CLINICAL PERSPECTIVE

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(Circulation. 2006;113:1958-1965.)
© 2006 American Heart Association, Inc.

Epidemiology

Prevalence and Determinants of Troponin T Elevation in the General Population

Thomas W. Wallace, MD; Shuaib M. Abdullah, MD; Mark H. Drazner, MD, MHSc; Sandeep R. Das, MD, MPH; Amit Khera, MD, MSc; Darren K. McGuire, MD, MHSc; Frank Wians, PhD; Marc S. Sabatine, MD, MPH; David A. Morrow, MD, MPH; James A. de Lemos, MD

From the Donald W. Reynolds Cardiovascular Clinical Research Center and Department of Internal Medicine, University of Texas Southwestern Medical Center, Dallas (T.W.W., S.M.A., M.H.D., S.R.D., A.K., D.K.M., F.W., J.A.d.L.); and Donald W. Reynolds Cardiovascular Clinical Research Center, Brigham and Women’s Hospital, Boston, Mass (M.S.S., D.A.M.).

Correspondence to James A. de Lemos, MD, Division of Cardiology, University of Texas Southwestern Medical Center, 5909 Harry Hines Blvd, Room HA9.133, Dallas, TX 75390-9047. E-mail James.delemos{at}utsouthwestern.edu

Received November 7, 2005; de novo received December 21, 2005; revision received February 21, 2006; accepted February 23, 2006.

	Abstract

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Background— The prevalence and determinants of cardiac troponin T (cTnT) elevation in the general population are unknown, and the significance of minimally increased cTnT remains controversial. Our objective was to determine the prevalence and determinants of cTnT elevation in a large, representative sample of the general population.

Methods and Results— cTnT was measured from stored plasma samples in 3557 subjects of the Dallas Heart Study, a population-based sample. cTnT elevation (0.01 µg/L) was correlated with clinical variables and cardiac MRI findings. The sample weight-adjusted prevalence of cTnT elevation in the general population was 0.7%. In univariable analyses, cTnT elevation was associated with older age, black race, male sex, coronary artery calcium by electron beam CT, a composite marker of congestive heart failure (CHF), left ventricular hypertrophy (LVH), diabetes mellitus (DM), and chronic kidney disease (CKD) (P<0.001 for each). Subjects with minimally increased (0.01 to 0.029 µg/L) and increased (0.03 µg/L) cTnT had a similar prevalence of these characteristics. In multivariable logistic regression analysis, LVH, CHF, DM, and CKD were independently associated with cTnT elevation.

Conclusions— In the general population, cTnT elevation is rare in subjects without CHF, LVH, CKD, or DM, suggesting that the upper limit of normal for the immunoassay should be <0.01 µg/L. Even minimally increased cTnT may represent subclinical cardiac injury and have important clinical implications, a hypothesis that should be tested in longitudinal outcome studies.

Key Words: diabetes mellitus • hypertrophy • kidney • population • troponin

	Introduction

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Cardiac troponins are well established as specific biomarkers for myocyte injury in the setting of acute coronary syndromes (ACS).¹ Troponin measurement aids in the diagnosis of acute myocardial infarction (MI), facilitates risk stratification, and helps to direct treatment modalities.^1–3 Although troponin elevation in disorders such as congestive heart failure (CHF) and chronic kidney disease (CKD) portends worsened prognoses,^4–6 physicians struggle to interpret troponin values in non-ACS settings, especially when concentrations approach the lower limit of detection for the assay. Troponin levels are increasingly being measured in subjects without typical ischemic chest pain, and the resultant uncertainty as to the interpretation of values in these settings may promote clinical confusion.

Clinical Perspective p 1965

Compounding these clinical issues is controversy with regard to the appropriate lower limits to define troponin elevation and the importance of imprecision with current troponin assays around these lower limits of detection. Expert committees have recommended that troponin elevation be defined, with the use of a normal reference population, as the lowest detectable troponin concentration above the 99th percentile that has <10% coefficient of variation (CV).¹ For cardiac troponin T (cTnT), this level is 0.03 µg/L, whereas the lower detection limit is <0.01 µg/L. The choice of the threshold has important clinical implications because recent studies suggest that in patients with ACS, cTnT levels between 0.01 and 0.03 µg/L have important prognostic and therapeutic implications.² In addition, minimally increased cardiac troponin I levels in patients without definite ACS are also associated with poor prognosis.⁷

To date, few data are available with regard to the prevalence of cTnT elevation within the general population. To better understand the prevalence, etiology, and clinical implications of cTnT elevation that occurs in the general population (including subjects with and without cardiovascular disease), we measured cTnT levels within the Dallas Heart Study, a population-based, representative sample of the Dallas community.

	Methods

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Study Population
The Dallas Heart Study is a population-based, multiethnic, probability sample of residents of Dallas County, designed to study subclinical cardiovascular disease. Self-reported blacks were oversampled to ensure that 50% of the final sample included this ethnic group. Details of the study design and cohort have been described previously.⁸ The study was approved by the University of Texas Southwestern Medical Center institutional review board, and all subjects provided written informed consent. The initial in-home visit included 6101 participants and consisted of demographic and medical history data collection, as well as objective measurements (weight, heart rate, and blood pressure). Participants in the 30- to 65-year-old age group were invited for a second visit for collection of fasting blood and urine samples. Participants completing the second visit returned for a final visit, at which time ECG, cardiac and aortic MRI, electron beam CT, and dual-energy x-ray absorptiometry scanning studies were performed. A total of 3557 and 2971 subjects completed the second and third visits, respectively. No significant differences in demographics, medical history, blood pressure, or body mass index (BMI) occurred between the subjects in the second and third visits.⁸ Sampling weights, reflecting the different probabilities of selection for participants and sample attrition between visits, were constructed to generate unbiased estimates of population frequencies.⁸

Biomarker Assays
Fasting blood samples were collected in tubes containing EDTA and maintained at 4°C for 4 hours before being centrifuged at 1430g for 15 minutes. Plasma aliquots were frozen at –80°C until assays were performed. cTnT (Elecsys Troponin T, Roche Diagnostics, Inc, Indianapolis, Ind) was measured with a third-generation immunoassay. The 99th percentile value from the reference population of 1951 subjects used by the manufacturer of the assay was <0.01 µg/L, and the lowest level at which the CV was <10% was 0.03 µg/L.^9,10 B-type natriuretic peptide (BNP) and N-terminal-proBNP (NT-proBNP) measurements were performed with commercially available assays from Biosite, Inc (San Diego, Calif) and Roche Diagnostics, Inc, respectively.¹¹ High-sensitivity C-reactive protein measurements were performed on thawed samples with the use of the Roche/Hitachi 912 System, Tina-quant assay (Roche Diagnostics, Inc), a latex-enhanced immunoturbidimetric method with a measurement range of 0.1 to 20 µg/L.¹²

Cardiac Imaging
Electron beam CT scans were performed with an Imatron C-150XP electron beam CT scanner (Imatron Inc, San Bruno, Calif) as described.¹³ Coronary artery calcium (CAC) scores were classified with the use of a previously described classification scheme¹⁴: no calcium (CAC score 0 to 10), mild (>10 to 100), moderate (>100 to 400), and severe (>400).

Cardiac MRI was performed with the use of a Phillips Medical Systems 1.5-T Intera magnet (Bothell, Wash) as described.¹⁵ Low left ventricular ejection fraction (LVEF) was defined as <0.40.¹⁶ Sex-specific left ventricular hypertrophy (LVH) was defined as ratios of LV mass to body surface area >89 g/m² in women and >112 g/m² in men.¹⁵

Definition of Variables
Subjects completed an extensive self-reporting survey in which past medical history of MI, CHF, valvular heart disease, coronary artery bypass grafting, smoking, arrhythmias, recent hospitalization (<1 year before visit 1), alcohol and cocaine use, and medication use were obtained. Stable angina pectoris was defined as self-reported chest pain with exertion plus at least 1 affirmative answer to an additional criterion from the Rose Angina Questionaire¹⁷: location, effect of level of exertion on chest pain, improvement of pain with rest, or duration of chest pain.

Diabetes mellitus (DM) was defined by a fasting serum glucose 126 mg/dL (7 mmol/L), nonfasting serum glucose >200 mg/dL (>11.1 mmol/L), or use of an antihyperglycemic medication. Five sequential blood pressure measurements were obtained at visit 1, and hypertension was defined as mean systolic blood pressure 140 mm Hg, mean diastolic blood pressure 90 mm Hg, or use of antihypertensive medication. Hypercholesterolemia was defined as a calculated fasting low-density lipoprotein cholesterol 160 mg/dL (4.1 mmol/L), direct low-density lipoprotein 160 mg/dL (4.1 mmol/L) on a nonfasting sample, total cholesterol 240 mg/dL (6.2 mmol/L), or use of statin medication. Hypertriglyceridemia was defined as a fasting triglyceride concentration 200 mg/dL (2.3 mmol/L); low high-density lipoprotein was defined as 40 mg/dL (1.0 mmol/L) in men and 50 mg/dL (1.3 mmol/L) in women.

Estimated glomerular filtration rate (eGFR) was determined by the Modification of Diet and Renal Disease calculation [eGFR=186xserum creatinine (mg/dL)^–1.154xage (years)^–0.203x0.742 (if female)x1.21 (if black)] and classified with the use of standards set forth by the National Kidney Foundation’s Kidney Disease Outcomes Quality Initiative.¹⁸ The Modification of Diet and Renal Disease calculation may overestimate kidney disease when applied to the general population; for this reason, we defined chronic kidney disease as eGFR <60 mL/min.¹⁹

Statistical Analysis
All statistical analysis was performed with the use of SAS (version 9.1; Cary, NC) statistical software. Because of the skewed distribution, cTnT levels were analyzed as categorical variables as undetectable (<0.01 µg/L), minimally increased (0.01 to 0.029 µg/L), and increased (0.03 µg/L). To estimate the population prevalence of detectable cTnT, we used the SAS procedure SURVEYMEANS to account for the stratified sampling design and unequal sample weights due to intentional oversampling of blacks. Statistical comparisons of variables between cTnT categories were made with the use of the ² or Fisher exact test for categorical variables and the Kruskal-Wallis or Wilcoxon 2-sample test for continuous variables. The Cochran-Armitage trend test was used to evaluate the association between cTnT prevalence and CKD, BMI, and CAC classifications. Stepwise multivariable logistic regression was performed to identify variables independently associated with cTnT elevation requiring a probability value of 0.1 to be entered and 0.05 to remain in the model. Because of the small number of subjects with cTnT elevation, our ability to perform multivariable adjustment was limited; therefore, we created composite factors to characterize CHF and coronary artery disease (CAD).The CHF factor was defined as either a prior history of CHF, LVEF <0.40 by MRI, or BNP >100 pg/mL. The CAD factor was defined as either a history of stable angina, history of MI, or CAC score >100. Finally, in exploratory analyses, the quantitative association between the cumulative independent determinants and the probability of cTnT elevation was evaluated with the use of the Cochran-Armitage trend test to determine statistical significance.

The authors had full access to the data and take full responsibility for its integrity. All authors have read and agree to the manuscript as written.

	Results

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Prevalence of Troponin Elevation and Associations With Clinical Variables
Of the 3557 subjects who provided blood samples for cTnT testing, 41 subjects (1.15%) had detectable values of cTnT. After we accounted for sampling weights, the estimated population prevalence of cTnT elevation was 0.70% (95% CI, 0.34% to 1.07%). The range of detectable cTnT within our sample was 0.01 to 0.37 µg/L with a median value of 0.024 µg/L. Four subjects (0.1% of sample) had cTnT concentrations >0.1 µg/L. The subject with a cTnT of 0.37 µg/L had end-stage renal disease for 6 years requiring peritoneal dialysis with several recent hospitalizations for dehydration, nausea, and vomiting. He had a CAC score of 2326 but did not have evidence of a recent ACS event or stable angina, and he had normal LV mass and LVEF.

In univariable analyses, cTnT elevation (0.01 µg/L) was significantly associated with older age, black race, male gender, and a history of MI, coronary artery bypass grafting, CHF, valvular disease, arrhythmias, stable angina, DM, hypertension, and CKD. Additional factors demonstrating significant associations were low HDL cholesterol; high triglycerides; higher BMI; recent hospitalization; therapy with aspirin, statins, ACE inhibitors, or ß-blockers; LVH; LVEF <40%; increasing CAC score; and increased levels of BNP and NT-proBNP (Table 1).

View this table: [in this window] [in a new window]   TABLE 1. Comparison of Variables Between Subjects With Undetectable, Minimally Increased, and Increased cTnT Concentrations

When subjects with undetectable (<0.01 µg/L), minimally increased (0.01 to 0.029 µg/L), and increased (0.03 µg/L) cTnT values were compared, a threshold effect was evident (Table 1). There were marked differences in the presence of high-risk clinical characteristics when the undetectable group was compared with the minimally increased group; in contrast, the minimally increased and increased cTnT groups had a similar prevalence of these high-risk cardiovascular features (Table 1).

Quantitative Associations Between Clinical Variables and cTnT Elevation
The prevalence of cTnT elevation increased in a graded manner with increasing LV mass (Figure 1). Similarly, the prevalence of cTnT elevation increased with an increasing number of components of the CHF factor (history of CHF, EF <0.40, or BNP >100 pg/mL) (Figure 2). Decreasing eGFR was also associated with increased prevalence of cTnT elevation in a steep, dose-dependent fashion (Figure 3).

View larger version (11K): [in this window] [in a new window]   Figure 1. Association between LV mass index and the prevalence of elevated cTnT.

View larger version (12K): [in this window] [in a new window]   Figure 2. Association between CHF criteria and elevated cTnT. CHF criteria include history of CHF, LVEF <40%, and BNP >100 pg/mL.

View larger version (11K): [in this window] [in a new window]   Figure 3. CKD classification and the prevalence of elevated cTnT. CKD classification is as follows: I, eGFR >90 mL/min; II, eGFR 60 to 90 mL/min; III, eGFR 30 to 60 mL/min; IV, eGFR 15 to 30 mL/min; V, eGFR <15 mL/min or dialysis.

Multivariable Association of Clinical Variables and Troponin Elevation
In multivariable logistic regression analysis, the CHF factor (odds ratio [OR], 5.3; 95% CI, 1.9 to 14.8), DM (OR, 4.6; 95% CI, 1.8 to 11.6), LVH (OR, 5.4; 95% CI, 2 to 14.6), and CKD (OR, 20.4; 95% CI, 7.5 to 55.3) were independently associated with cTnT elevation (Table 2). Age, race, and the CAD factor were not significantly associated with cTnT elevation and were removed from the final multivariable model. When subjects were categorized on the basis of increasing numbers of independent determinants, a steep, additive association was observed between the number of independent risk determinants and cTnT elevation (Figure 4). At least 1 of these determinants was present in 37 of 41 subjects (90%) with cTnT elevation. When the study population was restricted to a very-low-risk cohort (n=1060) without DM, hypertension, CKD, LVH, CHF, low LVEF, history of MI, or BMI >30, no subjects had detectable cTnT.

View this table: [in this window] [in a new window]   TABLE 2. Multivariate Analysis of Risk Determinants for cTnT Elevation in the General Population

View larger version (12K): [in this window] [in a new window]   Figure 4. Association between the number of independent determinants (DM, CHF factor, LVH, or CKD) and elevated cTnT.

	Discussion

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Among Dallas County adults aged 30 to 65 years, the population prevalence of cTnT elevation was very low (0.7%). When cTnT was detected, it was associated with underlying cardiovascular disease or high-risk phenotypes associated with cardiovascular disease. Few data are available evaluating the prevalence of cTnT elevation in a large and representative sample of the general population. Previous studies have reported the prevalence of troponin elevation among dialysis patients, patients visiting emergency departments with angina, patients presenting to outpatient clinics, and healthy volunteers.^20–23 In addition, although LVH, CKD, and CHF have previously been demonstrated to be associated with elevated troponin levels in small patient populations or subgroups of patients,^{5,6,10,24–27} we describe the largest cohort of nonhospitalized subjects to date in which independent associations between these conditions and cTnT elevation have been demonstrated. A prior study by Apple et al²³ reported higher troponin I values in blacks versus whites and in men versus women with some troponin assays. We also found a higher prevalence of cTnT elevation among blacks and men, but these differences did not remain statistically significant after multivariable adjustment.

Implications for the Lower Detection Limit for Troponin T
The European Society of Cardiology and American College of Cardiology recommended that the lower detection limit for cardiac troponin be the 99th percentile of the assay in a standard reference population provided that the CV at that level was <10%.¹ If an assay did not meet that criterion, the recommendation was to set the lower detection limit for troponin T or I at the lowest level at which the CV was <10%. The cTnT immunoassay used in the present study had a 99th percentile value of <0.01 µg/L but a value of 0.03 µg/L at which the CV was <10%. The strong associations between troponin levels of 0.01 to 0.029 µg/L and cardiovascular abnormalities seen in our population-based sample argue that the detection limit for cTnT should be lowered to <0.01 µg/L, so that all detectable cTnT values are characterized as abnormal if the goal of testing is optimal sensitivity.

In the present study we observed no apparent clinical differences between those subjects with minimally increased and increased cTnT values. The present findings suggest that the mandate for assay development should focus on greater sensitivity to detect lower levels of cTnT, and such efforts will require increased assay precision. Our findings do not support the default assumption that troponin concentrations below the 10% CV level are unreliable. Indeed, our data demonstrate that levels in this range carry important clinical implications. Previous clinical trials also demonstrated that patients with minimally increased cTnT levels below the 10% CV level (regardless of etiology or the magnitude of elevation) have worse prognoses.^{2,3,6,7,28–30} Furthermore, a recent simulation study using assay imprecision values representative of current cTnI assays demonstrated a very low false-positive rate for diagnosing MI when the 99th percentile was used instead of the 10% CV level, thus supporting use of the 99th percentile to define troponin elevation.³¹

Mechanisms of Troponin Elevation in the Population
Multiple mechanisms may account for cardiac injury and concomitant troponin elevations in our population-based sample.³² Microvascular coronary disease, which occurs in CHF, DM, and CKD, may contribute to troponin elevation in these disease processes. LV strain, decreased subendocardial perfusion, endothelial dysfunction, and apoptosis are potential etiologies of troponin elevation in CHF subjects.^33–35 Troponin elevation seen with LVH may be the result of a supply/demand mismatch whereby hypertrophied myocytes physically impair adequate endocardial tissue perfusion.³⁶ Both microvascular disease and lipotoxic mechanisms may lead to myocardial damage in diabetic patients.^37,38 One study demonstrated that at autopsy, diabetic patients with normal coronary arteries on angiogram had multiple microvascular infarctions.^39,40 Microvascular disease has been demonstrated to be present in CKD patients, and uremia may lead to silent ischemia similar to that seen in diabetic subjects.^4,5 Furthermore, in patients with CKD, troponin elevation and LVH appear to be synergistic in regard to prognosis.⁴¹ Similarly, the mechanisms that cause cTnT elevation in patients with CHF and those with LVH may also be applicable in those with CKD.

Clinical Implications
In univariable analyses, cTnT elevation was associated with a large number of cardiac risk factors and evidence of cardiac structural and functional abnormalities. In multivariable analyses, cTnT elevation was strongly and independently associated with 4 independent risk determinants: CHF, LVH, DM, and CKD. Importantly, in the absence of these 4 risk determinants, cTnT elevation was extremely rare (0.18%). Indeed, in a cohort free of DM, hypertension, CKD, LVH, CHF, history of MI, low EF, or BMI >30 (n=1060), we did not observe any subjects with detectable cTnT. Thus, in this population-based cohort, cTnT elevation represented either prevalent cardiovascular disease or a high risk for cardiovascular disease. These findings suggest that primary and secondary prevention efforts should be intensified in subjects with otherwise unexplained troponin elevation and that additional cardiovascular evaluation may be warranted. Given the associations seen between troponin elevation and LV structural and functional abnormalities, DM, and renal failure, echocardiography, measurement of fasting glucose, and assessment of renal function would be reasonable. These data do not imply, however, that such an evaluation must occur urgently or require hospitalization. cTnT should only be interpreted together with available data from the patient’s history, physical examination, laboratory findings, and ECG.

These findings may also have implications for the diagnostic specificity of cTnT to detect MI in the setting of DM, LVH, CHF, and moderate CKD. The probability of cTnT elevation increases dramatically with a greater number of these risk determinants present. Clinicians should be aware that patients with multiple risk determinants may have detectable cardiac injury outside the setting of ACS. Such patients likely require evaluation and intervention, but not acutely.

Finally, our findings suggest that cTnT may merit consideration for further study as a screening test for cardiovascular abnormalities in high-risk population subsets. Although sensitivity of the test to detect cardiovascular disease will be low in apparently healthy subjects, given the low prevalence of troponin elevation observed (<0.2%), specificity appears to be quite high. Sensitivity may be improved in high-risk subjects such as those with DM (4.7% prevalence of elevated cTnT) and hypertension (2.8% prevalence of elevated cTnT). If future studies demonstrate increased risk for cardiac events in high-risk subjects with troponin elevation, and appropriate therapies for these subjects are identified, we speculate that troponin may prove to be a useful component of multiple-biomarker panels for screening of at-risk subjects in the general population. These multiple-biomarker panels may include other highly specific but relatively insensitive markers of cardiovascular risk that in the aggregate provide sufficient sensitivity for screening. Development of more sensitive troponin assays may improve the performance of troponin as a screening test.

Limitations
Several limitations of this study should be noted. First, and most notably, the number of subjects with troponin elevation was small, limiting the depth of multivariable analyses that could be performed and reducing statistical power to detect differences between subjects with minimally elevated and elevated cTnT levels. As a result, our conclusion that subjects with minimally elevated and elevated cTnT levels had similar clinical characteristics should be viewed with caution until these findings are replicated in larger data sets. Second, the study is a cross-sectional analysis of a large and ethnically diverse cohort and thus may not be applicable to other populations. Third, our study design cannot fully account for the potential influence of false-positive cTnT values due to analytic random noise or due to heterophile interference with the assay.^42,43 However, recent studies suggest that the probability of analytic false-positives is extremely low³¹ and that heterophile antibodies have a minimal influence on the assay used in the present study.⁹ Moreover, the finding that almost all subjects with elevated troponin, whether minimally increased or increased, had an abnormal cardiac phenotype identified argues that the influence of false-positives in our study is minimal. Finally, cardiovascular outcome data from this cohort are not yet available, and the prognostic implications of troponin elevation in the general population require further study.

Conclusion
The estimated population prevalence of cTnT elevation among Dallas County residents was 0.7%. cTnT was undetectable among healthy subjects, and almost every subject with cTnT elevation had underlying cardiovascular disease or a high-risk phenotype for cardiovascular disease. Furthermore, the prevalence of high-risk cardiovascular features (including LVH, DM, CKD, and CHF) was increased similarly in subjects with cTnT levels in the minimally increased and increased range. These data suggest that cTnT elevation is indicative of cardiovascular disease or at least a high-risk cardiovascular profile. The clinical and therapeutic implications of these findings require prospective study with outcome data.

	Acknowledgments

 
This study was supported by grants from the Donald W. Reynolds Foundation, Roche Diagnostics, and Biosite Inc. This study was also supported in part by US Public Health Service General Clinical Research Centers grant M01-RR00633 from National Institutes of Health/National Center for Research Resources–Clinical Research. Reagents for NT-proBNP, cTnT, and C-reactive protein were provided by Roche Diagnostics. Assays for BNP were provided by Biosite. We thank Dr Allan Jaffe for his critical review and insightful comments on this manuscript.

Disclosures

Dr McGuire reports having received research grant support from Biosite via University of Texas Southwestern Medical Center ($10 000) and having served as a consultant and/or on the advisory board for Biosite (<$10 000). Dr Sabatine reports having received research grant support from Roche Diagnostics <$10 000) and Biosite (<$10 000). Dr Morrow reports having received research grant support from Bayer Diagnostics ($10 000), Beckman-Coulter ($10 000), Biosite ($10 000), Dade-Behring ($10 000), and Roche Diagnostics ($10 000) via Brigham and Women’s Hospital; having received honoraria from Bayer Diagnostics (<$10 000), Dade-Behring (<$10 000), and Beckman-Coulter (<10 000); and having served as a consultant and/or on the advisory board for OrthoClinical Diagnostics (<$10 000). Dr de Lemos reports having received research grant support from Roche (<$10 000) and Biosite ($10 000) via University of Texas Southwestern Medical Center; having received other research support from Roche ($10 000) and Biosite ($10 000) via University of Texas Southwestern Medical Center; having served on the Speakers Bureau for Biosite (<$10 000); and having served as a consultant and/or on the advisory board for Biosite (<$10 000). The remaining authors report no conflicts of interest.

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CLINICAL PERSPECTIVE

Cardiac troponins are increasingly being measured in patients without typical symptoms of ischemic chest pain, and physicians struggle to interpret troponin elevation in these settings, especially when levels are only minimally elevated. In part, this difficulty arises because little is known about the frequency and clinical correlates of troponin elevation in the ambulatory setting. We measured cardiac troponin T (cTnT) in a large population sample from Dallas, Tex, and identified that 0.7% of adult subjects had an elevated cTnT (0.01 µg/L). cTnT elevation was associated with a high-risk cardiovascular profile, even when levels were only minimally elevated (0.01 to 0.03 µg/L). We identified 4 major risk determinants for elevated cTnT in the community (diabetes mellitus, left ventricular hypertrophy, chronic kidney disease, and heart failure); the prevalence of cTnT elevation ranged from 0.2% in subjects with 0 determinants to 36% in subjects with 3 of these risk determinants present. Practicing physicians should realize that cTnT elevation is extremely rare among healthy subjects but is relatively common in the presence of cardiac structural and functional abnormalities, diabetes, or renal insufficiency. For example, in the patient with diabetes, moderate renal insufficiency, and left ventricular hypertrophy who presents to the emergency department with atypical chest pain symptoms, minimal troponin elevation may reflect the influence of underlying chronic disease and not be indicative of an acute coronary syndrome event.

	Footnotes

 
Guest Editor for this article was Harvey D. White, DSc.

Presented in abstract form at the 2005 Scientific Sessions of the American Heart Association, Dallas, Tex, November 13–16, 2005.

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