Association of Plasma Level of Eotaxin in Recurrent Coronary events and In-Stent Restenosis

Abstract

Background: In-Stent Restenosis (ISR) is a malignant process in patients who have undergone coronary artery stent implantation as it causes mortality and morbidity. Predicting ISR, when initial percutaneous coronary intervention is performed is difficult. Various clinical and angiographic models have been proposed but their value in the real world is far from ideal. Inflammatory markers have been linked with atherosclerosis and the risk of acute coronary syndrome. Recently it has been shown that these markers may act as clinically useful predictors of ISR. Eotaxin has been recognised as a novel marker of atherosclerosis. Its inverse relationship in abdominal aortic aneurysm has been confirmed by the Otago vascular research group. In this study we have investigated this novel marker in patients with ISR after bare metal stent implantation. We also have analysed 23 other inflammatory markers and high sensitivity C-reactive protein (hsCRP).

Method: In this prospective study, 494 patients were approached and 402 who had undergone bare metal stent implantation were enrolled. Pre procedural and three month serum samples were analysed for a panel of inflammatory markers. Demographic data were collected by completing a questionnaire. Subsequent cardiovascular events were classified as either ISR, or non ISR events. Patients with events were compared to a matched control group with no events during follow up. Results: Twenty-two patients had ISR, 16 had non ISR events and there were 60 matched control subjects. The majority of our study population (>90%) was New Zealand European and 42 (70%) were males. The mean (± standard deviation) age of the control and ISR cases was 62.2 ± 10.2 years and 68.8 ± 9.8 years respectively (p=0.01). There were no significant difference in cardiovascular risk factors including smoking, hypertension, hyperlipidaemia and diabetes mellitus. The commonest clinical presentation in the ISR group was non-ST elevation myocardial infarction 12 (55%), and stable angina 6 (27%). Only 2 (9%) patients presented with ST elevation myocardial infarction. Even though median baseline plasma eotaxin level was lower in the ISR group compared with controls [median (IQR), 4.82 pg/mL (0.00 – 7.25) vs 5.84 pg/mL (3.08 – 9.54), statistical analysis showed it was not significant (p=0.3). In contrast to these findings in the non-ISR events group the eotaxin level was higher than control [8.89 pg/mL (4.95 – 13.2) vs 5.84 pg/mL (3.08 – 9.54), p=0.05]. Further analysis also showed eotaxin level was higher in three vessel disease patients compared to single vessel disease patients [8.66 pg/mL (3.49 – 14.95) vs 5.06 pg/mL (3.13 – 6.56), p=0.03], however the analysis for trend across three groups of coronary artery severity was not significant (p = 0.16). As shown in previous studies, the hsCRP level was significantly higher in the ISR group at baseline compared to controls [9.05 mg/mL (3.80 – 16.45) vs 3.00 mg/mL (1.30 – 6.97), p=0.01] indicating our sample is comparable to previously studied patients with ISR. Although the main focus of this thesis was to identify the association between eotaxin levels and ISR, 23 other inflammatory markers were also measured. All of these inflammatory markers showed numerically lower levels in the ISR group compared to control without reaching statistical significance. Conclusion: This study indicates no difference between pre-intervention eotaxin levels in ISR group compared with controls after bare metal coronary stent implantation. Further studies are needed to explore this novel marker to understand the molecular mechanisms of ISR and also to formulate preventive and therapeutic strategies in the future.