Pathogenesis Of Cardiac Syndrome Research Articles

Receptor for advanced glycation end products gene polymorphisms in cardiac syndrome X.

Endothelial and microvascular dysfunction serve important roles in the formation and pathogenesis of cardiac syndrome X (CSX). Expression of receptor for advanced glycation end products (RAGE) is suggested to be increased in several conditions, including diabetes, inflammation and vascular diseases. In the present study, RAGE gene polymorphisms in patients with CSX and healthy controls were investigated. A total of 114 patients, diagnosed with CSX using coronary angiography results following complaints of angina and objective ischemia, and 103 healthy controls participated in the study. Whether there was a difference in genotype distributions of RAGE gene -374T/A, -429T/C and Glys82Ser polymorphisms between patients with CSX and healthy controls was investigated. Following DNA isolation from blood samples of the participants, the polymorphic regions were examined by quantitative polymerase chain reaction, and the genotyping results were statistically analyzed. When the genotypic distributions of -374T/A, -429T/C and Gly82Ser polymorphisms were investigated in patients with CSX and healthy controls, no statistically significant differences were identified between the two groups (P>0.05). Likewise, no statistically significant differences were observed in the allelic distributions of all 3 polymorphic regions (P>0.05). To the best of our knowledge, the present study also investigated the association between CSX and RAGE gene polymorphisms for the first time. No statistically significant differences in RAGE gene polymorphisms between the CSX and control groups were observed. We hypothesized that significant results may be obtained by increasing the numbers of patients and healthy controls in future studies.

Does Inflammation Have a Role in the Pathogenesis of Cardiac Syndrome X? A Genetic-Based Clinical Study With Assessment of Multiple Cytokine Levels.

We compared Turkish patients with cardiac syndrome X (CSX) and controls with respect to serum pro- and anti-inflammatory cytokine levels, as well as the single-nucleotide polymorphisms located in the promoter regions of their related genes. This study included 111 consecutive patients angiographically diagnosed with CSX and 111 healthy controls with similar demographic characteristics. Serum interleukin (IL) 6, tumor necrosis factor α (TNF-α), and IL-10 levels were measured, and the genotypes of the patients and controls were determined using standard methods. Serum IL-6 and IL-10 levels were significantly higher in the CSX group than in the control group (P < .01, respectively). Serum TNF-α level was lower in the CSX group than in the control group (P < .001). On the other hand, participants with CSX and healthy controls were not significantly different with respect to the genotype distributions of IL-6, TNF-α, and IL-10 genes. As a result of our study, both pro-inflammatory and anti-inflammatory cytokines may play a role in the pathogenesis of CSX. In contrast, the studied gene polymorphisms did not influence CSX pathogenesis.

Therapeutic Development in Cardiac Syndrome X: A Need to Target the Underlying Pathophysiology

Morbidity of patients with cardiac syndrome X (typical anginal-like chest pain and normal coronary arteriogram) is high with continuing episodes of chest pain and frequent hospital readmissions. Management of this syndrome represents a major challenge for the treating physician. Conventional therapies with antianginal agents such as nitrates, calcium channel antagonists, classic beta-adrenoceptor blockers and nicorandil have been tried, with variable success. However, this might be related to a failure to target the underlying pathophysiology and, clearly, more effective therapies are needed. Supporting evidence for the important role of endothelial dysfunction and oxidative stress in the pathogenesis of cardiac syndrome X has come from the recent observation that basal superoxide production predicts future cardiovascular events in this patient group. This review will discuss the pathophysiology, current medical management and potential new pharmacological treatment for patients with cardiac syndrome X which target endothelial dysfunction and oxidative stress. What's already known about this topic? Morbidity of patients with cardiac syndrome X is high. The important role of endothelial dysfunction and oxidative stress in the pathogenesis of cardiac syndrome X. What does this article add? This review will discuss the pathophysiology, current medical management and potential new pharmacological treatment for patients with cardiac syndrome X which target endothelial dysfunction and oxidative stress.

Elevated circulating inflammatory markers in female patients with cardiac syndrome X

Background. The pathophysiological mechanism in cardiac syndrome X has been suggested as impairment in normal endothelial function of the coronary microvasculature, resulting in inadequate flow reserve. However, despite the extensive studies, the precise mechanisms in cardiac syndrome X remain unclear. Purpose. The present study was, therefore, to investigate whether inflammatory cells and markers such as C-reactive protein (CRP) and interleukin-6 (IL-6) might be involved in the pathogenesis of cardiac syndrome X. Methods. Thirty-six female patients with cardiac syndrome X and 30 sex-matched normal controls were prospectively enrolled in this study. Blood samples were drawn for measuring white blood and monocyte cells, inflammatory markers such as CRP and IL-6, and data were compared between patients with cardiac syndrome X and normal controls. Results. The data showed that increased numbers of white blood and monocyte cells were found in patients with cardiac syndrome X compared with normal controls (white blood cells: 7072 ± 1146/mm 3 vs. 6138 ± 1079/mm 3; monocyte cells: 612 ± 186/mm 3 vs. 539 ± 190/mm 3 p < 0.05, respectively). Moreover, patients with cardiac syndrome X were detected to have significantly higher plasma CRP and IL-6 levels in comparison with patients with normal controls (CRP: 0.48 ± 0.26 mg/L vs. 0.22 ± 0.15 mg/L; IL-6: 13.4 ± 1.2 pg/dl vs. 6.2 ± 0.6 pg/dl, p < 0.01, respectively). The multivariate analysis showed that CRP was the independent variable most strongly associated with cardiac syndrome X. Conclusions. Our data suggested that low-grade, chronic inflammation might contribute to the development of cardiac syndrome X manifested by increased plasma levels of inflammatory cells and inflammatory markers.

Paraoxonase and arylesterase activities in patients with cardiac syndrome X, and their relationship with oxidative stress markers

Paraoxonase-1 is a high-density lipoprotein-associated enzyme with three activities, which are paraoxonase, arylesterase and dyazoxonase. Paraoxonase-1 was shown to decrease in patients with cardiovascular diseases. We aimed to examine serum paraoxonase and arylesterase activities, and their relation with oxidative stress markers such as lipid hydroperoxide and total antioxidant status in patients with cardiac syndrome X. Forty-one consecutive patients with cardiac syndrome X (CSX group), 33 consecutive patients without cardiac syndrome X (non-cardiac syndrome X group) and 20 healthy volunteers as control group were taken into the study. Serum paraoxonase and arylesterase activities were measured spectrophotometrically. Lipid hydroperoxide levels were measured by ferrous oxidation with xylenol orange assay. Total antioxidant status was determined using an automated measurement method. Basal paraoxonase, salt-stimulated paraoxonase and arylesterase activities were significantly lower in patients with cardiac syndrome X than those of the non-cardiac syndrome X and control groups (P<0.001, for both). Moreover, lipid hydroperoxide was found at high level, and total antioxidant status was found at low level in patients with cardiac syndrome X than control and non-cardiac syndrome X groups (P<0.001, for all). In patients with cardiac syndrome X, in multiple linear regression analysis, both paraoxonase and arylesterase activities were independently correlated with lipid hydroperoxide levels (P=0.001, P=0.003, respectively), and also arylesterase activity was independently correlated with magnitude of ST depression (P=0.002). Reduced paraoxonase and arylesterase activities and total antioxidant status levels and enhanced lipid hydroperoxide levels in patients with cardiac syndrome X might indicate increased oxidative stress that can play a role in pathogenesis of cardiac syndrome X.

Role of Inflammation and Endothelial Dysfunction in the Pathogenesis of Cardiac Syndrome X

Chest pain with normal coronary arteriograms represents a major diagnostic and therapeutic challenge to contemporary cardiology. Cardiac syndrome X (CSX), defined as typical angina-like chest pain, a positive response to exercise stress testing and normal coronary arteriograms, encompasses patients with a variety of pathogenic mechanisms. Cardiac ischemia has been documented in approximately 25% of CSX patients and is associated with endothelial dysfunction and microvascular vasodilator abnormalities. Increased endothelin-1, a powerful vasoconstrictor, has been suggested to play a pathogenic role. There is a high prevalence of postmenopausal women with CSX and thus estrogen deficiency has also been proposed to represent a possible pathogenic mechanism. Inflammatory mechanisms and endothelial dysfunction at the coronary microvascular level appear to be important in the pathogenesis of CSX. Treatment with agents that have protective effects on the vasculature and also anti-inflammatory properties, such as statins and angiotensin-converting enzyme inhibitors have been effective in improving both symptoms and electrocardiographic signs of myocardial ischemia in patients with CSX. This review discusses the roles for endothelial dysfunction and inflammation in the pathogenesis of CSX, as well as the potential therapeutic implications of these mechanisms.

Inflammation: A possible pathogenic link to cardiac syndrome X

Cardiac syndrome X is defined as a typical angina pectoris, positive treadmill exercise test, negative intravenous ergonovine test and normal coronary angiography. The pathogenesis of cardiac syndrome X has previously ascribed to myocardial ischemia that may be caused by microvascular dysfunction and increased sensitivity to intracardiac pain. Despite the extensive studies, the pathophysiological mechanisms in cardiac syndrome, however, remain unclear. More recently, the data has been suggested that chronic inflammation has been associated with cardiac syndrome X. The evidence for the hypotheses included that inflammatory marker are increased, and associated with the disease activity in patients with cardiac syndrome X. And also, statin, a lipid-lowering as well as anti-inflammatory drug, has significantly modified the disease process in this special syndrome. Despite the good prognosis of cardiac syndrome X, the chronic, frequent nature of the persistent angina and reduced exercise tolerance can significantly impair quality of life. Thus, lowering inflammatory response by, for example, use of statin and/or aspirin, might improve coronary microvascular dysfunction. Whether this is a valid approach, however, is still unknown and deserves further investigation. Indeed, as mediators of inflammation are multiple, the strategy of identifying triggers and mechanisms of inflammation in each special clinical setting and directing treatment at the special triggers or to rate limiting steps in effector pathways appears more reasonable or a promising strategy.

Provocation of Microvessel Spasm by Low-Dose Acetylcholine in Patients with Suspected Coronary Artery Disease

Endothelial dysfunction plays an important role in the pathogenesis of cardiac syndrome X, and intracoronary low-dose acetylcholine infusion is a widely used diagnostic modality for studying the coronary artery endothelial function. The authors herein report 2 cases of cardiac syndrome X with coronary artery endothelial dysfunction and microvessel spasm. The findings of non-invasive testing were positive for ischemia. Coronary angiograms appeared entirely normal in both cases. However, the intracoronary infusion of low-dose (1.5-15 microg/minute) acetylcholine demonstrated an impairment of the coronary blood flow response and consequently provoked an ST-segment elevation in an electrocardiogram. The coronary angiograms showed no spasm in the epicardial arteries. These patients are thus suggested to have cardiac syndrome X with microvessel spasms associated with coronary artery endothelial dysfunction.