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30.08.2022 | Coronary Heart Disease (S. Virani and M. Al Rifai, Section Editors)

Extra-coronary Calcification and Cardiovascular Events: What Do We Know and Where Are We Heading?

verfasst von: Dixitha Anugula, Rhanderson Cardoso, Gowtham R. Grandhi, Ron Blankstein, Khurram Nasir, Mouaz Al-Mallah, Dipan J. Shah, Miguel Cainzos-Achirica

Erschienen in: Current Atherosclerosis Reports | Ausgabe 10/2022

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Abstract

Purpose of Review

The coronary artery calcium score is a guideline-endorsed aid for further risk stratification in the primary prevention of atherosclerotic cardiovascular disease. The non-contrast scan performed for detection of coronary artery calcium also gives an opportunity to visualize calcifications in the thoracic aorta and in the heart valves, at no additional cost or radiation exposure. The purpose of this review was to discuss the potential clinical value of measuring thoracic aortic calcification, aortic valve calcification, and mitral annulus calcification.

Recent Findings

After two decades of active research, all three calcifications have been extensively evaluated, across various cohorts. We discuss classic and recent studies, current knowledge gaps, and future directions in this space.

Summary

The added value of these measurements has traditionally been considered modest at best, and they are not currently discussed in relevant primary prevention guidelines in North America and Europe. However, recent studies evaluating high thoracic calcification thresholds and younger populations have further enriched this space. Specifically, some studies suggest that detection of severe thoracic aortic calcification may be helpful in further risk assessment and that detection of aortic valve calcifications may have important prognostic implications in younger individuals. Although more research is needed, particularly in larger young-to-middle-aged cohorts, future guidelines might consider including these features as risk-enhancing factors.

Erbel R, Budoff M. Improvement of cardiovascular risk prediction using coronary imaging: subclinical atherosclerosis: the memory of lifetime risk factor exposure. Eur Heart J. 2012;33(10):1201–13. https://doi.org/10.1093/eurheartj/ehs076.CrossRefPubMed

Greenland P, Blaha MJ, Budoff MJ, Erbel R, Watson KE. Coronary calcium score and cardiovascular risk. J Am Coll Cardiol. 2018;72(4):434–47. https://doi.org/10.1016/j.jacc.2018.05.027.CrossRefPubMedPubMedCentral

Nasir K, Cainzos-Achirica M. Role of coronary artery calcium score in the primary prevention of cardiovascular disease. BMJ. 2021;373:n776. https://doi.org/10.1136/bmj.n776.CrossRefPubMed

Agatston AS, Janowitz WR, Hildner FJ, Zusmer NR, Viamonte M Jr, Detrano R. Quantification of coronary artery calcium using ultrafast computed tomography. J Am Coll Cardiol. 1990;15(4):827–32. https://doi.org/10.1016/0735-1097(90)90282-t.CrossRefPubMed

Grundy SM, Stone NJ, Bailey AL, Beam C, Birtcher KK, Blumenthal RS, et al. 2018 AHA/ACC/AACVPR/AAPA/ABC/ACPM/ADA/AGS/APhA/ASPC/NLA/PCNA guideline on the management of blood cholesterol: a report of the American College of Cardiology/American Heart Association Task Force on clinical practice guidelines. Circulation. 2019;139(25):e1082–143. https://doi.org/10.1161/CIR.0000000000000625.CrossRefPubMed

Arnett DK, Blumenthal RS, Albert MA, Buroker AB, Goldberger ZD, Hahn EJ, et al. 2019 ACC/AHA guideline on the primary prevention of cardiovascular disease: a report of the American College of Cardiology/American Heart Association Task Force on clinical practice guidelines. Circulation. 2019;140(11):e596–646. https://doi.org/10.1161/CIR.0000000000000678.CrossRefPubMedPubMedCentral

Visseren FLJ, Mach F, Smulders YM, Carballo D, Koskinas KC, Bäck M, ESC National Cardiac Societies, ESC Scientific Document Group, et al. 2021 ESC guidelines on cardiovascular disease prevention in clinical practice. Eur Heart J. 2021;42(34):3227–337.CrossRef

Miedema MD, Duprez DA, Misialek JR, Blaha MJ, Nasir K, Silverman MG, et al. Use of coronary artery calcium testing to guide aspirin utilization for primary prevention: estimates from the multi-ethnic study of atherosclerosis. Circ Cardiovasc Qual Outcomes. 2014;7(3):453–60. https://doi.org/10.1161/CIRCOUTCOMES.113.000690.CrossRefPubMedPubMedCentral

McEvoy JW, Martin SS, Dardari ZA, Miedema MD, Sandfort V, Yeboah J, 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. https://doi.org/10.1161/CIRCULATIONAHA.116.025471.CrossRefPubMed

10.

Cainzos-Achirica M, Miedema MD, McEvoy JW, Al Rifai M, Greenland P, Dardari Z, et al. Coronary artery calcium for personalized allocation of aspirin in primary prevention of cardiovascular disease in 2019: the MESA Study (Multi-Ethnic Study of Atherosclerosis). Circulation. 2020;141(19):1541–53. https://doi.org/10.1161/CIRCULATIONAHA.119.045010.CrossRefPubMedPubMedCentral

11.

Mszar R, Nasir K, Santos RD. Coronary artery calcification in familial hypercholesterolemia: an opportunity for risk assessment and shared decision making with the power of zero? Circulation. 2020;142(15):1405–7. https://doi.org/10.1161/CIRCULATIONAHA.120.049057.CrossRefPubMed

12.

Ajufo E, Ayers CR, Vigen R, Joshi PH, Rohatgi A, de Lemos JA, Khera A. Value of coronary artery calcium scanning in association with the net benefit of aspirin in primary prevention of atherosclerotic cardiovascular disease. JAMA Cardiol. 2021;6(2):179–87. https://doi.org/10.1001/jamacardio.2020.4939.CrossRefPubMed

13.

Cardoso R, Dudum R, Ferraro RA, Bittencourt M, Blankstein R, Blaha MJ, et al. Cardiac computed tomography for personalized management of patients with type 2 diabetes mellitus. Circ Cardiovasc Imaging. 2020;13(9):e011365. https://doi.org/10.1161/CIRCIMAGING.120.011365.CrossRefPubMed

14.

Wong ND. Is there more to the calcium scan than just coronary calcium? JACC Cardiovasc Imaging. 2016;9(10):1186–7. https://doi.org/10.1016/j.jcmg.2016.01.031.CrossRefPubMed

15.

Blaha MJ, Mortensen MB, Kianoush S, Tota-Maharaj R, Cainzos-Achirica M. Coronary artery calcium scoring: is it time for a change in methodology? JACC Cardiovasc Imaging. 2017;10(8):923–37. https://doi.org/10.1016/j.jcmg.2017.05.007.CrossRefPubMed

16.

Stary HC, Chandler AB, Dinsmore RE, Fuster V, Glagov S, Insull W Jr, et al. A definition of advanced types of atherosclerotic lesions and a histological classification of atherosclerosis. A report from the Committee on Vascular Lesions of the Council on Arteriosclerosis, American Heart Association. Circulation. 1995;92(5):1355–74. https://doi.org/10.1161/01.cir.92.5.1355.CrossRefPubMed

17.

Wexler L, Brundage B, Crouse J, Detrano R, Fuster V, Maddahi J, et al. Coronary artery calcification: pathophysiology, epidemiology, imaging methods, and clinical implications. A statement for health professionals from the American Heart Association. Writing Group. Circulation. 1996;94(5):1175–92. https://doi.org/10.1161/01.cir.94.5.1175.CrossRefPubMed

18.

Falk E. Pathogenesis of atherosclerosis. J Am Coll Cardiol. 2006;47(8 Suppl):C7-12. https://doi.org/10.1016/j.jacc.2005.09.068.CrossRefPubMed

19.

Samady H, Eshtehardi P, McDaniel MC, Suo J, Dhawan SS, Maynard C, et al. Coronary artery wall shear stress is associated with progression and transformation of atherosclerotic plaque and arterial remodeling in patients with coronary artery disease. Circulation. 2011;124(7):779–88. https://doi.org/10.1161/CIRCULATIONAHA.111.021824.CrossRefPubMed

20.

Abedin M, Tintut Y, Demer LL. Vascular calcification: mechanisms and clinical ramifications. Arterioscler Thromb Vasc Biol. 2004;24(7):1161–70. https://doi.org/10.1161/01.ATV.0000133194.94939.42.CrossRefPubMed

21.

Doherty TM, Fitzpatrick LA, Inoue D, Qiao JH, Fishbein MC, Detrano RC, et al. Molecular, endocrine, and genetic mechanisms of arterial calcification. Endocr Rev. 2004;25(4):629–72. https://doi.org/10.1210/er.2003-0015.CrossRefPubMed

22.

O’Brien KD. Pathogenesis of calcific aortic valve disease: a disease process comes of age (and a good deal more). Arterioscler Thromb Vasc Biol. 2006;26(8):1721–8. https://doi.org/10.1161/01.ATV.0000227513.13697.ac.CrossRefPubMed

23.

Sell S, Scully RE. Aging changes in the aortic and mitral valves. histologic and histochemical studies, with observations on the pathogenesis of calcific aortic stenosis and calcification of the mitral annulus. Am J Pathol. 1965;46(3):345–65.PubMedPubMedCentral

24.

Nestico PF, Depace NL, Morganroth J, Kotler MN, Ross J. Mitral annular calcification: clinical, pathophysiology, and echocardiographic review. Am Heart J. 1984;107(5 Pt 1):989–96. https://doi.org/10.1016/0002-8703(84)90840-8.CrossRefPubMed

25.

Roberts WC, Perloff JK. Mitral valvular disease. A clinicopathologic survey of the conditions causing the mitral valve to function abnormally. Ann Intern Med. 1972;77(6):939–75. https://doi.org/10.7326/0003-4819-77-6-939.CrossRefPubMed

26.

Adler Y, Fink N, Spector D, Wiser I, Sagie A. Mitral annulus calcification–a window to diffuse atherosclerosis of the vascular system. Atherosclerosis. 2001;155(1):1–8. https://doi.org/10.1016/s0021-9150(00)00737-1.CrossRefPubMed

27.

Pawade T, Clavel MA, Tribouilloy C, Dreyfus J, Mathieu T, Tastet L, et al. Computed tomography aortic valve calcium scoring in patients with aortic stenosis. Circ Cardiovasc Imaging. 2018;11(3):e007146. https://doi.org/10.1161/CIRCIMAGING.117.007146.CrossRefPubMed

28.

Post W, Bielak LF, Ryan KA, Cheng YC, Shen H, Rumberger JA, et al. Determinants of coronary artery and aortic calcification in the Old Order Amish. Circulation. 2007;115(6):717–24. https://doi.org/10.1161/CIRCULATIONAHA.106.637512.CrossRefPubMedPubMedCentral

29.

McClelland RL, Chung H, Detrano R, Post W, Kronmal RA. Distribution of coronary artery calcium by race, gender, and age: results from the Multi-Ethnic Study of Atherosclerosis (MESA). Circulation. 2006;113(1):30–7. https://doi.org/10.1161/CIRCULATIONAHA.105.580696.CrossRefPubMed

30.

Allison MA, Budoff MJ, Nasir K, Wong ND, Detrano R, Kronmal R, et al. Ethnic-specific risks for atherosclerotic calcification of the thoracic and abdominal aorta (from the Multi-Ethnic Study of Atherosclerosis). Am J Cardiol. 2009;104(6):812–7. https://doi.org/10.1016/j.amjcard.2009.05.004.CrossRefPubMedPubMedCentral

31.

Allison MA, Cheung P, Criqui MH, Langer RD, Wright CM. Mitral and aortic annular calcification are highly associated with systemic calcified atherosclerosis. Circulation. 2006;113(6):861–6. https://doi.org/10.1161/CIRCULATIONAHA.105.552844.CrossRefPubMed

32.

Allison MA, Criqui MH, Wright CM. Patterns and risk factors for systemic calcified atherosclerosis. Arterioscler Thromb Vasc Biol. 2004;24(2):331–6. https://doi.org/10.1161/01.ATV.0000110786.02097.0c.CrossRefPubMed

33.

Tison GH, Blaha MJ, Nasir K. Atherosclerosis imaging in multiple vascular beds–enough heterogeneity to improve risk prediction? Atherosclerosis. 2011;214(2):261–3. https://doi.org/10.1016/j.atherosclerosis.2010.10.014.CrossRefPubMed

34.

Wong ND, Gransar H, Shaw L, Polk D, Moon JH, Miranda-Peats R, et al. Thoracic aortic calcium versus coronary artery calcium for the prediction of coronary heart disease and cardiovascular disease events. JACC Cardiovasc Imaging. 2009;2(3):319–26. https://doi.org/10.1016/j.jcmg.2008.12.010.CrossRefPubMed

35.

Budoff MJ, Nasir K, Katz R, Takasu J, Carr JJ, Wong ND, et al. Thoracic aortic calcification and coronary heart disease events: the multi-ethnic study of atherosclerosis (MESA). Atherosclerosis. 2011;215(1):196–202. https://doi.org/10.1016/j.atherosclerosis.2010.11.017.CrossRefPubMed

36.

Yeboah J, Carr JJ, Terry JG, Ding J, Zeb I, Liu S, et al. Computed tomography-derived cardiovascular risk markers, incident cardiovascular events, and all-cause mortality in nondiabetics: the Multi-Ethnic Study of Atherosclerosis. Eur J Prev Cardiol. 2014;21(10):1233–41. https://doi.org/10.1177/2047487313492065.CrossRefPubMed

37.•

Kim J, Budoff MJ, Nasir K, Wong ND, Yeboah J, Al-Mallah MH, et al. Thoracic aortic calcium, cardiovascular disease events, and all-cause mortality in asymptomatic individuals with zero coronary calcium: the Multi-Ethnic Study of Atherosclerosis (MESA). Atherosclerosis. 2017;257:1–8. https://doi.org/10.1016/j.atherosclerosis.2016.12.012. The study focused on CAC = 0 participants from MESA, and the findings suggested that TAC > 0 was not associated with ASCVD, CHD events, and all-cause mortality adjusting for traditional risk factors.CrossRefPubMed

38.

Allison MA, Hsi S, Wassel CL, Morgan C, Ix JH, Wright CM, Criqui MH. Calcified atherosclerosis in different vascular beds and the risk of mortality. Arterioscler Thromb Vasc Biol. 2012;32(1):140–6. https://doi.org/10.1161/ATVBAHA.111.235234.CrossRefPubMed

39.

Mahabadi AA, Lehmann N, Möhlenkamp S, Pundt N, Dykun I, Roggenbuck U, Heinz Nixdorf Investigative Group, et al. Noncoronary measures enhance the predictive value of cardiac CT above traditional risk factors and CAC score in the general population. JACC Cardiovasc Imaging. 2016;9(10):1177–85. https://doi.org/10.1016/j.jcmg.2015.12.024.CrossRefPubMed

40.

Santos RD, Rumberger JA, Budoff MJ, Shaw LJ, Orakzai SH, Berman D, et al. Thoracic aorta calcification detected by electron beam tomography predicts all-cause mortality. Atherosclerosis. 2010;209(1):131–5. https://doi.org/10.1016/j.atherosclerosis.2009.08.025.CrossRefPubMed

41.••

Han D, Kuronuma K, Rozanski A, Budoff MJ, Miedema MD, Nasir K, et al. Implication of thoracic aortic calcification over coronary calcium score regarding the 2018 ACC/AHA Multisociety cholesterol guideline: results from the CAC Consortium. Am J Prev Cardiol. 2021;8:100232. https://doi.org/10.1016/j.ajpc.2021.100232. Findings from this study suggest that a TAC score >300 can be useful in identifying individuals at increased risk of CVD death among those with CAC = 0.CrossRefPubMedPubMedCentral

42.

Obisesan OH, Osei AD, Berman D, Dardari ZA, Uddin SMI, Dzaye O, et al. Thoracic aortic calcium for the prediction of stroke mortality (from the Coronary Artery Calcium Consortium). Am J Cardiol. 2021;148:16–21. https://doi.org/10.1016/j.amjcard.2021.02.038.CrossRefPubMedPubMedCentral

43.

Blaha MJ, Budoff MJ, Rivera JJ, Khan AN, Santos RD, Shaw LJ, et al. Relation of aortic valve calcium detected by cardiac computed tomography to all-cause mortality. Am J Cardiol. 2010;106(12):1787–91. https://doi.org/10.1016/j.amjcard.2010.08.019.CrossRefPubMed

44.

Han D, Cordoso R, Whelton S, Rozanski A, Budoff MJ, Miedema MD, et al. Prognostic significance of aortic valve calcium in relation to coronary artery calcification for long-term, cause-specific mortality: results from the CAC Consortium. Eur Heart J Cardiovasc Imaging. 2021;22(11):1257–63. https://doi.org/10.1093/ehjci/jeaa336.CrossRefPubMed

45.

Owens DS, Budoff MJ, Katz R, Takasu J, Shavelle DM, Carr JJ, et al. Aortic valve calcium independently predicts coronary and cardiovascular events in a primary prevention population. JACC Cardiovasc Imaging. 2012;5(6):619–25. https://doi.org/10.1016/j.jcmg.2011.12.023.CrossRefPubMedPubMedCentral

46.•

Cainzos-Achirica M, Acquah I, Dardari Z, Mszar R, Greenland P, Blankstein R, et al. Long-term prognostic implications and role of further testing in adults aged ≤55 years with a coronary calcium score of zero (from the Multi-Ethnic Study of Atherosclerosis). Am J Cardiol. 2021;161:26–35. https://doi.org/10.1016/j.amjcard.2021.08.067. This study among MESA participants aged 45–55 years suggested that when present, AVC > 0 may identify a subgroup of younger adults at high ASCVD risk; however, replication in larger studies is needed as there were few participants with AVC > 0.CrossRefPubMed

47.

Kizer JR, Wiebers DO, Whisnant JP, Galloway JM, Welty TK, Lee ET, et al. Mitral annular calcification, aortic valve sclerosis, and incident stroke in adults free of clinical cardiovascular disease: the Strong Heart Study. Stroke. 2005;36(12):2533–7. https://doi.org/10.1161/01.STR.0000190005.09442.ad.CrossRefPubMed

48.

Kohsaka S, Jin Z, Rundek T, Boden-Albala B, Homma S, Sacco RL, Di Tullio MR. Impact of mitral annular calcification on cardiovascular events in a multiethnic community: the Northern Manhattan Study. JACC Cardiovasc Imaging. 2008;1(5):617–23. https://doi.org/10.1016/j.jcmg.2008.07.006.CrossRefPubMedPubMedCentral

49.

Tison GH, Guo M, Blaha MJ, McClelland RL, Allison MA, Szklo M, et al. Multisite extracoronary calcification indicates increased risk of coronary heart disease and all-cause mortality: The Multi-Ethnic Study of Atherosclerosis. J Cardiovasc Comput Tomogr. 2015;9(5):406–14. https://doi.org/10.1016/j.jcct.2015.03.012.CrossRefPubMedPubMedCentral

50.

Kianoush S, Al Rifai M, Cainzos-Achirica M, Al-Mallah MH, Tison GH, Yeboah J, et al. Thoracic extra-coronary calcification for the prediction of stroke: the Multi-Ethnic Study of Atherosclerosis. Atherosclerosis. 2017;267:61–7. https://doi.org/10.1016/j.atherosclerosis.2017.10.010.CrossRefPubMedPubMedCentral

51.

Hoffmann U, Massaro JM, D’Agostino RB Sr, Kathiresan S, Fox CS, O’Donnell CJ. Cardiovascular event prediction and risk reclassification by coronary, aortic, and valvular calcification in the Framingham Heart Study. J Am Heart Assoc. 2016;5(2):e003144. https://doi.org/10.1161/JAHA.115.003144.CrossRefPubMedPubMedCentral

52.

Bos D, Leening MJ, Kavousi M, Hofman A, Franco OH, van der Lugt A, et al. Comparison of atherosclerotic calcification in major vessel beds on the risk of all-cause and cause-specific mortality: the Rotterdam Study. Circ Cardiovasc Imaging. 2015;8(12):e003843. https://doi.org/10.1161/CIRCIMAGING.115.003843.CrossRefPubMed

53.

Iribarren C, Sidney S, Sternfeld B, Browner WS. Calcification of the aortic arch: risk factors and association with coronary heart disease, stroke, and peripheral vascular disease. JAMA. 2000;283(21):2810–5. https://doi.org/10.1001/jama.283.21.2810.CrossRefPubMed

54.

Tamarappoo BK, Lin A, Commandeur F, McElhinney PA, Cadet S, Goeller M, et al. Machine learning integration of circulating and imaging biomarkers for explainable patient-specific prediction of cardiac events: a prospective study. Atherosclerosis. 2021;318:76–82. https://doi.org/10.1016/j.atherosclerosis.2020.11.008.CrossRefPubMed

55.

Quer G, Arnaout R, Henne M, Arnaout R. Machine learning and the future of cardiovascular care: JACC state-of-the-art review. J Am Coll Cardiol. 2021;77(3):300–13. https://doi.org/10.1016/j.jacc.2020.11.030.CrossRefPubMedPubMedCentral

56.

Dey D, Slomka PJ, Leeson P, Comaniciu D, Shrestha S, Sengupta PP, Marwick TH. Artificial intelligence in cardiovascular imaging: JACC state-of-the-art review. J Am Coll Cardiol. 2019;73(11):1317–35. https://doi.org/10.1016/j.jacc.2018.12.054.CrossRefPubMedPubMedCentral

57.

Margolies L, Salvatore M, Hecht HS, Kotkin S, Yip R, Baber U, Bishay V, Narula J, Yankelevitz D, Henschke C. Digital mammography and screening for coronary artery disease. JACC Cardiovasc Imaging. 2016;9(4):350–60. https://doi.org/10.1016/j.jcmg.2015.10.022.CrossRefPubMed

58.

Iribarren C, Chandra M, Lee C, Sanchez G, Sam DL, Azamian FF, Cho HM, Ding H, Wong ND, Molloi S. Breast arterial calcification: a novel cardiovascular risk enhancer among postmenopausal women. Circ Cardiovasc Imaging. 2022;15(3):e013526. https://doi.org/10.1161/CIRCIMAGING.121.013526.CrossRefPubMed

59.

Hendriks EJ, Beulens JW, de Jong PA, van der Schouw YT, Sun WN, Wright CM, Criqui MH, Allison MA, Ix JH. Calcification of the splenic, iliac, and breast arteries and risk of all-cause and cardiovascular mortality. Atherosclerosis. 2017;259:120–7. https://doi.org/10.1016/j.atherosclerosis.2017.01.029.CrossRefPubMedPubMedCentral

Titel: Extra-coronary Calcification and Cardiovascular Events: What Do We Know and Where Are We Heading?
verfasst von: Dixitha Anugula
Rhanderson Cardoso
Gowtham R. Grandhi
Ron Blankstein
Khurram Nasir
Mouaz Al-Mallah
Dipan J. Shah
Miguel Cainzos-Achirica
Publikationsdatum: 30.08.2022
Verlag: Springer US
Erschienen in: Current Atherosclerosis Reports / Ausgabe 10/2022
Print ISSN: 1523-3804
Elektronische ISSN: 1534-6242
DOI: https://doi.org/10.1007/s11883-022-01051-5

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Extra-coronary Calcification and Cardiovascular Events: What Do We Know and Where Are We Heading?