Evaluation of clinical utility of serum enzymes and troponin—T in the early stages of acute myocardial infarction

Laboratory infarction diagnostics are based on the detection of elevated serum activities of total Creatine Kinase (CK), Creatine Kinase isoensyme MB, (CKMB), Lactate dehydrogenase (LDH), isoenzyme forms of LDH and transaminases. Determination of these cardiac marker enzymes permits a highly sensitive diagnosis of transmural myocardial infarction. In such patients the diagnosis of acute myocardial infarction can be confirmed by the clinical, symptoms, and changes in the ECG in addition to the enzyme assays. The 50 AMI patients selected in the present study were those admitted to the ICCU of Shri Krishna Hospital, Karamsad. The blood samples were taken at the time of admission (ie. within four hours of the start of chest pain). The samples were analyzed for CK, CKMB, SGOT, (Serum glutamate oxaloactate transaminase) αHBDH α-hydroxybutyrate dehydrogenase and troponin T. The serum CKMB activity in AMI showed an increase only 5–6 hours after the commencement of chest pain. The elevation in SGOT and αHBDH was still delayed. At the same time we could observe that the cardiac Troponin T (cTnT) was elevated at the time of admission of the patient itself. This increase of cTnT in AMI patients was 20 times higher than the normal blood donors. The controls included 25 normal blood donors and 25 patients with polytraumatic injuries with no chest contusion. The study shows that cTnT estimation could serve in the early diagnosis of AMI. The increase of cardiac troponin T in AMI patients was 20 times higher than the normal blood donors in AMI patients at the time of admission. Cardiac troponin T in serum appears to be a more sensitive indicator of myocardial cell injury than CKMB activity and its detection in the circulation may be a useful prognostic indicator in patients with unstable angina as well. When the blood of normal blood donors or that of patients with polytraumatic injury was analysed the troponin T values were well within the normal range in both the above categories showing that cardiac troponin T is highly specific for heart tissue. Although CKMB and cardiac troponin T are released soon after the myocardial injury, the release of cardiac troponin T is much earlier than CKMB thereby invalidating the important role of cardiac troponin T in diagnosing AMI. Cardiac troponin T has been shown to be highly sensitive for cardiac injury and not elevated in any other trauma, heavy exercise or skeletal muscle injury. Cardiac troponin T is ordinarily undetectable in healthy individuals, and so its measurement can serve as a powerful tool in the diagnosis of AMI.     

Inflammatory Cytokines,Apoptotic, Tissue Injury and Remodeling Biomarkers in Children with Congenital Heart Disease

The present study aims to evaluate specific biomarkers involved in congenital heart disease (CHD), and whether there is a significant differences between the levels of these biomarkers in the cyanotic CHD (CCHD) and acyanotic CHD (ACHD). We prospectively measured tumor necrosis factor (TNF-α), interleukin-6 (IL-6), C-reactive protein (CRP), vasoendothelial growth factor (VEGF), troponin T, creatin kinase MB (CKMB), and Caspase 3 levels in 120 consecutive children with CHD (60 cyanotic and 60 a cyanotic with age 1:4 years), and 30 healthy control children. Significant elevated levels of inflammatory markers; TNF-α, IL-6 and CRP was detected in CHD, with percentage increase in cyanotic than a cyanotic subjects as compared to the normal one. Apoptotic biomarker; caspase 3 showed also significant increases in CCHD than ACHD. In addition, tissue injury mechanisms included troponin T and CKMB, exhibited significant increase in cyanotic than a cyanotic CHD. The present results demonstrate also, significant enhancement in remodeling process (VEGF), in cyanotic than a cyanotic patients. Thus, it could be concluded that, the children with CCHD were shown to have elevated levels of inflammatory cytokines, caspase 3, troponin T, and CKMB as these biomarkers may implicated in cardiac functional status.     

A serial follow up study of cardiac marker enzymes during the week after acute myocardial infarction

Laboratory infarction diagnostics are based on the detection of elevated serum activities of creatine kinase (CK) Creatine kinase Isoenzyme MB (CKMB) and Transaminases. Determination of these cardiac marker enzymes permits the diagnosis of transmural myocardial infarction. However in such patients the diagnosis of acute myocardial infarction can be confirmed by the clinical symptoms and changes in the ECG, in addition to the enzyme assays. The 50 AMI patients selected in the present study were those admitted to the ICCU of Shri Krishna Hospital, Karamsad. The blood samples were taken at Zero hours (i.e. at the time of admission of the patient). Within 6 hrs of the starting of chest pain, 1.5 million units of streptokinase were mixed with 100 to 150ml of normal saline and administered by infusion over a period of one hour. The blood samples were further collected at intervals of 6 hrs, 14hrs, 32hrs, 48hrs, 5^th day and 7^th day. The blood samples were analyzed for CK, CKMB, SGOT, α HBDH and Cardiac specific Troponin T. By 6hrs the CK and CKMB values had started rising, the rise continuing at 14hrs with peak values at 32hrs. The CK showed a slight decrease by 48 hrs. The cardiac Troponin T showed wide time window from 4 hrs to 7^th day for detecting myocardial damage. The maximum cardiac Troponin T values were during the first 24hrs. Cardiac Troponin T in serum appears to be a more sensitive and early indicator of myocardial cell injury in comparison to CKMB.     

Comparison of Mass Versus Activity of Creatine Kinase MB and Its Utility in the Early Diagnosis of Re-infarction

Currently employed markers for the detection of acute coronary syndrome are Troponin T, CK (Creatine Kinase) and CKMB activity. CKMB activity measured by immunoinhibition method can give falsely elevated results due to the presence of atypical CK and CKBB and at times lead to the mis-diagnosis of acute coronary syndrome. Hence, CKMB mass (CKMB) measured by electrochemiluminence sandwich principle was employed. In this cross-sectional study 183 samples of 61 patients were analyzed within 6 h of diagnosis of acute coronary syndrome and followed up to 72 h. The correlation coefficient between CKMB activity and CKMBM at 4–6 h was 0.744, while at 12–24 h it was 0.909 and at 48–72 h it was 0.337. Thus there was good association between the two methods at 12–24 h but, statistically for method comparison studies and for replacing one method by another, the two methods need to be in agreement with one another. In this study the two methods are not in agreement with one another and thus analytically not replaceable. Another finding was obtained that CKMBM reached cut off levels prior to CKMB enzyme activity and hence, CKMBM is clinically better than CKMB activity to detect reinfarction.     

Evaluation of serum adenosine deaminase and 5′-nucleotidase activities as probable markers in ovarian cancer

Adenosine deaminase (ADA) and 5′-nucleotidase (5′-NT) activities were measured in sera of patients with ovarian cancer and patients with benign ovarian tumour. The results were compared with that of a control group consisting of healthy women. ADA levels were significantly increased (P<0.001) in the ovarian cancer group (n=50) but not in the benign group (n=28) when compared to the controls (n=20). The results indicate that ADA and 5′-NT levels may help to differentiate malignant conditions from benign tumours of the ovary in addition to the existing tests such as serum CA-125 levels and histopathological study.     

Ischemia modified albumin: A novel marker for acute coronary syndrome

Early identification of patients with acute myocardial infarction is of prime importance due to the associated very high mortality. Only 22% of the patients presenting at emergency cardiology care with chest pain have coronary disease. A number of biochemical tests like CKMB and Troponin-T/I have been introduced for early detection of the coronary syndrome (ACS). Ischemia modified albumin (IMA) has been recently introduced as a marker of myocardial ischemia. We estimated serum IMA in four sequential samples from 25 patients admitted to ICCU. Twenty five healthy volunteers formed the control group from which the normal range was derived. IMA was significantly raised in ischemia patients than in controls as well as compared to the patients who did not have cardiac ischemia. IMA demonstrated good discrimination between the ischemic and the non-ischemic patients with an Odds Ratio of 16.9 (6.29–46.87) than CKMB which showed an Odds Ratio of 2.07 (1.18–6.08). Sensitivity and specificity of IMA for the detection of ACS was 78.0% and 82.7% compared to 58.0% and 60.0%, respectively for the CK-MB assay. The area under the ROC curve of IMA for ischemic v/s non-ischemic patients was 0.834. IMA appears to be developing into a new and very potent marker, of cardiac ischemia.     

Non-commutability of results of highly sensitive troponin I and T immunoassays

Introduction:

The measurement of cardiospecific troponins is pivotal in the diagnostic and prognostic approach of patients with suspected acute myocardial infarction (AMI). However, no information is available on the commutability of results between the novel highly-sensitive (HS) troponin T (TnT) and I (TnI) immunoassays.

Materials and methods:

The study population consisted in 47 consecutive patients presenting at the emergency department (ED) of the Academic Hospital of Parma with suspected AMI. TnI was measured with the novel prototype Beckman Coulter HS-AccuTnI immunoassay on Access 2, whereas TnT was measured with the Roche HS-TnT immunoassay on Cobas.

Results:

Eight out of the 47 patients (17%) were finally diagnosed as having an AMI. The overall correlation between TnT and TnI for total patient group was acceptable (r = 0.944; P < 0.01). Nevertheless, when the analysis of data was carried out in separate groups according to the final diagnosis of AMI, two different equation results were obtained, i.e., HS-TnT = HS-AccuTnI × 0.349 + 20 (r = 0.823; P < 0.01) in non-AMI patients, and HS-TnT = HS-AccuTnI × 0.134 + 67 (r = 0.972; P < 0.01) in those with AMI.

Conclusions:

This study suggests the existence of two biological relationships between TnI and TnT in plasma, depending on the source of release from the myocardium. Moreover, the non-commutability of data between HS-TnT and HS-AccuTnI jeopardizes the clinical decision making, makes it impossible to calculate the delta or reference change value using the two biomarkers and to finally establish a reliable kinetics of troponin release from the injured myocardium.     

“Real life use” of troponin in the emergency department: a survey of over 3000 cases

Introduction

The aim of this study was to identify clinical variables which may be independently associated with positivity of a cardiac troponin I (cTnI) assay in a large population of patients admitted to the emergency department (ED).

Materials and methods

3166 subjects, with at least two troponin I tests ordered within 6 hours in the ED, were studied. Patient data were statistically analyzed to identify clinical associations with increased values of Troponin I.

Results

Although patients with diagnosis of acute coronary syndrome displayed troponin I values significantly higher than those of other groups, positivity to troponin I (> 40 ng/L) was also observed in patients with other clinical conditions. In multivariate analysis, age, elevated heart rate and electrocardiographyc changes were independently associated with troponin I positivity at admission. In the whole study population troponin I positivity exhibited high sensitivity and negative predictive value, counterbalanced by low specificity and limited positive predictive value.

Conclusions

Troponin I positivity should be combined with history and clinical evaluation and cautiously interpreted in the ED, especially in patients exhibiting factors associated with higher troponin I levels such as older age, elevated heart rate or ECG changes.Key words: troponin I, acute coronary syndrome, emergency service, hospital, chest pain     

Lipid abnormalities,lipoprotein (a) and apoprotein pattern in non-dialyzed patients with chronic kidney disease

The present study was carried out to explore the altered lipid, lipoprotein and apoprotein abnormalities along with lipoprotein (a) in chronic kidney disease patients with stage I to V which were further divided into group 1 (stage I and II), group 2 (stage III and IV) and group 3 (stage V). 50 chronic kidney disease patients with stage I to V and 20 healthy normal subjects as controls were recruited for this study. Among the various parameters tested triglyceride levels were high in group 1 and 2, whereas VLDL cholesterol, Lp (a) and apo B levels were significantly high in all the groups when compared to controls (P<0.05). However, LDL cholesterol level was significantly low in group 3 only as compared to control group (P<0.05). Apoprotein AI values also showed significant decrease in all groups as compared to controls (P<0.05). Though total cholesterol levels in group 1 and LDL levels in group 1 and 2 were higher than controls, but the values attained not statistically significant (P>0.05). In conclusion high levels of VLDL cholesterol, Lp (a), apo B and low levels of apoprotein AI as reported in this study are the major lipid disorders in the development of cardiovascular complications at all the stages in these patients.     

Diagnosis of acute myocardial infarction: CK-MB versus cTn-T in Indian patients

The comparative diagnostic efficacy of two cardiac markers: CK-MB and cTn-T, has scarcely been investigated in Indian patients of acute myocardial infarction. The present study was conducted for the same objective. The present study comprised of 59 patients. Males were 44 (75%) and females were 15 (25 %). The age of patients ranged from 32–84 years with mean age of 62.8 yrs. The mean age of males and females were 60 and 63 yrs respectively. All patients presented with history of chest pain with a 12 leads ECG proven MI (ST Elevation, discordant T-waves). CK-MB was estimated in peripheral blood samples at 0,24,48 and 72 hours by an autoanalyzer. Following 12 hours of admission bed side Troponin-T test was done employing cTn-T marker kit. Initially (0 hr), in 50% patients CK-MB was elevated. By end of 24 hours all the patients were CKMB positive and peak level was attained at 24 hrs. Then it tended to decline over next 48 hrs. There were no false positive or negative results. The cTn-T test was positive only in 22 % of ECG positive infarctions. However, the cTn-T positive cases were always accompanied by a higher CK-MB levels. A significantly lower cTn-T positive cases in Indian patients can only be attributed to some difference in amino acid sequence of Indian cTn-T and occidental cTn-T. A larger study from other Indian cardiac centers can either substantiate or contradict our results.     

Pregnancy Associated Plasma Protein-A (PAPP-A) Levels in Acute Coronary Syndrome: A Case Control Study in a Tertiary Care Centre

In recent years, an important objective of cardiovascular research has been to find new markers that would improve the risk stratification and diagnosis of patients presenting with symptoms of acute coronary syndrome (ACS). Established biomarkers for diagnosis of ACS includes troponins and creatine kinase MB (CK-MB). Pregnancy associated plasma protein A (PAPP-A) is an emerging marker which has been described as a marker of plaque instability. PAPP-A is a large metalloproteinase involved in insulin-like growth factor signaling and has been shown to be involved in pathological processes like atherosclerosis. Many studies have been published regarding release of PAPP-A in circulation during ACS. The objective of this study was to evaluate the role of PAPP-A as an early marker of ACS by comparing levels of PAPP-A in patients with acute myocardial infarction (AMI) and unstable angina (UA) with asymptomatic controls. The association of PAPP-A with markers of myocardial necrosis and the association of PAPP-A levels to the presence of risk factors for coronary artery disease was also studied. We measured PAPP-A levels in patients with AMI (30), UA (23) and asymptomatic controls (45). PAPP-A was estimated using PAPP-A US (ultra sensitive) ELISA manufactured by DRG (Germany). PAPP-A levels were significantly elevated in patients with AMI and in patients with UA (mean levels 64.26 ± 1.05 and 36.23 ± 1.05 ng/ml respectively; p < 0.001). Mean PAPP-A levels in controls were 10.68 ± 1.04 ng/ml. In UA cases PAPP-A levels were elevated when the troponin I and CK-MB levels were within the normal range. No correlation was observed between PAPP-A with markers of myocardial necrosis. PAPP-A can serve as a useful biomarker in the diagnosis of ACS, especially UA, where cardiac troponin levels and CK-MB levels are not elevated and ECG changes are inconclusive.     

Glycogen Phosphorylase BB: A more Sensitive and Specific Marker than Other Cardiac Markers for Early Diagnosis of Acute Myocardial Infarction

Cardiac markers are used to evaluate functions of heart. However, there are no satisfactory cardiac biomarkers for the diagnosis of acute myocardial infarction (AMI) within 4 h of onset of chest pain. Among novel cardiac markers, glycogen phosphorylase BB (GPBB) is of particular interest as it is increased in the early hours after AMI. The present study was conducted with the objective to find out the sensitivity and specificity of GPBB over other cardiac markers i.e. myoglobin and CKMB in patients of AMI within 4 h after the onset of chest pain. The study includes 100 AMI patients and 100 normal healthy individuals as controls. In all the cases and controls, serum GPBB and myoglobin concentrations were measured by ELISA where as CK-MB was measured by diagnostic kit supplied by ERBA. The sensitivity and specificity of glycogen phosphorylase BB (GPBB) were greater than CK-MB and myoglobin in patients of AMI within 4 h after the onset of chest pain. Hence, glycogen phosphorylase BB (GPBB) can be used as additional biomarker for the early diagnosis of AMI.     

Assessment of oxidative stress and effect of antioxidant supplementation during radiotherapy in carcinoma of upper digestive tract

Oxidative stress was studied by estimating plasma levels of malondialdehyde (MDA), beta carotene, vitamin E and erythrocytic superoxide dismutase(E-SOD) activity in 50 cases of carcinoma of upper digestive tract which included carcinoma of oral cavity, pharynx and oesophagus. While plasma MDA level was found to be increased (3.5±1.0 nmole/ml), a significant decrease in beta carotene (81.2±14.5mg%), vitamin E (8.5±1.1 mg/L) level and E-SOD activity (657.0±80.6 U/G Hb) were observed in carcinoma of upper digestive tract. Patients were treated with radiotherapy which itself was toxic enough and produced its deleterious effects by generation of reactive oxygen species (ROS). As antioxdiants can detoxify ROS, beneficial effect if any, of antioxidant administration during radiotherapy was studied in two groups of patients, group A (n=5, supplemented with antioxidants) and group B (n=5, without antioxidant supplementation). Plasma MDA level was found to be elevated in both the groups but the increase in group B was significant, compared to pretreatment level. Further, body weight was found to be significantly decreased in group B patients, which was maintained in group A patients. Moreover, group A patients showed significant elevation in beta carotene concentration, thus showing beneficial effect of administration of antioxidants during radiotherapy without disturbing the desirable therapeutic effect of radiotherapy.     

Relationship between hs-CRP and cardiac efficiency in chronic alcoholics

High sensitive C-reactive protein (hs-CRP), a non-specific marker of inflammatory status has considerable interest focused due to its ability to predict myocardial infarction, stroke, peripheral arterial disease and sudden cardiac death. Alcoholics are known to be associated with inflammation of heart. This study was taken up to look for an association between consumption of alcoholic beverages over 10 years and serum concentration of hs-CRP. 3 groups were studied, 30 age matched control, 30 non-drinkers with cardio vascular complications and 30 alcoholics with history of cardio-vascular disease. Blood was analyzed for hs-CRP. Results indicated that the level of hs-CRP was 0.17 ± 0.16 mg/lit in group 1; 0.79 ± 0.41 mg/lit in group 2 and 1.67 ± 0.16 mg/lit in group 3. A correlation was also obtained between the hs-CRP levels and cardiac efficiency in chronic alcoholics. The elevated hs-CRP levels in chronic alcoholic with heart disease could probably be due to enhanced damaging effect of alcohol on the heart and other organs.     

The association of ABO blood groups with extent of coronary atherosclerosis in Croatian patients suffering from chronic coronary artery disease

Aim:

The aim of study was to: 1) examine the relationship between ABO blood groups and extent of coronary atherosclerosis in patients with chronic coronary artery disease (CAD), 2) compare ABO blood groups distribution in CAD patients and general population, 3) examine possible differences in traditional risk factors frequency in CAD patients with different ABO blood groups.

Materials and methods:

In the 646 chronic CAD patients (72.4% males) coronary angiograms were scored by quantitative assessment using multiple angiographic scoring system, Traditional risk factors were self reported or measured by standard methods. ABO blood distribution of patients was compared with group of 651 healthy blood donors (74.6% males).

Results:

Among all ABO blood group patients there was no significant difference between the extent of coronary atherosclerosis with regard to all the three scoring systems: number of affected coronary arteries (P = 0.857), Gensini score (P = 0.818), and number of segments narrowed > 50% (P = 0.781). There was no significant difference in ABO blood group distribution between CAD patients and healthy blood donors. Among CAD patients, men with blood group AB were significantly younger than their pairs with non-AB blood groups (P = 0.008). Among CAD patients with AB blood group, males < 50 yrs were significantly overrepresented when compared with the non-AB groups (P = 0.003).

Conclusions:

No association between ABO blood groups and the extent of coronary atherosclerosis in Croatian CAD patients is observed. Observation that AB blood group might possibly identify Croatian males at risk to develop the premature CAD has to be tested in larger cohort of patients.     

pre-operative serum potassium levels and peri-operative outcomes in patients undergoing cardiac surgery

Although potassium is critical for normal electro physiology, the associations between pre-operative serum potassium level and peri-operative adverse events such as arrhythmias in cardiac surgery have not been examined in detail. The objective of this study was to determine the prevalence of abnormal pre-operative serum potassium levels and whether such levels were associated with adverse peri-operative events in 50 patients undergoing coronary artery bypass grafting. Intra-operative and post-operative arrhythmias, the need for cardio-pulmonary resuscitation, cardiac death and death due to any cause prior to discharge from the post-operative intensive care unit were studied. The incidence for adverse outcome was 0.5% for death, 0.5% for cardiac death and 2% for cardio pulmonary resuscitation in patients with hypokalemia (serum potassium level <3.5 meq. L⁻¹). Hypokalemia was found to be a predictor of serious peri-operative (OR:2.2; 95% Cl: 1.2–4.1) and post-operative arrhythmias (OR: 1.7;95%Cl: 1.0–2.7). Pre-operative potassium repletion is low cost and low risk treatment measure and the data from this study suggests that screening and repletion be considered in patients scheduled for cardiac surgery.     

Effect of short term supplementation of tomatoes on antioxidant enzymes and lipid peroxidation in type-II diabetes

The objective of the present study is to evaluate the beneficial effect of tomatoes, which are rich source of Lycopene, relatively a new carotenoid known to play an important role in human health and disease. In this study lipid peroxidation rate was measured by estimating Malondialdehyde and the levels of serum enzymes involved in antioxidant activities like Super Oxide Dismutase, Glutathione Peroxidase, Glutathione Reductase, Reduced Glutathione, in type-II diabetic group (n=40) and age matched control group (n=50), and observed significantly lower levels of antioxidant enzymes and very high lipid peroxidation rate in type-II diabetes when compared to control group (p<0.001). Short term supplementation with tomatoes (cooked) to diabetic group for a period of 30 days, showed a significant improvement in antioxidant enzyme levels (p<0.001) and decreased lipid peroxidation rate (p<0.001) suggesting the supplementation with tomato lycopene may serve as the best method of preventing the oxidative stress in diabetic patients.     

Attempting to maintain normoglycemia during cardiopulmonary bypass with insulin may initiate post-operative hypoglycemia

Cardiopulmonary bypass is known to cause alterations in insulin secretion and resistance, resulting in profound hyperglycemia. Aggressive treatment of the resulting hyperglycemia intra-operatively could result in a severe degree of post-operative hypoglycemia. We undertook this prospective non-randomized clinical study to compare the alterations in glucose homeostasis in diabetic (group A, n=50) and non-diabetic (Group B, n=50) patients undergoing moderate hypothermic (30°C) cardiopulmonary bypass for coronary artery bypass grafting (CABG). All patients had a fasting blood sugar level done on the morning of surgery. Blood sugars were monitored intra-operatively and post-operatively at fixed time intervals. Intra-operative hyperglycemia was treated aggressively by a continuous, infusion of injecting plain insulin. Both the groups experienced similar significant increase in blood glucose levels during bypass (‘p’=0.00003). However, the mean blood glucose level upon arrival in the intensive care unit was significantly decreased in group B compared to group A (p=0.0002). 60% of group B and 10% of group A patients required treatment for post-operative hypoglycemia (blood glucose level <60mg/dl). This clinical study reveals that attempting to maintain normoglycemia in this setting with Insulin may initiate post-operative hypoglycemia.     

Copper and ceruloplasmin levels in relation to total thiols and GST in type 2 diabetes mellitus patients

Presence of oxidative stress in type 2 diabetes mellitus (DM) is well proved. Current study was undertaken to know the relation between fasting plasma glucose (FPG) and copper along with antioxidants like total thiols and ceruloplasmin, and antioxidant enzyme glutathione S transferase (GST). The study group consisted of a total of 201 subjects which included nondiabetic healthy control subjects (n = 78) and diabetic patients (n = 123). Plasma total thiols, GST, copper and ceruloplasmin levels were measured all the subjects using spectrophotometric methods and FPG levels were determined in clinical chemistry analyzer Hitachi 912. There was significant increase in FPG (P<0.001) and copper (P<0.001) and decrease in ceruloplasmin (P<0.001) and protein thiols (P<0.001) in type 2 DM cases compared to healthy controls. There was no significant change in GST between type 2 DM cases and controls. There was significant negative correlation of FPG with antioxidants like ceruloplasmin (r = −0.420, P<0.001) and total thiols (r = −0.565, P<0.001). Protein thiols correlated positively with ceruloplasmin (r = 0.364, P<0.001). Our study indicates possible increase in copper mediated generation of ROS leading to increased consumption of available antioxidants in the body.