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Robert H Christenson

Publications and source records attributed to Robert H Christenson.

At least 19 recordsLinked to original sources
PubMed2006

Toward standardization of cardiac troponin I measurements part II: assessing commutability of candidate reference materials and harmonization of cardiac troponin I assays.

BACKGROUND: Cardiac tropoin I (cTnI) measurements show an approximately 20- to 40-fold difference between assays, and better standardization and harmonization are needed. Toward this goal, the AACC cTnI Standardization Committee collaborated with the National Institute of Standards and Technology (NIST) in an earlier study to select 2 candidate reference materials (cRMs). METHODS: Two troponin cRMs, a troponin C-troponin I-troponin T (CIT) complex from human heart tissue and a CIT complex from recombinant technology, were supplied to NIST for assessment of composition and purity, and cTnI value assignment. These cRMs and 6 cTnI-positive human serum pools were shipped to manufacturers of 15 cTnI assays. Commutability of the materials was examined by determining the numerical relationship for the cRM preparations between each manufacturer-specified field method and each of the other 14 field methods. These relationships were then compared with the corresponding numerical relationships for the human serum pools. Harmonization of methods was accomplished by determining regression parameters relative to the analytical system yielding values closest to the median for each serum pool. These regression parameters were used to recalculate pool values to harmonize the assays. Interassay CVs before and after harmonization were determined. RESULTS: Characterization of the CIT and CI cRMs showed that these materials were of specified composition. The proportion of cTnI methods that demonstrated commutability for the CIT cRM was 45%; for the CI cRM, 39% of methods demonstrated commutability. Interassay cTnI variability for the field methods ranged from 82% to 97%, median 88%. After harmonization, variability of the serum pools for the cTnI methods was decreased to between 9.0% and 23%, median 15.5%. CONCLUSIONS: The proportion of methods demonstrating commutability was too low for use as a common calibrator for the cTnI field methods. However a simple strategy using serum pools can improve harmonization of field cTnI methods by more than 5-fold. The CIT cRM was selected by the AACC cTnI standardization committee, and a new lot has been classified as the cTnI certified reference material Standard Reference Material 2921 by NIST.

Calibration↗
PubMed2006

Influence of imprecision on ROC curve analysis for cardiac markers.

BACKGROUND: There has been considerable debate regarding the impact of assay imprecision on the performance of cardiac biomarkers for diagnosis of acute coronary syndromes (ACS) and risk stratification for future adverse cardiac events. METHODS: Using existing data from 2 published clinical trials, we used a resampling method to statistically introduce 5%, 10%, and 20% imprecision to results for B-type natriuretic peptide (BNP) and cardiac troponin I (cTnI) and examined its impact on ROC curve analysis. RESULTS: Superimposition of artificial imprecision produced no significant difference in the area under the ROC curve observed for BNP for diagnosis of heart failure or for cTnI for 30-day risk stratification of patients with ACS. CONCLUSION: Assay imprecision does not appear to be a critical determinant in the interpretation of cardiac marker results for patients with heart disease.

Acute Disease↗
PubMed2006

Frequency and clinical implications of discordant creatine kinase-MB and troponin measurements in acute coronary syndromes.

OBJECTIVES: We sought to evaluate the association between discordant cardiac marker results and in-hospital mortality and treatment patterns in patients with non-ST-segment elevation acute coronary syndromes (NSTE ACS). BACKGROUND: Creatine kinase-MB (CK-MB) and cardiac troponins (cTn) are often measured concurrently in patients with NSTE ACS. The significance of discordant CK-MB and cTn results is unknown. METHODS: Among 29,357 ACS patients in the CRUSADE initiative who had both CK-MB and cTn measured during the first 36 hours, we examined relationships of four marker combinations (CK-MB-/cTn-, CK-MB+/cTn-, CK-MB-/cTn+, and CK-MB+/cTn+) with mortality and American College of Cardiology/American Heart Association guidelines-recommended acute care. RESULTS: The CK-MB and cTn results were discordant in 28% of patients (CK-MB+/cTn-, 10%; CK-MB-/cTn+, 18%). In-hospital mortality was 2.7% among CK-MB-/cTn- patients; 3.0%, CK-MB+/cTn-; 4.5%, CK-MB-/cTn+; and 5.9%, CK-MB+/cTn+. After adjustment for other presenting risk factors, patients with CK-MB+/cTn- had a mortality odds ratio (OR) of 1.02 (95% confidence interval [CI] 0.75 to 1.38), those with CK-MB-/cTn+ had an OR of 1.15 (95% CI 0.86 to 1.54), and those with CK-MB+/cTn+ had an OR of 1.53 (95% CI 1.18 to 1.98). Despite variable risk, patients with CK-MB+/cTn- and CK-MB-/cTn+ were treated similarly with early antithrombotic agents and catheter-based interventions. CONCLUSIONS: Among patients with NSTE ACS, an elevated troponin level identifies patients at increased acute risk regardless of CK-MB status, but an isolated CK-MB+ status has limited prognostic value. Recognition of these risk differences may contribute to more appropriate early use of antithrombotic therapy and invasive management for all cTn+ patients.

Aged↗
PubMed2006

The influence of risk status on guideline adherence for patients with non-ST-segment elevation acute coronary syndromes.

BACKGROUND: Practice guidelines for patients with non-ST-segment elevation (NSTE) acute coronary syndromes (ACS) recommend targeting evidence-based therapies for the highest-risk patients. We characterized guideline adherence for NSTE ACS by risk status. METHODS: We analyzed inhospital treatments and outcomes for 77760 patients with NSTE ACS (ischemic ST-segment changes and/or positive cardiac markers) included in the CRUSADE initiative from January 2001 to September 2003 at 457 US hospitals. Compliance with the American College of Cardiology/American Heart Association Class guideline recommendations for NSTE ACS was evaluated in subgroups of eligible patients without listed contraindications at increased risk for mortality and among risk categories designated by an adapted version of the PURSUIT risk model designed to predict inhospital mortality. RESULTS: Inhospital mortality was increased in patients with diabetes mellitus (5.8% vs 4.3%), renal insufficiency (10.0% vs 3.9%), signs of congestive heart failure on presentation (10.6% vs 3.1%), and age > or = 75 years (8.6% vs 2.7%), compared with patients without these features. Use of guideline-recommended acute medications, invasive cardiac procedures, and discharge medications and interventions was significantly lower in patients with these high-risk features. Patients designated as high-risk for inhospital mortality were less likely to be treated with guideline-recommended therapies compared with low-risk and moderate-risk patients. CONCLUSIONS: Patients with NSTE ACS with the highest risk of mortality are less likely to receive guideline-recommended therapies and interventions. These findings highlight the need to clarify guideline recommendations for high-risk patients and to develop novel quality improvement approaches that target undertreated subgroups of patients with NSTE ACS.

Acute Disease↗
PubMed2006

Meta-analysis of ischemia-modified albumin to rule out acute coronary syndromes in the emergency department.

BACKGROUND: Because of possible adverse outcomes, many of the >6 million annual emergency department (ED) patients with suspected acute coronary syndromes (ACS) undergo extensive evaluations. To minimize medical errors, chest pain evaluations are structured to identify accurately nearly 100% of patients with ACS. This is at a cost of negative evaluation rates that can exceed 90%. Ischemia-modified albumin (IMA), a serum biomarker with a high negative predictive value (NPV) at ED presentation, may exclude ACS. Our objective was to perform a meta-analysis of IMA use for ACS risk stratification. METHODS: By computer literature search and communication with authors of unpublished information, all IMA data were considered. This analysis included studies if they reported IMA results from an ED presentation for suspected ACS. We defined a negative triple prediction test (TPT) as a nondiagnostic electrocardiogram, negative troponin, and negative IMA. RESULTS: Eight studies of >1800 patients met the entry criteria. The TPT sensitivity and NPV for acute ACS were 94.4% and 97.1% and, for longer-term outcomes, were 89.2% and 94.5%, respectively. CONCLUSIONS: A negative TPT of a nondiagnostic electrocardiogram, negative troponin, and negative IMA has a high NPV for excluding ACS in the ED.

Angina, Unstable↗
PubMed2006

B-type natriuretic peptide and N-terminal pro B-type natriuretic peptide are depressed in obesity despite higher left ventricular end diastolic pressures.

BACKGROUND: B-type natriuretic peptide (BNP) and N-terminal proBNP (NT-proBNP) are frequently used in diagnosing and monitoring patients with heart failure. Recent studies have demonstrated that concentrations of these peptides are decreased in obese patients, but whether lower natriuretic peptide concentrations are really due to different hemodynamics is unknown. The relationship between these markers and left ventricular end diastolic pressure (LVEDP) in obesity has not been elucidated. METHODS: We examined patients undergoing cardiac catheterization who had creatinine of < 2.0, no evidence of myocardial infarction or pulmonary embolism, and no cardiac transplant. Body mass index and LVEDP were determined, and BNP and NT-proBNP obtained at the start of each case. Obesity was defined as body mass index of > or = 30 kg/m2. RESULTS: Of 203 patients enrolled, 101 were obese. The groups were similar in respect to race, creatinine, cholesterol, and history of dyslipidemia and cardiomyopathy. The obese patients tended to be younger, were more likely to have diabetes and hypertension, and were less likely to have coronary artery disease. The obese patients had higher LVEDP but reduced BNP and NT-pro-BNP. The relationship between the natriuretic peptides and LVEDP was poor, with r values of < 0.1. CONCLUSIONS: Obese patients have reduced concentrations of BNP and NT-proBNP compared to nonobese patients despite having elevated LVEDP. This suggests that factors other than cardiac status impact on BNP and NT-proBNP concentrations. The poor relationship between natriuretic peptide concentrations and LVEDP also suggests that these concentrations should not be considered surrogates for cardiac filling pressures or volumes.

Aged↗
PubMed2005

Unbound free fatty acids and heart-type fatty acid-binding protein: diagnostic assays and clinical applications.

BACKGROUND: A biomarker that reliably detects myocardial ischemia in the absence of necrosis would be useful for initial identification of unstable angina patients and for differentiating patients with chest pain of an etiology other than coronary ischemia, and could provide clinical utility complementary to that of cardiac troponins, the established markers of necrosis. Unbound free fatty acids (FFA(u)) and their intracellular binding protein, heart-type fatty acid-binding protein (H-FABP), have been suggested to have clinical utility as indicators of cardiac ischemia and necrosis, respectively. METHODS: We examined results of clinical assessments of FFA(u) and H-FABP as biomarkers of cardiac ischemia and necrosis. Data published on FFA(u) and H-FABP over the past 30 years were used as the basis for this review. RESULTS: Although little clinical work has been done on FFA(u) since the initial reports, recent studies documented an association between increased serum FFAs and ventricular dysrhythmias and death in patients with acute myocardial infarction (AMI). Recent data suggest that serum FFA(u) concentrations increase well before markers of cardiac necrosis and are sensitive indicators of ischemia in AMI. H-FABP is abundant in cardiac muscle and is presumed to be involved in myocardial lipid homeostasis. Similar to myoglobin, plasma H-FABP increases within 3 h after AMI and returns to reference values within 12-24 h. CONCLUSIONS: FFA(u) may have a potential role in identifying patients with cardiac ischemia. H-FABP is useful for detecting cardiac injury in acute coronary syndromes and predicting recurrent cardiac events in acute coronary syndromes and in congestive heart failure patients. Assays are available for both markers that could facilitate further clinical investigations to assess their possible roles as markers of cardiac ischemia and/or necrosis.

Biomarkers↗
PubMed2005

Relationship between risk stratification by cardiac troponin level and adherence to guidelines for non-ST-segment elevation acute coronary syndromes.

BACKGROUND: The threshold of troponin elevation that stimulates changes in clinical decision making for patients with non-ST-segment elevation acute coronary syndromes (NSTE ACSs) has not been previously evaluated. METHODS: A total of 23 298 patients with NSTE ACSs from the CRUSADE (Can Rapid Risk Stratification of Unstable Angina Patients Suppress Adverse Outcomes With Early Implementation of the ACC/AHA Guidelines) initiative were separated into categories of maximum troponin ratios (ratio of the highest recorded troponin value in the first 24 hours to the local laboratory troponin assay upper limit of normalization [ULN]). RESULTS: Unadjusted rates of in-hospital mortality increased from the group with troponin levels below the reference limit (maximum troponin ratio 0-1 x ULN; n = 5291) to those with minor (1-2 x ULN; n = 2499), intermediate (2-5 x ULN; n = 3825), and major (>5 x ULN; n = 11 683) elevations (-2.8% vs 4.6% vs 4.7% vs 6.0%). The use of early (<24 hours) aspirin, heparin, glycoprotein IIb/IIIa inhibitors, and beta-blockers was similar for the group with troponin levels below the reference limit compared with those with minor troponin elevations, and greater use of medications was demonstrated in patients with intermediate and major troponin elevations. Use of cardiac catheterization and percutaneous coronary intervention was higher in patients with troponin levels below the reference limit compared with those with minor troponin elevations, and procedures were used most frequently in patients with major troponin elevations. Similar patterns of care were demonstrated after excluding patients with chronic renal insufficiency. CONCLUSIONS: Any degree of troponin elevation is associated with a higher risk of mortality for patients with NSTE ACSs, but guideline-recommended medical therapies are used more commonly only in patients with intermediate and major troponin elevations, whereas patients with troponin levels below the reference limit underwent invasive procedures more frequently than those with mild troponin elevations.

Acute Disease↗
PubMed2005

Enzyme estimates of infarct size correlate with functional and clinical outcomes in the setting of ST-segment elevation myocardial infarction.

BACKGROUND: Cardiac biomarkers are routinely obtained in the setting of suspected myocardial ischemia and infarction. Evidence suggests these markers may correlate with functional and clinical outcomes, but the strength of this correlation is unclear. The relationship between enzyme measures of myocardial necrosis and left ventricular performance and adverse clinical outcomes were explored. METHODS: Creatine kinase (CK) and CK-MB data were analyzed, as were left ventricular ejection fraction (LVEF) by angiogram, and infarct size by single-photon emission computed tomography (SPECT) imaging in patients in 2 trials: Prompt Reperfusion In Myocardial-infarction Evolution (PRIME), and Efegatran and Streptokinase to Canalize Arteries Like Accelerated Tissue plasminogen activator (ESCALAT). Both trials evaluated efegatran combined with thrombolysis for treating acute ST-segment elevation myocardial infarction (STEMI). RESULTS: Peak CK and CK area-under-the-curve (AUC) correlated significantly with SPECT-determined infarct size 5 to 10 days after enrollment. Peak CK had a statistically significant correlation with LVEF, but CK-AUC and LVEF correlation were less robust. Statistically significant correlations exist between SPECT-determined infarct size and peak CK-MB and CK-MB AUC. However, there was no correlation with LVEF for peak CK-MB and CK-MB AUC. The combined outcome of congestive heart failure and death were significantly associated with CK AUC, CK-MB AUC, peak CK, and peak CK-MB measurements. CONCLUSION: Peak CK and CK-MB values and AUC calculations have significant correlation with functional outcomes (LVEF- and SPECT-determined infarct size) and death or CHF outcomes in the setting of STEMI. Cardiac biomarkers provide prognostic information and may serve as valid endpoint measurements for phase II clinical trials.

Journal Article↗
PubMed2005

Future biomarkers for detection of ischemia and risk stratification in acute coronary syndrome.

BACKGROUND: Evaluation of patients who present to the hospital with a complaint of chest pain or other signs or symptoms suggestive of acute coronary syndrome (ACS) is time-consuming, expensive, and problematic. Recent investigations have indicated that increases in biomarkers upstream from biomarkers of necrosis (cardiac troponins I and T), such as inflammatory cytokines, cellular adhesion molecules, acute-phase reactants, plaque destabilization and rupture biomarkers, biomarkers of ischemia, and biomarkers of myocardial stretch may provide earlier assessment of overall patient risk and aid in identifying patients with higher risk of an adverse event. APPROACH AND CONTENT: The purpose of this review is to provide an overview of the pathophysiology and clinical and analytical characteristics of several biomarkers that may have potential clinical utility to identify ACS patients. These biomarkers (myeloperoxidase, metalloproteinase-9, soluble CD40 ligand, pregnancy-associated plasma protein A, choline, ischemia-modified albumin, unbound free fatty acids, glycogen phosphorylase isoenzyme BB, and placental growth factor) have demonstrated promise and need to be more thoroughly evaluated for commercial development for implementation into routine clinical and laboratory practice. SUMMARY: Specifications that have been addressed for cardiac troponins and natriuretic peptides will need to be addressed with the same scrutiny for the biomarkers discussed in this review. They include validating analytical imprecision and detection limits, calibrator characterization, assay specificity and standardization, pre-analytical issues, and appropriate reference interval studies. Crossing boundaries from research to clinical application will require replication in multiple settings and experimental evidence supporting a pathophysiologic role and, ideally, interventional trials demonstrating that monitoring single or multiple biomarkers improves outcomes.

Acute Disease↗
PubMed2005

Influence of timing of troponin elevation on clinical outcomes and use of evidence-based therapies for patients with non-ST-segment elevation acute coronary syndromes.

STUDY OBJECTIVE: Previous studies in clinical trial populations have demonstrated that patients presenting with positive troponin levels have a higher risk of mortality than patients with later positive troponin levels, but the influence of the timing of troponin elevation has not been previously characterized. We evaluate the impact of the timing of troponin elevation on clinical outcomes and adherence to the American College of Cardiology/American Heart Association acute care guidelines for patients with non-ST-segment elevation acute coronary syndromes. METHODS: We examined inhospital outcomes and use of acute (<24 hours) medications and invasive cardiac procedures in 23,184 high-risk patients with non-ST-segment elevation acute coronary syndromes (positive cardiac markers or ischemic ST-segment changes) during 2001 to 2002 from 396 US hospitals participating in the Can Rapid Risk Stratification of Unstable Angina Patients Suppress ADverse Outcomes with Early Implementation of the American College of Cardiology/American Heart Association Guidelines (CRUSADE) Initiative. Baseline and peak troponin values were recorded and were designated as positive if above the cutoff value used at each institution to designate definite myocardial necrosis. RESULTS: In the study cohort, 53.2% of patients presented with baseline positive troponin levels, 30.6% had baseline negative/later positive troponin levels, and 16.2% had negative troponin levels during the entire hospitalization. Patients with baseline positive troponin levels had a higher risk of inhospital mortality than patients with baseline negative/later positive troponin levels (6.5% versus 4.1%) and were less likely to undergo early cardiac catheterization or percutaneous coronary intervention. The use of acute aspirin (in approximately 91% of patients), heparin (85%), and beta-blockers (78%) was similar in patients with baseline-positive versus later-positive troponin levels. CONCLUSION: These findings demonstrate that evidence-based therapies and interventions for non-ST-segment elevation acute coronary syndromes are underused in patients with elevated troponin levels, but baseline troponin elevations, which are associated with a higher risk of inhospital mortality, do not stimulate more aggressive care.

Acute Disease↗
PubMed2005

Doping in the recombinant era: strategies and counterstrategies.

Advances in recombinant DNA technology have created one of the most powerful weapons in the current doping arsenal: recombinant proteins [Sweeney HL. Gene doping. Sci Am 2004;291:62-9; Unal M, Ozer Unal D. Gene doping in sports. Sports Med 2004;34:357-62]. Recombinant erythropoietin (EPO) and human growth hormone (hGH) are currently being abused but are fortunately detectable either directly by employing isoelectric focusing and immunoassays or indirectly by assessing changes in selected hematopoietic parameters. The detection is technically demanding due to the extent of similarity between the recombinant proteins and their endogenous counterparts. Another issue facing detection efforts is the speed and conditions at which blood samples are collected and analyzed in a sports setting. Recently, gene doping, which stemmed out of legitimate gene therapy trials, has emerged as the next level of doping. Erythropoietin (EPO), human growth hormone (hGH), insulin-like growth factor-1 (IGF-1), peroxisome proliferator-activated receptor-delta (PPAR delta), and myostatin inhibitor genes have been identified as primary targets for doping. Sports clinical scientists today are racing against the clock because assuring the continued integrity of sports competition depends on their ability to outpace the efforts of dopers by developing new detection strategies.

Animals↗
PubMed2005

Quality specifications for B-type natriuretic peptide assays.

BACKGROUND: The objective of this report is to improve the quality of immunochemical measurements of B-type natriuretic peptide (BNP) and its N-terminal propeptide (NT-proBNP). The recommendations proposed are intended for use by manufacturers of commercial assays, by clinical laboratories using those assays, by clinical trial groups and research investigators, and by regulatory agencies, such as the United States Food and Drug Administration. METHODS: A group of cardiac biomarker experts reviewed and abstracted the scientific literature to provide recommendations pertaining to the quality specifications for BNP/NT-proBNP assays. RESULTS: The evidence-based recommendations encourage manufacturers to endorse and consistently follow the proposed recommendations; encourage that all package inserts for BNP/NT-proBNP immunoassays include uniform information on assay design, preanalytical performance characteristics, analytical performance characteristics, and clinical performance; and encourage regulatory agencies to adopt a minimal and uniform set of criteria for manufacturers to provide when seeking clearance for new and/or improved assays. CONCLUSIONS: These recommendations address the use of BNP and NT-proBNP as cardiac biomarkers and not their physiologic and/or pathophysiologic relevance.

Biomarkers↗
PubMed2004

Evaluation of a point-of-care assay for cardiac markers for patients suspected of acute myocardial infarction.

BACKGROUND: Creatine kinase MB (CK-MB), and cardiac troponin I (cTnI) are important biomarkers for the diagnosis and rule-out of acute myocardial infarction (AMI) of patients who presented to the emergency department (ED) with chest pain. With new rapid ED assessment protocols, there is increasing pressure to produce results with a short turnaround time (TAT), and point-of-care (POC) testing is one alternative for providing fast results. METHODS: In a multicenter study, we evaluated the analytical precision, sensitivity and specificity of the RAMP (Response Biomedical) CK-MB and cTnI POC assays and compared results against the Triage (Biosite) POC and the Dimension RxL (Dade Behring) central-laboratory assays on 365 subjects, including 185 patients suspected of AMI, and determined the normal range on 180 healthy individuals. At one site, the clinical sensitivity and specificity were estimated in 121 patients and healthy subjects with AMI using the European Society of Cardiology (ESC)/American College of Cardiology (ACC) definition of AMI. Results from healthy individuals and those with ST elevation and non-ST elevation AMI were included in a receiver operating characteristic (ROC) curve analysis. RESULTS: Intra- and total imprecision ranged from 7.2% to 11.4% for cTnI at 0.22, 1 and 5 ng/ml and 4.8% to 8.6% for CK-MB at 7, 14 and 25 ng/ml. The upper limit of linearity was 32 ng/ml with an average recovery of 105% for cTnI and 80 ng/ml with a 106% recovery for CK-MB. The lower limit of detection was 0.03 ng/ml (10% coefficient of variance [CV] = 0.21 ng/ml) for cTnI and 0.32 ng/ml for CK-MB. The upper reference limit (normal range) was < 0.03 ng/ml for cTnI and 0-3.7 ng/ml for CK-MB. Analytical correlation against Dimension RxL were RAMP=(0.456 x RxL) + 0.11 (r = 0.988, n = 364) for cTnI and RAMP=(0.966 x RxL) + 0.60 (r = 0.986, n = 363) for CK-MB and against Triage, RAMP=(0.626 x Triage) + 0.164 (r = 0.969, n = 364) for cTnI and RAMP=(0.845 x RxL) - 0.495 (r = 0.952, n = 363) for CK-MB. On 39 AMI and 67 non-AMI patients, the clinical sensitivity, specificity and diagnostic efficiency of the cTnI and CK-MB RAMP assays were not significantly different from predicate assays. CONCLUSIONS: The RAMP cardiac marker assays are alternatives to other FDA-cleared central laboratory and POC testing devices.

Acute Disease↗
PubMed2004

Feasibility of endovascular cooling as an adjunct to primary percutaneous coronary intervention (results of the LOWTEMP pilot study).

In a nonrandomized feasibility study of therapeutic hypothermia in acute myocardial infarction, 18 patients were treated with endovascular cooling (Alsius, Irvine, California) as adjunctive therapy to primary percutaneous coronary intervention to assess measures of infarct size (area under the curve creatinine kinase-MB and technetium-99m single-photon emission computed tomography sestamibi) and the quality of myocardial perfusion (continuous ST-segment monitoring). Periprocedural endovascular cooling successfully decreased core body temperature (median 33.5 degrees C) and was well tolerated, which supports the evaluation of adjunctive hypothermia in pivotal trials to limit infarct size and decrease reperfusion injury.

Angioplasty, Balloon, Coronary↗