In This Issue...

PlGF Sensitive Predictor of Preeclampsia
A multicenter prospective study by British researchers found that in women presenting before 35 weeks’ gestation with suspected preeclampsia, low plasma concentration of placental growth factor (PlGF) has high sensitivity and negative predictive value for preeclampsia within 14 days (Circulation 2013;128:2121–31). The authors also found low PlGF to be a better predictor of preeclampsia than other currently used tests, including blood pressure, uric acid, alanine transaminase, and proteinuria.

The findings suggest that adding PlGF measurement to the diagnostic workup of suspected preeclampsia could improve risk stratification, lead to earlier diagnosis of the condition, and improve management and outcomes for preeclamptic patients.

The study involved 625 women in seven maternity centers in the United Kingdom and Ireland. Eligible patients—all between 20 and 40 weeks’ gestation and at least 16 years of age—either presented or were referred with signs or symptoms of preeclampsia. The study’s primary analysis was diagnostic accuracy of low plasma PlGF to predict the need to deliver patients because of preeclampsia within 14 days of testing who were suspected of having preeclampsia before 35 weeks’ gestation. The secondary analysis included women presenting later in their pregnancy and a lower PlGF threshold, <12 pg/mL. The researchers defined low PlGF as <5th centile for gestational age. All seven centers used the Alere Triage PlGF assay.

Overall, 55% of patients developed confirmed preeclampsia. In 287 who enrolled before 35 weeks’ gestation, PlGF <5th centile had 0.96 sensitivity and a negative-predictive value of 0.98 for preeclampsia within 14 days. Specificity was 0.55. The area under the receiver operating characteristic curve for low PlGF in predicting preeclampsia within 14 days, 0.87, was greater than all other measurements in the study, singly or in combination.

Rapid Influenza Testing in Emergency Settings Leads to Fewer Tests, Antibiotics
Among emergency patients being evaluated for influenza, influenza diagnoses associated with rapid influenza diagnostic tests (RIDT) also were associated with fewer ancillary tests and antibiotic prescriptions and greater use of antivirals (J Pediatric Infect Dis Soc 2013; doi:10.1093/jpids/pit071). The findings suggest that RIDT results influence physician behavior, thereby impacting patient care and resource utilization.

The authors conducted the study because influenza-like illness is common among emergency department (ED) patients in winter, yet influenza shares signs and symptoms with other respiratory illnesses. Uncertainty about the diagnosis of influenza can lead to inappropriate use of antibiotics, under-utilization of antivirals, as well as unnecessary ancillary testing. While studies have linked use of RIDT with reduced antibiotic prescriptions, and more use of antivirals, the sensitivity of RIDT varies from poor to moderate across settings, populations, and tests.

The study involved a retrospective analysis using data from the National Hospital Ambulatory Medical Care Survey, which involves a nationally representative sample of visits to U.S. EDs. Of 51,844 sampled visits from three influenza seasons, RIDT was performed in 995. These numbers equated to an estimated 178.1 million ED visits, of which an estimated 4.2 million RIDT were performed. Overall, 42% of influenza diagnoses were associated with RIDT.

In comparison to those without RIDT, diagnosed influenza cases associated with RIDT had fewer ancillary tests (45% versus 53%), fewer antibiotic prescriptions (11% versus 23%), and higher antiviral use (56% versus 19%).

NT-proBNP, hs-cTn T Improve Cardiovascular Disease Risk Prediction in Diabetics
N-terminal pro-B-type natriuretic peptide (NT-proBNP) and high sensitivity-cardiac troponin T (hs-cTn T) in combination greatly improve risk prediction of cardiovascular events or death in type 2 diabetics (Diabetes Care 2014;37:295–303). The findings have implications for both clinical care and research, according to the authors.

The investigators conducted the study because of the high incidence of cardiovascular disease (CVD) among diabetics, and the need to identify those at highest risk. Existing risk prediction methods are imperfect and traditional CVD risk factors are relatively poor predictors in diabetics. Prior studies have demonstrated that BNP and NT-proBNP enhance risk prediction in community populations and in patients with stable coronary heart disease, but limited evidence about their predictive role in diabetics is available.

The study was a nested case-cohort of the Action in Diabetes and Vascular Disease (ADVANCE) study, which involved patients who were at least 55 years old, had been diagnosed with type 2 diabetes after age 30, and either had a history of CVD or one or more CVD risk factors. Out of 11,140 ADVANCE patients, 3,862 were included in the nested case-cohort. All had baseline measurements of NT-proBNP, hs-cTn T, and other biomarkers taken and were followed for a median of 5 years.

After adjusting for all established risk predictors, the researchers found that the hazard ratio for cardiovascular events for NT-proBNP was 1.95 per 1 standard deviation increase, while the hazard ratio for hs-cTn T was 1.50 per 1 standard deviation increase. Adding either NT-proBNP or hs-cTn T improved 5-year risk classification for cardiovascular events, and the combination of both provided optimal risk discrimination.

Genetic Variants Linked to Vitamin D-Binding Protein Differences in African-Americans
In comparison to whites, community dwelling African-Americans had low levels of both total 25-hydroxyvitamin D (25(OH)D) and vitamin D-binding protein, yet both races had similar concentrations of estimated bioavailable 25(OH)D (N Engl J Med 2013;369:1991–2000). Genetic variants in two common polymorphisms appeared independently to explain 79.4% of the variation in vitamin D-binding protein levels between whites and blacks after the researchers accounted for other factors.

Based on these findings the authors suggested that low total 25(OH)D levels do not always translate into vitamin D deficiency. They also questioned the practice of routinely advising individuals to take vitamin D supplements when they have low levels of both 25(OH)D and vitamin D-binding protein but lack signs and symptoms of vitamin D deficiency.

The study involved 2,085 participants, including 1,181 blacks and 904 whites, all of whom were 30–64 years of age and living in Baltimore, Md. at the time of recruitment. In addition to bone densitometry, patients underwent a physical examination, completed a dietary survey, and had blood specimens taken. Measurements for total 25(OH)D, vitamin D-binding protein, parathyroid hormone, calcium, and serum albumin were taken. In addition, researchers genotyped participants for two common single-nucleotide polymorphisms in the coding region of the vitamin D-binding protein gene, rs4588 and rs7041.

The researchers found that mean levels of 25(OH)D and vitamin D-binding protein were significantly lower in blacks than in whites; 15.6±0.2 ng/mL versus 25.8±0.4 ng/mL in the case of 25(OH)D, and 168±3 µg/mL versus 337±5 µg/mL for vitamin D-binding protein. Blacks were more likely than whites to have the T allele at rs7041, which was associated with decreased levels of vitamin D-binding protein in both blacks and whites. Blacks also had significantly higher bone mineral density than whites.

The researchers suggested that low levels of vitamin D-binding protein in blacks might provide protection against the manifestations of vitamin D deficiency despite their having low levels of total 25(OH)D.