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Insight into coronary artery ectasia
Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin.
2019 (engelsk)Doktoravhandling, med artikler (Annet vitenskapelig)
Abstract [en]

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.

sted, utgiver, år, opplag, sider
Umeå: Umea University , 2019. , s. 84
Serie
Umeå University medical dissertations, ISSN 0346-6612 ; 2058
Emneord [en]
Coronary artery ectasia, atherosclerosis, acute coronary syndrome, lipidomic profile, cytokines, prognosis of coronary artery ectasia
HSV kategori
Forskningsprogram
kardiologi
Identifikatorer
URN: urn:nbn:se:umu:diva-163476ISBN: 978-91-7855-129-3 (tryckt)OAI: oai:DiVA.org:umu-163476DiVA, id: diva2:1353304
Disputas
2019-11-21, Major Groove, Target point JO, Umeå, 09:00 (engelsk)
Opponent
Veileder
Tilgjengelig fra: 2019-10-31 Laget: 2019-09-23 Sist oppdatert: 2019-11-19bibliografisk kontrollert
Delarbeid
1. Patterns of coronary artery ectasia and short-term outcome in acute myocardial infarction
Åpne denne publikasjonen i ny fane eller vindu >>Patterns of coronary artery ectasia and short-term outcome in acute myocardial infarction
Vise andre…
2014 (engelsk)Inngår i: Scandinavian Cardiovascular Journal, ISSN 1401-7431, E-ISSN 1651-2006, Vol. 48, nr 3, s. 161-166Artikkel i tidsskrift (Fagfellevurdert) Published
Abstract [en]

Objective. To assess the relationship between hematological inflammatory signs, cardiovascular risk (CV) factors and prognosis in patients presenting with acute myocardial infarction (AMI) and coronary artery ectasia (CAE). Design. We investigated 3321 AMI patients who required urgent primary percutaneous intervention in two centres in the United Kingdom between January 2009 and August 2012. Thirty patients with CAE were compared with 60 age-and gender-matched controls. Blood was collected within 2 h of the onset of chest pain. CV risk factors were assessed from the records. Major acute cardiac events and/or mortality (MACE) over 2 years were documented. Results. CAE occurred in 2.7% and more often affected the right (RCA) (p = 0.001) and left circumflex artery (LCx) (0.0001). Culprit lesions were more frequently related to atherosclerosis in non-CAE patients (p = 0.001). Yet, CV risk factors failed to differentiate between the groups, except diabetes, which was less frequent in CAE (p = 0.02). CRP was higher in CAE (p = 0.006), whereas total leucocyte, neutrophil counts and neutrophil/lymphocyte ratio (N/L ratio) were lower (p = 0.002, 0.002 and 0.032, respectively) than among non-CAE. This also was the case in diffuse versus localised CAE (p = 0.02, 0.008 and 0.03, respectively). The MACE incidence did not differ between CAE and non-CAE (p = 0.083) patients, and clinical management and MACE were unrelated to the inflammatory markers. Conclusion. In AMI, patients with CAE commonly have aneurysmal changes in RCA and LCx, and their inflammatory responses differ from those with non-CAE. These differences did not have prognostic relevance, and do not suggest different management.

Emneord
coronary artery ectasia, inflammatory response, MACE, myocardial infarction, short-term outcome
HSV kategori
Identifikatorer
urn:nbn:se:umu:diva-91060 (URN)10.3109/14017431.2014.902495 (DOI)000336974200005 ()
Tilgjengelig fra: 2014-07-11 Laget: 2014-07-10 Sist oppdatert: 2019-09-23bibliografisk kontrollert
2. Dysregulated fatty acid metabolism in coronary ectasia: An extended lipidomic analysis
Åpne denne publikasjonen i ny fane eller vindu >>Dysregulated fatty acid metabolism in coronary ectasia: An extended lipidomic analysis
Vise andre…
2017 (engelsk)Inngår i: International Journal of Cardiology, ISSN 0167-5273, E-ISSN 1874-1754, Vol. 228, s. 303-308Artikkel i tidsskrift (Fagfellevurdert) Published
Abstract [en]

BACKGROUND: Coronary artery ectasia (CAE) is not an uncommon clinical condition, which could be associated with adverse outcome. The exact pathophysiology of the disease is poorly understood and is commonly interpreted as a variant of atherosclerosis. In this study, we sought to undertake lipidomic profiling of a group of CAE patients in an attempt to achieve better understanding of its disturbed metabolism.

METHODS: Untargeted lipid profiling and complementary modelling strategies were employed to compare serum samples from 16 patients with CAE (mean age 63.5±10.1years, 6 female) and 26 controls with normal smooth coronary arteries (mean age 59.2±6.6years and 7 female). Sample preparation, LC-MS analysis and metabolite identification were performed at the Swedish Metabolomics Centre, Umeå, Sweden.

RESULTS: Phosphatidylcholine levels were significantly distorted in the CAE patients (p=0.001-0.04). Specifically, 16-carbon fatty acyl chain phosphatidylcholines (PC) were detected in lower levels. Similarly, 11 meioties of Sphyngomyelin (SM) species were detected at lower concentrations (p=0.000001-0.01) in the same group. However, only three metabolites were significantly higher in the pure CAE subgroup (6 patients) when compared with the 10 mixed CAE patients (two meioties of SM species and one of PC). Atherosclerosis risk factors were not different between groups.

CONCLUSION: This is the first lipid profiling study reported in coronary artery ectasia. While the lower concentration and dysregulation of sphyngomyelin suggests an evidence for premature apoptosis, that of phosphatidylcholines suggests perturbed fatty acid elongation/desaturation, thus may be indicative of non-atherogenic process in CAE.

Emneord
Atherosclerosis, Coronary artery ectasia, Lipidomic analysis, Phosphatidylcholine, Sphyngeomyeline
HSV kategori
Identifikatorer
urn:nbn:se:umu:diva-130607 (URN)10.1016/j.ijcard.2016.11.093 (DOI)000393408600050 ()27866019 (PubMedID)
Tilgjengelig fra: 2017-01-26 Laget: 2017-01-26 Sist oppdatert: 2019-09-23bibliografisk kontrollert
3. Cytokine Disturbances in Coronary Artery Ectasia Do Not Support Atherosclerosis Pathogenesis
Åpne denne publikasjonen i ny fane eller vindu >>Cytokine Disturbances in Coronary Artery Ectasia Do Not Support Atherosclerosis Pathogenesis
Vise andre…
2018 (engelsk)Inngår i: International Journal of Molecular Sciences, ISSN 1422-0067, E-ISSN 1422-0067, Vol. 19, nr 1, artikkel-id 260Artikkel i tidsskrift (Fagfellevurdert) Published
Abstract [en]

BACKGROUND: Coronary artery ectasia (CAE) is a rare disorder commonly associated with additional features of atherosclerosis. In the present study, we aimed to examine the systemic immune-inflammatory response that might associate CAE.

METHODS: Plasma samples were obtained from 16 patients with coronary artery ectasia (mean age 64.9 ± 7.3 years, 6 female), 69 patients with coronary artery disease (CAD) and angiographic evidence for atherosclerosis (age 64.5 ± 8.7 years, 41 female), and 140 controls (mean age 58.6 ± 4.1 years, 40 female) with normal coronary arteries. Samples were analyzed at Umeå University Biochemistry Laboratory, Sweden, using the V-PLEX Pro-Inflammatory Panel 1 (human) Kit. Statistically significant differences (p < 0.05) between patient groups and controls were determined using Mann-Whitney U-tests.

RESULTS: The CAE patients had significantly higher plasma levels of INF-γ, TNF-α, IL-1β, and IL-8 (p = 0.007, 0.01, 0.001, and 0.002, respectively), and lower levels of IL-2 and IL-4 (p < 0.001 for both) compared to CAD patients and controls. The plasma levels of IL-10, IL-12p, and IL-13 were not different between the three groups. None of these markers could differentiate between patients with pure (n = 6) and mixed with minimal atherosclerosis (n = 10) CAE.

CONCLUSIONS: These results indicate an enhanced systemic pro-inflammatory response in CAE. The profile of this response indicates activation of macrophages through a pathway and trigger different from those of atherosclerosis immune inflammatory response.

sted, utgiver, år, opplag, sider
Basel, Switzerland: MDPI, 2018
Emneord
atherosclerosis, coronary artery disease, coronary artery ectasia, cytokines, immune inflammatory response, macrophage activation
HSV kategori
Forskningsprogram
epidemiologi
Identifikatorer
urn:nbn:se:umu:diva-144041 (URN)10.3390/ijms19010260 (DOI)000424407200254 ()29337902 (PubMedID)
Forskningsfinansiär
Swedish Heart Lung Foundation
Tilgjengelig fra: 2018-01-26 Laget: 2018-01-26 Sist oppdatert: 2019-09-23bibliografisk kontrollert
4. Coronary artery ectasia carries worse prognosis: a long-term follow-up study
Åpne denne publikasjonen i ny fane eller vindu >>Coronary artery ectasia carries worse prognosis: a long-term follow-up study
Vise andre…
2019 (engelsk)Inngår i: Polish Archives of Internal Medicine, ISSN 0032-3772, E-ISSN 1897-9483Artikkel i tidsskrift, Letter (Fagfellevurdert) Epub ahead of print
HSV kategori
Identifikatorer
urn:nbn:se:umu:diva-163322 (URN)10.20452/pamw.14959 (DOI)31469119 (PubMedID)
Tilgjengelig fra: 2019-09-16 Laget: 2019-09-16 Sist oppdatert: 2019-09-23

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