CLN Article

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Optimal Screening Threshold for Gestational Diabetes Mellitus Proposed in Twin Pregnancies

The optimal screening threshold for gestational diabetes mellitus (GDM) in twin pregnancies using a 1-hour, 50-gram glucose challenge test (GCT) is ≥135 mg/dL, according to findings by researchers at the Icahn School of Medicine at Mount Sinai and at New York University School of Medicine, both in New York City (Amer J Obstet Gynec 2014; doi.org/10.1016/j.ajog.2014.08.030). The investigators conducted this study because while GDM screening cutoffs have been recommended for singleton pregnancies, optimal thresholds for twin pregnancies have not been evaluated specifically.

Organizations including the American Diabetes Association have endorsed a one-step GDM screening process involving a 2-hour, 75-gram oral glucose tolerance test (OGTT). However, others, such as the American Congress of Obstetricians and Gynecologists, also support GDM screening using a non-fasting 1-hour GCT followed by a diagnostic fasting 3-hour, 100-gram OGTT for women who exceed a GCT cutoff, usually 130–140 mg/dL.

The GCT cutoffs were based on data from singleton pregnancies, yet “in twin pregnancies, normal physiologic changes are amplified, which may change the characteristics of the GCT and therefore affect the screen-positive rates leading to excessive testing and increased cost with no real improvement in the accuracy of diagnosis,” according to the authors. A dearth of data about an ideal GCT cutoff in twin pregnancy prompted the authors’ study.

The study involved 475 patients with twin pregnancies between 24–28 weeks’ gestation, who underwent a 1-hour, 50-gram GCT. Those with a GCT ≥130 mg/dL subsequently took a 3-hour, 100-g OGTT. Patients who had at least two abnormal OGTT values out of four were diagnosed with GDM.

The authors evaluated the testing characteristics of GCT using three cutoffs, ≥130 mg/dL, ≥135 mg/dL, and ≥140 mg/dL. In evaluating the sensitivity and specificity associated with these three cutoffs, they determined that ≥135 mg/dL—associated with 100% sensitivity, 76.4% specificity, 22.8% positive-predictive value, and 100% negative-predictive value—was optimal. Using a ≥130 mg/dL cutoff increased the test-positive rate to 34.7, whereas a ≥140 mg/dL cutoff decreased the test-positive rate to 23.4% but also failed to identify 6.5% of GDM patients.

In comparison to a cutoff of ≥130 mg/dL, ≥135 mg/dL “could potentially decrease cost and anxiety, without decreasing the sensitivity of the test,” wrote the investigators.

The authors called for more research to better understand GDM screening in twin pregnancies, to confirm their findings in other populations, and to establish the optimal GDM screening and treatment paradigm.

Troponin, CK-MB Testing Common in Emergency Patients Even Without Acute Coronary Syndrome Symptoms

An analysis by UT Southwestern Medical Center researchers in Dallas found that cardiac biomarker testing in emergency patients is common even among those without symptoms suggestive of acute coronary syndrome (ACS) (JAMA Intern Med 2014; doi:10.1001/jamainternmed.2014. 5830). The findings suggest more attention is needed to develop strategies for appropriate use of cardiac biomarkers, according to the authors.

The investigators conducted the study because chest pain is one of the most common complaints among emergency patients, yet troponin (cTn) and creatine kinase-MB (CK-MB) testing are not recommended for all such patients. When used inappropriately in patients with a low pre-test possibility of ACS, cTn testing could lead to patient anxiety, additional inappropriate testing, and unnecessary treatment, they contended.

The researchers accessed data from the National Hospital Ambulatory Medical Care Survey; the primary outcome among 44,448 emergency department (ED) visits was whether cTn or CK-MB tests were ordered. Overall, these tests were ordered in 16.9% of visits, including 8.2% of visits in which patients did not have ACS-related symptoms. Among patients subsequently hospitalized, CK-MB or cTn tests were performed in 47% of related ED visits, including 35.4% in which the patient did not have ACS-related symptoms.

Cardiac biomarker tests also were performed frequently during ED visits with a high volume of other tests or services, independent of the patient’s clinical presentation.

NT-proBNP Improves CVD Risk Prediction in Women

N-terminal pro-B-type natriuretic peptide (NT-proBNP) modestly improves cardiovascular disease (CVD) risk prediction in women, according to a Women’s Health Initiative (WHI) observational study (J Am Coll Cardio 2014;64: 1789–97). The authors conducted the study to better understand the relationship between natriuretic peptides (NPs) and CVD risk in women. NP tests have gained “widespread acceptance” as diagnostic and CVD risk-stratification tools, according to the authors. In that context, women typically have higher NT-proBNP levels than men, yet lower absolute risk for CVD than men with similar risk factors. While studies have shown a consistent relationship between NP levels and CVD risk, many included only men, reported the number of CVD events in women but not the association between NP levels and CVD risk, or had too few events in women to analyze.

The study included 1,821 incident cases of CVD and a randomly selected reference cohort of 1,992 women without CVD at baseline.

The researchers divided cases into quartiles based on NT-proBNP levels, and estimated their relative risk of CVD per quartile. Women in the highest quartile with levels ≥140.8 ng/L had the highest risk of CVD, with a hazard ratio of 1.53 versus those in the reference quartile with levels <50.9 ng/L.

The investigators also added NT-proBNP levels as co-variables in traditional risk factor and Reynolds Risk Score (RRS) algorithms. In the case of traditional risk factors, NT-proBNP improved the c-statistic to 0.774 from 0.765, the categorical net reclassification, and the integrated discrimination. The authors found similar results when they added NT-proBNP concentrations to RRS algorithms.

Though statistically significant, the improvements in risk prediction were “relatively modest,” according to the authors. They suggested that while NPs might be useful CVD risk prediction markers in women “for whom a decision to start statin therapy otherwise is unclear,” they cautioned that “the therapeutic response to an elevated NP level in an otherwise healthy individual is not clear.”

Sickle Cell Trait Contributes to CKD Risk in African Americans

Sickle cell trait (SCT) is associated with increased risk of chronic kidney disease (CKD), decline in estimated glomerular filtration rate (eGFR), and albuminuria, compared with non-carriers (JAMA 2014; doi:10.1001/jama.2014.15063). These findings suggest that SCT also could be associated with the higher risk of kidney disease in African Americans, according to the authors.

The authors conducted the study to further understanding of the relationship between SCT and CKD. Although renal problems like impaired urinary concentration, asymptomatic hematuria, and papillary necrosis are common among patients with SCT, how this relates to long-term functional impairment of the kidney has not been determined clearly, wrote the authors.

To investigate the SCT-CKD relationship, the investigators drew subjects from five large, prospective studies for a total of 15,975 African Americans, 1,248 of whom had SCT. Each study had slightly different kidney function assessment parameters and follow-up periods, but in general they measured serum creatinine at baseline or early in the study and at defined intervals. Some also measured cystatin C and urinary albumin:creatinine ratio. The researchers calculated effect sizes for each cohort and then meta-analyzed the data using a random-effects model.

In addition to genotyping for the sickle cell mutation, some participants also underwent genotyping for APOL1, as variants of this gene have been associated with CKD in African Americans.

More SCT carriers than non-carriers­ had CKD (19.2% versus 13.5%), experienced incident CKD (20.7% versus 13.7%), experienced declining eGFR (22.6% versus 19%), or had albuminuria (31.8% versus 19.6%) during the study period. SCT carriers had increased risk for all these conditions compared with noncarriers. All these associations were independent of APOL1 risk variant.

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