Highly-Sensitive Cardiac Troponin-I and Beta-2-Glycoprotein-I IgA Antibodies May Guide Atherosclerosis Screening and Surveillance in Rheumatoid Arthritis
Main Article Content
Abstract
Methods. The sample included 144 patients with complete biomarker data who underwent plaque evaluation with coronary computed tomography angiography; 95 were re-imaged within 6.9±0.3 years. Presence of >5 segments with plaque or coronary artery calcium >100 constituted extensive disease; lesions rendering >50% stenosis were considered obstructive. The Framingham 2008 cardiovascular risk score was included in all models.
Results. Hs-cTnI added to the cardiovascular risk score increased area-under-the curve (AUC) from 0.710 to 0.729 and improved prediction accuracy for baseline plaque presence [Net Reclassification Improvement =0.538 (95% confidence interval 0.143-0.895)] and Integrated Discrimination Improvement (IDI) =0.035 (0.001-0.128). In contrast, a-b2GPI-IgA did not, and the combination offered no added benefit over hs-cTnI alone. While hs-cTnI alone did not predict plaque progression, a-b2GPI-IgA presence did (p=0.005), especially in patients with >median hs-cTnI (p=0.015). In patients with >median hs-cTnI, adding a-b2GPI-IgA to a cardiovascular risk score model predicting progression from non-extensive/non-obstructive to extensive/obstructive plaque increased AUC from 0.796 to 0.878 and improved model precision [IDI=0.277 (0.011-0.946)].
Conclusion. High hs-cTnI significantly improved prediction of baseline plaque presence and may trigger an initial non-invasive coronary atherosclerosis evaluation. A-b2GPI-IgA presence may justify a follow-up interrogation in patients with non-extensive, non-obstructive plaque at baseline.
Keywords:
Rheumatoid arthritis, cardiovascular disease, coronary plaque, atherosclerosis progression, computed tomography, highly-sensitive cardiac troponin-I, anti-beta-2-Glycoprotein-I IgA antibodies
Article Details
How to Cite
KARPOUZAS, George A et al.
Highly-Sensitive Cardiac Troponin-I and Beta-2-Glycoprotein-I IgA Antibodies May Guide Atherosclerosis Screening and Surveillance in Rheumatoid Arthritis.
Medical Research Archives, [S.l.], v. 11, n. 1, jan. 2023.
ISSN 2375-1924.
Available at: <https://esmed.org/MRA/mra/article/view/3536>. Date accessed: 20 apr. 2024.
doi: https://doi.org/10.18103/mra.v11i1.3536.
Section
Research Articles
The Medical Research Archives grants authors the right to publish and reproduce the unrevised contribution in whole or in part at any time and in any form for any scholarly non-commercial purpose with the condition that all publications of the contribution include a full citation to the journal as published by the Medical Research Archives.
References
1. Naranjo A, Sokka T, Descalzo MA, et al. Cardiovascular disease in patients with rheumatoid arthritis: results from the QUEST-RA study. Arthritis Res Ther. 2008;10(2):R30.
2. Crowson CS, Gabriel SE, Semb AG, et al. Rheumatoid arthritis-specific cardiovascular risk scores are not superior to general risk scores: a validation analysis of patients from seven countries. Rheumatology (Oxford). 2017;56(7):1102-1110.
3. Colaco K, Ocampo V, Ayala AP, et al. Predictive utility of cardiovascular risk prediction algorithms in inflammatory rheumatic diseases: a systematic review. J Rheumatol. 2020;47(6):928-938.
4. Karpouzas GA, Malpeso J, Choi TY, Li D, Munoz S, Budoff MJ. Prevalence, extent and composition of coronary plaque in patients with rheumatoid arthritis without symptoms or prior diagnosis of coronary artery disease. Ann Rheum Dis. 2014;73(10):1797-1804.
5. Karpouzas GA, Estis J, Todd J, Budoff MJ. Occult coronary plaque presence and burden predict cardiovascular events in patients with rheumatoid arthritis. Arthritis Rheumatol. 2017;69 (suppl 10).
6. Karpouzas GA, Estis J, Rezaeian P, Todd J, Budoff MJ. High-sensitivity cardiac troponin I is a biomarker for occult coronary plaque burden and cardiovascular events in patients with rheumatoid arthritis. Rheumatology (Oxford). 2018;57(6):1080-1088.
7. Karpouzas GA, Ormseth SR, Hernandez E, Budoff MJ. Biologics may prevent cardiovascular events in rheumatoid arthritis by Inhibiting coronary plaque formation and stabilizing high-risk lesions. Arthritis Rheumatol. 2020;72:1467-1475.
8. Nakazato R, Gransar H, Berman DS, et al. Statins use and coronary artery plaque composition: results from the International Multicenter CONFIRM Registry. Atherosclerosis. 2012;225(1):148-153.
9. SCOT-HEART investigators. CT coronary angiography in patients with suspected angina due to coronary heart disease (SCOT-HEART): an open-label, parallel-group, multicentre trial. Lancet. 2015;385(9985):2383-2391.
10. SCOT-HEART Investigators, Newby DE, Adamson PD, et al. Coronary CT angiography and 5-year risk of myocardial infarction. N Engl J Med. 2018;379(10):924-933.
11. Douglas PS, Hoffmann U, Lee KL, et al. PROspective Multicenter Imaging Study for Evaluation of chest pain: rationale and design of the PROMISE trial. Am Heart J. 2014;167(6):796-803.e1.
12. Karpouzas GA, Ormseth SR, Hernandez E, Bui VL, Budoff MJ. Beta-2-glycoprotein-I IgA antibodies predict coronary plaque progression in rheumatoid arthritis. Semin Arthritis Rheum. 2020;51(1):20-27.
13. Miyakis S, Lockshin MD, Atsumi T, et al. International consensus statement on an update of the classification criteria for definite antiphospholipid syndrome (APS). J Thromb Haemost. 2006;4(2):295-306.
14. Budoff MJ, Dowe D, Jollis JG, et al. Diagnostic performance of 64-multidetector row coronary computed tomographic angiography for evaluation of coronary artery stenosis in individuals without known coronary artery disease: results from the prospective multicenter ACCURACY (Assessment by Coronary Computed Tomographic Angiography of Individuals Undergoing Invasive Coronary Angiography) trial. J Am Coll Cardiol. 2008;52(21):1724-1732.
15. Leipsic J, Abbara S, Achenbach S, et al. SCCT guidelines for the interpretation and reporting of coronary CT angiography: a report of the Society of Cardiovascular Computed Tomography Guidelines Committee. J Cardiovasc Comput Tomogr. 2014;8(5):342-358.
16. Agatston AS, Janowitz WR, Hildner FJ, Zusmer NR, Viamonte M, Detrano R. Quantification of coronary artery calcium using ultrafast computed tomography. J Am Coll Cardiol. 1990;15(4):827-832.
17. Pagali SR, Madaj P, Gupta M, et al. Interobserver variations of plaque severity score and segment stenosis score in coronary arteries using 64 slice multidetector computed tomography: a substudy of the ACCURACY trial. J Cardiovasc Comput Tomogr. 2010;4(5):312-318.
18. Bittencourt MS, Hulten E, Ghoshhajra B, et al. Prognostic value of nonobstructive and obstructive coronary artery disease detected by coronary computed tomography angiography to identify cardiovascular events. Circ Cardiovasc Imaging. 2014;7(2):282-291.
19. D’Agostino RB, Vasan RS, Pencina MJ, et al. General cardiovascular risk profile for use in primary care: the Framingham Heart Study. Circulation. 2008;117(6):743-753.
20. Swainson MG, Batterham AM, Tsakirides C, Rutherford ZH, Hind K. Prediction of whole-body fat percentage and visceral adipose tissue mass from five anthropometric variables. PLoS One. 2017;12(5):e0177175.
21. Plank F, Friedrich G, Dichtl W, et al. The diagnostic and prognostic value of coronary CT angiography in asymptomatic high-risk patients: a cohort study. Open Heart. 2014;1(1):e000096.
22. Cho I, Al’Aref SJ, Berger A, et al. Prognostic value of coronary computed tomographic angiography findings in asymptomatic individuals: a 6-year follow-up from the prospective multicentre international CONFIRM study. Eur Heart J. 2018;39(11):934-941.
23. Piepoli MF, Hoes AW, Agewall S, et al. 2016 European Guidelines on cardiovascular disease prevention in clinical practice. Eur Heart J. 2016;37(29):2315-2381.
24. Taylor AJ, Cerqueira M, Hodgson JM, et al. ACCF/SCCT/ACR/AHA/ASE/ASNC/NASCI/SCAI/SCMR 2010 appropriate use criteria for cardiac computed tomography. A report of the American College of Cardiology Foundation Appropriate Use Criteria Task Force, the Society of Cardiovascular Computed Tomography, the American College of Radiology, the American Heart Association, the American Society of Echocardiography, the American Society of Nuclear Cardiology, the North American Society for Cardiovascular Imaging, the Society for Cardiovascular Angiography and Interventions, and the Society for Cardiovascular Magnetic Resonance. J Am Coll Cardiol. 2010;56(22):1864-1894.
25. Maradit-Kremers H, Crowson CS, Nicola PJ, et al. Increased unrecognized coronary heart disease and sudden deaths in rheumatoid arthritis: a population-based cohort study. Arthritis Rheum. 2005;52(2):402-411.
26. Agca R, Heslinga SC, Rollefstad S, et al. EULAR recommendations for cardiovascular disease risk management in patients with rheumatoid arthritis and other forms of inflammatory joint disorders: 2015/2016 update. Ann Rheum Dis. 2017;76(1):17-28.
27. Korosoglou G, Lehrke S, Mueller D, et al. Determinants of troponin release in patients with stable coronary artery disease: insights from CT angiography characteristics of atherosclerotic plaque. Heart. 2011;97(10):823-831.
28. Seifarth H, Schlett CL, Lehman SJ, et al. Correlation of concentrations of high-sensitivity troponin T and high-sensitivity C-reactive protein with plaque progression as measured by CT coronary angiography. J Cardiovasc Comput Tomogr. 2014;8(6):452-458.
29. Altintas S, Cardinaels EPM, Versteylen MO, et al. Unstable coronary plaque characteristics are associated with high-sensitivity cardiac troponin T and N-terminal Pro-Brain Natriuretic Peptide. J Cardiovasc Comput Tomogr. 2016;10(1):82-88.
30. Motoyama S, Ito H, Sarai M, et al. Plaque characterization by coronary computed tomography angiography and the likelihood of acute coronary events in mid-term follow-up. J Am Coll Cardiol. 2015;66(4):337-346.
31. Gu H, Gao Y, Wang H, et al. Sex differences in coronary atherosclerosis progression and major adverse cardiac events in patients with suspected coronary artery disease. J Cardiovasc Comput Tomogr. 2017;11(5):367-372.
32. Moore KJ, Tabas I. Macrophages in the pathogenesis of atherosclerosis. Cell. 2011;145(3):341-355. doi:10.1016/j.cell.2011.04.005
33. Matsuura E, Kobayashi K, Koike T, Shoenfeld Y. Autoantibody-mediated atherosclerosis. Autoimmun Rev. 2002;1(6):348-353.
34. Staub HL, Franck M, Ranzolin A, Norman GL, Iverson GM, von Mühlen CA. IgA antibodies to beta2-glycoprotein I and atherosclerosis. Autoimmun Rev. 2006;6(2):104-106.
35. Karpouzas GA, Ormseth SR, Hernandez E, Budoff MJ. Impact of cumulative inflammation, cardiac risk factors, and medication exposure on coronary atherosclerosis progression in rheumatoid arthritis. Arthritis Rheumatol. 2020;72(3):400-408.
36. Karpouzas GA, Ormseth SR, Hernandez E, Budoff MJ. The impact of statins on coronary atherosclerosis progression and long-term cardiovascular disease risk in rheumatoid arthritis. Rheumatology (Oxford). 2022;61(5):1857-1866.
2. Crowson CS, Gabriel SE, Semb AG, et al. Rheumatoid arthritis-specific cardiovascular risk scores are not superior to general risk scores: a validation analysis of patients from seven countries. Rheumatology (Oxford). 2017;56(7):1102-1110.
3. Colaco K, Ocampo V, Ayala AP, et al. Predictive utility of cardiovascular risk prediction algorithms in inflammatory rheumatic diseases: a systematic review. J Rheumatol. 2020;47(6):928-938.
4. Karpouzas GA, Malpeso J, Choi TY, Li D, Munoz S, Budoff MJ. Prevalence, extent and composition of coronary plaque in patients with rheumatoid arthritis without symptoms or prior diagnosis of coronary artery disease. Ann Rheum Dis. 2014;73(10):1797-1804.
5. Karpouzas GA, Estis J, Todd J, Budoff MJ. Occult coronary plaque presence and burden predict cardiovascular events in patients with rheumatoid arthritis. Arthritis Rheumatol. 2017;69 (suppl 10).
6. Karpouzas GA, Estis J, Rezaeian P, Todd J, Budoff MJ. High-sensitivity cardiac troponin I is a biomarker for occult coronary plaque burden and cardiovascular events in patients with rheumatoid arthritis. Rheumatology (Oxford). 2018;57(6):1080-1088.
7. Karpouzas GA, Ormseth SR, Hernandez E, Budoff MJ. Biologics may prevent cardiovascular events in rheumatoid arthritis by Inhibiting coronary plaque formation and stabilizing high-risk lesions. Arthritis Rheumatol. 2020;72:1467-1475.
8. Nakazato R, Gransar H, Berman DS, et al. Statins use and coronary artery plaque composition: results from the International Multicenter CONFIRM Registry. Atherosclerosis. 2012;225(1):148-153.
9. SCOT-HEART investigators. CT coronary angiography in patients with suspected angina due to coronary heart disease (SCOT-HEART): an open-label, parallel-group, multicentre trial. Lancet. 2015;385(9985):2383-2391.
10. SCOT-HEART Investigators, Newby DE, Adamson PD, et al. Coronary CT angiography and 5-year risk of myocardial infarction. N Engl J Med. 2018;379(10):924-933.
11. Douglas PS, Hoffmann U, Lee KL, et al. PROspective Multicenter Imaging Study for Evaluation of chest pain: rationale and design of the PROMISE trial. Am Heart J. 2014;167(6):796-803.e1.
12. Karpouzas GA, Ormseth SR, Hernandez E, Bui VL, Budoff MJ. Beta-2-glycoprotein-I IgA antibodies predict coronary plaque progression in rheumatoid arthritis. Semin Arthritis Rheum. 2020;51(1):20-27.
13. Miyakis S, Lockshin MD, Atsumi T, et al. International consensus statement on an update of the classification criteria for definite antiphospholipid syndrome (APS). J Thromb Haemost. 2006;4(2):295-306.
14. Budoff MJ, Dowe D, Jollis JG, et al. Diagnostic performance of 64-multidetector row coronary computed tomographic angiography for evaluation of coronary artery stenosis in individuals without known coronary artery disease: results from the prospective multicenter ACCURACY (Assessment by Coronary Computed Tomographic Angiography of Individuals Undergoing Invasive Coronary Angiography) trial. J Am Coll Cardiol. 2008;52(21):1724-1732.
15. Leipsic J, Abbara S, Achenbach S, et al. SCCT guidelines for the interpretation and reporting of coronary CT angiography: a report of the Society of Cardiovascular Computed Tomography Guidelines Committee. J Cardiovasc Comput Tomogr. 2014;8(5):342-358.
16. Agatston AS, Janowitz WR, Hildner FJ, Zusmer NR, Viamonte M, Detrano R. Quantification of coronary artery calcium using ultrafast computed tomography. J Am Coll Cardiol. 1990;15(4):827-832.
17. Pagali SR, Madaj P, Gupta M, et al. Interobserver variations of plaque severity score and segment stenosis score in coronary arteries using 64 slice multidetector computed tomography: a substudy of the ACCURACY trial. J Cardiovasc Comput Tomogr. 2010;4(5):312-318.
18. Bittencourt MS, Hulten E, Ghoshhajra B, et al. Prognostic value of nonobstructive and obstructive coronary artery disease detected by coronary computed tomography angiography to identify cardiovascular events. Circ Cardiovasc Imaging. 2014;7(2):282-291.
19. D’Agostino RB, Vasan RS, Pencina MJ, et al. General cardiovascular risk profile for use in primary care: the Framingham Heart Study. Circulation. 2008;117(6):743-753.
20. Swainson MG, Batterham AM, Tsakirides C, Rutherford ZH, Hind K. Prediction of whole-body fat percentage and visceral adipose tissue mass from five anthropometric variables. PLoS One. 2017;12(5):e0177175.
21. Plank F, Friedrich G, Dichtl W, et al. The diagnostic and prognostic value of coronary CT angiography in asymptomatic high-risk patients: a cohort study. Open Heart. 2014;1(1):e000096.
22. Cho I, Al’Aref SJ, Berger A, et al. Prognostic value of coronary computed tomographic angiography findings in asymptomatic individuals: a 6-year follow-up from the prospective multicentre international CONFIRM study. Eur Heart J. 2018;39(11):934-941.
23. Piepoli MF, Hoes AW, Agewall S, et al. 2016 European Guidelines on cardiovascular disease prevention in clinical practice. Eur Heart J. 2016;37(29):2315-2381.
24. Taylor AJ, Cerqueira M, Hodgson JM, et al. ACCF/SCCT/ACR/AHA/ASE/ASNC/NASCI/SCAI/SCMR 2010 appropriate use criteria for cardiac computed tomography. A report of the American College of Cardiology Foundation Appropriate Use Criteria Task Force, the Society of Cardiovascular Computed Tomography, the American College of Radiology, the American Heart Association, the American Society of Echocardiography, the American Society of Nuclear Cardiology, the North American Society for Cardiovascular Imaging, the Society for Cardiovascular Angiography and Interventions, and the Society for Cardiovascular Magnetic Resonance. J Am Coll Cardiol. 2010;56(22):1864-1894.
25. Maradit-Kremers H, Crowson CS, Nicola PJ, et al. Increased unrecognized coronary heart disease and sudden deaths in rheumatoid arthritis: a population-based cohort study. Arthritis Rheum. 2005;52(2):402-411.
26. Agca R, Heslinga SC, Rollefstad S, et al. EULAR recommendations for cardiovascular disease risk management in patients with rheumatoid arthritis and other forms of inflammatory joint disorders: 2015/2016 update. Ann Rheum Dis. 2017;76(1):17-28.
27. Korosoglou G, Lehrke S, Mueller D, et al. Determinants of troponin release in patients with stable coronary artery disease: insights from CT angiography characteristics of atherosclerotic plaque. Heart. 2011;97(10):823-831.
28. Seifarth H, Schlett CL, Lehman SJ, et al. Correlation of concentrations of high-sensitivity troponin T and high-sensitivity C-reactive protein with plaque progression as measured by CT coronary angiography. J Cardiovasc Comput Tomogr. 2014;8(6):452-458.
29. Altintas S, Cardinaels EPM, Versteylen MO, et al. Unstable coronary plaque characteristics are associated with high-sensitivity cardiac troponin T and N-terminal Pro-Brain Natriuretic Peptide. J Cardiovasc Comput Tomogr. 2016;10(1):82-88.
30. Motoyama S, Ito H, Sarai M, et al. Plaque characterization by coronary computed tomography angiography and the likelihood of acute coronary events in mid-term follow-up. J Am Coll Cardiol. 2015;66(4):337-346.
31. Gu H, Gao Y, Wang H, et al. Sex differences in coronary atherosclerosis progression and major adverse cardiac events in patients with suspected coronary artery disease. J Cardiovasc Comput Tomogr. 2017;11(5):367-372.
32. Moore KJ, Tabas I. Macrophages in the pathogenesis of atherosclerosis. Cell. 2011;145(3):341-355. doi:10.1016/j.cell.2011.04.005
33. Matsuura E, Kobayashi K, Koike T, Shoenfeld Y. Autoantibody-mediated atherosclerosis. Autoimmun Rev. 2002;1(6):348-353.
34. Staub HL, Franck M, Ranzolin A, Norman GL, Iverson GM, von Mühlen CA. IgA antibodies to beta2-glycoprotein I and atherosclerosis. Autoimmun Rev. 2006;6(2):104-106.
35. Karpouzas GA, Ormseth SR, Hernandez E, Budoff MJ. Impact of cumulative inflammation, cardiac risk factors, and medication exposure on coronary atherosclerosis progression in rheumatoid arthritis. Arthritis Rheumatol. 2020;72(3):400-408.
36. Karpouzas GA, Ormseth SR, Hernandez E, Budoff MJ. The impact of statins on coronary atherosclerosis progression and long-term cardiovascular disease risk in rheumatoid arthritis. Rheumatology (Oxford). 2022;61(5):1857-1866.