Evaluation of the diagnostic performance of heart-type fatty acid binding protein in the BWH-TIMI ED chest pain study.

Chest pain is one of the most common reasons for presentation to the Emergency Department and the ability to rapidly and correctly diagnose the minority of patients who have a myocardial infarction is of critical importance. We assessed the diagnostic performance of a multimarker strategy using heart-type fatty acid binding protein (H-FABP) in combination with a contemporary sensitive troponin (cTn) assay. We measured H-FABP (Randox) and a sensitive cTn (TnI-Ultra, Siemens) at baseline in 343 patients with chest pain enrolled in the prospective BWH-TIMI ED chest pain study. Final presenting diagnosis was adjudicated using all diagnostic data, including the local cTnI results, but reviewers were blinded to H-FABP and the sensitive cTn assays. The diagnostic accuracy of H-FABP and local cTn together (AUC 0.962) was superior to local cTn alone (AUC 0.910, p = 0.0009) with an especially marked improvement in early presenters (AUC 0.983 vs. 0.840, p = 0.0098). In contrast, when combined with the sensitive cTn assay, there was no significant difference in the AUC with H-FABP as compared with the sensitive cTn alone, either in the overall cohort (AUC 0.963 vs. 0.956, p = 0.23) or in early presenters (AUC 0.999 for both). In early presenters, the addition of H-FABP resulted in a NPV of 100% when combined with either the local or sensitive cTn assay. In our study, the addition of H-FABP significantly enhanced the sensitivity and accuracy of diagnosis as compared to a prior-generation troponin assay alone, especially in patients who presented early. H-FABP but did improve overall diagnostic accuracy when added to a current-generation sensitive troponin assay; however, their combination offered the best NPV in early presenters. Further studies are needed to determine the utility a very rapid "rule out" of MI with a single blood draw of troponin and H-FABP at presentation.

Diabetes and mortality following acute coronary syndromes.

CONTEXT: The worldwide epidemic of diabetes mellitus is increasing the burden of cardiovascular disease, the leading cause of death among persons with diabetes. The independent effect of diabetes on mortality following acute coronary syndromes (ACS) is uncertain. OBJECTIVE: To evaluate the influence of diabetes on mortality following ACS using a large database spanning the full spectrum of ACS. DESIGN, SETTING, AND PATIENTS: A subgroup analysis of patients with diabetes enrolled in randomized clinical trials that evaluated ACS therapies. Patients with ACS in 11 independent Thrombolysis in Myocardial Infarction (TIMI) Study Group clinical trials from 1997 to 2006 were pooled, including 62,036 patients (46,577 with ST-segment elevation myocardial infarction [STEMI] and 15,459 with unstable angina/non-STEMI [UA/NSTEMI]), of whom 10 613 (17.1%) had diabetes. A multivariable model was constructed to adjust for baseline characteristics, aspects of ACS presentation, and treatments for the ACS event. MAIN OUTCOME MEASURES: Mortality at 30 days and 1 year following ACS among patients with diabetes vs patients without diabetes. RESULTS: Mortality at 30 days was significantly higher among patients with diabetes than without diabetes presenting with UA/NSTEMI (2.1% vs 1.1%, P < .001) and STEMI (8.5% vs 5.4%, P < .001). After adjusting for baseline characteristics and features and management of the ACS event, diabetes was independently associated with higher 30-day mortality after UA/NSTEMI (odds ratio [OR], 1.78; 95% confidence interval [CI], 1.24-2.56) or STEMI (OR, 1.40; 95% CI, 1.24-1.57). Diabetes at presentation with ACS was associated with significantly higher mortality 1 year after UA/NSTEMI (hazard ratio [HR], 1.65; 95% CI, 1.30-2.10) or STEMI (HR, 1.22; 95% CI, 1.08-1.38). By 1 year following ACS, patients with diabetes presenting with UA/NSTEMI had a risk of death that approached patients without diabetes presenting with STEMI (7.2% vs 8.1%). CONCLUSION: Despite modern therapies for ACS, diabetes confers a significant adverse prognosis, which highlights the importance of aggressive strategies to manage this high-risk population with unstable ischemic heart disease.

Adding clopidogrel to aspirin improves outcome in ST-elevation myocardial infarction patients receiving fibrinolytic therapy.

Acute coronary syndromes result from the rupture of an atherosclerotic plaque with superimposed thrombosis. In an ST-elevation myocardial infarction, the thrombus occludes the coronary vessel, leading to an abrupt decrease in myocardial perfusion. The focus of initial management is the timely restoration of flow in the infarct-related artery via fibrinolytic therapy or percutaneous coronary intervention. Adjunctive therapy aimed at inhibition of platelets and the coagulation cascade is critical to establish and maintain vessel patency. Clopidogrel, an oral antiplatelet agent, has recently been shown to offer significant clinical benefit in STEMI (ST-elevation myocardial infarction) and is a welcome addition to standard fibrinolytic therapy.

Evaluation of CD8+ T-cell and antibody responses following transient increased viraemia in rhesus macaques infected with live, attenuated simian immunodeficiency virus.

In vivo depletion of CD8+ T cells results in an increase in viral load in macaques chronically infected with simian immunodeficiency virus (SIVmac239deltanef). Here, the cellular and humoral immune responses associated with this transient period of enhanced viraemia in macaques infected with SIVmac239deltanef were characterized. Fourteen days after in vivo CD8+ T-cell depletion, two of six macaques experienced a 1-2 log10 increase in anti-gp130 and p27 antibody titres and a three- to fivefold increase in gamma interferon-ecreting SIV-specific CD8+ T cells. Three other macaques had modest or no increase in anti-gp130 antibodies and significantly lower titres of anti-p27 antibodies, with minimal induction of functional CD8+ T cells. Four of the five CD8-depleted macaques experienced an increase in neutralizing antibody titres to SIVmac239. Induction of SIV-specific immune responses was associated with increases in CD8+ T-cell proliferation and fluctuations in the levels of signal-joint T-cell receptor excision circles in peripheral blood cells. Five months after CD8+ T-cell depletion, only the two high-responding macaques were protected from intravenous challenge with pathogenic SIV, whilst the remaining animals were unable to control replication of the challenge virus. Together, these findings suggest that a transient period of enhanced antigenaemia during chronic SIV infection may serve to augment virus-specific immunity in some, but not all, macaques. These findings have relevance for induction of human immunodeficiency virus (HIV)-specific immune responses during prophylactic and therapeutic vaccination and for immunological evaluation of structured treatment interruptions in patients chronically infected with HIV-1.