Prognostic significance of troponin I in assessing cardiovascular risk in the Russian population. Data from ESSE-RF1 and ESSE-RF2 multicenter studies

Aim. To assess the significance of troponin I (hs-cTnI) for cardio­vascular risk stratification in a population of Russian working-age men and women of.

Material and methods. The data of 13976 men and women aged 25-64 from the ESSE-RF1 and ESSE-RF2 multicenter studies were analyzed. The examination included following points: standard questionnaire, measurements of height, weight, waist circumference, body mass index, blood pressure, pulse rate, biochemical tests. The level of hs-cTnI in blood serum samples stored at -70^оC in the Biobank of the National Medical Research Center for Therapy and Preventive Medicine was determined by chemiluminescent immunoassay analysis. Individual cardiovascular risk was calculated using the SCORE scale: values <1% — low risk; 1-4% — moderate, 5-9% — high and ≥10% very high. Similar to the BiomarCaRE study, participants were divided into 3 sex-adjusted cTnI levels: men <6, 6 to 12, and >12 pg/ml; women <4, 4 to 10, and >10 pg/ml. We analyzed following hard endpoints: cardiovascular death or non-fatal myocardial infarction, and composite endpoint: the same and stroke.

Results. The prospective analysis of the relationship between troponin levels and endpoints and composite endpoints showed that in participants without prior CVD, hs-cTnI levels >12 pg/ml in men and >10 pg/ml in women are associated with an increased risk of endpoints and composite endpoints by 3,39 (1,91-6,03) and 2,69 (1,6-4,52) times (p<0,001), respectively. Similarly to BiomarCaRE, the SCORE-calculated risk reclassification was validated by adding the hs-cTnI value. The net reclassification improvement index (NRI) for endpoints and composite endpoints was 13% and 11% (p<0,001), respectively. Among men, the reclassification for NRI composite endpoints was more accurate than among women: 19% and 11%, respectively.

Conclusion. The hs-cTnI level is an independent predictor of myo­cardial infarction, stroke, and death from CVD in people aged 35-64 years without prior CVD. Adding the hs-cTnI level to the SCORE model makes the risk prediction more accurate.

1. Wilson PW, D’Agostino R, Levy D. Prediction of coronary heart disease using risk factor categories. Circulation. 1998;97(18):1837-47. doi:10.1161/01.cir.97.18.1837.

2. Conroy RM, Pyorala K, Fitzgerald AP, et al. Estimation of ten-year risk of fatal cardiovascular disease in Europe: the SCORE project. Eur Heart J. 2003;24:987-1003. doi:10.1016/s0195-668x(03)00114-3.

3. Hippisley-Cox C, Coupland Y, Vinogradova Y. Predicting cardiovascular risk in England and Wales: prospective derivation and validation of QRISK2. BMJ. 2008;336(7659):1475-82. doi:10.1136/bmj.39609.449676.25.

4. Sachdeva A, Cannon CP, Deedwania PC, et al. Lipid levels in patients hospitalized with coronary artery disease: an analysis of 136,905 hospitalizations in Get with The Guidelines. Am Heart J. 2009;157(1):111-7.e2. doi:10.1016/j.ahj.2008.08.010.

5. Gerszten RE, Wang TJ. The search for new cardiovascular biomarkers. Nature. 2008;451:949-52. doi:10.1038/nature06802.

6. Apple FS, Ler R, Murakami MM. Determination of 19 cardiac troponin I and T assay 99th percentile values from a common presumably healthy population. Clin Chem. 2012;58:1574-81. doi:10.1373/clinchem.2012.192716.

7. Collinson PO, Saenger AK, Apple FS; on behalf of the IFCC C-CB. High sensitivity, contemporary, and point-of-care cardiac troponin assays: educational aids from the IFCC Committee in Cardiac Biomarkers (IFCC C-CB). Clin Chem Lab Med. 2019;57:623-32. doi:10.1515/cclm-2018-1211.

8. Jia X, Sun W, Hoogeveen RC, et al. High-Sensitivity Troponin I and Incident Coronary Events, Stroke, Heart Failure Hospitalization, and Mortality in the ARIC Study. Circulation. 2019;139(23):2642-53. doi:10.1161/CIRCULATIONAHA.118.038772.

9. Omland T, de Lemos JA, Holmen OL, et al. Impact of sex on the prognostic value of high-sensitivity cardiac troponin I in the general population: the HUNT study. Clin Chem. 2015;61:646-56. doi:10.1373/clinchem.2014.234369.

10. Lyngbakken MN, Rosjo H, Holmen OL, et al. Gender, high-sensitivity troponin I, and the risk of cardiovascular events (from the Nord-Trondelag Health Study). Am J Cardiol. 2016;118:816-21. doi:10.1016/j.amjcard.2016.06.043.

11. Blankenberg S, Salomaa V, Makarova N, et al. Troponin I and cardiovascular risk prediction in the general population: The BiomarCaRE consortium. Eur Heart J. 2016;37:2428-37. doi:10.1093/eurheartj/ehw172.

12. Farmakis D, Mueller C, Apple FS, et al. High-sensitivity cardiac troponin assays for cardiovascular risk stratification in the gene­ral population. Eur Heart J. 2020;41(41):4050-6. doi:10.1093/eurheartj/ehaa083.

13. Shalnova SA, Drapkina OM, Kontsevaya AV, et al. A pilot project to study troponin I in a representative sample of the region from the ESSE-RF study: distribution among population and associations with risk factors. Cardiovascular Therapy and Prevention 2021;20(4):2940. (In Russ.) doi:10.15829/1728-8800-2021-2940.

14. Shalnova SA, Drapkina OM, Kontsevaya AV, et al. A pilot project to study the association of troponin I with cardiovascular complications in the population of the Russian region. Cardiovascular Therapy and Prevention 2021;20(5):2980. (In Russ.) doi:10.15829/1728-8800-2021-2980.

15. Scientific Organizing Committee of the ESSE-RF. Epidemiolny of cardiovascular diseases in different regions of Russia (ESSE-RF). The rationale for and design of the study. Preventive Medicine 2013;6:25-34. (In Russ.)

16. Koenker R, Chernozhukov V, He X, Peng L. (Eds.). Handbook of Quantile Regression (1st ed.). Chapman and Hall/CRC. 2017. P. 483. ISBN 9781315120256. doi:10.1201/9781315120256.

17. Leening MJG, Vedder MM, Witteman JCM, et al. Net reclas­sification improvement: computation, interpretation, and cont­roversies: a literature review and clinician’s guide. Annals of internal medicine. 2014;160(2):122-31. doi:10.7326/M13-1522.

18. Thorsteinsdottir I, Aspelund T, Gudmundsson E, et al. High-sensitivity cardiac troponin I is a strong predictor of car­diovascular events and mortality in the AGES-Reykjavik com­munity-based cohort of older individuals. Clin Chem. 2016;62:623-30. doi:10.1373/clinchem.2015.250811.

19. Eggers KM, Johnston N, Lind L, et al. Cardiac troponin I levels in an elderly population from the community — the implications of sex. Clin Biochem. 2015;48:751-6. doi:10.1016/j.clinbiochem.2015.04.013.