Association of monocyte/HDL-C ratio with SYNTAX scores in patients with stable coronary artery disease.

PURPOSE: The aim of this study was to investigate the relationship between monocyte count/high density lipoprotein cholesterol (HDL-C) ratio (MHR) and the severity of coronary atherosclerosis, as assessed by the SYNTAX score (SXscore), in patients with stable coronary artery disease (CAD) undergoing coronary angiography. MATERIALS AND METHODS: A total of 428 patients were included in the study between March 2012 and February 2015. The SXscore was determined with baseline coronary angiography. An SXscore ≥ 23 was regarded as severe CAD by definition, and the patients were divided into two groups: those with low SXscores (< 23) and those with high SXscores (≥ 23). RESULTS: MHR and C-reactive protein (CRP) were significantly higher in patients with high SXscores (p < 0.001 and p < 0.001, respectively). Left ventricular ejection fraction (LVEF) was lower in the group with high MHR and high SXscores. The cutoff value of MHR that predicted a high SXscore was 24, with a sensitivity of 66 % and a specificity of 65.1 %. CONCLUSION: To the best of our knowledge, this is the first study in the literature showing that MHR is significantly associated with SXscores. Our results suggest that MHR can be used as a prognostic marker in patients with stable CAD, since it is an easily available and inexpensive test.

Femoral pseudoaneurysm in patients undergoing primary percutaneous coronary intervention for ST-elevation myocardial infarction: incidence, clinical course and risk factors.

AIM: Various peripheral vascular complications may be observed after cardiac catheterization. However, no data are available about femoral pseudoaneurysm (FPA) after urgent primary percutaneous coronary intervention (PCI). We sought to determine the in-hospital incidence, clinical course and predictors of FPA in patients with ST elevation myocardial infarction (STEMI) undergoing primary PCI. METHODS: Two thousand six hundred consecutive STEMI patients (mean age: 56.5 ± 11.7 years; 2158 men) undergoing primary PCI were retrospectively enrolled into this study. Patients were evaluated with Doppler ultrasonography following PCI and categorized into two groups according to whether FPA developed or not. All the parameters were compared between FPA and non-FPA groups. RESULTS: The incidence of FPA after primary PCI was determined to be 2.3%. The mean age was higher in the FPA group compared to the non-FPA group (mean age: 60.6 ± 11.6 vs. 56.5 ± 11.8, respectively, P=0.007). Furthermore, the FPA developing group experienced prolonged hospitalizations compared to the non-FPA group, but no differences in in-hospital or long term mortality were noticed. In the multivariate analysis of this study, female gender and age (>75 years), after primary PCI, were found to be independent predictors of FPA. CONCLUSION: High incidence of FPA was noticed in STEMI patients undergoing primary PCI, which prolonged in-hospital stay. Extra care must be given, especially to women and those who are >75 years of age, for this complication.

Specific stimulation of peripheral blood mononuclear cells from patients with acute myocarditis by peptide-bound flavin adenine dinucleotide (FAD), a naturally occurring autologous hapten.

The tryptic FAD-peptide carrying the flavin in 8alpha-(N3)histidyl linkage as natural hapten was isolated by HPLC from the bacterial enzyme 6-hydroxy-d-nicotine oxidase. The same flavin protein linkage is found in the mitochondrial succinate dehydrogenase flavoprotein subunit, the predominant flavoprotein with covalently bound FAD in mitochondria of cardiomyocytes. Peripheral blood mononuclear cells (PBMC) were isolated from four patients with acute myocarditis, seven patients with dilated cardiomyopathy (DCM) and from four healthy control individuals. The response of PBMC to the FAD-peptide was evaluated by measuring proliferation ([3H]-dThd incorporation) and cytokine secretion [interferon (IFN)-gamma]. PBMC from all patients with acute myocarditis showed positive responses to the FAD-peptide, in contrast to PBMC from patients with DCM or control individuals. Following the recovery of the patients from the acute inflammation of the heart, PBMC no longer exhibited a proliferation response to the FAD-peptide. A chemically synthesized FAD-free peptide with identical amino acid sequence induced no response of PBMC. The results are consistent with a recall response by activated T cells, specific for the normally cryptic mitochondrial flavin-hapten, which may be liberated following cardiomyocyte destruction during the inflammation of the heart.

Analysis of mitochondrial antigens reveals inner membrane succinate dehydrogenase flavoprotein subunit as autoantigen to antibodies in anti-M7 sera.

The role of mitochondrial proteins as antigens to antibodies of anti-M7 sera was analysed by flavin fluorescence, one- and two-dimensional Western blots and blue native gel electrophoresis. Flavin fluorescence of succinate dehydrogenase (SucDH, complex II of the respiratory chain) of rat liver inner mitochondrial membranes correlated with the immunoreactivity of a representative anti-M7 myocarditis serum. Antigens of isolated bovine heart mitochondria reacting with antibodies of myocarditis serum on two-dimensional Western blots were identified by MALDI-TOF and NanoESI mass spectrometry as myosin heavy chain beta and as dihydrolipoamide dehydrogenase of the mitochondrial 2-oxoacid dehydrogenase complexes. The SucDH-flavoprotein was not resolved as a discrete protein spot on two-dimensional polyacrylamide gels. However, separation of the rat liver inner mitochondrial membrane complexes by blue native gel electrophoresis followed by Western blotting, and Western blots of purified Escherichia coli SucDH complex revealed that anti-M7 sera contained antibodies directed against the SucDH-flavoprotein subunit.

Coxsackievirus B3 infection induces anti-flavoprotein antibodies in mice.

Enteroviruses, the most common cause of acute myocarditis, are also supposed aetiological agents of dilated cardiomyopathy. Autoantibodies (anti-M7; Klein & Berg, Clin Exp Immunol 1990; 58:283-92) directed against flavoproteins with covalently bound flavin (alphaFp-Ab; Otto et al., Clin Exp Immunol 1998; 111:541-2) are detected in up to 30% of sera of patients with myocarditis and idiopathic dilated cardiomyopathy (IDCM). Mice inoculated with a myocarditic variant of coxsackievirus B3 (CVB3) were employed to study the occurrence of serum alphaFp-Ab following viral infection. The presence of alphaFp-Ab was analysed by Western blotting with the flavoprotein antigens 6-hydroxy-D-nicotine oxidase (6HDNO) and sarcosine oxidase (SaO). Of 10 sera from CVB3-infected mice, five showed a strong reaction with both antigens. The sera were reactive also to the mitochondrial covalently flavinylated proteins dimethylglycine dehydrogenase and sarcosine dehydrogenase. Sera of non-infected mice did not react with these antigens. A 6HDNO mutant protein with non-covalently bound FAD no longer reacted on Western blots with sera of CVB3-infected mice. Preincubation with FAD abolished or reduced the reaction of the sera with the 6HDNO antigen. At 2 weeks p.i. the alphaFp-Ab were of the IgM and IgG isotypes, at 7 and 9 weeks p.i. of the IgG isotype. The sera of CVB3-infected mice reproduced closely the antigenic specificity of the anti-M7 sera of patients, lending further support to the role of coxsackieviruses in the pathogenesis of IDCM.

Reduced IFN-gamma production in elderly people following in vitro stimulation with influenza vaccine and endotoxin.

Cytokine interferon gamma (IFN-gamma) is pivotal in the defence against viruses and intracellular pathogens and an age-related decreased IFN-gamma production may explain the increased infectious disease morbidity and mortality in the elderly. Therefore, we performed a series of clinical experiments evaluating the influence of age and health status on IFN-gamma production following in vitro stimulation with influenza vaccine or endotoxin. Both healthy and frail elderly people produced significantly lower amounts of IFN-gamma following ex vivo stimulation with influenza vaccine or endotoxin. We conclude that ageing is accompanied by a decreased capacity to produce IFN-gamma. This may explain the increased incidence and case-fatality caused by viruses and intracellular pathogens in the elderly.