March 2007 Clinical Laboratory News: Diagnostic Profiles

March 2007: Volume 33, Number 3

Study Shows NT-proBNP Is Independent Marker for CV Events, Death
Levels of NT-proBNP could help determine risk of cardiac events for patients with CHD, according to a study published in Journal of the American Medical Association (2007;297:169–176). Elevated NT-proBNP levels predicted cardiovascular morbidity and mortality, independent of other prognostic markers, and identified at-risk patients even in the absence of systolic or diastolic dysfunction data determined by echocardiography. The team of California researchers analyzed data from a prospective cohort study of 987 California Heart and Soul Study patients with stable coronary disease. Mean follow-up was 3.7 years (range: 0.1–5.3). Of the cohort, 26.2%, or 256 participants, had a cardiovascular event or died. The researchers found that each increasing quartile of NT-proBNP level was associated with a greater risk of cardiovascular events or death, with patients in the highest quartile having a nearly 8-fold increase in rate of cardiovascular disease or mortality compared to those in the lower quartile, with annual event rates of 19.6% and 2.6%, respectively (unadjusted HR for quartile 4 versus quartile 1, 7.8, 95% CI, 5.0–12.1). Each incremental increase in log NT-proBNP level (1.3 pg/mL) was associated with a 2.3-fold increased rate of adverse cardiovascular outcomes (unadjusted HR, 2.3, 95% CI, 2.0–2.6), even after adjustment for all of the other prognostic measures (unadjusted HR, 1.7, 95% CI, 1.3–2.2), including clinical factors, echocardiograph parameters, ischemia, serum biomarkers, and functional limitations.
Androgen Levels Linked to Men’s Risk for Diabetes
Low androgen levels may be a diabetes risk factor for men, according to research published in Diabetes Care (2007;30:234–238). Low free and bioavailable testosterone concentrations in the normal range were associated with diabetes, independent of adiposity, investigators wrote. They calculated bioavailable and free testosterone levels from serum total cholesterol, sex hormone-binding globulin, and albumin concentrations in 1,413 adult men age 20 or older who participated in the first phase of the NHANES III Study. In multivariate models adjusted for age, race/ethnicity, and adiposity, men in the first and lowest tertile of free testosterone level were four times more likely to have prevalent diabetes than men in the third tertile (OR 4.12, 95% CI, 1.25–13.55). Men in the first tertile of bioavailable testosterone level were also about four times more likely to have prevalent diabetes than men in the third tertile (OR 3.93, 95% CI, 1.39–11.13). Associations persisted even after researchers excluded men with clinically abnormal testosterone concentrations, defined as total testosterone less than 3.25 ng/mL or free testosterone less than 0.07 ng/mL. Researchers observed no clear association between total testosterone level and diabetes after multivariate adjustment. 
Rapid Flu Tests Spur Drop in Antibiotic Use
Rapid influenza testing leads to reduced use of antibiotics in hospitalized adults, but better tools are needed to rule out concomitant bacterial infection, according to recent research published in Archives of Internal Medicine (2007;167:354–360). Researchers at Rochester General Hospital and the University of Rochester School of Medicine and Dentistry in N.Y. reviewed the medical records of 166 patients with documented influenza hospitalized at their facility during four winters (1999 to 2003), when hospital policy mandated influenza testing by antigen or culture for all patients with acute cardiopulmonary diseases. Eighty-six patients tested positive for influenza, and 80 either tested negative or did not receive the test. A smaller proportion of patients with positive test results got antibiotics, 86%, versus 99% of patients with negative results, but a larger proportion of patients with positive results discontinued antibiotics, researchers found. Fourteen percent of the positive group did so, versus 2% of negative patients. Authors noted no significant differences in antibiotic days, length of hospital stay, or antibiotic complications. After controlling for other variables, including underlying heart disease or other conditions, researchers determined that a positive rapid test result was independently associated with withholding or discontinuing antibiotic therapy. Antiviral therapy was greater among positive patients, with 73% receiving treatment, versus 8% of those who tested negative for flu. Of 44 positive patients considered at low risk for bacterial infection, 27 remained on antibiotics. These patients tended to have pulmonary disease and more abnormal lung examination results, compared with counterparts whose antibiotics were withheld or discontinued.
New Biomarker Indicates Risk for Non-ST Elevation ACS Patients 

A new biomarker, growth-differentiation factor-15 (GDF-15), is useful for predicting mortality risk in patients with non-ST-elevation ACS. According to the researchers, the newly published study represents the first description of GDF-15, a member of the transforming growth factor-ß cytokine superfamily that is induced in the heart after ischemia-and-reperfusion injury, as a biomarker of cardiovascular disease and increased risk of death in this patient population (Circulation 2007;115:962–971). The international team determined GDF-15 levels by immunoradiometric assay from blood samples collected from 2,081 participants in the GUSTO-IV in NSTE-ACS trial who were admitted to hospitals with acute chest pain and either ST-segment depression or troponin elevation. Researchers also measured GDF levels from a matching cohort of 329 apparently healthy individuals. About two-thirds of hospitalized patients presented with GDF-15 levels higher than 1,200 ng/L, which the researchers identified as the upper limit of the normal range in healthy controls. One-third of the hospitalized patients had levels higher than 1,800 ng/L. Increasing tertiles of GDF-15 were associated with greater risk of death after one year (1.5%, 5.0% and 14.1%). After multiple Cox regression analysis, only the levels of GDF-15 and NT-proBNP, plus age and history of myocardial infarction, contributed independently to 1-year mortality risk. Receiver operating characteristic curve analyses gave more evidence that GDF-15 is a strong marker of 1-year mortality risk, with an AUC of 0.757. At the best cutoff value for identification of a high 1-year mortality risk, 1808 ng/L, GDF-15 added significant prognostic information in patient subgroups defined by age, gender, time from symptom onset to admission, cardiovascular risk factors, and previous cardiovascular disease. GDF -15 also added prognostic information to the established risk markers ST-segment depression, troponin T, NT-proBNP, CRP, and creatinine clearance.

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