International Journal of Cardiology 186 (2015) 299–301
Contents lists available at ScienceDirect
International Journal of Cardiology journal homepage: www.elsevier.com/locate/ijcard
Letter to the Editor
Anxiety and depression scores in patients with coronary artery disease and coronary artery ectasia S. Ozturk a, H.D. Yalvac b, N. Sivri c, H.M. Ozturk d, Y. Kılıc a, E. Bulut a, A. Celik a, Y. Barlas a, I. Tengiz e, E. Yetkin f,⁎ a
Abant Izzet Baysal University Izzet Baysal Research and Training Hospital, Department of Cardiology, Bolu, Turkey DR Abdurrahman Yurtaslan Oncology Research and Training Hospital, Department of Psychiatry, Ankara, Turkey Trakya University Faculty of Medicine, Department of Cardiology, Edirne Turkey d Abant Izzet Baysal University Izzet Baysal Research and Training Hospital, Department of Psychiatry, Bolu, Turkey e Izmir University Medical Park Hospital, Department of Cardiology, Izmir, Turkey f Middle East Hospital, Department of Cardiology, Mersin, Turkey b c
a r t i c l e
i n f o
Article history: Received 17 March 2015 Accepted 19 March 2015 Available online 20 March 2015 Keywords: Coronary artery disease Coronary artery ectasia Anxiety Depression
The relation of negative emotions such as depression and anxiety with cardiovascular disease has been reported in numerous studies [1, 2]. In patients with stable coronary artery disease (CAD), it has been demonstrated that depression is a strong predictor of cardiovascular events [3]. Also, anxiety symptoms are associated with an increased risk of death or myocardial infarction among patients with CAD [4]. The long term activation of autonomic nervous system may increase the risk of atherosclerosis, cardiac ischemia, blood pressure variability, heart rate variability, myocardial infarction or sudden death [5]. Coronary artery ectasia (CAE) is localized or diffuse dilation of epicardial coronary arteries, 1.5 times the diameter of the adjacent normal coronary segment [6,7]. Although CAE has been supposed to be a variant of atherosclerosis, clinical parameters and pathophysiologic processes show considerable differences compared to those of obstructive coronary artery disease, which is well reviewed by Yetkin and Waltenberger [8]. Recently we have documented increased anxiety and depression scores in patients with slow coronary flow compared to patients with normal coronary arteries and normal coronary flow (unpublished data). Accordingly, we aimed to test whether anxiety and depression status of patients with CAE are different from those of patients with CAD. ⁎ Corresponding author. E-mail address: [email protected] (E. Yetkin).
http://dx.doi.org/10.1016/j.ijcard.2015.03.305 0167-5273/© 2015 Elsevier Ireland Ltd. All rights reserved.
We prospectively included 328 patients who had coronary artery disease. Of whom 310 patients had only CAD and 18 patients had both CAE and CAD. The patients were individually approached by the registered nurses and invited to participate in the study. The nurse briefly explained the study and asked patient to complete the questionnaires. To minimize the environmental factors, the participants were asked to be alone in a silent room unless they asked for help to read or write. All patients were asked to complete the questionnaires including State-Trait Anxiety Inventory (STAI), Beck Depression Inventory (BDI) and Beck Anxiety Inventory (BAI) at least 2 h before coronary angiography. The Spielberger State-Trait Anxiety Inventory state and trait scores (STAI-S and STAI-T) were used to characterize anxiety symptoms of the patients. The STAI-S measures the transitional emotional status evoked by a stressful situation, like surgery. The STAI-T score reflects relatively enduring individual differences in anxiety proneness [9]. The 21-item Beck Depression Inventory — Version 2 (BDI-2) is a widely used measure of psychological and physical symptoms of depression in adults. Each item consists of four statements indicating the degree of severity of the symptom. All patients' angiographic results were told immediately after the procedure. At least 1 h later after the patients were informed about their coronary artery lesions, they were asked to recomplete STAI-S. Each set of questionnaires took approximately 15–20 min to complete. All of the patients completed the questionnaire on the day of the coronary angiography. The validity and reliability of the BDI and BAI have been studied in the Turkish Population by Ulusoy and Hisli [10,11]. Coronary angiography was performed with standard Seldinger's technique by femoral approach in all patients. In order to evaluate each coronary artery, at least four views from the left and two views from the right system were taken. Angiographic images were evaluated by two independent researchers. CAE was defined as dilatation of at least one epicardial coronary artery 1.5 times the reference vessel diameter in any of the coronary arteries. CAD was defined as nonsignificant or significant atherosclerotic lesions in any of the coronary arteries. Patients with known systemic diseases, malignancies, psychiatric disorders, acute coronary syndromes and previous coronary angiography or coronary artery bypass grafting were not included in the study. Continuous variables were given as mean ± S.D.; categorical variables were defined as percentage. Comparison of categorical data was
300
S. Ozturk et al. / International Journal of Cardiology 186 (2015) 299–301
Table 1 Clinical characteristics of patients. Variables
Patients with CAD (n = 310)
Patients with CAD + CAE (n = 18)
p value
Age Gender (male/female) Smoking Previous MI Hypertension Hypercholesterolemia Diabetes mellitus Family history Age
62 ± 10 207/103 139 (%45) 105 (%34) 195 (%63) 111 (%36) 114 (%37) 130 (%42)
64 ± 9 11/7 8 (%44) 5 (%27) 8 (%44) 3 (%16) 4 (%22) 7 (%38)
0.18 0.58 0.97 0.54 0.11 0.08 0.20 0.77
CAD: coronary artery disease (including nonsignificant atherosclerotic lesions); CAE: coronary artery ectasia.
made by using Chi-square test. Comparison of continuous variables was made by using unpaired t test between groups and paired or Wilcoxon match test where suitable. Continuous variables and categorical variables were compared by using unpaired t test and Chisquare test respectively. All tests of significance were two-tailed. Statistical significance was defined as p b 0.05. The SPSS statistical software (SPSS for windows 15, Inc., Chicago, IL, USA) was used for all statistical calculations. Three hundred and twenty eight consecutive patients with coronary artery disease, of whom 18 had CAE and CAD and 310 had only coronary artery disease, were included in statistical analysis. There were no statistically significant differences between two groups in terms of clinical characteristics namely; age, gender, smoking, previous myocardial infarction, hypertension, hyperlipidemia and diabetes mellitus (Table 1). In patients with CAD, STAI-S scores before and after coronary angiography were significantly higher than the other group (42.7 ± 10.5, 33.7 ± 10.1, p b 0.001; 39.7 ± 11.4, 29.1 ± 9.5, p b 0.001). Decrease in STAI-S scores before and after coronary angiography in both groups was statistically significant (p b 0.001, p = 0.01). STAI-T scores of patients with CAD and CAE tended to be lower than those of patients with CAD (42.7 ± 7.9, 46.2 ± 7.7, respectively, p = 0.06). In patients with CAD, BAI scores were significantly higher than the patients with CAD and CAE (17.8 ± 11.9, 11.8 ± 9.1, p = 0.03). Although patients with CAD and CAE have lower BDI score compared to patients with CAD, it did not yield statistical significance (7.6 ± 6.2, 10.3 ± 7.9, respectively, p = 0.14) (Table 2). The main finding of our study is that depression and anxiety scores (STAI-S, BAI and STAI-S after coronary angiography) are significantly lower in patients with CAE than those with CAD alone. Secondly STAIS scores of both patients have significantly decreased after completing the angiographic procedure and informing patients about the results. Additionally STAI-T scores of patients with CAE have a tendency to be lower than those with CAD alone. Increasing evidences have supported the hypothesis that CAE is a local manifestation of systemic dilating vascular disease differing from obstructive coronary disease. In a study reported by Yetkin et al., carotid intima media thickness was thinner in CAE patients with stenotic CAD
Conflict of interest
Table 2 Depression and anxiety scores of patients.
STAI-S (before CAG) STAI-S (after CAG) STAI-T BAI BDI
when compared to patients with CAD only and they stated that ectasia was not an atherosclerotic process limited to coronary arteries [12]. It has also shown that extracellular matrix remodeling in CAE might differ from that in atherosclerosis [13]. These results indicate that different mechanisms rather than atherosclerotic process may be responsible for CAE physiopathology. In terms of systemic involvement and dilating process of disease, nitric oxide (NO) plays an important role in the pathophysiology of CAE [8,14,15]. England has reported an increased frequency of CAE in individuals who had been exposed to herbicide sprays. A herbicide containing acetylcholinesterase inhibitor directly stimulates NO production by increasing acetylcholine [16]. Johanning et al. has experimentally shown that NO production plays a major role in inflammation and aneurysm pathogenesis [15]. The overexpression of iNOS has been shown in varicose veins together with an increased expression of TGF-β1 and the presence of macrophages [17]. It is therefore interesting to note that the association of peripheral varicose veins with CAE and varicocele has been documented recently [18]. Inhibition of NO has been shown to limit aneurysmal dilatation of the aorta [15]. Therefore it is reasonable to speculate that dilatation of vascular wall may be triggered by NO mediating mechanism through autonomic nervous system. Autonomic regulation of cardiovascular system in anxiety and depression has been modulated by activation of the sympathetic nervous system, withdrawal of vagal tone to the heart, leading to elevations in heart rate, reductions in heart rate variability, and altered baroreceptor reflex function [19,20]. Activation of neuroendocrine systems manifested in both generalized and specific HPA (hypothalamic-pituitaryadrenal) axis dysfunction and RAAS (renin angiotensin aldosterone system) activation may induce autonomic nervous system changes that are common to both depression and cardiovascular disease. This activation may stimulate increased sympathetic drive and activation of pro-inflammatory cytokines, promoting vascular injury, endothelial dysfunction, catecholamine release and cardiac arrhythmias [21]. Additionally, in a study described by Markovitz et al.; mental stress, hostility, and depressive disorders are accompanied by increased platelet activity [22]. Recently our group has shown that patients with normal coronary arteries and slow coronary flow assessed by TIMI frame count are more anxious and depressive than those with normal coronary artery and normal coronary flow [23]. Moreover, having normal coronary artery has not improved their emotional status score in patients with slow coronary flow. In conclusion patients with coronary artery ectasia are less anxious and less depressive than the coronary obstructive disease patients suggesting a possible role of autonomic nervous system imbalance. Additionally this finding underlines the pathophysiological differences between obstructive coronary artery disease and coronary artery ectasia. We may speculate that possible parasympathetic system activation and subsequent NO release might contribute to dilatation of coronary arteries. We need further studies to explain the relationship between psychological factors and cardiovascular disease in coronary artery ectasia patients.
Patients with CAD (n = 310)
Patients with CAD + CAE (n = 18)
p value
42.7 ± 10.5¶ 39.7 ± 11.4 46.2 ± 7.7 17.8 ± 11.9 10.3 ± 7.9
33.7 ± 10.1* 29.1 ± 9.5 42.7 ± 7.9 11.8 ± 9.1 7.61 ± 6.26
b0.001 b0.001 0.06 0.03 0.14
¶p b 0.001 vs after coronary angiography; *p = 0.013 vs after coronary angiography; BAI: Beck Anxiety Inventory; BDI: Beck Depression Inventory; CAD: coronary artery disease (including nonsignificant atherosclerotic lesions); CAE: coronary artery ectasia; CAG: coronary angiography; STAI: State-Trait Anxiety Inventory.
The authors report no relationships that could be construed as a conflict of interest.
References [1] J.C. Barefoot, M. Schroll, Symptoms of depression, acute myocardial infarction, and total mortality in a community sample, Circulation 93 (1996) 1976–1980. [2] I. Kawachi, D. Sparrow, P.S. Vokonas, et al., Symptoms of anxiety and risk of coronary heart disease. The Normative Aging Study, Circulation 90 (1994) 2225–2259. [3] P.W. Hoen, M.A. Whooley, E.J. Martens, et al., Differential associations between specific depressive symptoms and cardiovascular prognosis in patients with stable coronary heart disease, J. Am. Coll. Cardiol. 56 (2010) 838–844.
S. Ozturk et al. / International Journal of Cardiology 186 (2015) 299–301 [4] J.I. Rosenbloom, G.A. Wellenius, K.J. Mukamal, et al., Self-reported anxiety and the risk of clinical events and atherosclerotic progression among patients with coronary artery bypass grafts (CABG), Am. Heart J. 158 (2009) 867–873. [5] M. Hausberg, U. Hillebrand, K. Kisters, Addressing sympathetic overactivity in major depressive disorder, J. Hypertens. 25 (2007) 2004–2005. [6] P.S. Swaye, L.D. Fisher, P. Litwin, P.A. Vignola, M.P. Judkins, H.G. Kemp, J.G. Mudd, A.J. Gosselin, Aneurysmal coronary artery disease, Circulation 67 (1983) 134–138. [7] J.E. Markis, C.D. Joffe, P.F. Cohn, D.J. Feen, M.V. Herman, R. Gorlin, Clinical significance of coronary arterial ectasia, Am. J. Cardiol. 37 (1976) 217–222. [8] E. Yetkin, J. Waltenberger, Novel insights into an old controversy: is coronary artery ectasia variant of coronary atherosclerosis? Clin. Res. Cardiol. 96 (2007) 331–339. [9] Susanne S. Pedersen, Krista C. van den Broek, Dominic A.M.J. Theuns, Ruud A.M. Erdman, Marco Alings, Albert Meijer, Luc Jordaens, Johan Denollet, Risk of chronic anxiety in implantable defibrillator patients: a multi-center study, Int. J. Cardiol. 147 (2011) 420–423. [10] M. Ulusoy, N.H. Sahin, H. Erkmen, Turkish version of the Beck Anxiety Inventory: psychometric properties, J. Cogn. Psychother. 12 (1998) 163–172. [11] N. Hisli, Validity and accuracy of Beck depression inventory among university students [in Turkish], Psikoloji Derg. 7 (1989) 3–13. [12] E. Yetkin, N. Acıkgoz, Y. Aksoy, E. Barıskaner, N. Sivri, E. Akturk, H. Turhan, F. Kosar, S. Cehreli, Decreased carotid intima-media thickness in patients with coronary artery ectasia compared with patients with coronary artery disease, Coron. Artery Dis. 16 (2005) 495–498. [13] E. Yetkin, N. Acikgoz, N. Sivri, G.O. Tekin, J. Yagmur, Y. Aksoy, H. Turhan, Increased plasma levels of cystatin C and transforming growth factor-beta1 in patients with coronary artery ectasia: can there be a potential interaction between cystatin C and transforming growth factor-beta1, Coron. Artery Dis. 18 (3) (2007) 211–214.
301
[14] J.F. England, Herbicides and coronary artery ectasia, Med. J. Aust. 1 (1981) 140. [15] J.W. Calvert, Cardioprotective effects of nitrite during exercise, Cardiovasc. Res. 89 (2011) 499–506. [16] J.M. Johanning, D.P. Franklin, D.C. Han, et al., Inhibition of inducible nitric oxide synthase limits nitric oxide production and experimental aneurysm expansion, J. Vasc. Surg. 33 (2001) 579–586. [17] T. Jacob, A. Hingorani, E. Ascher, Overexpression of transforming growth factorbeta1 correlates with increased synthesis of nitric oxide synthase in varicose veins, J. Vasc. Surg. 41 (2005) 523–530. [18] E. Yetkin, S. Kilic, N. Acikgoz, H. Ergin, Y. Aksoy, I. Sincer, E. Aktürk, A. Beytur, N. Sivri, H. Turhan, Increased prevalence of varicocele in patients with coronary artery ectasia, Coron. Artery Dis. 16 (5) (2005) 261–264. [19] M. Esler, J. Turbott, R. Schwarz, B. Leonard, A. Bobik, H. Skews, G. Jackman, The peripheral kinetics of norepinephrine in depressive illness, Arch. Gen. Psychiatry 39 (1982) 295–300. [20] T. Rechlin, M. Weis, D. Claus, Heart rate variability in depressed patients and differential effects of paroxetine and amitriptyline on cardiovascular autonomic functions, Pharmacopsychiatry 27 (1994) 124–128. [21] J. Francis, T.G. Beltz, A.K. Johnson, R.B. Felder, Mineralocorticoids act centrally to regulate blood-borne tumor necrosis factor-alpha in normal rats, Am. J. Physiol. Regul. Integr. Comp. Physiol. 285 (2003) R1402–R1409. [22] J.H. Markovitz, K.A. Matthews, Platelets and coronary artery disease: potential psychophysiologic mechanisms, Psychosom. Med. 53 (1991) 643–668. [23] D. Yalvac, S. Ozturk, N. Sivri, Y. Kılıç, E. Bulut, A. Celik, Y. Barlas, I. Tengiz, E. Yetkin, Effects of patients anxiety and depression scores on coronary flow in patients with normal coronary arteries, Int. J. Cardiol. 180C (2014) 55–57.
Contents lists available at ScienceDirect
International Journal of Cardiology journal homepage: www.elsevier.com/locate/ijcard
Letter to the Editor
Anxiety and depression scores in patients with coronary artery disease and coronary artery ectasia S. Ozturk a, H.D. Yalvac b, N. Sivri c, H.M. Ozturk d, Y. Kılıc a, E. Bulut a, A. Celik a, Y. Barlas a, I. Tengiz e, E. Yetkin f,⁎ a
Abant Izzet Baysal University Izzet Baysal Research and Training Hospital, Department of Cardiology, Bolu, Turkey DR Abdurrahman Yurtaslan Oncology Research and Training Hospital, Department of Psychiatry, Ankara, Turkey Trakya University Faculty of Medicine, Department of Cardiology, Edirne Turkey d Abant Izzet Baysal University Izzet Baysal Research and Training Hospital, Department of Psychiatry, Bolu, Turkey e Izmir University Medical Park Hospital, Department of Cardiology, Izmir, Turkey f Middle East Hospital, Department of Cardiology, Mersin, Turkey b c
a r t i c l e
i n f o
Article history: Received 17 March 2015 Accepted 19 March 2015 Available online 20 March 2015 Keywords: Coronary artery disease Coronary artery ectasia Anxiety Depression
The relation of negative emotions such as depression and anxiety with cardiovascular disease has been reported in numerous studies [1, 2]. In patients with stable coronary artery disease (CAD), it has been demonstrated that depression is a strong predictor of cardiovascular events [3]. Also, anxiety symptoms are associated with an increased risk of death or myocardial infarction among patients with CAD [4]. The long term activation of autonomic nervous system may increase the risk of atherosclerosis, cardiac ischemia, blood pressure variability, heart rate variability, myocardial infarction or sudden death [5]. Coronary artery ectasia (CAE) is localized or diffuse dilation of epicardial coronary arteries, 1.5 times the diameter of the adjacent normal coronary segment [6,7]. Although CAE has been supposed to be a variant of atherosclerosis, clinical parameters and pathophysiologic processes show considerable differences compared to those of obstructive coronary artery disease, which is well reviewed by Yetkin and Waltenberger [8]. Recently we have documented increased anxiety and depression scores in patients with slow coronary flow compared to patients with normal coronary arteries and normal coronary flow (unpublished data). Accordingly, we aimed to test whether anxiety and depression status of patients with CAE are different from those of patients with CAD. ⁎ Corresponding author. E-mail address: [email protected] (E. Yetkin).
http://dx.doi.org/10.1016/j.ijcard.2015.03.305 0167-5273/© 2015 Elsevier Ireland Ltd. All rights reserved.
We prospectively included 328 patients who had coronary artery disease. Of whom 310 patients had only CAD and 18 patients had both CAE and CAD. The patients were individually approached by the registered nurses and invited to participate in the study. The nurse briefly explained the study and asked patient to complete the questionnaires. To minimize the environmental factors, the participants were asked to be alone in a silent room unless they asked for help to read or write. All patients were asked to complete the questionnaires including State-Trait Anxiety Inventory (STAI), Beck Depression Inventory (BDI) and Beck Anxiety Inventory (BAI) at least 2 h before coronary angiography. The Spielberger State-Trait Anxiety Inventory state and trait scores (STAI-S and STAI-T) were used to characterize anxiety symptoms of the patients. The STAI-S measures the transitional emotional status evoked by a stressful situation, like surgery. The STAI-T score reflects relatively enduring individual differences in anxiety proneness [9]. The 21-item Beck Depression Inventory — Version 2 (BDI-2) is a widely used measure of psychological and physical symptoms of depression in adults. Each item consists of four statements indicating the degree of severity of the symptom. All patients' angiographic results were told immediately after the procedure. At least 1 h later after the patients were informed about their coronary artery lesions, they were asked to recomplete STAI-S. Each set of questionnaires took approximately 15–20 min to complete. All of the patients completed the questionnaire on the day of the coronary angiography. The validity and reliability of the BDI and BAI have been studied in the Turkish Population by Ulusoy and Hisli [10,11]. Coronary angiography was performed with standard Seldinger's technique by femoral approach in all patients. In order to evaluate each coronary artery, at least four views from the left and two views from the right system were taken. Angiographic images were evaluated by two independent researchers. CAE was defined as dilatation of at least one epicardial coronary artery 1.5 times the reference vessel diameter in any of the coronary arteries. CAD was defined as nonsignificant or significant atherosclerotic lesions in any of the coronary arteries. Patients with known systemic diseases, malignancies, psychiatric disorders, acute coronary syndromes and previous coronary angiography or coronary artery bypass grafting were not included in the study. Continuous variables were given as mean ± S.D.; categorical variables were defined as percentage. Comparison of categorical data was
300
S. Ozturk et al. / International Journal of Cardiology 186 (2015) 299–301
Table 1 Clinical characteristics of patients. Variables
Patients with CAD (n = 310)
Patients with CAD + CAE (n = 18)
p value
Age Gender (male/female) Smoking Previous MI Hypertension Hypercholesterolemia Diabetes mellitus Family history Age
62 ± 10 207/103 139 (%45) 105 (%34) 195 (%63) 111 (%36) 114 (%37) 130 (%42)
64 ± 9 11/7 8 (%44) 5 (%27) 8 (%44) 3 (%16) 4 (%22) 7 (%38)
0.18 0.58 0.97 0.54 0.11 0.08 0.20 0.77
CAD: coronary artery disease (including nonsignificant atherosclerotic lesions); CAE: coronary artery ectasia.
made by using Chi-square test. Comparison of continuous variables was made by using unpaired t test between groups and paired or Wilcoxon match test where suitable. Continuous variables and categorical variables were compared by using unpaired t test and Chisquare test respectively. All tests of significance were two-tailed. Statistical significance was defined as p b 0.05. The SPSS statistical software (SPSS for windows 15, Inc., Chicago, IL, USA) was used for all statistical calculations. Three hundred and twenty eight consecutive patients with coronary artery disease, of whom 18 had CAE and CAD and 310 had only coronary artery disease, were included in statistical analysis. There were no statistically significant differences between two groups in terms of clinical characteristics namely; age, gender, smoking, previous myocardial infarction, hypertension, hyperlipidemia and diabetes mellitus (Table 1). In patients with CAD, STAI-S scores before and after coronary angiography were significantly higher than the other group (42.7 ± 10.5, 33.7 ± 10.1, p b 0.001; 39.7 ± 11.4, 29.1 ± 9.5, p b 0.001). Decrease in STAI-S scores before and after coronary angiography in both groups was statistically significant (p b 0.001, p = 0.01). STAI-T scores of patients with CAD and CAE tended to be lower than those of patients with CAD (42.7 ± 7.9, 46.2 ± 7.7, respectively, p = 0.06). In patients with CAD, BAI scores were significantly higher than the patients with CAD and CAE (17.8 ± 11.9, 11.8 ± 9.1, p = 0.03). Although patients with CAD and CAE have lower BDI score compared to patients with CAD, it did not yield statistical significance (7.6 ± 6.2, 10.3 ± 7.9, respectively, p = 0.14) (Table 2). The main finding of our study is that depression and anxiety scores (STAI-S, BAI and STAI-S after coronary angiography) are significantly lower in patients with CAE than those with CAD alone. Secondly STAIS scores of both patients have significantly decreased after completing the angiographic procedure and informing patients about the results. Additionally STAI-T scores of patients with CAE have a tendency to be lower than those with CAD alone. Increasing evidences have supported the hypothesis that CAE is a local manifestation of systemic dilating vascular disease differing from obstructive coronary disease. In a study reported by Yetkin et al., carotid intima media thickness was thinner in CAE patients with stenotic CAD
Conflict of interest
Table 2 Depression and anxiety scores of patients.
STAI-S (before CAG) STAI-S (after CAG) STAI-T BAI BDI
when compared to patients with CAD only and they stated that ectasia was not an atherosclerotic process limited to coronary arteries [12]. It has also shown that extracellular matrix remodeling in CAE might differ from that in atherosclerosis [13]. These results indicate that different mechanisms rather than atherosclerotic process may be responsible for CAE physiopathology. In terms of systemic involvement and dilating process of disease, nitric oxide (NO) plays an important role in the pathophysiology of CAE [8,14,15]. England has reported an increased frequency of CAE in individuals who had been exposed to herbicide sprays. A herbicide containing acetylcholinesterase inhibitor directly stimulates NO production by increasing acetylcholine [16]. Johanning et al. has experimentally shown that NO production plays a major role in inflammation and aneurysm pathogenesis [15]. The overexpression of iNOS has been shown in varicose veins together with an increased expression of TGF-β1 and the presence of macrophages [17]. It is therefore interesting to note that the association of peripheral varicose veins with CAE and varicocele has been documented recently [18]. Inhibition of NO has been shown to limit aneurysmal dilatation of the aorta [15]. Therefore it is reasonable to speculate that dilatation of vascular wall may be triggered by NO mediating mechanism through autonomic nervous system. Autonomic regulation of cardiovascular system in anxiety and depression has been modulated by activation of the sympathetic nervous system, withdrawal of vagal tone to the heart, leading to elevations in heart rate, reductions in heart rate variability, and altered baroreceptor reflex function [19,20]. Activation of neuroendocrine systems manifested in both generalized and specific HPA (hypothalamic-pituitaryadrenal) axis dysfunction and RAAS (renin angiotensin aldosterone system) activation may induce autonomic nervous system changes that are common to both depression and cardiovascular disease. This activation may stimulate increased sympathetic drive and activation of pro-inflammatory cytokines, promoting vascular injury, endothelial dysfunction, catecholamine release and cardiac arrhythmias [21]. Additionally, in a study described by Markovitz et al.; mental stress, hostility, and depressive disorders are accompanied by increased platelet activity [22]. Recently our group has shown that patients with normal coronary arteries and slow coronary flow assessed by TIMI frame count are more anxious and depressive than those with normal coronary artery and normal coronary flow [23]. Moreover, having normal coronary artery has not improved their emotional status score in patients with slow coronary flow. In conclusion patients with coronary artery ectasia are less anxious and less depressive than the coronary obstructive disease patients suggesting a possible role of autonomic nervous system imbalance. Additionally this finding underlines the pathophysiological differences between obstructive coronary artery disease and coronary artery ectasia. We may speculate that possible parasympathetic system activation and subsequent NO release might contribute to dilatation of coronary arteries. We need further studies to explain the relationship between psychological factors and cardiovascular disease in coronary artery ectasia patients.
Patients with CAD (n = 310)
Patients with CAD + CAE (n = 18)
p value
42.7 ± 10.5¶ 39.7 ± 11.4 46.2 ± 7.7 17.8 ± 11.9 10.3 ± 7.9
33.7 ± 10.1* 29.1 ± 9.5 42.7 ± 7.9 11.8 ± 9.1 7.61 ± 6.26
b0.001 b0.001 0.06 0.03 0.14
¶p b 0.001 vs after coronary angiography; *p = 0.013 vs after coronary angiography; BAI: Beck Anxiety Inventory; BDI: Beck Depression Inventory; CAD: coronary artery disease (including nonsignificant atherosclerotic lesions); CAE: coronary artery ectasia; CAG: coronary angiography; STAI: State-Trait Anxiety Inventory.
The authors report no relationships that could be construed as a conflict of interest.
References [1] J.C. Barefoot, M. Schroll, Symptoms of depression, acute myocardial infarction, and total mortality in a community sample, Circulation 93 (1996) 1976–1980. [2] I. Kawachi, D. Sparrow, P.S. Vokonas, et al., Symptoms of anxiety and risk of coronary heart disease. The Normative Aging Study, Circulation 90 (1994) 2225–2259. [3] P.W. Hoen, M.A. Whooley, E.J. Martens, et al., Differential associations between specific depressive symptoms and cardiovascular prognosis in patients with stable coronary heart disease, J. Am. Coll. Cardiol. 56 (2010) 838–844.
S. Ozturk et al. / International Journal of Cardiology 186 (2015) 299–301 [4] J.I. Rosenbloom, G.A. Wellenius, K.J. Mukamal, et al., Self-reported anxiety and the risk of clinical events and atherosclerotic progression among patients with coronary artery bypass grafts (CABG), Am. Heart J. 158 (2009) 867–873. [5] M. Hausberg, U. Hillebrand, K. Kisters, Addressing sympathetic overactivity in major depressive disorder, J. Hypertens. 25 (2007) 2004–2005. [6] P.S. Swaye, L.D. Fisher, P. Litwin, P.A. Vignola, M.P. Judkins, H.G. Kemp, J.G. Mudd, A.J. Gosselin, Aneurysmal coronary artery disease, Circulation 67 (1983) 134–138. [7] J.E. Markis, C.D. Joffe, P.F. Cohn, D.J. Feen, M.V. Herman, R. Gorlin, Clinical significance of coronary arterial ectasia, Am. J. Cardiol. 37 (1976) 217–222. [8] E. Yetkin, J. Waltenberger, Novel insights into an old controversy: is coronary artery ectasia variant of coronary atherosclerosis? Clin. Res. Cardiol. 96 (2007) 331–339. [9] Susanne S. Pedersen, Krista C. van den Broek, Dominic A.M.J. Theuns, Ruud A.M. Erdman, Marco Alings, Albert Meijer, Luc Jordaens, Johan Denollet, Risk of chronic anxiety in implantable defibrillator patients: a multi-center study, Int. J. Cardiol. 147 (2011) 420–423. [10] M. Ulusoy, N.H. Sahin, H. Erkmen, Turkish version of the Beck Anxiety Inventory: psychometric properties, J. Cogn. Psychother. 12 (1998) 163–172. [11] N. Hisli, Validity and accuracy of Beck depression inventory among university students [in Turkish], Psikoloji Derg. 7 (1989) 3–13. [12] E. Yetkin, N. Acıkgoz, Y. Aksoy, E. Barıskaner, N. Sivri, E. Akturk, H. Turhan, F. Kosar, S. Cehreli, Decreased carotid intima-media thickness in patients with coronary artery ectasia compared with patients with coronary artery disease, Coron. Artery Dis. 16 (2005) 495–498. [13] E. Yetkin, N. Acikgoz, N. Sivri, G.O. Tekin, J. Yagmur, Y. Aksoy, H. Turhan, Increased plasma levels of cystatin C and transforming growth factor-beta1 in patients with coronary artery ectasia: can there be a potential interaction between cystatin C and transforming growth factor-beta1, Coron. Artery Dis. 18 (3) (2007) 211–214.
301
[14] J.F. England, Herbicides and coronary artery ectasia, Med. J. Aust. 1 (1981) 140. [15] J.W. Calvert, Cardioprotective effects of nitrite during exercise, Cardiovasc. Res. 89 (2011) 499–506. [16] J.M. Johanning, D.P. Franklin, D.C. Han, et al., Inhibition of inducible nitric oxide synthase limits nitric oxide production and experimental aneurysm expansion, J. Vasc. Surg. 33 (2001) 579–586. [17] T. Jacob, A. Hingorani, E. Ascher, Overexpression of transforming growth factorbeta1 correlates with increased synthesis of nitric oxide synthase in varicose veins, J. Vasc. Surg. 41 (2005) 523–530. [18] E. Yetkin, S. Kilic, N. Acikgoz, H. Ergin, Y. Aksoy, I. Sincer, E. Aktürk, A. Beytur, N. Sivri, H. Turhan, Increased prevalence of varicocele in patients with coronary artery ectasia, Coron. Artery Dis. 16 (5) (2005) 261–264. [19] M. Esler, J. Turbott, R. Schwarz, B. Leonard, A. Bobik, H. Skews, G. Jackman, The peripheral kinetics of norepinephrine in depressive illness, Arch. Gen. Psychiatry 39 (1982) 295–300. [20] T. Rechlin, M. Weis, D. Claus, Heart rate variability in depressed patients and differential effects of paroxetine and amitriptyline on cardiovascular autonomic functions, Pharmacopsychiatry 27 (1994) 124–128. [21] J. Francis, T.G. Beltz, A.K. Johnson, R.B. Felder, Mineralocorticoids act centrally to regulate blood-borne tumor necrosis factor-alpha in normal rats, Am. J. Physiol. Regul. Integr. Comp. Physiol. 285 (2003) R1402–R1409. [22] J.H. Markovitz, K.A. Matthews, Platelets and coronary artery disease: potential psychophysiologic mechanisms, Psychosom. Med. 53 (1991) 643–668. [23] D. Yalvac, S. Ozturk, N. Sivri, Y. Kılıç, E. Bulut, A. Celik, Y. Barlas, I. Tengiz, E. Yetkin, Effects of patients anxiety and depression scores on coronary flow in patients with normal coronary arteries, Int. J. Cardiol. 180C (2014) 55–57.
