Robert H Christenson

Loyola University Maryland, Baltimore, Maryland, United States

Are you Robert H Christenson?

Claim your profile

Publications (209)1196.22 Total impact

  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Patients with stable coronary heart disease (CHD) have widely varying prognoses and treatment options. Validated models for risk stratification of patients with CHD are needed. We sought to evaluate traditional and novel risk factors as predictors of secondary cardiovascular (CV) events, and to develop a prediction model that could be used to risk stratify patients with stable CHD. We used independent derivation (912 participants in the Heart and Soul Study) and validation (2876 participants in the PEACE trial) cohorts of patients with stable CHD to develop a risk prediction model using Cox proportional hazards models. The outcome was CV events, defined as myocardial infarction, stroke, or CV death. The annual rate of CV events was 3.4% in the derivation cohort and 2.2% in the validation cohort. With the exception of smoking, traditional risk factors (including age, sex, body mass index, hypertension, dyslipidemia, and diabetes) did not emerge as the top predictors of secondary CV events. The top 4 predictors of secondary events were the following: N-terminal pro-type brain natriuretic peptide, high-sensitivity cardiac troponin T, urinary albumin:creatinine ratio, and current smoking. The 5-year C-index for this 4-predictor model was 0.73 in the derivation cohort and 0.65 in the validation cohort. As compared with variables in the Framingham secondary events model, the Heart and Soul risk model resulted in net reclassification improvement of 0.47 (95% CI 0.25 to 0.73) in the derivation cohort and 0.18 (95% CI 0.01 to 0.40) in the validation cohort. Novel risk factors are superior to traditional risk factors for predicting 5-year risk of secondary events in patients with stable CHD. © 2015 The Authors. Published on behalf of the American Heart Association, Inc., by Wiley Blackwell.
    Journal of the American Heart Association 07/2015; 4(7). DOI:10.1161/JAHA.114.001646 · 4.31 Impact Factor
  • Digestive Diseases and Sciences 07/2015; DOI:10.1007/s10620-015-3771-0 · 2.61 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: Equations used to estimate glomerular filtration rate (GFR) are not accurate in patients with cirrhosis. We aimed to develop a new equation to estimate the GFR in subjects with cirrhosis and compare its performance with chronic kidney disease epidemiology collaboration (CKD-EPI) cystatin C and creatinine-cystatin C equations, which were derived in populations without cirrhosis. From 2010 through 2014, we measured GFR in 103 subjects with cirrhosis based on non-radiolabeled iothalamate plasma clearance. We measured blood levels of creatinine, cystatin C, β-trace protein, β2 microglobulin, L-arginine, and symmetrical and asymmetrical dimethylarginines simultaneously with GFR. Multivariate linear regression analysis was performed to develop models to estimate GFR. Overall accuracy, defined by the root mean square error (RMSE) of our newly developed model to estimate GFR, was compared with that of the CKD-EPI equations. To obtain an unbiased estimate of our new equation to estimate GFR, we used a leave-one-out cross-validation strategy. After we considered all the candidate variables and blood markers of GFR, the most accurate equation we identified to estimate GFR included serum levels of creatinine and cystatin C, as well as patients' age, sex and race. Overall, the accuracy of this equation (RMSE=22.92) was superior to that of the CKD-EPI cystatin C equation (RSME=27.27, P=.004). Among subjects with cirrhosis and diuretic-refractory ascites, the accuracy of the equation we developed to estimate GFR (RMSE=19.36) was greater than that of the CKD-EPI cystatin C (RSME=27.30, P=.003) and CKD-EPI creatinine-cystatin C equations (RSME=23.37, P=.004). We developed an equation that estimates GFR in subjects with cirrhosis and diuretic-refractory ascites with greater accuracy than the CKD-EPI cystatin C equation or CKD-EPI creatinine-cystatin C. Copyright © 2015 AGA Institute. Published by Elsevier Inc. All rights reserved.
    Clinical gastroenterology and hepatology: the official clinical practice journal of the American Gastroenterological Association 06/2015; DOI:10.1016/j.cgh.2015.06.021 · 7.90 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Copeptin has demonstrated a role in early rule out for acute myocardial infarction (AMI) in combination with a negative troponin. However, management of patients with chest pain with a positive copeptin in the setting of a negative troponin is unclear. The multicentre CHOPIN trial enrolled 2071 patients with acute chest pain. Of these, 476 subjects with an initial negative troponin but an elevated copeptin (>14 pmol/L) were included in this study. Copeptin and troponin levels were rechecked at 2 h and the final diagnosis of AMI was made by two independent, blinded cardiologists. Follow-up at 30 days was obtained for major adverse cardiac events (MACEs), including death, AMI and urgent revascularisation. Of the 476 patients analysed, 365 (76.7%) had a persistently elevated copeptin at 2 h and 111 patients (23.3%) had a copeptin that fell below the cut-off of 14 pmol/L. When the second copeptin was elevated there were 18 AMIs (4.9%) compared with 0 (0%) when the second copeptin was negative (p=0.017), yielding a negative predictive value of 100% (95% CI 96.7% to 100%). On 30-day follow-up there were 36 MACEs (9.9%) in the positive second copeptin group and 2 (1.8%) MACEs in the negative second copeptin group (p=0.006). Patients with chest pain with an initial negative troponin but positive copeptin are common and carry an intermediate risk of AMI. A second copeptin drawn 2 h after presentation may help risk stratify and potentially rule out AMI in this cohort. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to
    Emergency Medicine Journal 06/2015; DOI:10.1136/emermed-2015-204692 · 1.84 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Chest pain is a common complaint to emergency departments (EDs) and clinical risk factors are used to predict which patients are at risk for worse outcomes and mortality. The goal was to assess the novel biomarker midregional proadrenomedullin (MR-proADM) in prediction of mortality and major adverse cardiac events (MACE). This was a subanalysis of the CHOPIN study, a 16-center prospective trial that enrolled 2,071 patients presenting with chest pain within 6 hours of onset. The primary endpoint was 6-month all-cause mortality and the secondary endpoint was 30-day and 6-month MACE: ED visits or hospitalization for acute myocardial infarction, unstable angina, reinfarction, revascularization, and heart failure. MR-proADM performed similarly to troponin (cTnI; c-statistic = 0.845 and 0.794, respectively) for mortality prediction in all subjects and had similar results in those with noncardiac diagnoses. MR-proADM concentrations were stratified by decile, and the cohort in the top decile had a 9.8% 6-month mortality risk versus 0.9% risk for those in the bottom nine deciles (p < 0.0001). MR-proADM, history of coronary artery disease (CAD), and hypertension were predictors of short-term MACE, while history of CAD, hypertension, cTnI, and MR-proADM were predictors of long-term MACE. In patients with chest pain, MR-proADM predicts mortality and MACE in all-comers with chest pain and has similar prediction in those with a noncardiac diagnosis. This exploratory analysis is primarily hypotheses-generating and future prospective studies to identify its utility in risk stratification should be considered. © 2015 by the Society for Academic Emergency Medicine.
    Academic Emergency Medicine 04/2015; 22(5). DOI:10.1111/acem.12649 · 2.01 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: As a part of an International Federation of Clinical Chemistry and Laboratory Medicine (IFCC) project to prepare a commutable reference material for cardiac troponin I (cTnI), a pilot study evaluated current cTnI assays for measurement equivalence and their standardization capability. cTnI-positive samples collected from 90 patients with suspected acute myocardial infarction were assessed for method comparison by 16 cTnI commercial assays according to predefined testing protocols. Seven serum pools prepared from these samples were also assessed. Each assay was assessed against median cTnI concentrations measured by 16 cTnI assays using Passing-Bablok regression analysis of 79 patient samples with values above each assay's declared detection limit. We observed a 10-fold difference in cTnI concentrations for lowest to highest measurement results. After mathematical recalibration of assays, the between-assay variation for patient samples reduced on average from 40% to 22% at low cTnI concentration, 37%-20% at medium concentration, and 29%-14% at high concentration. The average reduction for pools was larger at 16%, 13% and 7% for low, medium and high cTnI concentrations, respectively. Overall, assays demonstrated negligible bias after recalibration (y-intercept: -1.4 to 0.3 ng/L); however, a few samples showed substantial positive and/or negative differences for individual cTnI assays. All of the 16 commercial cTnI assays evaluated in the study demonstrated a significantly higher degree of measurement equivalence after mathematical recalibration, indicating that measurement harmonization or standardization would be effective at reducing inter-assay bias. Pooled sera behaved similarly to individual samples in most assays.
    Clinical Chemistry and Laboratory Medicine 04/2015; 53(5):677-690. DOI:10.1515/cclm-2014-1197 · 2.71 Impact Factor
  • Christopher R deFilippi · Robert H Christenson
    JACC: Heart Failure 03/2015; 3(3):253-6. DOI:10.1016/j.jchf.2014.12.009
  • [Show abstract] [Hide abstract]
    ABSTRACT: This article is a systematic review of the effectiveness of four practices (assay selection, decision point cardiac troponin (cTn) threshold selection, serial testing, and point of care testing) for improving the diagnostic accuracy Non-ST-Segment Elevation Myocardial Infarction (NSTEMI) in the Emergency Department. The CDC-funded Laboratory Medicine Best Practices (LMBP) Initiative systematic review method for quality improvement practices was used. The current ACC/AHA guidelines recommend using cardiac troponin assays with a 99th percentile upper reference limit (URL) diagnostic threshold to diagnose NSTEMI. The evidence in this systematic review indicates that contemporary sensitive cTn assays meet the assay profile requirements (sensitivity, specificity, PPV, and NPV) to more accurately diagnose NSTEMI than alternate tests. Additional biomarkers did not increase diagnostic effectiveness of cTn assays. Sensitivity, specificity, and NPV were consistently high and low PPV improved with serial sampling. Evidence for use of point of care cTn testing was insufficient to make recommendation, though some evidence suggests that use may result in reduction to patient length of stay and costs. Based on the review of and the LMBP recommendation criteria, we recommend the use of cardiac troponin assays without additional biomarkers using the 99th percentile URL as the clinical diagnostic threshold for the diagnosis of NSTEMI. We recommend serial sampling with one sample at presentation and at least one additional second sample taken at least 6h later to identify a rise or fall in the troponin level. No recommendation is made either for or against the use of point of care tests. The findings and conclusions in this article are those of the authors and do not necessarily represent the official position of the Centers for Disease Control and Prevention/the Agency for Toxic Substances and Disease Registry (CDC/ATSDR). Copyright © 2015. Published by Elsevier Inc.
    Clinical Biochemistry 02/2015; 48(4-5). DOI:10.1016/j.clinbiochem.2015.01.014 · 2.28 Impact Factor
  • Paul O Collinson · Lisa Garrison · Robert H Christenson
    [Show abstract] [Hide abstract]
    ABSTRACT: Professor P. O. Collinson MA MB BChir FRCPath MD FACB FRCP edin.EurClinChem FESC is Consultant Chemical Pathologist at St George’s Hospital and Professor of Cardiovascular Biomarkers at St George’s Medical School. He is responsible for the Clinical services of the Blood Sciences laboratory and provides the Vascular Risk management service for the Cardiac Department. He has published over 200 papers and review articles, over 220 abstracts and 15 book chapters.
    Clinical Biochemistry 11/2014; 48(4-5). DOI:10.1016/j.clinbiochem.2014.11.014 · 2.28 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: High-sensitivity troponin T (hsTnT) and N-terminal pro-B-type natriuretic peptide (NT-proBNP) strongly predict heart failure (HF) in the general population. However, the interpretation of levels of these biomarkers as predictors of HF is uncertain among patients with CKD. Here, we investigated whether hsTnT and NT-proBNP are associated with incident HF among patients with CKD. In a prospective cohort analysis, we studied 3483 people with CKD in the Chronic Renal Insufficiency Cohort (CRIC) Study recruited from June of 2003 to August of 2008 who were free of HF at baseline. We used Cox regression to examine the association of baseline levels of hsTnT and NT-proBNP with incident HF after adjustment for demographic factors, traditional cardiovascular risk factors, markers of kidney disease, pertinent medication use, and mineral metabolism markers. At baseline, hsTnT levels ranged from ≤5.0 to 378.7 pg/ml, and NT-proBNP levels ranged from ≤5 to 35,000 pg/ml. Compared with those who had undetectable hsTnT, participants in the highest quartile (>26.5 ng/ml) had a significantly higher rate of HF (hazard ratio, 4.77; 95% confidence interval, 2.49 to 9.14). Similarly, compared with those in the lowest NT-proBNP quintile (<47.6 ng/ml), participants in the highest quintile (>433.0 ng/ml) experienced a substantially higher rate of HF (hazard ratio, 9.57; 95% confidence interval, 4.40 to 20.83). In conclusion, hsTnT and NT-proBNP were strongly associated with incident HF among a diverse cohort of individuals with mild to severe CKD. Elevations in these biomarkers may indicate subclinical changes in volume and myocardial stress that subsequently contribute to clinical HF.
    Journal of the American Society of Nephrology 10/2014; 26(4). DOI:10.1681/ASN.2014010108 · 9.34 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: Background Peak creatine kinase (CK)-MB concentration is related to reperfusion success and clinical outcomes after fibrinolytic therapy for acute myocardial infarction. However, prognostic implications of CK-MB measurements after primary percutaneous coronary intervention (PCI), which provides more predictable and consistent reperfusion, are unknown. Methods We pooled 2042 primary PCI-treated ST-segment elevation myocardial infarction (STEMI) patients from 3 trials with serial core laboratory-determined CK-MB measurements; 1799 patients (88.1%) who survived to 36 hours and had ≥4 CK-MB measurements were studied. Cox regression modeling was performed to quantify the association between peak CK-MB concentration (and area under the time-concentration curve [AUC]) and mortality at 6 months, and death or congestive heart failure (CHF) at 90 days. Results The median (25th–75th percentiles) peak CK-MB concentration and AUC measurement through 36 hours were 239 (109–429) ng/mL and 4263 (2081–7124) ng/mL · h, respectively. By multivariable analysis, peak CK-MB concentration and AUC measurement were independently associated with 6-month mortality (adjusted HR 1.15, 95% CI 1.05–1.25, per 100 ng/mL increase, p = 0.002; and adjusted HR 1.09, 95% CI 1.03–1.14, per 1000 ng/mL · h increase, p < 0.001, respectively) and 90-day death or CHF (adjusted HR 1.26, 95% CI 1.18–1.34, p < 0.001; and adjusted HR 1.15, 95% CI 1.11–1.19, p < 0.001, respectively). Conclusions Peak CK-MB concentration and AUC measurement are independent predictors of 3- to 6-month cardiovascular outcomes in primary PCI-treated STEMI patients. Our findings guide application of these measurements as efficacy endpoints in early-phase studies evaluating new therapies for STEMI.
    American Heart Journal 10/2014; 168(4). DOI:10.1016/j.ahj.2014.06.008 · 4.46 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Objectives: We investigated absolute and relative cardiac troponin I (TnI) delta changes, optimal sampling protocols, and decision thresholds for early diagnosis of myocardial infarction (MI). Serial cardiac biomarker values demonstrating a rise and/or fall define MI diagnosis; however the magnitude of change, timing, and diagnostic accuracy of absolute versus relative (percentage) deltas remains unsettled. Methods: We prospectively measured TnI (AccuTnI+3™, Beckman Coulter) at serial time intervals in 1929 subjects with chest pain or equivalent symptoms of acute coronary syndrome at 14 medical centers. Diagnosis was adjudicated by an independent central committee. Results: Elevated TnI above a threshold of 0.03ng/mL demonstrated significant diagnostic efficacy (AUC 0.96). For patients with TnI<0.03ng/mL and symptom onset≥8h, 99.1% (NPV) were diagnosed with conditions other than MI. Absolute delta performed significantly better than relative delta at 1-3h (AUC 0.84 vs 0.69), 3-6h (0.85 vs 0.73), and 6-9h (0.91 vs 0.79). Current recommendations propose ≥20% delta within 3-6h; however, results were optimized using an absolute delta of 0.01 or 0.02ng/mL. Sensitivity results for absolute delta at 1-3h and 3-6h (75.8%, 78.3%) were superior to relative delta (48.0%, 61.3%). NPV (rule out) was 99.6% when baseline TnI<0.03ng/mL and absolute delta TnI<0.01ng/mL. Conclusions: Absolute delta performed significantly better than relative delta at all time intervals. Baseline TnI and absolute delta may be used in conjunction to estimate probability of MI. Consensus recommendations are supported for sampling on admission and 3h later, repeated at 6h in patients when clinical suspicion remains high.
    Clinical Biochemistry 09/2014; 48(4-5). DOI:10.1016/j.clinbiochem.2014.09.012 · 2.28 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Objectives: To compare emergency department TnI serial sampling intervals, determine optimal diagnostic thresholds, and report representative diagnostic performance characteristics for early rule-in and rule-out of MI. Methods: We prospectively measured TnI (AccuTnI+3™, Beckman Coulter) at serial time intervals in 1929 subjects with chest pain or equivalent ischemic symptoms suggestive of acute coronary syndromes at 14 medical centers. Diagnosis was adjudicated by an independent central committee. Results: TnI ≥0.03ng/mL provided 96.0% sensitivity and 89.4% specificity at 1-3h after admission, and 94.9% sensitivity and 86.7% specificity at 3-6h. NPV (rule-out, non-MI) was 99.5% at 1-3h, and 99.0% at 3-6h when TnI is <0.03ng/mL. NPV was 99.1% when TnI is <0.03ng/mL and time of symptom onset is ≥8h. Approximately 50-58% (PPV) of patients with TnI ≥0.03ng/mL were diagnosed with MI, depending upon time from onset or admission; PPVs emphasize the importance of serial samples and delta TnI (rising or falling pattern) when low cutoffs are used. Nevertheless, even a single elevated TnI value increased the risk of MI. As TnI values rose, the probability of MI increased. Values ≥0.20ng/mL were associated with nearly 90% probability of MI. Conclusions: We report a large multicenter prospective adjudicated trial assessing troponin for early rule-in and rule-out using the Universal Definition of MI and conducted in primary care hospital-associated emergency departments. Our study demonstrates high diagnostic accuracy at early observation times, and reinforces consensus recommendations for sampling on admission and 3h later, repeated at 6h when clinical suspicion remains high.
    Clinical Biochemistry 09/2014; 48(4-5). DOI:10.1016/j.clinbiochem.2014.08.018 · 2.28 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: Concentrations of endothelin I (ET1) are elevated in CHF patients, and, like other biomarkers that reflect hemodynamic status and cardiac pathophysiology, are prognostic. The Singulex assay (Sgx-ET1) measures the active form of ET1, with a short in-vivo half-life and C-terminal endothelin-1 (CT-ET1) is measured by the Brahms assay and is a modified (degraded) product with longer half-life. We aimed to determine the prognostic importance of active and modified forms of endothelin 1 (Singulex and Brahms assays) in comparison with other commonly measured biomarkers of inflammation, hemodynamic status and cardiac physiology in CHF. Plasma biomarkers (Sgx-ET1, CT-ET1, NTproBNP, IL-6, TNFα, cTnI, VEGF, hs-CRP, Galectin-3, ST2) were measured in 134 NYHA class II and III CHF patients with systolic dysfunction. Prognostic importance of biomarkers for hospitalization or death were calculated by both logistic regression and Kaplan-Meier survival analyses. CT-ET1 (OR 5.2, 95% CI 1.7-15.7) and Sgx-ET1 (OR 2.9, CI 1.1-7.7) were independent predictors of hospitalization and death and additively predicted events after adjusting for age, sex and other significant biomarkers. Other biomarkers did not improve the model. Similarly, in Cox regression analysis, only CT-ET1 (HR 3.4, 95% CI 1.4-8.4), VEGF (2.7, 95% CI 1.3-5.4) and Sgx-ET1 (HR 2.6, 95% CI 1.2-5.6) were independently prognostic. Elevated concentrations of endothelin 1 predict mortality and hospitalizations in HF patients. Endothelin 1 was more prognostic than commonly obtained hemodynamic, inflammatory and fibrotic biomarkers. Two different assays of endothelin 1 independently and synergistically were prognostic, suggesting either complementary information or extreme prognostic importance. Copyright © 2014. Published by Elsevier Inc.
    Clinical Biochemistry 08/2014; 20(8S):S78. DOI:10.1016/j.cardfail.2014.06.221 · 2.28 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: Background: Renal hemodynamic measurements are complicated to perform in patients with cirrhosis, yet they provide the best measure of risk to predict hepatorenal syndrome (HRS). Currently, there are no established biomarkers of altered renal hemodynamics in cirrhosis validated by measured renal hemodynamics. Methods: In this pilot study, simultaneous measurements of glomerular filtration rate (GFR), renal plasma flow (RPF), renal resistive indices and biomarkers were performed to evaluate renal hemodynamic alterations in 10 patients with cirrhosis (3 patients without ascites, 5 with diuretic-sensitive and 2 diuretic-refractory ascites). Results: Patients with diuretic-refractory ascites had the lowest mean GFR (36.5 ml/min/1.73 m(2)) and RPF (133.6 ml/min/1.73 m(2)) when compared to those without ascites (GFR 82.9 ml/min/1.73 m(2), RPF 229.9 ml/min/1.73 m(2)) and with diuretic-sensitive ascites (GFR 82.3 ml/min/1.73 m(2), RPF 344.1 ml/min/1.73 m(2)). A higher mean filtration fraction (FF) (GFR/RPF 0.36) was noted among those without ascites compared to those with ascites. Higher FF in patients without ascites is most likely secondary to the vasoconstriction in the efferent glomerular arterioles (normal FF ~0.20). In general, renal resistive indices were inversely related to FF. While patients with ascites had lower FF and higher right kidney main and arcuate artery resistive indices, those without ascites had higher FF and lower right kidney main and arcuate artery resistive indices. While cystatin C and β2-microglobulin performed better compared to Cr in estimating RPF, β-trace protein, β2-microglobulin, and SDMA, and (SDMA+ADMA) performed better in estimating right kidney arcuate artery resistive index. Conclusion: The results of this pilot study showed that identification of non-invasive biomarkers of reduced RPF and increased renal resistive indices can identify cirrhotics at risk for HRS at a stage more amenable to therapeutic intervention and reduce mortality from kidney failure in cirrhosis.
    American Journal of Nephrology 06/2014; 39(6):543-552. DOI:10.1159/000363584 · 2.67 Impact Factor
  • Source
    Robert H Christenson · Cheryl A Kassed
    Journal of Comparative Effectiveness Research 05/2014; 3(3):221-4. DOI:10.2217/cer.14.11 · 0.72 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: There is uncertainty regarding treatment of hypertension in hemodialysis patients due to the observed J-shaped association between blood pressure (BP) and death. We hypothesized that this association reflects confounding by cardiovascular disease (CVD) and that stratification by CVD biomarkers, cardiac troponin I (cTnI) and N-terminal fragment of prohormone brain natriuretic peptide (NT-proBNP), might change this association. National prospective cohort study. 446 incident hemodialysis patients. Predialysis systolic BP. Mortality (all-cause and CVD) and first CVD event assessed using Cox regression adjusted for demographics, comorbid conditions, and clinical factors. Participants with cTnI level≥0.1ng/mL or NT-proBNP level≥9,252pg/mL were classified as the high-biomarker group; remaining participants were included in the low-biomarker group. Participants in the high-biomarker group (n=138 [31%]) were older (61 vs 57 years) and had a higher prevalence of CVD (67% vs 23%), but similar baseline BPs (152 vs 153mmHg). There were 323 deaths (143 from CVD) and 271 CVD events. The high-biomarker group had a higher risk of mortality than the low-biomarker group (HR, 1.75; 95%CI, 1.37-2.24). The association between BP and outcomes differed between the 2 biomarker groups (P for interaction=0.01, 0.2, and 0.07 for all-cause mortality, CVD mortality, and first CVD event, respectively). In the low-biomarker group, BP was associated with greater risk of outcomes: HR per 10mmHg higher BP was 1.07 (95%CI, 1.01-1.14), 1.10 (95%CI, 0.96-1.25), and 1.04 (95%CI, 0.96-1.13) for all-cause mortality, CVD mortality, and first CVD event, respectively. Importantly, lower BP was not associated with increased risk of outcomes in stratified models, including for those in high biomarker group. BP measurements not standardized. The observed J-shaped association between BP and outcomes in hemodialysis patients is due to confounding by subclinical CVD. A stratification approach based on cTnI and NT-proBNP levels has the potential to inform BP treatment in hemodialysis patients.
    American Journal of Kidney Diseases 04/2014; 64(3). DOI:10.1053/j.ajkd.2014.03.015 · 5.90 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: Background: Heart failure is a syndrome characterized by the inability of the heart to meet the body's circulatory demands. Heart failure is a growing health issue worldwide and the prevalence of heart failure is expected to rise as populations age. Therapies and interventions for a variety of cardiac conditions continue to advance and biomarkers will play an increasing role in patient management. Methods: This is a review of the clinical research in blood based biomarkers for diagnosis, prognosis and therapeutic guidance of heart failure. The focus of this review is biomarkers that are currently available for clinical measurement, and their current and potential for applications for managing heart failure patients. Results: The various biologic pathways and physiologic processes of heart failure biomarkers represent a host of different including inflammation, remodeling, strain, neurohormonal activation, metabolism and cardiac myocyte injury. The clinical characteristics and applications of each heart failure biomarker are discussed. Conclusion: As populations age and effective treatments and interventions for coronary artery disease improve, heart failure will increase in incidence and prevalence. Blood biomarkers will play an increasing role in the early diagnosis, therapeutic monitoring and management of heart failure patients in the future.
    Clinical biochemistry 04/2014; 47(6). DOI:10.1016/j.clinbiochem.2014.01.032 · 2.28 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: Unlabelled: Conventional creatinine-based glomerular filtration rate (GFR) equations are insufficiently accurate for estimating GFR in cirrhosis. The Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) recently proposed an equation to estimate GFR in subjects without cirrhosis using both serum creatinine and cystatin C levels. Performance of the new CKD-EPI creatinine-cystatin C equation (2012) was superior to previous creatinine- or cystatin C-based GFR equations. To evaluate the performance of the CKD-EPI creatinine-cystatin C equation in subjects with cirrhosis, we compared it to GFR measured by nonradiolabeled iothalamate plasma clearance (mGFR) in 72 subjects with cirrhosis. We compared the "bias," "precision," and "accuracy" of the new CKD-EPI creatinine-cystatin C equation to that of 24-hour urinary creatinine clearance (CrCl), Cockcroft-Gault (CG), and previously reported creatinine- and/or cystatin C-based GFR-estimating equations. Accuracy of CKD-EPI creatinine-cystatin C equation as quantified by root mean squared error of difference scores (differences between mGFR and estimated GFR [eGFR] or between mGFR and CrCl, or between mGFR and CG equation for each subject) (RMSE = 23.56) was significantly better than that of CrCl (37.69, P = 0.001), CG (RMSE = 36.12, P = 0.002), and GFR-estimating equations based on cystatin C only. Its accuracy as quantified by percentage of eGFRs that differed by greater than 30% with respect to mGFR was significantly better compared to CrCl (P = 0.024), CG (P = 0.0001), 4-variable MDRD (P = 0.027), and CKD-EPI creatinine 2009 (P = 0.012) equations. However, for 23.61% of the subjects, GFR estimated by CKD-EPI creatinine-cystatin C equation differed from the mGFR by more than 30%. Conclusion: The diagnostic performance of CKD-EPI creatinine-cystatin C equation (2012) in patients with cirrhosis was superior to conventional equations in clinical practice for estimating GFR. However, its diagnostic performance was substantially worse than reported in subjects without cirrhosis.
    Hepatology 04/2014; 59(4). DOI:10.1002/hep.26556 · 11.06 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Objectives To determine the 99th percentile upper reference limit for the highly sensitive cardiac troponin T assay (hs-cTnT) in three large independent cohorts. Background The presently recommended 14 ng/L cutpoint for the diagnosis of myocardial infarction using the hs-cTnT assay was derived from small studies of presumably healthy individuals, with relatively little phenotypic characterization. Methods Data were included from three well characterized population-based studies: the Dallas Heart Study (DHS), the Atherosclerosis Risk in Communities (ARIC) Study, and the Cardiovascular Health Study (CHS). Within each cohort, reference subcohorts were defined excluding individuals with recent hospitalization, overt cardiovascular disease and kidney disease (subcohort 1) and further excluding those with subclinical structural heart disease (subcohort 2). Data were analyzed stratified by age, sex and race. Results The 99th percentile values for the hs-cTnT assay in DHS, ARIC and CHS were 18, 22 and 36 ng/L respectively (subcohort 1) and 14, 21 and 28 ng/L respectively (subcohort 2). These differences in 99th percentile values paralleled age differences across cohorts. Analyses within sex/age strata yielded similar results between cohorts. Within each cohort, 99th percentile values increased with age and were higher in men. More than 10% of men aged 65-74 with no cardiovascular disease in our study had cTnT values above the current myocardial infarction threshold. Conclusions Use of a uniform 14 ng/L cutoff for the hs-cTnT assay may lead to over-diagnosis of myocardial infarction, particularly in men and the elderly. Clinical validation is needed of new age- and sex-specific cutoff values for this assay.
    Journal of the American College of Cardiology 04/2014; 63(14). DOI:10.1016/j.jacc.2013.12.032 · 16.50 Impact Factor

Publication Stats

8k Citations
1,196.22 Total Impact Points


  • 1999–2015
    • Loyola University Maryland
      Baltimore, Maryland, United States
  • 1992–2015
    • University of Maryland, Baltimore
      • • Department of Pathology
      • • Department of Medicine
      • • Department of Medical and Research Technology
      Baltimore, Maryland, United States
  • 1993–2014
    • University of Maryland Medical Center
      • Department of Pathology
      Baltimore, Maryland, United States
  • 2008
    • Cleveland Clinic
      Cleveland, Ohio, United States
  • 1999–2007
    • Hennepin County Medical Center
      Minneapolis, Minnesota, United States
  • 2006
    • The American University in Cairo
      • School of Sciences and Engineering
      Cairo, Muhafazat al Qahirah, Egypt
  • 2005–2006
    • University of Milan
      Milano, Lombardy, Italy
    • University of California, San Francisco
      San Francisco, California, United States
  • 2003–2005
    • Duke University
      • Department of Medicine
      Durham, North Carolina, United States
    • Harvard University
      Cambridge, Massachusetts, United States
    • St. Michael's Hospital
      Toronto, Ontario, Canada
  • 2004
    • University System of Maryland
      Adelphi, Maryland, United States
    • University of North Carolina at Chapel Hill
      North Carolina, United States
    • University of Innsbruck
      Innsbruck, Tyrol, Austria
  • 1991
    • Duke University Medical Center
      • Department of Pathology
      Durham, North Carolina, United States