Evaluation of serum platelet-derived growth factor receptor-ß and brain-derived neurotrophic factor levels in microvascular angina.

OBJECTIVE: Microvascular angina (MVA) is a coronary microcirculation disease. Research on microcirculatory dysfunction has revealed several biomarkers involved in the etiopathogenesis of MVA. Platelet-derived growth factor receptor ß (PDGFR-ß) and brain-derived neurotrophic factor (BDNF) are 2 biomarkers associated with microcirculation, particularly pericytes function. The aim of this study was to investigate the role of PDGFR-ß and BDNF in MVA. METHODS: Ninety-one patients (median age, 56 y; age range, 40-79 y; 36 men) with MVA and 61 control group subjects (median age, 52 y; age range, 38-76 y; 29 men) were included in the study. Serum concentrations of PDGFR-ß and BDNF were measured with commercially available enzyme-linked immunosorbent assay kits. RESULTS: PDGFR-ß [2.82 ng/ml; interquartile range (IQR), 0.57-7.79 ng/ml vs. 2.27 ng/ml; IQR, 0.41-7.16 ng/ml; p<0.0005] and BDNF (2.41 ng/ml; IQR, 0.97-7.97 ng/ml vs. 1.92 ng/ml; IQR, 1.07-6.67 ng/ml; p=0.023) concentrations were significantly higher in patients with MVA compared with the controls. PDGFR-ß correlated positively with age (r=0.26, p=0.001), low-density lipoprotein (r=0.18; p=0.02), and BDNF (r=0.47; p<0.001), and BDNF showed a significant positive correlation with age (r=0.20; p=0.01). In binary logistic regression analysis, high-sensitivity C-reactive protein, uric acid, and PDGFR-ß values were found to be independent predictors of MVA. CONCLUSION: MVA is associated with higher PDGFR-ß and BDNF levels. This association may indicate an abnormality in microvascular function. Future studies are required to determine the role of these biomarkers in the pathogenesis of MVA.

Whole blood viscosity in microvascular angina and coronary artery disease: Significance and utility.

INTRODUCTION AND OBJECTIVES: Whole blood viscosity (WBV) is the intrinsic resistance of blood flow in vessels, and when elevated induces endothelial shear stress and endothelial inflammation and can accelerate the atherosclerotic process. This study aims to compare WBV levels in patients with microvascular angina (MVA), patients with coronary artery disease (CAD), and normal controls, and to identify the relationship between WBV and high-sensitivity C-reactive protein as a marker of inflammation in MVA and CAD. METHODS: A total of 573 patients were studied. The MVA group consisted of 189 subjects, the CAD group consisted of 203 subjects, and the control group consisted of 181 age- and gender-matched individuals. WBV was calculated from hematocrit and plasma protein concentration at a low shear rate (0.5 s-1) and high shear rate (208 s-1) by a validated equation. RESULTS: Patients with CAD and MVA had significantly higher WBV at both low and high shear rates compared to the control group. Correlation analysis revealed a significant relationship between high-sensitivity C-reactive protein and WBV at low (r=0.556; p<0.001) and high shear rates (r=0.562) in the CAD group and at low (r=0.475) and high shear rates (r=0.493) in the MVA group. CONCLUSIONS: Overall, this study demonstrated a significant and independent association between blood viscosity and the existence of endothelial inflammation and the atherosclerotic process.

Utility of discovery approach using proteomics to create a biomarker profile for coronary microvascular dysfunction.

INTRODUCTION: Coronary microvascular dysfunction (CMD) is a complex disease, difficult to diagnose and often requires advanced imaging. We used mass spectrometry (MS) using discovery approach to search for serum proteins as potential biomarkers in these patients. METHODS: We used serum samples from 10 patients with CMD and 10 with normal coronary flow reserve (CFR) admitted to an observation unit where acute myocardial infarction was excluded. We identified CMD using 82Rb positron emission tomography/computed tomography as CFR <2 in response to regadenoson, in the absence of coronary calcification or regional perfusion defects. We used MS to identify potential protein biomarkers that were differentially expressed in cases and controls. RESULTS: Baseline characteristics were not different between cases and controls, except for beta-blocker use and which was higher in cases, and mean (SD) CFR which was lower in cases [1.19 (0.23) and 2.78 (0.78) in cases and controls respectively; p < 0.01]. We identified 5345 peptides corresponding to 209 proteins, and identified 197 proteins by peptides with suitable properties to infer relative quantitation values. While the calculated values for some proteins (e.g. vascular cell adhesion molecule-1, apolipoprotein C and Von Willebrand Factor) indicate fold-differences between groups, these are most likely a result of high values in only 1-2 patients and are not statistically significant. CONCLUSION: Mass spectrometry using discovery approach may not be an adequate method for quantitative assessment of serum proteins in CMD patients. Future MS studies should evaluate other approaches including tissue samples or serial measurements.

Evaluation of serum sST2 and sCD40L values in patients with microvascular angina.

OBJECTIVES: Coronary microvascular dysfunction plays a major role in the pathogenesis of microvascular angina (MVA). Along with endothelial dysfunction, microvascular atherosclerosis and inflammation seem to contribute to the development of coronary microvascular dysfunction. Serum soluble ST2 (sST2) and serum soluble CD40 ligand (sCD40L) are two biomarkers associated with inflammation and atherosclerosis. The aim of this study was to investigate the role of these biomarkers in the pathogenesis of MVA and determine their possible association with coronary microvascular dysfunction. METHODS: A total of 152 patients were included in the study. Ninety-one patients with MVA {median age 56 years (40-79), of which 55 are women} and sixty-one controls {median age 52 (38-76), of which 29 are women} were included in the study. Serum concentration of sST2 and sCD40L were measured with a commercially available ELISA kit. RESULTS: Serum sST2 (median 13.6 ng/ml; interquartile range (IQR), 3.5-63.8 ng/ml vs median 10.6 ng/ml; IQR, 2.9-34.2 ng/ml, p < 0.0005) and sCD40L (median 5.3 ng/ml; IQR, 0.5-20.6 ng/ml vs median 2.2 ng/ml; IQR, 0.7-10.8 ng/ml, p < 0.0005) were significantly higher in patients with MVA compared to controls. Analysis of the associations between these biomarkers and potential contributors of MVA revealed that serum sST2 showed a positive correlation with LDL-cholesterol (r = 0.19, p = 0.016) and serum sCD40L concentrations correlated positively with hs-CRP (r = 0.22, p = 0.005). In logistic regression analysis, sCD40L and hs-CRP but not sST2 were found to be significantly associated with MVA. CONCLUSION: Higher serum concentrations of sST2 and sCD40L in MVA patients may be associated with inflammatory activation and coronary microvascular dysfunction. Larger studies are required for understanding their role in the pathogenesis of inflammatory and possibly fibrotic process in MVA patients.

Serum endocan levels in patients with cardiac syndrome X.

BACKGROUND: Endocan is a recently introduced marker of endothelial dysfunction and is also associated with inflammation and atherosclerosis. To date, the relationship between cardiac syndrome X (CSX) and endocan has not been studied. The objective of this study was to compare the serum endocan levels of patients with CSX with those of control subjects. PATIENTS AND METHODS: In this study, 50 patients were included in the CSX group and 28 patients in the control group. Patients with pathological conditions that could potentially influence endothelial functions were excluded. Endocan serum concentrations were measured using an enzyme-linked immunosorbent assay. RESULTS: The mean endocan level of the CSX group was significantly higher than that of the control group (3051.3 ± 1900.5 ng/l vs. 2088.1 ± 522.2 ng/l; p = 0.002). There was no difference between the two groups in terms of age, gender, hypertension, diabetes mellitus, dyslipidemia, and smoking status. In receiver operating characteristic (ROC) curve analysis, endocan levels greater than 2072 ng/l had a 72% sensitivity and 54% specificity (p = 0.002) for accurately predicting a diagnosis of CSX. CONCLUSION: The results of this study suggest that patients with CSX have higher endocan levels. Therefore, endocan may be valuable in helping uncover the underlying pathogenesis of CSX.

Hemorheological dysfunction in cardiac syndrome X.

BACKGROUND: Cardiac syndrome X (CSX) is often described as angina or angina-like chest pain with a normal coronary arteriogram, yet the underlying pathophysiological mechanisms have not been fully elucidated. The aim of the current study was to determine alterations in blood rheology (erythrocyte aggregation and deformability, plasma viscosity - PV) in patients with CSX. METHODS: The study comprised 26 CSX patients (55.77 ± 12.33 years) and 37 age- and sex-matched (56.32 ± 11.98 years) healthy controls. Erythrocyte aggregation and deformability were measured by an ektacytometer and PV with a rotational viscometer. RESULTS: Erythrocyte deformability measured at 1.69 and 3.00 Pa was lower in the CSX patients compared to the controls (p = .0001 and .017, respectively). Erythrocyte aggregation index (AI) (72.758 ± 7.65 vs. 66.483 ± 6.63, p = .002) and PV measured at a shear rate of 375 s-1 (1.932 ± 0.225 vs. 1.725 ± 0.331, p = .019) were significantly higher in patients with CSX. When AI, RDW and erythrocyte deformability measured at 1.69 Pa were evaluated together, it was observed that the increase in AI and RDW augments the risk of having CSX (OR: 1.2 and 2.65, respectively), while the rise in deformability decreases this risk (OR = 0.02). CONCLUSIONS: Hemorheological impairments are associated with CSX.

The APEX trial: Effects of allopurinol on exercise capacity, coronary and peripheral endothelial function, and natriuretic peptides in patients with cardiac syndrome X.

The role of endothelial dysfunction and oxidative stress in the pathogenesis of cardiac syndrome X has recently been recognized. Allopurinol has previously been shown to improve endothelial dysfunction, reduce oxidative stress burden, and improve myocardial efficiency. In this "proof of concept" study, we investigated the effect of allopurinol on exercise capacity, coronary and peripheral endothelial function, and serum B-type natriuretic peptide (BNP: a marker of cardiac function and myocardial ischemia) in patients with cardiac syndrome X. METHODS AND RESULTS: This study was a randomized, double-blind, placebo-control crossover trial. Nineteen patients (mean age 59 ± 10 years, 11 women and 8 men) with cardiac syndrome X were randomized to a 6-week treatment with either allopurinol (600 mg/day) or placebo. After 4 weeks of washout period, they were crossed over to the other arm. Outcomes measured at baseline and after treatment were maximum exercise time (ET) derived from Bruce protocol exercise treadmill test, serum BNP measurement, coronary flow reserve (CFR) as assessed by measuring the response of flow velocity in the left anterior descending artery to adenosine, and flow-mediated vasodilatation of the brachial artery (FMD). Allopurinol significantly reduced serum uric acid levels when compared with placebo (-48 ± 24% vs 1.9 ± 11%, P < .001). There was no significant difference in maximum ET, CFR, and FMD between allopurinol and placebo. However, there was a trend that allopurinol reduced serum BNP when compared to placebo (-8% [interquartile range -22% to 65%] vs 44% [interquartile range -18% to 140%]; P = .07). CONCLUSION: In patients with cardiac syndrome X, high-dose allopurinol did not improve exercise capacity, and coronary or peripheral endothelial function.

Increased monocyte-to-HDL cholesterol ratio is related to cardiac syndrome X.

OBJECTIVE: Cardiac syndrome X (CSX) is typically identified with ischaemia in treadmill exercise test or stress myocardial perfusion scintigraphy as well as angina-like chest pain without stenosis in coronary angiography. The purpose of the present study is to investigate the association between cardiac syndrome X and monocyte-to-HDL cholesterol ratio (MHR) which is a new marker associated with inflammation. PATIENTS AND METHODS: A total of 230 patients (105 patients with cardiac syndrome X and 125 normal controls) were included in the study. Peripheral venous blood samples were drawn from all study population before coronary angiography for measuring MHR and other haematological parameters. RESULTS: The patients with cardiac syndrome X were more likely to have higher platelet counts, plateletcrit (PCT), monocyte count and MHR values. Monocyte count and MHR of the CSX group were significantly higher than the control group [0.53 (0.35-1) vs. 0.49 (0.23-0.96); p = .002, .011 (0.006-0.038) vs. 0.010 (0.004-0.034); p < .001, respectively]. HDL-cholesterol levels of the CSX group were significantly lower than the control groups (46.3 ± 10.1 vs. 49.6 ± 11.6; p = .021). Higher MHR and PCT values were found to be associated with the presence of CSX by multivariate logistic regression analysis. CONCLUSIONS: Elevated MHR level independently was found in association with the presence of CSX. The value of MHR appears additive to conventional expensive methods commonly used in CSX prediction.

Differential expression of circulating vascular cell adhesion molecule-1 in subjects with coronary artery disease and cardiac syndrome X without known diabetes mellitus.

CONTEXT: Inflammation is one of the mechanisms underlying cardiac syndrome X (CSX). OBJECTIVES: Few studies have compared the expression of inflammatory or adhesion molecules between coronary artery disease (CAD) versus CSX. MATERIALS AND METHODS: Ninety-two CSX and 145 CAD subjects without known diabetes mellitus underwent coronary angiogram for angina. RESULTS: Vascular cell adhesion molecule (VCAM)-1 (median, 507 versus 431 ng/ml, p = 0.001) was significantly higher in the CAD group. In the binary regression, VCAM-1 was a significant differential factor for CAD versus CSX. DISCUSSION AND CONCLUSION: Adhesion molecules might be implicated in the differential expression of macro versus microvascular coronary disease. TRIAL REGISTRATION NUMBER: NCT01198730 at https://clinicaltrials.gov.

Hemorheological abnormalities and their associations with coronary blood flow in patients with cardiac syndrome X: a comparison between males and females.

AIM: The role of elevated whole blood viscosity (WBV) in the pathogenesis of atherosclerosis is well known. We sought to investigate the gender differences in the association between WBV, coronary blood flow and tissue oxygen delivery index (TODI) in cardiac syndrome X (CSX). METHODS: Forty-six CSX patients and 14 healthy volunteers were enrolled. The coronary flow parameters were obtained with transthoracic Doppler echocardiography and WBV was measured (at high-shear and low-shear rates of 300s-1 and 5s-1, respectively) using a scanning capillary tube viscometer. TODI was determined from the ratio of hematocrit to WBV measured at a low-shear rate of 5s-1. RESULTS: In male patients, the mean diastolic coronary flow velocity (CFV) and diastolic velocity time integral (VTI) were significantly decreased compared to control group (all p<0.05) and the WBV showed significant negative correlation with peak systolic CFV (r = -0.559 at 300s-1, r = -0.438 at 5s-1), mean systolic CFV (r = -0.577 at 300s-1, r = -0.488 at 5s-1), systolic VTI (r = -0.576 at 300s-1, r = -0.530 at 5s-1) and diastolic VTI (r = -0.553 at 300s-1, r = -0.551 at 5s-1) (all p<0.01). Meanwhile, although female patients showed no significant relationships between WBV and coronary flow parameters, TODI were significantly decreased compared to the control group (3.64 ± 0.34 vs. 4.07 ± 0.38%/centipoises (cP), respectively, p=0.008). CONCLUSION: Our study suggests that there are gender-related differences in the pathogenesis of microvascular angina and gender-specific approaches for CSX patients might be needed.

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.

Evaluation of thiol levels, thiol/disulfide homeostasis and their relation with inflammation in cardiac syndrome X.

OBJECTIVES: Cardiac syndrome X (CSX) is characterized by the presence of myocardial ischemia in the absence of coronary artery stenosis on angiograms. Its relation to oxidative stress and inflammation is well known. There are no data on thiols and their relation with inflammation in CSX. The aim of this study was to investigate thiol levels and thiol/disulfide homeostasis in CSX patients. MATERIALS AND METHODS: Fifty consecutive patients who had documented myocardial ischemia and normal coronary angiogram (CSX group), and 45 age-matched and sex-matched consecutive patients who had normal coronary angiogram without myocardial ischemia (control group) were enrolled in this study. C-reactive protein (CRP), neutrophil/lymphocyte ratio (NLR), native thiol, total thiol, and disulfide levels were measured and disulfide/thiol ratios were calculated in all patients. RESULTS: Demographic, clinical, basic laboratory, and echocardiographic characteristics were similar in the two groups (P>0.05). Serum total thiol, native thiol, and disulfide levels decreased significantly in the CSX group compared with the control group (P<0.001). CRP and NLR increased significantly in the CSX group compared with the control group (P<0.001). Although disulfide/native thiol levels increased in the CSX group, this reduction did not reach statistical significance (5.8 vs. 5.5, P>0.05). The reduction of thiols was correlated negatively with CRP and NLR (P<0.001). Although univariate logistic regression analyses showed that serum total and native thiol levels, CRP and NLR were independent predictors for CSX estimation, stepwise multivariate logistic regression analysis showed only total thiol levels as an independent predictor for CSX (odds ratio=0.966, 95% confidence interval: 0.950-0.982, P<0.001). Also, receiver operating characteristic curve analysis showed that serum total thiol values of 338.4 or below could predict the CSX with 86% sensitivity and 84% specificity (area under curve=0.903; 95% confidence interval: 0.842-0.965). CONCLUSION: Serum total thiol levels decreased significantly in CSX and this reduction independently predicted CSX with strong sensitivity and specificity. This suggests that the reduction in thiols along with increased inflammation may play a pathophysiological role in the development of CSX.

Human Endothelial Cell-Specific Molecule-1 (Endocan) and Coronary Artery Disease and Microvascular Angina.

Endothelial cell-specific molecule-1 (endocan) is an immunoinflammatory marker linked to endothelial activation and dysfunction. We investigated the relationship between obstructive coronary artery disease (CAD), microvascular angina (MVA), and plasma levels of endocan. We included 53 healthy individuals as controls, 40 MVA patients, and 120 patients with obstructive CAD. The severity of CAD was assessed by the Gensini and SYNergy between percutaneous coronary intervention with TAXUS and Cardiac Surgery (SYNTAX) scores. Endocan levels were 382.7 (313.8-470.2) pg/mL in patients with obstructive CAD; 324.3 (277.1-460.7) pg/mL in MVA group, and 268.0 (226.4-336.5) pg/mL (P < .001) in controls. Endocan levels in obstructive CAD and MVA groups were similar but both were significantly higher than for the control group (P < .001 and P = .002, respectively). In subgroup analysis, similar to the hypertensive subgroup results, endocan was still an independent predictor of presence of obstructive CAD in normotensives (odds ratio = 1.005, 95% confidence interval = 1.001-1.010, P = .024). There was also an independent positive correlation between endocan levels and SYNTAX score both in the hypertensives (ß = 0.414, t = 3.21, P = .002) and in the normotensives (ß = .301, t = 2.23, P = .031). In conclusion, endocan could be a common predictor of the endothelium-dependent inflammatory processes, rather than related with specific risk factors.

Relationship between neutrophil-to-lymphocyte ratio and impaired myocardial perfusion in cardiac syndrome X.

OBJECTIVE: Myocardial tissue perfusion is decreased in patients with cardiac syndrome X (CSX). Systemic inflammation appears to be an important contributor to the diseased microvascular network of these patients. The neutrophil-to-lymphocyte ratio (NLR) is a surrogate marker of inflammation. Accordingly, we evaluated this biomarker concerning the microvascular circulation of CSX patients. PATIENTS AND METHODS: This study included 60 consecutive patients (54.1 ± 7.8 years of age, 49 females) with CSX (typical chest pain, positive exercise stress test results, and normal coronary angiograms) and 60 consecutive age- and sex-matched control subjects. In all coronary territories, epicardial coronary flow was assessed by the Thrombolysis In Myocardial Infarction frame count (TFC) method, and myocardial tissue perfusion was assessed by the myocardial blush grade (MBG) method. Normal myocardial perfusion was accepted as an MBG score of 3 in all coronary territories. RESULTS: Patients with CSX had higher NLRs than those of control subjects (1.98 ± 0.77 vs 1.72 ± 0.55, respectively; p = 0.04). Among patients with CSX, those with impaired myocardial perfusion had higher NLRs than those with normal myocardial perfusion (2.13 ± 0.82 vs 1.71 ± 0.59, respectively; p = 0.028). There was a negative correlation between the NLR and total MBG score (p = 0.027, r = -0.29). Logistic regression analysis showed that the NLR was an independent and negative predictor of myocardial tissue perfusion (p = 0.027; Beta, -1.057; odds ratio, 2.878; 95% confidence interval, 1.129-7.335). CONCLUSIONS: Patients with CSX have high NLRs, and inflammation seems to be associated with distorted myocardial perfusion in these patients.

Interleukin-10 promotor -592A/C polymorphism is associated with slow coronary flow in Han Chinese.

An accumulating body of evidence suggests that slow coronary flow (SCF) phenomenon seems to be an early-form of atherosclerosis and low-grade inflammation plays a major role in the atherosclerotic vascular processes. Interleukin (IL)-10 is a multifunctional cytokine involved in both innate and adaptive immune response. The aim of the present study is to investigate the association of IL-10 gene -592A/C polymorphism with SCF in Han Chinese. 250 patients who underwent coronary angiography and had angiographically normal coronary arteries of varying coronary flow rates without any atherosclerotic lesion were enrolled in this study. Patients who had thrombolysis in myocardial infarction frame counts (TFC) above the normal cutoffs were considered to have SCF and those within normal limits were considered to have normal coronary flow (NCF). The PCR-based restriction fragment length polymorphism (PCR-RFLP) technique was used to assess the genotypes frequencies. The distribution of the IL-10 -592A/C genotypes (AA, AC, and CC) was 46.34%, 41.46%, and 12.20% in the NCF group, and 66.51%, 28.71%, and 4.78% in SCF subjects, respectively (P = 0.0280). The frequency of the A allele in the SCF group was significantly higher than that in the NCF group (80.86% vs. 67.07%, P = 0.0054). Compared with the CC genotype, the AA genotype had increased risk of SCF in both unadjusted and adjusted analyses. In SCF patients, the average serum IL-10 levels in AA genotype were statistically lower than in AC + CC genotype (P = 0.0000). These findings suggest that IL-10 -592A/C polymorphism is associated with SCF and the A allele has increased risk for SCF in Han Chinese.

Evaluation of adiponectin and lipoprotein(a) levels in cardiac syndrome X.

AIMS: Low adiponectin and high lipoprotein(a) [Lp(a)] levels are associated with endothelial dysfunction, atherosclerosis, and coronary artery disease. Cardiac syndrome X (CSX) is characterized by anginal symptoms, positive stress test, and documentation of normal epicardial coronary arteries with angiography. In this study we aimed to investigate the relationship between CSX and circulating levels of adiponectin and Lp(a). PATIENTS AND METHODS: We enrolled 53 female patients with CSX and 33 patients as the control group. The diagnosis of CSX was made according to presence of angina, findings suggestive of ischemia during stress electrocardiography or myocardial perfusion scintigraphy, and documentation of normal coronary arteries in coronary angiography. The control group consisted of patients with atypical angina and normal stress electrocardiography test results. Both groups were matched in terms of hypertension, diabetes mellitus, and metabolic syndrome. RESULTS: Adiponectin levels were significantly decreased in patients with CSX (4.57 µg/ml vs. 13.18 µg/ml; p=0.001); however, Lp(a) levels were significantly increased (36.30 mg/dl vs. 7.24 mg/dl; p < 0.001). Low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), and triglycerides (TG) concentrations did not differ between the case group and the control group (p=0.14, p=0.62, p=0.64, respectively). There was no significant difference between groups in terms of age, body mass index, waist circumference hypertension, hyperlipidemia, diabetes mellitus, or metabolic syndrome. In multivariate analysis, Lp(a) and adiponectin were found to be independent predictors of CSX. An Lp(a) level of > 21 mg/dl had 84 % sensitivity and 96 % specificity {area under the curve (AUC)= 0.922, p < 0.0001, 95 % CI [0.842-0.970]} and an adiponectin level of ≤ 5.18 µg/ml also had 58.7 % sensitivity and 82.1 % specificity (AUC=0.726, p=0.0003, 95 % CI [0.609-0.823]) for detecting CSX. CONCLUSION: We detected low adiponectin and high Lp(a) levels in patients with CSX and these findings may be related to the microvascular injury in CSX.

A prospective study of C-reactive protein as a state marker in Cardiac Syndrome X.

Cardiac Syndrome X (CSX), the presence of angina pectoris despite normal epicardial coronary arteries seen on invasive angiography, is known to be associated with an elevation of several inflammatory biomarkers, suggesting a possible role for inflammation in its pathogenesis. We sought to establish if C-reactive protein (CRP) levels varied with disease severity and so whether it is a state or trait marker. We studied 16 CSX patients with typical angina pectoris, normal coronary arteries and an electrically positive exercise stress test (EST) and 13 age- and sex-matched healthy controls (HC). CSX patients were followed up at a subsequent visit with repeated exercise stress testing and CRP measurement. We found that CRP levels were significantly higher in the CSX group compared to the HC (1.5 [0.8-4.5] v 0.8 [0.4-1.4] mg/L, p=0.02). This elevation in CRP persisted throughout the study length. CRP correlated with time to symptoms on EST at enrolment and at the second visit (r=-0.690, df=10, p=0.013 and r=-0.899, df=4, p=0.015, respectively). At the follow-up visit, 50% of CSX patients developed electrically and symptomatically negative ESTs. The mean CRP of this group was significantly lower than that of the CSX patients with ongoing symptoms and positive ESTs (1.2±0.2 v 2.8±0.6mg/L, p=0.018) and did not differ significantly from that of healthy controls. CRP levels also dropped in patients whose symptoms improved while they increased in patients who became more symptomatic (p=0.027). We conclude that the results of this small study support the concept of CSX being an inflammatory-mediated condition with CRP levels prospectively varying with functional measures of disease severity. This indicates that CRP is a state marker in CSX.

The relationship between eosinophil and cardiac syndrome X.

AIM: The pathophysiology of cardiac syndrome X (CSX) has not been clearly identified, although multiple abnormalities including microvascular spasm, endothelial dysfunction, and atherothrombosis have been reported. It is known that eosinophils play an important role in vasoconstruction and thrombosis. We aimed to compare the eosinophil counts in patients with CSX versus controls. MATERIALS AND METHODS: This study included 50 patients with CSX (20 male, mean age 50.42 ± 9.6 years) and 30 control persons (10 male, mean age 49.16.11 ± 9.2 years). These participants underwent concurrent routine biochemical tests, and their eosinophil counts were obtained on whole blood count. These parameters were compared between groups. RESULTS: Baseline characteristics of the study groups were comparable. Patients with CSX had a higher eosinophil count and mean platelet volume (MPV) value than the controls (339.4 ± 188 vs 132.7 ± 75 and 8.8 ± 0.2 vs 7.2 ± 0.1 fL; P < .001, respectively). CONCLUSION: As a result, our study revealed a relationship between eosinophil count and MPV in patients with CSX.

Intermittent warm blood versus cold crystalloid cardioplegia for myocardial protection: a propensity score-matched analysis of 12-year single-center experience.

OBJECTIVES: This study analyzes the efficacy in myocardial protection of two types of cardioplegia solutions, namely, blood and crystalloid cardioplegia, both given intermittently in patients undergoing coronary artery bypass grafting (CABG). METHODS: Adult patients undergoing primary isolated coronary artery bypass grafting between January 1998 and January 2011 with cardiopulmonary bypass, using either blood or crystalloid cardioplegia, were identified in our database. Propensity score matching was performed to create comparable patient groups. Multivariate logistic regression analysis was performed to identify independent risk factors for perioperative myocardial damage. The primary endpoint of the study was the maximum creatine kinase-MB (CK-MB) value within 5 days postoperatively with a cut-off point of 100 U/L. Early mortality and perioperative low cardiac output syndrome in both groups were compared. RESULTS: The study included 7138 CABG patients: 3369 patients using crystalloid cardioplegia and 3769 using blood cardioplegia. After propensity score matching, 2585 patients per study group remained for the analysis. Wilcoxon signed-rank test revealed significantly higher CK-MB levels in patients operated with the use of blood cardioplegia. Multivariate regression analysis identified blood cardioplegia as an independent risk factor for elevated CK-MB levels. However, it was associated with lower aspartate aminotransferase (AST) levels. The type of cardioplegia had no influence on early mortality, postoperative low cardiac output syndrome or intensive care unit stay. CONCLUSIONS: Blood cardioplegia was identified as an independent risk factor for elevated levels of CK-MB after CABG, but was associated with lower AST levels. The authors conclude that the type of cardioplegia had no significant influence on clinical outcome.