October 2007 Clinical Laboratory News: Diagnostic Profiles

October 2007: Volume 33, Number 10

Knowledge of BNP Levels Favorably Affects Long-Term Morbidity, Costs

Rapid B-type natriuretic peptide (BNP) testing in acute dyspnea patients has no effect on long-term mortality, but improves 12-month morbidity in terms of days spent in the hospital and treatment cost, researchers concluded in a recent paper published in Clinical Chemistry (2007; 53: 1415–1422). Because BNP tests have recently been criticized for uncertain diagnostic value and for affecting final discharge diagnosis, Swiss researchers did a follow-up analysis of the BASEL (B-Type Natriuretic Peptide for Acute Shortness of Breath Evaluation) trial, a 6-month randomized study of 452 patients who presented to the emergency department of the University Hospital in Basel, Switzerland with acute dyspnea. In the present study, the team randomly assigned 225 patients to a diagnostic strategy using BNP concentration and 227 to a conventional diagnostic strategy and then assessed mortality at about 24 months and morbidity and economic data at 12 months. The researchers found that BNP testing induced several important changes in initial patient management, including reductions in initial hospital admission rates, use of intensive care, and initial time to discharge. At 720 days, a total 172 patients had died. The cumulative all-cause 720-day mortality rate was 72% for the BNP group and 36% for the control group. Morbidity, defined as days spent in the hospital within 360 days, was significantly lower in the BNP. That group spent a median of 12 days in the hospital, compared with 16 for the control group. The total treatment cost at 360 days was $10,144 for the BNP group, versus $12,748 for controls. Researchers noted that one of their study’s strengths was that its population is very similar to patients with acute dyspnea seen in clinical practice. Patients’ mean age was 71, and they commonly had coexisting conditions. “The rapid and accurate differentiation of heart failure and other causes of acute dyspnea and corresponding long-term management in such patients is often very difficult,” the researchers wrote.

PEACE Trial: Natriuretic Peptides Have Prognostic Value for Some Patients

In low-risk patients, BNPs add strong and incremental prognostic information to traditional risk factors, according to a recent paper (Journal of the American College of Cardiology 2007; 50: 205–14) by an international team of researchers from the U.S., Norway, and Canada. The team assessed the association between BNP and NT-pro-BNP and incidence of specific cardiovascular events in subjects enrolled in the PEACE (Prevention of Events with Angiotensin-Converting Enzyme Initiation) trial. The team also looked at the incremental prognostic information obtained from BNP and NT-pro-BNP, compared it with traditional risk factors, and determined if the natriuretic peptides were useful in identifying patients who may benefit from angiotensin-converting enzyme (ACE) inhibitors. The researchers measured baseline plasma BNP and NT-proBNP levels in 3,761 patients with stable coronary artery disease and preserved left ventricular function. Using multivariate Cox regression, they assessed the association between natriuretic peptide concentrations and incidence of cardiovascular mortality, fatal or nonfatal myocardial infarction, and stroke. During a median of 4.8 years of follow-up, there were 127 cardiovascular deaths, 104 fatal or first nonfatal congestive heart failure events, 241 fatal or first nonfatal acute myocardial infarctions, and 86 first or nonfatal stroke events. In multivariate analysis, the BNP and NT-proBNP levels were strongly related to the incidence of cardiovascular mortality, heart failure, and stroke but not to myocardial infarction. C-statistic calculations revealed that BNP and NT-proBNP significantly improved the predictive accuracy of the best available model for incident heart failure and the model for cardiovascular death. The magnitude of ACE inhibitors’ effect on likelihood of experiencing cardiovascular end points was similar, regardless of either BNP or NT-proBNP concentration. “Current data support measurement of BNPs in low-risk populations for prognostic assessment but do not provide a mandate for the use of these peptides for tailoring therapy in individual patients,” the authors concluded.

POC and Central Lab Lactate Values Correlate

Lactate values from point-of-care (POC) and central laboratory analyzers show good correlation with central laboratory analyzers, according to recent research at the Mayo Clinic in Rochester, Minn. (American Journal of Clinical Pathology 2007; 128: 168–171). Because whole-blood lactate testing used in POC is increasingly common and few studies have correlated it with central plasma methods used in central labs, the researchers compared two plasma-based lactate assays with three whole-blood applications. The plasma-based assays were Lactate Gen.2 performed on a Roche Cobas Integra 400 analyzer (Roche Diagnostics, Indianapolis, Ind.) and the Vitros LAC slide assay performed on a Vitros 250 analyzer (Ortho Clinical Diagnostics, Raritan, N.J.). Whole-blood applications included the i-STAT (i-STAT, East Windsor, N.J), the Radiometer ABL 725 blood gas analyzer (Radiometer Medical A/S, Bronshoj, Denmark), and the newly developed, experimental Lactate Plus (Nova Biomedical, Waltham, Mass.). Method correlation determined by least squares regression, using the Vitros as the reference standard, yielded a slope of 0.95 for the Integra 400 Plus, 0.87 for the Radiometetr ABL and i-STAT, and 1.06 for the Nova, with r2 of 0.99 or more in each case, indicating strong correlation between the methods. For the Radiometer and i-STAT methods, two of 31 samples that would have been classified as high risk by central laboratory plasma analysis were determined to be intermediate risk by POC, whole- blood measurement. “This could be particularly problematic if the first measurement were performed on a point-of-care platform and a follow-up measurement were performed in the central laboratory,” researchers wrote. “Institutions that use the i-STAT or Radiometer with a central laboratory method should inform clinicians that caution must be used when comparing high lactate values between point-of-care and central laboratory methods.”

NHANES: Bone Mineral Density in Whites May Be Affected by Lead Exposure

A significant inverse association between childhood lead exposure and bone mineral density (BMD) in adults has been identified in whites (Environmental Health Perspectives 2007; 115: 1018–1022). Researchers from Rochester Medical Center in New York analyzed data on 8,654 subjects age 50 or older who participated in the Third National Health and Nutrition Examination Survey (NHANES). Defining lead exposure by a concurrent venous blood lead level, the researchers analyzed data from non-Hispanic whites and African Americans by conducting bivariate analysis between hip bone density and covariates known to be associated with bone density. These covariates included age, body mass index, calcium intake, consumption of tobacco and alcohol, physical activity, and socioeconomic status. The significant covariates were analyzed to determine the association between BMD and blood level level terciles. Although researchers found a negative trend between blood level tercile and BMD among African Americans, differences were not significant. There was no association between blood lead level tercile and clinical outcomes. Given the large number of lead-exposed adults, future studies should investigate whether a causative association exists between lead exposure and osteoporosis, the researchers suggested.

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