Diagnostic and prognostic role of cardiac troponin I (cTnI) measured on the DPC Immulite.

OBJECTIVE: To evaluate the diagnostic and prognostic role of the Immulite cTnI assay for the detection of acute coronary syndromes (ACS). POPULATION: 150 males and 63 females with a median age of 63 years, range 28 to 88, and an interquartile range of 18 years were admitted within 24 h of chest pain and non-ST segment elevation ACS were studied. The median onset of symptoms was 3 h (range 0-23). METHODS: Venous samples were taken on admission (t = 0) and at 24 h (t = 24). The serum samples were assayed for CK, CK-MB and cTnT on an Elecsys 1010 (Roche Diagnostics, Lewes, UK). The cTnT assay CV was 5.5% at 0.32 microg/l and 5.4% at 6.0 microg/l, and the detection limit was 0.01 microg/l with an upper limit of 25 microg/l. For cTnI using the Immulite (DPC, Gwynedd, Wales), the detection limit was 0.1 microg/l, and the upper limit was 180 microg/l. Final diagnostic categorization was performed by both WHO and European Society of Cardiology criteria using cTnT as the diagnostic cardiac biomarker. Patients were followed for the major adverse cardiac events (MACE), endpoints cardiac death, AMI or need for urgent revascularization. ROC curves were constructed using final diagnosis. Outcome prediction was assessed by ROC curves and Kaplan-Meier survival curves. RESULTS: Both methods had equivalent diagnostic efficiency using WHO criteria for AMI. When ESC criteria were used the AUC for admission and 24 h cTnT and cTnI values were 0.945 vs. 0.910, P = 0.20 and 0.998 vs. 0.937, P = 0.005, respectively. Both methods predicted outcome as either death or MI or MACE and were not significantly different. CONCLUSION: The Immulite cTnI assay can be used for diagnosis and risk stratification in patients admitted with non-ST segment elevation acute coronary syndromes.

Multicentre evaluation of the diagnostic value of cardiac troponin T, CK-MB mass, and myoglobin for assessing patients with suspected acute coronary syndromes in routine clinical practice.

OBJECTIVE: To assess the diagnostic efficiency of the third generation cardiac troponin T assay in routine clinical practice. DESIGN: Prospective observational study of unselected consecutive admissions. SETTING: Multicentre study in 43 teaching and non-teaching hospitals in 13 countries. SUBJECTS: 1105 hospital admissions, median age 67 years (range 15-96 years, 63.7% male) with suspected acute coronary syndromes (72.3% of cases) or other non-specific symptoms where cardiac disease required exclusion (27.7%). INTERVENTIONS: Over the study period, myoglobin, creatine kinase MB isoenzyme (CK-MB), and cardiac troponin T where measured in parallel with conventional diagnostic tests. Final diagnostic classification involved standard ECG changes and CK-MB mass exceeding 5.0 microg/l. MAIN OUTCOME MEASURES: Diagnostic efficiency was assessed by receiver operator characteristic curve analysis including and excluding patients with unstable angina. RESULTS: Measurement of cardiac troponin T was diagnostically equivalent to CK-MB and both were better than myoglobin, with areas under the curve at 12 hours of 0.94, 0.99, and 0.80, respectively. Diagnostic criteria using CK-MB were inadequate and showed bias when patients with unstable angina were included. Elevations of cardiac troponin T did not occur when cardiac disease could be categorically excluded but were found in clinical conditions other than suspected acute coronary syndromes. CONCLUSIONS: CK-MB is unsuitable as a diagnostic gold standard even at the proposed lower threshold. A lower cut off for cardiac troponin T of 0.05 microg/l should be used for diagnosis of acute myocardial infarction. Diagnosis of acute myocardial infarction cannot be made solely on the basis of a cardiac troponin T result.

Plasma insulin-like growth factor-1 elevated in mild-to-moderate but not severe heart failure.

BACKGROUND: Insulin-like growth factor 1 (IGF-1) promotes favorable cardiac remodeling in heart failure. However, the relation of plasma IGF-1 in patients with various degrees of heart failure is not known. METHODS: Venous plasma samples were collected from patients with clinically documented heart failure (n = 24) and from control subjects (n = 21) for measurements of IGF-1 levels. In the heart failure group, functional assessment of the physical capacity was determined by means of the New York Heart Association (NYHA) score. Objective determination of ventricular performance was made by transthoracic echocardiographic measurement of left ventricular fractional shortening (FS). RESULTS: IGF-1 levels were higher in patients with heart failure (mean age, 67 +/- 2 years; 17 men) than in control subjects (age, 71 +/- 2 years; 9 men) (20.2 +/- 2 mU/L, 14.1 +/- 2 mU/L, respectively, P <.05). However, the elevated IGF-1 levels were demonstrated only in patients with mild-to-moderate symptoms (NYHA classes I and II) of heart failure (24.7 +/- 3.3 mU/L, n = 12, P =.005 vs control subjects) but not in patients with severe symptoms (NYHA classes III and IV) (15.7 +/- 2.3 mU/L, n = 12). There was a strong positive correlation between IGF-1 levels and left ventricular FS (%) (r = 0.58, P =.003, n = 24). Adjustments for other potential confounders including age, sex, treatment received, and underlying cause of heart failure did not alter the relation between IGF-1 and left ventricular FS (odds ratio, 2.01; 95% confidence interval, 1.26 to 6.24; P =.01). CONCLUSIONS: Plasma levels of IGF-1 show distinct variations with the severity of heart failure and may play a vital role in compensated heart failure.

Acute and convalescent changes in plasma homocysteine concentrations in acute coronary syndromes.

BACKGROUND: Raised plasma homocysteine is a risk factor for coronary artery disease. Patients with myocardial infarction or unstable angina show greater activation of coagulation, greater troponin release, and a worse outcome. OBJECTIVE: To examine variations in plasma homocysteine concentration in relation to C reactive protein (CRP) in patients presenting with acute coronary syndromes. METHODS: Consecutive patients presenting with acute myocardial infarction (22) and unstable angina pectoris (12) were studied. Plasma samples were obtained on admission (before clinical intervention), on days 2, 7, and 28, and again six months after admission. Plasma homocysteine, assayed by high performance liquid chromatography, and CRP were both determined at the same time points. Changes were assessed by analysis of variance. RESULTS: CRP concentrations showed a classical rise on day 2, followed by a gradual decline to normal values taken at six months from admission in both myocardial infarction (p < 0.0001) and unstable angina (p = 0.02). Homocysteine concentrations in myocardial infarction (median, 25th to 75th interquartile range) were: 11.9 (10.7 to 12.6), 11.5 (9.1 to 13.4), 12.1 (11.4 to 14.1), 12.4 (11.1 to 14.4), and 12.1 (11.2 to 14.0) micromol/l, for days 1, 2, 7, 28, and 180, respectively (p = 0.02). Significant differences were observed only between day 2 and day 7 (p < 0.05). The final homocysteine measurement was not different from the admission level. Homocysteine concentrations in unstable angina did not differ between admission and convalescence (12.5 (9.1 to 14.5) micromol/l and 12.3 (7.7 to 14.9) micromol/l, respectively). CONCLUSIONS: Plasma homocysteine concentrations are minimally influenced by acute phase variations with reliable measurements obtained on admission in patients with myocardial infarction and unstable angina.

Elevated homocysteine levels are associated with increased ischemic myocardial injury in acute coronary syndromes.

OBJECTIVES: This study was conducted to determine whether the amount of myocardial damage during acute coronary syndromes (ACS) is related to the admission plasma homocysteine concentration. BACKGROUND: Elevated homocysteine levels are associated with increased thrombosis in patients presenting with ACS. It is not known whether this association is reflected in the degree of myocardial injury in those patients. METHODS: We studied consecutive patients presenting with acute myocardial infarction (MI) (n = 205) and unstable angina pectoris (UAP) (n = 185). Plasma samples were collected on admission and prior to clinical intervention and were assayed for homocysteine by high performance liquid chromatography (HPLC). Myocardial necrosis was assessed by measurements of cardiac troponin T (cTnT) on admission and 12 h after admission (peak cTnT). The patients were studied by quintiles of homocysteine concentration. RESULTS: There was a significant increase in peak cTnT in the 5th homocysteine quintile in MI (analysis of variance [ANOVA], p = 0.005), the levels being 4.10, 3.86, 4.13, 6.20 and 7.85 microg/liter for quintiles 1 to 5, respectively (p < 0.0001, for top vs. bottom quintile). Similarly, there was a step-up in peak cTnT levels in the top homocysteine quintile in UAP (ANOVA, p < 0.0001), the levels being 0.03, 0.03, 0.02, 0.04 and 0.15 microg/liter, (p < 0.0001 for top vs. bottom quintile). In a multivariate regression model, the association between peak cTnT and the top homocysteine quintile remained strong after adjustment of other confounders including age, gender, final diagnosis and thrombolysis treatment (odds ratio [OR]: 2.92 (1.75-4.87) p < 0.0001). The patients with UAP were further examined according to peak cTnT levels below (cTnT negative) or above (cTnT positive) 0.1 microg/liter. Homocysteine levels were significantly higher in cTnT positive than cTnT negative patients; 13.8 (11.7-15.3) vs. 10.3 (9.4-11.3) micromol/liter, respectively, p = 0.002. CONCLUSIONS: Elevated homocysteine levels are associated with a higher risk of ischemic myocardial injury in patients presenting with ACS.

Effect of plasma homocysteine concentration on early and late events in patients with acute coronary syndromes.

BACKGROUND: Although a raised plasma homocysteine is a risk factor for vascular disease, it is not known whether it is associated with an adverse cardiac outcome in patients admitted with acute coronary syndromes. We evaluated the relationship between plasma homocysteine and short-term (28 days) and long-term (median 2.5 years) prognosis in acute coronary syndromes. METHODS AND RESULTS: We evaluated the relationship of quintiles of homocysteine to fatal and nonfatal coronary disease early (28 days) and late (29 days to a median of 2. 5 years) after admission to a single unit of patients with unstable angina (n=204) and myocardial infarction (n=236). The end points studied were cardiac death (n=67) and/or myocardial (re)infarction (n=30). Cox regression and logistic regression were used to estimate the relationship of homocysteine to coronary events. The event rate within the first 28 days (22 cardiac deaths and 5 nonfatal infarctions) was not related to the admission homocysteine level. In the 203 unstable angina and 214 myocardial infarction survivors, an apparent threshold effect was seen on long-term follow-up, with a significant step-up in the frequency of events between the lowest 3 quintiles (14 cardiac deaths and 11 nonfatal infarctions) and the upper 2 quintiles (31 fatal and 12 nonfatal events). Patients in the upper 2 quintiles (>12.2 micromol/L) had a 2.6-fold increase in the risk of a cardiac event (95% CI, 1.5 to 4.3, P<0.001). CONCLUSIONS: Elevated total homocysteine levels on admission strongly predict late cardiac events in acute coronary syndromes.

Relationships between homocysteine, factor VIIa, and thrombin generation in acute coronary syndromes.

BACKGROUND: It has been suggested by clinical, epidemiological, and experimental in vitro studies that homocysteine potentiates thrombin generation. This prothrombotic effect however has not previously been demonstrated in patients presenting with acute coronary syndromes (ACS). METHODS AND RESULTS: Patients with ACS (n =117) presenting with confirmed acute myocardial infarction (MI) (n =57) or unstable angina pectoris (UAP) (n =60) were consecutively recruited together with patients (n =18) in whom the presenting chest pain was not of cardiac origin (NCP), included as controls. Plasma samples were collected on admission and before clinical intervention. Homocysteine was assayed by high performance liquid chromatography, and both Factor VIIa and prothrombin fragment F1+2 were analyzed by ELISA. There were significant elevations in F1+2 in MI (P<0.001) and UAP (P=0.003), and modest elevations in Factor VIIa in UAP (P<0.05) compared with NCP but no differences in homocysteine levels among those groups. On dividing patients with ACS into quartiles of homocysteine, there was a stepwise increase in F1+2 (P<0.0001) and of Factor VIIa (P<0.05). There were significant correlations in ACS between homocysteine and F1+2 (r=0.46, P<0.0001), homocysteine and Factor VIIa (r=0.24, P<0.01), and F1+2 and Factor VIIa (r=0.41, P<0.0001). There was no correlation between homocysteine and either F1+2 (r=-0.15, P=0.57) or Factor VIIa (r=0. 22, P=0.37) in the NCP patients. CONCLUSIONS: Elevated plasma homocysteine is associated with and may cause elevated Factor VIIa and thrombin generation in patients presenting with ACS. These findings suggest an explanation for the prothrombotic effect of homocysteine in ACS.

Identification and characterization of a thrombomodulin gene mutation coding for an elongated protein with reduced expression in a kindred with myocardial infarction.

Thrombomodulin is an endothelial cell receptor for thrombin. It functions as a natural anticoagulant by greatly accelerating activation of protein C by thrombin. Using a direct gene screening strategy we identified a frameshift insertion mutation, insT 1689, in the thrombomodulin gene of a patient with myocardial infarction. The mutation predicts an elongated gene product because of substitution of the 12 C-terminal amino acids by 61 abnormal residues. Pedigree analysis showed that the mutation was also likely to have been present in a sibling who had had fatal myocardial infarction. Carriers of the mutant allele express significantly lower amounts of thrombomodulin on the surface of their monocytes detected by flow cytometry and have lower levels of soluble thrombomodulin in plasma. Wild type and the mutant thrombomodulin were expressed in COS-7 cells. Cellular distribution of the expressed proteins was evaluated by immunofluorescence microscopy, which showed reduced cell surface expression and intense juxtanuclear localization of the abnormal protein. This suggests impaired translocation through the endoplasmic reticulum/Golgi apparatus. Cells expressing abnormal thrombomodulin had reduced ability ( approximately 2.5-fold) to accelerate the thrombin mediated activation of protein C. This is the first demonstration of reduced expression arising from a natural thrombomodulin gene mutation. The results provide support for the suggestion that gene mutation of thrombomodulin may be important in the pathogenesis of some cases of occlusive thrombotic disease. (Blood. 2000;95:569-576)

Significance of an index of insulin resistance on admission in non-diabetic patients with acute coronary syndromes.

BACKGROUND: Insulin resistance is associated with ischaemic heart disease and has been proposed as a risk factor for subsequent myocardial infarction. AIM: To investigate the potential use of a recently proposed insulin resistance index in identifying insulin resistance in patients admitted with an acute coronary syndrome. METHODS: Single centre study of 441 non-diabetic patients admitted with chest pain to a coronary care unit and followed prospectively for a median of three years for outcome. Admission glucose and insulin concentrations were measured and from these values an admission index of insulin resistance (AIRI) calculated. Its association with other known factors in the insulin resistance syndrome, and subsequent outcome, was examined. RESULTS: The AIRI was greater in patients with myocardial infarction than in a control group without myocardial infarction (p < 0.0001). A Cox regression model for subsequent cardiac death identified previous myocardial infarction (p < 0.0001), infarct size (p < 0.0001), and AIRI (p = 0. 0033) as positive risk predictors. Patients of Indian subcontinent ethnic origin had greater AIRI values than white patients: mean (SD) 7.5 (1.3) v 4.6 (0.2), p < 0.001. CONCLUSIONS: A simple index of insulin resistance measured on patients admitted with myocardial infarction provides an important predictive measure of poor outcome and is superior to admission glucose measurement. It may be useful in identifying patients admitted with myocardial infarction who could benefit from alternative early management strategies.

Circulating stress hormone and insulin concentrations in acute coronary syndromes: identification of insulin resistance on admission.

We re-examined, in the context of modern practice, plasma insulin and stress hormone concentrations in patients admitted to hospital with acute coronary syndromes. Venous blood sampling was carried out prior to anti-thrombotic therapy in 148 patients with myocardial infarction (MI); 76 patients with unstable angina (UA) pectoris were also studied, together with 27 patients with non-cardiac chest pain (NCP). There were significant progressive increases in the concentrations of catecholamines, cortisol, glucose and insulin from NCP to UA to MI patients. Hyperglycaemia (glucose >8 mmol/l) was present in over 50% of MI patients. The plasma cortisol and insulin levels were both significantly positively correlated with the glucose concentration on admission. Only the cortisol concentration was correlated with peak cardiac enzyme levels. The glucose and insulin concentrations on admission in 141 MI and UA patients were related to insulin resistance, as judged from subsequent insulin and glucose concentrations measured while fasting and during a glucose tolerance test. The product of admission insulinxglucose (divided by 25; the admission insulin-resistance index, or AIRI) was significantly correlated with indices of insulin resistance, and was significantly higher (approximately double) in the MI group (7. 81+/-0.76) and the UA group (6.88+/-1.19) than in the control NCP group (3.59+/-0.06; Kuskul-Wallis: P=0.0001), implying that the insulin levels in the first two groups were approximately twice as high as is appropriate for the glucose levels. The ethnic origin of 20% of the patients was the Indian subcontinent; admission insulin and glucose levels in this subgroup were higher than in the non-Asians across all the groups with chest pain. Cortisol was the only stress hormone that was raised in proportion to the size of the infarct, and is a likely partial cause of the elevation in blood glucose. The high insulin levels were related to the prevalence of insulin resistance, and this was particularly important in the Asian subgroup presenting with MI and UA. Thus it appears feasible to identify acute coronary syndrome patients who are insulin-resistant at a time (on admission) when alternative early therapeutic strategies can be instituted.

A mutation in the thrombomodulin gene, 127G to A coding for Ala25Thr, and the risk of myocardial infarction in men.

Thrombomodulin is an endothelial cell surface receptor that transforms the procoagulant thrombin into an anticoagulant. A mutation in the thrombomodulin gene is a potential risk factor for venous and arterial thrombosis. We screened a region within the coding sequence of the thrombomodulin gene by single-strand conformation polymorphism analysis (SSCP) in a pilot study of 104 patients with myocardial infarction and 104 age, sex and race matched controls. We identified a 127G to A mutation in the gene, which predicts an Ala25Thr substitution, in 2 out of 104 patients (1 man and 1 woman) with myocardial infarction but in no controls. We assessed the risk of myocardial infarction associated with the mutation in a larger "Study of Myocardial Infarctions Leiden" (SMILE). Among 560 men with a first myocardial infarction before the age of 70, 12 were carriers of the Ala25Thr substitution. In a control group of 646 men, frequency-matched for age, seven were carriers of the Ala25Thr substitution. The allelic frequencies were 1.07% among patients and 0.54% among controls suggesting risk associated with the mutation [odds ratio (OR) 2.0, 95% confidence interval (CI) 0.8-5.1]. In patients aged below 50, the predicted risk was almost seven times increased (OR 6.5, CI 0.8-54.2). In the presence of additional risk factors, such as smoking and a metabolic risk factor, the predicted risk increased to 9-fold (OR 8.8. CI 1.8-42.2) and 4-fold (OR 4.4, CI 0.9-21.3), respectively. While not conclusive, these results strongly suggest that the Ala25Thr substitution is a risk factor for myocardial infarction, especially in young men, and when in the presence of additional risk factors.

Cardiac troponins in patients with renal dysfunction.

Cardiac troponin T (cTnT) and cardiac troponin I (cTnI) were measured in 198 patients with renal dysfunction [132 men: median (range) age 66.1 (8.2-90.3) years]. cTnT was measured by two methods: ELISA and Enzymun (Boehringer Mannheim UK, Lewes, UK), both with a detection limit of 0.05 microgram/L in 179 and 78 patients, respectively. cTnI was measured in 80 patients by the OPUS plus and OPUS Magnum systems (Dade-Behring, Milton Keynes, UK) with a detection limit of 0.5 microgram/L. Patients were classified as having chronic renal impairment (CRI), chronic renal failure (CRF), acute renal failure including those with multiple organ failure on renal replacement therapy (ARF), and patients with chronic renal failure treated with haemodialysis (HD). Cardiac troponins were detectable in the serum of patients with renal dysfunction. cTnT was detectable in 113/179 (63.1%) and 33/78 (42.3%) by the ELISA and Enzymun methods respectively. cTnI was detectable in 17/80 (21.3%). cTnT (ELISA and Enzymun methods) and cTnI were detectable with increased frequency in the CRF, HD and ARF patient groups compared with the CRI group. Cardiac troponin concentrations did not correlate with serum creatine kinase (CK) activity, CK-MB, or urea or creatinine levels. Serial cardiac troponin measurements may be required to confirm or exclude a diagnosis of acute coronary syndromes in patients with renal dysfunction.

Thrombomodulin gene mutations associated with myocardial infarction.

BACKGROUND: Thrombomodulin is an important receptor for thrombin on the endothelial cell surface of most blood vessels, including those of the heart. Thrombin-bound thrombomodulin activates protein C, which inhibits thrombin generation by degrading factors Va and VIIIa. The aim of this study was to analyze the 5' region of the thrombomodulin gene to determine whether mutations contribute a risk for myocardial infarction. METHODS AND RESULTS: We screened the promoter region of the thrombomodulin gene by single-stranded conformation polymorphism analysis in 104 patients with diagnosed myocardial infarction. Five mutations (three distinct) were identified (GG-9/-10AT, G-33A, and C-133A). The dinucleotide mutation GG-9/-10AT was identified in 3 individuals (2 heterozygous, 1 homozygous). Only one of the three different mutations was identified in 104 patient control subjects matched for age, sex, and race (G-33A in a single individual). All mutations identified were in close proximity to consensus sequences for transcription control elements within the thrombomodulin gene. In contrast, no difference was observed between patients and control subjects for the allelic frequency of a previously identified neutral polymorphism GCC/GTC coding for Ala/Val455, with 3 individuals homozygous for GTC (Val) in both groups. CONCLUSIONS: The findings suggest that mutations in the promoter region of the thrombomodulin gene may constitute a risk for arterial thrombosis.

A novel specific immunoassay for plasma two-chain factor VIIa: investigation of FVIIa levels in normal individuals and in patients with acute coronary syndromes.

We report the development of an enzyme-linked immunosorbent assay (ELISA) that is specific for factor VIIa (FVIIa). This assay uses a neoantigen specific capture antibody directed to the amino acid peptide sequence N terminal to the FVII cleavage activation site. The antibody exhibits approximately 3,000-fold greater reactivity to FVIIa than FVII on a molar basis. Experiments using plasma with added (exogenous) human FVIIa gave quantitative recovery in the ELISA over a range of 0.20 to 3.2 ng/mL of FVIIa. The intra- and inter-assay coefficient of variation (CVs) of the ELISA are 4.5% and 9.8%, respectively. The ELISA shows excellent correlation (r = .99) with a functional assay (using recombinant soluble tissue factor) in detecting FVIIa added to plasma over the range 0.05 to 18.0 ng/mL. However, a major discrepancy exists between the two assays when normal endogenous plasma concentrations of FVIIa are measured. Using normal plasma (n = 14) the functional assay reported 3.10 +/- 0.30 ng/mL (mean +/- SE) whereas only 0.025 +/- 0.010 ng/mL was detected in the same samples by the immunoassay. Patients (n = 43) presenting with acute coronary syndromes (myocardial infarction and unstable angina) exhibited elevations (P < .05) in immunologically detected FVIIa, 0.093 +/- 0.013 ng/mL (mean +/- SE) compared to patient controls (n = 20) contemporaneously admitted with noncardiac chest pain, 0.048 +/- 0.007 ng/mL (mean +/- SE). These elevations in the acute coronary syndromes were accompanied by increased (P < .05) and correlating prothrombin fragment F1 + 2 levels (Spearman correlation coefficient rs = .4, P < .01), demonstrating that thrombin generation is certainly associated with, and may even be caused by, extrinsic pathway activation.

Early 'rule-in' diagnosis of acute myocardial infarction 4 h post admission for rapid risk stratification by creatine kinase increment (creatine kinase change).

The use of creatine kinase (CK) measurement on admission, CK at 4 h, percentage CK change and electrocardiography (ECG) were compared for early risk stratification in the diagnosis of acute myocardial infarction (AMI). A total of 248 patients (median age 62 years, range 26-84) were studied (187 men, 61 women) of whom 118 had a final diagnosis of AMI. Median time to presentation was 3.92 h (range 0-11.17 h). Overall, the admission ECG had a sensitivity of 72.6% [95% confidence interval (CI) 64.6-80.7] with specificity of 88.9% (CI 83.4-94.4); 4 h CK change had a sensitivity of 100% (CI 96.1-100) with a specificity of 90.4% (CI 83.5-95.1). After excluding those with contraindication to anti-thrombotic therapy there were 109 patients with an uncertain initial diagnosis. In this group, admission CK had a sensitivity of 37.5% (CI 18.8-59.4) with a specificity of 94% (CI 86.8-98.1); 4 h ECG had a sensitivity of 43.8% (CI 19.8-70.1) with specificity of 97.4% (CI 86.5-99.9%); 4 h CK had a sensitivity of 79.2% (CI 57.8-92.9) with a specificity of 96.5% (CI 90-99.3); 4 h CK increment had a sensitivity of 100% (CI 85.8-100) with a specificity of 94% (CI 86.8-98.1). The admission ECG remains the investigation of choice for early 'rule-in' diagnosis of AMI for thrombolysis. Admission measurement of CK offers a small advantage in the patient with an uncertain diagnosis but the overall benefit is low. A strategy of admission ECG plus serial testing allows diagnosis to be complete by 4 h for accurate risk stratification. Whether this can be used for selection for therapeutic options (thrombolytic, anti-coagulation, anti-platelet or anti-anginal agents) requires further clinical trials.

Measurement of serum troponin T, creatine kinase MB isoenzyme, and total creatine kinase following arduous physical training.

We have compared measurement of cardiac troponin T by enzyme linked immunosorbent assay with creatine kinase MB isoenzyme (CK-MB) concentration measurement in 219 Royal Marine commandos with no evidence of cardiovascular disease who have elevated creatine kinase (CK) produced by arduous physical training. CK was elevated up to 22.6 times and CK-MB mass up to 6.6 times the upper reference limit. Only two commandos had detectable cardiac troponin T, with neither exceeding the upper reference limit of 0.2 micrograms/L. At decision thresholds optimized for diagnosis of acute myocardial infarction in previous published work, 58.3% of the total CK activity, 13.8% of the CK-MB concentration/CK activity ratio and 1.6% of CK-MB concentration measurements showed elevated values but no elevations in cardiac troponin T occurred. Cardiac troponin T is currently the investigation of choice for the differential diagnosis of patients with an elevated CK due to skeletal muscle trauma to exclude myocardial damage.

Rapid troponin T measurement in whole blood for detection of myocardial damage.

A dry chemistry system for rapid qualitative measurement of cardiac troponin T in whole blood, serum, EDTA and lithium heparin plasma was studied in 197 admissions to the coronary care unit and general wards of a typical district general hospital for whom troponin T was requested. This included patients with unexplained collapse, acute dysrythmia or elevated creatine kinase of unknown origin. EDTA whole blood and plasma proved the most satisfactory sample matrices. Lithium heparin whole blood was equally appropriate but lithium heparin plasma gave a false negative result. Serum was an unsatisfactory sample material. Comparison with the conventional wet chemistry quantitative enzyme-linked immunosorbent assay showed a positive bias for EDTA plasma, particularly in the range 0-1 microgram/L and a significant negative bias for lithium heparin plasma. There was no difference between serum from plain or gel separator tubes. The whole blood method allows troponin T measurement to be performed rapidly and simply in the laboratory, either as an emergency test to alter patient management, or for those laboratories that wish to offer troponin T for selected cases but do not have the ability to measure troponin T quantitatively.