American Association for Clinical Chemistry
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March 2011 Clinical Laboratory News: Diagnostic Profiles

Diagnostic Profiles

Baseline CRP Levels Not Associated with Statin Efficacy

British researchers have found that reducing low density lipoprotein cholesterol (LDL-C) with the statin drug simvastatin lowers the risk of major vascular events to about the same extent, regardless of baseline C-reactive protein (CRP) concentrations (Lancet DOI:10.1016/50140-6736(10)62174–5). The study was designed to test the hypothesis that the effects of statin therapy differ according to baseline CRP and LDL-C levels.

The findings are from the Heart Protection Study, a randomized trial of statin therapy that involved 20,536 subjects at high risk of vascular events who were recruited from 69 U.K. hospitals and followed for a mean of 5 years. Patients were assigned to receive 40 mg simvastatin daily or placebo.

The researchers were interested in this issue because CRP levels have been associated with risk of coronary heart disease, whereas any associations between CRP concentrations and ischemic vascular disease might be already reflected in conventional risk factors like smoking, diabetes, and physical inactivity, to which CRP levels also have been linked. In addition, some studies have suggested that there would be greater benefits from statin therapy in patients with inflammation than in those without.

The researchers assigned patients to six groups according to baseline CRP levels. Overall, in comparison to those in the placebo arm, patients who received simvastatin experienced a 24% proportional reduction in the incidence of first major vascular event after randomization. The investigators found no evidence that this endpoint varied proportionally with baseline CRP concentrations. Even in patients with baseline CRP levels <1.25 mg/L there was a 29% significant reduction in major vascular events.

Interferon-γ Release Assay Tops Skin Test in Identifying Latent TB Infection

New research indicates that using an interferon-γ release assay is more reliable than tuberculin skin testing (TST) for identifying individuals who will progress to active tuberculosis (TB), especially in children (Am J Respir Crit Care Med 2011;183:88–95). The study built on the investigators’ initial analysis comparing the QuantiFERON-TB Gold in-tube assay (QFT) with TST in close contacts of patients with TB.

The original study, which involved 601 close contacts of TB patients, found that 15% of those who were QFT-positive, in comparison to 2.3% of those who were TST-positive, progressed to active TB within 2 years. However, that study had only 41 QFT-positive subjects, just six of whom progressed to active TB. Consequently, the researchers monitored for 4 years a much larger cohort to improve the study’s statistical power.

In addition to the original 601 contacts, this phase of the study included a further 816 contacts, associated with 101 different culture-determined TB source individuals. Results for both QFT and TST were available for 954 of the contacts who had remained in the study area for the duration of the investigation.

The researchers found that QFT, but not TST results were associated with exposure time. In total, 10.8% of contacts had positive QFT results in comparison to 63% who were TST positive at >5 mm, and 25.4% at >10 mm. Overall, 19 contacts went on to develop TB, representing a 12.9% progression rate. All had been QFT-positive, in comparison to 89.5% for TST at >5mm and 52.6% at >10mm. Progression rates for TST-positive contacts at >5 mm and >10 mm were 3.1% and 4.8%, respectively. Among children age 15 or younger, 21.7% were QFT-positive, versus 37.8% by TST with a 5 mm cutoff and 28.9% at a 10 mm cutoff.

The authors conclude that testing with QFT rather than TST in at-risk populations with a high pre-test probability of TB infection resulted in a higher positive predictive value for determining latent TB infection status and identifying those most likely to progress to TB in the near future.

Implementing New Gestational Diabetes Recommendations Entails Major Change

Researchers at Quest Diagnostics have documented that nearly 90% of women currently do not undergo the type of testing for gestational diabetes recommended in new diagnostic criteria for the disorder (Obstet Gynecol 2011;117:61–8). These findings suggest that a significant change in clinical practice will be necessary to adopt these criteria.

The investigators sought to estimate the screening rate and prevalence for both gestational diabetes and postpartum diabetes in a large, national sample of pregnant women. They also wanted to estimate how implementation of recommendations proposed by the International Association of Diabetes and Pregnancy Study Group (IADPSG) might impact gestational diabetes prevalence and testing practices. The IADPSG recommendations call for using a 75-g oral glucose tolerance test (OGTT), whereas other guidelines already in widespread use involve a 100-g OGTT.

The researchers extracted testing data for 924,873 pregnant and postpartum women from the Quest Diagnostics informatics data warehouse, which includes information on all individuals for whom Quest performs diagnostic testing. They found that 68% of pregnant women between ages 25 and 40 were screened for gestational diabetes. Of the entire adult pregnant population who received gestational diabetes testing, which includes both women ages 25–40 and 18–24, 4.9% had positive test results under current diagnostic criteria, but 5.3% would have had positive results with the IADPSG recommendations. However, nearly 90% of the confirmatory gestational diabetes tests recorded in the data warehouse were by 100-g OGTT. “This means that a significant adjustment from medical providers is needed for the IADPSG recommendations to be fully adopted,” according to the researchers.

Findings Support Offering HCV Surveillance to HIV-Infected Individuals

An analysis of incident hepatitis C virus (HCV) infection among HIV-infected men participating in HIV therapeutic trials in the U.S. found that 0.51 cases per 100 person-years seroconverted after an initial negative HCV antibody test (Clin Infect Dis DOI: 10.1093/ccid/ciq201). The results suggest that HIV-infected individuals at-risk for HCV should have access to HCV surveillance. This has important implications for public health because until recently, researchers thought HCV preceded HIV infection in most cases. Consequently, U.S. Public Health Service HIV guidelines endorse HCV antibody testing only at the time of HIV diagnosis, and individuals found to be HCV-seronegative are rarely screened later, according to the authors.

The researchers accessed data from the AIDS Clinical Trial Group (ACTG) Longitudinal Linked Randomized Trials (ALLRT) study. ACTG is the largest HIV clinical trial organization in the world, and ALLRT is a prospective cohort study of HIV-1-seropositive individuals who have been randomized into selected ACTG-conducted clinical trials.

Out of 1,830 men with an initial negative and one subsequent HCV antibody test, 36 subsequently seroconverted. Among those who seroconverted, 75% reported no injection drug use. Although these individuals may have under-reported their actual injection drug use, the authors contend that in light of accumulating evidence, sexual transmission is the likely cause of incident HCV infection in the study population. HCV antibody development was not related to immune status but was associated with inadequate HIV suppression.

The investigators call for further study to understand specific behaviors associated with HCV transmission and predictors of HCV antibody seroconversion.