High levels of C-reactive protein with low total cholesterol concentrations additively predict all-cause mortality in patients with coronary artery disease.

BACKGROUND: This study aimed to investigate independent and additive predictive effects of raised C-reactive protein (CRP) levels and decreased total cholesterol levels on mortality in patients with chronic coronary artery disease (CAD). Low total cholesterol (TC) levels are associated with worsened survival in chronic and acute diseases. Elevated CRP level is an important predictor of vascular events and mortality in patients with CAD. Potential inhibition of immune activation by circulating lipoproteins could be a link between cholesterol and inflammatory markers. MATERIALS AND METHODS: A group of 387 patients (median age 59 years) with CAD and with or without severe heart failure (HF) were followed for a median of 5.06 years. Serum total cholesterol and CRP concentrations were measured at enrollment. RESULTS: The relationship between lipoproteins, CRP and survival was explored. High CRP concentrations were in significant association with severity of HF and predicted worsened survival in patients with CAD (hazard ratio 5.214, 95% CI 1.762-15.427). The association between CRP levels and mortality was independent of potential confounding factors such as age, body-mass index, severity of HF, smoking habits, hypertension and TC levels. The prediction of mortality by low TC levels was significant (hazard ratio 2.932, 95% CI 1.021-8.422). Furthermore, patients with increased CRP and decreased TC (additive predictive effect) phenotype had 11.714-times higher risk (95% CI 2.619-52.385) of being nonsurvivors than patients with low CRP/high TC. CONCLUSIONS: High CRP levels and low TC concentrations are independent and additive predictors of mortality in patients with CAD. Our data indicate that joint analysis of circulating lipoproteins and inflammatory biomarkers may improve prediction of survival in patients with CAD.

Involvement of polymorphisms in the chemokine system in the susceptibility for coronary artery disease (CAD). Coincidence of elevated Lp(a) and MCP-1 -2518 G/G genotype in CAD patients.

The central role of chemokines in the pathogenesis of atherosclerosis has been made clear. Recently polymorphisms in the gene regulatory region of MCP-1 and in the promoter region of RANTES have been found, which increase the expression of these chemokines. We investigated the role of these polymorphisms together with the chemokine SDF-1-801A and the chemokine receptors CCR2-64I and CCR5Delta32 mutations in 318 patients with coronary artery disease (CAD) referred to coronary bypass surgery, comparing them with 320 healthy controls. The prevalence of the MCP-1 -2518 G/G homozygotes was significantly higher among CAD patients than among controls (P<0.005; OR=2.2 (95% CI 1.25-3.92). The Lp(a) levels of CAD patients with G/G genotype were significantly higher than those in patients with G/A or A/A genotypes. No CAD patients homozygous for the CCR5Delta32 and CCR2-64I mutations have been found. The genotype distributions of the two alleles deviated from the Hardy Weinberg equilibrium in patients, indicating that the numbers of homozygotes were significantly lower than expected. The MCP-1 -2518G variant in homozygous form appears as a genetic risk factor for severe CAD. This genotype is associated with elevated Lp(a) levels in patients. Individuals homozygous for CCR2-64I or CCR5Delta32 mutations are at reduced risk for severe CAD.

Comparative study on antibodies to human and bacterial 60 kDa heat shock proteins in a large cohort of patients with coronary heart disease and healthy subjects.

BACKGROUND: Recent observations indicate an association between antibodies against mycobacterial heat shock protein (hsp65) and coronary heart disease (CHD). Previously, we reported on marked differences in antigen specificity and complement activating ability of anti-hsp65 antibodies and auto-antibodies against human heat shock protein, hsp60. Here, we investigated whether there are differences between antih-sp65 and anti-hsp60 antibodies in their association with CHD. DESIGN: We measured by ELISA the levels of antibodies to hsp65, hsp60 and E. coli-derived GroEL in three groups: Group I, 357 patients with severe CHD who underwent by-pass surgery; Group II, 67 patients with negative coronary angiography; Group III, 321 healthy blood donors. Antibodies against Helicobacter pylori were also measured by commercial ELISA. RESULTS: As calculated by multiple regression analysis, the levels of anti-hsp60 auto-antibodies were significantly higher in Group I compared to Group II (P = 0.007) or Group III (P < 0.0001). By contrast, although concentrations of anti-hsp65 and anti-GroEL antibodies in Group I were higher than in Group III, no significant differences between Group I and Group II were found. Antibodies to the two bacterial hsp strongly correlated to each other, but either did not correlate or weakly correlated to hsp60. In Group I, serum concentrations of anti-H.pylori antibodies significantly correlated with those of anti-hsp65 and anti-GroEL antibodies but they did not correlate with the anti-hsp60 antibodies. CONCLUSIONS: As to their clinical relevance, a remarkable difference become evident between antibodies to human hsp60 and antibodies against bacterial hsp in the extent of association with CHD. On the basis of these findings and some pertinent literature data, an alternative explanation for the association between high level of anti-hsp antibodies and atherosclerotic vascular diseases is raised.

Independent and joint effects of antibodies to human heat-shock protein 60 and Chlamydia pneumoniae infection in the development of coronary atherosclerosis.

BACKGROUND: Studies have suggested that the prevalence of antibodies against heat-shock proteins (HSPs), Chlamydia pneumoniae (CPN), and cytomegalovirus (CMV) is associated with coronary artery disease (CAD), but the independent or joint effects of human (h) HSP60 antibodies and these pathogens in patients have not been fully elucidated. METHODS AND RESULTS: A total of 405 subjects (276 patients with CAD and 129 control individuals) were tested for serum antibodies to hHSP60, CPN, and CMV immediate-early-1 (IE1) antigens. Patients were also assessed for serum cholesterol, triglyceride levels, and smoking habit. Significantly elevated levels of antibodies to hHSP60 and CPN but not to CMV-IE1 antigens were documented in CAD patients. Multiple logistic regression analysis and subanalyses of selected subjects showed that these associations were independent of age, sex, smoking, and serum lipid levels. Antibodies to hHSP60 and CPN did not correlate quantitatively; however, the relative risk of disease development was substantially increased in subjects with high antibody levels to both hHSP60 and CPN:, reaching an odds ratio of 82.0 (95% CI 10.6 to 625.0). CONCLUSIONS: High levels of antibodies to hHSP60 and CPN: are independent risk factors for coronary atherosclerosis, but their simultaneous presence substantially increases the risk for disease development.

[Mass occurrence of mycotic tracheitis in chickens]. / Hromadný výskyt mykotické tracheitidy kurat.

An enzootic of chick mycosis, caused by the spores of the fungus Aspergillus fumigatus, is described. The mycotic infection affected the respiratory tract of the birds; pathological changes were located mainly in the region of the trachea. The changes had the nature of diphtheroid necrotic inflammation destroying the mucous membrane and causing almost an obstruction of the trachea. Deposits of granulomatous inflammation, containing fungus elements, were detected in the peritracheal tissue, and in individual birds also in the lungs. Litter contaminated with Aspergillus was the source of infection.