follow-up, 20 (28.6%) patients had major adverse cardiovascular events: events occurred in 9 (25.7%) patients with endothelial dysfunction and in 11 (31.5%) patients with normal endothelial function (P = .52). There was an association between the prevalence of diabetes mellitus at baseline and the occurrence of major adverse cardiovascular events during follow-up (univariate analysis: hazard ratio = 2.8; 95% confidence interval, 1.0-7.8; P < .05), and even in multivariate analyses the risk appeared to be increased, although not significantly (multivariate analysis: hazard ratio = 2.5; 95% confidence interval, 0.8-7.5).

Conclusions

In this series of patients who survived an ST-segment elevation myocardial infarction, endothelial dysfunction, as assessed by reactive hyperemia peripheral artery tonometry 4 weeks to 6 weeks after myocardial infarction, did not predict future clinical events during a mean follow-up of 4 years.

Resumen

Introducción y objetivos

Escasean datos a largo plazo sobre la relación entre disfunción endotelial tras infarto agudo de miocardio con elevación del segmento ST y futuros eventos clínicos adversos. El objetivo de este estudio es evaluar de manera no invasiva si la disfunción endotelial 4–6 semanas tras una intervención coronaria percutánea primaria por infarto agudo de miocardio con elevación del segmento ST predice la aparición futura de eventos clínicos.

Métodos

Este estudio prospectivo de cohortes se llevó a cabo en 70 pacientes del ensayo aleatorizado RESPONSE, a los que se evaluó de manera no invasiva la función endotelial 4–6 semanas después de la intervención coronaria percutánea primaria. Se determinó la función endotelial por el método de tonometría arterial periférica con hiperemia reactiva; la disfunción endotelial se identificó por un índice < 1,67.

Resultados

El índice de tonometría arterial periférica con hiperemia reactiva fue en promedio 1,90 ± 0,58. Un total de 35 (50%) pacientes presentaban disfunción endotelial y 35 (50%) tenían función endotelial normal. Las «complicaciones» periintervención (como shock cardiogénico o bloqueo auriculoventricular completo) fueron más frecuentes entre los pacientes con disfunción endotelial que entre quienes no la presentaban (el 25,7 frente al 2,9%; p < 0,01). Durante un seguimiento medio de 4,0 ± 1,7 años, 20 pacientes (28,6%) presentaron eventos adversos cardiovasculares mayores: se produjeron eventos de este tipo en 9 pacientes (25,7%) con disfunción endotelial y 11 (31,5%) con función endotelial normal (p = 0,52). Se observó asociación entre la prevalencia basal de diabetes mellitus y la aparición de eventos adversos cardiovasculares mayores durante el seguimiento (análisis univariable, hazard ratio = 2,8; intervalo de confianza del 95%, 1,0-7,8; p < 0,05) e incluso en los análisis multivariable el riesgo parecía aumentar, aunque sin alcanzar significación estadística (análisis multivariable, hazard ratio = 2,5; intervalo de confianza del 95%, 0,8-7,5).

Conclusiones

En esta serie de pacientes que habían sobrevivido a un infarto agudo de miocardio con elevación del segmento ST, la disfunción endotelial evaluada mediante tonometría arterial periférica con hiperemia reactiva 4–6 semanas tras el infarto de miocardio, no predijo los eventos clínicos futuros en una media de seguimiento de 4 años.

Section snippets

INTRODUCTION

Endothelial dysfunction of coronary conductance and resistance vessels, which is more often observed in the presence of certain cardiovascular risk factors, contributes significantly to the process of artherogenesis1, 2, 3, 4, 5 and may cause myocardial ischemia.6, 7, 8 The improvement of clinical outcome in response to modification of risk factors may primarily be the result of functional recovery of the impaired coronary vasomotor function, while structural changes of the atherosclerotic

Study Population and Design

This prospective cohort study was performed in 70 STEMI patients of the RESPONSE trial,24 who underwent treatment by PPCI for acute STEMI (≤ 12 hours after symptom onset) and noninvasive assessment of endothelial function with the RH-PAT method after 4 weeks to 6 weeks. The PPCI were performed between October 2007 and December 2008 at Thoraxcentrum Twente. Of a total of 75 STEMI patients of the RESPONSE trial with RH-PAT measurements, 71 had analyzable RH-PAT registrations, and follow-up was

Patient and Procedural Characteristics, in-hospital Course, and Endothelial Function

Of all 70 patients, who had a mean age of 56.9 ± 9.6 years, 55 (78.6%) were men. Primary PCI procedures were performed via the femoral route in all but one patient (98.4%); eight patients (11.4%) had prior percutaneous intervention and 1 (1.4%) had a history of coronary artery bypass grafting; manual thrombus aspiration was performed in 38 (62.3%), direct stenting in 36 (51.4%), and stent postdilatation in 56 (93.3%) patients. At discharge, the left venticular ejection fraction was preserved (>

DISCUSSION

While endothelial dysfunction is a key component of atherogenesis, contributes to the development of cardiovascular disease, and predicts outcome in patients with or without overt coronary artery disease,1, 2, 3, 4, 5, 6, 7 its significance for the highest risk category—patients with STEMI—was less certain. In the present prospective cohort study in STEMI patients of the RESPONSE trial that involved medical treatment according to evidence-based pharmacological concepts,24 endothelial

CONCLUSIONS

In this series of patients who survived a STEMI, endothelial dysfunction, as assessed by RH-PAT 4 weeks weeks to 6 weeks from PPCI, did not predict future MACE during an average follow-up of 4 years. Future large-scale studies with other techniques to assess endothelial dysfunction after PPCI may still be warranted.

CONFLICTS OF INTEREST

The research department of Thoraxcentrum Twente has received research grants funded by AstraZeneca, Biotronik, Boston Scientific, and Medtronic. C. von Birgelen has been a consultant for Boston Scientific and Medtronic, and has received lecture fees from AstraZeneca and MSD. R. J. G. Peters has been a consultant for Amgen, AstraZeneca, and Sanofi, and has received lecture fees from AstraZeneca, Boehringer Ingelheim, and Sanofi.

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