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Abstract Introduction In the current systematic review and meta-analysis, we aim to analyze the existing literature to evaluate the role of inflammatory biomarkers, including neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), C-reactive protein (CRP), tumor necrosis factor-a (TNF-a), and interleukin-6 (IL-6) among individuals with cardiac syndrome X (CSX) compared to healthy controls. Methods We used PubMed, Web of Science, Scopus, Science Direct, and Embase to systematically search relevant publications published before April 2, 2023. We performed the meta-analysis using Stata 11.2 software (Stata Corp, College Station, TX). So, we used standardized mean difference (SMD) with a 95% confidence interval (CI) to compare the biomarker level between patients and healthy controls. The I2 and Cochran’s Q tests were adopted to determine the heterogeneity of the included studies. Results Overall, 29 articles with 3480 participants (1855 with CSX and 1625 healthy controls) were included in the analysis. There was a significantly higher level of NLR (SMD = 0.85, 95%CI = 0.55–1.15, I2 = 89.0 %), CRP (SMD = 0.69, 95%CI = 0.38 to 1.02, p

Introduction: In the current systematic review and meta-analysis, we aim to analyze the existing literature to evaluate the role of inflammatory biomarkers, including neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), C-reactive protein (CRP), tumor necrosis factor-a (TNF-a), and interleukin-6 (IL-6) among individuals with cardiac syndrome X (CSX) compared to healthy controls. Methods: We used PubMed, Web of Science, Scopus, Science Direct, and Embase to systematically search relevant publications published before April 2, 2023. We performed the meta-analysis using Stata 11.2 software (Stata Corp, College Station, TX). So, we used standardized mean difference (SMD) with a 95% confidence interval (CI) to compare the biomarker level between patients and healthy controls. The I2 and Cochran's Q tests were adopted to determine the heterogeneity of the included studies. Results: Overall, 29 articles with 3480 participants (1855 with CSX and 1625 healthy controls) were included in the analysis. There was a significantly higher level of NLR (SMD = 0.85, 95%CI = 0.55–1.15, I2 = 89.0 %), CRP (SMD = 0.69, 95%CI = 0.38 to 1.02, p < 0.0001), IL-6 (SMD = 5.70, 95%CI = 1.91 to 9.50, p = 0.003), TNF-a (SMD = 3.78, 95%CI = 0.63 to 6.92, p = 0.019), and PLR (SMD = 1.38, 95%CI = 0.50 to 2.28, p = 0.02) in the CSX group in comparison with healthy controls. Conclusion: The results of this study showed that CSX leads to a significant increase in inflammatory biomarkers, including NLR, CRP, IL-6, TNF-a, and PLR. [ABSTRACT FROM AUTHOR]

Introduction: Chronic coronary syndrome is predominantly related to the atherosclerotic obstruction of the coronary artery or arteries. However, this phenomenon is not the only causative factor in this disease. It is usually forgotten, that there is a possibility of ischemia of the cardiac muscle with no obstruction found in the main vessel. The trigger of such pathology might be underlying in the microcirculatory system and the inappropriate dilation or constriction of those small vessels, which results in insufficient blood supply to the cardiomyocytes, similarly to the typical obstructive coronary artery disease. In this article we are willing to show that such dysfunction poses a great danger to the health and life and therefore we should be able to properly diagnose and treat it. Purpose of the work: The aim of this review of up-to-date literature is to raise awareness among both doctors and patients about the phenomenon of coronary artery disease but with no significant obstruction in the vessels supplying the cardiac muscle. The common cause of such condition is coronary microvascular dysfunction, that leads to a disease called microvascular angina. Our purpose was to reveal, how dangerous to the health of the patients this could be and therefore how essential it is to provide a proper diagnose and management. In addition, we have noticed a need for a summary of what has already been discovered on this topic, available therapeutic methods and future perspectives.

Objectives: Treatment of cardiac syndrome X (CSX) remains a major challenge for conventional medicine. In this regard, developing new natural treatments could be an alternative choice. This study was planned to appraise the efficacy of chamomile-lemon balm syrup on chest pain and quality of life in patients with conventional drug-resistant CSX. Materials and Methods: 29 participants with conventional drug-resistant were enrolled in a single-arm clinical trial, and 14 participants completed the study protocol. Chamomile (Matricaria chamomilla L.)-lemon balm (Melissa officinalis L.) syrup was provided for the treatment for the 90-day study period. All conventional treatments of CSX remained unchanged. Efficacy assessment included Seattle Angina Questionnaires (SAQ), 36-item short form survey, and the Hospital Anxiety and Depression Scale (HADS). Results: An improvement was observed in the total score of all questionnaires with statistically significant changes over time of the study (P

Abstract İntroduction Patients with normal coronary arteries in whom increased vasospasm cannot be detected with the stress test should be evaluated in terms of cardiac syndrome x (CSX). İnflammatory systems are effective in endothelial activation and dysfunction in CSX. The systemic immune inflammation index (SII) is thought to be an important factor in determining the course of diseases, especially in infectious diseases or other diseases, as an indicator of the inflammation process. The aim of this study is to determine the role of SII levels in the diagnosis of CSX disease. Methods The study group included 80 patients who applied to the cardiology department of Fırat University with typical anginal complaints between October 2021 and April 2022, and were diagnosed with ischemia after the myocardial perfusion scan, and then coronary angiography was performed and normal coronary arteries were observed. Results When the study and control groups were examined according to age, gender and body mass index, hypertension, smoking, diabetes mellitus, dyslipidemia and family history, no statistical significant difference was observed between the groups. It was observed that there was a significant difference between the high sensitive C- reactive protin levels of the individuals in the study and control groups (p = 0.028). SII levels measured in samples taken from patients were significantly higher than control subjects (p = 0.003). SII cutoff at admission was 582 with 82% sensitivity and 84% specificity (area under the curve 0.972; 95% CI:0.95–0.98;p

Objectives: Treatment of cardiac syndrome X (CSX) remains a major challenge for conventional medicine. In this regard, developing new natural treatments could be an alternative choice. This study was planned to appraise the efficacy of chamomile-lemon balm syrup on chest pain and quality of life in patients with conventional drug-resistant CSX. Materials and Methods: 29 participants with conventional drug-resistant were enrolled in a single-arm clinical trial, and 14 participants completed the study protocol. Chamomile (Matricaria chamomilla L.)-lemon balm (Melissa officinalis L.) syrup was provided for the treatment for the 90-day study period. All conventional treatments of CSX remained unchanged. Efficacy assessment included Seattle Angina Questionnaires (SAQ), 36-item short form survey, and the Hospital Anxiety and Depression Scale (HADS). Results: An improvement was observed in the total score of all questionnaires with statistically significant changes over time of the study (P < 0.001). Conclusions: Chamomile-lemon balm syrup showed promising results in improving effect on angina symptoms, quality of life, and anxiety and depression in the patients with drug-resistant CSX. However, a placebo-controlled trial should be performed to verify these data. [ABSTRACT FROM AUTHOR]

İntroduction: Patients with normal coronary arteries in whom increased vasospasm cannot be detected with the stress test should be evaluated in terms of cardiac syndrome x (CSX). İnflammatory systems are effective in endothelial activation and dysfunction in CSX. The systemic immune inflammation index (SII) is thought to be an important factor in determining the course of diseases, especially in infectious diseases or other diseases, as an indicator of the inflammation process. The aim of this study is to determine the role of SII levels in the diagnosis of CSX disease. Methods: The study group included 80 patients who applied to the cardiology department of Fırat University with typical anginal complaints between October 2021 and April 2022, and were diagnosed with ischemia after the myocardial perfusion scan, and then coronary angiography was performed and normal coronary arteries were observed. Results: When the study and control groups were examined according to age, gender and body mass index, hypertension, smoking, diabetes mellitus, dyslipidemia and family history, no statistical significant difference was observed between the groups. It was observed that there was a significant difference between the high sensitive C- reactive protin levels of the individuals in the study and control groups (p = 0.028). SII levels measured in samples taken from patients were significantly higher than control subjects (p = 0.003). SII cutoff at admission was 582 with 82% sensitivity and 84% specificity (area under the curve 0.972; 95% CI:0.95–0.98;p < 0.001). Conclusion: It has been demonstrated that systemic SII parameters, which can be simply calculated with the data obtained from the complete blood count and do not require additional costs, can contribute to the prediction of CSX disease. [ABSTRACT FROM AUTHOR]

Guang-Yun Cao,1 Jian-Chao Li,1,2 Wen-Jing Wang,1 Hai-Bo Wu1 1Department of Cardiology, Hebei General Hospital, Shijiazhuang, Hebei Province, 050051, People’s Republic of China; 2HeBei North University, Zhangjiakou, Hebei Province, 050051, People’s Republic of ChinaCorrespondence: Hai-Bo Wu, Department of Cardiology, Hebei General Hospital, 348 Heping West Road, Shijiazhuang, Hebei Province, 050051, People’s Republic of China, Tel +86 15128138630, Email wuhb929@163.comObjective: This study aims to investigate the relationship between the neutrophil to lymphocyte ratio (NLR), the platelet to lymphocyte ratio (PLR), and cardiac syndrome X (CSX).Methods: A total of 102 patients with CSX who were hospitalized in the Cardiology Department of our hospital from December 2018 to December 2020 were enrolled in the CSX group, and 102 subjects who underwent physical examinations during the same period were included in the control group. An automatic blood cell analyzer was adopted to detect the neutrophil count (NC), lymphocyte count (LC), and number of platelets (PLT) in the whole blood of the subjects in both groups, and the NLR and PLR were calculated. Electrocardiography was conducted on the subjects in both groups to detect whether any abnormality existed in the ST segment. The receiver operating curve (ROC) was used to evaluate the diagnostic value of each indicator of CSX, and multivariate logistic regression analysis was adopted for the analysis of the influencing factors.Results: No significant differences existed in age, gender, smoking history, or family history of diabetes mellitus, hypertension, and tumors between the two groups (p > 0.05). When compared with the control group, the NC, PLT, NLR, PLR, and rate of abnormality of the ST segment on the electrocardiogram were significantly higher, and the LC was significantly lower in the CSX group (p < 0.05). Multivariate logistic regression analysis showed that the ST-segment abnormality (3.95 [2.10∼ 7.41]; NLR > 2.21, 3.46 [1.87∼ 6.39]; and PLR > 119.77, 3.66 [1.99∼ 6.73]) was a correlated risk factor for the occurrence of CSX (p < 0.05).Conclusion: Both the NLR and PLR in patients with CSX were significantly elevated, and both have a certain predictive value for the occurrence of CSX and are expected to be effective biomarkers for CSX.Keywords: cardiac syndrome X, neutrophil to lymphocyte ratio, platelet to lymphocyte ratio, correlation analysis, inflammation

Objective: The pathogenesis of elevated uric acid (UA) levels in patients with cardiac syndrome X (CSX) is unclear, and the results presented in recent papers on UA levels in patients with CSX are controversial. Therefore, we conducted a meta-analysis to assess the relationship between UA levels and CSX. Methods: Three databases, including the Web of Science, EMBASE and PubMed, were systematically searched until January 2022. Fixed-effect and random-effects models were used to analyze the relationship between UA levels and CSX. Subgroup analysis and sensitivity analysis were also performed. Results: Six studies involving 406 CSX patients and 267 non-CSX were included. Our results showed a significant relationship between UA levels and CSX, with a pooled SMD of 0.68 (95% CI 0.37 to 1.00; p < 0.0001). We also found a close relationship between UA levels and CSX for patients ≥ 55 years old (SMD:0.70, 95% CI: 0.41 to 0.99, p < 0.00001), for patients < 55 years old (SMD: 0.68, 95% CI: 0.25 to 1.12, p =0 .002), for women ≥ 60% (SMD: 0.77, 95% CI: 0.33 to 1.14, p =0 .0004), for women < 60% (SMD: 0.61, 95% CI:0.23 to 0.98, p =0 .001), for BMI ≥ 28 Kg/m² (SMD :0.61, 95% CI: 0.23 to 0.98, p =0 .001), for BMI < 28 Kg/m² (SMD: 0.75, 95% CI: 0.31 to 1.19, p =0 .0009), for publication years ≥ 2012 (SMD :0.69, 95% CI: 0.23 to 1.15, p = 0.003), for publication years < 2012 (SMD: 0.73, 95% CI:0.41 to 1.05, p < 0.00001), and for Turkey (SMD :0.75, 95% CI:0.38 to 1.11, p <.0001). Sensitivity analysis showed that the pooled results remained consistent after removing any one study or converting the random-effects model to fixed-effects model. Conclusion: Our results indicated a strong association between high UA levels and CSX. However, more well-designed studies are needed to investigate whether early treatment of hyperuricemia can reduce the incidence of CSX. [ABSTRACT FROM AUTHOR]

The systemic immune inflammation index (SII; platelet count x neutrophil-lymphocyte ratio), a new marker, predicts adverse clinical outcomes in many conditions, including acute and chronic coronary syndromes, pulmonary embolism, cancers, and contrast nephropathy. The aim of this study was to determine the relationship between SII and microvascular dysfunction in patients with Cardiac Syndrome X (CSX); 105 patients with CSX and 105 patients with normal coronary arteries were included. Microvascular dysfunction was determined angiographically using myocardial blush grade (MBG) and total myocardial blush score (TMBS). We observed that the SII levels were higher in the CSX (+) group (687 [355–2211] vs 418 [198–1614], P <.001). The SII levels were also found to be significant independent predictors for CSX in multiple regression analysis (P =.001). SII levels >440 had 83.8% sensitivity and 55.2% specificity (area under the curve [AUC]:.923, 95% CI:.895–.999, P <.001) for predicting CSX. There is a significant correlation between SII levels and CSX. [ABSTRACT FROM AUTHOR]

No hemodynamically significant atherosclerotic plaques are observed in up to 30% of patients reporting angina and undergoing coronary angiography. To investigate risk factors associated with non-obstructive coronary artery disease (NOCAD), we analyzed the medical records of, consecutively, 136 NOCAD subjects and 128 patients with significant stenosis in at least one coronary artery (the OCAD group). The blood concentrations of the TC (4.40 [3.78–5.63] mmol/L vs. 4.12 [3.42–5.01] mmol/L; p = 0.026), LDL-C (2.32 [1.80–3.50] mmol/L vs. 2.10 [1.50–2.70] mmol/L; p = 0.003), non-HDL-C (2.89 [2.29–4.19] mmol/L vs. 2.66 [2.06–3.39] mmol/L; p = 0.045), as well as the LDL-C/HDL-C ratio (1.75 [1.22–2.60] vs. 1.50 [1.10–1.95]; p = 0.018) were significantly increased in the NOCAD patients compared to the OCAD group due to the lower prevalence and intensity of the statin therapy in the NOCAD individuals (p < 0.001). Moreover, the abovementioned lipid parameters appeared to be valuable predictors of NOCAD, with the LDL-C (OR = 1.44; 95%CI = 1.14–1.82) and LDL-C/HDL-C (OR = 1.51; 95%CI = 1.13–2.02) showing the highest odds ratios. Furthermore, multivariable logistic regression models determined female sex as the independent risk factor for NOCAD (OR = 2.37; 95%CI = 1.33–4.20). Simultaneously, arterial hypertension substantially lowered the probability of NOCAD (OR = 0.21; 95%CI = 0.10–0.43). To conclude, female sex, the absence of arterial hypertension, as well as increased TC, LDL-C, non-HDL, and LDL-C/HDL-C ratio are risk factors for NOCAD in patients reporting angina, potentially as a result of poor hypercholesterolemia management. [ABSTRACT FROM AUTHOR]

PurposeCardiac syndrome X (CSX) is a condition with normal coronary angiography but angina pectoris. Chronic inflammation caused by Helicobacter pylori (H. pylori) infection may play a pathogenic role in CSX. Therefore, we conducted a meta-analysis to explore the relationship between H. pylori infection and risk of CSX.MethodsA systematic search in the Web of Science, Medline, Embase and Chinese databases (CNKI and Wanfang) was conducted up to October 2021. Articles on the association between H. pylori infection and the risk of CSX were included and were analyzed by R software (version 4.1.0).ResultsTen case-control studies involving 703 CSX patients and 731 healthy controls were included. H. pylori infection was associated with an increased risk of CSX (OR: 8.29, 95% CI: 4.64–14.82). We also found a significant association in those 25–40 years of age (OR: 1.34, 95% CI: 1.04–1.72), those 40–50 years of age (OR: 11.27, 95% CI: 4.29–29.61), those over 50 years of age (OR: 7.18, 95% CI: 3.59–14.36), those in developing countries [Iran (OR: 12.99, 95% CI: 8.61–19.60) and China (OR: 5.14, 95% CI: 3.09–8.56)]. However, this association was not apparent in a developed country [Italy (OR: 0.93, 95% CI: 0.37–2.33)].ConclusionsOur study suggested a possible association between H. pylori infection and the risk of CSX. Its pathogenicity is stronger in middle-aged individuals and some developing countries. However, more studies are needed to further investigate whether early eradication of H. pylori can reduce the incidence rate of CSX, especially in middle-aged individuals and some developing countries.

OBJECTIVE: Cardiac syndrome X (CSX) is typically described with ischemia in stress tests in addition to angina-like chest pain and without stenosis in coronary angiography. We aimed at determining the relationship between LMR and CSX. PATIENTS AND METHODS: We retrospectively collected patients with CSX between January 2016 and December 2019. Patients with typical angina-like chest pain, normal 12-lead electrocardiography at rest, a positive response to the exercise test (> 0.1 mV ST-segment depression at 80 ms after the J point in two or more contiguous leads) or ischemia on myocardial perfusion scintigraphy and normal coronary angiography were included in the study as CSX patients. RESULTS: This study consisted of 116 patients with CSX and 153 control groups. The mean age of the patients with CSX was 52.7±9.7 years, and the mean age of the control group was 53.7±10.6 years (p= 0.416). The patients with CSX were more likely to have higher monocyte counts and LMR. According to the Pearson correlation test, the CRP value negatively correlated with the LMR. In multivariate logistic regression analysis, LMR remained a significant predictor of CSX. In ROC analysis, LMR < 4.1 had 64% sensitivity and 50% specificity (ROC area under curve: 0.587, 95% CI: 0.519-0.655, p=0.015) in accurately predicting a CSX diagnosis. CONCLUSIONS: We showed that lower LMR levels were associated with the presence of CSX. [ABSTRACT FROM AUTHOR]

Background: Patients with chest pain may have normal coronary arteries and suffer from microvascular angina (MVA). The aim of this study was to determine if patients with suspected MVA have lower global myocardial perfusion (global MP) during adenosine stress compared with healthy controls and coronary artery disease (CAD) patients and to determine if there are sex differences in global MP. Methods: Twenty‐three patients with suspected MVA (66 ± 11 years), 19 CAD patients (69 ± 5 years) with stress‐induced ischaemia and 24 healthy controls (61 ± 10 years) underwent cardiac magnetic resonance (CMR) including coronary sinus flow measurements and first‐pass perfusion at rest and during adenosine stress. Global MP was quantified as coronary sinus flow normalized to left ventricular mass. Results: Global perfusion was lower during stress in patients with suspected MVA (2.9 ± 1.0 ml/min/g) compared with healthy volunteers (3.7 ± 1.1 ml/min/g, p = 0.018), but higher compared with CAD patients (2.0 ± 0.9 ml/min/g, p = 0.019). Female controls had higher global MP than male controls both at rest (1.0 ± 0.3 vs. 0.7 ± 0.2 ml/min/g, p = 0.003) and during stress (4.4 ± 1.0 vs. 3.1 ± 0.6 ml/min/g, p = 0.001). Furthermore, females with suspected MVA showed higher global MP than males with suspected MVA (3.3 ± 1.0 vs. 2.4 ± 0.7, p = 0.04). Conclusions: Patients with suspected MVA have lower global MP at stress than healthy volunteers but higher than patients with CAD. Furthermore, there seems to be a sex difference in global MP at stress both in healthy volunteers and in patients with suspected MVA, with higher global MP in females, which implies a need for sex‐specific normal limits when assessing quantitative MP. [ABSTRACT FROM AUTHOR]

Background and Aim: The aim of this study was to assess the nature of myocardial dysfunction in the cardiac syndrome X (CSX) and insignificant coronary artery disease (ICAD) using dobutamine stress echocardiography (DSE) and coronary calcium scoring (CAC). Methods: We prospectively studied 35 consecutive patients who complained of exertional angina, had ≥1 mm ST shift on exercise stress test but normal or no obstructive CAD (<50%) on angiography. Patients were divided into CSX (n = 27) with normal arteries and ICAD (n = 8) with insignificant stenosis. Results: CSX patients had more females, lower calcium score and less prevalent cardiac risk factors compared to ICAD (p < 0.05 for all). At peak stress, MAPSE and TAPSE failed to increase in both groups. LV septal and lateral s' increased in the two groups but the increment increase was less in CSX than ICAD (p < 0.05) while other diastolic indices did not differ between groups (p > 0.05 for all). CAC correlated modestly with LV and RV systolic velocities: septal s' (r = −0.65, p < 0.001) lateral s' (r = −0.35, p = 0.04) and right s' (r = −0.53, p = 0.005) in CSX, while in ICAD patients only with RV s' (r = −0.58, p = 0.02). On multivariate model, only septal s' OR 1.816 (1.1090–3.820, p = 0.04) proved the most powerful independent predictor of CAC. Conclusions: Compromised LV longitudinal systolic velocities were more pronounced and calcium score as a surrogate for atherosclerosis was lower in CSX than ICAD. These findings strengthen the evidence for different pathogenesis of CSX compared to ICAD, with microvascular disease in the former and calcification in the latter. [ABSTRACT FROM AUTHOR]

Literature reveals two kinds of menstruation-related anginas-cardiac syndrome X (CSX) and catamenial angina. CSX generally occurs in perimenopausal or postmenopausal women; catamenial angina affects females from puberty to menopause with existing/preexisting or predisposed to coronary artery disease. CSX involves recurring anginal-type retrosternal chest pains during exercise or rest with no significant findings on angiogram. Catamenial angina is menstruation-associated recurrent nonexertional left-sided chest pain alongside diaphoresis, hot flushes, and persistent lethargy. Pathophysiology of both anginas revolve around decreased levels of estrogen. Estrogen is known to act via genomic and nongenomic pathways on cardiomyocytes, endothelial cells, and smooth muscle cells to exert its cardioprotective effect. These cardioprotective effects could be lost during the postovulation phase and at the end of menstruation as well as during perimenopause or menopause owing to the decreased levels of estrogen. Evaluation should begin with a history and physical examination and focus on noninvasive tests such as exercise tolerance test, electrocardiogram, and echocardiogram. Reducing symptoms that cause discomfort and improving quality of life should be the main goal in management. Nitrates along with β blockers and analgesics for pain are the main pharmacologic modalities. Exercise training, smoking cessation, weight loss, and dietary changes are nonpharmacological modalities. Proper awareness and effective communication with patients or caregivers can lead to early diagnosis and treatment initiation., Competing Interests: Conflict of Interest None declared., (International College of Angiology. This article is published by Thieme.)