Clinical Features and Outcomes of Emergency Department Patients With High-Sensitivity Cardiac Troponin I Concentrations Within Sex-Specific Reference Intervals
Authors: Yader Sandoval, Stephen W. Smith, Anne Sexter, Ian L. Gunsolus, Karen Schulz, Fred S. Apple
Journal: Circulation (2019)

troponin Clinical implications of measurable cardiac troponin (cTn) within the reference interval in emergency department patients remain uncertain.Using highsensitivity (hs) cTnI, our goals were 3-fold.First, we examined clinical features of patients with hs-cTnI within sex-specific reference intervals.Second, we examined the prognostic impact of hs-cTnI within sex-specific reference intervals using baseline and serial measurements.Third, using hs-cTnI reference change values (RCVs; biological variation), we determined the prognostic impact of serial changes within sex-specific intervals.After obtaining institutional review board approval and confirmation of patient disclosure agreement for specimen use (residual waste specimens), we studied emergency department patients with serial cTnI (UTROPIA [Use of Abbott High Sensitivity Troponin I Assay in Acute Coronary Syndromes], clinicaltrials.govunique identifier NCT02060760).Design and primary results have been reported. 1This is a post hoc analysis focused on patients with serial hs-cTnI less than or equal to the sex-specific 99th percentile upper-reference limits (URLs) in whom myocardial injury and infarction were excluded. 2The limit of detection (LoD) of the hs-cTnI assay (Abbott) is 1.9 ng/L, and 99th percentile URLs are 16 ng/L for women and 34 ng/L for men.RCVs of 69% and -41% were used to interpret data produced by serial testing within the sex-specific reference ranges. 3Multivariable proportional hazards models (assumptions checked) with adjustment for age, sex, baseline hs-cTnI, diabetes mellitus, ischemic heart disease, hypertension, dyslipidemia, and congestive heart failure were constructed.A total of 1216 patients (58±15 years old, 41% women) met inclusion criteria.Compared with patients with baseline undetectable (<LoD) hs-cTnI (n=440), those with measurable (LoD to 99th percentile URLs; n=776) hs-cTnI within the reference range were older and more likely to have comorbidities.Compared with patients with baseline hs-cTnI less than the LoD, those with measurable hs-cTnI were at >3-fold higher risk of major adverse cardiac events (MACE; postdischarge death, myocardial infarction, unstable angina, revascularization, or congestive heart failure) at 180 days (1.6% [7/440] versus 9.0% [70/776], P<0.0001; adjusted hazard ratio [HR], 3.2; 95% CI, 1.4-7.3;P=0.005), predominantly because of more deaths (n=41) and congestive heart failure (n=19) among those with measurable hs-cTnI.At 30 days, 0.5% (2/440) with baseline hs-cTnI less than the LoD had MACE, whereas 3.0% (23/776) with measurable hs-cTnI had MACE, including 13 deaths.Both men and women with baseline measurable hs-cTnI had worse outcomes at 180 days than did those with undetectable concentrations (Figure , A andB).After adjustment, differences remained in men (adjusted HR, 4.3; 95% CI, 1.3-14.3;P=0.016) but not women (adjusted HR, 2.2; 95% CI, 0.7-6.9;P=0.19).No differences in MACE rates between men and women were observed in those with undetectable (1.4% versus 1.8%; P=1.0) or measurable (9.3% versus 8.6%; P=0.7)