Abstract
The use of cardiac troponins (cTn) is the gold standard for diagnosing myocardial infarction. Independent of myocardial infarction (MI), however, sex, age and kidney function affect cTn levels. Here we developed a method to adjust cTnI levels for age, sex, and renal function, maintaining a unified cut-off value such as the 99th percentile. A total of 4587 individuals enrolled in a prospective longitudinal study were used to develop a model for adjustment of cTn. cTnI levels correlated with age and estimated glomerular filtration rate (eGFR) in males/females with rage = 0.436/0.518 and with reGFR = −0.142/−0.207. For adjustment, these variables served as covariates in a linear regression model with cTnI as dependent variable. This adjustment model was then applied to a real-world cohort of 1789 patients with suspected acute MI (AMI) (N = 407). Adjusting cTnI showed no relevant loss of diagnostic information, as evidenced by comparable areas under the receiver operator characteristic curves, to identify AMI in males and females for adjusted and unadjusted cTnI. In specific patients groups such as in elderly females, adjusting cTnI improved specificity for AMI compared with unadjusted cTnI. Specificity was also improved in patients with renal dysfunction by using the adjusted cTnI values. Thus, the adjustments improved the diagnostic ability of cTnI to identify AMI in elderly patients and in patients with renal dysfunction. Interpretation of cTnI values in complex emergency cases is facilitated by our method, which maintains a single diagnostic cut-off value in all patients.
Highlights
Based on the derivation cohort, we created a mathematical model that allows contemporary sensitive cTnI (cs-cTnI) adjustment for the confounders age and kidney function in males and females. Applying this model to the derivation cohort eliminated the correlation between cs-cTnI and age or kidney function, as intended, for males (Supplementary Table 3) and females (Supplementary Table 4)
The specificity for acute MI (AMI) in patients older than 70 years improved by using the adjusted cs-cTnI, from 0.84 and 0.87 to 0.96 and 0.93 in males and females, respectively (Supplementary Table 9)
We developed a statistical model using data from more than 4000 individuals from an epidemiological study to account for age, sex, and renal function by adjusting cs-cTnI values
Summary
We aimed to develop a method to adjust cTnI levels for age, sex, and renal function prior to clinical application. Our goal was to keep a single diagnostic cTnI cut-off value. The aim of the present work was to provide a tool that accounts for the most important confounders of cTn concentrations and at the same time affords the use of a single clinical cut-off value
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