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

June 2007: Volume 33, Number 6

Estimated GFR Helps
Determine Risk in ACS Patients

The estimated glomerular filtration rate (eGFR), in combination with an increased cardiac troponin level (cTn), provides powerful risk stratification of patients with ischemic symptoms suggestive of acute coronary syndromes (ACS), according to recent research (American Journal of Clinical Pathology 2007; 127: 598–603). Researchers from Hennepin County Medical Center measured cTn with four commercial cTn assays—cTnI from Dade Behring (Deerfield, Ill.), Beckman Coulter (Brea, Calif.), and Tosoh (Grove City, Ohio), and cTnT from Roche (Indianapolis, Ind.)—in 490 emergency department patients with ACS symptoms and varying renal function. Researchers stratified patients according to eGFRs and along European Society of Cardiology/American College of Cardiology sex-specific 99th percentile reference cutoffs for myocardial injury determined in the same normal population. Average patient age was 58.3 years, 57% were male, and 35% were African American. Sixty-two percent had hypertension and 26% had diabetes. Fourteen percent to 25% of patients had increased cTn levels. In 68%, the eGFR was 60/mL/min/173 m2 or more. In 17%, eGFR was between 41 and 59, and in 15%, it was 40 or less. Patients suffered nine cardiac events and 36 deaths. Risk stratification was significant at 30 days and 6 months. Relative risks ranged from 3.1 to 3.7, and cumulative event rates ranged from 22.4% to 24.2% for an increased troponin level, compared with 6.7% to 8.9% for a normal level. The 6-month event rate for patients whose eGFR was less than 60/mL/min/173 m2 and had increased troponin levels ranged from 29.9% to 50.8%, compared with 4.9% to 6.6% for patients with normal troponin levels and eGFR greater than 0/mL/min/173 m2. These findings contrast with previous research, which found that cTnT levels predicted 30-day prognosis in patients with ACS, regardless of their creatinine clearance rate, researchers noted.

CRP Has Strong Predictive Value
for Cardiovascular Events

Among asymptomatic patients with stable coronary artery disease, even a small increase in CRP predicts adverse cardiovascular events, according to a recent study (Circulation 2007; 115: 1528–536). Researchers from Boston’s Brigham and Women’s and Children’s Hospitals, George Washington University (Washington, D.C.), University of Calgary (Alberta, Canada), Mayo Clinic Foundation (Rochester, Minn.), and the National Heart, Blood, and Lung Institute measured CRP in 3,771 patients with stable coronary artery disease in the PEACE (Prevention of Events with Angiotensin-Converting Enzyme Inhibition) trial, a study of the ACE inhibitor trandolapril. The investigators determined independent prognostic significant of CDC/American Heart Association risk categories based on CRP levels. During an average of 4.8 years of follow-up, researchers tracked incidence of cardiovascular death, myocardial infarction, stroke, heart failure, and diabetes. After adjustment for baseline characteristics and treatments, higher CRP levels were associated with a much greater risk of cardiovascular death, myocardial infarction, or stroke (CRP 1 to 3 mg/L, adjusted HR 1.39, 95% CI, 1.06–1.81 and CRP >3 mg/L, adjusted HR 1.52, 95% CI 1.15–2.02). Elevated CRP levels were an independent predictor of new heart failure and new diabetes. There were no significant interactions between CRP levels and the effects of trandolapril on any of these outcomes. Researchers noted that the CDC and American Heart Association have recognized prognostic utility of CRP in a joint statement, but called for resolution of several issues, especially appropriate cut points and implications of CRP levels that exceed those cut points in different populations.

Novel Cardiac Biomarkers’ Utility Uncertain

Certain novel biomarkers are associated with CVD, but add only modest prognostic information to that provided by traditional risk factors and the ankle brachial index, a recent study found (Circulation 2007; 115: 1528–1537). Researchers from Scotland’s University of Aberdeen and University of Glasgow used data from 416 subjects of the Edinburgh Artery Study to compare associations of 17 circulating cardiac markers with incidence of major CVD. Subjects suffered at least one cardiovascular event. After adjustment for cardiovascular risk factors and CVD history, those markers with significant hazard ratios for incident CVD were CRP, interleukin-6, fibrogen, fibrin D-dimer, tissue plasminogen activator, leukocyte elastase, lipoprotein(a), as well as von Willebrand factor and plasma viscosity. Intereukin-6 showed the strongest, most consistent associations with different disease manifestations. Further adjustment for a measure of subclinical atherosclerosis had little impact on these associations. The HRs (95% CI) for incident CVD between top and bottom tertiles in the latter analysis were 1.78 (1.30–2.45) for CRP, 1.85 (1.33–2.58) for interleukin-6, and 1.76 (1.35–2.31) for fibrogen. Single biomarkers provided little additional discrimination; however, an incremental score of multiple markers including interleukin-6, tissue plasminogen activation, intercellular adhesion molecule 1, and lipoprotein(a) provided some added discrimination.

Reduced Natriuretic Peptides
Could Signal Metabolic Syndrome

Having several metabolic risk factors is associated with low levels of circulating BNP and N-terminal pro-atrial natriuretic (N-ANP), according to recent research (Circulation 2007; 115: 1345–1353). Researchers from Boston’s University of Massachusetts Medical School, Harvard Medical School, Boston University School of Medicine, and the National Heart, Lung, and Blood Institute examined the association of BNP and N-ANP with metabolic risk factors, the metabolic syndrome, and insulin resistance in 3,333 Framingham Offspring Study participants who did not have heart failure. Their mean age was 58%, and 54% were women. After regression analysis and adjustment for clinical and echocardiographic variables, their natriuretic peptide levels were inversely associated with all components of the metabolic syndrome except for elevated blood pressure. Adjusted natriuretic peptide levels were low in patients with the metabolic syndrome, compared to those without the syndrome. In men, the decrease in BNP was 24% and 16% for N-ANP. In women, the decrease in BNP was 29% and 18% for N-ANP. Individuals with insulin resistance had lower levels of BNP and N-ANP. These data raise the possibility that interpretation of natriuretic peptide levels should take into account other metabolic traits, the researchers wrote. They called for more data on temporal relations of low natriuretic peptide levels and insulin resistance; the effect of endogenous versus exogenous natriuretic peptide levels and insulin resistance on insulin signaling; and the impact of reduced natriuretic peptide activity on the risk of cardiovascular events in the metabolic syndrome.