Insight into coronary artery ectasia

Background: Coronary artery ectasia (CAE) is defined as a diffuse dilatation of the epicardial coronary arteries exceeding 1.5 folds the diameter of the normal adjacent arterial segment and/ or the remaining non-dilated part of the same artery. (1) The incidence of CAE has been variably reported between different nations and ranges between 1.4 -10 % (2-5). This wide range of variability is related to many factors including diverse definition of CAE, geographical distribution, association with other conditions (i.e. inflammatory, congenital or atherosclerosis) hence the existent uncertainty about disease burden and prevalence. (6) The main pathophysiology of CAE is initially understood to be part of atherosclerosis, (3) yet others reported the non-atherosclerotic nature of the disease. (2,7) The exact disease pathophysiology, prognosis and clinical outcome are not well studied; particularly the isolated, non-atherosclerotic, form of the disease has not been fully determined nor well identified. Methods: In paper 1, we examined the clinical presentation, prevalence and cardiovascular risk profile of the CAE patients in acute myocardial infarction (MI). We investigated the inflammatory response and short-term outcome in CAE patients of 3,321 acute consecutive MI patients who underwent primary PCI in two different centres in the UK (Royal Free Hospital, London and Norfolk, and Norwich University Hospital) between January 2009 and August 2012. In paper 2, we studied the personalised lipid profile and immune-inflammatory response in CAE patients from two different destinations (16 patients, mean age 64.9 ± 7.3 years, 6 female) Umea, Sweden and Letterkenny, Ireland. The lipidomic profile was compared with 26 control group (mean age 59.2 ± 6.6, 7 female) with normal coronary arteries. In paper 3, the plasma levels of 16 CAE (mean age 64.9 ± 7.3 years, 6 female) were compared with 69 age and gender matched (mean age 64.5 ± 8.7 years, 41 female) subjects with evidence of coronary artery disease and 140 controls with normal coronary arteries (mean age 58.6 ± 4.1 years, 81 female) in order to determine differences in inflammatory markers and cytokines, specific for CAE. In paper 4, we investigated long term follow up data of CAE patients without atherosclerotic burden. This represents follow up data of 66 patients with CAE, among 16,464 patients, who underwent diagnostic coronary angiography in Umea, Sweden and Letterkenny university Hospital, Ireland between 2003 and 2009. Of the 66 patients, long-term follow up (mean 11.3 ± 1.6 years) data was complete in 41 patients (age 66 ± 9 years), 12 Female. All hospital readmissions with Major Acute Cardiac Events (MACE) including mortality and morbidity and hospital readmissions for acute coronary syndrome (ACS) were compared with gender matched 41 controls. No subject had >20% coronary stenosis in any coronary branch. Results: Paper 1: The prevalence of CAE with acute MI was 2.7%. Apart from diabetes mellitus (DM) that was significantly less common in the CAE group (p=0.02), the other conventional cardiovascular risk factors were similar between ectatic and non-ectatic coronary arteries. The RCA and LCx were predominantly involved in patients with CAE (p=0.001 and 0.0001, respectively). CRP was higher (p=0.006) in CAE, but both WCC, neutrophil and neutrophil/lymphocyte ratio (N/L ratio) was lower (p = 0.002, 0.002 and 0.032). The short-term follow-up of 2 years showed no relationship between the inflammatory markers and MACE [(8/28, 28.6%) CAE vs. (13/60, 21.7%) without CAE, (p = 0.42)]. Paper 2: We identified 65 different metabolites between CAE group and controls, 27 of them were identifiable using metabolomics library software (15 were fully identified and 12 were identified through the size of the side chains). Sixteen species of phosphatidylcholines (PC); and 11 sphyngomyelins (SM) species had significantly lower intensities in patients with CAE. Paper 3: Systemic levels of IFN-γ, TNF-α, IL-1β, IL-6 and IL-8 were significantly higher in the CAE group compared to the CAD group (p = 0.006, 0.001, 0.001, 0.046 and 0.009, respectively) and the control group (p = 0.032, 0.002, 0.001, 0.049 and 0.007 in the same order), while the levels of IL-2 and IL-4 were lower (P < 0.001 for both) compared to the CAD and the control group. No differences were detected in the systemic levels of cytokines IL-10, IL-12P “subunits IL-12 and IL-23”, and IL-13 between the two patient groups Paper 4: While CAE patients were slightly older, they had longer follow up period (p<0.001) than controls. The overall mortality in the CAE group was higher (p<0.001) and similarly was CV mortality (p<0.03) compared with controls. MACE was similar in both groups (p=0.18). More patients smoked (p<0.001) and have family history for CAD (p<0.02) than controls but these variables were not different between survivals (36 patients) and non-survivors (5 patients). Females had more MACE than males (p<0.03). Finally, all non-survivors and 12/36 survivors had smoked and had dyslipidemia. Conclusion: Coronary artery ectasia, despite of common association with atherosclerosis, had a lower disease prevalence and dysregulated lipid metabolic profile than atherosclerosis. The pro-systemic inflammatory response in CAE is also different from atherosclerosis with different Cytokines milieu. In the context of CAE with acute coronary syndrome with obstructive atherosclerotic CAD, the management options should follow the standard guidelines for revascularization. CAE may lead to exaggerated inflammatory response in acute settings but the short-term outcome is similar to non-ectatic obstructive CAD. However, long term follow up data showed higher mortalities and hospital readmissions, yet no difference in MACE