Matthias Bossard1,2,3,4, Sébastien Thériault4,5, Stefanie Aeschbacher2,6, Tobias Schoen1,2, Seraina Kunz2, Mirco von Rotz2,6, Joel Estis7, John Todd7, Martin Risch8,9, Christian Mueller1,2,6, Lorenz Risch8,10,11, Guillaume Paré4,5, David Conen12,13,14. 1. Cardiology Division, Department of Medicine, University Hospital Basel, Petersgraben 4, 4031, Basel, Switzerland. 2. Cardiovascular Research Institute Basel, University Hospital Basel, Spitalstrasse 2, 4031, Basel, Switzerland. 3. Division of Cardiology, Hamilton General Hospital, Hamilton Health Sciences, 237 Barton Street East, Hamilton, ON, L8L 2X2, Canada. 4. Population Health Research Institute, David Braley Cardiac, Vascular and Stroke Research Institute, 237 Barton Street East, Hamilton, ON, L8L 2X2, Canada. 5. Department of Pathology and Molecular Medicine, Michael G. DeGroote School of Medicine, McMaster University, 1280 Main Street West, Hamilton, ON, L8S 4K1, Canada. 6. Division of Internal Medicine, Department of Medicine, University Hospital Basel, Petersgraben 4, 4031, Basel, Switzerland. 7. Singulex Inc, Clinical Research, 1701 Harbor Bay Pkwy 200, Alameda, CA, 94502, USA. 8. Labormedizinisches Zentrum Dr. Risch, Landstrasse 157, 9494, Schaan, Principality of Liechtenstein. 9. Division of Laboratory Medicine, Kantonsspital Graubünden, 7000, Chur, Switzerland. 10. Division of Clinical Biochemistry, Medical University, 6020, Innsbruck, Austria. 11. Private University, Dorfstrasse 24, 9495, Triesen, Principality of Liechtenstein. 12. Cardiology Division, Department of Medicine, University Hospital Basel, Petersgraben 4, 4031, Basel, Switzerland. david.conen@usb.ch. 13. Cardiovascular Research Institute Basel, University Hospital Basel, Spitalstrasse 2, 4031, Basel, Switzerland. david.conen@usb.ch. 14. Division of Internal Medicine, Department of Medicine, University Hospital Basel, Petersgraben 4, 4031, Basel, Switzerland. david.conen@usb.ch.
Abstract
BACKGROUND: Determinants of cardiomyocyte injury as quantified by high-sensitivity cardiac troponin I (cTnI) in young and healthy individuals, and sex-specific 99th percentiles are largely unknown. METHODS: Our study included 2077 adults from the general population aged 25-41 years without cardiovascular disease. cTnI was measured using a high-sensitivity assay. We performed stepwise backward linear regression analyses to identify variables independently associated with hs-cTnI levels, and calculated narrow-sense heritability from 1638-genotyped participants. RESULTS: Median age was 37 years. cTnI was quantifiable in all but 11 participants (99.5 %). Median (interquartile range) cTnI was significantly higher in men than in women [0.99 (0.71; 1.65) versus 0.47 (0.33; 0.71) ng/L, p < 0.0001]. The 99th percentile of cTnI was 15.79 ng/L in men and 5.11 ng/L in women. Out of 46 variables, 22 independent determinants for cTnI were identified. The strongest associations were observed with sex, age, systolic blood pressure, heart rate, left ventricular mass, N-terminal pro B-type natriuretic peptide, and creatine kinase (all p < 0.0001). The final model explained 36 % of the overall cTnI variability. Heritability of cTnI was estimated to be 29 % (p = 0.005), but became non-significant when the residuals of the multivariable model were used for analysis (5 %, p = 0.36). CONCLUSIONS: Sex, age, and systolic blood pressure belong to the strongest determinants of hs-cTnI in healthy adults. The 99th percentile was three times higher in men compared to women. Hence, sex-specific cut-off values may be preferable when applying hs-cTnI for screening purposes. Our results may also improve the interpretation of cTn levels in daily clinical practice.
BACKGROUND: Determinants of cardiomyocyte injury as quantified by high-sensitivity cardiac troponin I (cTnI) in young and healthy individuals, and sex-specific 99th percentiles are largely unknown. METHODS: Our study included 2077 adults from the general population aged 25-41 years without cardiovascular disease. cTnI was measured using a high-sensitivity assay. We performed stepwise backward linear regression analyses to identify variables independently associated with hs-cTnI levels, and calculated narrow-sense heritability from 1638-genotyped participants. RESULTS: Median age was 37 years. cTnI was quantifiable in all but 11 participants (99.5 %). Median (interquartile range) cTnI was significantly higher in men than in women [0.99 (0.71; 1.65) versus 0.47 (0.33; 0.71) ng/L, p < 0.0001]. The 99th percentile of cTnI was 15.79 ng/L in men and 5.11 ng/L in women. Out of 46 variables, 22 independent determinants for cTnI were identified. The strongest associations were observed with sex, age, systolic blood pressure, heart rate, left ventricular mass, N-terminal pro B-type natriuretic peptide, and creatine kinase (all p < 0.0001). The final model explained 36 % of the overall cTnI variability. Heritability of cTnI was estimated to be 29 % (p = 0.005), but became non-significant when the residuals of the multivariable model were used for analysis (5 %, p = 0.36). CONCLUSIONS: Sex, age, and systolic blood pressure belong to the strongest determinants of hs-cTnI in healthy adults. The 99th percentile was three times higher in men compared to women. Hence, sex-specific cut-off values may be preferable when applying hs-cTnI for screening purposes. Our results may also improve the interpretation of cTn levels in daily clinical practice.
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