Biomarker Of Myocardial Ischemia Research Articles

Study the Inflammatory Biomarkers of Acute Coronary Syndrome Patients in Wasit Province

This prospective study was performed in the coronary care unit at AL-Zahraa teaching hospital in Wasit Governorate during the period from January 2018 to June 2018. This study explained the role of inflammatory biomarkers in proper diagnosis, risk stratification and prognostic evaluation of patients with acute coronary syndrome (ACS). A total of 100 patients with ACS, 77 men aged 25–90 years and 23 women aged 45–85 years. They were divided into three age groups. The first group was ˂45years old, the second group was 45–60 years old and the third group was ˃60 years. The risk factors for ACS include gender, age, HT, diabetes, smoking, and dyslipidemia through a questionnaire. Our study revealed that male to female ratio was 3: 1 and demonstrate that male gender and HT were most prevalent risk factor for ACS. Regarding white blood cells and the rate of Erythrocyte sedimentation rate, the results showed a significant increase in white blood cells, neutrophils and the rate of red blood cell deposition at P≤0.05. The results of our study showed a significant increase in the markers of the acute phase protein, which showed a significant increase in the value of fibrinogen and C-reactive protein(CRP) at P≤0.05. Regarding biomarker of myocardial ischemia, there was a significant increase in troponin and creatinine kinase at P≤0.05. There was high 30 day mortality among patients with high level of inflammatory biomarker (fibrinogen and CRP), biomarkers of myocardial ischemia(troponin and CK-MB) and those with markedly elevated WBC count.

Integration of Metabolomics With Pharmacodynamics to Elucidate the Anti-myocardial Ischemia Effects of Combination of Notoginseng Total Saponins and Safflower Total Flavonoids.

Notoginseng (Sanqi), the roots and rhizomes of Panax notoginseng and safflower, the flowers of Carthamus tinctorius, are widely used traditional Chinese medicines (TCMs) for the treatment of cardiovascular diseases. Positive evidences have fueled growing acceptance for cardioprotective effects of the combination of the notoginseng total saponins and safflower total flavonoids (CNS) against myocardial ischemia (MI). However, the underlying cardioprotective mechanisms of CNS are still obscured. Metabolomics is a comprehensive tool for investigating biological mechanisms of disease, monitoring therapeutic outcomes, and advancing drug discovery and development. Herein, we investigated the cardioprotective effects of CNS on the isoproterenol (ISO)-induced MI rats by using plasma and urine metabolomics based on ultra-performance liquid chromatography coupled with quadrupole-time of flight mass spectrometry (UPLC-Q-TOF/MS) and multiple pharmacodynamics approaches. The results showed that pretreatment with CNS could attenuate the cardiac injury resulting from ISO, as evidenced by decreasing the myocardial infarct size, converting the echocardiographic, histopathological, and plasma biochemical abnormalities, and reversing the perturbations of plasma and urine metabolic profiles, particularly for the 55.0 mg/kg dosage group. In addition, 44 metabolites were identified as the potential MI biomarkers, mainly including a range of free fatty acids (FFAs), sphingolipids, and glycerophospholipids. CNS pretreatment group may robustly ameliorate these potential MI-related biomarkers. The accumulation of LysoPCs and FFAs, caused by PLA2, may activate NF-κB pathway and increase proinflammatory cytokines. However, our results showed that CNS at 55.0 mg/kg dosage could maximally attenuate the NF-κB signaling pathway, depress the expressions of TNF-α, IL-6, IL-1β, and PLA2. The results suggested that the anti-inflammatory property of CNS may contribute to its cardioprotection against MI. Our results demonstrate that the integrating of metabolomics with pharmacodynamics provides a reasonable approach for understanding the therapeutic effects of TCMs and CNS provide a potential candidate for prevention and treatment of MI.

Effects of Percutaneous Coronary Intervention on Serum Angiopoietin-2 in Patients with Coronary Heart Disease.

Background:Angiopoietin-2 (Ang-2) plays a crucial role in hypoxia-induced angiogenesis and is expressed only in sites of vascular remodeling. Ang-2 expression can be regulated by hypoxia inducible factors and other regulators with exposure to hypoxia. The objective of this study was to investigate the influence of percutaneous coronary intervention (PCI) on serum Ang-2 concentrations, and analyze the correlation between serum Ang-2 and the severity of coronary artery stenosis in patients with coronary heart disease (CHD).Methods:Sixty-four patients with CHD were selected as the study group, each undergone PCI. Thirty-two healthy subjects were selected as the control group. Pre-PCI and post-PCI serum Ang-2 were measured by enzyme-linked immunosorbent assay. The severity of coronary artery stenosis was evaluated using angiographic Gensini scores, and the coronary collateral vessels were scored according to Rentrop's classification.Results:Concentrations of pre-PCI serum Ang-2 in the study group were significantly higher than those in the control group (4625.06 ± 1838.06 vs. 1945.74 ± 1588.17 pg/ml, P < 0.01); however, concentrations of post-PCI serum Ang-2 were significantly lower than those of pre-PCI (3042.63 ± 1845.33 pg/ml vs. 4625.06 ± 1838.06 pg/ml, P < 0.01). Concentrations of pre-PCI serum Ang-2 were significantly correlated with Gensini scores (r = 0.488, P < 0.01); however, the decrease in serum Ang-2 after PCI was not correlated with Gensini scores, coronary collateral vessel grading, or left ventricular ejection fraction.Conclusions:Serum Ang-2 concentrations significantly increased in patients with CHD, and PCI treatment significantly decreased these concentrations. Serum Ang-2 concentrations, but not the decrease in serum Ang-2 concentrations, were significantly correlated with the severity of coronary artery stenosis. These results suggested that Ang-2 may be a biomarker of myocardial ischemia and vessel remodeling.

Utility of serum ischemia modified albumin in the early diagnosis of acute coronary syndrome

Context: Coronary artery disease (CAD) is the leading cause of death. Early detection of myocardial ischemia can decrease morbidity and mortality due to CAD. Ischemia modified albumin (IMA) is a newer biomarker for early detection of myocardial ischemia in patients of acute coronary syndrome (ACS) as compared to cardiac troponin T (cTnT). Aims: The aim of this study was to test the utility of IMA, a new biomarker of myocardial ischemia, in the early diagnosis of ACS. Settings and Design: The cross-sectional study group consisted of 101 patients between the age group of 27 and 85 years having ACS and 100 control from a healthy population. Materials and Methods: Blood was collected from all the enrolled patients immediately after admission, and samples were analyzed for cTnT on the fully automated analyzer and IMA on a spectrophotometer. Statistical Analysis Used: Statistical analysis was carried out by calculation of the area under a curve using receiver operating characteristics (ROC) curve analysis for the IMA test in the 101 patients included in the study population. Results: ROC curve area for IMA was 0.89 (95% confidence interval 0.81-0.94). At the cut-off 95 U/ml, sensitivity, and specificity were 85% and 82% and positive predictive value and negative predictive value (NPV) were 88% and 78%, respectively. Conclusions: IMA is a useful ischemic marker for diagnosis of myocardial ischemia due to high sensitivity, and it also facilitates to rule out myocardial ischemia due to high NPV.

Ischemia-Modified Albumin Levels in Patients with Acute Decompensated Heart Failure Treated with Dobutamine or Levosimendan: IMA-HF Study

OP-164 Ischemia-modified albumin (IMA) is a very sensitive biomarker of myocardial ischemia before necrosis. IMA has also been found to be elevated in the setting of oxidative stress, acidosis, hypoxia, inflammatory state and sodium and calcium pump disruptions which are also involved in the

Ischemia-modified albumin levels in patients with acute decompensated heart failure treated with dobutamine or levosimendan: IMA-HF study

Purpose: Ischemia-modified albumin (IMA) is a very sensitive biomarker of myocardial ischemia before necrosis. However, data about IMA levels specifically in patients with heart failure (HF) are still lacking. Dobutamine (DOB) is known to increase myocardial oxygen consumption, and thereby may precipitate myocardial ischemia and myocyte damage. In contrast to DOB, levosimendan (LEVO) does not increase myocardial oxygen demand and therefore is thought to have cardio protective properties. So, we aimed to evaluate 1-) serum IMA concentrations in acute decompensated HF and 2-) the effects of DOB and LEVO treatments on IMA levels. Methods: This prospective multicenter study was performed at the five independent sites. Fifty-nine patients admitted to participating centers with NYHA III-IV acute decompensated HF and LVEF <35% were enrolled in this study. Blood samples for IMA measurements were obtained from all patients at baseline and 24 h after the initiation of HF therapy. 18 patients were treated with guidelines-recommended HF therapy with oxygen, diuretic, vasodilators (control group), 18 patients received an additional 24-h infusion of LEVO with a loading dose of 12 μg/kg over 10 min followed by a continuous infusion of 0.2 μg/kg/min (LEVO group) and 23 patients had DOB treatment with a continuous infusion of 10 μg/kg/min for 24-h in addition to optimal pharmacologic therapy (DOB group). A single serum specimen was also collected from 32 apparently healthy individuals. IMA concentrations were measured by albumin cobalt binding colorimetric assay and results were given as absorbance units (AU). Results: In patients with acute decompensated HF, mean serum concentration of IMA was found to be significantly higher than those of apparently healthy population (0.894±0.23 AU vs 0.379±0.08 AU, p <0.0001). Overall, IMA levels significantly decreased after 24-h of the initiation of appropriate HF therapy (0.894±0.23 AU and 0.832±0.18 AU, p <0.013). Furthermore, IMA levels were also found to significantly decrease in control group (1.041±0.28 vs 0.884±0.15 AU, p<0.041), in LEVO group (0.771±0.18 vs 0.728±0.18 AU, p<0.046) and also in DOB group (0.892±0.18 vs 0.820±0.13 AU, p<0.035). Conclusions: This study suggested for the first time that patients with acute decompensated HF had elevated levels of IMA when compared to healthy controls and appropriate HF therapy significantly reduced serum IMA levels. The findings of this study also demonstrated that both DOB and LEVO treatments did not increase in IMA levels, suggesting lower potential in inducing myocardial ischemia when used in recommended doses.

Meta-Analysis of B-Type Natriuretic Peptide's Ability to Identify Stress Induced Myocardial Ischemia

Studies in victims of sudden cardiac death and those surviving a cardiac arrest have confirmed that extent of coronary artery disease is similar in those with and without angina, suggesting that it is the presence of myocardial ischemia rather than associated symptoms that determine the prognosis. Experimental models show that hypoxic myocardial tissue results in production of extra B-type natriuretic peptide (BNP), suggesting that BNP could potentially serve as a biomarker of myocardial ischemia. We performed a meta-analysis of the studies that link BNP to inducible myocardial ischemia as indicated by noninvasive stress tests. Values of true positive, false positive, true negative, and false negative were calculated from the reported sensitivity, specificity, disease prevalence, and total number of patients studied. Sixteen studies reporting data on 2,784 patients across 14 study populations were included in the final analysis. Mean age of participants was 55 to 69 years and 55% to 90% were men. Pooled sensitivity and specificity of BNP for detection of stress-induced myocardial ischemia were 71% (95% confidence interval [CI] 68 to 74) and 52% (95% CI 52 to 54), respectively. Pooled diagnostic odds ratio was 3.5 (95% CI 2.46 to 5.04) and summary receiver operating characteristic curve revealed an area under the curve of 0.71 ± 0.02 (mean ± SE). In conclusion, this meta-analysis suggests that an increased BNP level can identify inducible ischemia as detected by standard noninvasive stress tests. This raises the possibility of a whole new role for BNP in the diagnosis and management of myocardial ischemia.

Metabolomic strategy to study therapeutic and synergistic effects of tanshinone IIA, salvianolic acid B and ginsenoside Rb1 in myocardial ischemia rats

Tanshinone IIA (T), salvianolic acid B (S) and ginsenoside Rb1 (G) are the three major active ingredients of Compound Danshen Formula (CDF) for its protective effects on myocardial ischemia (MI). In this study, we aimed to investigate therapeutic and synergistic effects of TSG (combination of T, S and G) on MI rats with metabolomic strategy. MI model were induced in Sprague-Dawley rats by left anterior descending coronary artery ligation. MI rats were respectively administrated T, S, G, TSG and CDF. Plasma was analyzed by ultra-performance liquid chromatography/quadrupole time-of-flight mass spectrometry (UPLC-Q-TOF-MS). Partial least squares discriminate analysis (PLS-DA) models were built to evaluate the therapeutic and synergistic effects of TSG at whole level. 22 MI biomarkers in rat plasma were also investigated to explain that. TSG brings nearly equal therapeutic effects on MI as CDF and it plays more stable regulated action on those 22 identified metabolites than single compound. Overall, there were few methods for the study of synergistic effects of Chinese medicine. Our results suggested that metabolomics offers a new idea for Chinese medicine research.

Analysis of serum cardiac biomarkers and treadmill exercise test-electrocardiogram for the diagnosis of coronary heart disease in suspected patients

The serum proteins creatine kinase isoenzyme MB (CKMB) and cardiac troponin T are classic biomarkers of cardiac ischemic damage in clinical practice, which can sensitively detect myocardial necrosis, while other two serum proteins, ischemia-modified albumin and N-terminal pro-B-type natriuretic peptide (NT-proBNP), have been recently identified as novel biomarkers of myocardial ischemia. In this study, the four biomarkers were detected in sera from 44 eligible patients with suspected coronary heart disease (CHD) before and after treadmill exercise test (TET), electrocardiogram (ECG) was measured during TET (TET-ECG) and invasive examination of coronary angiography (CAG), which is the 'gold standard' of CHD diagnosis, was also performed. For CAG, 25 patients were positive and 19 were negative, whereas for TET-ECG the numbers were 19 and 25, respectively. Among these four biomarkers, the NT-proBNP level in CAG positive group was much higher than those in CAG negative group both before and after TET, with statistical significance before TET (P=0.008). Furthermore, according to receiver operating characteristic (ROC) curve, the serum biomarker NTproBNP showed diagnostic effect of CHD and its cutoff value was 67 pg/ml, thus 30 of the patients in this study were NT-proBNP positive and 14 were negative. And it was found that NT-proBNP obviously enhanced the sensitivity of examinations whether analyzed alone or in combination with TET-ECG. More importantly, all the patients who were negative in both NT-proBNP and TET-ECG tests turned out to be CAG negative, which means that the combination of these two non-invasive examinations might take the place of invasive examination of CAG for CHD diagnosis. Further studies with more patients are warranted to validate the findings in this paper.

Ischemia modified albumin in relation to pharmacologic stress testing in coronary artery disease

Background Ischemia modified albumin (IMA) is considered a biomarker of myocardial ischemia. We sought to investigate whether IMA plasma levels change during pharmacological stress test, in patients with stable coronary artery disease. Methods We studied 37 patients undergoing non-invasive evaluation with a pharmacological stress test, either with radionuclide myocardial perfusion imaging with adenosine or stress echocardiography with dobutamine. Peripheral venous samples were collected before the stress test (baseline), at the end of adenosine infusion or at the peak dose of dobutamine and 60 min after the completion of the stress test for IMA measurement. Results IMA plasma levels significantly increased at peak vs. baseline (91.28 ± 9.59 U/ml vs. 97.97 ± 9.69 U/ml, p < 0.0001) and subsequently, decreased significantly at 60 min compared to peak (97.97 ± 9.69 U/ml vs. 94 ± 15.22 U/ml, p = 0.016), returning to values similar to those at baseline ( p = 0.134). Similarly, in patients with a negative stress test, IMA significantly increased at peak compared to baseline (91.08 ± 10.03 U/ml vs. 99.58 ± 8.43 U/ml, p = 0.006) and returned to baseline at 60 min (99.58 ± 8.43 U/ml vs. 91.83 ± 7.93 U/ml, p = 0.019), the 60 minute levels being similar to baseline values ( p = 0.212). Conversely, in patients with a positive stress test, IMA significantly increased at peak compared to baseline (91.38 ± 10.13 U/ml vs. 97.17 ± 10.34 U/ml, p = 0.006) and although decreased at 1 h, this did not reach statistical significance compared either to the baseline or to the peak values (95.04 ± 17.76 U/ml vs. 91.38 ± 10.13 U/ml, p = 0.315 and 95.04 ± 17.76 U/ml vs. 97.17 ± 10.34 U/ml, p = 0.235, respectively). Conclusion IMA plasma levels change significantly during pharmacologic stress testing, in patients with coronary artery disease, but with no difference between the positive and the negative tests.

Ischemia Modified Albumin in Normal Pregnancy and Preeclampsia

Objective. Ischemia-modified albumin (IMA) has emerged as a new biomarker of myocardial ischemia. Currently, no information is available on maternal IMA levels during normal and complicated pregnancy. Preeclampsia is associated with ischemia and increased formation of free radicals in the placenta. We therefore hypothesized that production of IMA may occur in women with preeclampsia. Methods. Serum IMA and albumin concentrations were assessed in 12 patients with preeclampsia, 12 normal pregnant controls, and 12 nonpregnant controls. IMA levels were compared between groups and corrected for albumin by multivariate regression analysis. Results. Mean IMA levels were elevated in normal pregnant controls (107.3 U/mL; 95% CI, 102.5 to 112.01), compared with nonpregnant controls (94.5 U/mL; CI, 89.4 to 99.6; p = 0.015). In patients with preeclampsia, IMA levels were similar to those in normal pregnant controls (109.7 U/mL; CI, 102.2 to 117.2; p = 0.65). Also, no difference in IMA levels was observed between women with preeclampsia who delivered small-for-gestational-age (SGA) infants (99.0 U/mL; CI, 87.9 to 110.1; p = 0.13) and women with preeclampsia but without SGA. Conclusion. Serum IMA, which has been advocated as a clinical marker of cardiac ischemia, appears to be elevated during normal pregnancy. We found no significant relationship between IMA levels and preeclampsia, in women with or without SGA infants.

Influence of left ventricular filling pattern on exercise-induced changes of natriuretic peptides in patients with suspected coronary artery disease

Background Exertional change in brain natriuretic peptide (BNP) has recently been proposed as a biomarker of myocardial ischemia. However, in patients with abnormal left ventricular (LV) filling, BNP is frequently increased. Therefore, we studied the relationship of exertional changes in atrial and brain natriuretic peptides (ANP and BNP) with resting and exercise-induced changes of LV systolic function and filling pattern. Methods LV function at rest and peak exercise was assessed in 140 patients (mean age 65 years, 78 men) during symptom-limited exercise echocardiography for evaluation of suspected coronary artery disease. ANP and BNP were measured at rest and 5 min after exercise. Results ANP and BNP increased with exercise. The increase in BNP was significantly greater in the 65 patients with than in the 76 patients without ischemia [14.7 pg/ml (5.7–19.6) vs. 4.9 pg/ml (2.1–9.2), p < 0.0001]; there was no difference in increase of ANP [340 pg/ml (176–729) vs. 424 pg/ml (249–648), p = 0.54]. The exertional rise in BNP was also greater in patients with abnormal LV filling at rest [10.5 pg/ml (4.9–19.6) vs. 4.1 pg/ml (2.0–6.7), p < 0.0001]. By multivariate linear regression, exertional change in wall motion score index ( β = 0.23, p < 0.001), baseline BNP ( β = 0.71, p < 0.001), abnormal LV filling pattern ( β = 0.24, p < 0.001) and age ( β = − 0.15, p = 0.02) were predictors of change in BNP. Conclusions In patients with suspected coronary artery disease, exertional changes of BNP are related not only to ischemia, but also to the LV filling pattern at rest.

Cardiac performance during vasopressin infusion in postcardiotomy shock

Arginine-vasopressin (AVP) might be a potent vasopressor agent in catecholamine-resistant postcardiotomy shock. However, its use remains experimental because of considerations about deleterious effects on the heart. We report on the effects of continuous AVP-infusion on cardiac performance, biomarkers of myocardial ischemia, and systemic hemodynamics in catecholamine-resistant postcardiotomy shock. Retrospective study. Twenty-one-bed general and surgical intensive care unit. Forty-one patients with catecholamine-resistant postcardiotomy shock. Continuous infusion of AVP. Heart rate (HR), heart rhythm, mean arterial pressure (MAP), central venous pressure, mean pulmonary arterial pressure, cardiac index (CI), stroke volume index (SVI), left ventricular stroke work index (LVSWI), systemic vascular resistance (SVR) as well as milrinone and norepinephrine requirements were collected before and 1, 4, 12, 24, and 48 h after start of AVP infusion. Creatine kinase MB and troponin-I serum concentrations were measured daily. During AVP administration we observed a significant decrease in HR (-14.8%), milrinone (-17.5%), and norepinephrine requirements (-54.9%) as well as biomarkers of cardiac ischemia and a significant increase in LVSWI (+46.2%), MAP (+41.8%) and SVR (+60%). CI and SVI remained unchanged. Forty-five percent of postoperative new-onset tachyarrhythmias (TA) converted into sinus rhythm during AVP infusion. AVP was devoid of adverse effects on the heart in these patients with catecholamine-resistant postcardiotomy shock. The significant reduction in HR, vasopressor, and inotropic support suggest a substantial improvement in myocardial performance. These findings are supported by a significant decrease of cardiac enzymes and cardioversion of TA into sinus rhythm in 45.5% of patients with new-onset TA.