Determinants of High‐Sensitivity Cardiac Troponin T and I in US Children and Adolescents

Traditional cardiovascular risk factors are strongly associated with elevations in high‐sensitivity cardiac troponin T (hs‐cTnT) and I (hs‐cTnI) in the general adult population. However, determinants of elevated cardiac troponin in pediatric populations remain unclear. Prior studies have focused on infants in the clinical setting and have examined a limited range of correlates. ¹ Data on the determinants of cardiac troponin may provide insights into underlying mechanisms and advance our understanding of why levels differ across age and sex in youth. ² Our objective was to identify anthropomorphic and cardiometabolic measures that were associated with hs‐cTnT and hs‐cTnI among children and adolescents in the general US population.

The National Health and Nutrition Examination Survey (NHANES) is a nationally representative study of the noninstitutionalized US population. The National Center for Health Statistics institutional review board approved the study protocols, and all participants (or proxies) provided written informed consent. Data used in the present study are publicly available (https://wwwn.cdc.gov/Nchs/Nhanes/1999‐2000/SSTROP_A.XPT).

Our main analyses included participants aged 8 to 19 years with available measures of hs‐cTnT, hs‐cTnI, blood pressure, cholesterol, weight, and height (N=6762). Children younger than 8 years were excluded because clinical measures of interest were not systematically measured in these participants.

We measured hs‐cTnT and hs‐cTnI in stored serum samples collected in the 1999 to 2004 NHANES. Samples were stored at −80°C before measurement. hs‐cTnT was measured using the Gen 5 STAT assay (Roche Diagnostics; limit of detection, 3 ng/L). hs‐cTnI was measured using the ARCHITECT i2000SR (Abbott Laboratories; limit of detection, 1.7 ng/L). For the purpose of this study, we obtained and examined hs‐cTnT and hs‐cTnI concentrations below the limit of detection. Further details are available elsewhere. ²

Weight and height for age (z scores) were calculated using the 2000 Centers for Disease Control and Prevention growth charts. Body composition was assessed using whole‐body dual‐energy x‐ray absorptiometry in boys in 1999 to 2004 (n=3457) and girls in 2001 to 2004 (n=2251). Fat and lean mass index were calculated as fat or lean mass in kilograms divided by height in meters squared.

Up to 3 measurements of blood pressure were collected in youth 8 years and older. We calculated mean systolic and diastolic blood pressure using all available readings.

Serum cholesterol was measured enzymatically. We examined total cholesterol in all participants and triglycerides in youth 12 years and older who fasted overnight (n=3165).

Glycated hemoglobin was measured in youth 12 years and older (n=5471) and plasma glucose was assessed in youth 12 years and older who fasted overnight (n=2616).

We used quantile regression to characterize the association between correlates and hs‐cTnT and hs‐cTnI. We modeled correlates with restricted cubic splines, with 4 knots at the fifth, 35th 65th, and 95th percentiles. We used joint Wald tests to assess whether any splines terms differed significantly from zero and tested for interactions by participant sex for all correlates (modeled using splines). We observed significant sex interactions for all correlates (all P<0.01); therefore, we presented all results stratified by sex. All analyses were also age adjusted and used recommended survey weights to generate results representative of the US pediatric population. We calculated robust standard errors using Taylor Series linearization. Stata version 17.0 (StataCorp LLC) was used for analyses, and a 2‐sided P value <0.05 was considered statistically significant.

Among US youth, 24% and 82% had hs‐cTnT and hs‐cTnI concentrations below the limit of detection. hs‐cTnT and hs‐cTnI concentrations were stable in girls but were higher in older children after age ≈12 years in boys (Figure [A] and [B]). After age adjustment, weight, height, and lean mass were positively associated with hs‐cTnT and hs‐cTnI for boys (Figure [C] through [H]). In contrast, fat mass (Figure [I] and [J]) and measures of cardiometabolic health were generally not significantly associated with hs‐cTnT or hs‐cTnI (data not shown).

Figure . Associations between age, anthropometric measures, and body composition with hs‐cTnT and hs‐cTnI in US youth aged 8 to 19 years, by sex, NHANES 1999 to 2004.

A and B, association between age (years) and hs‐cTnT and hs‐cTnI; C and D, association between body weight (z score) and hs‐cTnT and hs‐cTnI; E and F, association between height (z score) and hs‐cTnT and hs‐cTnI; G and H, association between lean mass index (kg/m²) and hs‐cTnT and hs‐cTnI; and I and J, association between fat mass index (kg/m²) and hs‐cTnT and hs‐cTnI. All models were estimated separately for boys and girls. All exposures were modeled as restricted cubic splines with knots at the fifth, 35th, 65th, and 95th percentiles. Estimates in panels C–J were adjusted for age. P values were calculated using joint Wald tests that assessed whether any splines terms differed significantly from zero. *Height and weight z scores were calculated using the 2000 Centers for Disease Control and Prevention growth charts. †Body composition data were not available in girls in the 1999 to 2000 NHANES. hs‐cTnI indicates high‐sensitivity cardiac troponin I; hs‐cTnT, high‐sensitivity cardiac troponin T; and NHANES, National Health and Nutrition Examination Survey.

Among US youth, mean hs‐cTn concentrations were higher in older children for boys but not girls. Body size and lean mass were positively associated with hs‐cTn in boys, independent of age.

The heart grows significantly during childhood in response to rapid physical growth and development. ³ Increasing heart size may contribute to higher levels of cardiac troponin in heathy youth. The positive association between body size and hs‐cTn may therefore reflect differences in heart size and development. Sex differences in cardiac troponin may also be related to differential heart growth. While heart size is similar before puberty, left ventricular mass grows faster for boys after puberty, ⁴ potentially explaining why differences increased after the age of ≈12 years.

Sex hormones may also contribute to age and sex differences. Testosterone levels increase rapidly in boys after the age of 12 years, and emerging data have linked this hormone to elevated hs‐cTn levels in adults. ⁵

Study limitations included the cross‐sectional design, lack of echocardiographic data, and measurement of hs‐cTn from stored samples.

In this exploratory study, we found that physical growth and development may influence cardiac troponin levels in healthy youth.

Sources of Funding

This work was funded by a grant from the Foundation for the National Institutes of Health (NIH) Biomarkers Consortium to the Johns Hopkins Bloomberg School of Public Health (principal investigator: E.S.). The Foundation for the NIH received support for this project from Abbott Laboratories, AstraZeneca, Johnson & Johnson, the National Dairy Council, Ortho Clinical Diagnostics, Roche Diagnostics, and Siemens Healthcare Diagnostics. E.S. was also support by NIH/National Heart, Lung, and Blood Institute grant K24 HL152440. M.F. was supported by K01 DK138273.

Disclosures

R.H. Christenson has received grant support from Roche Diagnostics, Fujirebio Diagnostics, Beckman Coulter, Siemens Healthcare Diagnostics, Ortho Clinical Diagnostics, Becton Dickinson, Abbott Diagnostics, Mitsubishi, and Horiba Medical; and has consulting agreements with PixCell, Beckman Coulter, Quidel, Siemens Healthineers, and Roche Diagnostics. The remaining authors have no disclosures to report.