Association of Helicobacter pylori infection with coronary heart disease.

The role of Helicobacter pylori (HP) as the main etiological factor in gastritis and peptic ulcer disease is undisputable. Gastric mucosal damage caused by HP involves various bacterial and host-dependent toxic substances that have been recently associated with an increased risk of coronary artery disease (CAD), possibly through the activation acute phase response and of procoagulant hemostatic factors. Recent studies showed a close and strong correlation between plasma increments of some cytokines such as IL-6 or TNFalpha and cardiovascular diseases. HP infection induces platelet activation and aggregation that could be the pathogenic explanation of the association between HP infection and CAD. The aim of this study was to determine the seroprevalence of HP infection and antibodies to CagA, an antigen that is expressed by the most virulent HP strains inducing an enhanced gastric inflammatory response, in patients undergoing routine coronary artery examination. We studied 76 patients with CAD and 81 healthy controls patients without significant change in coronary circulation. Angiograms were read by two independent experienced cardiologists blinded to the results of HP status. The presence of serum IgG antibodies to HP and to CagA and plasma interleukin-8 (IL-8) levels was measured by ELISA. In addition plasma C-reactive protein fibrinogen, total cholesterol and lipids levels were measured in all studied patients. Seropositivity to HP was found in 81.5 % of cases and in 51% of controls and the difference in prevalence was statistically significant, the odds ratio being 4.3 for Hp patients. Antibody to CagA protein was detected in 47.3% of CAD but only in 28% of healthy controls (OR = 2.3 vs OR = 10). C-reactive protein, plasma fibrinogen and total cholesterol were, respectively higher in patients with CAD than in controls. Present data show that there is significant link between CAD and HP infection. The HP infection significantly increases the risk of CAD, especially when both the anti-HP IgG and anti-CagA IgG are considered. Higher prevalence of cytotoxic HP strains might enhance the atherosclerotic process by inducing a persistent, low grade inflammatory response in arterial wall with enhanced synthesis of acute phase reactants.     

Plasma protein thiolation index (PTI) as a biomarker of thiol-specific oxidative stress in haemodialyzed patients

The role of oxidative stress in patients with end stage renal disease (ESRD), which occurs at significantly higher levels than in the general population, is often underestimated in clinical practice. Emerging evidence highlights the strong correlation of oxidative stress with chronic inflammation and cardiovascular disease, which are highly prevalent in most patients on maintenance haemodialysis (HD) and are a major risk factor for mortality in this population. In this study, total plasma thiols and plasma S-thiolated proteins were measured in patients with ESRD, before and after a regular HD session, and compared to age-matched healthy subjects. We found a significant decrease in the level of total plasma thiols and, conversely, a significant increase in the level of S-thiolated proteins in these patients. In most patients, post-HD plasma level of total thiols did not differ from the one in healthy subjects, whereas plasma level of S-thiolated proteins was lower in HD patients than in age-matched healthy controls. This suggests that a single HD session restores plasma thiol redox status and re-establishes the antioxidant capacity of plasma thiols. Additionally, we determined protein thiolation index (PTI), i.e., the molar ratio between the sum of all low molecular mass thiols bound to S-thiolated plasma proteins and protein free cysteinyl residues. Patients with ESRD had a significantly higher PTI compared to age-matched healthy subjects and HD was associated with a decrease in PTI to normal, or lower than normal, levels. Although this study is limited in size, our results suggest that PTI is a useful indicator of thiol-specific oxidative stress in patients with ESRD on maintenance HD. This study also emphasizes that PTI determination is a cheap and simple tool suitable for large-scale clinical studies that could be used for routine screening of thiol-specific oxidative stress.     

ApoE and ApoC-I polymorphisms: association of genotype with cardiovascular disease phenotype in African Americans

Apolipoproteins (apo) E and C-I are components of triglyceride (TG)-rich lipoproteins and impact their metabolism. Functional polymorphisms have been established in apoE but not in apoC-I. We studied the relationship between apoE and apoC-I gene polymorphisms and plasma lipoproteins and coronary artery disease (CAD) in 211 African Americans and 306 Caucasians. In African Americans but not in Caucasians, apoC-I H2-carriers had significantly lower total and LDL cholesterol and apoB levels, and higher glucose, insulin, and HOMA-IR levels compared with H1 homozygotes. Differences across CAD phenotypes were seen for the apoC-I polymorphism. African-American H2-carriers without CAD had significantly lower total cholesterol (P < 0.001), LDL cholesterol (P < 0.001), and apoB (P < 0.001) levels compared with H1 homozygotes, whereas no differences were found across apoC-I genotypes for African Americans with CAD. Among African-American apoC-I H1 homozygotes, subjects with CAD had a profile similar to the metabolic syndrome (i.e., higher triglyceride, glucose, and insulin) compared with subjects without CAD. For African-American H2-carriers, subjects with CAD had a pro-atherogenic lipid pattern (i.e., higher LDL cholesterol and apoB levels), compared with subjects without CAD. ApoC-I genotypes showed an ethnically distinct phenotype relationship with regard to CAD and CAD risk factors.     

CXCL4 Plasma Levels Are Not Associated with the Extent of Coronary Artery Disease or with Coronary Plaque Morphology

Background

CXCL4 is a platelet chemokine released at micromolar concentrations upon platelet activation. CXCL4 has been shown to promote atherogenesis by various mechanisms. However, data on CXCL4 plasma levels in patients with coronary artery disease are largely inconclusive. Computed coronary artery angiography (CCTA) represents an excellent tool to quantify and characterize coronary atherosclerotic plaques. We hypothesized that increased CXCL4 plasma levels may be associated with features of plaque instability resulting in adverse cardiovascular events. Specifically, we sought to determine whether CXCL4 levels are correlated with specific features of coronary artery disease including (1) plaque volume, (2) calcium score, (3) degree of stenosis, or (4) vascular remodeling.

Methods and Results

CXCL4 plasma levels were measured by ELISA in 217 patients undergoing CCTA for suspected CAD (mean age 64.2 ± 9.4 years, 107 (49.3%) male). Mean CXCL4 plasma levels were 12.5 ± 4.6 ng/mL. There was no significant correlation between CXCL4 levels and any clinical or demographic parameters including cardiovascular risk factors. CXCL4 plasma levels did not differ between patient with or without coronary artery disease (CAD: 12.5 ± 4.5 ng/ml, no CAD: 12.5 ± 4.8 ng/ml). Neither univariate nor multivariate analysis showed an association between CXCL4 levels and plaque volume, total calcium score, degree of stenosis, or vascular remodeling. Subgroup analysis of patients with CAD as confirmed by CCTA did not show any association of CXCL4 levels with the extent of CAD.

Conclusions

While CXCL4 may be present and active within the arterial wall, local increase of CXCL4 may not translate into systemically elevated CXCL4 levels. Further studies will have to test whether CXCL4 may still represent a suitable therapeutic target in human atherosclerosis.     

血浆IIA分泌型磷脂酶A2水平与冠脉支架术后再狭窄关系

目的：测定稳定型冠心病患者支架植入术（percutanous coronary intervention,PCI）前血浆IIA分泌型磷脂酶A2（group IIA secretory phospholipase A2,IIA-sPLA2）的水平,以探讨该酶与冠脉支架术后再狭窄的可能关系。方法：稳定型冠心病行PCI患者63例,非冠心病患者39例,健康正常对照组42例,分别取外周静脉血测定血浆IIA-sPLA2酶浓度。PCI患者6个月后复查造影。结果：PCI患者术前该酶浓度显著高于正常对照组（P〈0．05）,支架内再狭窄率34．9％,再狭窄（restenosis,RS）患者支架术前该酶水平与无再狭窄患者该酶水平无统计学差异（P〉0．05）。结论：PCI患者术前血浆IIA-sPLA2酶浓度显著高于正常对照组,但可能与支架术后再狭窄无关。     

Resistin and adiponectin levels in subjects with coronary artery disease and type 2 diabetes

BACKGROUND: Resistin and adiponectin are implicated in insulin resistance and atherosclerosis. The objective of this study was to evaluate the association between plasma resistin levels and the presence of coronary artery disease (CAD) or diabetes compared to the controls. In a cross-sectional study, we measured glucose, fasting lipid panel, resistin, adiponectin, insulin, C-reactive protein (CRP) and TNF-alpha in 57 subjects with CAD, 58 subjects with diabetes compared to 45 normal control subjects. Results: Subjects with CAD compared to the control subjects had increased insulin resistance index (39+/-32 vs. 13.45+/-12.73 with p<0.0001), CRP levels (3.8+/-4.03 vs. 2.0+/-2.0 with p<0.05) and decreased levels of adiponectin (12.5+/-4.8 vs. 17.26+/-10.4 with p<0.0003). Subjects with diabetes compared to the controls had had increased insulin resistance index (69+/-19 vs. 13.45+/-12.73 with p<0.001), CRP levels (4.1+/-4.8 vs. 2.0+/-2.0 with p<0.01) and decreased levels of adiponectin (11.58+/-4.8 vs. 17.26+/-10.4 with p<0.001). Compared to the controls, there was no significant difference in the levels of resistin in subjects with CAD (4.92+/-3.2 vs. 4.1+/-2.4) as well as diabetes (4.92+/-3.2 vs. 4.6+/-2.6). Both CRP and resistin levels correlate with TNF-alpha (r=0.557, p<0.000001; r=0.84, p<0.000001). Conclusions: The present study shows decreased plasma adiponectin levels in subjects with diabetes as well as in subjects with CAD is similar to the literature. Plasma levels of resistin in subjects with CAD or diabetes are similar to the controls. However, there was a strong correlation of resistin levels with inflammatory markers. This suggests resistin as an inflammatory marker associated with CAD.     

Oxidized low density lipoproteins induce apoptosis in PHA-activated peripheral blood mononuclear cells and in the Jurkat T-cell line.

Oxidized low density lipoproteins (oxLDLs) and activated T lymphocytes are present in early atherosclerotic plaques. It has been shown that oxLDLs are cytotoxic to cultured vascular cells but their possible toxic action on T lymphocytes has not been described. Peripheral blood lymphocytes from healthy individuals were stimulated in vitro with the polyclonal activator phytohemagglutinin and treated with various doses of native and mildly oxidized LDLs. Low doses of oxLDLs inhibited cell growth and DNA synthesis after 48 h culture and at 200 microg apoB/ml we observed a loss of cell viability. Dead cells did not exhibit significant increase of alteration of membrane integrity (i.e., necrosis) but showed chromatin fragmentation evaluated by DNA staining with 4', 6-diamidino-2-phenylindole and propidium iodide. This fragmentation increased with TBARS and hydroperoxide levels. The expression of early apoptosis marker Apo2.7 rose among the CD3(+) T-cell population. In addition, morphological analysis showed apoptotic features (cell shrinking, nucleus condensation, and fragmentation). Study of phosphatidylserine expression using Annexin V confirmed that oxLDLs induced apoptosis in activated lymphocytes. In the Jurkat T-cell line cultured with oxLDLs, apoptotic morphological changes (condensation and nucleus fragmentation) were observed and they were accompanied by DNA fragmentation visualized by propidium iodide staining and electrophoresis showing apoptotic ladder.These results demonstrate that mildly oxidized LDLs induce apoptosis in a part of activated and proliferating T cells. T-lymphocyte apoptosis induction in atherosclerotic lesions might contribute to the development of an inappropriate local T cell response.     

Plasma inactive renin in patients with diabetes mellitus: effects of standing and the relation to serum protease inhibitor

In order to investigate the mechanisms of increased plasma inactive renin in diabetics with microvascular complications, changes in active and inactive renin with the progress of diabetes mellitus were studied, and effects of standing on inactive renin release and the relationship between plasma inactive renin and serum trypsin or protease inhibitors wee also studied. Inactive renin increased with the aggravation of diabetes mellitus, but active renin didn't show significant changes with the aggravation of diabetes mellitus. Active renin was significantly increased both in the healthy subjects and in the diabetic patients when they were in an upright position, but no significant change was observed in inactive renin. Serum trypsin in diabetics with retinopathy and nephropathy was lower than that in those with no clinical sign of microangiopathy, but the correlation between plasma inactive renin and serum trypsin was not significant. There was a significant correlation between plasma inactive renin and serum alpha 2-globulin (r = 0.52, p less than 0.01). Although plasma inactive renin was not significantly correlated with serum alpha 1-antitrypsin, there was a significant correlation between plasma inactive renin and serum alpha 2-macroglobulin (r = 0.61, p less than 0.01). These results show that the increased levels of plasma inactive renin observed with the development of diabetic microangiopathy are probably related to the altered plasma protein metabolism observed in patients with diabetes mellitus. However, it is not clear whether this altered protein metabolism is related to the conversion from inactive to active renin.     

Relationships between serum levels of autoantibodies against oxidized low density lipoproteins, lipid-soluble antioxidants and apolipoprotein B in patients with coronary heart disease

High affinity IgG autoantibodies against oxidized low density lipoproteins (oxLDLs), apolipoprotein B and lipid-soluble antioxidants--alpha-tocopherol and beta-carotene, were tested in patients with coronary heart disease. Correlation relationships between these parameters were analysed. Fifty one patients with coronary heart disease (37 males/14 females) defined as Q-wave myocardial infarction and/or stenosis of more than 50%, and 51 healthy blood donors (34 males/17 females) as controls participated in this study. LDLs were isolated by density gradient ultracentrifugation and oxidized with Cu2+. OxLDLs or native LDLs (nLDLs) were used as antigens in enzyme immunoassay (ELISA) to detect IgG autoantibodies in the serum. The contents of alpha-tocopherol and beta-carotene were measured by HPLC. Apolipoprotein B was determined by immunoturbidimetry. Correlation analysis of the parameters was carried out by Spearmann's test. Alpha-tocopherol was decreased significantly in the serum of patients with coronary heart disease (2.96+/-1.63 nmol/mg serum protein vs 6.23+/-2.28 nmol/mg serum protein in Control group) (p < 0.01). Also, the serum level of beta-carotene was decreased in patients with coronary heart disease (174.0+/-95.7 pmol/mg serum protein vs 313.2+/-141.5 pmol/mg serum protein in Control group) (p < 0.01), while apolipoprotein B was increased significantly (1.20+/-0.34 g/l in patients with coronary heart disease vs 0.86+/-0.23 g/l in Control group) (p < 0.001). In a previous study we established that the mean serum level of IgG autoantibodies against oxLDLs (expressed in optical density units) was about 2.5 times higher in patients with coronary heart disease as compared to control subjects (p < 0.001). A good positive linear correlation was observed between alpha-tocopherol and apolipoprotein B levels in Control group (r = 0.78, p < 0.001), as well as in the group of patients with coronary heart disease (r = 0.42, p < 0.001). Poor nonsignificant correlations were established between all another measured parameters. In conclusion, the lipid-soluble antioxidants--alpha-tocopherol and beta-carotene, are not informative with respect to the susceptibility of the serum to oxidative modifications and as to the extent of the subsequent humoral immune response. Presumably, the reduction of the correlation coefficient between apolipoprotein-B and alpha-tocopherol in patients with coronary heart disease in comparison with control subjects could provide indirect information on modifications of apolipoprotein-B and on a decrease of its susceptibility to interact with this major lipid-soluble antioxidant in atherogenesis.     

Transforming growth factor beta1 and prostaglandin E2 concentrations are associated with bone formation markers in ulcerative colitis patients

Osteoporosis is a significant complication of a multifactoral etiology associated with inflammatory bowel disease. The aim of study was to evaluate the relationships between bone mineral density as well as bone turnover markers and inflammatory activity modulators (i.e., PGE2 and TGFbeta1) in ulcerative colitis (UC). Twenty-one active ulcerative colitis subjects and 14 healthy individuals were included into the study. We observed no significant differences in serum concentrations of osteoprotegerin and osteocalcin, as well as bone mineral density between UC patients and healthy individuals. Plasma concentrations of PGE2, TGFbeta1 and TNF-alpha were significantly higher in UC patients than in controls. Serum osteocalcin demonstrated a positive correlation with both serum PGE2 and plasma TGFbeta1. Moreover there was significant correlation between osteoprotegerin and TGFbeta1 as well as serum TNF-alpha concentrations. In conclusion a positive association between PGE2 and TGFbeta1 and bone formation markers-osteoprotegerin and osteocalcin, as well as a comparable BMD in UC patients and healthy individuals was shown. Our results may indicate that increase of PGE2 as well as TGFbeta1 concentrations may play a protective role against bone loss in ulcerative colitis patients.     

Multiparameter analysis of clastogenic factors, pro-oxidant cytokines, and inflammatory markers in HIV-1-infected patients with asymptomatic disease, opportunistic infections, and malignancies.

HIV-1-infected patients are in chronic oxidative stress and clastogenic factors (CFs) are present in their plasma. CFs from patients with HIV are formed via superoxide anion radical and stimulate further superoxide production. The pathophysiolgic significance and the exact composition of the circulating clastogenic material in patients with HIV is unknown. Cytokines, such as tumor necrosis factor-alpha (TNF-alpha), are increased in the plasma of patients with HIV and TNF-alpha shows clastogenic activity in vitro. The aim of this clinical study was to compare levels of CF in HIV-1-positive patients with asymptomatic disease, opportunistic infections, and malignancies with those in HIV-1-negative control groups and to correlate CF activity with CD4+ T cell numbers, the cytokines (TNF-alpha, interleukin-2 [IL-2], IL-6), and the inflammatory markers (C-reactive protein [CRP], neopterin, granulocyte elastase). CFs were significantly increased in all HIV-1-positive patients and in HIV-1-negative patients with malignant tumors. HIV-1-positive patients with Kaposi's sarcoma showed the highest CF activity in their plasma (p < 0.08). CFs appear very early in HIV infection, and they correlate negatively with CD4+ T cells, which are an indicator of disease activity. The presence of CF in the plasma of HIV-infected patients is not a general response to a viral infection because these factors are not increased in HIV-1-negative patients with viral infection (zoster). CFs are not specific for the HIV-1 infection; they also occur in HIV-1-negative patients with malignant tumors. There was a tendency towards a positive correlation (p < 0.14) between CF and TNF-alpha but there was no positive correlation of CF with IL-2, IL-6, CRP, elastase, and neopterin levels. This indicates that TNF-alpha may be among the components of CF in HIV-1-infected patients. In addition, other unidentified components may contribute to the clastogenic activity of the plasma or the composition of CF may vary from patient to patient. Further clinical studies with larger sample populations are necessary to analyze the composition of CF in HIV-1-positive patients.     

Determinants of homocysteine-thiolactonase activity of the paraoxonase-1 (PON1) protein in humans.

Homocysteine (Hcy)-thiolactonase (HTase) activity of the paraoxonase-1 (PON1) protein detoxifies Hcy-thiolactone in human blood and could thus delay the development of atherosclerosis. To gain insight into physiological role(s) of the PON1 protein, we studied HTase activities and PON1 genotypes in a group of 184 subjects, 32.6% of whom were healthy, 27.7% had angiographically proven coronary artery disease but did not have myocardial infarction (CAD), and 39.7% had myocardial infarction (MI). We found that the hydrolytic activities of the serum PON1 protein towards Hcy-thiolactone and the organophosphate paraoxon substrates were strongly correlated. PON1-192-RR and PON1-55-LL genotypes were associated with high HTase activity. HTase activity was negatively correlated with age (beta = -0.135, p =0.002), plasma total Hcy (in 192-QR subjects only; r = -0.46, p = 0.001), and positively correlated with total cholesterol (beta = 0.169, p<0.001), but not with HDL cholesterol. Mean HTase activities were similar in CAD subjects, MI subjects, and in healthy controls. However, the frequency of the PON1-192-RR genotype tended to be lower in CAD subjects than in controls (2% vs 10.0%, p = 0.057) and higher in MI subjects that in CAD subjects (10.9% vs 2.0%, p = 0.001). The R-allele was marginally associated with CAD (26.7% in controls vs 17.6% in CAD, p = 0.146) and significantly associated with MI (17.6% in CAD vs 31.5% in MI, p = 0.018). Multiple regression analysis suggests that PON1 genotype, total Hcy, total cholesterol, and age are major determinants of HTase activity in humans.     

Decreased plasma superoxide scavenging activity in immunological disorders — carboxyethylgermanium sesquioxide (Ge-132) as a promoter of prednisolone

Summary We investigated so-called superoxide scavenging activity (SSA) of plasma in patients with several immunological disorders, such as rheumatoid arthritis (RA), systemic lupus erythematosus (SLE), polymyo-dermatomyositis (PM), progressive systemic sclerosis (PSS), myasthenia gravis (MG) and autoimmune thyroid disease (AT), using the electron paramagnetic resonance/spin trapping technique. Since carboxyethylgermanium sesquioxide, Ge-132, has been reported to modulate both the immune response and leukocyte functions, we have studiedin vivo effect of Ge-132 on plasma SSA and other laboratory parameters in these disorders. The plasma SSA was significantly lower in RA, SLE, PM and PSS, but not in MG and AT, as compared with that in healthy controls. An inverse correlation was observed between plasma SSA and parameters such as erythrocytes sedimentation rates, absolute number of leukocytes, C-reactive protein and serum globulin levels. Furthermore, plasma SSA was significantly decreased in rheumatoid factor-positive patients as compared to negative patients. No correlation was observed between plasma SSA and factors such as ages, sex of patients or the other laboratory parameters, such as serum albumin, triglyceride, cholesterol, hemoglobin and serum iron levels. Patients treated with prednisolone, especially ones with RA, showed an increase of plasma SSA. It appears that Ge-132 promotes prednisolone effects. Our results indicate that a decrease in plasma SSA is not disease specific, but inversely correlates with the severity and activity of inflammation. The methodology to measure plasma SSA presented in this work provides a helpful tool for determining the actual activity of the diseases as well asin vivo studies of antiinflammatory agents.     

C-reactive protein gene polymorphisms affect plasma CRP and homocysteine concentrations in subjects with and without angiographically confirmed coronary artery disease

Human C-reactive protein (CRP) is a reactant involved in the acute phase response and one of the many molecular factors involved in pathogenesis of coronary artery disease (CAD). CRP gene variants potentially mediate CRP plasma concentrations and the development of CAD. 220 Croatian subjects with angiographically confirmed CAD and 132 control subjects were included in the study. CRP gene polymorphisms 1059G/C and -717G/A were determined by RFLPs, using MaeIII and KspI endonuclease, respectively. Plasma concentrations of CRP and homocysteine were determined by immunoturbidimetry and FPIA, respectively. CRP 1059G/C gene variants were significantly associated with CAD (OR = 0.50; 95% CI = 0.27, 0.94; P = 0.032). Wild GG genotype and rare allele C carrier genotypes were 184 and 22 in CAD(+) group, and 101 and 24 in CAD(−) group, respectively. Multivariate analysis with age, gender, BMI, smoking status, hypertension and diabetes as covariates showed that 1059C carriers had lower CRP concentrations in CAD(−) (P = 0.010) and CAD(+) subjects (P = 0.028). This allele was also significantly associated with lower plasma homocysteine concentrations in both groups (P = 0.018 for CAD(−) and 0.002 for CAD(+). There was no significant difference between CAD(+) and CAD(−) subjects in absolute frequencies for CRP -717A/G gene variant, but multivariate analysis showed that carriers of the rarer G allele had significantly higher CRP plasma concentrations in CAD(−) subjects (P = 0.031) and higher homocysteine concentrations in CAD(+) group (P < 0.001). Atherosclerosis is an inflammatory disease resulting from different genetic and environmental factors. Results presented here support the contribution of CRP genetic variations in the development of CAD.     

The association of MDR1 C3435T and G2677T/A polymorphisms with plasma platelet-activating factor levels and coronary artery disease risk in Turkish population

Increased levels of peripheral proinflammatory mediators can contribute to the development of coronary artery disease (CAD). Platelet activating factor (PAF) is an important proinflammatory mediator and plasma levels of PAF correlate with transmembrane transporter multidrug resistant 1 P-glycoprotein (MDR1 Pgp) expression and activity. MDR1 polymorphisms can affect the expression and activity of Pgp and plasma PAF levels. Therefore, we investigated the possible relationship between MDR1 C3435T and G2677T/A polymorphisms and plasma PAF levels and the risk of CAD. The study population consisted of 198 patients angiographically documented CAD, including 113 cases with at least 1 coronary artery with ≥ 50% luminal diameter stenosis and 85 control subjects with strictly normal coronary angiograms. Genotypes of the MDR1 C3435T and G2677T/A polymorphisms were determined by polymerase chain reaction (PCR) followed by restriction fragment length polymorphism (RFLP). Plasma PAF levels were detected by enzyme-linked immunosorbent assay (ELISA). There were no significant differences among plasma PAF levels in regard to MDR1 C3435T and G2677T polymorphisms in CAD patients and controls. No statistically significant difference was found for the genotypic and allelic distributions of the polymorphisms in the MDR1 gene between the patients and the control subjects. Furthermore, analysis of MDR1 haplotypes did not show any associations with increased plasma PAF levels and risk of CAD. Our results suggest that plasma PAF levels are not associated with MDR1 gene polymorphisms. There is no association between MDR1 C3435T and G2677T/A polymorphisms and the risk of CAD in Turkish patients.     

Association of polymorphism in the thermolabile 5, 10-methylene tetrahydrofolate reductase gene and hyperhomocysteinemia with coronary artery disease

Objective To determine the incidence of methylene tetrahydrofolate reductase (MTHFR) gene 677C→T polymorphism and plasma homocysteine (Hcy) levels in a group of subjects who underwent coronary angiography, in an attempt to establish a correlation between these parameters and the severity of coronary artery disease (CAD) and to investigate the correlation between hyperhomocysteinemia (HHcy) and the presence of 677C→T polymorphism. Background Elevated plasma Hcy level is an independent risk factor for CAD. A common mutation (677C→T) in the gene coding for MTHFR has been reported to reduce the enzymatic activity and is associated with elevated levels of Hcy, especially in subjects with low folate intake. Methods The study group comprised of 84 patients with CAD and 100 age-and-sex matched controls who had no history or clinical evidence of CAD and/or MI. DNA was extracted from peripheral blood and genotypes were determined by polymerase chain reaction, restriction mapping with Hinf1, and gel electrophoresis. Conventional risk factors for CAD were prospectively documented. Results Allele and genotype frequencies in cases and control subjects were compatible with Hardy–Weinberg equilibrium. The frequencies of TT, CT, and CC genotypes among CAD patients were 4.8, 27.4, and 67.8% and in controls were 1.0, 19.0, and 80%. Hcy levels were higher in patients with triple-vessel disease compared to single and double vessel disease (P = 0.002). Multivariate analyses identified HHcy, diabetes mellitus, and hypertension as the independent predictors of CAD. Conclusions HHcy appears to have a graded effect on the risk of CAD as well as the severity and extent of coronary atherosclerosis. Our findings support that homozygous genotype of MTHFR is a genetic risk factor for CAD. A further study with larger sample size including assessment of vitamin status is needed to better clarify the relationship between MTHFR genotypes and CAD.     

血浆中D- 二聚体、C- 反应蛋白及FDP 比值在急性脑梗死中 应用价值研究

目的:探讨血浆中D-二聚体、C-反应蛋白及FDP比值在急性脑梗死中应用价值,为临床诊断提供指导。方法:抽取我院于2010年1月至2011年1月收治的30名急性脑梗死患者编为实验组。30名陈旧性脑梗死患者编为对照组。检测血浆中的D-二聚体、C-反应蛋白、FDP及其相互之间比值。结果:两组相比,实验组血浆D-二聚体、C-反应蛋白、FDP均与对照组差异无统计学意义(P>0.05);两组相比,实验组D-二聚体/FDP,C-反应蛋白/FDP均高于对照组,差异有统计学意义(P<0.05)。结论:急性和陈旧性脑梗死患者血浆中单独比较D-二聚体、C-反应蛋白、FDP差异均不明显,但D-二聚体/FDP,C-反应蛋白/FDP的阳性检出率较高,对临床有一定的指导意义。     

Alpha-tocopherol supplementation does not affect monocyte endothelial adhesion or C-reactive protein levels but reduces soluble vascular adhesion molecule-1 in the plasma of healthy subjects

Vascular monocyte retention in the subintima is pivotal to the development of cardiovascular disease and is facilitated by up-regulation of adhesion molecules on monocytes/endothelial cells during oxidative stress. Epidemiological studies have shown that cardiovascular disease risk is inversely proportional to plasma levels of the dietary micronutrients, vitamin C and vitamin E (alpha-tocopherol). We have tested the hypothesis that alpha-tocopherol supplementation may alter endothelial/monocyte function and interaction in subjects with normal ascorbate levels (> 50 microM), as ascorbate has been shown to regenerate tocopherol from its oxidised tocopheroxyl radical form in vitro. Healthy male subjects received alpha-tocopherol supplements (400 IU RRR-alpha-tocopherol/day for 6 weeks) in a placebo-controlled, double-blind intervention study. There were no significant differences in monocyte CD11b expression, monocyte adhesion to endothelial cells, plasma C-reactive protein or sICAM-1 concentrations post-supplementation. There was no evidence for nuclear translocation of NF-kappaB in isolated resting monocytes, nor any effect of alpha-tocopherol supplementation. However, post-supplementation, sVCAM-1 levels were decreased in all subjects and sE-selectin levels were increased in the vitamin C-replete group only; a weak positive correlation was observed between sE-selectin and alpha-tocopherol concentration. In conclusion, alpha-tocopherol supplementation had little effect on cardiovascular disease risk factors in healthy subjects and the effects of tocopherol were not consistently affected by plasma vitamin C concentration.     

Studies of low density lipoprotein molecular weight in human beings with coronary artery disease

Low density lipoprotein molecular weight (LDL MW) correlates positively with coronary artery disease in cholesterol-fed nonhuman primates. To evaluate this in human beings with coronary artery disease (CAD) we measured LDL MW in 93 volunteers undergoing coronary angiography (47 controls and 46 CAD patients). LDL MW of CAD patients was less than that of controls (patients, 2.79 +/- 0.17 g/mumol; controls, 2.93 +/- 0.19 g/mumol; P less than 0.001). However, LDL MW decreased as plasma triglyceride increased and concentrations of triglyceride were greater in CAD patients than in controls. Since decreased LDL MW is likely to result, in part, from increased plasma triglyceride concentrations, we attempted to determine the effect of triglyceride on the relation of LDL MW to CAD in this study. After covariance adjustment for triglyceride, there was no LDL MW difference between CAD patients and controls. Because LDL heterogeneity has been identified in other studies and was apparent on inspection of agarose column profiles of LDL of these volunteers, we sought differences in the profiles that might distinguish coronary disease cases from controls. No differences could be found. In addition, we used density gradient ultracentrifugation to characterize LDL in more detail in a subset of volunteers who had a wide range of plasma triglyceride concentrations (50 mg/dl to 900 mg/dl). LDL mean hydrated density was inversely related to LDL MW and increased as triglyceride increased. The increase in peak density was reflected in an increase in percent of total protein in LDL found to have d greater than 1.045 g/ml and a decrease in protein in LDL of d 1.035-1.040 g/ml. These interrelationships were not apparently influenced by coronary artery status.     

A study of C-reactive protein,lipid metabolism and peripheral blood to identify a link between periodontitis and cardiovascular disease

Periodontitis is characterized by systemic inflammatory host responses that may contribute to a higher risk for cardiovascular disease. We hypothesized that periodontitis may be associated with altered C-reactive protein levels, serum levels of lipids and peripheral blood counts, and that these characteristics may serve as markers for a link between periodontitis and cardiovascular disease. Sixty subjects, 25–60 years old, were divided into three groups of 20 subjects each. Group 1, age and sex matched healthy controls; group 2, patients diagnosed with chronic periodontitis; group 3, patients diagnosed with acute periodontal lesions including periodontal abscess and pericoronal abscesses. Serum C-reactive protein levels, lipid levels and peripheral blood counts were obtained for all three groups. Significant increases in C-reactive protein and serum lipid levels, and altered peripheral blood counts were observed between the experimental groups; these factors were correlated with chronic periodontitis and cardiovascular disease. These simple, economical clinical measurements can be used to assess periodontal tissue damage and may be useful for predicting risk of cardiovascular disease in these subjects.