[Show abstract][Hide abstract]ABSTRACT: Background:
The association between galectin-3 and heart failure (HF) or death is well established for white, but not for black, adults.
Methods and results:
Galectin-3 was measured in 1809 participants (1375 white, 434 black), enrolled in a substudy of the Atherosclerosis Risk in Communities (ARIC) observational cohort during 2004-2005. We used Cox proportional hazard models to estimate the adjusted association between galectin-3 and outcomes. Analyses were conducted overall and by race category. Median (interquartile range) galectin-3 levels were 13.4 (11.2-16.4) and 14.8 (12-17.6) ng/mL, in white and black participants, respectively. In the sample overall, galectin-3 was not independently associated with HF or death over a maximum of 7.9 years. However, in race-stratified analyses, galectin-3 was independently associated with a composite of HF or death among whites (eg, hazard ratio 2.2, 95% CI 1.2-3.9, comparing Q4 versus Q1); but not among blacks (hazard ratio of 0.8 [0.4-1.8] for Q4 versus Q1, race interaction P=0.03). Associations between galectin-3 and both outcomes analyzed individually also demonstrated similar racial differences. Furthermore, results were qualitatively similar with galectin-3 modeled as a continuous exposure. In addition, galectin-3 improved discrimination for the composite of HF or death among whites (increase in Harrell's C statistic from 0.729 to 0.735 [difference of +0.006], P=0.049), but not among blacks (0.696 to 0.695 [difference of -0.001], P=0.814).
In contrast to whites, galectin-3 may have limited prognostic utility for predicting HF and death in blacks. While our results require replication, they could reflect racial differences in the processes by which galectin-3 mediates disease.
Full-text · Article · May 2016 · Journal of the American Heart Association
[Show abstract][Hide abstract]ABSTRACT: Objectives:
To evaluate the impact of age- and gender-specific cut-offs for high-sensitivity cardiac troponin T (hs-cTnT) compared to the general 99th percentile hs-cTnT cut-off on diagnosis and prognosis of acute myocardial infarction (AMI).
1282 unselected patients presenting to the emergency department with suspected AMI were enrolled as part of the TRAPID-AMI study. In the present sub-analysis, reclassification of AMI diagnosis was performed by comparing the general hs-cTnT cut-off of 14ng/L to previously proposed age- and gender-dependent hs-cTnT 99th percentile cut-offs (28ng/L for ≥65years, 9ng/L for female and 15.5ng/L for male patients). Patients were further clinically adjudicated into acute coronary syndrome (ACS) and non-ACS.
For patients ≥65years, application of age-specified cut-offs resulted in a decrease of AMI from 29.8% to 18.3% in the entire cohort (n=557) and 54.7% to 40.9% in the ACS subcohort (n=225). Using gender-specific cut-offs, AMI-rate increased from 16.6% to 22.6% (entire cohort, n=477) and 62.6% to 71.7% (ACS subcohort, n=99) in women, whereas in men, rates decreased from 23.1% to 21.1% (entire cohort, n=805) and 48.8% to 45.9% (ACS, n=281), respectively. Age-specified cut-offs significantly reclassified patients for outcomes of 1-month and 3-month mortality in the entire and ACS cohort (14.2% net reclassification improvement, p<0.001, respectively). Contrary, no significant differences in outcomes could be found using gender-specific cut-offs.
While influence of gender-specific hs-cTnT cut-offs on diagnostic and prognostic reclassification was only modest in patients with suspected AMI, age-specific cut-offs showed a significant impact and may be considered for further validation.
No preview · Article · Feb 2016 · International journal of cardiology
[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 http://group.bmj.com/group/rights-licensing/permissions.
Full-text · Article · Jun 2015 · Emergency Medicine Journal
[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.
No preview · Article · Apr 2015 · Clinical Chemistry and Laboratory Medicine
[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.
No preview · Article · Nov 2014 · Clinical Biochemistry
[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.
No preview · Article · Oct 2014 · Journal of the American Society of Nephrology
[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.
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.
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).
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.
No preview · Article · Oct 2014 · American Heart Journal
[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.
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.
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.
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.
[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.
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.
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.
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.
[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.
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).
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.
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.
No preview · Article · Jun 2014 · American Journal of Nephrology