CORRESPONDENCE: RESEARCH CORRESPONDENCE
Impaired Coronary Microvascular Functions in Patients With Behçet Disease
Hakan Gullu, MD*,
Mustafa Caliskan, MD,
Dogan Erdogan, MD,
Sema Yilmaz, MD,
Recep Dursun, MD,
Ozgur Ciftci, MD,
Eftal Yucel, MD and
Haldun Muderrisoglu, MD
* Baskent University, Konya Teaching and Medical Research Center, Cardiology Department, Hoca Cihan Mah, Saray Cad, No 1, Selcuklu, Konya, Turkey (Email: gulluhakan{at}hotmail.com).
To the Editor: Vascular involvement is well known characteristic of Behçet disease (BD), which is a multisystem inflammatory disease (1). Coronary vascular involvement resulting in acute myocardial infarction without coronary atherosclerosis and in an increased prevalence of silent myocardial ischemia has been reported in BD patients with angiographically normal coronary arteries (2,3). We hypothesized that BD, which causes several cardiovascular complications, might cause coronary microvascular dysfunction, therefore impairing coronary flow reserve (CFR).
Subjects with BD were diagnosed according to the International Study Group Criteria (4). Inclusion criteria were having BD without any previous vascular involvement. Exclusion criteria were any identifiable factor that might cause coronary microvascular dysfunction, such as diabetes mellitus, hypertension, hyperlipidemia, smoking, drinking alcohol, using any vasoactive drug, corticosteroids, and/or methotrexate therapy.
Fulfilling the criteria, 33 patients with BD who had had at least 15 lesion-free days were admitted for the study. For the control group, 40 age- and gender-matched healthy subjects were entered from our hospital staff. Written informed consent was obtained from each subject, and the institutional ethics committee approved the study protocol.
Transthoracic Doppler harmonic echocardiographic examination was performed on each subject using an Acuson Sequoia C256 Echocardiography System (Acuson, Mountain View, California) equipped with a high-resolution transducer with second harmonic capability (5V2c). Coronary diastolic peak velocities of the left anterior descending coronary artery were measured at baseline and after dipyridamole infusion (0.84 mg/kg over 6 min). By averaging the three highest Doppler signals for each measurement, CFR was defined as the ratio of hyperemic to baseline diastolic peak velocities (5). One investigator, blinded to the study’s parameters, performed all of the measurements. Images were recorded on VHS videotapes. Two experienced echocardiographers analyzed the recordings.
The analyses were performed using SPSS for Windows version 9.0 (SPSS Inc., Chicago, Illinois). Comparison analyses were made using the Student t test and the Mann-Whitney U test when appropriate. The Pearson correlation test was used to search possible associations. Stepwise linear regression analysis was performed to identify the independent associations of CFR. All p values <0.05 were considered significant.
The two groups were similar regarding age, body mass index, total cholesterol, high-density lipoprotein (HDL) cholesterol, low-density lipoprotein cholesterol, and high-sensitivity C-reactive protein values (Table 1). Mitral E velocity and mitral A velocity were similar between the 2 groups; however, the mitral E/A ratio was lower in BD patients (1.33 ± 0.30 vs. 1.52 ± 0.37; p = 0.030), indicating left ventricular diastolic dysfunction (Table 1). Resting coronary diastolic peak flow velocity values were similar between the 2 groups (24.2 ± 7.5 vs. 23.6 ± 3.6; p = 0.629). Hyperemic coronary diastolic peak flow velocity values tended to differ between the 2 groups, although not statistically significantly (61.2 ± 17.5 vs. 67.4 ± 13.3, p = 0.093). The CFR values were significantly different between the 2 groups (2.55 ± 0.46 vs. 2.87 ± 0.53, p = 0.013) (Table 1). When the BD group was divided into 2 subgroups, the BD patients on colchicine treatment (27 patients) and the BD patients without treatment, the Mann-Whitney U test showed that the CFR values of the 2 groups were similar (2.52 ± 0.42 vs. 2.58 ± 0.51, p = 0.744).
In 3 of the 33 subjects, the CFR value was <2.0, and in 13 of the subjects the CFR value was <2.5. When the subjects were divided into 2 subgroups, the subjects with CFR <2.5 and the subjects with CFR >2.5, HDL cholesterol (39.1 ± 8.0 vs. 44.2 ± 9.8, p = 0.067) was lower in the subjects with CFR <2.5, and disease duration was higher in the subgroup of subjects with CFR <2.5 (74.8 ± 54.9 vs. 58.7 ± 38.5, p = 0.560).
The Pearson correlation analysis showed that in BD patients (33 patients), CFR correlated significantly with BD duration (r = –0.511, p = 0.002), HDL cholesterol level (r = 0.445, p = 0.009), age, and body mass index (r = –0.396, p = 0.022). The mitral E/A ratio correlated significantly with age, systolic blood pressure, diastolic blood pressure, and left ventricular mass index; however, not significantly with BD duration (r = –0.314, p = 0.075) (Table 2).
When CFR was entered as a dependent variable and age, body mass index, BD duration, and HDL cholesterol were entered as independent variables in a stepwise linear regression model, disease duration (ß = –453, p = 0.005) and HDL cholesterol value (ß = 0.335, p = 0.033) were independent predictors of CFR (standard error of the estimate = 0.375, R2 = 0.390, total significance = 0.002).
In this study, we found that CFR is impaired in BD patients. Chambers et al. (6) established endothelial dysfunction by showing impaired brachial artery flow-mediated dilation. Turkolmez et al. (3) have investigated the prevalence of silent myocardial ischemia in BD patients. They have found that an exercise electrocardiogram showed ischemic changes in 8 of 41 BD patients and in 1 of 35 control patients. Silent myocardial ischemia was found in those 8 (19.5%) patients with BD and 1 (2.9%) in a control group with thallium-201 myocardial perfusion scintigraphy. In this study, the mean duration of BD was higher in the patients with silent myocardial ischemia. In our study, confirming the result of Turkolmez et al. (3), we found an association between BD duration and CFR. Additionally, linear regression analysis showed that BD duration and HDL cholesterol value were independent predictors for the CFR values of BD patients. The pathophysiology of silent ischemia in BD patients is unclear. Our finding that BD patients have impaired coronary flow reserve compared with healthy control patients may be an explanation for the silent myocardial ischemia. In their study, Turkolmez et al. (3) performed coronary angiography in patients with silent myocardial ischemia, but they did not find any significant coronary stenosis in patients with BD. Our results implicate that the silent myocardial ischemia suggested by Turkolmez et al. (3) might have been related to an impairment of coronary microvascular function.
In conclusion, our study showed that coronary microvascular function and, therefore, CFR, is impaired in BD patients without a previous vascular manifestation. The independent predictors for CFR in BD patients are disease duration and HDL cholesterol values. Impaired CFR might have been one of the causes of cardiovascular manifestations in BD patients.
In this study, we have excluded subjects with known coronary risk factors and patients with known previous vascular manifestations. Additionally, we did not perform coronary angiography on the subjects; therefore, it cannot be precisely suggested that these subjects are free of coronary atherosclerosis, and the study does not provide information about BD effects on CFR in patients with coronary risk factors.
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1. Koc Y, Gullu I, Akpek G, et al. Vascular involvement in Behçet disease J Rheumatol 1992;19:402-410.[Web of Science][Medline]2. Kosar F, Sahin I, Gullu H, Cehreli S. Acute myocardial infarction with normal coronary arteries in a young man with the Behçet disease Int J Cardiol 2005;99:355-357.[CrossRef][Web of Science][Medline] 3. Turkolmez S, Gokcora N, Alkan M, Gorer MA. Evaluation of myocardial perfusion in patients with Behçet disease Ann Nucl Med 2005;19:201-206.[Web of Science][Medline] 4. International Study Group for Behçet Disease Criteria for diagnosis of Behçet’s disease Lancet 1990;335:1078-1080.[Web of Science][Medline] 5. Korcarz CE, Stein JH. Noninvasive assessment of coronary flow reserve by echocardiographytechnical considerations. J Am Soc Echocardiogr 2004;17:704-707.[CrossRef][Web of Science][Medline] 6. Chambers JC, Haskard DO, Kooner JS. Vascular endothelial function and oxidative stress mechanisms in patients with Behçet syndrome J Am Coll Cardiol 2001;37:517-520.[Abstract/Free Full Text]
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