Relationship between two estrogen receptor-alpha gene polymorphisms and angiographic coronary artery disease.

OBJECTIVE: To investigate the association of estrogen receptor-alpha PvuII and BtgI polymorphisms with angiographic presence and severity of coronary artery disease (CAD). METHODS: Our cross-sectional study included 140 patients with >or=50% coronary stenoses (CAD group) and 47 patients with normal angiograms (CAD-free group) (total n=187, age 59.6+/- 13.2 years; 66 women). PvuII and BtgI genotype and allele distributions were determined by standard method of polymerase chain reaction and restriction fragment length polymorphism. The CAD subgroups by the number of diseased vessels were also defined. Variable associations and group differences were analyzed by independent t test, one-way ANOVA, Pearson's Chi-square, Spearman's correlation tests and logistic regression analyses. RESULTS: While there was no association between PvuII polymorphism and angiographic CAD (p=0.384), BtgI polymorphism was more prevalent in CAD-free group (23.4% vs. 10% (CAD group), OR=2.75, 95% CI=1.150 to 6.579, p=0.019). This difference was more pronounced in women (28.6% vs. 4.4%; OR=8.6; 95% CI=1.564 to 47.303; p=0.005) compared to men (p=0.391). Logistic regression analysis confirmed BtgI polymorphism as the most important predictor for a normal coronary angiogram among parameters such as body mass index, diabetes and age (OR 8.13, 95% CI 1.257 to 52.627, p=0.028). However, no significant association between BtgI polymorphism and the number of stenotic arteries was detected. CONCLUSION: ESR1 PvuII polymorphism is not associated with angiographically significant CAD. ESR1 BtgI polymorphism is strongly associated with the presence of normal coronary angiograms in women, which suggests protective effect. Further confirmation of these findings is required.

DNA repair gene XRCC1 and XPD polymorphisms and their association with coronary artery disease risks and micronucleus frequency.

Coronary artery disease (CAD) is a multifactorial process that appears to be caused by the interaction of environmental risk factors with multiple predisposing genes. In this study, we investigated the effects of the XPD Lys751Gln and XRCC1 Arg399Gln polymorphisms on the presence and the severity of CAD. We also investigated the presence of DNA damage in the peripheral lymphocytes of patients with CAD by using the micronucleus (MN) test and the effect of XPD Lys751Gln and XRCC1 Arg399Gln polymorphisms on this damage. The study population consisted of 147 patients with angiographically documented CAD and 48 healthy controls. No association between XPD Lys751Gln or XRCC1 Arg399Gln polymorphisms and the presence or the severity of CAD was observed. On the other hand, a significantly higher frequency of MN was observed in CAD patients compared with controls (5.7 +/- 1.9 vs 5.0 +/- 2.1, respectively, P = 0.018). We found an elevated frequency of MN in CAD patients with the XPD 751Gln allele (Gln/Gln genotype) or the XRCC1 399Gln (Arg/Gln or Gln/Gln genotypes) allele compared with the XPD 751Lys (Lys/Lys genotype) allele or XRCC1 399 Arg (Arg /Arg genotype) allele, respectively. These preliminary results suggest that XPD Lys751Gln and XRCC1 Arg399Gln polymorphisms may not be a significant risk factor for developing CAD. In addition, our results indicate that the MN frequency is associated with presence, but not severity, of CAD and is related to the XRCC1 Arg399Gln and XPD Lys751Gln polymorphisms, suggesting an elevated frequency of MN in CAD patients with the XPD 751Gln or XRCC1 399Gln alleles.

Preliminary study showing the relationship between platelet fibronectin, sialic acid, and ADP-induced aggregation levels in coronary heart disease.

Several studies indicate that thrombosis plays an important role in the pathogenesis of coronary heart disease (CHD). Fibronectin is a multifunctional protein in plasma, other body fluids, and cell surface and plays an important role in platelet functions, including mediation of cell-cell and cell-surface interactions. Sialic acid is a regular constituent of glycoproteins and gangliozides in the outer cell membrane of mammalian cells. Therefore, the sialic acid content of platelets, which are characterized by their ability to aggregate with each other, can be important in leading to thrombus formation. In this study, platelet fibronectin, sialic acid-, and adenosine diphosphate (ADP)-induced platelet aggregation levels were determined in patients with CHD. Platelet sialic acid concentrations were determined by Warren's method. Platelet aggregation tests with ADP in platelet-rich plasma (PRP) were analyzed by use of an aggregometer. Platelet homogenate fibronectin levels were determined by ELISA. Total protein levels were determined by Lowry method. Our results indicate that, in patients with no vessel disease (patients with no obstructed vessel but suffering from chest pain, like angina pectoris) platelet fibronectin levels were significantly lower than the total of the other patients (patients with 1, 2, or 3 obstructed coronary vessels) (p<0.05). Sialic acid levels in patients with no vessel disease were significantly lower than the total of the patient group (p<0.05). There was significant (+) correlation between platelet aggregation, platelet fibronectin, platelet sialic acid, and severity of disease (p<0.05). Our preliminary findings suggest that, especially platelet fibronectin levels potentially represent a pathogenic factor for CHD.

Comparison of platelet fibronectin, ADP-induced platelet aggregation and serum total nitric oxide (NOx) levels in angiographically determined coronary artery disease.

INTRODUCTION: Coronary thrombosis is an important determinant of prognosis in patients with acute coronary syndromes. Fibronectin is also found in platelets within the alpha secretory granules and secreted following platelet stimulation by a variety of agonist. Available data suggest that expression of platelet fibronectin on the cell surface may indicate a role in platelet aggregation and adhesion to fibrin thrombi and connective tissue. Clear evidence has emerged that a concerted action of nitric oxide (NO) generated by either endothelial or platelet NO synthases regulates platelet activation, causing inhibition of adhesion and aggregation. The aim of the present study was determining and correlating the serum total NO (NOx), platelet fibronectin and ADP-induced platelet aggregation levels in coronary artery disease (CAD) patient subgroups. MATERIALS AND METHODS: A total of 43 coronary artery disease patients were included in this study. Peripheral blood samples from patients with coronary artery disease were obtained from the Department of Cardiology. Platelet aggregation tests with adenosine diphosphate (ADP) were analyzed by using aggregometer. Platelet fibronectin concentrations were determined by enzyme-linked immunosorbent assay (ELISA). Serum total nitric oxide (NOx) levels were determined by colorimetric method. RESULTS: In patients with double-vessel disease, platelet fibronectin levels were found to be significantly higher than no-vessel disease (p<0.001), single-vessel disease (p<0.01) and triple-vessel disease (p<0.001). In addition, in patients with single-vessel disease platelet fibronectin levels significantly higher than no-vessel disease (p<0.05). We could not find any significant differences in ADP-induced platelet aggregation and serum NOx values between CAD patient subgroups. There was a positive correlation between platelet fibronectin levels and severity of disease (r=0.315, p<0.05).

Evaluation of fibronectin, vitronectin, and leptin levels in coronary artery disease: impacts on thrombosis and thrombolysis.

In this study, the levels of fibronectin, vitronectin, leptin, tissue plasminogen activator (t-PA), and lipid parameters were investigated in patients with coronary artery disease (CAD) and control group. The average plasma fibronectin levels in CAD patients group were significantly higher compared with the control group (p=0.006). Moreover, in patients with triple-vessel disease, plasma fibronectin levels were found to be significantly higher than those in the control group (p<0.05). Plasma vitronectin levels in patients with CAD were found to be significantly higher than those in the control group (p=0.000). In addition, in patients with double vessel disease plasma vitronectin levels were significantly higher than no vessel disease and control group, triple vessel disease was significantly higher as compared with no vessel disease, single vessel disease, and control group (p<0.05). We could not find any significant differences in t-PA values between CAD patients and control group. On the other hand, the average leptin levels in the group of patients were higher than those in the control group but there were no statistically significant differences found between them (p>0.05) because of high SD values. There was strong (+) correlation between fibronectin, vitronectin, and severity of disease [vitronectin/severity of disease, r = 0.5074 (p = 0.000), fibronectin/severity of disease, r = 0.2971 (p = 0.007)]. In conclusion, we can say that fibronectin and vitronectin have become greatly important in pathogenesis of coronary artery disease. High leptin levels may be contribute to platelet aggregation in patients with coronary artery disease. But, elevated serum levels of leptin cannot be useful diagnostic and monitoring markers in patients with coronary artery disease.

The relationship of TFPI, Lp(a), and oxidized LDL antibody levels in patients with coronary artery disease.

OBJECTIVES: The aim of the present study was to determine and correlate tissue factor pathway inhibitor (TFPI), lipoprotein (a) (Lp(a)), oxidized low-density lipoprotein (LDL) antibody (oLAB), and thiobarbituric acid reactive substances (TBARS; as a marker of lipid peroxidation) levels in patients with coronary artery disease (CAD) and in a control group. DESIGN AND METHODS: Peripheral blood samples from patients with coronary heart disease were provided by the Department of Cardiology. Serum oLAB, Lp(a), plasma total TFPI, and plasma-free TFPI levels were determined by ELISA. Serum TBARS levels were determined by a spectrophotometric method using thiobarbituric acid. RESULTS: The CAD and the control group were matched for age and sex. Serum Lp(a), oLAB, and plasma total TFPI levels in patients with coronary heart disease were found to be significantly higher than in the control group (P < 0.001). But there was no difference in plasma-free TFPI levels between patients with CAD and the control group (P > 0.05). In patients with single (P < 0.05), double, and triple vessel (P < 0.01) disease, the mean serum Lp(a) levels were significantly higher than in the control group. On the other hand, in patients with single vessel disease (P < 0.05), double vessel disease (P < 0.05), and triple vessel disease (P < 0.001), plasma total TFPI levels were found to be significantly higher than in the control group. We also found a significant positive correlation (r = 0.28, P < 0.05) between serum Lp(a) and plasma total TFPI levels in CAD. In the patient group, TBARS, total cholesterol, triglyceride (TRG), and LDL cholesterol levels were found to be significantly higher than those in the control group. In addition, high-density lipoprotein (HDL) cholesterol levels were found to be significantly lower than the control group. CONCLUSIONS: These results suggest that elevated plasma levels of total TFPI, Lp(a), and oLAB may be useful diagnostic and monitoring markers in patients with CAD.

Guideline implementation in a multicenter study with an estimated 44% relative cardiovascular event risk reduction.

BACKGROUND: The extent of cardiovascular risk reduction by implementing coronary prevention guidelines needs to be documented in various population samples. HYPOTHESIS: This is a multicenter study to assess the impact of risk reduction in cardiovascular events upon implementation of coronary prevention guidelines in patients with or at high risk for coronary heart disease (CHD) in the setting of clinical practice. METHODS: Enrolled volunteers numbered 2,021. Inclusion criteria postulated a minimum of 20-40% cardiovascular event risk in the subsequent 10 years as estimated from the risk table of the European Society of Cardiology (ESC) Guidelines. The estimated CHD risk reduction was assessed in terms of the Framingham risk scores at baseline and at 12 months, computed from the data of each individual. Data of the compliant group (making up half of the initial participants) at the end of the study, along with absolute and relative risk reductions in the compliant group, were analyzed. RESULTS: Mean global risk burden was 25.9% at baseline, reduced through multilateral preventive measures in absolute terms by 9.4% at 6 months and by 11.7% at 12 months; the latter represents a relative risk reduction of 44%. Independent variables determining the (enhanced) reduction in risk level at the end of 12 months included (high) level of baseline risk, (high) degree of compliance with treatment, younger age, female gender, smoking, and (high) baseline triglyceride/high-density lipoprotein cholesterol (TC/HDL-C) ratio. While the relative reduction in patients with CHD amounted to 43%, a reduction of 46% (p<0.001) was obtained in the setting of primary prevention. Diabetes emerged as a factor modestly limiting the extent of risk reduction. While subjects without hypertension revealed a decline of coronary risk by merely 8.7%, those with hypertension showed a decline by 12.7% (p<0.001). Risk reductions were accompanied by a decrease of mean low-density lipoprotein cholesterol (LDL-C) level of 25.4%, a rise in mean HDL-C level of 5 mg/dl, a decrease in mean systolic blood pressure of 26 mmHg. Forty-five percent of smokers succeeded in discontinuing the habit. CONCLUSION: By implementing standard prevention guidelines in the Turkish population among 1,000 compliant high-risk men and women and among 1,000 patients with CHD, prevention of cardiovascular events could be expected in 117 persons in the subsequent 10 years.

Plasma vitronectin levels in patients with coronary atherosclerosis are increased and correlate with extent of disease.

BACKGROUND: Acute thrombosis after atherosclerotic plaques disruption is a major complication of primary atherosclerosis, leading to acute ischemic syndromes and atherosclerotic progression. Vitronectin (VN) is multifunctional glycoprotein in blood and in the extracellular matrix. It binds glycosaminoglycans, collagen, plasminogen and urokinase receptor. VN stabilizes the inhibitory confirmation of plasminogen activation inhibitor-1 (PAI-1). Vitronectin may control the clearance of vascular thrombi by binding and stabilizing PAI-1, a key regulator of fibrinolysis. Therefore, VN is generally regarded as a cofactor for PAI-1 activity. On the other hand vitronectin binds to platelet glycoproteins may mediate platelet adhesion and aggregation at sites of vascular injury. Previous studies showed that anti-VN antibodies inhibit platelet aggregation in vitro, suggesting that vitronectin contributes to platelet accumulation at sites of vascular injury. In this study; we investigated the levels of plasma vitronectin in patients with Coronary Artery Disease (CAD) and control group. METHODS: The patient group was divided into four subgroups: patients with no, single, double and triple vessel disease according to their angiography results. ELISA procedure (Technoclone) was used to determine the plasma vitronectin levels. RESULTS: Plasma vitronectin levels in patient with CAD (% 125.87 +/- 58.38) were found to be significantly higher than control group (% 89.47 +/- 25.3) (p:0.000). In addition, in patients with double vessel disease (% 146.03 +/- 71.69) plasma vitronectin levels were significantly higher than no vessel disease (% 87.84 +/- 22.30) and control group, triple vessel disease (% 160.81 +/- 57.02) significantly higher as compare with no, single vessel disease (% 111.68 +/- 45.34) and control group (p < 0.05). There was no correlation between vitronectin and lipid parameters. CONCLUSION: These findings suggested that vitronectin is a marker of CAD. Elevated levels may indicate its role in the genesis and/or progression of CAD or may be the results of a compensatory mechanism.