December 8, 2010
Detection Of Cardiac Biomarker Associated With Structural Heart Disease, Increased Risk Of Death
With the use of a highly sensitive test, detection of the blood biomarker cardiac troponin T, a cardiac-specific protein, is associated with structural heart disease and an increased risk of all-cause death, according to a study in the December 8 issue of JAMA.
Cardiac troponin T (cTnT) is a preferred biomarker for the diagnosis of heart attack, and increasingly it has been recognized that elevated troponin levels may be detected in several chronic disease states, including coronary artery disease (CAD), heart failure, and chronic kidney disease (CKD). Some research has suggested that troponin may be useful for detecting subclinical cardiovascular disease and assessing cardiovascular disease risk in the general population; however, the low prevalence of detection with standard tests would limit the use of troponin measurement for these clinical applications, according to background information in the article.
"Recently, a highly sensitive assay for cTnT has been developed that detects levels approximately 10-fold lower than those detectable with the standard assay," the authors write. "In patients with chronic heart failure and chronic CAD, circulating cTnT is detectable in almost all individuals with the highly sensitive assay, and higher levels correlate strongly with increased cardiovascular mortality."
James A. de Lemos, M.D., of the University of Texas Southwestern Medical Center, Dallas, and colleagues conducted a study to determine the prevalence of detectable cTnT in the population using a highly sensitive assay and to assess whether cTnT levels measured with this new test were associated with cardiac abnormalities and subsequent death. Cardiac troponin T levels were measured using both the standard and the highly sensitive assays in 3,546 multiethnic individuals, ages 30 to 65 years, enrolled between 2000 and 2002 in the Dallas Heart Study. Mortality follow-up was complete through 2007. Participants were placed into 5 categories based on cTnT levels. Cardiac structure and function was measured with magnetic resonance imaging.
The researchers found that the prevalence of detectable cTnT in Dallas County adults was 25 percent using the highly sensitive cTnT assay and 0.7 percent using the standard assay. Large differences in prevalence were seen according to sex and race/ethnicity: men were 3-fold more likely to have detectable levels than women (37.1 percent vs. 12.9 percent), and black participants had a significantly higher prevalence of detectable cTnT than Hispanic or white participants. The prevalence of detectable cTnT also varied with age, ranging from 14 percent in participants ages 40 to 50 years to 57.6 percent in those 60 to 65 years.
Two-thirds of participants in the highest cTnT category had undetectable cTnT levels with the standard assay. The prevalence of hypertension increased from 27.2 percent to 70.9 percent and prevalence of diabetes from 7.7 percent to 41 percent across categories of increasing cTnT levels. Left ventricular mass increased markedly across cTnT categories, as did left ventricular wall thickness, and the proportion of individuals classified as having left ventricular hypertrophy (enlargement) increased from 7.5 percent to 48.1 percent. Self-reported heart failure, coronary heart disease, and cardiovascular disease were more frequent with higher cTnT levels.
During a median (midpoint) follow-up of 6.4 years, there were 151 total deaths, including 62 cardiovascular disease deaths. All-cause mortality increased from 1.9 percent to 28.4 percent across higher cTnT categories. After adjustment for several factors, cTnT category remained independently associated with all-cause mortality. "Prior studies have described associations between increased troponin levels detected with standard assays and future risk for mortality. Here, we report that these associations extend to much lower troponin levels not detected with assays in current clinical use," the authors write.
The authors suggest that their finding of a high prevalence of detectable cTnT in the general population may have important, and complex implications for the use of highly sensitive troponin assays for diagnosing heart attack in the hospital setting. "Among patients with clinical presentations suspicious for myocardial infarction, higher-sensitivity assays improve diagnostic sensitivity, particularly early after presentation, but reduce specificity. When applied to patients with a high clinical suspicion for myocardial infarction, the net result is improved accuracy."
These findings suggest that future studies should be performed to assess whether measurement of cTnT levels with a highly sensitive assay adds value to traditional cardiovascular risk factors, the researchers add.
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