September 2007 Clinical Laboratory News: Diagnostic Profiles

September 2007: Volume 33, Number 9

cTnT and BNP Useful in Serial Monitoring of CHF

Elevations of cardiac troponin (cTnT) and B-type natriuretic peptide (BNP) above normal levels detected at any time during clinical follow-up in ambulatory patients with chronic heart failure (CHF) are highly associated with increased risk for short-term cardiac events including death. Combined elevations of cTnT and BNP substantially add to that risk, so monitoring changes through serial measurements would improve risk assessment, according to a recent paper (Circulation 2007; 116: 249–257). To determine the best way to use these biomarkers, researchers from the Mayo Clinic in Rochester, Minn., evaluated serial measurements of cTnT and BNP done every 3 months over a 2-year period in clinically stable outpatients with New York Heart Association class III-IV heart failure. Primary end points were death, cardiac transplantation, or hospitalization. At enrollment, cTnT was <0.01 ng/mL in 45.8% of patients, 0.01 to 0.03 ng/mL in 26.3% of patients, and >.03 ng/mL in 27.9% of patients. An increase in cTnT above normal, or < 0.01 ng/mL, carried a 3.4-fold increased risk. Further increases ≥20% from an elevated level worsened the overall risk (HR 5.09). BNP level was elevated above the 95th percentile for age and gender in 64.2% of patients. An elevation of BNP from normal at any time during the study was associated with a poor outcome, but once elevated, further changes in BNP—either increases or decreases—remained associated with the same risk (HR 5.09). Combined elevations of cTnT >0.03 ng/mL and BNP defined the highest risk group (HR 8.58). The authors pointed out that elevated cTnT, particularly >0.03 ng/mL, conferred an 8-fold increased risk. They also noted that their study is unique because it evaluated clinically stable patients over 2 years, while other research evaluating changes over time has typically looked at changes over a 6-month period, starting when subjects were acutely decompensated in the hospital.

MPO and NT-proBNP Can Stratify Risk in STEMI Patients

Myeloperoxidase (MPO) and N-terminal pro-B type natriuretic peptide (NT-proBNP) may be useful tools for risk stratification in all acute coronary syndromes (ACS), even ST segment elevation myocardial infarctions (STEMI), according to recent research (Heart 2007; 93: 826–831). To assess the use of these markers for prognosis of patients with acute myocardial infarction (AMI), researchers from University of Leicester, U.K., assessed 384 post-STEMI patients for the combined end point of death or readmission with non-fatal MI. Researchers noted that among the 40 deaths and 37 readmissions for MI, those patients who died or had a subsequent MI had a median MPO value of 50.6 ng/mL (15.3–124.1 ng/mL), which was higher than the median of 33.5 ng/mL (6.6–400.2 ng/mL) for survivors without recurrent MI. Using a Cox proportional hazards model, log median MPO (HR 6.91, 95% CI, 1.79–26.73) and log median NT-proBNP (HR 4.21, 95% CI, 1.53–11.58) independently predicted death or non-fatal MI. MPO had predictive power in both below and above median NT-BNP levels (log ranks 5.60 and 5.12, respectively). The receiver operating curve for median NT-proBNP yielded an area under the curve of 0.72 (95% CI, 0.65–0.79). For median MPO, the area under the curve was 0.62 (95% CI, 0.55–0.69). The logistic model combined the two markers yielded and an area under the curve of 0.76 (95% CI, 0.69–0.82). “The results of this study confirm the independent prognostic value of MPO and NT-BNP in determining death or non-fatal MI in patients who have an acute STEMI. The predictive value of MPO provides risk prediction independent of NT-BNP and other known clinical predictors of death or non-fatal MI,” the authors wrote. They noted that their study is the first to report use of MPO in combination with NT-proBNP in patients with STEMI.

LpPLA2 Predicts Cardiac Mortality

Lipoprotein-associated phospholipase A2 (LpPLA2) activity is an independent risk factor for 5-year mortality in patients with low and medium CRP concentrations, adding useful information beyond that provided by established risk stratification strategies, according to recent research (Clinical Chemistry 2007; 53: 1440–1447). To examine the prognostic value of LpPLA2 in relation to CRP and other risk factors, German researchers participating in the Ludwigshafen Risk and Cardiovascular Health Study measured LpPLA2 activity in 3,232 patients scheduled for angiography, 2,513 of whom had angioraphically confirmed coronary artery disease (CAD). During a median observation period totaling 5.5 years, 501 patients died. Researchers divided patients into tertile ranges of LpPLA2 actvity of ≤419 U/L (first), 420–509 U/L (second), and ≥510 U/L (third). In those patients with LpPLA2 activity in the second and third tertiles, unadjusted hazard ratios were 1.7 and 1.9, respectively (95% CI 1.3–2.4 and 1.4–2.5, respectively), compared with patients with LpPLA2 activity in the first tertile. After accounting for established risk factors and data on LpPLA2 combined with angiographic CAD status, CRP, and N-terminal pro-B-type natriuretic peptide, LpPLA2 activity in the third tertile predicted cardiac 5-year mortality with a hazard ratio of 2.0 (95% CI, 1.4–3.1). In patients with CRP concentrations <10 mg/L, additional information of LpPLA2 increased the adjusted HR for cardiac death by twofold. The researchers, who noted that their study is the first cohort study to address long-term cardiac mortality associated with LpPLA2 , emphasized that it cannot become a clinically relevant indicator until methods assessing its mass and activity are standardized. 

PT Problems in Microbiology Labs Revealed

Since implementation of CLIA, lab performance in physicians’ offices and clinics has generally improved, but problems persist in microbiology labs, according to a recent study (Lab Medicine 2007; 38: 237–239). To determine whether proficiency testing (PT) improves lab performance, researchers from the American Proficiency Institute in Traverse City, Mich., and Missouri State University-West Plains examined data on PT failure rates during 1994-2007 for selected analytes representing the major clinical laboratory practice areas of chemistry, hematology, and microbiology. Researchers examined data from PT results submitted in 1994, the year PT program participation was first mandated under CLIA. They subsequently re-examined failure rates in 1995, 2001, and 2004 for chemistry and hematology analytes and in 1995 to 1999, 2001, and 2004 for microbiology analytes. The study team analyzed PT results using API’s proprietary software, stratified them into appropriate peer groups, and then evaluated the data according to CMS criteria. Analytes with a failure rate of ≥5% were considered problematic. Failure rates for chemistry and hematology analytes declined significantly during the 10-year period. Failure rates for microbiology analytes also declined, but remained above 5% in 2005 for positive genital/GC cultures, positive urine cultures, and Gram stains. The failure rates for the positive cultures greatly exceeded the failure rates for the negative cultures, indicating that labs may miss many positive cultures and Gram stains from patient samples, according to the researchers. “We believe microbiology testing urgently needs improvement, and we urge medical directors, laboratory administrators, and microbiology supervisors to focus attention in this area,” the researchers wrote.

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