Association of Low Ficolin-Lectin Pathway Parameters with Cardiac Syndrome X.

In patients with typical angina pectoris, inducible myocardial ischaemia and macroscopically normal coronaries (cardiac syndrome X (CSX)), a significantly elevated plasma level of terminal complement complex (TCC), the common end product of complement activation, has been observed without accompanying activation of the classical or the alternative pathways. Therefore, our aim was to clarify the role of the ficolin-lectin pathway in CSX. Eighteen patients with CSX, 37 stable angina patients with significant coronary stenosis (CHD) and 54 healthy volunteers (HC) were enrolled. Serum levels of ficolin-2 and ficolin-3, ficolin-3/MASP-2 complex and ficolin-3-mediated TCC deposition (FCN3-TCC) were determined. Plasma level of TCC was significantly higher in the CSX than in the HC or CHD group (5.45 versus 1.30 versus 2.04 AU/ml, P < 0.001). Serum levels of ficolin-2 and ficolin-3 were significantly lower in the CSX compared to the HC or CHD group (3.60 versus 5.80 or 5.20 µg/ml, P < 0.05; 17.80 versus 24.10 or 26.80 µg/ml, P < 0.05). The ficolin-3/MASP-2 complex was significantly lower in the CSX group compared to the HC group (92.90 versus 144.90 AU/ml, P = 0.006). FCN3-TCC deposition was significantly lower in the CSX group compared to the HC and CHD groups (67.8% versus 143.3% or 159.7%, P < 0.05). In the CSX group, a significant correlation was found between TCC and FCN3-TCC level (r = 0.507, P = 0.032) and between ficolin-3/MASP-2 complex level and FCN3-TCC deposition (r = 0.651, P = 0.003). In conclusion, in patients with typical angina and myocardial ischaemia despite macroscopically normal coronary arteries, low levels of several lectin pathway parameters were observed, indicating complement activation and consumption. Complement activation through the ficolin-lectin pathway might play a role in the complex pathomechanism of CSX.

Inflammation and microvascular dysfunction in cardiac syndrome X patients without conventional risk factors for coronary artery disease.

OBJECTIVES: The aim of this study was to ascertain whether coronary microvascular dysfunction (CMD) and inflammation are related in cardiac syndrome X (CSX). BACKGROUND: CMD can lead to CSX, defined as typical angina and transient myocardial ischemia despite normal coronary arteriograms. Inflammation has been suggested to play a role in the pathogenesis of myocardial ischemia in CSX. METHODS: We assessed 21 CSX patients (age 52 ± 10 years; 17 women) without traditional cardiovascular risk factors and 21 matched apparently healthy control subjects. Positron emission tomography was used to measure myocardial blood flow (MBF) and coronary flow reserve (CFR) in response to intravenous adenosine, whereas high-sensitivity C-reactive protein (CRP) was measured to assess inflammation. Patients were subdivided a priori into 2 groups according to CRP concentrations at study entry (i.e., ≤3 or >3 mg/l). RESULTS: There were no differences in resting (1.20 ± 0.23 ml/min/g vs. 1.14 ± 0.20 ml/min/g; p = 0.32) or hyperemic MBF (3.28 ± 1.02 ml/min/g vs. 3.68 ± 0.89 ml/min/g; p = 0.18) between CSX patients and the control group, whereas CFR was mildly reduced in CSX patients compared with the control group (2.77 ± 0.80 vs. 3.38 ± 0.80; p = 0.02). Patients with CRP >3 mg/l had more severe impairment of CFR (2.14 ± 0.33 vs. 3.16 ± 0.76; p = 0.001) and more ischemic electrocardiographic changes during adenosine administration than patients with lower CRP, and a negative correlation between CRP levels and CFR (r = -0.49, p = 0.02) was found in CSX patients. CONCLUSIONS: CSX patients with elevated CRP levels had a significantly reduced CFR compared with the control group, which is indicative of CMD. Our study thus suggests a role for inflammation in the modulation of coronary microvascular responses in patients with CSX.

Association of inflammation and cytotoxin-associated gene a positive strains of helicobacter pylori in cardiac syndrome x.

BACKGROUND: Cardiac syndrome X (CSX) is a condition in which patients have the pain of angina despite normal coronary angiogram. Helicobacter pylori (H. pylori) infection causes chronic inflammation which may play a pathogenic role in CSX. We surveyed the association of inflammation with H. pylori and its virulent strain (cytotoxin-associated gene A positive; CagA+) infections with CSX. MATERIAL AND METHODS: Sixty patients with CSX (38 women/22 men; mean age: 51.8 ± 12.3) and 60 age- and gender-matched healthy controls (39 women/21 men; mean age: 48.9 ± 6.3) were enrolled. Plasma samples were tested for the presence of IgG antibody to H. pylori using enzyme linked immunosorbent assay (ELISA) method. IgG- positive patients were determined by the presence of IgG antibody to CagA, also by ELISA method. Also, plasma levels of interleukin-6 (IL-6) and tumor necrosis factor-alpha (TNF-α) were measured by ELISA method. RESULTS: Patients with CSX were detected to have significantly higher plasma IL-6 and TNF-α level in comparison with normal controls (33.6 ± 3.5 vs 3.2 ± 0.4 and 24.2 ± 2.3 vs 3.1 ± 0.4, respectively; p < 0.01). The plasma levels of these inflammatory factors in CgA+ were significantly higher than those in CagA- (CSX: IL-6: 43.05 ± 5.04 vs 23.97 ± 4.58 and TNF-α: 31.43 ± 3.13 vs 16.47 ± 2.93, CONTROLS: IL-6: 3.52 ± 1.39 vs 2.90 ± 0.67 and TNF-α: 5.39 ± 1.17 vs 2.22 ± 0.43, respectively; p < 0.05). CONCLUSION: The CagA+ strain of H. pylori, can not only be a trigger, and may also have a role via chronic inflammation in the pathogenesis of CSX.

Endothelial dysfunction as assessed by flow-mediated dilation in patients with cardiac syndrome X: role of inflammation.

BACKGROUND: Endothelial dysfunction, reduced coronary flow reserve and increased markers of inflammation are detectable in cardiac syndrome X (CSX). In this study we investigated the relation between inflammation and systemic endothelial function in CSX patients. METHODS: We studied 42 CSX patients (55 +/- 6 years, 14 men) and 20 healthy subjects (52 +/- 7 years, 9 men). Systemic endothelial function was assessed by flow-mediated dilation (FMD) of the brachial artery after 5-minute of forearm cuff inflation. Serum C-reactive protein (CRP) was measured by a high-sensitivity method. RESULTS: FMD was significantly lower in CSX patients compared to controls (4.8 +/- 4.4 vs. 13.7 +/- 4%, p < 0.001), whereas CRP levels were higher in CSX patients than in controls (2.7 +/- 2.4 vs. 0.7 +/- 0.4 mg/L, p = 0.001). In CSX patients FMD showed a significant inverse correlation with CRP levels, even after adjustment for potentially confounding variables (r = -0.34, p = 0.006). CONCLUSION: An impaired FMD is detectable in CSX patients, suggesting a generalized abnormality in vascular function. Subclinical inflammation se is to play a significant role in the impairment of endothelium-dependent vasodilator function of these patients.

Relation between cardiovascular risk factors and coronary microvascular dysfunction in cardiac syndrome X.

BACKGROUND: The causes of coronary microvascular dysfunction (CMVD) in patients with cardiac syndrome X (CSX) are largely unknown. Common cardiovascular risk factors (CVRFs) and increased markers of inflammation have been associated with CMVD in some studies, but their role in determining CMVD in CSX patients remains poorly known. METHODS AND RESULTS: We studied 71 CSX patients (56 ± 9 years, 23 men) and 20 healthy volunteers (52 ± 7 years, nine men). Using transthoracic Doppler echocardiography, coronary microvascular vasodilator function was assessed in the left anterior descending coronary artery as the ratio of diastolic coronary blood flow (CBF) velocity at peak intravenous adenosine administration and during cold pressor test (CPT) to the respective basal CBF velocity values. Common CVRFs tended to be more frequent and C-reactive protein (CRP) levels were higher (P < 0.001) in CSX patients than in controls. Both CBF responses to adenosine (2.05 ± 0.6 vs. 2.92 ± 0.9, P < 0.001) and to CPT (1.71 ± 0.6 vs. 2.42 ± 0.7, P < 0.001) were lower in CSX patients than in controls. The differences between the two groups in CBF response to adenosine and in CBF response to CPT remained highly significant (P < 0.01 for both) after adjustment for all CVRFs, including serum CRP levels. CONCLUSION: In CSX patients, both endothelium-dependent and endothelium-independent CMVD cannot be reliably predicted by CVRFs (including serum CRP levels), alone or in combination.

Effects of nebivolol therapy on endothelial functions in cardiac syndrome X.

Endothelial dysfunction is major pathophysiologic mechanism in cardiac syndrome X (CSX), which causes a decrease in plasma nitrite oxide (NO) levels. It was demonstrated that nebivolol improves endothelial function and increases NO release. Despite this pathophysiologic relation, the effect of nebivolol therapy on endothelial function in patients with CSX is unknown. The aim of this study is to evaluate the effect of nebivolol on patients in CSX. Thirty-eight patients who were diagnosed with CSX were prospectively enrolled in the study. The treatment group consisted of 20 patients and the control group consisted of 18 patients. An oral 5-mg dose of nebivolol was given daily and maintained for 4 weeks in the treatment group. Ultrasonographic parameters (brachial artery flow-mediated dilatation [FMD], brachial artery lumen diameters) and inflammatory markers (high-sensitivity C-reactive protein [hsCRP], von Willebrand factor [vWf], and fibrinogen) were measured at baseline and end of the 4 weeks. Brachial baseline lumen diameter, brachial lumen diameter after reactive hyperemia, and FMD were 4.61 +/- 0.49 mm, 4.87 +/- 0.53 mm, and 5.6% +/- 2.3% at baseline. After the nebivolol therapy, there was a significant increase in both brachial artery baseline lumen diameter and lumen diameter after reactive hyperemia (P < 0.001 and P = 0.002). However, there was no significant change in FMD (5.6% +/- 2.2% vs 5.3% +/- 2.1%, P not significant). Levels of hsCRP, vWf, and fibrinogen were significantly decreased (hsCRP: 3.4 +/- 0.49 mg/dl vs 2.97 +/- 0.74 mg/dl, P = 0.001; vWf: 107 +/- 62 vs 86 +/- 58, P = 0.004; fibrinogen: 341 +/- 89 mg/dl vs 299 +/- 87 mg/ dl, P = 0.01) in the treatment group. Nebivolol therapy may have a favorable effect on endothelial function in CSX. Further studies are needed to confirm the clinical significance of nebivolol therapy in CSX.

Possible role of Helicobacter pylori infection via microvascular dysfunction in cardiac syndrome X.

Recently, some investigators have reported seeing microvascular dysfunction in patients with cardiac syndrome X (CSX). In addition, Helicobacter pylori (H. pylori), a bacterium causing chronic gastritis and peptic ulcers, has recently been associated with CSX. Yet the mechanism(s) by which H. pylori infection leads to CSX is poorly understood. We propose a link between H. pylori and microvascular dysfunction infection in the development of CSX.

Transcriptional activity of genes encoding interferon gamma (IFNgamma) and its receptor assessed in peripheral blood mononuclear cells in patients with cardiac syndrome X.

BACKGROUND: Cardiac syndrome X is typically characterized by effort induced anginal pain with ST segment depression suggestive of myocardial ischemia and normal coronary arteries at angiography. The possible mechanism that may participate in the pathology of CSX is a microvascular dysfunction related to inflammatory process affecting endothelium. Interferon gamma (IFN-gamma) is an important cytokine in inflammatory reaction. It acts through its specific receptor composed of 2 subunits IFN-gamma R1 (ligand binding) and R2 (signal transduction). The expression and proportion of these subunits influences IFN-gamma activity. The aim of the study was to assess the gene expression of IFN-gamma and its receptors in peripheral blood mononuclear cells (PBMC) from patients with syndrome X. METHODS: The study was carried out in 36 patients aged 44-77 (average 57 years old) with cardiac syndrome X and 23 sex- and age-matched healthy subjects (control group). To evaluate gene expression of IFNgamma and its receptor total mRNA was extracted from peripheral blood mononuclear cells (PBMC) and the number of mRNA copies were assessed by quantitive reverse transcriptase polymerase chain reaction (QRT-PCR). RESULTS: We have not observed statistically significant differences in INFgamma gene expression between studied group and control. Genes encoding IFNgamma receptor subunits showed higher expression in PBMCs from patients with cardiac syndrome X vs control subjects (IFNgammaR1, 97,244 +/- 26,956 c/microg vs 12,120 +/- 2,940 c/microg, p < 0.005, respectively and IFNgammaR2, 129,153 +/- 36,883 c/microg vs 16,445 +/- 2,923 c/microg, p < 0.005, respectively). CONCLUSION: Variation in transcriptional activity of genes encoding INF-gamma receptor subunits may affect function of microvasculature and thereby participate in the pathology of cardiac syndrome X.

[Laboratory diagnosis of changes in regulation of the immune system]. / Laboratornaia diagnostika izmeneniia reguliatsii immunnoi systemy.

To evaluate the body's immunity, to diagnose immunodeficiencies is a pressing problem. The paper discusses whether a complex approach can be used to evaluate immunity objectively. The data on humoral and cellular immunity in patients with varying responses to the changes occurring in the body are analyzed. The changes in cellular and humoral immunity were studied by enzyme immunoassay of hormones and antibodies in combination with immunomorphological assay of lymphocytic subpopulations.