The findings suggest that mutations in the promoter region of the thrombomodulin gene may constitute a risk for arterial thrombosis.

Objective-To exane the prognostic significance and role in risk stratification of the biochemical marker troponin T in patients admitted with unstable angina.Design-Single centre, blinded, prospective study ofpatients admitted with chest pain.Setting

The presence of admission troponin T in patients with myocardial infarction defines a subgroup, particularly those with ST-segment elevation, at increased risk of subsequent cardiac events and identifies a group that may benefit from alternative early management strategies.

Elevated total homocysteine levels on admission strongly predict late cardiac events in acute coronary syndromes.

SUMMARY. 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 pg/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 pg/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, H D 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. Additional key phrases: haemodialysis; multiple organ failureThere is a high prevalence of cardiovascular complications in patients receiving renal replacement therapy.' The precise genesis of these are unknown, but hypertension, problems in fluid and electrolyte balance, metabolic abnormalities, including hyperlipidaemia and a direct toxic cardiomyopathy all contribute.2 We have measured cardiac troponin T (cTnT) and cardiac troponin I (cTnI) in the serum of patients with renal dysfunction to see if cardiac troponins were detectable and if they correlated with any other clinical or biochemical findings. METHODSPatients were classified as having chronic renal impairment (CRI, creatinine 120-200 pmol/L, Correspondence: Dr. P 0 Collinson.

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 ϭ117) presenting with confirmed acute myocardial infarction (MI) (n ϭ57) or unstable angina pectoris (UAP) (n ϭ60) were consecutively recruited together with patients (n ϭ18) 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 F1ϩ2 were analyzed by ELISA. There were significant elevations in F1ϩ2 in MI (PϽ0.001) and UAP (Pϭ0.003), and modest elevations in Factor VIIa in UAP (PϽ0.05) 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 F1ϩ2 (PϽ0.0001) and of Factor VIIa (PϽ0.05). There were significant correlations in ACS between homocysteine and F1ϩ2 (rϭ0.46, PϽ0.0001), homocysteine and Factor VIIa (rϭ0.24, PϽ0.01), and F1ϩ2 and Factor VIIa (rϭ0.41, PϽ0.0001). There was no correlation between homocysteine and either F1ϩ2 (rϭϪ0.15, Pϭ0.57) or Factor VIIa (rϭ0.22, Pϭ0.37) 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.

SummaryThrombomodulin 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.

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