In the present study, we wanted to (1) evaluate whether high-sensitive troponin T levels correlate with the grade of renal insufficiency and (2) test the accuracy of high-sensitive troponin T determination in patients with renal insufficiency for diagnosis of acute myocardial infarction (AMI). In this cross-sectional analysis, all patients who received serial measurements of high-sensitive troponin T from August 1, 2010, to October 31, 2012, at the Department of Emergency Medicine were included. We analyzed data on baseline characteristics, reason for referral, medication, cardiovascular risk factors, and outcome in terms of presence of AMI along with laboratory data (high-sensitive troponin T, creatinine). A total of 1,514 patients (67% male, aged 65 ± 16 years) were included, of which 382 patients (25%) had moderate to severe renal insufficiency and significantly higher levels of high-sensitive troponin T on admission (0.028 vs 0.009, p <0.0001). In patients without AMI, high-sensitive troponin T correlated inversely with the estimated glomerular filtration rate (R = −0.12, p <0.0001). Overall, sensitivity of an elevated high-sensitive troponin for diagnosis of AMI was 0.64 (0.56 to 0.71) and the specificity was 0.48 (0.45 to 0.51). The area under the curve of the receiver operating characteristic for all patients was 0.613 (standard error [SE] 0.023), whereas it was 0.741 (SE 0.029) for patients with a Modification of Diet in Renal Disease estimated glomerular filtration rate >60 ml/min presenting with acute chest pain or dyspnea and 0.535 (SE 0.056) for patients with moderate to severe renal insufficiency presenting with acute chest pain or dyspnea. In conclusion, the diagnostic accuracy for presence of AMI of a baseline measurement of high-sensitive troponin in patients with renal insufficiency was poor and resembles tossing a coin.
Elevations of cardiac troponins are not specific to acute coronary syndrome (ACS). Several conditions, such as acute pulmonary embolism, peri- or myocarditis, acute heart failure, strenuous exercise, cardioverter-defibrillator shocks, cardiac amyloidosis, blunt chest trauma, epileptic seizures, and rhabdomyolysis, have been described to be associated with increased levels of troponins without the presence of ACS. Additionally, increased cardiac troponin levels have been described in patients with renal insufficiency. These findings led to a discussion in the medical community about how to interpret elevated high-sensitive troponin levels in patients with impaired renal function. Current guidelines of the European Society of Cardiology only state that troponin elevations without presence of ACS are commonly found in patients with a serum creatinine level >221 μmol/L. We aimed to investigate (1) whether renal insufficiency per se is associated with increased baseline high-sensitive troponin T levels and (2) the diagnostic accuracy of a baseline measurement of high-sensitive troponin T for acute myocardial infarction (AMI) in patients with renal insufficiency presenting to the emergency department.
Methods
In this cross-sectional analysis, all patients aged 16 years or older who received serial measurements (at least 2) of high-sensitive troponin T from August 1, 2010 (implementation of high-sensitive troponin T measurement at our central laboratory) to October 31, 2012 at the Department of Emergency Medicine, Inselspital, University Hospital Bern, were included. Only patients with serial high-sensitive troponin T measurements were included in the analysis to ensure that patients with AMI detectable only by troponin kinetics were not missed. High-sensitive troponin T was determined using the Roche Modular E170 (Roche Diagnostics, Basel, Switzerland), an electrochemiluminescence immunoassay. A value of high-sensitive troponin T <0.014 μg/L, equaling the ninety-ninth percentile in a normal collective, is considered normal according to our local reference ranges. Only high-sensitive troponin T levels ordered at the Department of Emergency Medicine were considered for analysis. The decision to order a measurement of high-sensitive troponin T was at the discretion of the physician in charge.
Of all patients with serial high-sensitive troponin T measurements, we gathered the following data: age, gender, reason for emergency department referral, presence of chest pain or dyspnea, previously known coronary arteries disease and severity in terms of vessels affected, cardiovascular risk factors (diabetes mellitus, dyslipidemia, arterial hypertension, smoking, obesity, positive family history for cardiovascular events), present medication (including platelet inhibitors and coumarin derivates), presence of electrocardiogram changes in the emergency department, and final diagnosis in the emergency department. Additionally, we obtained data on hospitalization and in-hospital mortality as well as results of coronary catheterization including interventions. Laboratory data including high-sensitive troponin T levels and serum creatinine levels were gathered. We calculated estimated glomerular filtration rate (eGFR) according to the Modification Diet in Renal Disease formula (MDRD). The diagnosis of ACS was made at the discretion of the emergency physician using patient history, physical examination, electrocardiogram, and laboratory values (i.e., high-sensitive value). If ACS was suspected, cardiologists were informed, who then usually hospitalized patients on their intermediate care ward for monitoring and treatment before potential coronary angiography. Only when patients were found to have AMI by both the emergency physician and the cardiologist on call were they considered positive.
All data were collected prospectively and administered in the research database of the Department of Emergency Medicine. Data are presented as means and SD or medians and first and third quartiles, as appropriate. Correlation between continuous variables was quantified by Pearson’s correlations coefficient. Sensitivity, specificity, positive and predictive values, test efficiency, and likelihood ratios were calculated using standard formulas. Area under the receiver operator characteristic curves and all other statistical operations were performed by SPSS version 17.0. A p value of <0.05 was considered to be significant for all analyses. The study was approved by our local institutional review board, the Ethics Commission of the Canton of Bern ( www.kek-bern.ch ).
Results
During the study period 1,514 patients received serial measurements of high-sensitive troponin T at the Department of Emergency Medicine, of which, 1,022 (67%) patients were men and 492 (33%) were women. Mean age was 65 years (SD 16). Most common types of admission were classified as cardiologic in 782 (52%) patients, neurologic in 236 (16%), and trauma in 125 (8%). Table 1 provides an overview on the types of admission to the emergency department. Symptoms suggestive of the presence of ACS (acute chest pain, dyspnea) were observed in 559 (37%) patients on admission to the emergency department, of which 447 (29%) patients had known coronary artery disease with 56 (13%) having 1 vessel, 78 (17%) 2 vessels, 101 (23%) 3 vessels, 13 (3%) 4 vessels, and 1 (0.2%) 5 vessels affected. One hundred ninety-eight (44%) patients had known coronary artery disease without further information on how many vessels were affected. Four hundred twenty-two (28%) patients had 1, 358 (24%) had 2, 192 (13%) had 3, 102 (7%) had 4, 33 (2%) had 5, and 1 (0.1%) patient had 6 cardiovascular risk factors.
| Admission Type | Number (1,514 Patients) | Percentage |
|---|---|---|
| Angiology | 24 | 2 |
| Endocrinology | 11 | 0.7 |
| Gastroenterology and hepatology | 42 | 3 |
| Hematology | 8 | 0.5 |
| Ear, nose, and throat | 12 | 0.8 |
| Infectious | 78 | 5 |
| Intoxication | 13 | 0.8 |
| Cardiology | 782 | 52 |
| Nephrology | 7 | 0.5 |
| Neurology | 236 | 16 |
| Oncology | 15 | 1 |
| Orthopedics | 13 | 0.9 |
| Psychiatry | 17 | 1 |
| Pulmology | 24 | 2 |
| Surgery | 38 | 3 |
| Trauma | 125 | 8 |
| Urology | 15 | 1 |
| Other | 54 | 4 |
Median serum creatinine level was 85 μmol/L (71 to 105) resulting in an MDRD-eGFR of 77 ml/min (59 to 95). Three hundred eighty-two patients (25%) had moderate to severe renal insufficiency with an eGFR of <60 ml/min. Known coronary artery disease, dyslipidemia, arterial hypertension, and diabetes mellitus were most significantly present in patients with an MDRD-eGFR of <60 ml/min (see Table 2 ). Significantly more patients with an MDRD-eGFR of <60 ml/min took acetylsalicylic acid (40% vs 30%, p = 0.0001), clopidogrel (12% vs 7%, p = 0.0012), and coumarin derivates (19% vs 8%, p <0.0001). Significantly more patients with an MDRD-eGFR of >60 ml/min presented with symptoms suggestive for ACS compared with patients with moderate to severe renal insufficiency (39% vs 31%, p = 0.005).
| Risk Factor | eGFR (ml/min) | p | |||
|---|---|---|---|---|---|
| <60 (n = 382) | >60 (n = 1,132) | ||||
| n | Percentage | n | Percentage | ||
| Known CAD | 162 | 42 | 285 | 25 | <0.0001 |
| Diabetes | 100 | 26 | 162 | 14 | <0.0001 |
| Dyslipidemia | 146 | 38 | 324 | 29 | 0.0005 |
| Hypertension | 272 | 71 | 549 | 48 | <0.0001 |
| Smoker | 101 | 26 | 339 | 30 | 0.1918 |
| Family history | 27 | 7 | 114 | 10 | 0.808 |
| Obesity | 50 | 13 | 109 | 10 | 0.0565 |
Median baseline high-sensitive troponin T was significantly higher in patients with moderate to severe renal insufficiency compared with those with an MDRD-eGFR of >60 ml/min (0.028 [0.017 to 0.058] vs 0.009 μg/L [0.003 to 0.024], p <0.0001). Accordingly, control values of high-sensitive troponin T were significantly higher in patients with an MDRD-eGFR of <60 ml/min (0.029 [0.017 to 0.062] vs 0.011 μg/L [0.003 to 0.028], p <0.0001). Percent changes between baseline and control measurements of high-sensitive troponin were similar between the 2 groups (0% [0 to 17] vs 0% [−8 to 14], p = 0.0759).
Of the 808 patients (321 with an MDRD eGFR of <60 ml/min, 40%) who had initial high-sensitive troponin T levels above the normal range (<0.014 μg/L), 176 (22%) had pathologies other than AMI, which could explain the elevation in high-sensitive troponin T levels. Table 3 gives an overview of the potential causes for the elevated high-sensitive troponin T at baseline.
| Noncardiac Causes of Troponin Elevation | Overall (%), n = 176 | eGFR (ml/min) | |
|---|---|---|---|
| <60 (n = 83) | >60 (n = 93) | ||
| Angina pectoris | 2 (1) | 2 (2) | 0 (0) |
| Aortic dissection | 2 (1) | 2 (2) | 0 (0) |
| Tachyarrhythmias | 32 (18) | 15 (18) | 17 (18) |
| Cardiac arrest | 1 (0.5) | 1 (1) | 0 (0) |
| Generalized seizures | 26 (15) | 8 (10) | 18 (19) |
| Acute heart failure | 40 (23) | 23 (28) | 17 (18) |
| Hypertensive emergencies | 20 (11) | 9 (11) | 11 (12) |
| CAD | 11 (6) | 7 (8) | 4 (4) |
| Cocaine | 1 (0.5) | 0 (0) | 1 (1) |
| Peri- or myocarditis | 6 (3) | 1 (1) | 5 (5) |
| Pulmonary embolism | 9 (5) | 5 (6) | 4 (4) |
| Rhabdomyolysis | 4 (2) | 2 (2) | 2 (2) |
| Shock | 2 (1) | 1 (1) | 1 (1) |
| Sepsis | 9 (5) | 5 (6) | 4 (4) |
| Thoracic trauma | 11 (6) | 2 (2) | 9 (10) |
High-sensitive troponin T correlated significantly with MDRD-eGFR (R = −0.1, p <0.0001) and with serum creatinine concentrations (R = 0.23, p <0.0001) for all patients, but the correlation was poor (see Figure 1 ). Excluding patients with AMI, high-sensitive troponin T correlated better with MDRD-eGFR (R = −0.12, p <0.0001) and serum creatinine level (R = 0.33, p <0.0001). Figure 1 shows the correlations between high-sensitive troponin T and serum creatinine level or MDRD-eGFR in patients without AMI, respectively.
