Pure coronary artery ectasia and main atherosclerotic risk factors: a study of Iranian population

Б  том ХXXI, 2025, № 3 ДРУЖЕСТВО НА КАРДИОЛОЗИТЕ В БЪЛГАРИЯ АВТОРСКИ СТАТИИ ORIGINAL ARTICLES PURE CORONARY ARTERY ECTASIA AND MAIN ATHEROSCLEROTIC PURE CORONARY ARTERY ECTASIA AND MAIN ATHEROSCLEROTIC RISK FACTORS: A STUDY OF IRANIAN POPULATION RISK FACTORS: A STUDY OF IRANIAN POPULATION H. Nough1, F. Moradi1, H. Varasteravan1, M. Motamedzade1, N. Sartipzade1, S. Vaziribozorg2, A. Nouah3 1Cardiovascular Research Center, 2Otorhinolaryngology Research Center, 3General Practitioner Shahid Sadoughi University of Medical Sciences – Yazd, Iran ЧИСТА ЕКТАЗИЯ НА КОРОНАРНИТЕ АРТЕРИИ И ОСНОВНИ АТЕРОСКЛЕРОТИЧНИ ЧИСТА ЕКТАЗИЯ НА КОРОНАРНИТЕ АРТЕРИИ И ОСНОВНИ АТЕРОСКЛЕРОТИЧНИ РИСКОВИ ФАКТОРИ: ИЗСЛЕДВАНЕ НА ИРАНСКОТО НАСЕЛЕНИЕ РИСКОВИ ФАКТОРИ: ИЗСЛЕДВАНЕ НА ИРАНСКОТО НАСЕЛЕНИЕ Х. Наф1, Ф. Moради1, Х. Варастераван1, M. Moтамедзаде1, Н. Сартипзаде1, С. Вазирибозорг2, A. Наф3 1Център за сърдечно-съдови изследвания, 2Център за оториноларингологични изследвания, 3Общопрактикуващ лекар, Медицински университет „Шахид Садуги“ – Язд, Иран Abstract. Introduction: Coronary artery ectasia (CAE) is an uncommon angiographic fi nding often associated with atherosclerosis. However, the risk profi le of patients with pure CAE (defi ned as ectasia in the absence of signifi cant obstructive coronary artery disease) remains incompletely understood. This study aimed to evaluate the association between traditional atherosclerotic risk factors and pure CAE in an Iranian population. Material and methods: In this retrospective crosssectional study, 354 patients with pure CAE were identifi ed among 23,000 consecutive coronary angiography reports from two tertiary hospitals (2015–2022). Pure CAE was defi ned as segmental or diffuse coronary artery dilatation ≥1.5fold the adjacent normal segment in the absence of ≥50% stenosis in any epicardial vessel. Patients with diffuse but non-obstructive atherosclerosis, history of vasculitis, autoimmune disease, congenital syndromes, or incomplete records were excluded. Demographic data and cardiovascular risk factors (hypertension, diabetes, hyperlipidemia, smoking, family history) were collected. Statistical analysis included both univariate comparisons and multivariable logistic regression to identify independent predictors of CAE. Results: The mean age was 57.5 ± 12.6 years; 64.1% were male. Hypertension (64.7%) and hyperlipidemia (57.9%) were the most prevalent risk factors. Multivariable regression identifi ed male sex (OR 1.8, 95% CI 1.1–2.9, p = 0.01), hypertension (OR 2.1, 95% CI 1.3–3.2, p = 0.002), and hyperlipidemia (OR 1.7, 95% CI 1.1–2.5, p = 0.01) as independent predictors of CAE. Diabetes mellitus and smoking were not signifi cantly associated. Family history showed borderline signifi cance (OR 1.4, p = 0.06). The most common angiographic pattern was threevessel ectasia (37.9%). Conclusion: Pure CAE is more frequent in men and strongly associated with hypertension and hyperlipidemia, supporting a shared risk profi le with atherosclerosis. The absence of association with diabetes and smoking suggests a distinct underlying pathophysiology. Key words: coronary artery ectasia, pure CAE, atherosclerosis, risk factors, angiography Address for correspondence: Arman Nough, General Practitioner, Shahid Sadoughi University of medical sciences, Yazd, Iran, e-mail: [email protected], phone: 00983538224000, fax: 00983538224100 Резюме.Въведение: Ектазията на коронарните артерии (CAE) е рядко срещано ангиографско нарушение, често свързано с атеросклероза. Въпреки това рисковият профил на пациентите с чиста CAE (определена като ектазия при липса на значителна обструктивна коронарна болест) остава не напълно изяснен. Целта на това проучване е да оцени връзката между традиционните атеросклеротични рискови фактори и чистата CAE при иранската популация. Материал и методи: В това ретроспективно кроссекционно проучване бяха идентифицирани 354 пациенти с чиста CAE сред 23 000 последователни доклада за коронарна ангиография от две третични болници (2015-2022 г.). Чистата CAE бе дефинирана като сегментна или дифузна дилатация на коронарната артерия ≥ 1,5 пъти по-голяма от съседния нормален сегмент при липса на ≥ 50% стеноза в някой от епикардиалните съдове. Пациентите с дифузна, но необструктивна атеросклероза, анамнеза за васкулит, автоимунно заболяване, вродени синдроми This is an open access article distributed under the terms of the Creative Commons Attribution License (CC BY 4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. doi: 10.3897/bgcardio.31.e164364 107 Pure coronary artery ectasia and main atherosclerotic risk... I Coronary artery ectasia (CAE) is a relatively rare angiographic fi nding, reported in 1.2-4.9% of patients undergoing coronary angiography worldwide [1]. Pure CAE was defi ned as segmental or diff use coronary artery dilatation ≥ 1.5-fold the adjacent normal segment in the absence of ≥ 50% stenosis in any epicardial vessel [2]. Although CAE is most commonly associated with atherosclerosis, other etiologies such as vasculitis, autoimmune diseases, and congenital syndromes have also been described [3]. From a pathophysiological point of view, CAE is the result of the degradation of the extracellular matrix of the media by matrix metalloproteinase which has been similarly observed in coronary heart disease [1, 2, 4]. More interesting, the clinical manifestations of the two coronary events are comparable as angina and acute coronary syndrome [3, 5]. Therefore, it is now assumed that there must be a signifi cant overlap between the risk factors for coronary artery atherosclerosis and the CAE. Therefore, the present study aimed to investigate the prevalence of traditional atherosclerotic risk factors among patients with pure CAE in an Iranian population and to determine the independent predictors of this condition. M   This cross-sectional study was approved by the local ethics committee, and written informed consent was obtained. The study was included patients undergoing coronary angiography at two tertiary referral hospitals in Yazd, Iran, between January 2015 and December 2022. Out of 23,000 angiograms, 369 cases of CAE were identifi ed. After applying exclusion criteria, 354 patients with pure CAE were enrolled. Pure CAE was defi ned as focal or diff use coronary dilatation ≥ 1.5-fold compared to an adjacent reference segment in the absence of ≥ 50% luminal stenosis in any major epicardial vessel [2]. Exclusion criteria Obstructive CAD (≥ 50% stenosis); Diff use atherosclerosis without focal stenosis; Known vasculitis, autoimmune disease, or congenital coronary anomalies; Incomplete demographic or laboratory data. A standardized checklist was used to collect data on demographics and cardiovascular risk factors: Hypertension: SBP ≥ 140 mm Hg or DBP ≥ 80 mm Hg, or use of antihypertensive drugs; Diabetes mellitus: Fasting glucose ≥ 7.0 mmol/L, use of insulin or oral hypoglycemics; Hyperlipidemia: Total cholesterol ≥ 4.7 mmol/L, triglycerides ≥ 2.3 mmol/L, or LDL ≥ 4.1 mmol/L; Smoking: ≥ 10 pack-years; Family history: CAD in male relatives < 55 years or female relatives < 65 years. Continuous variables were presented as mean ± SD and compared using t-test or Mann-Whitney U test as appropriate. Categorical variables were analyzed with chi-square test. Multivariable logistic regression was applied to identify independent associations of risk factors with pure CAE. Results were expressed as odds ratios (OR) with 95% confi dence intervals (CI). A p-value < 0.05 was considered signifi cant. Analyses were performed using SPSS v23. R Of 354 patients with pure CAE, the mean age was 57.5 ± 12.6 years (range 25–89), and 64.1% were male. Hypertension (64.7%) and hyperlipidemia (57.9%) were the most common risk factors, followed by diaили непълни записи бяха изключени от проучването. Бяха събрани демографски данни и данни за сърдечно-съдови рискови фактори (хипертония, диабет, хиперлипидемия, тютюнопушене, фамилна анамнеза). Статистическият анализ включваше както едномерни сравнения, така и многомерна логистична регресия за идентифициране на независими предиктори на CAE. Резултати: Средната възраст на обхванатите в проучването лица беше 57,5 ± 12,6 години; 64,1% бяха мъже. Хипертония (64,7%) и хиперлипидемия (57,9%) бяха най-разпространените рискови фактори. Многовариантната регресия идентифицира мъжкия пол (OR 1,8, 95% CI 1,1–2,9, p = 0,01), хипертонията (OR 2,1, 95% CI 1,3–3,2, p = 0,002) и хиперлипидемията (OR 1,7, 95% CI 1,1–2,5, p = 0,01) като независими предиктори на CAE. Захарният диабет и тютюнопушенето не показаха статистически значима връзка. Семейната анамнеза показва гранична значимост (OR 1,4, p = 0,06). Най-често срещаният ангиографски модел е ектазия на три съда (37,9%). Заключение: Чистата CAE е по-честа при мъжете и е силно свързана с хипертония и хиперлипидемия, което подкрепя обща рискова характеристика с атеросклерозата. Липсата на връзка с диабета и тютюнопушенето предполага различна основна патофизиология. Ключови думи:ектазия на коронарната артерия, чиста CAE, атеросклероза, рискови фактори, ангиография Адрес за кореспонденция: д-р Арман Наф, общопрактикуващ лекар, Медицински университет „Шахид Садуги“, Язд, Иран, e-mail: [email protected], телефон: 00983538224000, факс: 00983538224100 H. Nough, F. Moradi, H. Varasteravan et al. 108 betes mellitus (30.2%), smoking (45.5%), and positive family history (50.6%). The baseline characteristics are shown in (Table 1). As shown in (Table 2), the pattern of three-vessel involvement with ectasia was signifi cantly higher in the ages ranged 25 to 37 years followed by 64 to 76 years, while other patterns of involvements were seen mostly in the age range of 51 to 63 years indicating an age-dependent diff erence in the patterns of CAE (p = 0.02). Also, multiple vessel ectasia was revealed more in men than in women (p = 0.03). Moreover, multiple CAE was signifi cantly higher in hypertensive than in normotensive patients (p = 0.004), hyperlipidemic than normal lipid subgroups (p = 0.008), and those with family history of CAE (p = 0.02). However, we showed no diff erence in the pattern of CAE in smoker and non-smoker subgroups (p = 0.55). Multivariable regression identifi ed male sex (OR 1.8, 95% CI 1.1–2.9, p = 0.01), hypertension (OR 2.1, 95% CI 1.3–3.2, p = 0.002), and hyperlipidemia (OR 1.7, 95% CI 1.1–2.5, p = 0.01) as independent predictors of CAE. Diabetes mellitus and smoking were not signifi cantly associated. Family history showed borderline signifi cance (OR 1.4, p = 0.06). The most common angiographic pattern was three-vessel ectasia (37.9%). The most frequent angiographic pattern was three-vessel ectasia (37.9%), followed by isolated LAD involvement (21.8%). Men and hypertensive patients were more likely to have multivessel ectasia. D In this study of Iranian patients with pure CAE, we found that hypertension, hyperlipidemia, and male sex were independent predictors, whereas diabetes and smoking were not associated. These fi ndings support the hypothesis that CAE shares major risk factors with atherosclerosis but may follow a distinct pathophysiological pathway. CAE, known as aneurysm or ectasia, is a rare condition that is usually seen as an accidental fi nding in those undergoing angiography, and its prevalence varies from 1.2 to 4.9% [1, 6]. The most common cause is atherosclerosis, followed by Kawasaki disease and congenital aneurysmal diseases [7-9]. Due to the most common cause of this disease, in this study we investigated the role of main risk factors for atherosclerotic diseases in CAE to fi nd prognostic factors and determine their possible association with this disease. Table 2. The pattern of coronary CAE according to baseline variables Variables LAD LCX RCA LAD & LCX LAD & RCA LCX & RCA LAD & LCX & RCA Gender Male 43 (18.9) 13 (5.7) 25 (11.0) 19 (8.4) 26 (11.5) 6 (2.6) 95 (41.9) Female 34 (26.8) 12 (9.4) 9 (7.1) 17 (13.4) 13 (10.2) 3 (2.4) 39 (30.7) Age (Years) 25 to 37 4 (18.2) 1 (4.5) 0 (0.0) 2 (9.1) 2 (9.1) 0 (0.0) 13 (59.1) 38 to 50 25 (29.4) 4 (4.7) 9 (10.6) 10 (11.8) 11 (12.9) 0 (0.0) 26 (30.6) 51 to 63 28 (22.8) 10 (8.1) 14 (11.4) 17 (13.8) 16 (13.0) 4 (3.3) 34 (27.6) 64 to 76 17 (16.5) 6 (5.8) 9 (8.7) 6 (5.8) 10 (9.7) 3 (2.9) 52 (50.0) 77 to 89 3 (14.3) 4 (19.0) 2 (9.5) 1 (4.8) 0 (0.0) 2 (9.5) 9 (42.9) History of hypertension Positive 42 (18.3) 18 (7.9) 24 (10.5) 21 (9.2) 20 (8.7) 3 (1.3) 101 (44.1) Negative 35 (28.0) 7 (5.6) 10 (8.0) 15 (12.0) 19 (15.2) 6 (4.8) 33 (26.4) History of hyperlipidemia Positive 37 (18.0) 14 (6.8) 21 (10.2) 17 (8.3) 19 (9.3) 5 (2.4) 92 (44.9) Negative 40 (26.8) 11 (7.4) 13 (8.7) 19 (12.8) 20 (13.4) 4 (2.7) 42 (28.2) History of coronary disease Positive 32 (17.9) 9 (5.0) 15 (18.4) 16 (8.9) 18 (10.1) 4 (2.2) 85 (47.5) Negative 45 (25.7) 16 (9.1) 19 (10.9) 20 (11.4) 21 (12.0) 5 (2.9) 49 (28.0) History of smoking Positive 41 (25.5) 11 (6.8) 18 (11.2) 15 (9.3) 19 (11.8) 4 (2.5) 53 (32.9) Negative 36 (18.7) 14 (7.3) 16 (8.3) 21 (10.9) 20 (10.4) 5 (2.6) 81 (42.0) Table 1. Baseline characteristics and cardiovascular profi le in study population (n = 354) Mean age, year 57.5 ± 12.6 Male gender, % 227 (64.1) History of hypertension, % 229 (64.7) History of diabetes mellitus, % 107 (30.2) History of hyperlipidemia, % 205 (57.9) Family history of coronary disease, % 179 (50.6) History of smoking, % 161 (45.5) Pattern of coronary artery ectasia LAD 77 (21.8) LCX 25 (7.1) RCA 34 (9.6) LAD & LCX 36 (10.2) LAD & RCA 39 (11.0) LCX & RCA 9 (2.5) LAD & LCX & RCA 134 (37.9) 109 Pure coronary artery ectasia and main atherosclerotic risk... According to the results of our studies, descriptive and demographic fi ndings showed that the mean age of patients was 57.5 ± 12.6 years. It was also shown that the frequency CAE is higher in men than women and the highest frequency of the study population was in the age of 51 to 63 years. Accordingly, in the study of Fariba et al [10] conducted in 2016, 61.3% of patients were male and 38.7% were female, and the average age of patients was 59 years, which was consistent with our study. In a 2011 study by Riff at Sultana et al [11] the mean age was 52.1 ± 10.3 which was closely correlated with our study. Amirzadegan et al. [12] conducted a retrospective cohort study in Iran and showed that patients with CAE are signifi cantly older than patients with normal coronary arteries. Also in the studies of Pinar et al. [7] Qin et al [8], and Swanton et al. [13], the most patients with CAE were men, which was consistent with our study in this regard. In this study, it was shown that most patients (64.7%) with CAE had hypertension and based on our study, there was a signifi cant relationship between hypertension and CAE. Accordingly, in the study of Riff at Sultana et al [11], 55% of patients had high blood pressure and in the study of Fariba et al [10], 57.7% of patients had high blood pressure, which indicates that the majority of patients have high blood pressure. More interestingly, the complexity of CAE was associated with the hypertension, indicating raised blood pressure as the major risk factor for CAE complexity. Regarding the role of diabetes mellitus, in this study, 30.2% of patients were diabetic and 69.8% were non-diabetic, which showed that the prevalence of diabetes in patients with CAE was low. Accordingly, the study by Pinar et al [7] showed that 22.4% of patients had diabetes, which, like our study, indicates a low prevalence of diabetes in this disease. In the study of Riff at et al [11] and Fariba et al [10], the prevalence of diabetes was 22% and 13.4%, respectively. A study by Rashid et al [6] found that diabetes was independently but inversely related to CAE, which is consistent with the results of our study. In this study, 57.9% of the patients had abnormal lipid profi les, which among the patients with concomitant ectasia of LAD & LCX & RCA abnormal lipid profi les was more common. A study by Qin et al [8] showed that high levels of triglyceride and LDL/HDL ratio were identifi ed as risk factors for CAE, which is consistent with the results of our study. In other studies by LAM et al [9] in Singapore 63% of patients with ectasia had abnormal lipid profi le and this factor is strongly associated with CAE. In our study, 50.6% of patients with CAE had a positive family history of ischemic heart disease and 49.4% had no family history, which is a signifi cant fi nding in patients with CAE. A study by Lui et al [14] showed hyperlipidemia and a positive family history as independent variables that were strongly associated with coronary atherosclerosis but not with CAE. In our study, 45.5% of patients were smokers and 54.5% of patients were non-smokers. In our study, this factor did not show a signifi cant relationship with CAE and the frequency of smokers with ectasia was lower than non-smokers. While in the study of Amirzadegan et al [12] (53.7%) and Pinar et al [7] ,(56.5%) and Qin et al [8], (56.6%) smoking was also shown as a risk factor for CAE. Fariba et al [10], smoking was a common risk factor for CAE because smoking was considerably prevalent in men than in women. Our study showed that the prominent pattern of coronary involvement was related to simultaneous involvement of three coronary vessels (37.9%), followed by LAD (21.8%) and then LAD & RCA (11%) involvement respectively. In the study by Riff at Sultana et al [11], the left anterior descending artery (LAD) was the most commonly involved vessel (63%) followed by RCA (25%), whereas in the study of George D Giannoglou et al [15], the prevalence of ectasia in the right coronary artery was signifi cantly higher than the LAD and LCX arteries. Therefore, high variability in CAE involvement patterns has been observed in various reports. As the fi nal conclusion, according to our study, the critical role of the main risk factors for coronary artery atherosclerosis, such as raised blood pressure, abnormal lipid profi le, positive family history, male gender and old age has been evident in patients with CAE, while the role of diabetes and history of smoking remains already uncertain. Also, the diff erence in the prevalence of ectasia patterns in single or complex form as well as the type of vessel involved in diff erent communities also needs further pathophysiological studies. But what is clear from our study is the pivotal role of some risk factors for atherosclerosis, including hypertension, hyperlipidemia, and a positive family history in increasing the risk of CAE. Consequently, control of any of these risk factors can be very eff ective in tracking the occurrence of ectasia and therefore preventing its adverse consequences. C Pure CAE is signifi cantly associated with male gender, hypertension, and hyperlipidemia, but not with diabetes or smoking. These fi ndings suggest that while CAE shares major risk factors with atherosclerosis, its pathophysiology may be partially distinct. Careful risk factor management, especially blood pressure and lipid control, may play a crucial role in preventing complications in these patients. L  R Future prospective studies incorporating multimodality imaging and broader etiologic screening (oth- H. Nough, F. Moradi, H. 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