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      The Evaluation of the Impact of Age, Skin Tags, Metabolic Syndrome, Body Mass Index, and Smoking on Homocysteine, Endothelin-1, High-sensitive C-reactive Protein, and on the Heart


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          Skin tags (STs) are small, pedunculated skin-colored or brown papules that occur around any site where skin folds occur. The literature is short of comprehensive and controlled clinical studies aimed to evaluate the atherogenic risk factors in patients with STs.

          Aim of Work:

          The aim of this study is to evaluate the impact of age, STs, metabolic syndrome (METs), body mass index (BMI), and smoking on homocysteine (Hcy), endothelin-1 (ET-1), high-sensitive C-reactive protein (Hs-CRP), and on cardiovascular diseases.

          Materials and Methods:

          This study included 30 cardiac patients with STs, 30 non-cardiac patients with STs, and 30 healthy controls with neither heart disease nor STs. History of smoking, measurement of height, weight, BMI, waist circumference (WC), blood pressure, STs number, color, acanthosis nigricans, estimation of serum level of fasting glucose, triglycerides (TGs), cholesterol, high-dense lipoproteins (HDL), Hcy, ET-1, Hs-CRP, and the presence of the METs were elicited in the three groups.


          Regarding the Hcy, ET-1, and Hs-CRP, the cardiac-STs group showed the highest levels and the control group showed the least ( P < 0.001). The percents of patients with METs were 56.7% in the cardiac-STs, 40% in the non-cardiac-STs, and 0% in the control group ( P < 0.001). Mean BMI exceeded the limit of obesity in the cardiac-STs group (30.9 ± 3.9) and the non-cardiac-STs group (32.6 ± 6) and was normal in the control group (24.7 ± 2.8). Hyperpigmented STs were present in 66.7% of the cardiac-STs group. Multivariate regression analysis for the independent effectors on Hcy level were the presence of STs ( P < 0.001), METs ( P = 0.001), and BMI ( P = 0.024). Regarding ET-1, the effectors were the presence of STs and METs ( P = 0.032). For Hs-CRP, effectors were the presence of STs ( P < 0.001) and smoking ( P = 0.040). Multivariate logistic regression of the predictors of cardiac disease showed that the independent predictors of the occurrence of cardiac disease were BMI ( P < 0.001), STs ( P = 0.002), and METs ( P = 0.037).


          STs may act as a physical sign of underlying raised cardiac atherogenic factors. This may indicates an ongoing risk on coronary circulation which may indicate further corrective action, hopefully early enough. The association of ST with obesity and METs represents a Bermuda Triangle that act against the heart.

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          Most cited references22

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          Homocysteine level and coronary heart disease incidence: a systematic review and meta-analysis.

          To determine whether an elevated homocysteine level is an independent risk factor for the development of coronary heart disease (CHD) to aid the US Preventive Services Task Force in its evaluation of novel risk factors for incident CHD. Studies of homocysteine and CHD were identified by searching MEDLINE (1966 through March 2006). We obtained additional articles by reviewing reference lists from prior reviews, original studies, editorials, and Web sites and by consulting experts. We included prospective cohort studies that measured homocysteine and Framingham risk factors and the incidence of CHD in the general adult population without known CHD. Each study was quality rated using criteria developed by the US Preventive Services Task Force. We conducted a meta-analysis using a random-effects model to determine summary estimates of the risk of major CHD associated with each 5-micromol/L increase in homocysteine level. The systematic review and meta-analysis were conducted between January 25, 2005, and September 17, 2007. We identified 26 articles of good or fair quality. Most studies found elevations of 20% to 50% in CHD risk for each increase of 5 micromol/L in homocysteine level. Meta-analysis yielded a combined risk ratio for coronary events of 1.18 (95% confidence interval, 1.10-1.26) for each increase of 5 micromol/L in homocysteine level. The association between homocysteine and CHD was similar when analyzed by sex, length of follow-up, outcome, study quality, and study design. Each increase of 5 micromol/L in homocysteine level increases the risk of CHD events by approximately 20%, independently of traditional CHD risk factors.
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            Endothelin in coronary endothelial dysfunction and early atherosclerosis in humans.

            The endothelium modulates vascular tone through release of vasodilating substances, such as endothelium-derived relaxing factors, and vasoconstricting substances, such as endothelin. Endothelin concentrations are elevated in humans with atherosclerosis and in hypercholesterolemic pigs. Furthermore, the endothelium-dependent vasodilator acetylcholine increases endothelin in hypercholesterolemia in association with coronary vasoconstriction. The present study was designed to test the hypotheses that coronary endothelial dysfunction in humans is characterized by enhanced coronary and circulating endothelin and that the vasoconstriction associated with acetylcholine results in further release of coronary endothelin. Coronary and circulating endothelin concentrations were measured at baseline and during intracoronary acetylcholine administration in 20 patients undergoing diagnostic coronary angiography. Patients were divided into two groups on the basis of their response to intracoronary acetylcholine. Group 1 (n = 7) demonstrated a normal vasodilatory response, but group 2 (n = 13) demonstrated coronary vasoconstriction. Baseline coronary and circulating endothelin concentrations (as determined by coronary sinus and femoral artery measurements, respectively) were higher in patients who responded to acetylcholine with coronary vasoconstriction (group 2) than in group 1 patients (coronary sinus, 15.9 +/- 1.0 pg/mL versus 7.1 +/- 1.0 pg/mL; femoral, 14.1 +/- 0.9 pg/mL versus 6.8 +/- 1.0 pg/mL, respectively; P < .01). In response to intracoronary acetylcholine, a further increase in coronary endothelin was observed only in group 2; this increase correlated with changes in coronary artery diameter. This study demonstrates that endothelin immunoreactivity is enhanced in the coronary and systemic circulation in humans with coronary endothelial dysfunction. Moreover, acetylcholine further increased coronary endothelin concentration in patients with coronary endothelial dysfunction and was associated with coronary vasoconstriction. These observations strongly support a role for endothelin as an early participant in and marker for coronary endothelial dysfunction in humans.
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              Mechanisms of ET-1-induced endothelial dysfunction.

              There is now increasing evidence that endothelial dysfunction is an early event in the pathophysiology of cardiovascular diseases and can be corrected with certain therapies such as angiotensin converting enzyme inhibitors angiotensin type I receptor antagonists and stains independently of blood pressure lowering effects. Restoring endothelial function appears to be a crucial target since endothelial dysfunction predicts cardiovascular events in various situations such as coronary artery disease peripheral artery disease, or hypertension and in patients undergoing vascular surgery. Preclinical and clinical data strongly support that endothelin receptor antagonists belong to this restricted class of pharmacological agents able to act on the endothelium, and offer a potential therapeutic approach for numerous diseases associated with endothelial dysfunction. The purpose of this review will be therefore, 1) to propose mechanisms by which ET-1 can cause endothelial dysfunction; 2) to provide an overview of pathological situations associated with endothelial dysfunction related to ET-1; and 3) to assemble evidence on efficacy of endothelin receptor antagonists for improvement of endothelial function.

                Author and article information

                Indian J Dermatol
                Indian J Dermatol
                Indian Journal of Dermatology
                Medknow Publications & Media Pvt Ltd (India )
                Jul-Aug 2013
                : 58
                : 4
                : 326
                [1] From the Department of Dermatology, Cairo University, Cairo, Egypt
                [1 ] Department of Dermatology and Andrology, National Research Center, Giza, Egypt
                [2 ] Department of Biochemistry, National Research Center, Giza, Egypt
                Author notes
                Address for correspondence: Dr. Omar Soliman El Safoury, 1, Ibn Kotaiba, Nasr City, Cairo, Egypt. E-mail: omar_safoury@ 123456hotmail.com
                Copyright: © Indian Journal of Dermatology

                This is an open-access article distributed under the terms of the Creative Commons Attribution-Noncommercial-Share Alike 3.0 Unported, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

                : July 2012
                : September 2012

                blood pressure,cardiac risk factors,cholesterol,endothelin-1,high-sensitive c-reactive protein,high-dense lipoproteins,homocysteine,metabolic syndrome,obesity,skin tags,smoking,triglycerides,waist circumference


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