American Association for Clinical Chemistry
Better health through laboratory medicine
February 2007 Clinical Laboratory News: Diagnostic Profiles

February 2007: Volume 33, Number 2

Obstetrics Group Recommends Universal Down's Syndrome Screening

Laboratorians may see a rise in demand for serum marker tests used to screen for fetal chromosomal abnormalities following publication of an obstetric practice bulletin that recommends genetic screening for all pregnant women. Published in Obstetrics & Gynecology (2007;109:217–227), the bulletin from the American College of Obstetricians and Gynecologists (ACOG) calls for screening with biochemical serum markers and nuchal translucency measurement for all pregnant women before 20 weeks of gestation, regardless of the mother's age. Previously, ACOG advised obstetricians to offer diagnostic testing for Down's syndrome with amniocentesis or chorionic villus sampling to women starting at age 35. Lab tests used to detect Down's syndrome in the first trimester include pregnancy-associated plasma protein and human chorionic gonadotropin. Good, consistent evidence shows that the newly suggested strategy results in a higher Down's syndrome detection rate than the second-trimester serum triple screen and is comparable to the quadruple screen, according to the ACOG panel that wrote the new guideline.

Study Identifies Link Between CRP Gene Variants and CHD
A recent paper in Circulation (2006;114: 2458–2465) confirms that differences in the genetic sequence for CRP are associated with variations observed in the serum level of the protein in the general population and newly identifies a specific genetic variant associated with CHD. After identifying nine CRP gene variants in 7,159 NHANES III participants of different racial and ethnic backgrounds, the authors linked specific haplotypes with serum levels of CRP. Researchers found two variants associated with increased serum CRP levels: one single-nucleotide polymorphism (SNP) in samples from individuals of non-Hispanic black heritage and the other in samples from those non-Hispanic black and Mexican American backgrounds. Two other SNPs were associated with decreased serum CRP in study subjects from non-Hispanic black and Mexican American backgrounds. The researchers found that three haplotypes inferred from seven SNPs (ATTGCGA, TTAGCGA, and AAAGAGA) were associated with increased levels of serum CRP in the non-Hispanic blacks, two haplotypes (ATTGCGA and AAAGCGA) associated with increased CRP levels in Mexican Americans, and one (AAAGCGA) associated with increased levels in non-Hispanic whites. Posthoc analysis that adjusted for covariates revealed for the first time a link between a specific SNP and prevalent CHD in the non-Hispanic white population sample. According to the authors, the study was limited by the lack of a CRP assay with high sensitivity and the large proportion of study participants—65%—who had CRP levels at or below the level of detection.
Troponin Predicts Longer ICU Stay and Greater Mortality
Clinicians should not dismiss elevated troponin (cTn) levels in intensive care unit (ICU) patients because they are associated with longer ICU stays and appear to independently predict mortality, according to a study recently published in Archives of Internal Medicine (2006;166:2446–2454). Canadian researchers reviewed 23 observational studies involving 4,492 critically ill patients. All studies reported frequency of an elevated cTn level or the association of elevated cTn with mortality or length of stay. Twenty studies found elevated cTn in a median of 43% of patients. Adjusted analysis including six studies comprising 1,706 patients showed elevated cTn associated with increased risk of death (odds ratio 2.5, 95% CI 1.9–3.4). In unadjusted analysis of eight studies comprising 1,019 patients, elevated cTn was associated with increased length of stay in the ICU of 3 days (95% CI 1.0–5.1) and increased length of stay in the hospital of 2.2 days (95% CI 0.6–4.9). Noting that elevated cTn is common in ICU patients and may be related to sepsis, hypotension, renal failure, and other conditions other than ACS, the authors called for more studies to clarify the underlying causes of elevated cTn in this population and to examine its clinical significance.
NT-proBNP Levels Predict Recurrent Cardiovascular Events 
N-terminal pro-B natriuretic peptide (NT-proBNP) measurement may aid in risk stratification of patients with manifest CHD, according to a recent article in Archives of Internal Medicine (2006;166:2455–2460). The researchers found that NT-proBNP is a strong, independent predictor of secondary CVD events and may be better than CRP and creatinine clearance (CrCl) at determining risk of subsequent cardiovascular events in patients with stable CHD. In the study, they compared NT-proBNP's prognostic value with that of CRP and CrCl in 1,051 patients with stable CHD soon after first clinical events or diagnoses and during a mean follow-up time of 48.7 months. Ninety-five patients had a second cardiovascular event. After controlling for age, sex, smoking, diabetes, initial CHD management, blood cholesterol levels, rehabilitation clinic treatment, and use of lipid-lowering drugs, patients in the top quartile of the NT-proBNP distribution had a baseline hazard ratio (HR) of 3.34 (95% CI, 1.74–6.45 ) for subsequent events than those in the bottom quartile. The corresponding HR for CRP was 1.76 (95% CI, 0.96–3.24). Patients with CrCl levels lower than 60 mL/min had a HR of 2.39 (95% CI, 1.06–5.40), compared with those with CrCl level 90 mL/min or higher. When the researchers included all three markers simultaneously in one model, NT-proBNP showed predictive ability for recurrent CVD events. These results extend similar findings pointing to the independent predictive value of NT-proBNP versus CRP and may warrant future emphasis on NT-proBNP, but the authors noted that their study included “everday” patients from one large geographic area. Other similar studies of NT-proBNP included highly selected populations from as many as 40 countries.
Lipids and CRP Predict Both Ischemic Stroke and CHD
Evaluating levels of lipids and CRP at the same time may improve risk assessment for both ischemic stroke and CHD, according to a paper in Journal of the American College of Cardiology (2006;48:2235–2242). The authors examined data on more than ten years of levels of CRP, TC, LDL-C, non-HDL-C, HDL-C, apolipoproteins A-I and B100, and lipid ratios in 15,632 initially healthy participants in the Women's Health Study. After the researchers adjusted data for age, smoking status, blood pressure, diabetes, and obesity, they determined that lipid levels are significant predictors of ischemic stroke, but are more effective at determining risk of CHD. The adjusted hazard ratios (HRs) for the third versus the first tertile for future ischemic stroke compared with CHD were 1.91 (95% CI 1.13–3.21) and 2.26 (95% CI 1.64–3.12) for TC, 1.29 (95% CI 0.83–2.02) and 2.09 ( 95% CI 1.53–2.85) for LDL-C, 0.57 (95% CI 0.36–0.92) and 0.38 (95% CI 0.27–0.52) for HDL-C, 1.72 (95% CI 1.03–2.86) and 2.93 (95% CI 2.02–4.21) for non-HDL-C, and 2.76 (95% CI 1.51–5.05) and 1.66 (95% CI 1.17–2.34) for CRP. TC to HDL-C was the best of all the lipid ratios at predicting both future ischemic stroke and CHD, with HRs of 1.95 (95% CI 1.16–3.26) and 4.20 (95% CI 2.79–6.32), respectively.