CLN Article

Diagnostic Profiles

Higher HbA1c Levels Linked to Better Outcomes in Advanced Heart Failure

A study of patients with advanced heart failure found higher levels of HbA1c to be associated with improved outcomes in patients who also had diabetes (Am J Cardiol 2012; doi:10.1016/j.amj card.2012.02.022). The authors called for further investigations to understand the mechanisms underlying this finding.

Despite the evidence linking diabetes, insulin resistance, and hyperglycemia to worse outcomes in patients with heart failure, there is insufficient data and guidance on optimal strategies to manage diabetes in patients with chronic heart failure. This prompted the researchers to reevaluate the relationship between HbA1c levels and outcomes in a large cohort of advanced heart failure patients.

The study involved 845 patients followed by physicians at the University of California Los Angeles' David Geffen School of Medicine. The patients had baseline HbA1c and other diagnostic testing at the time of referral and were followed for 2 years. Nearly three-quarters were men, more than three-quarters had New York Heart Association class III or IV heart failure, and 42% had diabetes. In those with diabetes, the mean HbA1c level was 7.6% compared with 6.0% in those without. The researchers stratified patients both with and without diabetes by HbA1c quartiles. The primary endpoints of the study were death or need for urgent heart transplant, or all-cause mortality.

When the authors analyzed HbA1c as a continuous variable in multivariate analysis, they found that for each unit increase in HbA1c, there was an 8% decreased risk for death or need for urgent heart transplantation. In the cohort with diabetes, survival free from death or urgent heart transplantation was significantly higher in the highest HbA1c quartile. In this group, analyzing HbA1c as a continuous variable, the authors found that for each unit increase in HbA1c there was a 15% decrease in risk of death, urgent heart transplantation, and all-cause mortality. In the cohort without diabetes, there was no difference in outcomes by HbA1c quartile.

In-hospital Lipid Testing Falls Short of Guideline Recommendations

Canadian researchers found over the course of a decade a significant temporal increase in in-hospital statin therapy in patients with acute coronary syndrome (ACS), but only a modest increase in in-hospital lipid testing (Am J Cardiol 2012;109:1418–24). However, at the same time they also found a strong association between lipid testing and in-hospital statin therapy. Patients who had lipid testing performed and had higher low-density lipoprotein cholesterol (LCL-C) levels were more likely to be treated with a statin during hospitalization. The authors concluded that a substantial portion of patients with ACS are not receiving guideline-recommended lipid testing, and that strategies to boost adherence to these guidelines would likely improve patient outcomes.

The authors examined temporal trends in lipid testing and statin therapy in hospitalized patients using prospective registry data that had been collected in a standardized format for adult patients with a presumptive diagnosis of ACS and diagnostic findings consistent with ACS. The researchers accessed data from 57 hospitals representing 13,947 patients and stratified the study population into three groups based on the years in which the participants were registered.

Overall, 70.8% of patients had lipid testing, and 79.4% received in-hospital statin therapy. However, during the 9-year study period, while there was a significant increase in in-hospital statin therapy—rising from 70% in the 1999–2004 cohort to 84.5% in the 2007-2008 group—there was only a minor increase in in-hospital lipid testing, from 69.4% in the 1999–2004 group to 72.4% in the 2007–2008 cohort. Lipid testing was independently associated with in-hospital statin use, and patients with LDL-C levels >130 mg/L were more than twice as likely as those with levels <100 mg/L to have statin therapy while hospitalized.

hs-cTn Assays Complicate Differential AMI Diagnosis in CAD Patients

New, high-sensitivity cardiac troponin (cTn I/T) assays have excellent diagnostic performance in early acute myocardial infarction (AMI) in patients with pre-existing coronary artery disease (CAD) (Eur Heart J 2012;33:988–97). However, mild cTn elevations are common in non-AMI CAD patients, making test-specific optimal cutoffs higher in CAD patients and less helpful in the differential AMI diagnosis.

New high-sensitivity cTn assays have been shown to improve early AMI diagnosis in unselected patients with acute chest pain. However, recent studies also have demonstrated that they detect elevated cTn levels in more than 10% of patients with stable CAD. This led the researchers to examine the diagnostic performance of these assays for the early diagnosis of AMI in patients with pre-existing CAD who presented to the emergency department (ED) with acute chest pain.

The study involved 1,247 consecutive patients with chest pain onset within the past 12 hours suggestive of AMI. The researchers assessed serial cTn levels using four different cTn assays: one high-sensitivity cTn T assay with a limit of detection of 0.003 ng/mL; two sensitive cTn I assays with lower limits of detection of 0.006 ng/mL and 0.0l ng/mL, respectively; and a standard cTn T assay with lower limit of detection of 0.01 ng/mL.

The three sensitive or high-sensitivity assays detected cTn at levels >99th percentile in 13–40% of CAD patients with an adjudicated diagnosis of AMI. The high incidence of elevated cTn levels in this patient population challenges application of the 99th percentile as the decision limit for diagnosing AMI. The authors also determined that cutoffs for CAD patients tended to be higher than in patients without a history of CAD, and that the performance of the sensitive cTn assays was most pronounced in CAD patients with recent onset of chest pain. However, the accuracy of these assays in diagnosing acute coronary syndrome was significantly lower in patients with pre-existing CAD than in those who did not have pre-existing CAD.

ESR, CRP, and WBC Markers of Pre-Arthroplasty Infection, Not just Inflammation

Erythrocyte sedimentation rate (ESR), C-reactive protein (CRP) level, and synovial fluid white blood cell (WBC) count with differential are useful for diagnosing periprosthetic joint infection in patients with inflammatory or non-inflammatory arthritis (J Bone Joint Surg Am 2012;94:594–600). The findings dispel the common belief that these markers do not accurately identify periprosthetic joint infection in patients with underlying inflammatory conditions.

The study involved 871 consecutive patients who underwent hip or knee arthroplasty and who were evaluated for periprosthetic joint infection. All had serum ESR and CRP levels tested at the time of initial evaluation, and joint aspiration for synovial fluid WBC count with differential culture.

The researchers found the rate of periprosthetic joint infection to be significantly higher in patients with inflammatory arthritis versus those without (31% versus 18%). Optimal ESR cutoffs for patients with noninflammatory and inflammatory arthritis were 32 and 30 mm/hr, respectively; for CRP, 15 and 17 mg/L, respectively; and for WBC, 3450/µL and 3444/µL, respectively. Areas under the curves, sensitivities, specificities, negative- and positive-predictive values for all tests were comparable in both sets of patients.

Based on these findings, the authors concluded that physicians evaluating patients with failed or painful total hip or knee arthroplasty should not assume that elevated ESR, CRP levels, and WBC with differential are secondary to inflammatory arthritis. Instead, these biomarkers may indicate periprosthetic joint infection and should prompt further evaluation for infection.