Cystatin C for enhancement of risk stratification in non-ST elevation acute coronary syndrome patients with an increased troponin T.

BACKGROUND: We assessed the value of cystatin C for improvement of risk stratification in patients with non-ST elevation acute coronary syndrome (nSTE-ACS) and increased cardiac troponin T (cTnT), and we compared the long-term effects of an early invasive treatment strategy (EIS) with a selective invasive treatment strategy (SIS) with regard to renal function. METHODS: Patients (n = 1128) randomized to an EIS or an SIS in the ICTUS trial were stratified according to the tertiles of the cystatin C concentration at baseline. The end points were death within 4 years and spontaneous myocardial infarction (MI) within 3 years. RESULTS: Mortality was 3.4%, 6.2%, and 13.5% in the first, second, and third tertiles, respectively, of cystatin C concentration (log-rank P < 0.001), and the respective rates of spontaneous MI were 5.5%, 7.5%, and 9.8% (log-rank P = 0.03). In a multivariate Cox regression analysis, the cystatin C concentration in the third quartile remained independently predictive of mortality [hazard ratio (HR), 2.04; 95% CI, 1.02-4.10; P = 0.04] and spontaneous MI (HR, 1.95; 95% CI, 1.05-3.63; P = 0.04). The mortality rate in the second tertile was lower with the EIS than with the SIS (3.8% vs 8.7%). In the third tertile, the mortality rates with the EIS and the SIS were, respectively, 15.0% and 12.2% (P for interaction = 0.04). Rates of spontaneous MI were similar for the EIS and the SIS within cystatin C tertiles (P for interaction = 0.22). CONCLUSIONS: In patients with nSTE-ACS and an increased cTnT concentration, mild to moderate renal dysfunction is associated with a higher risk of death and spontaneous MI. Use of cystatin C as a serum marker of renal function may improve risk stratification.

Early invasive versus selectively invasive management for acute coronary syndromes.

BACKGROUND: Current guidelines recommend an early invasive strategy for patients who have acute coronary syndromes without ST-segment elevation and with an elevated cardiac troponin T level. However, randomized trials have not shown an overall reduction in mortality, and the reduction in the rate of myocardial infarction in previous trials has varied depending on the definition of myocardial infarction. METHODS: We randomly assigned 1200 patients with acute coronary syndrome without ST-segment elevation who had chest pain, an elevated cardiac troponin T level (> or =0.03 mug per liter), and either electrocardiographic evidence of ischemia at admission or a documented history of coronary disease to an early invasive strategy or to a more conservative (selectively invasive) strategy. Patients received aspirin daily, enoxaparin for 48 hours, and abciximab at the time of percutaneous coronary intervention. The use of clopidogrel and intensive lipid-lowering therapy was recommended. The primary end point was a composite of death, nonfatal myocardial infarction, or rehospitalization for anginal symptoms within one year after randomization. RESULTS: The estimated cumulative rate of the primary end point was 22.7 percent in the group assigned to early invasive management and 21.2 percent in the group assigned to selectively invasive management (relative risk, 1.07; 95 percent confidence interval, 0.87 to 1.33; P=0.33). The mortality rate was the same in the two groups (2.5 percent). Myocardial infarction was significantly more frequent in the group assigned to early invasive management (15.0 percent vs. 10.0 percent, P=0.005), but rehospitalization was less frequent in that group (7.4 percent vs. 10.9 percent, P=0.04). CONCLUSIONS: We could not demonstrate that, given optimized medical therapy, an early invasive strategy was superior to a selectively invasive strategy in patients with acute coronary syndromes without ST-segment elevation and with an elevated cardiac troponin T level.

N-terminal pro-brain natriuretic peptide for additional risk stratification in patients with non-ST-elevation acute coronary syndrome and an elevated troponin T: an Invasive versus Conservative Treatment in Unstable coronary Syndromes (ICTUS) substudy.

BACKGROUND: New evidence has emerged that the assessment of multiple biomarkers such as cardiac troponin T (cTnT) and N-terminal pro-brain natriuretic peptide (NT-proBNP) in patients with non-ST-elevation acute coronary syndrome (nSTE-ACS) provides unique prognostic information. The purpose of this study was to assess the association between baseline NT-proBNP levels and outcome in patients who have nSTE-ACS with an elevated cTnT and to determine whether patients with elevated NT-proBNP levels benefit from an early invasive treatment strategy. METHODS: Baseline samples for NT-proBNP measurements were available in 1141 patients who have nSTE-ACS with an elevated cTnT randomized to an early or a selective invasive strategy. Patients were followed-up for the occurrence of death, myocardial infarction (MI), and rehospitalization for angina. RESULTS: We showed that increased levels of NT-proBNP were associated with several indicators of risk and severe coronary artery disease. Mortality by 1 year was 7.3% in the highest quartile (> or = 1170 ng/L for men, > or = 2150 ng/L for women) compared with 1.1% of patients in the lower 3 quartiles (P < .0001). N-terminal pro-brain natriuretic peptide (highest quartile vs lower 3 quartiles) was a strong independent predictor of mortality (hazard ratio 5.0, 95% CI 2.1-11.6, P = .0002). However, NT-proBNP levels were not associated with the incidence of recurrent MI by 1 year. Furthermore, we could not demonstrate a benefit of an early invasive strategy compared with a selective invasive strategy in patients with an elevated NT-proBNP level. CONCLUSIONS: We confirmed that NT-proBNP is a strong independent predictor of mortality by 1 year but not of recurrent MI in patients who have nSTE-ACS with an elevated cTnT. We could not demonstrate a benefit of an early invasive strategy compared with a selective invasive strategy.

Prognostic value of predischarge dobutamine stress echocardiography in chest pain patients with a negative cardiac troponin T.

OBJECTIVES: We prospectively studied the prognostic value of predischarge dobutamine stress echocardiography (DSE) in low-risk chest pain patients with a normal or nondiagnostic electrocardiogram (ECG) and a negative serial troponin T. BACKGROUND: Noninvasive stress testing is recommended before discharge or within 72 h in patients with low-risk chest pain. The prognostic value of immediate DSE has not been studied in a blinded, prospective fashion. METHODS: Patients presenting at the emergency room within 6 h of symptom onset and a normal or nondiagnostic ECG were eligible. Dobutamine stress echocardiography was performed after unstable coronary artery disease was ruled out by a standard rule-out protocol and a negative serial troponin T; the occurrence of any new wall motion abnormality was considered positive. Results were kept blinded. End points were cardiac death, myocardial infarction, rehospitalization for unstable angina or revascularization. RESULTS: In total, 377 patients were included. There were 2 deaths, 2 myocardial infarctions, 8 rehospitalization for unstable angina, and 10 revascularizations at six-month follow-up. The end points occurred in 8/26 (30.8%) patients with a positive versus 14/351 (4.0%) patients with a negative DSE (odds ratio, 10.7; 95% confidence interval, 4.0 to 28.8; p < 0.0001). By multivariate analysis, DSE remained a predictor of end points (p < 0.0001). CONCLUSIONS: A predischarge DSE had important, independent prognostic value in low-risk, troponin negative, chest pain patients.

The prognostic value of markers of inflammation in patients with troponin T-negative chest pain before discharge from the emergency department.

PURPOSE: To assess the prognostic value of markers of inflammation for rule-out purposes in patients admitted to the emergency department with troponin T-negative chest pain. METHODS: Patients presenting to the emergency department within 6 hours of symptom onset and who had a normal or nondiagnostic electrocardiogram were eligible. The standard rule-out protocol, which included serial creatine kinase and creatine kinase-MB measurements, was applied, and markers of inflammation (C-reactive protein, erythrocyte sedimentation rate, and total white blood cell count and differential count) were measured. The study group comprised patients with negative serial troponin T results (<0.06 microg/L) who were discharged home after unstable coronary artery disease was ruled out. Endpoints during the 6-month follow-up were cardiac death, myocardial infarction, or rehospitalization for unstable angina. RESULTS: A total of 382 troponin T-negative patients were discharged, of whom 2 died, 2 had a myocardial infarction, and 7 were rehospitalized for unstable angina. A positive C-reactive protein test result (>0.3 mg/dL) was associated with future clinical events (hazard risk [HR] = 4.5; 95% confidence interval [CI]: 1.2 to 17.0; P = 0.03), as was a positive test (>13 mm/h) for erythrocyte sedimentation rate (HR = 5.6; 95% CI: 1.5 to 22.2; P = 0.01). Patients with positive results for both tests were at highest risk of clinical events (9.3%) compared with patients with other combinations of test results (1.1% to 2.1%; HR = 7.5; 95% CI: 2.2 to 25.5; P = 0.001). CONCLUSION: The combination of C-reactive protein and erythrocyte sedimentation rate had prognostic value in patients with troponin T-negative chest pain and a normal or nondiagnostic electrocardiogram in whom unstable coronary artery disease was ruled out.

C-reactive protein and coronary events following percutaneous coronary angioplasty.

PURPOSE: We investigated the associations between baseline C-reactive protein levels in patients undergoing percutaneous coronary angioplasty and death, nonfatal myocardial infarction, and repeat revascularization during 14 months of follow-up. METHODS: In a single-center, prospective, cohort study, plasma levels of C-reactive protein were measured in 1458 consecutive patients undergoing elective or urgent coronary angioplasty. Patients were followed at 12 to 14 months for the occurrence of death, nonfatal myocardial infarction, and repeat revascularization. RESULTS: The incidence of death or myocardial infarction was 6.1% (44/716) in patients with an increased C-reactive protein level (>3 mg/L) and 1.5% (11/742) in patients with a normal level (relative risk [RR] = 4.4; 95% confidence interval [CI]: 2.2 to 8.5; P <0.0001). In a multivariate logistic regression model, an increased C-reactive protein level was an independent predictor of death or nonfatal myocardial infarction (RR = 3.6; 95% CI: 1.8 to 7.2; P =0.0001). The incidence of repeat revascularization was similar in patients with or without an increased C-reactive protein level (23% [168/716] vs. 22% [163/742], P = 0.54). Statin therapy at the time of the procedure was associated with a lower mean (+/- SD) C-reactive protein level (5.8 +/- 9.7 mg/L vs. 7.2 +/- 12.1 mg/L, P =0.02), but was not associated with the risk of death, nonfatal myocardial infarction, and repeat revascularization during follow-up. CONCLUSION: An increased C-reactive protein level is an independent prognostic indicator for the occurrence of death or nonfatal myocardial infarction following coronary angioplasty, but is not associated with the need for repeat revascularization.

Plasma N-terminal pro-B-type natriuretic peptide for prediction of death or nonfatal myocardial infarction following percutaneous coronary intervention.

B-type natriuretic peptide (BNP) and the N-terminus of pro-BNP (NT-pro-BNP) have prognostic value in patients with heart failure and patients with acute coronary syndromes. Little is known about the prognostic value of baseline NT-pro-BNP alone or in combination with C-reactive protein (CRP) for clinical outcome after percutaneous coronary intervention (PCI). Within a single center registry of contemporaneous PCI, we investigated the prognostic value of baseline plasma NT-pro-BNP and CRP concentrations for the prediction of death or nonfatal myocardial infarction (MI) during 12 to 14 months of follow-up. Among 1,172 consecutive patients, the occurrence of death or MI increased significantly with baseline NT-pro-BNP before PCI (first quartile 0 of 294, second quartile 6 of 291 [2.1%], third quartile 4 of 294 [1.4%], fourth quartile 22 of 293 [7.5%)]; p <0.0001). NT-pro-BNP in the top quartile significantly predicted death (odds ratio [OR] 13.37, 95% confidence interval [CI] 4.50 to 40.38, p <0.0001) and was associated with nonfatal MI (OR 2.53, 95% CI 0.77 to 8.34, p = 0.22) An abnormal CRP was significantly associated with death (OR 3.47, 95% CI 1.26 to 9.54, p = 0.019). Stepwise multivariate logistic regression analysis identified age >65 years and NT-pro-BNP as independent significant predictors of death/MI (age OR 3.18, 95% CI 1.32 to 7.67, p = 0.01; NT-pro-BNP OR 4.57, 95% CI 2.07 to 10.10, p = 0.0001). Baseline NT-pro-BNP before PCI provides important, independent prognostic information for the occurrence of death or nonfatal MI during long-term follow-up.

Value of C-reactive protein in patients with stable angina pectoris, coronary narrowing (30% to 70%), and normal fractional flow reserve.

This study is the first that combines a serum marker of inflammation (C-reactive protein) and intracoronary-derived fractional flow reserve. A low C-reactive protein level was strongly associated with uncomplicated follow-up in patients with hemodynamic nonsignificant coronary lesions. These results show that C-reactive protein provides additional information relevant for clinical decision-making in patients with intermediate (30% to 70%) coronary lesions.

Indications for requesting laboratory tests for concurrent diseases in patients with carpal tunnel syndrome: a systematic review.

BACKGROUND: Carpal tunnel syndrome (CTS) is known as a repetitive motion disorder, but the role of other diseases in the development or prognosis of CTS is uncertain. We reviewed the literature to determine whether there is evidence for an increased prevalence of specific conditions in CTS patients and whether this evidence would support laboratory screening for these conditions. METHODS: Medline, Embase, and Cochrane Controlled Trial Register were searched for key words related to CTS and associated diseases. Relevant articles were selected according to specific criteria. Sources of bias and heterogeneity attributable to differences in study design and in patient selection were investigated by subgroup analysis. RESULTS: After an initial search, we limited ourselves to three potentially important conditions: diabetes mellitus (DM), hypothyroidism (HT), and rheumatoid arthritis (RA). We identified nine articles with a total of 4908 CTS patients and 7671 controls that met our selection criteria. The nine studies were heterogeneous with respect to clinical and methodologic factors. In general, the prevalence of concurrent diseases was higher in CTS patients than in controls: the pooled odds ratios were 2.2 (95% confidence interval, 1.5-3.1) for DM, 1.4 (1.0-2.0) for HT, and 2.2 (1.4-3.4) for RA. Studies of lower methodologic quality reported, on average, higher odds ratios. Only one study provided information about whether the diagnosis of the concurrent condition was already made at the time of the CTS diagnosis. CONCLUSIONS: We found evidence that the prevalences of DM, HT, and RA are higher in CTS patients, but only one study specifically addressed the issue of the prevalence of nonmanifest cases of the concurrent condition. At present, there is insufficient evidence for routine laboratory screening for concurrent conditions in all newly diagnosed CTS patients.

Preprocedural C-reactive protein is not associated with angiographic restenosis or target lesion revascularization after coronary artery stent placement.

BACKGROUND: We assessed the predictive value of preprocedural plasma C-reactive protein (CRP) concentrations and statin therapy on 6 months angiographic and 1-year clinical outcome after nonurgent coronary stent placement. METHODS AND RESULTS: Baseline plasma high-sensitivity CRP concentrations were prospectively measured in 345 patients undergoing elective stent placement in a native coronary artery. The binary angiographic in-stent restenosis (ISR; stenosis > or = 50% of vessel diameter) rate was 19% in patients with CRP values within the reference interval (< or = 3 mg/L) and 22% in patients with CRP >3 mg/L [odds ratio (OR) = 1.2; 95% confidence interval (CI), 0.73-2.09]. Statin therapy in a univariate analysis significantly reduced both angiographic and clinical ISR rates. Multivariate logistic regression analysis identified unstable angina, smoking, and stent length, but neither CRP concentration nor statin therapy as independent predictors for angiographic ISR. Patients with an abnormal CRP value showed a trend toward a higher risk of nonfatal myocardial infarction (3.8% vs 0.5%; OR = 7.43; 95% CI, 0.87-61.65). Target lesion revascularization rates did not differ between the two groups (9.6% vs 10.6%; OR = 1.13; 95% CI, 0.56-2.28). In multivariate analysis, male sex (OR = 0.44, 95% CI, 0.19-0.97) and statin therapy (OR = 0.26; 95% CI, 0.09-0.68) were independent predictors for the occurrence of target lesion revascularization. CONCLUSIONS: This study demonstrated a lack of association between preprocedural plasma CRP concentrations and angiographic coronary ISR or clinically driven target lesion revascularization. Patients with an abnormal CRP concentration showed a trend toward higher risk of nonfatal myocardial infarction during 1 year of follow-up. Statin therapy was independently associated with decreased clinically driven target lesion revascularization, underlining the beneficial effects of statins on clinical outcome.

The practice of clinical chemistry in the European Union.

The European Communities Confederation of Clinical Chemistry has been actively engaged in raising the level of clinical chemistry in the European Union. Closer contacts between the national societies for clinical chemistry have resulted in more comparable programs for postgraduate training of clinical chemists, closer similarity of contents and practice of the profession in the different countries, and the official registration of professionals. This article reviews some of the characteristics of professional organisation, practice, and regulation in the fifteen European Union countries. Many similarities appear. In half of the countries microbiology, blood-banking and transfusion medicine fall within the domain of clinical chemistry. The minimum number of years for training (university and postgraduate) is eight, but in practice this will extend to 10 or more years. Official regulation of the profession by law exists in a minority of countries. Continuing education and re-registration have not been officially instituted yet in any country, but these issues will be the next steps forward. In those countries that prepare themselves for entering the European Union, training and practice of clinical chemistry are moving towards the common standards of the European Communities Confederation of Clinical Chemistry.