American Association for Clinical Chemistry
Better health through laboratory medicine
June 2008 Clinical Laboratory News: Diagnostics Profiles

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June 2008: Volume 34, Number 6

Independent Risk Factors for Heart Failure Found

Certain inflammatory markers and albuminuria are independent predictors of CHF, a recent paper concludes (J Am Coll Cardiol 2008; 51:1775–1783). Amidst increasing interest in both the role novel risk factors, such as systemic inflammation, insulin resistance, and albuminuria, play in the pathophysiology of CHF and their relationship with obesity, a multicenter research team studied a cohort of 6,814 participants enrolled in the MESA (Multi-Ethnic Study of Atherosclerosis) trial. The Caucasian, African American, Hispanic and Chinese American participants from six communities ranged in age from 45 to 84 and had no history of symptomatic CVD. Median follow-up time was 4 years. The researchers used Cox proportional hazards models to analyze the associations of the metabolic syndrome, inflammatory markers, insulin resistance, and albuminuria with incident CHF, independent of established risk factors (age, sex, hypertension, diabetes mellitus, left ventricular hypertrophy, obesity, serum total cholesterol, and smoking), an interim MI, and baseline magnetic resonance imaging parameters of left ventricular structure and function. A total of 79 participants developed CHF during follow-up, while 26 participants, or 32.9%, had an MI prior to CHF. Sixty-five percent of the cases had CHF with preserved function (left ventricular ejection fraction ≥40%). In multivariable analyses, serum interleukin-6 (HR for 1 standard deviation 1.50, 95% CI, 1.10–2.03) or CRP (HR for 1 standard deviation 1.38; 95% CI, 1.01–1.86) and macroalbuminuria (HR 4.31, 95% CI, 1.58–11.76) were predictors of CHF, independent of obesity and the other established risk factors. Although obesity was significantly associated with incident CHF, this association was no longer significant after adding either interleukin-6 or CRP to the model. 

Total Homocysteine Levels Drop After Folic Acid Fortification

Plasma total homocysteine (tHcy) levels among NHANES subjects decreased approximately 10% after the FDA required fortification of enriched cereal-grain products with folic acid, according to a recently published study (Clin Chem 2008; 54: 801–813). Inadequate folic acid intake leads to increased tHcy concentrations, which research has associated with birth defects and cognitive decline and osteoporosis in the elderly. Because studies with smaller populations had reported decreases in tHcy concentrations following introduction of folate fortification, CDC, NIH, and FDA researchers sought to study the effects of fortification on tHcy in the NHANES population. Although NHANES has monitored tHcy levels since 1991, researchers didn’t have the ability to compare data across study periods until recently. New analytical methods and specimen matrices have made such comparisons possible. To supplement knowledge about how the program has modified tHcy levels, the researchers examined tHcy data in the prefortification NHANES III survey periods (phase II, 1991–1994) and in three postfortification survey periods (1999–2000, 2001–2002, and 2003–2004). The researchers applied method adjustment equations to the survey data based on method comparison studies of separate samples, excluding people with chronic kidney disease from the analyses. From the period before fortification to after fortification, mean plasma tHcy concentrations decreased by 8%, 9%, and 10% for adolescent, adult, and older men, respectively, and by 6%, 3%, and 13% for adolescent, adult, and older women, respectively. Between the first and third postfortification survey periods, tHcy concentrations remained unchanged. From the prefortification period to postfortification period, prevalence estimates of increased plasma tHcy concentrations—defined as >13 µmol/L—decreased the most for older men and women. Among these older men, these prevalence estimates decreased from 32% to 14%, and among older women, they dropped from 20% to 5%. During the postfortification periods, prevalence estimates changed little.

Rapid Multimarker Test Triages ER Chest Pain Patients

A rapid multimarker protocol is superior to a TnI-only approach for rapidly triaging patients with chest pain or acute MI, according to a recent paper (Am J Clin Pathol 2008; 5: 788–795). Researchers compared a rapid, POC multimarker protocol with a single and serial TnI-only protocol in 5,244 patients admitted to the emergency room with chest pain. The researchers based diagnosis of acute MI on one of three criteria: a doubling myoglobin level accompanied by at least a 50% increase in the CK-MB level, with no detectable TnI; a doubling of myoglobin level together with any detectable TnI; or a TnI level of 0.4 ng/mL (0.4 μg/L) or more, irrespective of myoglobin or CK-MB results. With the new criteria, 145 of 148 cases were positive for acute MI (PPV 92.4%) and three were negative by both the multimarker protocol and the core laboratory TnI assay. The new protocol confirmed 12 acute MI cases that were previously considered negative by TnI alone, with 10 of the 12 confirmed by the core laboratory as positive for TnI. The negative predictive value (NPV) was 99.9% and the overall diagnostic accuracy was 99.7%. The TnI-only protocol had a sensitivity of 68.2% with an NPV of 99.1%. With lower TnI-only cutoffs, researchers found that four patients had false-negative results and observed a PPV of 36.4%.

Systemic cTn and ECG Screening Finds MIs in the ICU

Systemic screening with cTn and ECGs increased identification of elevated cTn and MI among patients admitted to an ICU, according to a multinational research team (Critical Care 2008, 12:R36doi:10.1186/cc6815). In their prospective screening study, researchers analyzed data from 103 patients who had systematic screening with cTn and ECGs upon admission to a general medical-surgical ICU 112 times during a 2-month period. Patients had these screenings daily for the first week in the ICU, on alternate days for up to one month afterward, and weekly thereafter for up to 2 months or until death or discharge. The research team interpreted all ECGs independently and in duplicate for ischemic changes meeting ESC/ACC criteria for MI diagnosis and classified patients as having MI (elevated cTn and ECG evidence supporting diagnosis of MI), elevated cTn only (no ECG evidence supporting diagnosis of MI), or no cTn elevation. Overall, 37 patients (35.9%) had an MI, 15 patients (14.6%) had elevated cTn only, and 51 patients (49.5 %) had no cTn elevation. Patients with MI had longer duration of mechanical ventilation, longer ICU stay, higher ICU mortality and higher hospital mortality, compared with those with no cTn elevation. After adjusting for APACHE II score, MI and advanced life support, elevated cTn was associated with increased hospital mortality (OR 27.3, 95% CI, 1.7–449.4). The ICU team diagnosed 18 patients (17.5 %) as having MI on clinical grounds, but based on test results researchers determined that four of these patients did not have MI. The screening protocol detected an additional 23 MIs not diagnosed in practice, reflecting 62.2 % of MIs ultimately diagnosed. Patients with MI diagnosed by the ICU team had similar outcomes to patients with MI detected by screening alone.