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| ORIGINAL ARTICLE |
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| Year : 2014 | Volume
: 34
| Issue : 2 | Page : 114-119 |
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Serum leptin, retinol-binding protein 4, lipid profile, and carotid intima - media thickness in psoriasis
Ghada A Al-Aziz1, Nagla A Ahmed1, Amal A El Aleim2, Eman G Alsaadawy3, Basma El-sayed Risha1
1 Department of Dermatology and Venereology, Faculty of Medicine for Girls, Al-Azhar University, Cairo, Egypt
2 Department of Clinical Pathology, Faculty of Medicine for Girls, Al-Azhar University, Cairo, Egypt
3 Department of Radiology, Faculty of Medicine for Girls, Al-Azhar University, Cairo, Egypt
| Date of Submission | 02-Nov-2014 |
| Date of Acceptance | 02-Dec-2014 |
| Date of Web Publication | 29-Jan-2015 |
Correspondence Address:
Nagla A Ahmed
MD, Dermatology and Venereology Department, Faculty of Medicine for Girls, Al-Azhar University
Egypt
 Source of Support: None, Conflict of Interest: None  | Check |
DOI: 10.4103/1110-6530.150266
Background
Patients with moderate to severe forms of psoriasis have been found to be at a greater risk of developing comorbidities such as metabolic syndrome and vascular disorders. White adipose tissue is a known source of adipokines and cytokines that can mediate the development of insulin resistance, endothelial dysfunction, and atherosclerosis. The interaction between adipocytokines [such as leptin and retinol-binding protein 4 (RBP4)] and chronic skin and systemic inflammation in psoriasis can be bidirectional. Th1 and Th17 lymphocyte activation in psoriasis is a shared pathway with adipokine activation.
Aim
Evaluation of serum leptin, RBP4, the lipid profile, and carotid - intima media thickness (CIMT) levels in psoriatic patients as indicators of subclinical atherosclerosis.
Patients and methods
This study included 45 patients with psoriasis vulgaris compared with 45 age-matched and sex-matched healthy individuals as a control group.
Results
A highly significant difference was found in the mean leptin (P < 0.001) and the mean RBP4 (P < 0.001) of patients compared with controls. There was a highly significant difference in the mean RT CIMT and in the mean LT CIMT of patients compared with controls.
Conclusion
Psoriatic patients must be advised to assess their lipid profile, serum leptin, and intima - media thickness routinely in order to predict early cardiovascular morbidity and mortality. Keywords: Atherosclerosis, leptin, lipid profile, psoriasis
How to cite this article:
Al-Aziz GA, Ahmed NA, El Aleim AA, Alsaadawy EG, Risha BE. Serum leptin, retinol-binding protein 4, lipid profile, and carotid intima - media thickness in psoriasis. Egypt J Dermatol Venerol 2014;34:114-9 |
How to cite this URL:
Al-Aziz GA, Ahmed NA, El Aleim AA, Alsaadawy EG, Risha BE. Serum leptin, retinol-binding protein 4, lipid profile, and carotid intima - media thickness in psoriasis. Egypt J Dermatol Venerol [serial online] 2014 [cited 2022 Jul 6];34:114-9. Available from: http://www.ejdv.eg.net/text.asp?2014/34/2/114/150266 |
| Introduction | |  |
Psoriasis is a common inflammatory skin disease affecting ~2% of our population. The inflammation process responsible for psoriasis also plays a role in the development of risk factors for atherosclerosis and cardiovascular complications. Patients with psoriasis may carry an excess risk of heart disease, which would represent an important and previously unrecognized cause of morbidity and mortality [1].
Prevention requires early identification of individuals at risk of developing cardiovascular disease (CVD) but who are still clinically asymptomatic, such that intensive preventive measures may be instituted to arrest the progression of disease. Carotid intima-media thickness (CIMT) measurement is a promising tool for detecting atherosclerosis in its preocclusive/subclinical phase [1],[2]. Increased adiposity is associated with increased levels of circulating cytokines, including leptin, which may promote the activation of T cells and monocytes, both driving the Th1 immune response and at the same time impairing the function of regulatory T cells [3].
Retinol-binding protein 4 (RBP4), retinol, the alcohol form of vitamin A, is an essential nutrient for growth, and the development pathophysiological mechanisms may provide a link among obesity, the concomitant inflammatory state, and long-term consequences [4],[5].
| Patients and methods | | |
This study included 45 patients with psoriasis vulgaris diagnosed on the basis of typical clinical features. Forty-five age-matched and sex-matched healthy individuals, with nearly similar life style and dietary habits were also included, representing the control group. All patients were collected from the Outpatient Clinic of Dermatology and Venereology Department of Al-Zahraa University Hospital during the period from November 2012 to February 2013. An informed written consent was obtained from the participants or their guardians before their participation in this study. Approval was obtained from the research ethics committee of the Faculty of Medicine for Girls, Al-Azhar University.
Patients
The following demographic data of the patient and the control groups were collected: full medical history, dietary habits, lifestyle, and physical activity.
A history of associated diseases was taken into consideration, such as vitiligo, diabetes mellitus (DM), hypertension, arthritis, CVD, or others.
Exclusion criteria
- Patients with a history of hypertension, hypercholesterolemia, BMI>30, hyperthyroidism, DM, or renal failure, alcoholics, smokers, pregnant women, women on oral contraceptives, and patients with other joint diseases were excluded.
- Patients with a family history of atherosclerosis and CVDs were excluded.
- Patients on previous or current medications likely to affect the outcome of the study were excluded.
- Obese patients were excluded as the leptin level correlates with the BMI, and obesity increases leptin.
Methods
Clinical assessment
- Psoriasis Area Severity Index (PASI) score evaluation (for the patient group only) was carried out (Yune et al., 2003) [6].
- BMI.
Blood sampling: Five milliliters of venous blood was withdrawn from each patient after at least 12 h of fasting. The blood was collected in a plain tube and left at room temperature to clot. The serum was separated by centrifugation for 10 min at 300 rpm. The serum was divided into three portions, and placed in Eppendorf tubes. One was used fresh for lipid profile determination .Two Eppendorf tubes were stored at −20°C until the time of assay for the estimation of RBP4 and leptin.
The lipid profile was determined by Cobas C311 using Roche reagent kits.
The expected values:
- Total cholesterol: normal 0-200 mg/dl;
- serum triglyceride (TG): normal 50-200 mg/dl;
- high-density lipoprotein-cholesterol (HDL-C): normal up to 45 mg/dl;
- low-density lipoprotein-cholesterol (LDL): normal up to 120 mg/dl.
Principle of leptin estimation : Serum leptin was estimated by enzyme-linked immunosorbent assay kits for quantitative determination of leptin in the human serum.
Principle of RBP4 estimation: This assay uses a quantitative sandwich enzyme immunoassay that measures RBP4 in 4 h. A polyclonal antibody specific for RBP4 was precoated onto a microplate. The RBP4 in standards and samples was sandwiched by the immobilized antibody and the biotinylated polyclonal antibody specific for RBP4.
Carotid intima-media thickness estimation
Patients and controls were examined while in the supine position, with the neck extended and turned slightly to the contralateral side. CIMT was measured using a high-resolution B-mode ultrasound machine (Esaote my lab 50).
It was adjusted to visualize the lumen-intimal and the medial-adventitial interfaces defining CIMT in the far wall. Intima media thickness (IMT) was measured offline in the distal common carotid artery (the arterial segment 1 cm proximal and distal to the carotid bulb).
Assessment of carotid atherosclerosis
- Direct visualization and measurement.
- Velocity criteria.
Statistical analysis
Data were analyzed using the Statistical Package for the Social Sciences (SPSS) 0.17 program: qualitative data were expressed in the form of number and percentages, and quantitative data were presented in the form of mean ± SD. The χ2 -test and the t-test were used for comparison between the studied groups. The level of significance was taken at P value of 0.05 or less, that is, P value of 0.05 or less was considered significant. The correlation coefficient test (r test) was used to rank variables against each other either positively or inversely.
Pearson's correlation coefficient when applied to a sample is commonly represented by the letter r.
| Results | | |
A total of 90 participants were enrolled in this study: 45 with psoriasis and 45 controls. The patient group in our study consisted of 15 (33.33%) women and 30 (66.67%) men, and their age ranged from 12 to 75 years (mean ± SD = 36.04 ± 16.44); the control group in our study consisted of 18 (40%) women and 27 (60%) men, and their age ranged from 17 to 53 years (mean ± SD = 33.42 ± 10.29). No statistically significant differences were found among patients and controls regarding their age and sex. Four (8.89%) patients had a positive family history of psoriasis.
There was a statistically significant difference (P < 0.05) between male and female patients with regard to the PASI score [Table 1].
The BMI of the patient group ranged from 21.4 to 29.7 kg/m 2 , with a mean level of 26.52+2.04, whereas the BMI of the control group ranged from 23.4 to 28.5 kg/m 2 , with a mean level of 26.13+2.38. There were no statistically significant differences between patients and controls.
There was a statistically highly significant difference between the patient and the control groups regarding the serum cholesterol level and the serum LDL level.
There was no statistically significant difference between patients and controls regarding the serum TG level and the serum HDL level [Table 2]. | Table 1: Comparison between male and female patients regarding the PASI score
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There was a highly significant difference (P < 0.001) in the mean leptin and the mean RBP4 of patients compared with controls [Table 3]. | Table 2: Comparison between serum cholesterol, TG, HDL, and LDL levels of patients and controls
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There was a highly significant difference (P < 0.001) in the mean RT CIMT and in the mean LT CIMT of patients compared with controls [Table 4], but there was no statistically significant difference between male and female patients. | Table 3: Comparison between patients and controls as regard mean leptin and retinol binding protein 4 (RBP4) levels
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There were no significant correlations found between leptin, RBP4, and the following parameters: age, the duration of disease, the PASI score, BMI, CHOL, TG, HDL, LDL, RT CIMT, and LT CIMT in the patient group; however, we found a significant correlation between leptin and RBP4. Regarding the correlation of the PASI score with age, the duration of disease, BMI, CHOL, TG, HDL, LDL, RT CIMT, and LT CIMT, there was a statistically highly significant positive correlation with the duration of disease, RT CIMT, and TG, and a significant positive correlation with regard to age and cholesterol, whereas there was a highly significant negative correlation with regard to HDL [Table 5]. | Table 4: Comparison between patients and controls as regard right carotid intima media thickness (RT CIMT) and left carotid intima media thickness (LT CIMT)
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| Discussion | | |
Systemic inflammation plays an important role in the pathogenesis of atherosclerosis in patients with psoriasis [7]. Serum lipids are strong predictors of cardiovascular risk. Clinical cardiovascular morbidity increased in patients with psoriasis in general, and psoriatic arthritis in particular was explained in part by the presence of a pathogenic lipid profile and increased lipoprotein A in psoriatic patients [8]. Leptin hormone, which helps control food intake, body weight, and fat stores, also plays a role in immune and inflammatory processes [9]. RBP4 plays an inflammatory role by inducing the expression and the secretion of proinflammatory cytokines in primary human macrophages [10].
Patients with psoriasis may carry an excess risk of heart disease, which would represent an important and previously unrecognized cause of morbidity and mortality [1]. CIMT has been used as a surrogate marker for the measurement of early atherosclerotic changes, with the capability of determining the anatomic extent and the progression of atherosclerosis. The absolute value and the progression in the thickness of CIMT have been shown to predict the risk for coronary events [11].
This was a case - control study in which serum leptin, RBP4, lipid profile levels, and the CIMT were estimated in 45 patients with psoriasis and 45 age-matched and sex-matched controls as indicators of subclinical atherosclerosis.
Thus, we excluded patients known to be preatherosclerotic to investigate whether psoriasis as a monofactor can be risky for atherosclerosis.
Exclusion criteria included patients with hypertension, DM, hypercholesterolemia, BMI greater than 30, and those on previous or current medications likely to affect the outcome of the study.
Findings of the present study with regard to the BMI showed that the mean values of BMI were elevated in our patients, with no statistically significant difference between the control and the patient groups and no correlation with the PASI score.
In accordance with Enany et al. [12] but in contrast to Amira et al. [13] we reported that there was an increasing BMI in psoriatic patients compared with controls, that is, the PASI score and the risk of psoriasis is directly related to the BMI and that patients with obesity are likely to have severe psoriasis [14].
The current study revealed a statistically highly significant difference between patients and controls regarding serum cholesterol and serum LDL, whereas serum levels of TG and HDL were slightly higher in patients than in controls without statistical significance. Also, there was a significant positive correlation of serum cholesterol and TG with the PASI score in our psoriatic patients, thus highlighting the effect of dyslipidemia and the severity of the disease.
These findings are in agreement with those of Enany et al. [12] and Mallbris et al. [15]. Also, Mallbris [16] concluded that lipid abnormalities in psoriasis patients may be genetically determined in contrast to our study. Kim and Lee [17] reported that there was no significant difference in serum cholesterol, HDL, LDL, and TGs between psoriasis patients and controls.
The present study demonstrated that serum leptin was significantly higher in the patient group than in the control group, and the dose did not show a significant correlation with the PASI score.
This was in accordance with the study of Cerman and colleagues [18],[19],[20], Enanay et al. (2012), and Zhu et al. [21] but they added that leptin plays an important role in the pathogenesis of psoriasis as leptin can promote type 1 cytokine synthesis and suppress type 2 cytokine production, suggesting that leptin might serve as a marker of severity in psoriasis and may also be a pathogenetic cofactor contributing to the chronicity of the disease. They also suggested that drugs targeting the proinflammatory effects of leptin may be a new adjuvant therapeutic approach in psoriasis.
In contrast, Aktan et al. [22] found no difference in leptin levels between psoriasis patients and the healthy control group, and there was no correlation with the PASI score.
The current study revealed that the serum level of RBP4 was significantly higher in the patient group than in the control group and showed no correlation with the PASI score. We also found a negative correlation between RBP4 and leptin.
Our findings do not concur with the study of Gerdes et al. [23] who found a significantly lower serum RBP4 level in the patient group. The difference between our study and that of Gerdes et al. [23] may be due to the relatively small number of participants, the older control group compared with the patient group in their study, and the higher lower level of RBP4 detection (7.5 mg/l) in comparison with our study (6 mg/l).
In the present study, CIMT values were highly significantly increased in patients than in controls. We considered an IMT value of more than 1 mm as a positive result; 64% of our patients showed positive results in RT CIMT and 63% in LT CIMT, thus proving that an increased cardiovascular risk manifested as an increased CIMT in psoriatic patients. These findings concur with those of Mazlan et al. [24], Enany et al. [12], who proved that patients with psoriasis have a significantly increased CIMT compared with controls. They considered an IMT value more than 1 mm as a positive result. They found that 62% of their patients showed positive results.
In our study, we found no significant correlation between CIMT and the sex, the BMI, or the duration of the disease. This concurs with Balci et al. [25].
However, CIMT indicates the degree of atherosclerosis caused by chronic inflammation, and it is expected to increase parallel to the duration of the inflammation.
In contrast to our results, Arias-Santiago et al (2009). [26] and Enany et al. [12] demonstrated a significantly increased CIMT in patients with severe psoriasis. They also demonstrated a significant increase in CIMT in male patients compared to female patients.
The current study showed a significant positive correlation of CIMT with the age of the patients and the PASI score.
In accordance with Arias-Santiago et al. [26] and Enany et al. [12] proved that CIMT positively correlated with the patient's age and the severity of psoriasis (PASI).
In our study, we found the CIMT in psoriatic patients to be positively correlated with serum levels of cholesterol, TG, and LDL and negatively correlated with HDL. Our results are consistent with Tam et al. [27], Eder et al. [28], and Enany et al. [12]. The present study found that there was no correlation between CIMT and the serum level of leptin.
In contrast to our results, Enany et al. [12] reported that there was a positive correlation between CIMT and serum leptin, suggesting that leptin may have an unfavorable influence on the development of atherosclerosis. It has been proposed that leptin is able to enhance ADP-induced platelet aggregation and angiogenesis. The presence of leptin receptors has been demonstrated in human atherosclerotic human arteries [29].
Overall, the exact mechanism of the predisposition to CVD in psoriasis has not been explained satisfactorily. Four factors contribute to the CVD risk profile in psoriasis patients. First, systemic and chronic inflammation due to the persistent secretion of tumor necrosis factor-a and other proinflammatory cytokines plays a major role in the excessively high CVD risk [30]. Second, angiogenesis has been one of the fundamental inflammatory responses in the pathogenesis of psoriasis [31]. Thus, it is possible that psoriasis and atherosclerosis share the same pathogenic mechanism that is manifested by angiogenesis [32]. Third, all comorbidities, such as increased smoking, DM, hypertension, metabolic syndrome, and dyslipidemia in patients with psoriasis, could contribute to atherosclerosis [30].
The fourth factor is the atherogenic side effects of systemic therapy in psoriasis [33]. As none of our patients had other comorbidities or had been treated with medications likely to promote atherosclerosis, the mechanisms of psoriasis pathogenesis, namely chronic inflammation and angiogenesis, contribute to atherosclerotic risk in psoriasis. Taken altogether, our study showed an increased atherosclerotic risk in psoriatic patients, particularly those with severe disease, as evidenced by an increased level of leptin and RBP4 compared with healthy controls. Moreover, we found a significant elevation in CIMT, with a positive correlation between CIMT and the PASI score.
Our data emphasize the need for early and proper treatment of the inflammatory process in psoriasis patients and better monitoring of traditional atherosclerotic risk factors to reduce CVD mortality and morbidity.
| Acknowledgements | | |
Conflicts of interest
None declared.
| References | | |
| 1. | Kremers H, McEvoy M, Dann F. Heart disease in psoriasis. J Am Acad Dermatol 2007; 57:347-354.  |
| 2. | G, Bhargava K, Bansal M, Yetkin E, Acikgoz N, Aksoy Y, et al. Carotid intima-media thickness and coronary artery disease: an Indian perspective. Asian Cardiovasc Thorac Ann 2003; 11:217-221. |
| 3. | ández-Riejos P, Najib S, Santos-Alvarez J, Martín-Romero C, Pérez-Pérez A, González-Yanes C, Sánchez-Margalet V. Role of leptin in the activation of immune cells. Mediators Inflamm 2010; 2010:568343. |
| 4. | I, Biebinger R, Lehmann R, L′allemand D, Spinas GA, Zimmermann MB. Serum retinol-binding protein 4 concentration and its ratio to serum retinol are associated with obesity and metabolic syndrome components in children. J Clin Endocrinol Metab 2007; 92:4359-4365. |
| 5. | DB, Utzschneider KM, Hull RL. Intra-abdominal fat is a major determinant of the national cholesterol education program adult treatment panel III criteria for the metabolic syndrome. Diabetes 2004; 53:2087-2094. |
| 6. | Yune YM, Park SY, Oh HS, et al. Objective assessment of involved surface area in patients with psoriasis. Skin Res Technol 2003; 9:339-342. |
| 7. | Spah F. Inflammation in atherosclerosis and psoriasis: common pathogenic mechanisms and the potential for an integrated treatment approach. Br J Dermatol 2008; 159:10-17. |
| 8. | Ludwig RJ, Herzog C, Rostock A, Ochsendorf FR, Zollner TM, Thaci D. Psoriasis: a possible risk factor for development of coronary artery calcification. Br J Dermatol 2007; 156:271-276. |
| 9. | Babaei A, Zarkesh-Esfahani SH, Bahrami E, Ross RJ. Restricted leptin antagonism as a therapeutic approach to treatment of autoimmune diseases. Hormones (Athens) 2011; 10:16-26. |
| 10. | Newcomer ME, Ong DE. Plasma retinol binding protein: structure and function of the prototypic lipocalin. Biochimica et Biophysica Acta 2005; 1482:57-64. |
| 11. | Hodis HN, Mack WJ, LaBree L, Selzer RH, Liu CR, Liu CH. The role of carotid arterial intima-media thickness in predicting clinical coronary events. Ann Intern Med 1998; 128:262-269. |
| 12. | Enany B, Zohary AK, El Elhilaly R, Badr T. Carotid intima-media thickness and serum leptin in psoriasis. Urban Vogel 2012; 37:527-533. |
| 13. | Amira A, Zayed M, NA El Maksoud, HM Ragab. Psoriasis vulgaris severity and body mass index: evaluating the role of leptin, tumor necrosis factor, and interleukin-6. J Egypt Women Dermatol Soc 2011; 9:86-91. |
| 14. | Chen YJ, Wu CY, Shen JL, Chu SY, Chen CK, Chang YT, Chen CM. Psoriasis independently associated with hyperleptinemia contributing to metabolic syndrome. Arch Dermatol 2008; 144:1571-1575. |
| 15. | Mallbris L, Granath F, Hamsten A, Ståhle M. Psoriasis is associated with lipid abnormalities at the onset of skin disease. J Am Acad Dermatol 2006a; 54:614-621. |
| 16. | Mallbris L. Metabolic disorders in patients with psoriasis and psoriatic artharitis. Curr Rhumatol Rip 2006b; 8:355-363. |
| 17. | CR Kim, JH Lee. An observational study on the obesity and metabolic status of psoriasis patients. Ann Dermatol 2013; 25:440-444. |
| 18. | Cerman AA, Bozkurt S, Sav A, Tulunay A, Elbaºi MO, Ergun T. Serum leptin levels, skin leptin and leptin receptor expression in psoriasis. Br J Dermatol 2008; 159: 820-826. |
| 19. | Wang Y, Chen J, Zhao LY, Geng F, Song F. Psoriasis is associated with increased levels of serum leptin. Br J Dermatol 2008; 158:113-115. |
| 20. | Takahashi H, Tsuji H, Takahashi I Takahashi H, Tsuji H, Takahashi I, et al. Plasma adiponectin and leptin levels in Japanese patients with psoriasis. Br J Dermatol 2008; 159:1207-1208. |
| 21. | Zhu KJ, Zhang C, Li M, Zhu CY, Shi G, Fan YM. Leptin levels in patients with psoriasis: a meta-analysis. Br Assoc Dermatol 2013; 38:478-483. |
| 22. | Aktan F, Rota S, Erdogan BS. A role of leptin in psoriasis? Turk J Med Sci 2007; 37135-37138. |
| 23. | Gerdes S, Osadtsch S, Yazdi MR Buhles N , Weichenthal M, Mrowietz U. Leptin, adiponectin, visfatin, and retinol-binding protein-4 mediators of comorbidities in patients with psoriasis. Exp Dermatol 2011; 21:43-47. |
| 24. | Mazlan SA, bin Mohamed Said MS, Hussein H, binti Shamsuddin K, Shah SA, Basri H. A study of intima media thickness and their cardiovascular risk factors in patients with psoriatic arthritis. Acta Medica (Hradec Kralove) 2009; 52:107-116. |
| 25. | Balci DD, Balci A, Karazincir S, Ucar E, Iyigun U, Yalcin F. Increased carotid artery intima-media thickness and impaired endothelial function in psoriasis. J Eur Acad Dermatol Venereol 2009; 23:1-6. |
| 26. | Arias-Santiago S, Gutiérrez-Salmerón MT, Castellote-Caballero L, Naranjo-Sintes R. Elevated aldosterone levels in patients with androgenic alopecia. Br J Dermatol 2009; 161:1196-1198. |
| 27. | Tam LS, Kitas GD, González-Gay MA. Subclinical carotid atherosclerosis in patients with psoriatic arthritis. Arthritis Care Res 2008; 59:1322-1331. |
| 28. | Eder L, Jayakar J, Shanmugarajah S, Thavaneswaran A, Pereira D, Chandran V, et al. Subclinical atherosclerosis in psoriatic arthritis: a case-control study. J Rheumatol 2008; 35:877-882. |
| 29. | Kang SM, Kwon HM, Hong BK. Expression of leptin receptor (Ob-R) in human atherosclerotic lesions: potential role in intimal neovascularization. Yonsei Med J 2000; 41:68-75. |
| 30. | Wakkee M, Thio HB, Prens EP, Sijbrands EJ, Neumann HA. Unfavorable cardiovascular risk profiles in untreated and treated psoriasis patients. Atherosclerosis 2007; 190:1-9. |
| 31. | Leong TT, Fearon U, Veale DJ. Angiogenesis in psoriasis and psoriatic arthritis: clues to disease pathogenesis. Curr Rheumatol Rep 2005; 7:325-329. |
| 32. | Shapiro J, Cohen AD, David M. The association between psoriasis, diabetes mellitus and atherosclerosis in Israel: a case-control study. J Am Acad Dermatol 2007; 56:629-634. |
| 33. | Landewe RB, V Den, Brone BE. Methotrexate effect in patients with rheumatoid arthritis with cardiovascular comorbidity. Lancet 2000; 355:1616-1617. |
[Table 1]
[Table 2], [Table 3], [Table 4], [Table 5]
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