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.     

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.     

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.     

Biochemical markers of myocardial injury

The serum markers of myocardial injury are used to help in establishing the diagnosis of myocardial infarction. The older markers like aspartate amino-transferase, creatine kinase, lactate dehydrogenase etc. lost their utility due to lack of specificity and limited sensitivities. Among the currently available markers cardiac troponins are the most widely used due to their improved sensitivity specificity, efficiency and low turn around time. Studies have shown that cardiac troponins should replace CKMB as the diagnostic ‘gold standard’ for the diagnosis of myocardial injury. The combination of myoglobin with cardiac troponins has further improved the accuracy in the diagnosis of acute coronary syndromes and thereby reducing the hospital stay and patients' money. Among the other new markers of early detection of myocardial damage, heart fatty acid binding protein, glycogen phosphorylase BB and myoglobin/carbonic anhydrase III ratio seem to be the most promising. But the search for the most ideal marker of myocardial injury is still on.     

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.     

Cardiac troponin-T and CK-MB (mass) levels in cardiac and non cardiac disease

Serum cardiac troponin T (cTnT) and CKMB (mass) were analysed in three groups of patients. The first group (n=32) were patients with acute coronary syndromes including myocardial infarction. The second group (n=35)were patients with hypertension. The third group (n=24) were patients who had succumbed to non cardiac diseases. In all 3 groups, cardiac troponin T was elevated when compared with controls (p<0.001). However, CKMB elevation was not significant in all groups. CKMB levels correlated well with troponin T levels only when CKMB was greater than 50 ng/ml (r=1.00). Small elevations of troponin T identifies minimal cardiac necrosis and patients can benefit from early invasive therapy.     

Estimation of CKMB from riqas control serum at 37 degree celsius

The quality control sera commonly available in market does not provide the value of CKMB. The CKMB kit of Randox laboratories contains two lyophilized control sera. But the stability of the control serum after reconstitution with 2ml of distilled water is 5 days at 2–8 degree Celsius, 8hrs at 25 degree Celsius and 4 weeks at-20 degree Celsius when frozen once. Hence stability after reconstitution is not sufficient to fulfill the daily need of a laboratory. In quest of a good internal quality assessment (IQA) sample trial run has been performed at 37 degree Celsius using external quality assessment (EQA) samples obtained from Randox international quality assessment sample (RIQAS). The trial run was found to be successful.     

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.     

Heart-Type Fatty Acid-Binding Protein,in Early Detection of Acute Myocardial Infarction: Comparison with CK-MB,Troponin I and Myoglobin

The study aimed to investigate whether heart-type fatty acid binding protein (H-FABP) measurement provides additional diagnostic value to that of conventional cardiac markers in acute myocardial infarction (AMI) within first 6 h after the onset of symptoms. The study included 120 subjects: 60 AMI cases and 60 age and sex matched controls. The cases and controls were further divided into 2 subgroups depending on the time since onset of chest pain as (1) subjects within 3 h and (2) between 3 and 6 h of onset of chest pain. In all the cases and controls, serum H-FABP concentration was measured by Immunoturbidimetric method, serum Troponin I and myoglobin concentrations by Chemiluminescence immunoassay and serum CK-MB concentration by Immuno-inhibition method. The sensitivity, specificity, positive and negative predictive values of H-FABP were significantly greater than CK-MB and myoglobin but were lesser than Troponin I in patients with suspected AMI in both within 3 h and 3–6 h groups. Receiver operating characteristic curves demonstrated greatest diagnostic ability for Troponin I (AUC = 0.99, p < 0.001) followed by H-FABP (AUC = 0.906, p < 0.001) within 3 h and 3–6 h after the onset of chest pain. In conclusion, the diagnostic value of H-FABP is greater than CK-MB and myoglobin but slightly lesser than troponin I for the early diagnosis of AMI within first 6 h of chest pain. H-FABP can be used as an additional diagnostic tool for the early diagnosis of AMI along with troponin I.     

Serum and platelet sialic acid in acute myocardial infarction

Blood samples from 39 patients with acute myocardial infarction and 15 healthy controls were analysed for serum and platelet sialic acid. Serum sialic acid levels in patients with acute myocardial infarction were significantly higher than controls (mean 2.7±0.46 μmol/ml Vs. 1.91±0.17 μmol/ml respectively). Levels of serum orosomucoid, an acute phase reactant, containing sialic acid, were also higher in these patients, suggesting a possible non-specific mechanism of increase in serum sialic acid concentration. In contrast, platelets contained significantly less sialic acid in patients with acute myocardial infarction than control (26.73±1.57 nmol/mg protein and 31.97±2.68 nmol/mg protein respectively).     

Serum lipid profile in patients with acute myocardial infarction

Serum lipids and lipoproteins were estimated in 29 patients with acute myocardial infarction during acute phase (day 1,2,3), predischarge and after three months. Serum total lipids, total cholesterol (TC) and LDL-cholesterol (LDLc) showed no significant change during the hospital stay and three months followup. HDL-cholesterol (HDLc), however, started falling from day 2 onwards with statistically significant reduction at pre-discharge and remained so at 3 months. The ratios of TC/HDLc and LDLc/HDLc showed significant increase on predischarge day as compared to day 1. Serum triglycerides also showed an increasing trend after myocardial infarction with a significant increase on day 3 and predischarge as compared to day 1. it is concluded that the optimum time for assessment of serum lipid profile in patients with myocardial infarction seems to be within 24 hours of the acute episode.     

Cholesterol synthesis and its regulation in acute myocardial infarction

Cholesterol synthesis and its suppression by LDL was measured in freshly isolated leucocytes from patients with acute myocardial infarction and healthy controls. Cells incubated for different time intervals in lipoprotein-deficient serum exhibited increased cholesterol synthesis. The magnitude of this increase was far greater in leucocytes of hyperlipemic patients than in normolipemic patients. Addition of LDL to the incubation medium produced suppression of cholesterol synthesis. This reduction was less in hyperlipemic patients as compared to normolipemic patients. These observations may imply reduced suppression of HMG-CoA reductase activity with high endogenous cholesterol synthesis in patients suffering with acute myocardial infarction.     

Homocysteine status and acute myocardial infarction among Tamilians

Myocardial infarction is a major consequence of coronary artery disease. Apart from the traditional risk factors of myocardial infarction, recently many reports have suggested that hyperhomocysteinemia plays important role in myocardial infarction. Plasma homocysteine level was determined in 60 myocardial infarction patients and in 35 age matched healthy individuals. Statistically significant differences (p<0.01) were observed in the mean of plasma homocysteine concentrations between the acute myocardial infarction patients (24.59±6.14 mM/L) and in normal healthy individuals (13.73 ±3.54 mM/L). The level of homocysteine in myocardial infarction patients is significantly high (p <0.01) among myocardial infarction patients when compared to that of the controls. The the present study indicates a strong association between plasma homocysteine and acute myocardial infarction among Tamilians, thus implying plasma homocysteine as a possible risk factor for myocardial infarction.     

Serum Paraoxonase (PON1) Activity in North-West Indian Punjabi’s with Acute Myocardial Infarction

Human serum paraoxonase-1 (PON1), an enzyme on HDL prevents oxidation of LDL thereby preventing the development of atherosclerosis. Studies done so far have lead to conflicting results. As studies are lacking in North-West Indian Punjabi’s, a distinct ethnic group with high incidence of coronary artery disease, we determined PONase activity in this population. It has been postulated that sudden lowering of serum PONase may lead to precipitation of acute myocardial infarction. We determined serum PONase activity and lipids in 100 patients each of AMI (within 24 h of onset), stable CAD and 100 age and sex matched healthy controls. These were again determined after 6 weeks in AMI patients. The mean serum PONase activity was lowest in AMI patients (23.26 U/ml) followed by stable CAD patients (102.0 U/ml) where as in controls was highest (179.8 U/ml). In patients with AMI, activity was significantly higher at 6 weeks as compared to that after acute event (49.39 %; p < 0.05). Sudden lowering of serum PONase activity in a population which already has lower activity may be one of the risk factors for development of AMI.     

Erythrocytic adenosine deaminase in post myocardial infarction angina patients

A comparative study on the levels of erythrocyte adenosine deaminase and lipid peroxidation has been undertaken in post myocardial infarction angina patients along with age and sex matched healthy individuals serving as control. Present findings show that levels of adenosine deaminase is highly elevated in post myocardial infarction angina patients compared to healthy persons. Malondialdehyde levels are also significantly increased in post myocardial infarction angina patients. The study shows that adenosine deaminase has an important implication in ischemic myocardial syndrome.     

Comparison Between Serum hsCRP and LDL Cholesterol for Search of a Better Predictor for Ischemic Heart Disease

Acute myocardial Infarction is one of the major causes of morbidity & mortality in world and atherosclerosis is the major cause of ischemic heart disease. In order to determine the better clinical marker of atherosclerosis, we estimated serum low-density lipoprotein (LDL-C) and high sensitivity C-reactive protein (hsCRP). Hundred patients of myocardial infarction and 100 controls irrespective of age and sex were studied for these parameters over a period of 2 years. The statistical analysis showed that the serum hsCRP was significantly raised in myocardial infarction cases than controls (P < 0.01) but LDL-C was not (P > 0.05). We conclude that the serum hsCRP has better predictive value for risk of atherosclerosis.     

Association of hyperhomocysteinemia to alcohol withdrawal in chronic alcoholics

This study is conducted in chronic alcoholics to assess the association of an Individual’s level of serum homocysteine with the success of achieving alcohol deaddiction in the patient. The patients’ nutrition status is also assessed. 50 chronic alcoholics admitted to a deaddiction center were inducted into the study. Patients underwent an 8 weeks holistic program to promote rehabilitation from alcoholism. All the patients were addicted to alcohol for 8 – 10 years. Of the 50 patients enrolled, 39 of them completed the 8 weeks program including complete abstinence from alcohol during this period. Fasting blood samples were collected on admission and again after 8 weeks of alcohol abstinence for analyses of serum homocysteine and serum prealbumin, transferrin, total proteins and albumin, gammaglutamyl transferase (GGT) and alanine transaminase (ALT). Of the 50 patients enrolled in the study, 39 completed the 8 weeks rehabilitation program. 11 patients discontinued within 2 weeks of admission. During the 8 weeks of complete alcohol abstinence, patients were given a balanced diet and multivitamin supplements. A significant improvement in their nutritional status was noted by the elevation of serum levels of prealbumin, transferrin, total proteins and albumin. Serum homocysteine levels decreased significantly (p<0.002) to normal levels from previous hyperhomocytenemia. This was accompanied by decrease in serum GGT and ALT levels indicating improved liver functions. Serum estimation of homocysteine in chronic alcoholics is important to assess whether the patient will have a successful rehabilitation. Normal homocysteine levels are achieved after dietary changes and abstinence from alcohol. Timely correction of hyperhomocysteinemia also provides successful rehabilitation.     

Effect of vitamin E on platelet enzymatic anti-oxidants in the patients of myocardial infarction

Effect of administration of 600 mg. vitamin E each day, for six days, was observed on activity of some of the anti-oxidant enzymes and levels of malondialdehyde (as an index of free radical mediated damage) in the platelets of patients reperfused after myocardial infarction. It has been found that vitamin E administration significantly lowers the level of malondialdehyde in the patients. Vitamin E administration increases the activities of anti oxidant enzymes (viz. superoxide dismutase, glutathione reductase and catalase) tested both in the patients and healthy controls. Vitamin E administration causes general stimulation of anti-oxidant enzyme activities both in healthy persons and the patients, however, lowering of lipid per-oxidation upon administration of vitamin E is specific for patients. These findings exhibit beneficial role of vitamin E administration in the management of the patients reperfused after myocardial infarction.     

Combinatorial Determination of Ischemia Modified Albumin and Protein Carbonyl in the Diagnosis of NonST-Elevation Myocardial Infarction

Ischemia modified albumin (IMA) and Protein Carbonyl (PC) have known as proteins that are modified on the similar basis of oxidative stress induced protein modification and may have diagnostic potential in acute myocardial infarction. This study aims to evaluate the ability of using IMA and PC content to diagnose Non-ST elevation myocardial infarction (NSTEMI) and efficiency of combining these two markers. Serum from NSTEMI and healthy control were determined for serum IMA and PC content. The results showed that both of serum IMA level and PC content in NSTEMI was significantly higher than that of healthy controls. However, the PC content showed greater diagnostic performance than IMA. Combinatorial determination of serum IMA level with PC content level was enhanced test efficiency. In conclusion, our finding demonstrated that IMA and PC content can be used as a diagnostic marker for NSTEMI.     

Diagnostic accuracy of heart fatty acid binding protein (H-FABP) and glycogen phosphorylase isoenzyme BB (GPBB) in diagnosis of acute myocardial infarction in patients with acute coronary syndrome

Introduction:

This study aimed to assess whether heart fatty acid-binding protein (H-FABP) and glycogen phosphorylase isoenzyme BB (GPBB) could be used for the accurate diagnosis of acute myocardial infarction (AMI) in acute coronary syndrome (ACS) patients.

Materials and methods:

The study included 108 ACS patients admitted to a coronary unit within 3 h after chest pain onset. AMI was distinguished from unstable angina (UA) using a classical cardiac troponin I (cTnI) assay. H-FABP and GPBB were measured by ELISA on admission (0 h) and at 3, 6, 12, and 24 h after admission; their accuracy to diagnose AMI was assessed using statistical methods.

Results:

From 92 patients with ACS; 71 had AMI. H-FABP and GPBB had higher peak value after 3 h from admission than cTnI (P = 0.001). Both markers normalized at 24 h. The area under the receiver operating characteristic curves was significantly greater for both markers in AMI patients than in UA patients at all time points tested, including admission (P < 0.001). At admission, the H-FABP (37%) and GPBB (40%) sensitivities were relatively low. They increased at 3 and 6 h after admission for both markers and decreased again after 24 h. It was 40% for H-FABP and approximately 2-times lower for GPBB (P < 0.01). In AMI patients, both biomarkers had similar specificities, positive- and negative-predictive values, positive and negative likelihood ratios, and risk ratios for AIM.

Conclusion:

H-FABP and GPBB can contribute to early AMI diagnosis and can distinguish AMI from UA.