Asife Sahinarslan

Plasma neutrophil gelatinase-associated lipocalin levels in acute myocardial infarction and stable coronary artery disease

IntroductionInflammation and polymorphonuclear neutrophils are shown to be important in the pathogenesis of acute myocardial infarction (AMI). Neutrophil gelatinase-associated lipocalin (NGAL) is secreted from neutrophils and may increase the proteolytic activity within the atherosclerotic plaque. We aimed to investigate whether the plasma levels of NGAL are higher in patients with AMI compared with stable coronary artery disease (CAD). MethodsThe study population consisted of 128 eligible patients who underwent coronary angiography with the clinical diagnosis of CAD. Of the 128 patients included in the study, the diagnosis was ST-segment elevation myocardial infarction (STEMI) in 53 patients, non-ST-elevation myocardial infarction (NSTEMI) in 38 patients and stable CAD in 37 patients. Plasma level of NGAL was measured in all patients with an enzyme-linked immunosorbent assay method. We compared the plasma NGAL levels among the groups. ResultsWe found higher plasma NGAL levels in patients with AMI compared with the patients with stable CAD (146±23 vs. 101±53 ng/ml, P<0.001). The plasma NGAL levels between the subgroups of AMI were similar (145±23.9 vs. 145±23.4 ng/ml, P=not significant). In multivariate analysis, the independent factors related to AMI were current smoking (P=0.024), extent and severity of coronary atherosclerosis (P=0.030), and NGAL levels. The plasma NGAL level was independently related to the existence of AMI (odds ratio: 1.045, 95% confidence interval: 1.019–1.072, P=0.001). In patients with plasma NGAL level above 127 ng/ml, we observed a 12 times higher incidence of AMI (odds ratio: 12.2, 95% confidence interval: 2.3–64, P=0.003). ConclusionThe plasma level of NGAL is higher in patients with AMI compared with the patients with stable CAD. This finding may suggest an active pathophysiological role for NGAL in development of acute coronary events.

Association of serum total bilirubin level with severity of coronary atherosclerosis is linked to systemic inflammation.

OBJECTIVE Although cardiovascular protective action of bilirubin has been attributed to its antioxidant effect, there was scarce data regarding the anti-inflammatory properties. Herein, we aimed to assess the relationship between serum total bilirubin level and severity of coronary artery disease (CAD) in association with the direct inflammatory marker such as C-reactive protein (CRP), the other indirect markers included in inflammation process such as neutrophil to lymphocyte ratio (NLR) and red cell distribution width (RDW) in patients with stable CAD. METHODS Angiographic data of 1501 patients were analyzed in this retrospective cross-sectional study. Patients were categorized according to Gensini scores as control, mild CAD and severe CAD groups. The association of clinical and laboratory parameters with the severity of CAD were determined by multivariable linear regression analysis. RESULTS Total bilirubin level in the control group was significantly higher than those of the other groups. After multivariable linear regression analysis total bilirubin [β=-3.131 (-4.481, -1.782), p<0.001] was significantly associated with the severity of CAD. Futhermore, there was a moderate and significant inverse correlation between serum total bilirubin level and the severity of CAD (r=-0.173, p<0.001), CRP (r=-0.112, p<0.001), NLR (r=-0.070, p=0.026) and RDW (r=-0.074, p=0.027). CONCLUSION Serum total bilirubin level was independently and inversely associated with the severity of coronary atherosclerosis in patients with stable CAD. In addition, total bilirubin level was inversely correlated with CRP, NLR and RDW. These results suggest that besides its already known effect on the oxidative stress, higher serum total bilirubin level may exhibit an anti-inflammatory effect in the coronary atherosclerotic process.

Asymmetrical dimethylarginine level in atrial fibrillation

Objective — Atrial fibrillation (AF) is known to be related with increased risk of thromboembolic events. Asymmetrical dimethylarginine (ADMA), which is an endogenous inhibitor of nitric oxide synthase (NOS), can cause endothelial dysfunction by decreasing nitric oxide (NO) and lead to increased risk of thrombosis. In the present study our aim was to compare plasma levels of ADMA in patients with acute onset (< 24 hours) and chronic AF (> 1 year) to determine the risk of thrombosis. Method — 17 patients with the first detected attack of AF within the first 24 hours of presentation (group I), 25 patients who had permanent chronic AF lasting at least 1 year or more (group II) and 18 healthy persons as the control group (group III) were included in the study. For each patient the plasma ADMA, L-arginine, symmetrical dimethylarginine (SDMA) concentrations were measured by high-performance liquid chromatography in venous blood samples collected before cardioversion. We compared the plasma ADMA, L-arginine and SDMA concentrations between the groups. Results — Plasma L-arginine (78.18 ± 28.29 vs. 73.14 ± 14.11 vs. 71.03 ± 21.31, P = 0.549) and plasma SDMA concentrations (0.38 ± 0.18 vs. 0.42 ± 0.21 vs. 0.32 ± 0.24, P = 0.224) were similar in all groups. There was a significant difference between plasma ADMA concentrations (0.76 ± 0.27 vs. 0.50 ± 0.26 vs. 0.36 ± 0.20, P < 0.001) among the groups.When we compared plasma ADMA levels between the subgroups, we also found a significant difference (P = 0.002 when comparing group I and group II, P < 0.001 when comparing of group I and group III, P = 0.042 when compareng of group II and group III). Conclusion — ADMA levels in patients with acute onset AF were significantly increased when compared with patients with chronic AF and the healthy control group indicating the presence of endothelial dysfunction and a prothrombotic state even in a very early phase of AF.

B-type natriuretic peptide and extent of lesion on coronary angiography in stable coronary artery disease.

ObjectiveAlthough it is well established that plasma B-type natriuretic peptide (BNP) levels are higher in patients with acute coronary syndromes, the relationship between plasma BNP level and stable coronary artery disease is not clear. The aim of this study was to examine the relationship between plasma BNP levels and the extent of obstructive lesions on coronary angiography in stable coronary artery patients. MethodsPlasma BNP concentrations were measured in 62 patients with a diagnosis of stable angina pectoris who had a left ventricular ejection fraction (LVEF) ≥45% on echocardiographic evaluation. Coronary angiography was performed for all patients, who were than divided into two groups according to the results of the angiography. Group I consisted of the patients who had a lesion leading to an obstruction of the lumen in any coronary artery by less than 50% or those who had normal coronary arteries. All other patients constituted group II. ResultsIn group I (n=26), the mean plasma BNP level was 64.8±29.5 pg/ml. In group II (n=36), it was 99.7±55.4 pg/ml. BNP was significantly higher in group II (P=0.007) than group I. The BNP concentration of the patients with one-vessel disease (n=12), two-vessel disease (n=16), and three-vessel disease (n=8) were 77.9±34.9 pg/ml, 109.3±67.9 pg/ml, 113.3±48.1 pg/ml consecutively. In this respect, the plasma BNP was significantly higher in the groups with more extended vessel disease (P=0.02). When we compared the patients according to involvement of left anterior descending artery (LAD), BNP levels were significantly higher in this group, (116.1±55.8 pg/ml versus 64.1±30.2 pg/ml; P=0.001). ConclusionPlasma levels of BNP were higher in patients who have stable coronary artery disease with preserved left ventricular systolic function. The level of increase in plasma BNP concentration was positively correlated with the extent of lesion and LAD involvement on coronary angiography.

Independent relationship of serum uric acid levels with leukocytes and coronary atherosclerotic burden.

BACKGROUND AND AIM Epidemiological studies have shown that increased serum uric acid (SUA) level is associated with coronary artery disease (CAD). Leukocytes have been shown to play an important role in the atherosclerotic process. The aim of the study was to investigate whether there is any relationship among SUA, leukocyte counts and coronary atherosclerotic burden in patients who are suspected of having CAD. METHOD AND RESULTS We enrolled 690 eligible patients who had undergone coronary angiography between October 2005 and June 2006 in a consecutive manner. The relationship of SUA with total and differential leukocyte counts and CAD was investigated. Serum uric acid levels (5.57+/-1.64 vs 4.63+/-1.27 mg/dl, p<0.001) and leukocytes were higher in patients with CAD than those with normal coronary arteries (NCA). When we divided the patients into four groups according to the quartiles of SUA, we found that the monocyte count was prominently related with SUA (478+/-165, 553+/-177, 565+/-199 and 607+/-229 mm(-)(3), Q1-Q4, p<0.001). In multivariate analysis, SUA was an independent predictor of CAD (OR, 1.270; 95% CI, 1.087-1.484, p=0.003). When we performed multiple linear regression analyses to determine the independent predictors of inflammatory cells in blood, we found a strong, positive and independent relationship between SUA with neutrophils (beta+/-SE: 206+/-60, p=0.001) and monocytes (beta+/-SE: 35+/-7, p<0.001). CONCLUSION Our study results demonstrated that neutrophils and monocytes which play an important role in inflammation and atherosclerosis were independently related with SUA. This finding suggests an important epidemiologic relation and may provide a possible causative mechanism of SUA in atherosclerotic process.

Plasma asymmetric dimethylarginine and L-arginine levels in patients with cardiac syndrome X.

BackgroundEndothelial dysfunction and subsequently impaired microvascular circulation are the leading mechanisms in the development of cardiac syndrome X (CSX). The study evaluated the plasma asymmetric dimethylarginine (ADMA) and L-arginine levels of the patients with CSX and the control group and aimed to determine any relationship between these parameters and epicardial coronary blood flow and myocardial tissue perfusion. MethodsThe study group consisted of 32 patients (mean age: 52.6±9.4 years, 14 men) with typical exertional angina, positive exercise test, and normal coronary arteries diagnosed as CSX. Plasma ADMA, L-arginine levels, and L-arginine/ADMA ratio were compared with the values of the control group, which consisted of 17 age-matched and sex-matched individuals. Concentrations of L-arginine and ADMA were measured by high-performance liquid chromatography. In all the coronary territories, epicardial coronary flow was assessed by thrombolysis in myocardial infarction (TIMI) frame count (TFC) method, and tissue level perfusion, by myocardial blush grade (MBG) method. A MBG score less than 3 was considered an impaired myocardial perfusion, and a MBG score of ‘3’ in all the coronary territories, a normal myocardial perfusion. ResultsThe plasma ADMA levels of the study group were higher than those of the control group (0.83±0.38 vs. 0.55±0.44 μmol/l, P=0.03), whereas plasma L-arginine levels were similar in both groups (70.25±21.89 vs. 76.09±18.22 μmol/l, P=0.36), resulting in a diminished L-arginine/ADMA ratio in the patients with CSX [82.3 (60.2–128.8) vs. 242.2 (76.7–386.4), P=0.003]. In CSX group, the patients with abnormal myocardial tissue perfusion had increased plasma ADMA levels compared with those with normal tissue perfusion (0.99±0.37 vs. 0.69±0.34 μmol/l, P=0.02), whereas plasma L-arginine levels were similar in both groups. No correlations were observed between TFC values and plasma ADMA, L-arginine levels, and L-arginine/ADMA ratio. Plasma ADMA levels, however, were negatively correlated with MBG scores (r=−0.349, P=0.014). ConclusionWe have shown for the first time that in the patients with CSX, increased plasma ADMA levels might be associated with impaired myocardial tissue perfusion when assessed by MBG.

The importance of fragmented QRS complexes in prediction of myocardial infarction and reperfusion parameters in patients undergoing primary percutaneous coronary intervention.

OBJECTIVES The QRS complex fragmentations (fQRS) frequently seen on admission electrocardiograms (ECGs) with narrow or wide QRS complex are associated with increased morbidity and mortality. The causative relationship between fQRS and cardiac fibrosis is known, but the relation of fragmented QRS before and after primary percutaneous coronary intervention (p-PCI) with myocardial infarction and reperfusion parameters has not been studied until now. STUDY DESIGN The study included 184 consecutive patients with ST elevation myocardial infarction (STEMI) who underwent p-PCI. Presence or absence of fQRS on pre- and post-PCI ECGs and its change following PCI were investigated. In addition, independent predictors of fQRS were also investigated. Patients with significant organic valve disease and patients having any QRS morphology with QRS duration ?120 ms as well as patients with permanent pacemakers were excluded from the study. RESULTS Patients with fQRS on admission ECG had higher leukocyte counts (p=0.001), higher CK-MB (p=0.001) and troponin levels (p=0.005), increased pain to balloon time (p=0.004), higher Killip score (p<0.001), prolonged QRS time (p<0.001), higher Gensini score (p<0.001) and more frequent Q waves on ECG (p<0.001) in comparison to patients with non-fragmented QRS. In addition, these patients usually had an infarction of anterior territory related to a lesion in proximal LAD and wider jeopardized myocardium (p<0.001). fQRS was significantly related to infarction and myocardial reperfusion parameters before and after p-PCI. In the setting of STEMI, absence of fQRS on admission ECG predicted increased ST resolution, higher reduction in QRS duration, and better myocardial reperfusion. CONCLUSION FQRS may be useful in identifying patients at higher cardiac risk with larger areas of ischemic jeopardized or necrotic myocardium.

Effect of serum YKL-40 on coronary collateral development and SYNTAX score in stable coronary artery disease

OBJECTIVE Many studies have revealed a role of YKL-40 as a new inflammatory biomarker in angiogenesis, inflammation, atherosclerosis and cardiovascular events. Thus, the aim of this study was to investigate the association of serum YKL-40 level with coronary collateral development and SYNTAX score in patients with stable coronary artery disease. METHODS A total of 165 patients who had ≥90% stenosis in at least one major coronary artery were prospectively enrolled in the study. Collateral degree was graded according to Rentrop-Cohen classification. Patients with grade 2 or 3 collateral degree were included in good collateral group and patients with grade 0 or 1 collateral degree were included in poor collateral group. The patients were also classified according to SYNTAX criteria, those with low (≤22) and those with high (>22) SYNTAX score. RESULTS Serum YKL-40 and hs-CRP levels were significantly lower in good collateral group. Furthermore, YKL-40 level showed significant positive correlations with SYNTAX score (r=0.486, p<0.001) and hs-CRP level (r=0.340, p<0.001). In multivariate regression analysis, serum YKL-40 (odds ratio: 0.928; 95% confidence interval: 0.917-0.940; p<0.001), duration of ischemic symptom and total occlusion were independent predictors of good collateral development. In ROC curve analysis, a YKL-40 value cut-off point of ≥168.5 predicted the high SYNTAX score with a sensitivity of 81.0% and specificity of 72.4%. CONCLUSIONS Increased serum YKL-40 level was related with poor collateral development and high SYNTAX score. According to these findings YKL-40 can be used as a predictor of good collateral development and high SYNTAX score.

The reliability of fractional flow reserve measurement in patients with diabetes mellitus.

BackgroundFractional flow reserve (FFR) is an invasive method to assess the functional significance of coronary stenoses. The value of FFR in diabetic patients is controversial because of microvascular dysfunction. The aim of this study is to investigate the effect of diabetes mellitus (DM) on FFR measurements. MethodsOne hundred and twenty-one patients with an intermediate lesion who had undergone FFR measurement were included in the study. Lesion severity was determined by quantitative coronary angiography. The patients were divided into groups according to the presence (group 1) or absence (group 2) of DM. The patients were further categorized according to the degree of luminal narrowing caused by the lesion (40–50, 51–60, and >60%) and reference vessel diameter (≥2.8 and <2.8 mm). FFR measurements were compared in each category. ResultsThere was no difference between the FFR values of diabetic and nondiabetic patients who had coronary lesions with similar degree of luminal narrowing (0.87±0.08 vs. 0. 0.85±0.07; 0.81±0.08 vs. 0.82±0.10; 0.81±0.10 vs. 0.83±0.09, P = 0.957). In the analysis comparing FFR measurements in the categories set according to reference vessel diameter, we did not find a difference either (0.82±0.09 vs. 0.83±0.09; 0.84±0.09 vs. 0.82±0.09, P = 0.878). The ΔFFR value, which is the difference between FFR values before and after adenosine administration, was also similar in diabetic and nondiabetic patients (8.4±6.0 vs. 8.4±5.5, P = 0.997). ConclusionThe presence of DM does not have a significant impact on FFR values in coronary stenoses of intermediate severity.

Relationship Between MMP-1, MMP-9, TIMP-1, IL-6 and Risk Factors, Clinical Presentation, Extent and Severity of Atherosclerotic Coronary Artery Disease.

Background: Matrix metalloproteinases (MMPs) and Tissue Inhibitor of Matrix Metalloproteinases (TIMPs) may be associated with atherogenesis and plaque rupture. We evaluated the relationship between MMP-1, MMP-9, TIMP-1 and IL-6 levels and risk factors, presentation, extent and severity of atherosclerotic coronary artery disease (CAD). Methods: Consecutive patients who underwent coronary angiography were randomly included. The serum concentrations of MMP-1, MMP-9, TIMP-1 and IL-6 were analyzed with ELISA method in 134 patients. Participants were divided into 5 groups; stable angina pectoris (SAP; n= 34), unstable angina pectoris (USAP; n=29), non-ST elevation myocardial infarction (NSTEMI; n=16), acute ST elevation myocardial infarction (STEMI; n=25) and controls (n=30). Coronary angiographic Gensini score was calculated. Results: MMP-1 levels were higher in STEMI and NSTEMI groups compared with USAP, SAP and control groups (STEMI vs USAP p=0.005; STEMI vs SAP p=0.001; STEMI vs control p<0.001; NSTEMI vs USAP p=0.02; NSTEMI vs SAP p=0.027; NSTEMI vs control p<0.001). In STEMI group, MMP-9 levels were higher than USAP and control groups (p=0.002; p<0,001). TIMP-1 levels were not significantly different within all 5 groups. MMP-1 levels were found to be elevated in diabetic patients (p=0.020); whereas MMP-9 levels were higher in smokers (p=0.043). Higher MMP-1, MMP-9 and IL-6 levels were correlated with severe Left Anterior Descending artery (LAD) stenosis and higher angiographic Gensini Score (for severe LAD stenosis; r = 0.671, 0.363, 0.509 p<0.001; for Gensini score; r = 0.717, 0.371, 0.578 p<0.001). Conclusions: Serum levels of MMP-1, MMP-9, and IL-6 are elevated in patients with CAD; more so in acute coronary syndromes. MMP-1, MMP-9 and IL-6 are associated with more extensive and severe CAD (as represented by Gensini score).