Coronary artery calcium: prognostic value for cardiovascular and non-cardiovascular diseases


DOI: https://dx.doi.org/10.18565/therapy.2021.6.81-90

Roytberg G.E., Slastnikova I.D., Davydova A.Sh.

N.I. Pirogov Russian National Research Medical University of the Ministry of Healthcare of Russia, Moscow
Abstract. Coronary calcification is a well-proved indicator of the presence of subclinical atherosclerosis. Article reflects the current viewpoint concerning scanning calcium in the coronary arteries – an important method for predicting cardiovascular events in asymptomatic persons and patients with suspected coronary heart disease. Specific features of a group of patients with an extremely high calcium index (CI >1000) are underlined, and the data from the largest-scale studies on the prognostic significance of coronary calcification for cardiovascular and non-cardiovascular diseases are presented. An expanded view of CI as a possible integral marker of a biological age of a person is presented.

Literature



  1. Ройтберг Г.Е., Струтынский А.В. Внутренние болезни. Сердечно-сосудистая система: учебное пособие. 7-е издание. М.: МЕДпресс-информ. 2021; 904 с. [Roitberg G.E., Strutynsky A.V. Internal illnesses. Cardiovascular system: a tutorial. 7th edition. Мoscow: MEDpress-inform. 2021; 904 pp. (In Russ.)]. ISBN: 978-5-00030-837-0.

  2. Agatston A.S., Janowitz W.R., Hildner F.J. et al. Quantification of coronary artery calcium using ultrafast computed tomography. J Am Coll Cardiol. 1990; 15(4): 827–32. doi: 10.1016/0735-1097(90)90282-t.

  3. Здравоохранение в России 2019. Статистический сборник. Росстат. М. 2019; 170 с. Доступ: https://rosstat.gov.ru/storage/mediabank/Zdravoohran-2019.pdf (дата обращения – 01.07.2021). [Healthcare in Russia 2019. Statistical collection. Federal State Statistics Service (Russia). Moscow. 2019; 170 pp. Available at: https://rosstat.gov.ru/storage/mediabank/Zdravoohran-2019.pdf (date of access – 01.07.2021) (In Russ.)]. ISBN: 978-5-89476-470-2.

  4. Greenland P., Blaha M.J., Budoff M.J. et al. Coronary calcium score and cardiovascular risk. J Am Coll Cardiol. 2018; 72(4): 434–47. doi: 10.1016/j.jacc.2018.05.027.

  5. Mitchell J.D., Paisley R., Moon P. et al. Coronary artery calcium and long-term risk of death, myocardial infarction, and stroke: The Walter Reed Cohort Study. JACC Cardiovasc Imaging. 2018; 11(12): 1799–806. doi: 10.1016/j.jcmg.2017.09.003.

  6. Carr J.J., Jacobs D.R. Jr, Terry J.G. et al. Association of coronary artery calcium in adults aged 32 to 46 years with incident coronary heart disease and death. JAMA Cardiol. 2017; 2(4): 391–99. doi: 10.1001/jamacardio.2016.5493.

  7. Grandhi G.R., Mirbolouk M., Dardari Z.A. et al. Interplay of coronary artery calcium and risk factors for predicting CVD/CHD mortality: The CAC Consortium. JACC Cardiovasc Imaging. 2020; 13(5): 1175–86. doi: 10.1016/j.jcmg.2019.08.024.

  8. Budoff M.J., Young R., Burke G. et al. Ten-year association of coronary artery calcium with atherosclerotic cardiovascular disease (ASCVD) events: the multi-ethnic study of atherosclerosis (MESA). Eur Heart J. 2018; 39(25): 2401–08. doi: 10.1093/eurheartj/ehy217.

  9. Valenti V., O Hartaigh B., Heo R. et al. A 15-year warranty period for asymptomatic individuals without coronary artery calcium: A prospective follow-up of 9,715 individuals. JACC Cardiovasc Imaging. 2015; 8(8): 900–09. doi: 10.1016/j.jcmg.2015.01.025.

  10. Peters S.A., Bakker M., den Ruijter H.M., Bots M.L. Added value of CAC in risk stratification for cardiovascular events: a systematic review. Eur J Clin Invest. 2012; 42(1): 110–16. doi: 10.1111/j.1365-2362.2011.02555.x.

  11. Blaha M.J., Matsushita K. Coronary artery calcium: Need for more clarity in guidelines. JACC Cardiovasc Imaging. 2017; 10(2): 154–56. doi: 10.1016/j.jcmg.2016.05.017.

  12. Orringer C.E., Maki K.C. HOPE for rational statin allocation for primary prevention: A coronary artery calcium picture is worth 1000 words. Mayo Clin Proc. 2020; 95(8): 1740–49. doi: 10.1016/j.mayocp.2020.01.016.

  13. Nasir K., Bittencourt M.S., Blaha M.J. et al. Implications of coronary artery calcium testing among statin candidates according to American College of Cardiology/American Heart Association cholesterol management guidelines: MESA (Multi-Ethnic Study of Atherosclerosis). J Am Coll Cardiol. 2015; 66(15): 1657–68. doi: 10.1016/j.jacc.2015.07.066.

  14. Mortensen M.B., Falk E., Li D. et al. Statin trials, cardiovascular events, and coronary artery calcification: Implications for a trial-based approach to statin therapy in MESA. JACC Cardiovasc Imaging. 2018; 11(2 Pt 1): 221–30. doi: 10.1016/j.jcmg.2017.01.029.

  15. Martin S.S., Blaha M.J., Blankstein R. et al. Dyslipidemia, coronary artery calcium, and incident atherosclerotic cardiovascular disease: implications for statin therapy from the multi-ethnic study of atherosclerosis. Circulation. 2014; 129(1): 77–86. doi: 10.1161/CIRCULATIONAHA.113.003625.

  16. Mortensen M.B., Fuster V., Muntendam P. et al. A simple disease-guided approach to personalize ACC/AHA-recommended statin allocation in elderly people: The BIOIMAGE study. J Am Coll Cardiol. 2016; 68(9): 881–91. doi: 10.1016/j.jacc.2016.05.084.

  17. Blaha M.J. Personalizing treatment: Between primary and secondary prevention. Am J Cardiol. 2016; 118(6 Suppl): 4A–12A. doi: 10.1016/j.amjcard.2016.05.026.

  18. Arnett D.K., Blumenthal R.S., Albert M.A. et al. 2019 ACC/AHA guideline on the primary prevention of cardiovascular disease: executive summary: a report of the American College of Cardiology/American Heart Association Task Force on Clinical Practice Guidelines. Circulation. 2019; 140: e563–e595. doi: 10.1161/CIR.0000000000000677.

  19. Mach F., Baigent C., Catapano A.L. et al.; ESC Scientific Document Group. 2019 ESC/EAS Guidelines for the management of dyslipidaemias: lipid modification to reduce cardiovascular risk: The Task Force for the management of dyslipidaemias of the European Society of Cardiology (ESC) and European Atherosclerosis Society (EAS). Eur Heart J. 2020; 41(1): 111–88. doi: 10.1093/eurheartj/ehz455.

  20. Parcha V., Malla G., Kalra R. et al. Coronary artery calcium score for personalization of antihypertensive therapy: A pooled cohort analysis. Hypertension. 2021; 77(4): 1106–18. doi: 10.1161/HYPERTENSIONAHA.120.16689.

  21. McEvoy J.W., Martin S.S., Dardari Z.A. et al. Coronary artery calcium to guide a personalized risk-based approach to initiation and intensification of antihypertensive therapy. Circulation. 2017; 135(2): 153–65. doi: 10.1161/CIRCULATIONAHA.116.025471.

  22. Peng A.W., Mirbolouk M., Orimoloye O.A. et al. Long-term all-cause and cause-specific mortality in asymptomatic patients with cac ≥1,000: Results from the CAC Consortium. JACC Cardiovasc Imaging. 2020; 13(1 Pt1): 83–93. doi: 10.1016/j.jcmg.2019.02.005.

  23. Peng A.W., Dardari Z.A., Blumenthal R.S. et al. Very high coronary artery calcium (≥1000) and association with cardiovascular disease events, non-cardiovascular disease outcomes, and mortality: Results from MESA. Circulation. 2021; 143(16): 1571–83. doi: 10.1161/CIRCULATIONAHA.120.050545.

  24. Engbers E.M., Timmer J.R., Ottervanger J.P. et al. Prognostic value of coronary artery calcium scoring in addition to single-photon emission computed tomographic myocardial perfusion imaging in symptomatic patients. Circ Cardiovasc Imaging. 2016; 9(5): e003966. doi: 10.1161/CIRCIMAGING.115.003966.

  25. Mittal T.K., Pottle A., Nicol E. et al. Prevalence of obstructive coronary artery disease and prognosis in patients with stable symptoms and a zero-coronary calcium score. Eur Heart J Cardiovasc Imaging. 2017; 18(8): 922–29. doi: 10.1093/ehjci/jex037.

  26. Villines T.C., Hulten E.A., Shaw L.J. et al; CONFIRM Registry Investigators. Prevalence and severity of coronary artery disease and adverse events among symptomatic patients with coronary artery calcification scores of zero undergoing coronary computed tomography angiography: results from the CONFIRM (Coronary CT Angiography Evaluation for Clinical Outcomes: An International Multicenter) registry. J Am Coll Cardiol. 2011; 58(24): 2533–40. doi: 10.1016/j.jacc.2011.10.851.

  27. Budoff M.J., Mayrhofer T., Ferencik M. et al; PROMISE Investigators. Prognostic Value of Coronary Artery Calcium in the PROMISE Study (Prospective Multicenter Imaging Study for Evaluation of Chest Pain). Circulation. 2017; 136(21): 1993–2005. doi: 10.1161/CIRCULATIONAHA.117.030578.

  28. Rozanski A., Berman D.S. Coronary artery calcium scanning in symptomatic patients: Ready for use as a gatekeeper for further testing? J Nucl Cardiol. 2017; 24(3): 835–38. doi: 10.1007/s12350-017-0794-2.

  29. Mouden M., Timmer J.R., Reiffers S. et al. Coronary artery calcium scoring to exclude flow-limiting coronary artery disease in symptomatic stable patients at low or intermediate risk. Radiology. 2013; 269(1): 77–83. doi: 10.1148/radiol.13122529.

  30. Ghadri J.R., Pazhenkottil A.P., Nkoulou R.N. et al. Very high coronary calcium score unmasks obstructive coronary artery disease in patients with normal SPECT MPI. Heart. 2011; 97(12): 998–1003. doi: 10.1136/hrt.2010.217281.

  31. Engbers E.M., Timmer J.R., Ottervanger J.P. Coronary artery calcium score as a gatekeeper in the non-invasive evaluation of suspected coronary artery disease in symptomatic patients. J Nucl Cardiol. 2017; 24(3): 826–31. doi: 10.1007/s12350-017-0792-4.

  32. Le V.T., Knight S., Min D.B. et al. Absence of coronary artery calcium during positron emission tomography stress testing in patients without known coronary artery disease identifies individuals with very low risk of cardiac events. Circ Cardiovasc Imaging. 2020; 13(1): e009907. doi: 10.1161/CIRCIMAGING.119.009907.

  33. Rubinshtein R., Gaspar T., Halon D.A. et al. Prevalence and extent of obstructive coronary artery disease in patients with zero or low calcium score undergoing 64-slice cardiac multidetector computed tomography for evaluation of a chest pain syndrome. Am J Cardiol. 2007; 99(4): 472–75. doi: 10.1016/j.amjcard.2006.08.060.

  34. Alshahrani A.M., Mahmood H., Wells G.A. et al. Point of care clinical risk score to improve the negative diagnostic utility of an Agatston score of zero: Averting the need for coronary computed tomography angiography. Circ Cardiovasc Imaging. 2019; 12(9): e008737. doi: 10.1161/CIRCIMAGING.118.008737.

  35. Lo-Kioeng-Shioe M.S., Rijlaarsdam-Hermsen D., van Domburg R.T. et al. Prognostic value of coronary artery calcium score in symptomatic individuals: A meta-analysis of 34,000 subjects. Int J Cardiol. 2020; 299: 56–62. doi: 10.1016/j.ijcard.2019.06.003.

  36. Handy C.E., Desai C.S., Dardari Z.A. et al. The association of coronary artery calcium with noncardiovascular disease: The multi-ethnic study of atherosclerosis. J Am Coll Cardiol Img. 2016; 9(5): 568–76. doi:10.1016/j.jcmg.2015.09.020.

  37. Whelton S.P., Rifai M.A., Marshall C.H. et al. Coronary artery calcium and the age-specific competing risk of cardiovascular versus cancer mortality: The coronary artery calcium consortium. Am J Med. 2020; 133(10): e575–e583. doi: 10.1016/j.amjmed.2020.02.034.

  38. Chen W.T., Huang J.H., Hsieh M.H., Chen Y.J. Extremely high coronary artery calcium score is associated with a high cancer incidence. Int J Cardiol. 2012; 155(3): 474–75. doi: 10.1016/j.ijcard.2011.12.077.

  39. Gal R., van Velzen S.G., Emaus M.J. et al. The risk of cardiovascular disease in irradiated breast cancer patients: The role of cardiac calcifications and adjuvant treatment. 2020 European Breast Cancer Conference. Abstract 7. Presented October 1, 2020.

  40. Fujiyoshi A., Jacobs D.R. Jr, Fitzpatrick A.L. et al. Coronary artery calcium and risk of dementia in MESA (Multi-Ethnic Study of Atherosclerosis). Circ Cardiovasc Imaging. 2017; 10(5): e005349. doi: 10.1161/CIRCIMAGING.116.005349.

  41. Kuller L.H., Lopez O.L., Mackey R.H. et al. Subclinical cardiovascular disease and death, dementia, and coronary heart disease in patients 80+ years. J Am Coll Cardiol. 2016; 67(9): 1013–22. doi: 10.1016/j.jacc.2015.12.034.

  42. Xia C., Vonder M., Sidorenkov G. et al. Coronary artery calcium and cognitive function in Dutch adults: Cross-sectional results of the population-based ImaLife Study. J Am Heart Assoc. 2021; 10(4): e018172. doi: 10.1161/JAHA.120.018172.

  43. Giannini F., Toselli M., Palmisano A. et al. Coronary and total thoracic calcium scores predict mortality and provides pathophysiologic insights in COVID-19 patients. J Cardiovasc Comput Tomogr. 2021: S1934-5925(21)00032-0. doi: 10.1016/j.jcct.2021.03.003.


About the Autors


Grigori E. Roytberg, MD, professor, academician of RAS, head of the Department of therapy, general practice and nuclear medicine, N.I. Pirogov Russian National Research Medical University of the Ministry of Healthcare of Russia. Address: 117997, Moscow, 1 Ostrovityaninova Str. Tel.: +7 (495) 251-56-84. ORCID: 0000-0003-0514-9114
Irina D. Slastnikova, PhD, associate professor of the Department of therapy, general practice and nuclear medicine, N.I. Pirogov Russian National Research Medical University of the Ministry of Healthcare of Russia. Address: 117997, Moscow, 1 Ostrovityaninova Str. Tel.: +7 (495) 251-56-84. E-mail: slastid@mail.ru. ORCID: 0000-0002-4076-2849
Alina Sh. Davydova, postgraduate student of the Department of therapy, general practice and nuclear medicine, N.I. Pirogov Russian National Research Medical University of the Ministry of Healthcare of Russia. Address: 117997, Moscow, 1 Ostrovityaninova Str. Tel.: +7 (917) 507-07-46. E-mail: alina.tsyganova@gmail.com. ORCID: 0000-0002-5738-0740


Similar Articles


Бионика Медиа