Non-traditional risk factors predict coronary calcification in chronic kidney disease in a population-based cohort.

The increased burden of cardiovascular disease in chronic kidney disease cannot be explained by traditional risk factors alone. Here, we evaluated the impact of non-traditional factors on the association of chronic kidney disease with coronary artery calcification using logistic regression among 2672 Dallas Heart Study patients of whom 220 had chronic kidney disease. The prevalence of coronary calcification significantly increased across all chronic kidney disease stages and this remained independently associated with coronary calcification after adjusting for traditional factors. The calcium x phosphorus product, homocysteine, and osteoprotegerin each diminished the magnitude of association between kidney disease and coronary calcification. After adjustment for these, the association between kidney disease and coronary calcification was no longer significant with the effects most prominent in the stages 3-5 subgroup. Our study has identified three non-traditional independent predictors of coronary calcification that diminished the association between chronic kidney disease and coronary calcification. These factors may represent novel mechanistic links warranting further investigation.

Trends in use of anti-thrombotic agents and outcomes in patients with non-ST-segment elevation myocardial infarction (NSTEMI) managed with an invasive strategy.

OBJECTIVE: To analyze trends in utilization of anti-thrombotic agents (ATA) and in-hospital clinical outcomes in non-ST-elevation myocardial infarction (NSTEMI) patients managed with an invasive strategy from 2007 to 2010. METHODS & RESULTS: Using ACTION Registry(®)-GWTG™ data, we analyzed trends in use of ATA and in-hospital clinical outcomes among 64,199 NSTEMI patients managed invasively between 2007 and 2010. ATA included unfractionated heparin (UFH), low molecular weight heparin (LMWH), glycoprotein IIb/IIIa inhibitors (GPI) and bivalirudin. Although the proportion of NSTEMI patients treated with PCI within 48h of hospital arrival was similar in 2007 and 2010, percentage use of bivalirudin (13.4-27.3%; p<0.01) and UFH increased (60.0-67.5%, p<0.01), and that of GPI (62.3-41.0%; p<0.01) and LMWH (41.5-36.8%; p<0.01) declined. Excess dosing of UFH (75.9-59.3%, p<0.01), LMWH (9.6-5.2%; p<0.01) and GPI (8.9-5.9%, p<0.01) was also significantly lower in 2010 compared with 2007. Though in-hospital mortality rates were similar in 2007 and 2010 (2.3-1.9%, p=0.08), the rates of in-hospital major bleeding (8.7-6.6%, p<0.01) and non-CABG related RBC transfusion (6.3-4.6%, p<0.01) were significantly lower in 2010 compared with 2007. CONCLUSION: Compared with 2007, patients with NSTEMI, who were managed invasively in 2010 received GPI and LMWH less often and bivalirudin and UFH more frequently. There were sizeable reductions in the rates of excess dosing of UFH (though still occurred in 67% of patients), GPI and LMWH. In-hospital major bleeding complications and post-procedural RBC transfusion were lower in 2010 compared with 2007.

TIMI risk score for ST-elevation myocardial infarction: A convenient, bedside, clinical score for risk assessment at presentation: An intravenous nPA for treatment of infarcting myocardium early II trial substudy.

BACKGROUND: Considerable variability in mortality risk exists among patients with ST-elevation myocardial infarction (STEMI). Complex multivariable models identify independent predictors and quantify their relative contribution to mortality risk but are too cumbersome to be readily applied in clinical practice. METHODS AND RESULTS: We developed and evaluated a convenient bedside clinical risk score for predicting 30-day mortality at presentation of fibrinolytic-eligible patients with STEMI. The Thrombolysis in Myocardial Infarction (TIMI) risk score for STEMI was created as the simple arithmetic sum of independent predictors of mortality weighted according to the adjusted odds ratios from logistic regression analysis in the Intravenous nPA for Treatment of Infarcting Myocardium Early II trial (n=14 114). Mean 30-day mortality was 6.7%. Ten baseline variables, accounting for 97% of the predictive capacity of the multivariate model, constituted the TIMI risk score. The risk score showed a >40-fold graded increase in mortality, with scores ranging from 0 to >8 (P:<0.0001); mortality was <1% among patients with a score of 0. The prognostic discriminatory capacity of the TIMI risk score was comparable to the full multivariable model (c statistic 0. 779 versus 0.784). The prognostic performance of the risk score was stable over multiple time points (1 to 365 days). External validation in the TIMI 9 trial showed similar prognostic capacity (c statistic 0.746). CONCLUSIONS: The TIMI risk score for STEMI captures the majority of prognostic information offered by a full logistic regression model but is more readily used at the bedside. This risk assessment tool is likely to be clinically useful in the triage and management of fibrinolytic-eligible patients with STEMI.

Combination therapy with abciximab reduces angiographically evident thrombus in acute myocardial infarction: a TIMI 14 substudy.

BACKGROUND: Use of abciximab in combination with administration of thrombolytics has been shown to improve epicardial and microvascular coronary blood flow in acute myocardial infarction (AMI). As a potential mechanism, we hypothesized that combination therapy would reduce angiographically evident thrombus (AET) and would increase lumen diameter compared with thrombolytic monotherapy. METHODS AND RESULTS: Patients who received combination therapy in TIMI 14 (low-dose thrombolytic plus abciximab, n=732) were compared with patients who received thrombolytic monotherapy without abciximab in the TIMI 4, 10A, 10B, and 14 trials (n=1662). Thrombus burden was assessed 90 minutes after treatment, and quantitative angiography was performed in an angiographic core laboratory by investigators blinded to treatment assignment. The frequency of AET was reduced in patients who received abciximab combination therapy compared with thrombolytic monotherapy (26.6% versus 35.4%, P<0.001). Similar findings were observed when the analysis was restricted to patients with patent arteries (14.7% versus 20.8%, P=0.001). Residual percent diameter stenosis at 90 minutes was also improved in the abciximab therapy group both in patent arteries (64.6+/-16.6 versus 68.3+/-14.8, P<0.001) and between patent and occluded arteries (69.3+/-19.5 versus 73.8+/-17.9, P<0.001). The absence of AET was associated with an increased frequency of >70% ST-segment resolution by 90 minutes (37.2%, 110/296 versus 18.9%, 54/286, P<0.001). CONCLUSIONS: Compared with thrombolytic monotherapy, combination therapy with abciximab reduces AET, which in turn is associated with reduced residual stenosis and improved ST-segment resolution in AMI. These data provide a pathophysiological link between platelet inhibition, reduced thrombus, and improvements in both epicardial and microvascular perfusion in AMI.

Abciximab improves both epicardial flow and myocardial reperfusion in ST-elevation myocardial infarction. Observations from the TIMI 14 trial.

BACKGROUND: In the presence of ST-elevation myocardial infarction, patients with successful epicardial reperfusion (TIMI 3 flow) but persistent ST elevation on a 12-lead ECG are at high risk for subsequent death and left ventricular dysfunction. In the TIMI 14 trial, a dose-ranging angiographic study, combined therapy with abciximab plus reduced-dose tPA enhanced the speed and efficacy of epicardial reperfusion. We determined whether the combination of abciximab plus reduced-dose tPA provided additional benefit in terms of myocardial reperfusion, as evidenced by greater resolution of ST elevation. METHODS AND RESULTS: All 346 patients with interpretable baseline and 90-minute ECGs, treated with either tPA alone or abciximab plus reduced-dose tPA (combination therapy), were included. Patients receiving combination therapy (n=221) had a 59% rate of complete (>/=70%) ST resolution at 90 minutes versus 37% in those treated with tPA alone (n=125) (P<0.0001). When the analysis was limited to patients with TIMI 3 flow, patients treated with combination therapy (n=151) remained significantly more likely to achieve complete ST resolution than those receiving tPA alone (n=80) (69% versus 44%; P=0.0002). CONCLUSIONS: Combination therapy with abciximab and reduced-dose tPA improves myocardial (microvascular) reperfusion, as reflected in greater ST-segment resolution, in addition to epicardial flow. This finding may translate into improved clinical outcomes by enhancing myocardial salvage.

ST segment resolution as a tool for assessing the efficacy of reperfusion therapy.

Rapid, simple and inexpensive measures are needed to assess the efficacy of reperfusion therapy both in clinical practice and in clinical trials testing novel reperfusion regimens. In the last decade, several observations have led to a favorable reappraisal of the utility of ST segment monitoring as a simple means of assessing reperfusion in patients receiving fibrinolytic therapy for acute ST elevation myocardial infarction, and ST resolution is being used increasingly in clinical practice and in clinical research. This review focuses on four interrelated roles for ST segment monitoring: the assessment of epicardial reperfusion and the identification of candidates for rescue percutaneous coronary intervention; the evaluation of microvascular and tissue-level reperfusion; the determination of prognosis early after fibrinolytic therapy; and the use of ST segment resolution to compare different reperfusion regimens.

Plasma concentration of soluble vascular cell adhesion molecule-1 and subsequent cardiovascular risk.

OBJECTIVES: The purpose of this study was to evaluate whether soluble vascular cell adhesion molecule-1 (sVCAM-1) is a marker for increased cardiovascular risk. BACKGROUND: Soluble forms of cellular adhesion molecules (CAMs) may be useful markers of endothelial activation and local or systemic inflammation. Recent studies indicate that plasma concentration of soluble intercellular adhesion molecule-1 (sICAM-1) is elevated many years before a first myocardial infarction (MI) occurs. However, only a few prospective studies have evaluated whether sVCAM-1 is also a marker for increased cardiovascular risk. METHODS: Baseline plasma samples were obtained prospectively from 14,916 healthy participants in the Physicians' Health Study. In a nested, case-control study design, the plasma concentration of sVCAM-1 was measured in 474 men with confirmed MI during the nine-year follow-up period, and in an equal number of control subjects who remained free of reported cardiovascular disease and who were matched for age, smoking status and length of follow-up. RESULTS: No significant difference in the median baseline sVCAM-1 concentration was found between case and control subjects (638 vs. 634 ng/ml; p = NS). Cardiovascular risk was similar between patients with sVCAM-1 levels in the highest quartile and those in the lowest quartile, in both crude (relative risk [RR] 1.28, 95% confidence interval [CI] 0.85 to 1.92) and adjusted (RR 1.17, 95% CI 0.71 to 1.91) matched-pairs analyses. CONCLUSIONS: In contrast to previous data on sICAM-1, we found no evidence of an association between sVCAM-1 levels and the risk of future MI in a large cohort of apparently healthy men. These data suggest important pathophysiologic differences between sVCAM-1 and sICAM-1 in the genesis of atherothrombosis.

Cardiac troponin I for stratification of early outcomes and the efficacy of enoxaparin in unstable angina: a TIMI-11B substudy.

OBJECTIVES: We sought to evaluate cardiac troponin I (cTnI) for predicting early clinical outcomes and the efficacy of enoxaparin among patients with non-ST segment elevation acute coronary syndrome (ACS) and negative creatine kinase, MB fraction (CK-MB) levels. BACKGROUND: Cardiac TnI identifies patients with unstable angina who are at higher risk of death or myocardial infarction (MI) by 30 days. The utility of cTnI for predicting very early clinical events, including recurrent ischemia, and the efficacy of enoxaparin are not yet established. METHODS: At baseline and 12 h to 24 h after enrollment in the Thrombolysis in Myocardial Infarction (TIMI)-11B trial, samples were collected for cTnI determination. RESULTS: Among 359 patients with negative serial CK-MB values, 50.1% had a cTnI result > or =0.1 ng/ml within the first 24 h. Patients with elevated cTnI were at higher risk of death or MI at 48 h (3.9 vs. 0%, p = 0.01) and 14 days (13.9 vs. 2.2%, p<0.0001). Elevated cTnI also correlated with higher risk of recurrent ischemia requiring urgent revascularization by 48 h (10.0 vs. 1.7%, p = 0.001) and 14 days (20.6 vs. 5.6%, p< or =0.0001). Enoxaparin had a greater benefit among patients with elevated vs. normal cTnI (p = 0.03), achieving a 47% reduction in the risk of death, MI or urgent revascularization by 14 days in cTnI-positive patients (p = 0.007). CONCLUSIONS: Elevation of cTnI among patients with non-ST segment elevation ACS and negative levels of CK-MB identifies those at higher risk for very early adverse outcomes, including severe recurrent ischemia. Treatment with enoxaparin reduces the risk associated with elevated cTnI.

Comparison of a 60- versus 90-minute determination of ST-segment resolution after thrombolytic therapy for acute myocardial infarction. In TIME-II Investigators. Intravenous nPA for Treatment of Infarcting Myocardium Early-II.

Determination of ST-segment resolution 60 minutes after the administration of thrombolytic therapy allows accurate risk stratification for mortality and congestive heart failure. Patients with complete ST resolution at 60 minutes tended to be at lower risk for 30-day mortality than patients with complete ST resolution at 90 minutes.

ST-segment resolution and infarct-related artery patency and flow after thrombolytic therapy. Thrombolysis in Myocardial Infarction (TIMI) 14 investigators.

Because patients who fail to achieve reperfusion after thrombolytic therapy remain at high risk for morbidity and mortality, noninvasive measures of infarct-related artery (IRA) patency are needed to identify candidates for rescue interventions. We prospectively studied 444 patients from the Thrombolysis In Myocardial Infarction (TIMI) 14 trial with interpretable baseline and 90 minute 12-lead electrocardiograms. The percent resolution of ST-segment deviation from baseline to 90 minutes was compared with 90-minute IRA TIMI flow grade, as determined in an angiographic core laboratory. Patients with complete (> or = 70%) ST resolution (n = 208; 47%) had a patency (TIMI 2 or 3 flow) rate of 94%, a TIMI 3 flow rate of 79%, and a 30-day mortality rate of 1.0%. Patients with partial (30% to 70%) or no (< or = 30%) ST resolution had significantly lower rates of patency (72% and 68%; p < 0.0001 vs complete ST resolution) and TIMI 3 flow (50% and 44%; p < 0.0001 vs complete ST resolution), and higher 30-day mortality (4.2% and 5.9%; p = 0.01 vs complete ST resolution). With use of electrocardiographic criteria alone, approximately 50% of patients can be classified as having a high (94%) probability of IRA patency and a very low risk for mortality. Angiography to determine patency of the IRA may be unnecessary in these patients. In patients without complete (> or = 70%) ST resolution, the IRA is still likely to be patent, and additional information from clinical variables or serum markers may help to identify candidates for coronary angiography. Patients with persistent ST elevation despite a patent IRA are at increased risk for mortality, likely due to extensive microvascular and tissue injury.

Early noninvasive detection of failed epicardial reperfusion after fibrinolytic therapy.

Available noninvasive techniques for identifying patients with failed epicardial reperfusion after fibrinolytic therapy are limited by poor accuracy. It is unknown whether combining multiple noninvasive predictors would improve diagnostic accuracy and facilitate identification of candidates for rescue percutaneous coronary intervention. In the Thrombolysis In Myocardial Infarction (TIMI) 14 trial, we evaluated the ability of ST-segment resolution (n = 606), chest pain resolution (n = 859), and the ratio of 60-minute/baseline serum myoglobin (n = 308) to identify patients with angiographic evidence of failed reperfusion 90 minutes after fibrinolysis. Three criteria were prospectively defined: <50% ST resolution at 90 minutes, presence of chest pain at the time of angiography, and myoglobin ratio <4. Patients who met any individual criterion were more likely to have less than TIMI 3 flow and an occluded infarct-related artery (TIMI 0/1 flow) than those who did not meet the criterion (p <0.005 for each). When the 3 criteria were used together (n = 169), patients who satisfied 0 (n = 29), 1 (n = 68), 2 (n = 51), or 3 (n = 21) of the criteria had a 17%, 24%, 35%, and 76% probability of failing to achieve TIMI 3 flow (p <0.0001 for trend), a 0%, 6%, 18%, and 57% probability of an occluded infarct-related artery (p <0.0001 for trend), and a 0%, 1.5%, 2.0%, and 9.5% rate of 30-day mortality (p = 0.05 for trend), respectively. Use of the criteria in combination increased positive predictive values without decreasing negative predictive values. In conclusion, ST-segment resolution, chest pain resolution, and early washout of serum myoglobin can be used in combination to aid in the early noninvasive identification of candidates for rescue percutaneous coronary intervention.

Heart-type fatty acid binding protein as a marker of reperfusion after thrombolytic therapy.

Accurate, rapid, and simple noninvasive measures of infarct-related artery (IRA) patency are needed to identify patients with failed coronary reperfusion for rescue percutaneous coronary intervention (PCI). Heart-type Fatty Acid Binding Protein (H-FABP) is a small, cytosolic protein found in high concentrations in the myocardium. We evaluated the efficacy of H-FABP as a marker for successful reperfusion after thrombolysis. Fifty-eight subjects from the TIMI 14 trial had H-FABP and myoglobin concentrations measured at baseline (immediately prior to thrombolysis) and 60, 90, and 180 min after thrombolysis. All patients underwent coronary angiography at 90 min. By 60 min after thrombolysis, median concentrations of H-FABP and myoglobin were significantly higher in patients with a patent IRA than in those with an occluded IRA (P<0.01 for each). Similarly, the 60 and 90 min/baseline H-FABP and myoglobin ratios were significantly higher among patients with a patent IRA (P<0.01 for each). There were no significant differences in marker concentrations or ratios between patients with TIMI grade 2 and TIMI grade 3 flow. The area under the ROC curve tended to be greater for the 60 and 90 min/baseline myoglobin ratios than for similar ratios of H-FABP (0.71 and 0.73 vs. 0.64 and 0.62; P=ns). In conclusion, successful reperfusion can be detected within the first 60 min after thrombolysis with either H-FABP or myoglobin. Despite a favorable kinetic profile, however, H-FABP does not appear to represent a significant advance over myoglobin in the noninvasive detection of reperfusion after thrombolysis.

ST-Segment resolution as a marker of epicardial and myocardial reperfusion after thrombolysis: insights from the TIMI 14 and in TIME-II trials.

Patients with persistent ST segment elevation after fibrinolysis are at high risk for death and congestive heart failure, even if normal epicardial flow has been restored. In the TIMI 14 trial, combination therapy with abciximab plus reduced-dose alteplase enhanced the speed and efficacy of epicardial reperfusion. We also found that combination therapy provided an additional benefit in terms of myocardial reperfusion, as evidenced by greater ST resolution on serial 12-lead electrocardiograms. Specifically, the proportion of patients with complete (> or =70%) ST resolution was higher among patients receiving combination therapy than in those treated with alteplase alone (59% vs 37%; p < 0.0001). Even among patients with normal (TIMI grade 3) epicardial blood flow, combination therapy was associated with a significantly greater likelihood of complete ST resolution than was fibrinolysis alone (69% vs 44%; p = 0.0002). In conclusion, combination reperfusion therapy improved myocardial (microvascular) reperfusion, independent of epicardial flow, suggesting an additional mechanism by which abciximab may improve outcomes in patients with acute MI.

Diagnosis and management of coronary artery disease in patients with end-stage renal disease on hemodialysis.

Cardiovascular disease accounts for almost half of the total mortality in patients with ESRD. Ischemic heart disease is responsible for many cardiovascular deaths, with myocardial infarction accounting for approximately 15% and sudden cardiac death or severe left ventricular dysfunction accounting for much of the remainder. The markedly increased prevalence of atherosclerotic cardiovascular disease in patients with ESRD is influenced, at least in part, by numerous risk factors for atherosclerosis, with hypertension, diabetes mellitus, and hypercholesterolemia being particularly important. Because atherosclerotic coronary artery disease (CAD), whether symptomatic or asymptomatic, is associated with an increased incidence of allograft failure and mortality, the results of this study suggest the need for careful evaluation for the presence of CAD in those persons who are under consideration for renal transplantation. Candidates with angina pectoris, previous myocardial infarction, or congestive heart failure are at particularly high risk of a cardiac event, and, therefore, should routinely undergo pretransplant coronary angiography and subsequent surgical revascularization if angina is refractory to medical therapy or CAD is extensive. In contrast, although young, nondiabetic transplant candidates without symptoms or electrocardiographic evidence of CAD have an increased relative risk of cardiac death when compared with age-matched control subjects, their absolute risk of such an event is very low. As a result, they do not require a cardiac evaluation before transplantation. For the remaining transplant candidates at neither low nor high risk of a fatal or nonfatal cardiac event (i.e., those at intermediate risk), the authors of this study routinely perform (1) thallium imaging with dipyridamole or (2) two-dimensional echocardiography with intravenous dobutamine. If the result of these investigations are normal, transplantation proceeds; if abnormal, coronary angiography is performed, followed by surgical revascularization if CAD is extensive. Percutaneous transluminal coronary angioplasty is not recommended in patients with ESRD because it appears to be accompanied by a high likelihood of acute and chronic complications. Although it is hoped that surgical revascularization before renal transplantation improves allograft and patient survival, prospectively obtained data proving that this, in fact, is true do not exist.

Clinical efficacy of three assays for cardiac troponin I for risk stratification in acute coronary syndromes: a Thrombolysis In Myocardial Infarction (TIMI) 11B Substudy.

BACKGROUND: Significant analytic variability exists between the multiple assays for cardiac troponin I (cTnI) approved for clinical use. Until adequate cTnI standardization is possible, an evidence-based approach evaluating each assay at specific thresholds appears warranted. METHODS: We examined the efficacy of three cTnI assays for predicting death, myocardial infarction (MI), or the composite of death, MI, or urgent revascularization at 43 days among patients with non-ST-elevation acute coronary syndromes enrolled in the Thrombolysis In Myocardial Infarction (TIMI) 11B study. RESULTS: Six hundred eighty-one patients with serum samples obtained at baseline and/or 12-24 h had cTnI determined using all three assays. Baseline cTnI was > or = 0.1 microg/L for 368, 395, and 418 patients with the Bayer Immuno 1(TM), ACS:180, and Dimension RxL assays, respectively. Correlation coefficients for the RxL with the ACS:180 and Bayer Immuno 1 results were 0.89 (P = 0.0001) and 0.87 (P = 0.0001), with a coefficient of 0.92 (P = 0.0001) for the ACS:180 and Bayer Immuno 1 assays. Patients with cTnI > or = 0.1 microg/L were at increased risk fo death or MI by 43 days (relative risk, 2.2-3.0; P <0.0006), regardless of the assay used. This prognostic capacity persisted among those with creatine kinase MB isoenzyme concentrations within the reference interval. Moreover, cTnI was the strongest multivariate predictor of death, MI, or urgent revascularization with adjusted odds ratios of 2.1-2.9 (P <0. 0006). CONCLUSION: This study demonstrates the prognostic efficacy of three independently developed cTnI assays at a threshold of 0.1 microg/L for the prediction of adverse clinical outcomes among patients with non-ST-elevation acute coronary syndromes.

The A-to-Z Trial: Methods and rationale for a single trial investigating combined use of low-molecular-weight heparin with the glycoprotein IIb/IIIa inhibitor tirofiban and defining the efficacy of early aggressive simvastatin therapy.

BACKGROUND: The A-to-Z Trial is an ongoing international, multicenter, randomized study designed to investigate 2 issues concerning contemporary care of patients with acute coronary syndromes (ACS). The first issue is whether the use of low-molecular-weight heparin versus unfractionated heparin affects outcomes and safety when used as a therapy adjunctive to baseline treatment with tirofiban and aspirin in patients with non-ST-elevation (nSTE) ACS. The second issue is whether early use of an aggressively dosed statin is superior to a current trial-based "accepted care" regimen of a lower-dose statin started 3 to 6 months after an acute event. METHODS: The study is conceptually and functionally divided into 2 sequential parts-the "A" Aggrastat and "Z" Zocar phases. The primary A-phase end point is a composite of all-cause mortality, myocardial infarction (MI), and documented refractory ischemia at 7 days. Both nSTE-ACS patients from the A phase and patients with ST-elevation ACS who meet specific risk criteria are eligible to enter the subsequent "Z" (Zocor) chronic phase (Z phase). The primary end point of the Z phase is a composite of cardiovascular death, MI, readmission for ACS, and stroke. The trial will continue until 970 primary events have occurred in the Z-phase population. CONCLUSION: This trial is evaluating 2 temporally connected sequences of phamacotherapy for ACS. At completion, trial results will provide definitive evidence regarding efficacy and safety of early, intensive statin therapy and better define the role of low-molecular-weight heparin in patients with nSTE ACS.

The prognostic value of B-type natriuretic peptide in patients with acute coronary syndromes.

BACKGROUND: Brain (B-type) natriuretic peptide is a neurohormone synthesized predominantly in ventricular myocardium. Although the circulating level of this neurohormone has been shown to provide independent prognostic information in patients with transmural myocardial infarction, few data are available for patients with acute coronary syndromes in the absence of ST-segment elevation. METHODS: We measured B-type natriuretic peptide in plasma specimens obtained a mean (+/-SD) of 40+/-20 hours after the onset of ischemic symptoms in 2525 patients from the Orbofiban in Patients with Unstable Coronary Syndromes-Thrombolysis in Myocardial Infarction 16 study. RESULTS: The base-line level of B-type natriuretic peptide was correlated with the risk of death, heart failure, and myocardial infarction at 30 days and 10 months. The unadjusted rate of death increased in a stepwise fashion among patients in increasing quartiles of base-line B-type natriuretic peptide levels (P< 0.001). This association remained significant in subgroups of patients who had myocardial infarction with ST-segment elevation (P=0.02), patients who had myocardial infarction without ST-segment elevation (P<0.001), and patients who had unstable angina (P<0.001). After adjustment for independent predictors of the long-term risk of death, the odds ratios for death at 10 months in the second, third, and fourth quartiles of B-type natriuretic peptide were 3.8 (95 percent confidence interval, 1.1 to 13.3), 4.0 (95 percent confidence interval, 1.2 to 13.7), and 5.8 (95 percent confidence interval, 1.7 to 19.7). The level of B-type natriuretic peptide was also associated with the risk of new or recurrent myocardial infarction (P=0.01) and new or worsening heart failure (P<0.001) at 10 months. CONCLUSIONS: A single measurement of B-type natriuretic peptide, obtained in the first few days after the onset of ischemic symptoms, provides powerful information for use in risk stratification across the spectrum of acute coronary syndromes. This finding suggests that cardiac neurohormonal activation may be a unifying feature among patients at high risk for death after acute coronary syndromes.

Impact of contrast agent type (ionic versus nonionic) used for coronary angiography on angiographic, electrocardiographic, and clinical outcomes following thrombolytic administration in acute myocardial infarction.

The goal of this study was to examine the relationship between contrast agent type (ionic vs. nonionic) and angiographic, electrocardiographic, and clinical outcomes after thrombolytic administration. Ionic or nonionic contrast agents were selected in a nonrandomized fashion for 90-min angiography and percutaneous coronary intervention (PCI) following thrombolytic administration in the TIMI 14 trial [tissue plasminogen activator (tPA) or reteplase (rPA) vs. low-dose lytic + abciximab]. There was no relationship between contrast agent type and overall patency, rate of TIMI grade 3 flow, or corrected TIMI frame counts (CTFCs) in open culprit arteries and in post-PCI patency rates or post-PCI CTFCs. In patients treated with ionic contrast, ejection fractions at 90 min were slightly but significantly lower (56.2 +/- 16.5, n = 122, vs. 59.8 +/- 14.4, n = 322; P = 0.02), chest pain duration was longer (2.8 +/- 4.1 hr, n = 255, vs. 1.7 +/- 3.6, n = 550; P = 0.0003), and complete ST segment resolution was less frequent (41.5% vs. 50.8%; P = 0.04). While there was no difference in epicardial blood flow, ionic contrast agent use was associated with poorer ST segment resolution, longer chest pain duration, and poorer ejection fractions, perhaps as a result of microvascular dysfunction.