Clinical trial
Evaluation of serum sCD40L and homocysteine levels with subclinical atherosclerosis indicators in patients with psoriasis: a pilot study _ oro glu2, MD, Ali Adilo glu3, MD, Ali M. Ceyhan1, MD, Ijlal Erturan1, MD, Banu Kale K€ Vahide B. Akkaya1, MD, Numan Tamer2, MD, Pınar Y. Basßak1, MD, Selma Korkmaz1, _ MD, Ismail H. Ersoy2, MD, and Osman Kılıncß4, MD
1 Department of Dermatology, Faculty of €leyman Demirel University, Medicine, Su 2 Division of Endocrinology, Department of Internal Medicine, Faculty of Medicine, €leyman Demirel University, Isparta, Su 3 Department of Microbiology, Ankara Training and Research Hospital, Ankara, and 4Department of Microbiology, Faculty €leyman Demirel University, of Medicine, Su Isparta, Turkey
Correspondence Ijlal Erturan, MD Dermatology Department, Faculty of Medicine €leyman Demirel University Su Isparta 32200 Turkey E-mail: [email protected]
Abstract Psoriasis is a chronic inflammatory process associated with an increased risk of cardiovascular risk factors. sCD40L has been suggested to have a possible role in the pathogenesis, of psoriasis and is known to be associated with inflammation, atherogenesis and cardiovascular events. This study investigated cardiovascular risk factors (sCD40L and homocysteine) as well as subclinical atherosclerosis indicators in psoriatic patients and control subjects. The study included 56 consecutive patients with chronic plaque-type psoriasis and 53 age and gender matched healthy controls admitted to a university hospital. Serum sCD40L and homocysteine levels were measured by ELISA. Carotid artery intima-media thickness and brachial artery flow mediated dilatation (FMD) measurements were determined ultrasonographically. Subjects who had a history of cardiovascular diseases and cardiovascular risk factors and receiving any systemic treatment were excluded from the study. Plasma sCD40L levels were significantly higher in psoriasis patients compared with healthy controls (1.33 0.72 vs. 0.98 0.70 ng/ml P = 0.012), whereas plasma homocysteine levels did not differ significantly between the two groups. FMD was significantly reduced in the psoriasis group compared to the controls (3.83 5.03 vs. 8.45 7.27% P = 0.0001). Multiple linear regression analyses indicated a significant association between psoriasis, sCD40L, and FMD. Psoriatic patients had higher sCD40L levels than healthy controls, which may lead to an increase in cardiovascular diseases. sCD40L may be a more reliable and early predictive marker of cardiovascular events in psoriatic patients. New treatment options that will be developed over sCD40L will benefit in prevention of psoriasis and its cardiovascular comorbidities.
Introduction Psoriasis is a chronic inflammatory skin disease that affects 2–3% of the general population worldwide. The characteristic skin lesion is a persistent and indurated erythematous scaly plaque, which reflects infiltration of inflammatory cells. Although psoriasis primarily manifests at the skin, recent studies have shown that psoriasis is not just a skin disease but a systemic inflammatory process that leads to increased risk of cardiovascular events. The pathogenesis of psoriasis includes T-lymphocyte activation by antigen presentation, which results in cytokine release and inflammation.1,2 Because inflammation plays an important role in the pathogenesis of all stages of atherosclerosis, cardiovascular diseases were found to be ª 2014 The International Society of Dermatology
more common in psoriatic patients than in the general population.3–5 The carotid artery intima-media thickness (CIMT) and brachial artery flow-mediated dilatation (FMD) measurements are used to evaluate premature atherosclerosis and can be non-invasively evaluated by using high-resolution B-mode ultrasonography. These methods are also widely used to evaluate early atherosclerosis in chronic inflammatory diseases, such as psoriasis.6,7 After understanding the presence of cardiovascular risk factors in patients with psoriasis, much work has been done on this issue.2,4,8 The CD40 ligand (CD40L) is a new inflammatory transmembrane protein that belongs to the tumor necrosis family. CD40L and its soluble form (sCD40L) are International Journal of Dermatology 2014, 53, 503–509
503
504
Clinical trial
sCD40L in psoriasis
expressed in a variety of cell types, including activated T-cells, and may serve as a link between inflammation and atherosclerosis.9,10 Studies have demonstrated that raised circulating levels of sCD40L have been associated with an increased risk of cardiovascular risk factors11–14 and cardiovascular events.15–17 It was recently suggested that CD40L-triggered signals could be involved in the early stage of psoriatic lesion formation. Thus, the induction of CD40–CD40L interaction was a major pathway for IL-12 production, a key monocyte cytokine for enhancing the T-helper-1 response.18 Hyperhomocysteinemia is another well-known risk factor for cardiovascular diseases. The mechanisms responsible for the association between hyperhomocysteinemia and cardiovascular disease are partially understood. A leading hypothesis is that homocysteine increases oxidative stress and impairs endothelial function, which is a key factor in the pathogenesis of atherosclerosis.19–21 In this investigation, we aimed to determine sCD40L and homocysteine levels as well as subclinical atherosclerosis indicators in patients with psoriasis. In addition, this study was conducted to explore the association between cardiovascular risk factors and subclinical atherosclerosis indicators in psoriatic patients. Materials and methods Chronic plaque-type psoriatic patients and healthy controls older than 18 years were included in this case-control and prospective study. Patients with known atherosclerotic cardiovascular disease and classic cardiovascular risk factors including hypertension, diabetes mellitus, and hyperlipidemia, and also individuals that received any systemic treatment (for psoriasis and/or any systemic disease) for at least three months before the investigation were excluded from the study. Participants who smoked at least one cigarette a day and who had stopped smoking
Evaluation of serum sCD40L and homocysteine levels with subclinical atherosclerosis indicators in patients with psoriasis: a pilot study _ oro glu2, MD, Ali Adilo glu3, MD, Ali M. Ceyhan1, MD, Ijlal Erturan1, MD, Banu Kale K€ Vahide B. Akkaya1, MD, Numan Tamer2, MD, Pınar Y. Basßak1, MD, Selma Korkmaz1, _ MD, Ismail H. Ersoy2, MD, and Osman Kılıncß4, MD
1 Department of Dermatology, Faculty of €leyman Demirel University, Medicine, Su 2 Division of Endocrinology, Department of Internal Medicine, Faculty of Medicine, €leyman Demirel University, Isparta, Su 3 Department of Microbiology, Ankara Training and Research Hospital, Ankara, and 4Department of Microbiology, Faculty €leyman Demirel University, of Medicine, Su Isparta, Turkey
Correspondence Ijlal Erturan, MD Dermatology Department, Faculty of Medicine €leyman Demirel University Su Isparta 32200 Turkey E-mail: [email protected]
Abstract Psoriasis is a chronic inflammatory process associated with an increased risk of cardiovascular risk factors. sCD40L has been suggested to have a possible role in the pathogenesis, of psoriasis and is known to be associated with inflammation, atherogenesis and cardiovascular events. This study investigated cardiovascular risk factors (sCD40L and homocysteine) as well as subclinical atherosclerosis indicators in psoriatic patients and control subjects. The study included 56 consecutive patients with chronic plaque-type psoriasis and 53 age and gender matched healthy controls admitted to a university hospital. Serum sCD40L and homocysteine levels were measured by ELISA. Carotid artery intima-media thickness and brachial artery flow mediated dilatation (FMD) measurements were determined ultrasonographically. Subjects who had a history of cardiovascular diseases and cardiovascular risk factors and receiving any systemic treatment were excluded from the study. Plasma sCD40L levels were significantly higher in psoriasis patients compared with healthy controls (1.33 0.72 vs. 0.98 0.70 ng/ml P = 0.012), whereas plasma homocysteine levels did not differ significantly between the two groups. FMD was significantly reduced in the psoriasis group compared to the controls (3.83 5.03 vs. 8.45 7.27% P = 0.0001). Multiple linear regression analyses indicated a significant association between psoriasis, sCD40L, and FMD. Psoriatic patients had higher sCD40L levels than healthy controls, which may lead to an increase in cardiovascular diseases. sCD40L may be a more reliable and early predictive marker of cardiovascular events in psoriatic patients. New treatment options that will be developed over sCD40L will benefit in prevention of psoriasis and its cardiovascular comorbidities.
Introduction Psoriasis is a chronic inflammatory skin disease that affects 2–3% of the general population worldwide. The characteristic skin lesion is a persistent and indurated erythematous scaly plaque, which reflects infiltration of inflammatory cells. Although psoriasis primarily manifests at the skin, recent studies have shown that psoriasis is not just a skin disease but a systemic inflammatory process that leads to increased risk of cardiovascular events. The pathogenesis of psoriasis includes T-lymphocyte activation by antigen presentation, which results in cytokine release and inflammation.1,2 Because inflammation plays an important role in the pathogenesis of all stages of atherosclerosis, cardiovascular diseases were found to be ª 2014 The International Society of Dermatology
more common in psoriatic patients than in the general population.3–5 The carotid artery intima-media thickness (CIMT) and brachial artery flow-mediated dilatation (FMD) measurements are used to evaluate premature atherosclerosis and can be non-invasively evaluated by using high-resolution B-mode ultrasonography. These methods are also widely used to evaluate early atherosclerosis in chronic inflammatory diseases, such as psoriasis.6,7 After understanding the presence of cardiovascular risk factors in patients with psoriasis, much work has been done on this issue.2,4,8 The CD40 ligand (CD40L) is a new inflammatory transmembrane protein that belongs to the tumor necrosis family. CD40L and its soluble form (sCD40L) are International Journal of Dermatology 2014, 53, 503–509
503
504
Clinical trial
sCD40L in psoriasis
expressed in a variety of cell types, including activated T-cells, and may serve as a link between inflammation and atherosclerosis.9,10 Studies have demonstrated that raised circulating levels of sCD40L have been associated with an increased risk of cardiovascular risk factors11–14 and cardiovascular events.15–17 It was recently suggested that CD40L-triggered signals could be involved in the early stage of psoriatic lesion formation. Thus, the induction of CD40–CD40L interaction was a major pathway for IL-12 production, a key monocyte cytokine for enhancing the T-helper-1 response.18 Hyperhomocysteinemia is another well-known risk factor for cardiovascular diseases. The mechanisms responsible for the association between hyperhomocysteinemia and cardiovascular disease are partially understood. A leading hypothesis is that homocysteine increases oxidative stress and impairs endothelial function, which is a key factor in the pathogenesis of atherosclerosis.19–21 In this investigation, we aimed to determine sCD40L and homocysteine levels as well as subclinical atherosclerosis indicators in patients with psoriasis. In addition, this study was conducted to explore the association between cardiovascular risk factors and subclinical atherosclerosis indicators in psoriatic patients. Materials and methods Chronic plaque-type psoriatic patients and healthy controls older than 18 years were included in this case-control and prospective study. Patients with known atherosclerotic cardiovascular disease and classic cardiovascular risk factors including hypertension, diabetes mellitus, and hyperlipidemia, and also individuals that received any systemic treatment (for psoriasis and/or any systemic disease) for at least three months before the investigation were excluded from the study. Participants who smoked at least one cigarette a day and who had stopped smoking
