Meltem Özden

Hemostatic System as a Risk Factor for Cardiovascular Disease in Women with Subclinical Hypothyroidism

Hypothyroidism has been associated with atherosclerosis. The mechanisms of atherosclerosis in patients with thyroid failure remain controversial. Hypofibrinolysis might be a risk factor for thromboembolic disease in subclinical hypothyroidism (SH). We measured fibrinolytic activity in patients with SH before and after levothyroxine (LT(4)) treatment and compared it to those of controls. We prospectively included 35 patients with SH and 30 healthy controls. We treated patients with LT(4) until almost 6 months after the euthyroid state has been achieved. We measured fibrinogen, D-dimer, antithrombin III (ATIII), plasminogen activator inhibitor-1 (PAI-1), tissue plasminogen activator (tPA) activity, and factor VII. Clinical and anthropometric variables were recorded for both groups. We found increased levels of fibrinogen, PAI-1, and factor VII and decreased levels of ATIII activity in patients compared to control (p < 0.001 and p < 0.05). Decrease of tPA was not significant (p > 0.05). At the end of the LT(4) treatment, significant decreases were determined in PAI-1 and factor VII (p < 0.05). In conclusion, our data suggest an important role of hypofibrinolytic and hypercoagulable state on the development of atherosclerosis in patients with SH and beneficial effects of LT(4 )treatment for decreasing the risk of atherosclerosis.

Erythrocyte glutathione peroxidase activity, plasma malondialdehyde and erythrocyte glutathione levels in hemodialysis and CAPD patients

OBJECTIVES Cardiovascular disease is the major cause of mortality in patients receiving hemodialysis (HD) and continuous ambulatory peritoneal dialysis (CAPD) due to chronic renal failure. Increased lipid peroxidation and depletion of antioxidants may contribute to increased risk of atherosclerosis. We have therefore assessed the effect of hemodialysis and CAPD on oxidant and antioxidant status. DESIGN AND METHODS Plasma malondialdehyde (MDA), Glutathione (GSH) levels and glutathione peroxidase (Gpx) activities were determined in 20 healthy persons (control), 20 patients on HD, 16 patients on CAPD. RESULTS MDA was elevated in posthemodialysis and CAPD patients in comparison to prehemodialysis and control groups (posthemodialysis 1.39 +/- 0.38 nmol/mL, CAPD 1.26 +/- 0.27 nmol/mL, prehemodilaysis 0.83 +/- 0.22 nmol/mL, controls 0.72 +/- 0.21 nmol/mL p < 0.0001). With respect to antioxidants, glutathione levels were significantly lower in prehemodialysis, posthemodialysis and CAPD groups than those in control group (prehemodialysis 16.82 +/- 6.73 mg/dL RBC, posthemodialysis 31.43 +/- 11.88 mg/dL RBC, CAPD 40 +/- 12.72 mg/dL RBC, controls 62.26 +/- 24.01 mg/dL RBC, p < 0.0001). While erythrocyte GSH levels were significantly lower in the prehemodialysis patients than those in posthemodialysis and CAPD patients (p < 0.0001), it was significantly lower in posthemodialysis patients than those in CAPD patients (p < 0.05). There were no significant differences with respect to erythrocyte Gpx levels among the groups (p > 0.05). CONCLUSIONS These findings indicate oxidative stress in patients with chronic renal failure which is further exacerbated by hemodialysis and CAPD, as evidenced by increased lipid peroxidation and low antioxidant levels.

Plasma lipid and lipoprotein concentrations in pregnancy induced hypertension.

OBJECTIVES Aim of this study was to evaluate implication of pregnancy induced hypertension on maternal plasma lipid, lipoprotein, apolipoprotein concentrations and lipid peroxidation products by a comparison of normal pregnancy vs. preeclampsia. DESIGN AND METHODS Thirty-four women with preeclampsia and 32 healthy pregnant women (controls) in the third trimester were recruited for this study. RESULTS In the preeclamptic group plasma total triglyceride, low density lipoprotein cholesterol (LDL-C), malondialdehyde (MDA) and apolipoprotein B (apo-B) were significantly increased, while plasma high density lipoprotein cholesterol (HDL-C) was significantly decreased compared to that of control group. There was no significant difference in total cholesterol and apolipoprotein A1 (apo-A1) concentrations. CONCLUSION Our findings suggest that preeclampsia share some metabolic characteristics with coronary artery disease such as dislipidemia and increased lipid peroxidation. However lipoprotein concentrations may be better biochemical markers of dislipidemia in the preeclamptic state than the corresponding apolipoproteins.

Malondialdehyde, glutathione, glutathione peroxidase and homocysteine levels in type 2 diabetic patients with and without microalbuminuria:

Background: High levels of homocysteine and oxidative stress are known to be associated with premature vascular disease in type 2 diabetes mellitus (DM). The aim of this study was to estimate homocysteine levels and oxidant-antioxidant status and to determine the relationship between them in type 2 diabetic patients with and without microalbuminuria. Methods: Fasting blood samples were obtained from 48 diabetic patients (17 with and 31 without microalbuminuria) and 20 healthy subjects. Serum total homocysteine (tHcy), plasma malondialdehyde (MDA) erythrocyte glutathione (GSH) and glutathione peroxidase (GPx) activity were measured in these patients and the results were compared with those of controls who were chosen among healthy subjects. Results: MDA levels were found to be significantly lower and GSH levels and GPx activities were found to be significantly higher in control subjects when compared with patients with and without microalbuminuria (MDA: P<0.0001, P<0.0001; GSH: P<0.0001, P<0.0001; GPx: P<0.0001, P<0.001, respectively). MDA levels were found to be significantly higher in patients with microalbuminuria compared with patients without microalbuminuria (P<0.0001), while similarly GSH levels were found to be significantly lower in patients with microalbuminuria (P<0.0001). Although there were no significant differences with respect to tHcy levels and GPx activities between the microalbuminuric and normoalbuminuric patients (P>0.05), there was a significant difference with respect to tHcy levels between healthy controls and patients with microalbuminuria (P<0.05). The serum levels of tHcy correlated best with plasma MDA and erythrocyte GSH concentrations in all diabetic patients (r=0.549, P<0.0001; r=0.385, P<0.01). Conclusion: Decreased antioxidant levels, increased lipid peroxidation and increased tHcy levels were observed in patients with microalbuminuria. These changes may contribute to vascular disease, which is particularly prevalent in type 2 DM patients with microalbuminuria.

The effects of antioxidants on exercise‐induced lipid peroxidation in patients with COPD

Objective:  The oxidant–antioxidant balance plays an important role in the pathogenesis of COPD. The aim of the present study was to evaluate the effects of exercise, as an oxidative stress factor on the oxidant–antioxidant balance and to investigate whether short‐term antioxidant treatment affects lipid peroxidation products.

Lipid Profile and Lipoprotein (a) as a Risk Factor for Cardiovascular Disease in Women with Subclinical Hypothyroidism

This study evaluated changes of lipids and lipoprotein (a) [Lp (a)] as atherosclerotic risk factors and the effects of levothyroxine (LT4) treatment on these parameters in patient with subclinical hypothyroidism (SH), defined by increased concentrations of thyrotropin (TSH) and normal thyroid hormone concentrations. We prospectively included 35 female patients with SH and 30 healthy controls. Serum lipid measurements and clinical score as well as fT3, fT4, and TSH levels were assessed at baseline. Body mass index (BMI) was also calculated. Women with proven SH received LT4 treatment that continued for 6 months. Twenty‐six of 35 patients completed the study. At the end of treatment period, the same parameters were determined. Total cholesterol was significantly increased in patients with SH when compared with those of controls (p < 0.01), but increase of LDL‐cholesterol (LDL‐C) and Lp (a) were not significant (p > 0.05). In the levothyroxine‐treated group, total cholesterol and LDL‐C were significantly reduced when compared with the baseline values of women with SH (p < 0.05). Zulewski clinical score assessing symptoms and signs of hypothyroidism improved significantly with treatment (p < 0.001). In conclusion, serum lipids as important atherosclerotic risk factors increased before treatment and decreased with treatment. Levothyroxine therapy is effective in SH and improvements in serum lipids suggests that LT4 treatment also decreases the risk of atherosclerotic diseases.

Protective antioxidant effects of carvedilol in a rat model of ischaemia- reperfusion injury

This study investigated the protective effects of carvedilol, a potent antioxidant, in a rat model of tourniquet-induced ischaemia-reperfusion injury of the hind limb. Thirty rats were divided equally into three groups: the control group (group 1) was only anaesthetized, without creating an ischaemia-reperfusion injury; group 2 was submitted to ischaemia (4 h), followed by a 2-h reperfusion period; and group 3 was pre-treated with carvedilol (2 mg/kg per day) for 10 days prior to ischaemia-reperfusion. Ischaemia-reperfusion produced a significant decrease in superoxide dismutase and glutathione peroxidase activities in the liver, lungs, muscle and serum compared with control treatment, and pre-treatment with carvedilol prevented these changes. Ischaemia-reperfusion caused a significant increase in malondialdehyde and nitric oxide (NO) levels in liver, lungs, muscle (except NO) and serum compared with control treatment, and carvedilol prevented these changes. In conclusion, it might be inferred that carvedilol could be used safely to prevent oxidative injury during reperfusion following ischaemia in humans.

Effect of clopidogrel on nitric oxide levels in an ischemia reperfusion model.

Ischemia and reperfusion injury is a pathologic process with serious consequences, arising due to interruption of arterial blood flow. Restored blood flow achieved after the ischemic period causes formation of oxygen radicals by activation of a variety of substances and systems. In this study, we investigated the effect of clopidogrel, an antithrombocyte agent, on tissue nitric oxide (NO) levels in an experimental ischemia reperfusion model. For this purpose, 6 hours of ischemia and 4 hours of subsequent reperfusion were applied to the right lower extremities of the subjects. Clopidogrel therapy was started in one of these groups 10 days before the process (study group). NO levels were measured in all groups in the muscle, lung, and liver tissues, and in plasma. Lung, plasma, and liver NO measurement values had statistically significant differences among the groups. There was no statistically significant difference in the measurements made on the muscle tissue. Clopidogrel, which has previously been reported to be suitable to be used as a preventive agent of ischemia reperfusion damage, has had a reducing effect on the NO levels in tissues in the ischemia reperfusion model created in our present study.