Atherosclerosis 237 (2014) 499e503

Contents lists available at ScienceDirect

Atherosclerosis journal homepage: www.elsevier.com/locate/atherosclerosis

Increased subclinical atherosclerosis in patients with chronic plaque psoriasis Kristin Evensen a, d, Ellen Slevolden b, Karolina Skagen a, d, Ole Morten Rønning c, d, Cathrine Brunborg e, Anne-Lene Krogstad b, David Russell a, d, * a

Department of Neurology, Oslo University Hospital, Rikshospitalet, Oslo, Norway Department of Dermatology, Oslo University Hospital, Rikshospitalet, Oslo, Norway Department of Neurology, Akershus University Hospital, Lorenskog, Norway d University of Oslo, Oslo, Norway e Department of Biostatistics, Epidemiology and Health Economics, Oslo University Hospital, Ullevål, Norway b c

a r t i c l e i n f o

a b s t r a c t

Article history: Received 7 July 2014 Received in revised form 10 October 2014 Accepted 13 October 2014 Available online 18 October 2014

Background: Psoriasis is an immune-mediated inflammatory skin condition of unknown aetiology which usually requires life-long treatment. It is regarded a systemic inflammatory disease with a possible increased risk of cardiovascular disease. The aim of this study was to assess carotid intima-media thickness (IMT), plaque prevalence and carotid stenosis as surrogate measures for cardiovascular disease in psoriasis patients and healthy controls. Methods: Sixty-two patients with psoriasis and thirtyone healthy controls were included in the study. All were examined by Colour duplex ultrasound of the carotid arteries to compare carotid IMT values, carotid plaques and carotid stenosis in the two groups. Adjustments were made for traditional cardiovascular risk factors. Results: Patients with psoriasis had increased carotid IMT values compared to the controls: mean ± SD 0.71 ± 0.17 mm vs. 0.59 ± 0.08 mm; p ¼ 0.001. When adjusted for known atherosclerotic risk factors this difference remained significant (p ¼ 0.04). Carotid plaques were also more common (p ¼ 0.03) in patients with psoriasis 13 (21%) compared to controls 1 (3%). There was no difference with regard to the number of carotid stenoses in patients and controls. Conclusion: The results of this study support previous evidence which suggests that psoriasis is associated with an increased risk for atherosclerosis and subsequent cardiovascular disease. © 2014 Elsevier Ireland Ltd. All rights reserved.

Keywords: Psoriasis Atherosclerosis Carotid IMT Carotid plaques Carotid stenosis Carotid ultrasound Co-morbidity

1. Introduction Psoriasis is a common chronic relapsing inflammatory skin disease, affecting between 1 and 3% of the white population in Northern Europe and the USA [1]. There is increasing interest regarding the inflammatory and systemic nature of this disease and the possibility that these patients may have a greater risk of cardiac and cerebrovascular disease [1e3]. The precise mechanism behind this condition still remains largely unknown. Psoriasis mainly affects the skin, but it has well known associations with other autoimmune diseases such as arthritis, Crohns disease and type 2 diabetes [1,3]. Because of the inflammatory nature of psoriasis, it has in several studies been linked to the development of

atherosclerosis which is also considered a chronic inflammatory disease [2,4e7]. Some studies have suggested that these two conditions share common inflammatory pathways [1,2,8,9]. The aim of this study was therefore to characterize a psoriasis population and assess the amount of subclinical atherosclerosis in patients compared to healthy controls. This was carried out using carotid ultrasound to measure intima - media thickness (IMT), plaque formation, and stenosis in the carotid arteries, which is a well -established method for evaluating generalized atherosclerotic arterial disease [10,11]. 2. Material and methods 2.1. Patients and controls

* Corresponding author. Department of Neurology, Oslo University Hospital, Rikshospitalet, Postboks 4950 Nydalen, 0424 Oslo, Norway. E-mail address: [email protected] (D. Russell). http://dx.doi.org/10.1016/j.atherosclerosis.2014.10.008 0021-9150/© 2014 Elsevier Ireland Ltd. All rights reserved.

Sixty-two consecutive patients with psoriasis, aged 18e65 years (mean age 44 ± 10, 48 males/14 females) and thirtyeone healthy controls (mean age 38 ± 10, 18 males/13 females) were included in

500

K. Evensen et al. / Atherosclerosis 237 (2014) 499e503

the study. Inclusion criteria were moderate to severe psoriasis with or without psoriasis arthritis for more than five years. Healthy controls were recruited from the staff of Oslo University Hospital. Patients or controls with previous cardiovascular symptoms, familiar hypercholesterolaemia, malignancies, pregnancy, concomitant inflammatory diseases such as infections or other autoimmune disorders were excluded. The study was approved by the Regional Ethics Committee (REK). 2.2. Clinical examination and cardiovascular risk assessment A clinical examination of patients and controls was carried out by a dermatologist. The patients were classified using the Psoriasis Area and Severity Index (PASI) score. Psoriasis Area and Severity Index (PASI) is a tool to measure the extent and severity of psoriasis [12]. This index is based on the degree of erythema, infiltration and scaling (respectively: 0 ¼ none, 1 ¼ mild, 2 ¼ moderate, 3 ¼ severe, 4 ¼ very severe) and the extent of involvement of the four body skin areas (head, trunk, arms and legs). According to European consensus definitions, plaque psoriasis is graded into mild or moderate to severe disease [13]. Psoriasis is classified as mild if the PASI is less than 10, and moderate to severe if it is 10 or above. Patients with on-going systemic or biological treatment were also defined as having moderate to severe psoriasis. Current and prior systemic therapy for psoriasis was registered. Patients were interviewed regarding duration of psoriasis and selfreported arthritis. Patients and controls were interviewed about co-morbidity (hypertension, diabetes, and hypercholesterolaemia) as well as treatment with anti-hypertensive medication, statins and smoking history. Systolic (SBP) and diastolic blood pressure (DBP) after 5 min rest in a supine position, body mass index (BMI) and hip/ waist ratios were also measured in all patients and healthy controls. 2.3. Laboratory assessments Blood was collected after an overnight fast in patients and controls and analysed for low density lipoprotein (LDL), high density lipoprotein (HDL), total cholesterol, triglycerides, high sensitivity C-reactive protein (CRP), glucose and HBA1C. 2.4. Carotid ultrasound Patients and controls were examined with Colour duplex ultrasound of the carotid arteries by a neurologist with long experience in ultrasonography of the carotid arteries. The examination was carried out in the supine position with the head angled at approximately 45 towards the contralateral side. IMT measurements were synchronized with the QRS- complex on the ECG. Measurements were made in each carotid artery at the peak of the R-wave where the lumen is widest. IMT was defined as the distance between the lumen-intima and media-adventitia borders of the vessel and identified as a double line in a longitudinal image [14]. IMT was measured in the carotid arteries on both sides in 3 segments: 1. In the far wall of the common carotid artery (CCA) 1 cm proximal to the bifurcation over an area of 1 cm and in 3 different projections: lateral, posterior and anterior. 2. In the far wall of the carotid bifurcations (BIF) over an area of 1 cm in the lateral position. 3. In the far wall of the proximal internal carotid arteries (ICA) immediately distal to the bifurcation over an area of 1 cm in the lateral projection.

This gave a total of 10 IMT measurements for each patient. We used the average value of these 10 IMT measurements in each subject for further analyses. Plaque detection was assessed as positive if one or more plaques were found and negative if no plaques were detected. A plaque was defined according to the Mannheim consensus [14] as a focal structure encroaching into the arterial lumen of at least 0.5 mm or 50% of the surrounding IMT value or demonstrates a thickness > 1.5 mm measured from the media-adventitia interface to the intima-lumen interface. The examination with regard to carotid stenosis detection was assessed as positive when the lumen was reduced by  50% and negative if the lumen reduction was 125 cm/s as > 50% stenosis. The carotid ultrasound examinations were completed according to the American Society of Echocardiography (ASE) [16] using General Electric Vivid 7 ultrasound instrumentation with a linear M12L probe (14MHZ) (General Electric, Horten Norway). 2.5. Statistical analyses A de facto power analysis was performed, based on the observed occurrence of the primary endpoint. The mean difference in carotid IMT values between patients and controls was used as a primary endpoint in this estimation. The estimated mean difference in IMT was 0.12 mm with a standard deviation of 0.1 mm in a sample of 62 cases and 31 controls. It was therefore possible, with a type 1 error of 5%, to reject the null hypothesis that the population means of the patient and control groups are equal with a power of 99%. Sample characteristics are presented as means with standard deviation (SD), medians with (25p, 75p) or proportions. Differences in continuous variables between patients and controls were tested with Student t-test for normally distributed data and ManneWhitney U test for data which was not normally distributed. The chi-square test for contingency tables or Fisher exact test was obtained to detect associations between categorical variables and patients vs. controls. Correlation analyses were performed separately for patients and controls using Pearson's correlation coefficient or Spearman's rho when appropriate. To identify possible confounders, we studied all known risk factors for increased carotid IMT. Only variables with significant relationships with both patients and controls and IMT were considered as possible confounders and included in the multivariable regression analysis. Adjustment for multiple confounding factors was carried out using multivariable linear regression analysis with a manual backward elimination procedure. A significance level of 5% was used. All statistical analyses were done using the PASW Statistics software version 18.0 (IBM SPSS Inc., Chicago, IL). 3. Results Sixty-two patients and thirty-one controls took part in the study. Baseline characteristics of the psoriasis patients and controls are shown in Table 1. Patients were six years older than the controls (mean age 44.2 ± 10.1 vs mean age 37.9 ± 10.4, p ¼ 0.007) and a higher percentage were current smokers (35.4% vs 3%, p ¼ 0.0001) or former smokers (29% vs 22.6%, p ¼ 0.0001). The plasma levels of CRP, HbA1c, total cholesterol, triglycerides and LDL were also higher in patients compared to controls. Systolic blood pressure (SBP) was higher in patients than controls (p¼ < 0.01). In the patient group 25.8% reported to have hypertension and none reported hypertension in the control group. Antihypertensive treatment was reported in 11.3% of the patients and none in controls. Statin

K. Evensen et al. / Atherosclerosis 237 (2014) 499e503 Table 1 Characteristics of psoriasis patients and controls.

Variable Age; years, mean (±SD) Male gender; n (%) Smoking status; n (%) Current; n (%) Former; n (%) Never; n (%) CRP (mg/L); median (25 p 75 p) BMI(kg/m2); mean (±SD) Diabetes mellitus; n (%)a Hypertension; n (%)a Disease duration; years, mean (±SD) Psoriasis type I; n (%) Psoriasis type II; n (%) PASI; median (25 p 75 p) Psoriasis arthritis; n (%) Systolic blood pressure (mmHg), mean (±SD) Diastolic blood pressure (mmHg), (mean ± SD) HbA1c; mean (±SD) Total cholesterol (mmol/L); mean (±SD) TG (mmol/L); median (25p-75p) HDL (mmol/L); mean (±SD) LDL (mmol/L); mean (±SD) Anti hypertensiva; n (%) Statin therapy; n (%)

Patients

Healthy controls

n ¼ 62 44.2 (±10.1) 48 (77.4%)

n ¼ 31 37.9 (±10.4) 18 (58.1%)

p-value 0.007 0.055

22 (35.4%) 18 (29%) 22 (35%) 1.6 (0.79e3.1)

1 (3%) 7 (22.6%) 23 (74.2%) 0.66 (0.19e1.19)

0.0001 0.0001 0.0001

Increased subclinical atherosclerosis in patients with chronic plaque psoriasis.

Psoriasis is an immune-mediated inflammatory skin condition of unknown aetiology which usually requires life-long treatment. It is regarded a systemic...
227KB Sizes 1 Downloads 8 Views