August 2010 Clinical Laboratory News: Diagnostic Profiles

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August 2010: Volume 36, Number 8 

Lp-PLA2 Index Linked to CAD in African Americans

New research indicates that while lipoprotein-associated phospholipase A2 (Lp-PLA2) activity and index are associated with the presence of coronary artery disease (CAD) in both African Americans and Caucasians, Lp-PLA2 index was independently associated with CAD in African Americans but not Caucasians (J Clin Endocrinol Metab 2010;95:2376–83). The findings suggest that cardiovascular inflammation may be particularly important as a risk factor among African Americans.

The study compared 560 African American and Caucasian patients scheduled for diagnostic coronary arteriography at either of two New York hospitals. From blood samples drawn approximately 2–4 hours prior to the procedure, researchers measured triglycerides, total, low- (LDL) and high-density lipoprotein (HDL) cholesterol, glucose, ApoA-I, ApoB, Lp-PLA2 mass, and Lp-PLA2 activity. They also calculated homeostatis model assessment-insulin resistance (HOMA-IR) and Lp-PLA2 index, an integrated measure of Lp-PLA2 mass and activity. In addition, a composite cardiovascular score was calculated based on results from the coronary angiogram.

The researchers found no difference between the two groups in levels of total and LDL cholesterol, ApoB or composite cardiovascular score. However, African Americans had significantly higher levels of HDL cholesterol and ApoA-I, and lower levels of triglyceride, glucose, insulin, and HOMA-IR than Caucasians. Lp-PLA2 activity and index was significantly higher among both African American and Caucasian patients with CAD, but African Americans with CAD had significantly higher Lp-PLA2 index. After multivariate analysis, Lp-PLA2 index remained independently associated with CAD in African Americans but not Caucasians.

Since Lp-PLA2 has been implicated as a marker of vascular inflammation, the results indicate that the degree of vascular inflammation in subjects with CAD may be more pronounced among African Americans, according to the researchers. They also suggest that the higher Lp-PLA20 index observed in African Americans with CAD may be associated with a different lipoprotein distribution in these patients.

Heart-Type Fatty Acid-Binding Protein Adds to cTn Prognostic Value

A study by British researchers indicates that heart-type fatty acid-binding protein (H-FABP) adds to the prognostic value of cardiac troponin I (cTn) in low- and intermediate-risk patients with suspected acute coronary syndrome (ACS) (J Am Coll Cardiol 2010;55:2590–8). The findings build on prior research demonstrating that H-FABP predicts long-term mortality in patients with ACS, independent of clinical risk factors, cTn, and high-sensitivity C-reactive protein levels.

The study involved 955 patients with suspected ACS presenting at a large teaching hospital in Leeds, U. K. The authors conducted the study because, despite enormous interest in cardiac biomarkers, few other than cTn have been established unequivocally in routine practice. cTn has been a mainstay of risk stratification in ACS, even though newer, high-sensitivity assays that could achieve the universal definition of myocardial infarction standard of a coefficient of variation <10% at the 99th percentile value have not been commercially available until recently. Emerging evidence indicates that the assay improvements have increased the early diagnostic and prognostic value of cTn, and raises the question of whether there would be any further value in novel markers like H-FABP.

The researchers found that the risk of death or recurrent MI increased with increasing concentrations of H-FABP, with a particularly increased risk for patients with H-FABP concentrations >6.58µg/L. These individuals had an adjusted hazard ratio of 2.62, and the authors suggest that they are in a “very high-risk” group, and that further investigations such as coronary angiography and pharmacotherapy may be warranted for them. The investigators also found that women and men with H-FABP concentrations ≥5.3 µg/L and ≥5.8 µg/L, respectively, had significantly increased event rates.

The authors suggested that their findings support the role of H-FABP as a marker of myocardial ischemia, even in the absence of frank necrosis.


Copeptin is Independent Risk Factor for Diabetes

New research indicates that plasma copeptin predicts diabetes independently of a broad range of established risk factors for the disease, including fasting blood glucose levels and insulin (Circulation 2010; 121:2102–8). This novel risk marker could be particularly useful in screening individuals with normal fasting blood glucose levels who are less likely to be closely monitored than patients with impaired fasting glucose, according to the authors.

The researchers also suggest that their findings support a role for the arginine vasopression (AVP) system in the pathophysiology of diabetes. Previous studies have indicated that the AVP system may have a role in glucose homeostasis, insulin resistance, and diabetes. However, AVP is an unstable molecule that is cleared rapidly from plasma and mostly attached to platelets in circulation. However, copeptin, a C-terminal fragment of the AVP prohormone, which is produced in equimolar amounts with AVP, is stable, has a long half-life and is not bound to platelets.

The study, which involved 4,742 individuals, sought to examine the association of increasing quartiles of copeptin with baseline diabetes and insulin resistance and incident diabetes on long-term follow-up.

After multivariate logistic regression analysis, the researchers found that the odds of developing diabetes increased across increasing quartiles of copeptin, even after adjustment for baseline fasting glucose and insulin, with adjusted odds ratio of 2.09 in the highest quartile. This association remained significant in analyses restricted to individuals with fasting blood glucose levels <5.4 mmol/L, with adjusted odds ratio of 3.48 in the highest quartile.


Meta-analysis Quantitates eGFR and ACR in Chronic Kidney Disease

A meta-analysis conducted by the Chronic Kidney Disease Prognosis Consortium indicates that estimated glomerular filtration rate (eGFR) <60 mL/min/1.73 m2 and albumin-to-creatinine ratio (ACR) ≥1.1 mg/mmol (10 mg/g) are independent predictors of all-cause mortality and cardiovascular mortality in the general population (Lancet 2010; 375:2073–81). These findings provide a quantitative basis for these two kidney measures in risk assessment, definition, and staging of chronic kidney disease.

The researchers conducted the analysis because there has been considerable controversy about the use of GFR and albuminuria to define and stage chronic kidney disease. Some investigators have proposed different GFR thresholds or higher ACR for these purposes. In addition, previous studies have reported an association between eGFR or albuminuria and clinical outcomes in the general population, but only investigated one measure at a time, or had other limitations. The meta-analysis sought to pool standardized data for all-cause and cardiovascular mortality from studies with baseline eGFR and ACR to adjust for each measure and test for their interactions on risk in narrow categories.

The analysis included 105,872 individuals from 14 studies with urine ACR measurements and 1,128,310 participants from seven studies with urine protein dipstick measurements. The researchers observed an “exponential” increase in mortality at low eGFRs, with risk becoming significant at 60 mL/min/1.73 m2. There also was a two times higher risk of mortality at ACR of approximately 11.3 mg/mmol.


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