JEADV

DOI: 10.1111/jdv.12297

ORIGINAL ARTICLE

Mean platelet volume is associated with aortic arterial stiffness in patients with Behc ß et’s disease without significant cardiovascular involvement I. Balta,1 S. Balta,2,* O.M. Koryurek,3 S. Demirkol,2 T. Celik,2 G. Akbay,3 M. Cakar,4 H. Sarlak,4 M. Eksioglu3 1

Department of Dermatology, Kecioren Training and Research Hospital, Ankara, Turkey Department of Cardiology, Gulhane Medical Academy, Ankara, Turkey 3 Department of Dermatology, Ankara Training and Research Hospital, Ankara, Turkey 4 Department of Internal Medicine, Gulhane Medical Academy, Ankara, Turkey *Correspondence: S. Balta. E-mail: [email protected] 2

Abstract Background Behcß et’s disease (BD), is a chronic, systemic vasculitis, which may affect all types and sizes of blood vessels. BD is associated with endothelial dysfunction and chronic inflammation. Endothelial dysfunction is the critical early step in the process of atherogenesis, and it is commonly investigated by measuring arterial stiffness. Mean platelet volume (MPV) has been investigated in relation with both thrombosis and inflammation. We aimed to investigate the relationship between an increased arterial stiffness and MPV in patients with Behcß et’s disease without significant cardiovascular involvement. Methods We studied 36 patients (20 males, mean age: 37.6  11.7 years) who were diagnosed by the international diagnostic criteria of BD and 35 healthy controls (15 males, mean age: 35.0  10.6 years), and the two groups were matched by age and gender. MPV levels and arterial stiffness measurements were compared in these groups. Results Arterial stiffness was higher in patients with BD compared to control group. (BD and controls; 7.28 m/s, 6.64 m/s; respectively) (p: 0.02). MPV levels were also significantly higher in patients with BD compared to control group. (BD and controls; 8.86  0.81 fl, 8.39  0.96 fl, respectively) (p: 0.02). Additionally, arterial stiffness correlated positively with age, the duration of disease and MPV levels in patients with BD (p: 0.002, 0.03, 0.02 respectively). Conclusions In our study, increased MPV is associated with arterial stiffness in patients with BD without significant cardiovascular involvement. It shows that there is a relationship between thrombosis and chronic inflammation in BD. Furthermore, MPV is also a moderate predictor of cardiovascular disease and represents an increase in platelet activation. These findings provide further evidence of a link between inflammation and thrombosis in patients with BD. Received: 31 July 2013; Accepted: 19 September 2013

Conflicts of interest None declared.

Funding sources None declared.

Introduction Behcßet’s disease (BD) is an inflammatory disorder characterized by recurrent oral and genital ulcers, skin lesions and uveitis. It is now recognized as a multisystem vasculitis that can affect all sizes and types of vessels.1–4 Although genetics, environmental factors, immunological findings and endothelial factors have been implicated, the aetiopathogenesis of the disease is not known.5 Several studies have revealed indirect evidences of endothelial dysfunction in BD, such as increased blood levels of soluble thrombomodulin, E-selectin and vascular endothelial growth factor (VEGF) were elevated in BD patients.6–12 These

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endothelial findings as well as coagulation and fibrinolytic pathway abnormalities may contribute to impaired endothelial function in BD.13 Several studies have shown increased platelet adhesion and aggregation, particularly in response to adenosine diphosphate in patients with BD.14 Platelet activation is a link in the pathophysiology of diseases prone to thrombosis and inflammation.15 Mean platelet volume (MPV), the most commonly used measure of platelet size, is a potential marker of platelet reactivity.16 Recently, MPV has been known as a inflammatory marker in various inflammatory diseases.17–19 MPV levels have also been investigated in BD.

© 2013 European Academy of Dermatology and Venereology

Aortic arterial stiffness and mean platelet volume in Behcß et’s disease

Acıkgoz et al. reported that the increase in MPV is independent of the disease activity, and the presence of thrombosis is associated with higher MPV in BD patients.20 Behcßet’s disease and atherosclerosis are both characterized by endothelial dysfunction. Endothelial dysfunction is commonly investigated by measuring arterial stiffness.21 Intima-media thickness of carotid artery (CIMT) is another marker of early atherosclerotic vessel wall changes.22 Previous studies have shown that CIMT and arterial stiffness were significantly increased in BD patients.23–25 Not only arterial stiffness and CIMT, but also elevated plasma levels of several markers of the systemic inflammation have been shown to predict future risk of atherosclerosis.26,27 So far, the relationship between an increased arterial stiffness and the markers of systemic inflammation, such as C-reactive protein (CRP) and MPV in patients with BD had not been investigated. Therefore, we aimed to investigate the relationship between an increased arterial stiffness and MPV (a marker of systemic inflammation) in patients with BD without cardiovascular involvement and known cardiovascular risk factors.

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after 20 min of supine rest, following fasting for 12 h. Total plasma cholesterol, triglyceride and HDL-C were measured by an enzymatic colorimetric method using an Olympus AU 600 autoanalyser and reagents from Olympus Diagnostics GmbH (Hamburg, Germany). LDL-C levels were calculated by the Friedewald formula. Blood glucose was measured by the glucose oxidase method. The blood was collected in tripotassium EDTA (7.2 mg) tubes. Haematological parameters, including haemoglobin (Hb), WBC count, platelet count, and MPV, were analysed by LH 780 analyser (Beckman Coulter Inc, Miami, Florida). We analysed the blood samples of all of the groups using an automatic blood counter within 1 h after venipuncture because delay in the measurement may change MPV values.30 Normal MPV value in our laboratory ranges between 6.9 and 10.8 fl. Measurement of Arterial Stiffness

Materials and methods

Arterial stiffness was measured non-invasively. TensioMed measurement of arterial stiffness (TensoMed Ltd. BudapestHungary) device was used. Systolic and diastolic pressures, pulse wave velocity (PWV), augmentation index (AIX) and central aortic pressure (CAP) measurements were recorded.

Patients selection

PWV, AIX and CAP Analysis

We studied 36 patients (20 males, mean age: 37.6  11.7 years) who were diagnosed by the international diagnostic criteria of BD28 and 35 healthy controls (15 males, mean age: 35.0  10.6 years), and the two groups were matched by age and gender, prospectively. Diabetes mellitus, hypertension, renal failure, a history of cardiovascular or cerebrovascular disease, inflammatory diseases, cigarette smoking, active infectious diseases were exclusion criteria. Subjects who were receiving lipidlowering therapy, antihypertensive or anti-aggregant drugs, nitrates or long-term systemic steroids were also excluded. The study approved by the local ethics committee. During physical examination, the presence of one or more of the following Behcet’s clinical features was considered as active disease: oral ulceration, genital ulceration, skin lesions, ocular lesions, active major vessel disease and active major organ involvement including active gastrointestinal or neurological lesions. Scoring for classification into active disease category was carried out according to clinical activity index proposed by ‘the Behcet’s Disease (BD) Research Committee of Japan’ in 2003.29 Body height and weight, blood pressure and body mass index (BMI) were measured.

TensioMed brand arteriography device automatically calculated the measurements. Measurements were made after 5 min rest of the patients, non-smoking or taking caffeinated beverages for at least the last 30 min, in a reserved quiet room, in the sitting position and away from external stimuli. Of the patients, the distance between the jugular notch and the symphysis pubis were measured and the data were recorded on the device. During the measurement period, brachial artery occlusion was made (only 8–20 s) and the blood flow was ceased as a part of the process. Then, the systolic pressure, diastolic pressure, mean arterial blood pressure, pulse rate, pulse pressure, PWV, AIX and CAP were derived from the device. The pressure waves were recorded along with the AIX, PWV and CAP values.

Biochemical measurements

Serum glucose, urea, creatinine, triglycerides, total cholesterol, high-density lipoprotein cholesterol (HDL-C) and low-density lipoprotein cholesterol (LDL-C) levels and CRP were measured in all subjects after obtaining a fasting venous blood sample. Blood samples were drawn without stasis at 7–8 a.m.

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Statistical analysis

For statistical analysis, SPSS (Statistical Package for the Social Sciences ver. 15.0, SPSS Inc, Chicago, IL, USA) computer program was used. Quantitative variables were expressed as mean  SD. In comparison of the groups, Student’s t-test was used. Categorical variables were compared by chi-squared test. Pearson and Spearman correlation analysis was used to evaluate the relationship between variables. P < 0.05 was considered as statistically significant.

Results The demographic and clinical features of patients with BD are shown Table 1. Table 2 shows the demographic features and laboratory findings for each group. No differences between

© 2013 European Academy of Dermatology and Venereology

Balta et al.

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Table 1 Demographic and clinical features in patients with Behcß et’s Disease BD (n:36) Sex (F/M)

16/20

Mean age

37.66  11.79

Onset age of disease

27.79  9.23 9.87  7.32

Mean duration of disease (years) Active/inactive disease

25/11 (69.7)

Family history

11 (30.6)

Oral ulcerations

36 (100)

Genital ulcerations

29 (80.6)

ENLL

19 (52.8)

PPL

26 (72.2)

Positive pathergy reaction

21 (58.3)

Ocular involvement

21 (58.3)

Articular involvement

11 (30.6)

Neurological involvement

1 (2.8)

Gastrointestinal involvement

1 (2.8)

Pulmonary involvement

0 (0)

Figure 1 Arterial stiffness was higher in patients with Behcet’s disease compared with control group.

ENLL, Erythema nodosum-like lesions; PPL, Papulopustular lesions.

Table 2 The demographic features and laboratory findings in patients with BD and controls BD (n:36) Age Sex (F/M) BMI

37.66  11.79 20/15

Controls (n:35) 35.29  10.60 16/20

25.44  5.05

23.66  3.00

P-value 0.32 0.28 0.08

SBP (mmHg)

129.97  20.19

122.45  16.22

0.09

DBP (mmHg)

76.30  11.52

72.80  8.78

0.15

Glucose(mg/dL)

90.86  12.21

88.11  11.34

0.33

0.85  0.21

0.81  0.20

0.68

Creatinine(mg/dL) AST (U/L)

22.25  8.62

21.14  8.05

0.58

ALT (U/L)

24.30  11.49

23.17  11.45

0.15

Total cholesterol (mg/dL)

168.41  35.01

165.31  35.25

0.71

LDL cholesterol (mg/dL)

101.16  27.79

98.45  29.90

0.69

7.28  1.42

6.64  0.87

0.02*

8.86  0.81

8.39  0.96

0.02*

248.80  48.27

258.65  60.65

0.45

PWV (m/s) MPV (fl) Total platelet count (x109/L)

7.85  2.39

5.95  1.38

Mean platelet volume is associated with aortic arterial stiffness in patients with Behçet's disease without significant cardiovascular involvement.

Behçet's disease (BD), is a chronic, systemic vasculitis, which may affect all types and sizes of blood vessels. BD is associated with endothelial dys...
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