Chlamydia LPS and MOMP seropositivity are associated with different cytokine profiles in patients with coronary heart disease

BACKGROUND: Persistent Chlamydia pneumoniae infection within atherosclerotic plaques are possible stimulators of inflammation in atherosclerosis. Why the microbe develops persistency in some individuals is unknown, but experimental studies in cell cultures and animals have demonstrated the levels of gamma interferon (IFNgamma) and interleukin 10 (IL-10) to be of crucial importance. DESIGN: We wanted to evaluate whether Chlamydia seropositivity in patients with coronary heart disease (CHD) (n = 193) was associated with elevated IFNgamma and IL-10. Two methods for detection of Chlamydia antibodies were included as well as analysis of tumour necrosis factor alpha (TNFalpha), soluble vascular cell adhesion molecule 1 (sVCAM-1) and soluble E-selectin for the evaluation of vascular inflammation. RESULTS: We found that patients with IgA antibodies towards Chlamydia lipopolysaccharide (LPS) had elevated levels of IFNgamma (P = 0.048), IL-10 (P = 0.029), TNFalpha (P = 0.009) and sE-selectin (P = 0.045), while Chlamydia LPS IgG seropositivity predicted elevated levels of IL-10 (P = 0.013). Patients with IgA antibodies towards C. pneumoniae major outer membrane protein (MOMP) without simultaneous LPS IgA seropositivity had lower levels of IFNgamma and sVCAM-1 when compared to patients with Chlamydia LPS IgA alone (P = 0.005 for IFNgamma, P = 0.016 for VCAM-1) and patients with combined Chlamydia MOMP and LPS IgA seropositivity (P = 0.046 and P = 0.013, respectively). CONCLUSIONS: In summary, we demonstrated an association between Chlamydia LPS IgA seropositivity and elevated levels of IFNgamma, IL-10, TNFalpha, sVCAM-1 and sE-selectin in CHD patients that might indicate persistent Chlamydia infection and a proinflammatory state. On the other hand, C. pneumoniae MOMP antibodies were not associated with elevated inflammatory markers and might merely be indicative of past infection, possibly with successful microbe clearance.     

Higher prevalence of Chlamydia pneumoniae seropositivity in Finnish twins compared with co-twins living in Sweden: relationships with markers of subclinical atherosclerosis

Mortality rates from coronary heart disease are lower in Swedish men and among Finnish migrants who have lived in Sweden for over 20 years than in men living in Finland. Sero-epidemiological studies, investigations of atheromatous plaque specimens, in vitro animal models and anti-chlamydial antibiotic trials have given support to the hypothesis that Chlamydia pneumoniae (Cpn) has a role in atherosclerosis. We investigated whether men with a similar genetic background but living permanently in Finland or Sweden have differences in the prevalence of Cpn seropositivity, and whether chronic Cpn infection is associated with markers of subclinical atherosclerosis. We measured anti-Cpn antibodies and ultrasonographic markers of subclinical atherosclerosis, including carotid intima-media thickness, carotid artery compliance and brachial artery flow-mediated dilatation, in a population of 76 migrant-discordant male twin pairs (152 men). The number of men with seropositivity to Cpn infection (defined as IgA>/=1:64 and IgG>/=1:128) was greater in Finland than in Sweden (21.5% compared with 10.5%; P =0.046). Cpn seropositivity accompanied by elevated C-reactive protein (CRP) levels (>1 mg/l) was associated with attenuated brachial artery flow-mediated dilatation (3.3+/-0.3%, compared with 5.5+/-0.4% in men with no signs of Cpn infection; P <0.001).Thus, among Finnish twin brothers discordant for migration to Sweden, the prevalence of Cpn seropositivity is higher for those living in Finland, and men with Cpn seropositivity combined with elevated CRP levels had attenuated endothelial function. These findings offer insight into the mechanism whereby chronic Cpn infection may increase the risk of coronary heart disease.     

Diabetes, but not the metabolic syndrome, predicts the severity and extent of coronary artery disease in women

BACKGROUND: Previous studies have suggested that diabetes and metabolic syndrome are significant risk factors for coronary artery disease (CAD). However, in women, their relative importance remains controversial. AIM: To evaluate risk factors for CAD in women and their association with the severity and extent of coronary angiographic findings. METHODS: We clinically evaluated 243 consecutive female patients with chest pain who underwent coronary angiography. The location and extent of coronary artery occlusions were assessed using the modified Gensini index. RESULTS: Compared with women with normal coronary arteries (n = 90), those with CAD (n = 153) reported less physical activity (p = 0.001), and had higher prevalences of diabetes (p = 0.046), hypertension (p = 0.002), and the metabolic syndrome (p = 0.001). They also had lower HDL cholesterol levels (p = 0.017), higher levels of triglycerides (p = 0.005), and higher fasting plasma glucose (FPG) (p < 0.001). Physical activity, FPG, serum triglycerides and HDL-cholesterol, but not the metabolic syndrome, were independent predictors of CAD. A score combining the extent and severity of angiographic findings was significantly higher in women with diabetes (p = 0.007), hypertension (p = 0.010) and FPG >or=100 mg/dl (p = 0.031), but showed no association with the metabolic syndrome. In a multivariate linear regression analysis, diabetes was an independent predictor of the extent and severity of angiographic score (p = 0.013). DISCUSSION: Diabetes, fasting plasma glucose and hypertension, but not the metabolic syndrome, were associated with severity of coronary angiographic findings in these women.     

Apolipoprotein B as the best predictor of coronary artery disease in Iranian normolipidemic patients

OBJECTIVES: A relatively high proportion of Iranian patients with coronary artery disease (CAD) have normal levels of traditional lipid risk factors and show early onset of CAD. In this study we examined the roles of apolipoprotein B (apoB), apolipoprotein AI (apoAI) and lipoprotein (a) [LP(a)] in predicting coronary heart disease in normolipidemic patients and those with premature CAD (age < or = 50). DESIGN AND METHODS: Serum levels of apoB, apoAI, and LP(a) were determined in a total of 567 Iranian patients who were candidates for coronary angiography. A subgroup of 142 patients (93 males, 49 females) with normal levels of classical lipid risk factors, and a subgroup of patients (130 males, 71 females) with age below 50 years were separately assessed for coronary risk factors. RESULTS: ApoB concentrations were significantly higher in patients with CAD (CAD+) relative to patients without CAD (CAD-) in the two subgroups. Multiple logistic regression after controlling for age and others risk factors showed apoB as the best determinant of CAD in the normolipidemic subgroup (OR, 4.3, p < 0.001) and in the men aged < or = 50 (OR, 5.7, p < 0.001). ApoB was the best predictor of CAD in a subgroup of very young patients (age < or = 40, n = 77, OR, 8.6, p < 0.009). There was a significant correlation between severity of atherosclerosis and serum apoB concentration in the normolipidemic subgroup (r = 0.22, p < 0.008). CONCLUSIONS: Our data indicate that serum concentration of apoB is the best discriminating factor to predict the presence or absence of atherosclerosis in Iranian normolipidemic individuals and young patients undergoing coronary angiography.     

Association of hyperhomocysteinemia and <Emphasis Type="Italic">Chlamydia pneumoniae</Emphasis> infection with carotid atherosclerosis and coronary artery disease in Japanese patients

An elevated plasma level of homocysteine (Hcy) and infection by Chlamydia pneumoniae (C. pneumoniae) have been suggested as independent risk factors for carotid atherosclerosis (CA) and coronary artery disease (CAD), but the mechanisms involved are unclear. We investigated the correlation between positivity for antibody to C. pneumonia (anti-C. pneumoniae) and the Hcy level in patients with CA and CAD. The total plasma homocysteine (tHcy) concentration was determined in 99 patients with CA and 31 patients with CAD, as well as 119 controls with matched risk factors for atherosclerosis. The tHcy level was measured with a Bio-Rad microplate enzyme immunoassay. In the CAD group, the tHcy level (13.67 micromol/l) was significantly higher than that in other groups (CA group, 10.96 micromol/l; control group, 9.95 micromol/l; ANOVA, P = 0.0006). Positivity for anti-C. pneumoniae IgG was significantly more common in the CAD group (77.4%) than in the other groups (CA group, 53.5%; control group, 54.6%; ANOVA, P = 0.0490). There was no association between anti-C. pneumoniae IgA positivity or tHcy and conventional risk factors. However, anti-C. pneumoniae IgG positivity was significantly more common in subjects with higher tHcy levels than in those with low tHcy levels from each of the 3 groups. The CAD group had significantly higher tHcy levels, and tHcy was significantly associated with anti-C. pneumoniae IgG positivity. These findings indicate that elevation of tHcy is related to positivity for anti-C. pneumoniae IgG in patients with CAD.     

外周血白细胞中肺炎衣原体核酸与冠状动脉粥样硬化关系的研究

目的　探讨外周血白细胞中肺炎衣原体核酸 (CpnDNA)与冠状动脉粥样硬化 (CAD)的关系及其可能机制。方法　选择 93例 (男 6 4例 ,女 2 9例 ;年龄 36～ 77岁 ,平均 5 3 81± 9 6 1岁 )成功进行冠状动脉造影患者 ,按冠脉造影结果分为对照组 (n =2 3)和冠心病组 (n =70 ) ,运用巢式PCR(nPCR)的方法检测外周血白细胞中CpnDNA及检测外周血CRP(C 反应蛋白 )等 ,比较CAD与各个因素之间 ,以及急性冠脉综合征(ACS)与各个因素之间相关性。结果　年龄及Cpn感染是CAD的独立危险因素 ;ACS者Cpn感染阳性率及CRP均数显著高于非ACS者。CRP除了与ACS有关外 ,还与Cpn、糖尿病有关。 结论　Cpn感染可能是CAD及ACS的病因之一 ,ACS与CRP显著相关。Cpn与CAD和 (或 )ACS的联系主要不是通过CRP实现的。Cpn引起的CRP增高可能主要是与IL 1、IL 6、TNF α、INF γ等共同起作用或可能起着关键的触发作用。     

Evaluation of C-reactive protein, a sensitive marker of inflammation, as a risk factor for stable coronary artery disease.

OBJECTIVES: Multiple lines of investigations have converged to suggest a prominent role for inflammation in coronary artery disease (CAD). The association of CRP level with active CAD is well documented. The relation, however, between levels of CRP and the presence and extent of stable CAD has seldom been studied in the developing countries. We investigated the association between serum concentration of C-reactive protein (CRP) and angiographically documented coronary artery disease (CAD) in a population of 450 individuals. DESIGN AND METHODS: Ultrasensitive immunoassay was used to measure CRP levels in 284 patients with CAD and 166 control healthy subjects. The association of CRP levels with severity of disease as indicated by > or = 50% stenosis in one vessel (n = 79), two vessels (n = 74), or three vessels (n = 131) was also investigated. RESULTS: CRP levels were greater in the patients with CAD (2.14 (0.88--3.38) vs. 1.45 (0.70--2.55) mg/L, p < 0.0001) than in the respective control subjects. Multiple logistic regression analysis showed CRP as an independent discriminating risk factor for CAD (odds ratio, 3.46, p < 0.001). Significant correlation was identified between CRP levels and severity of CAD (p < 0.0001). Prediction models that incorporated CRP in addition to other established coronary risk factors were significantly better at predicting risk than the models based on the other risk factors alone. CRP level was also an independent predictor of CAD in a subpopulation with normal levels of low density lipoprotein cholesterol (LDL-C < or = 3.4 mmol/L, p < 0.009). CONCLUSIONS: Our findings suggest that CRP has a strong association with stable CAD, as such, the measurement of CRP may improve the coronary risk assessment in Iranian CAD patients.     

Effect of respiratory infections on the clinical course of coronary artery disease

The subjects of the study were 64 patients with coronary artery disease (CAD), and 38 healthy controls. The study included determination of Chlamydia pneumonia (CLPN), Toxoplasma gondii (TG), Herpes simplex virus (HSV) 1, 2, Epstein-Barr virus (EBV), and antibodies to these microorganisms. Diagnostically significant elevation of the serum levels of IgG antibodies to CLPN, HSV 1, 2, or TG was associated with CAD progression, and seropositivity to several of the agents strongly correlated with CAD progression. Moreover, the risk of future coronary events increased depending on the level of total pathogen burden. These results suggest that intracellular infectious agents are involved in the development of atherosclerosis and CAD.     

Plasma cytokines, metabolic syndrome, and atherosclerosis in humans.

BACKGROUND: Interleukin-6 (IL-6) and tumor necrosis factor alpha (TNF-alpha) integrate inflammatory and adipose signaling but also have direct vascular effects. We hypothesized that plasma levels of IL-6 and soluble tumor necrosis factor alpha receptor 2 (sol-TNFR2) would be related to coronary atherosclerosis beyond established risk factors and the metabolic syndrome. METHODS: We examined the association of IL-6 and sol-TNFR2 with metabolic syndrome, C-reactive protein (CRP), and coronary artery calcification (CAC) in 875 asymptomatic participants in the Study of Inherited Risk of Coronary Atherosclerosis. RESULTS: IL-6 levels were 56% higher (p < .001) and sol-TNFR2 levels 16% higher (p < .001) in subjects with metabolic syndrome compared with those without. Both cytokines were associated with CAC beyond age, gender, Framingham risk scores, family history, metabolic syndrome, and CRP (odds ratio and 95% confidence interval of higher CAC for 1 SD increase in log-transformed cytokine levels: 1.23 [1.06-1.43], p = .006 for IL-6 and 1.15 [1.01-1.31], p = .04 for sol-TNFR2). In fact, cytokine levels were independently associated with CAC scores in the subgroup with metabolic syndrome and were additive to the homeostasis model assessment of insulin resistance in predicting CAC. CONCLUSIONS: Plasma IL-6 and sol-TNFR2 levels were independently associated with CAC, suggesting a role in integrating innate immune and adipose signaling in promoting atherosclerosis and cardiovascular risk. Measurement of their levels may facilitate cardiovascular risk prediction and targeting of therapeutic strategies.     

Insulin resistance as predictor of the angiographic severity and extent of coronary artery disease

BACKGROUND: Insulin resistance (IR) is frequently observed in patients with coronary artery disease (CAD). Aim. To examine the association between IR and severity and extent of CAD. METHODS: Quantitative coronary angiography (QCA) was used to assess coronary atherosclerosis in 107 patients with clinically suspected CAD. QCA-derived indexes reflecting CAD severity, extent, and overall atheroma burden were calculated for the entire coronary tree, and separately for different coronary segments. IR was quantified using the homeostasis model assessment insulin resistance index (HOMA IR). Nondiabetic subjects (n = 83) were divided into group 1 (n = 41) with HOMA IR <1.8 (the median value), and group 2 (n = 42) with HOMA IR >or=1.8. Group 3 comprised diabetic subjects (n = 24). RESULTS: Global age- and gender-adjusted indexes for severity (P = 0.007), extent (P = 0.038), and atheroma burden (P = 0.035) of CAD were higher in group 2 than in group 1. Similarly, the global severity (P = 0.027), extent (P = 0.090), and global atheroma burden (P = 0.024) indexes were higher in group 3 compared with group 1. IR was correlated with quantitative angiographic indexes for distal segments only, but not for proximal or mid segments of coronary vessels. CONCLUSIONS: Patients with more severe degree of IR have a more severe, extensive, and distal type of CAD than patients with lower degree of IR.     

Prognostic significance of interleukin-6 measurement in the diagnosis of acute myocardial infarction in emergency department

BACKGROUND: Markers of inflammation may predict both coronary artery disease (CAD) and adverse outcomes in patients with known CAD. Here, we investigated the role of interleukin-6 (IL-6) in the "triage" and risk assessment of patients admitted to emergency department (ED). METHODS: Serum IL-6 and high sensitivity C-reactive protein (hs-CRP) levels were prospectively evaluated in 88 patients with a history of precordial chest pain or shortness of breath of recent onset (<6 h). RESULTS: Of the 88 patients, 21% were discharged from the ED with diagnosis of non-ischemic chest pain (NICP), 39% had a final diagnosis of unstable angina (UA) and 40% experienced an acute myocardial infarction (AMI). Median IL-6 (p<0.001) and hs-CRP (p<0.01) levels on admission were significantly increased in patients with AMI compared with patients with NICP or UA. IL-6 levels correlated with hs-CRP (p<0.01). Multivariate analyses including known risk factors showed that elevated creatine kinase-MB (p<0.05) and IL-6 levels (p<0.01) were independently associated with a final diagnosis of AMI. Elevated IL-6 levels significantly predicted the risk of AMI (OR=2.47, p=0.006) in chest pain-enzyme negative patients. CONCLUSIONS: IL-6 may behave as an adjunctive diagnostic tool to assist in the risk assessment of enzyme-negative patients with precordial chest pain of recent onset.     

Anti-Saccharomyces cerevisiae Antibodies in Acute Myocardial Infarction.

BACKGROUND: Elevated anti-Saccharomyces cerevisiae antibody (ASCA) immunoglobulin (IgG) and IgA levels were first described in the serum of Crohn disease patients and have increasingly been reported in other inflammatory diseases. The role of in situ and remote inflammation in atherosclerosis is a major area of interest. In this study, we compared ASCA IgG and IgA levels in acute myocardial infarction (AMI) and controls to investigate the possible role of ASCA in AMI. METHODS: Serum samples were obtained from 140 consecutive patients who presented to the emergency department with acute chest pain. AMI was diagnosed by electrocardiography and serial enzymes. Patients ruled out for acute coronary event were grouped as controls. ASCA IgA and IgG levels were determined using enzyme-linked immunosorbent assay. Groups were compared for statistically significant difference. RESULTS: ASCA IgG titers ranged between 0.1 and 31.0 RIU/mL (mean 4.92) in the AMI group and 0.1 and 6.0 (mean 0.84) in the controls. The groups were found to differ very significantly (p = .001). ASCA IgA titers ranged between 2.0 and 200.0 RIU/mL (mean 13.73) in the AMI group and 2.0 and 11.5 RIU/mL, (mean 4.25) in controls. The groups differed significantly (p = .32). AMI and controls were also analyzed for ASCA IgA and IgG positivity. Both groups differed significantly from controls (p = .013). CONCLUSION: Elevated ASCA IgA and IgG levels as well as ASCA positivity in the AMI might suggest use of ASCA as a marker for atherosclerotic plaque instability. It might also provide a link between inflammatory processes and increased cardiovascular risk. Further studies are needed on a Saccharomyces cerevisiae-based diet, related intestinal colonization, and associated inflammation, autoimmune disorders, and cardiovascular events.     

Vitamin D receptor gene polymorphism BsmI is not associated with the prevalence and severity of CAD in a large-scale angiographic cohort of 3441 patients

BACKGROUND: Recent studies found a relationship between Vitamin D and atherosclerosis. A common genetic polymorphism of the Vitamin D receptor (VDR) has been associated with coronary artery disease (CAD) in small study populations. To assess its influence on the prevalence and severity of CAD we studied a large-scale population. METHODS: A total of 3441 consecutive patients were referred for diagnostic coronary angiography. The BsmI Vitamin D receptor polymorphism was analyzed by polymerase chain reaction. Angiography was used to define phenotypes with clear coronary arteries (n = 775), coronary sclerosis (diameter stenosis < 50%; n = 579), CAD (diameter stenosis > 50% in at least one vessel; n = 1524). Patients with CAD at a young age (females aged less than 65 years, males aged less than 55 years; n = 563) were specially defined as premature CAD. The risk profile of traditional cardiovascular risk factors was obtained for every patient. RESULTS: The genotype frequencies of the VDR BsmI polymorphism did not differ between all four phenotypes (P = 0.756). The allele frequencies for the B allele were 0.43 vs. 0.44 vs. 0.42 vs. 0.45 in the four phenotypic groups (P = 0.827). All traditional cardiovascular risk factors (hypercholesterolaemia, smoking, hypertension, diabetes mellitus, severe obesity, male gender) were significantly (P < 0.001) associated with the angiographic phenotype. CONCLUSIONS: The VDR gene variant BsmI was not associated with prevalence and severity of CAD in a large-scale cohort phenotyped by angiography.     

Osteoprotegerin is associated with silent coronary artery disease in high-risk but asymptomatic type 2 diabetic patients

OBJECTIVE: Osteoprotegerin (OPG) is an inhibitor of osteoclastogenesis, which has been recently involved in atherosclerosis. The relationship between coronary atherosclerosis and OPG has never been studied in asymptomatic type 2 diabetic patients. RESEARCH DESIGN AND METHODS: This is a nested case-control study; 162 asymptomatic type 2 diabetic patients were evaluated for silent myocardial ischemia using stress myocardial perfusion imaging; of 50 patients with positive results, 37 underwent coronary angiography, 20 of whom showed significant coronary artery disease (CAD group). Of 112 patients without silent myocardial ischemia, 20 subjects (NO-CAD group) were selected and matched by age and sex to patients with CAD. OPG, C-reactive protein, adiponectin, lipoprotein(a), albuminuria, and classical risk factors were measured. RESULTS: The percentages of subjects with OPG levels above median and with nephropathy were higher in the CAD group than in the NO-CAD group (70 vs. 25%, P = 0.004 and 50 vs. 5%, P = 0.001, respectively). LDL cholesterol levels were higher and HDL cholesterol levels lower in the CAD compared with the NO-CAD group (P = 0.033 and P = 0.005, respectively). No other variables were associated with CAD. Logistic regression analysis showed that OPG values above median (odds ratio 8.31 [95% CI 1.18-58.68], P = 0.034) and nephropathy (21.98 [1.24-388.36], P = 0.035) were significant independent predictors of asymptomatic CAD in type 2 diabetic patients. CONCLUSIONS: Our investigation reports the first evidence of an independent association of OPG with asymptomatic CAD in type 2 diabetic patients. The results of this nested case- control study with 20 cases need to be confirmed in a larger population.     

Association between interleukin-6 and the risk of cardiac events measured by coronary computed tomography angiography

Interleukin-6 (IL-6) has been found to be a predictor of heart attack. We aimed to investigate the relationship of risk factor IL-6 with extent and severity of the coronary artery disease (CAD) evaluated using coronary computed tomography angiography (CCTA). A total of 303 participants without history of CAD undergoing CCTA were enrolled. Using the model of risk-adjusted Cox proportional-hazards, the association of IL-6 level with major adverse cardiac events (MACE) was detected. The participants were assigned into three study groups based on serum IL-6 level. Compared with those in the lowest tertile, patients with highest IL-6 level displayed higher atherosclerotic burden such as plaque extent defined as prevalence of obstructive CAD and segments with any plaque. After a median 3.0 year follow-up period, we also found that patients with highest IL-6 level experienced higher MACE risk and all-cause death compared with those from the lowest tertile. Among participants without CAD history who underwent CCTA, patients with high level of IL-6 had increased burden of atherosclerosis and higher MACE risk compared to participants of low level of IL-6.     

Association between depression and anxiety symptoms and major atherosclerosis risk factors in patients with chest pain

Psychological variables, such as depression and anxiety, are known as independent risk factors for coronary artery disease (CAD), suggesting the interaction of psychological and physiological factors in the development of CAD. In the present study, we analyzed the possible association between depressive and anxiety symptoms and major atherosclerotic risk factors in patients with chest pain warranting coronary angiography. The patients without CAD (n = 159) and those with CAD (n = 155) were evaluated for the severity of depression and anxiety by the symptom scales; high scores indicate severe symptoms. Age, male/female ratio, prevalence of diabetes mellitus (DM), and depression level were significantly higher in the CAD group. Among a total of 314 patients with chest pain, the mean depression score was higher in patients with DM (16.01 +/- 8.12 vs 13.01 +/- 9.6, p = 0.01) and those with hypercholesterolemia (15.43 +/- 9.61 vs 12.53 +/- 9.61, p = 0.02). The mean anxiety score was also higher in patients with DM (20.81 +/- 12.85 vs 16.51 +/- 12.09, p = 0.008), hypercholesterolemia (20.67 +/- 13.11 vs 15.29 +/- 11.36, p = 0.002), or hypertension (20.74 +/- 12.94 vs 14.1 +/- 10.8, p = 0.001). Thus, DM and hypercholesterolemia are associated with depression and anxiety, while hypertension is only related to anxiety. In contrast, smoking and family history of atherosclerosis are not related to depression and anxiety scores. These results suggest depression and anxiety symptoms may contribute to the development and progression of CAD, especially in patients with DM or hypercholesterolemia.     

Relationship between airflow obstruction and coronary atherosclerosis in asymptomatic individuals: evaluation by coronary CT angiography

Airflow obstruction is associated with increased cardiovascular morbidity and mortality. However, the causal mechanisms linking airflow obstruction with higher incidence of cardiovascular events remain elusive. We evaluated the relationship between airflow obstruction, a key feature of chronic obstructive pulmonary disease (COPD), and prevalence, extent, and severity of coronary atherosclerosis in a large cohort of asymptomatic subjects. Participants were recruited from those undergoing spirometry and coronary computed tomography angiography (CCTA) as part of a general health evaluation from March 2009 to February 2011. Subjects were required to be over 40 years of age with no known CAD. Airflow obstruction was defined as forced expiratory volume in 1 s (FEV1)/forced vital capacity (FVC) <?70%. Obstructive CAD, as measured by CCTA, was defined as maximum intra-luminal stenosis ≥?50%. Participants with airflow obstruction or normal lung function were compared in terms of obstructive CAD prevalence, the extent and severity of coronary atherosclerosis; including coronary artery calcium score (CACS), atheroma burden score (ABS), atheroma burden obstructive score (ABOS), segment involvement score (SIS), and segment stenosis score (SSS). A total of 1888 subjects were eligible for study inclusion. Compared with participants with normal lung function, those exhibiting airflow obstruction were more likely to have obstructive CAD (p?=?0.002). Airflow obstruction was associated with higher CACS (p?=?0.043), ABS (p?=?0.002), ABOS (p?=?0.017), SIS (p?=?0.003), and SSS (p?=?0.002). Multivariable analyses adjusted for conventional cardiovascular risk factors revealed that airflow obstruction was independently associated with presence of CAD (odds ratio 1.673, confidence intervals [CI] 1.002–2.789, p?=?0.048). In this asymptomatic population, the presence of airflow obstruction was associated with a greater prevalence, extent, and severity of coronary atherosclerosis and was seen to be an independent predictor of the presence of CAD.     

Cytokines and growth factors in mostly atherosclerotic patients on hemodialysis determined by biochip array technology.

BACKGROUND: The lifespan of patients with chronic renal failure (CRF) is reduced, and coronary artery disease is the leading cause of morbidity and mortality in these patients. The progression of atherosclerosis is accelerated and angiogenesis is impaired in CRF. Risk factors that could contribute to further understanding of vascular pathology include markers of inflammation and growth factors. The purpose of this study was to determine the levels of cytokines (IL-2, IL4, IL-6, IL-8, IL-10, IL-1 alpha, IL-1 beta), vascular endothelial growth factor (VEGF), epidermal growth factor (EGF), interferon-gamma (IFN gamma), tumor necrosis factor-alpha (TNFalpha) and monocyte chemotactic protein-1 (MCP-1) in patients on chronic hemodialysis (HD; n=75), and to compare values with those of control subjects (n=113). METHODS: Evidence((R)) biochip array analyzer was used for quantification of plasma concentrations in samples. RESULTS: Significant differences were found between the control subjects and HD patients. IL-2 (p<0.001), IL-4 (p<0.001) and EGF (p<0.001) levels were higher in controls than in HD patients, while IL-6 (p<0.001), IL-8 (p=0.081), IL-10 (p=0.008), TNFalpha (p<0.001), IL-1 beta (p<0.001) and MCP-1 (p<0.001) levels were higher in HD patients. We also found IL-2 (p=0.015) and IL-1 alpha (p=0.035) levels to be significantly higher in males than females, while IL-4 (p=0.025) and IL-1 beta (p=0.049) levels were significantly higher in females. Among HD patients, IL-2 levels were higher in patients under the age of 50 years (p<0.048). It was also higher in female than in male patients (p<0.035) and in patients on HD for more than 10 years (p<0.009). IL-6 levels were higher in patients over the age of 50 years (p<0.047). Patients with previous glomerulonephritis had the highest level of IL-6 compared to patients with previous pyelonephritis and diabetes mellitus (p<0.063). IL-6 levels were higher in patients with concomitant hepatitis C virus (HCV) infection (p<0.036) and in patients with developed atherosclerosis (p<0.003). IL-8 levels were higher in patients over the age of 50 years (p<0.003) and in the group with previous glomerulonephritis (p<0.031). IL-10 levels were higher in the group with developed atherosclerosis (p<0.045). EGF was the highest in the group of patients with previous diabetes mellitus compared to pyelonephritis and glomerulonephritis groups (p<0.073). TNFalpha levels were higher in the patient population on HD for more than 10 years (p<0.032) and in the concomitant HCV group (p<0.073). IL-1 beta levels were higher in the HCV group (p<0.088). CONCLUSIONS: Plasma concentrations of some cytokines and growth factors could serve as useful diagnostic and prognostic parameters for patients with CRF on HD.     

Enhanced susceptibility to oxidation and diminished vitamin E content of LDL from patients with stable coronary artery disease.

BACKGROUND: Convincing evidence points to oxidative modification of LDL as an important trigger in a complex chain of events leading to atherosclerosis. We investigated the occurrence of enhanced susceptibility of LDL to oxidation and decreased vitamin E concentration in LDL as additional risk factors promoting atherosclerosis among patients with established coronary artery disease (CAD). METHODS: We examined 132 patients with angiographically confirmed CAD and compared them with 111 healthy control individuals. We measured conjugated diene production to assess susceptibility of LDL to copper-mediated oxidation. Vitamin E content of LDL was measured by HPLC. RESULTS: The mean lag time of LDL oxidation and LDL alpha-tocopherol/LDL-cholesterol ratio were lower in the patients with CAD (55 +/- 14 min and 2.4 +/- 1.0 mmol/mmol) than in the controls (63 +/- 13 min and 2.9 +/- 1.1 mmol/mmol; P <0.0001 and <0.001, respectively). Multiple stepwise regression analysis demonstrated the lag time (odds ratio, 1.96; 95% confidence interval, 1.34-2.87; P <0.0001) and concentration of vitamin E in LDL (odds ratio, 1.65; 95% confidence interval, 1.16-2.33; P <0.005) as independent determinants of CAD. Significant inverse Spearman rank correlations were found between lag time (r = -0.285; P <0.001) or concentration of vitamin E in LDL (r = -0.197; P <0.002) and severity of CAD. Lag times were not significantly correlated with serum C-reactive protein or ferritin. CONCLUSIONS: Our data suggest that a short LDL oxidation lag time and a low concentration of vitamin E in LDL might be independent coronary risk factors for stable CAD in Iranian people.     

Serum type III procollagen peptide levels in coronary artery disease (a marker of atherosclerosis)

The known shift in collagen synthesis from procollagen type I to type III in patients with atherosclerosis, suggested measurement of serum procollagen III peptide (PIIIP) levels in patients with coronary artery disease (CAD). Two groups of patients were studied: group I--thirty-six patients with CAD (male, mean age 56.9 +/- 7.5 years, hospitalized for coronary angiography. Risk factors included 16 patients with high blood pressure, four diabetics, 31 smokers and 15 with hypercholesterolaemia. Five patients had no significant lesions, seven had one vessel with over 50% stenosis, 10 had two vessels and 14 had three vessels. Group II--35 patients (male, mean age 39.4 +/- 13.3 years), with normal physical examination and ECG according to WHO criteria, formed the control group: the risk factors included nine patients with high blood pressure, 14 smokers and one with hypercholesterolaemia. Procollagen III peptide levels were determined by radioimmunoassay. In group I, PIIIP levels were 26.8 +/- 16 ng ml-1 vs. 10.4 +/- 3.2 for group II. Sixty-one per cent of group I had pathological levels of PIIIP with an absence of correlation with the severity of atherosclerosis or risk factors. Only 2.8% of patients in group II had pathological levels. Procollagen III peptide determination would appear to be a sensitive, specific and predictive test for atherosclerosis in patients with CAD.