Biomedical subjects

Andrew R MacRae

Publications and source records attributed to Andrew R MacRae.

6 recordsLinked to original sources

PubMed2007

Long-term health outcomes associated with detectable troponin I concentrations.

BACKGROUND: Recent data suggest that older men with detectable cardiac troponin I (cTnI) concentrations that remain below the 99th percentile concentration cutoff are at increased risk for subsequent cardiovascular events. We designed this study to extend this observation by examining risk prediction in both men and women presenting to an emergency department with chest discomfort. METHODS: We obtained data for all-cause mortality and hospital discharges associated with either acute myocardial infarction (AMI) or congestive heart failure (CHF) for up to 8 years after the initial presentation in 448 patients who originally presented in 1996 with acute coronary syndrome (ACS). We performed retrospective analysis for cTnI (AccuTnI; Beckman Coulter) in frozen plasma samples based on the patients' reported time from onset of symptoms. Peak cTnI concentration was used for risk assessment. RESULTS: Patients with cTnI concentrations > or =0.02 microg/L (i.e., limit of detection), including those whose peak values remained below the 99th percentile (0.04 microg/L), were at greater risk for death and AMI/CHF readmissions at 2, 5, and 8 years of follow-up compared with those with peak cTnI <0.02 microg/L. All results were statistically significant (P <0.05) except for death within 2 years among patients with normal but detectable cTnI (0.02 to 0.03 microg/L), relative to the group with values <0.02 microg/L. Kaplan-Meier analyses indicated that both men and women with cTnI > or =0.02 microg/L had worse outcomes (P <0.001). CONCLUSION: Both men and women who present with possible ACS with detectable cTnI concentrations that remain below the 99th percentile are at a greater risk for future adverse events.

Aged↗

PubMed2006

Health outcomes categorized by current and previous definitions of acute myocardial infarction in an unselected cohort of troponin-naïve emergency department patients.

BACKGROUND: In a population originally classified for acute myocardial infarction (AMI) by the World Health Organization (WHO) definition, we compared the health outcomes after retrospectively reclassifying with the European Society of Cardiology and the American College of Cardiology (ESC/ACC) AMI definition, using the peak cardiac troponin I (cTnI) concentrations. The health outcomes were based on the WHO definition and occurred in an era that preceded the use of cardiac troponin biomarkers. METHODS: For 448 patients who presented to the emergency department with symptoms suggestive of cardiac ischemia in 1996, we obtained data for all-cause mortality and recurrent AMI for up to 1 year after the initial presentation. We performed retrospective analysis of the patients' frozen plasma samples to measure cTnI (AccuTnI, Beckman Coulter). RESULTS: At 30, 120, and 360 days, the risk for AMI/death in patients positive for AMI by only the ESC/ACC criteria was significantly lower than the risk in patients positive by both ESC/ACC and WHO criteria, and significantly higher than in patients negative according to both criteria. In a separate analysis, patients with a peak cTnI>0.10 microg/L were at greater risk for AMI/death than patients with cTnI concentrations of 0.04-0.10 microg/L. Patients negative by both definitions or with peak cTnI concentrations<0.04 microg/L had the highest event-free survival rates (92% and 94%, respectively) at 1 year. CONCLUSION: In a troponin-naïve population, patients classified as positive for AMI by only the ESC/ACC criteria have a prognosis that appears to be intermediate between those classified positive by both the WHO and ESC/ACC definitions and those who meet neither criteria.

Aged↗

PubMed2006

Identifying Smith-Lemli-Opitz syndrome in conjunction with prenatal screening for Down syndrome.

BACKGROUND: Smith-Lemli-Opitz syndrome (SLOS) is a rare hereditary disorder of cholesterol metabolism. We examine the feasibility of identifying SLOS as a part of a routine prenatal screening and evaluate diagnostic testing in maternal urine (or serum), in addition to amniotic fluid. METHODS: Our SLOS risk algorithm utilized three Down syndrome screening markers (estimated 62% detection rate; 0.3% screen-positive rate). Fifteen North American prenatal screening programs implemented this algorithm. RESULTS: SLOS risk was assigned to 1 079 301 pregnancies; 3083 were screen-positive (0.29%). Explanations were found for 1174, including 914 existing fetal deaths. Among the remaining pregnancies, 739 were screen-positive only for SLOS; 1170 were also screen-positive for other fetal disorders. Five of six SLOS pregnancies (83%) were screen-positive. All six had sonographic findings, were biochemically confirmed, and were terminated. Maternal urine steroid measurements were confirmatory in four cases tested. Second-trimester prevalence among Caucasians was 1 in 101 000 (1 in 130 000 overall; no cases in other racial groups). Among 739 pregnancies screen-positive only for SLOS, two cases were identified; another 69 had major fetal abnormalities. CONCLUSIONS: Although SLOS occurred less often than previously reported, many other major abnormalities were detected. Implementing the algorithm as an adjunct to Down syndrome screening may be feasible.

Abnormalities, Multiple↗

PubMed2006

The impact of the ESC/ACC redefinition of myocardial infarction and new sensitive troponin assays on the frequency of acute myocardial infarction.

BACKGROUND: The prevalence of acute myocardial infarction (AMI) has increased due to the recent definitions, but the magnitude of this effect using contemporary highly sensitive troponin assays is unclear. The objective of this study is to compare the diagnosis of AMI using a contemporary troponin I (cTnI) biomarker and the 2003 American Heart Association (AHA) case definition with diagnoses made using the 1994 World Health Organization MONICA definition. METHODS: Contemporary troponin I measurements were performed with the Beckman Coulter AccuTnI assay (Chaska, MN) on plasma specimens originally assayed in 1996 for creatine kinase (CK)-MB mass from 486 emergency department patients presenting within 24 hours of onset of symptoms suggestive of cardiac ischemia. RESULTS: In a subgroup of 258 patients with 2 specimens drawn at least 6 hours apart (the AHA "adequate set of biomarkers"), AMI prevalence using CK-MB was 19.4% (95% CI 15.0-24.7) based on MONICA and 19.8% (15.4-25.1) based on the AHA case definition using the criterion for change of > or = 20% between specimens. Using cTnI as the biomarker of choice, under the AHA definition, the prevalence increased to as high as 35.7% (30.1-41.7, a relative increase of 84%, P < .001) using the 99th percentile cutoff. In 121 patients with a lower index of suspicion and without the requisite 6-hour interval between measurements, positivity increased from 5% with CK-MB by MONICA up to 12% to 16% with cTnI by AHA. CONCLUSIONS: A highly sensitive contemporary cTnI assay used with the AHA case definition results in a 62% to 84% increase in the frequency of AMI diagnosis compared with MONICA criteria.

Aged↗

PubMed2005

Second trimester serum markers.

Prenatal screening for Down syndrome in the early second trimester with multiple maternal serum markers has been available for more than 15 years. The multiple marker combination with the highest screening performance currently available is alpha-fetoprotein (AFP), unconjugated estriol (uE3), human chorionic gonadotropin (hCG), and inhibin A, together with maternal age (so-called quad marker test). With this combination, a detection rate of 80% at a 5% false positive rate is achieved. Inhibin A, the newest addition to second trimester serum screening, is an alpha-beta subunit hormone of placental origin, and is measured using a monoclonal two-site ELISA validated for use in prenatal screening. Quality control parameters for inhibin A measurement are acceptable and are monitored through the proficiency testing program administered by the College of American Pathologists. Research into other possible second trimester screening markers has included studies on the maternal urine and serum levels of an hCG variant, hyperglosylated hCG (h-hCG; invasive trophoblast antigen). Recent data indicate that h-hCG is similar to hCG itself, although its measurement in maternal urine may improve the performance of the established serum marker combinations. With the introduction of first trimester screening markers and their use in an integrated first and second trimester marker approach to screening, and with the fact that many women do not seek prenatal care until the early second trimester, prenatal screening for Down syndrome using second trimester serum markers remains a major resource in obstetrical care.

Chorionic Gonadotropin↗

PubMed2003

Outcome validation of the Beckman Coulter access analyzer in a second-trimester Down syndrome serum screening application.

BACKGROUND: Mid-trimester maternal serum alpha-fetoprotein (AFP) and unconjugated estriol (uE3) are 30% lower and human chorionic gonadotropin (hCG) is twofold higher in Down syndrome pregnancies compared with unaffected pregnancies. In maternal serum screening, patient-specific risks are calculated using published gaussian frequency distribution parameters for these three markers obtained with previously available immunoassays. New immunoassays must generate similar distribution parameters if the accuracy of assigned risks and overall performance of prenatal screening are to be maintained. METHODS: Agreement between the Beckman Coulter Access and the Bayer Immuno 1 assays for AFP and hCG and the Amersham Amerlex-M RIA for uE3 was assessed in 558 fresh sera. Precision was measured over 6 weeks. Median concentrations were calculated by regression of 568 Caucasian singleton pregnancy samples against gestational age in days. Frozen mid-trimester sera from 44 confirmed Down syndrome singleton pregnancies (cases) were selected without conscious bias for reanalysis, and each case was matched with five control specimens from unaffected pregnancies. Serum markers were expressed as the multiple of the median (MoM) concentration derived from the control samples, corrected for maternal weight and converted to their log-equivalent values. Normality was assessed using probability plots and the Shapiro-Wilk W-test. Gaussian distribution parameters were compared with established values, and Down syndrome risk calculations were assessed with a commonly used risk algorithm. RESULTS: The Access AFP and hCG assays had consistent proportional agreement with the established assays, whereas agreement between the uE3 methods was less consistent. Analytical imprecision was 3-6% at mid-trimester concentrations. Normal distributions were obtained for the log MoM values of all three markers in both the Down syndrome and unaffected populations, and their gaussian distribution parameters compared well with established values. The performance of the Access assays in an established trivariate risk algorithm for Down syndrome was equal to the performance exhibited by traditional methods. CONCLUSION: The Beckman Coulter Access analyzer provides valid mid-trimester serum AFP, uE3, and hCG results and risk assessments when applied in a prenatal Down syndrome screening service.

Biomarkers↗