Calcification of the heart arteries in coronary athero­sclerosis

Main Article Content

M. I. Lutay
I. P. Golikova
O. M. Lomakovsky
T. I. Gavrilenko


The review shows the participation of smooth muscle cells, macrophages, bone marrow stem cells in the calcification of arteries, the effect of microcalcifications and diffuse calcium accumulation on the vulnerability of plaque. The relationship between calcification of coronary arteries and such major factors of cardiovascular risk as age, hypercholesterolemia, diabetes mellitus has been clarified. Data on the effect of inflammation on calcium deposition in the vascular wall and the effect of statins on the calcification of atherosclerotic plaques are presented. Assessment of the presence and severity of vascular calcification can significantly improve the accuracy of the diagnosis of atherosclerosis and the prognosis of its course. Calcification mechanisms may be targets for pharmacological interventions, having significant impact on the development and progression of atherosclerosis.

Article Details


Atherosclerosis, calcification, heart arteries, inflammation, prognosis, statins


Коpyca NP, Dykun IJ. Possibilities of risk stratification of the development of complications of IHD in patients without severe clinical symptoms based on quantitative determination of calcium in the coronary arteries. Kardiologija:ot nauki k praktike [Cardiology: from science to practice ]. 2012;1:4–15 (in Russ.).

Lomakovsky ОМ, Golikova ІP, Gavrylenko ТІ, Pidgajna ОА, Ryzhkova НО, Bugaenko VV, Cyzh ОV, Lysenko GF. Systemic inflammation and calcification of coronary arteries in patients with stable ischemic heart disease. Ukrainskyi kardiolohichnyi zhurnal [Ukrainian Journal of Cardiology]. 2017;1:80 (in Ukr.).

Lutai МI, Golikova ІP. Calcification of coronary arteries and aorta in patients with chronic ischemic heart disease: age and gender characteristics, correlation with risk factors. Ukrainskyi kardiolohichnyi zhurnal [Ukrainian Journal of Cardiology]. 2017;1:25–30 (in Russ.).

Таlaeva ТV, Shumakov VА, Bratus VV. Vascular calcification: significance in pathogenesis, diagnosis, clinical course and prognosis of outcomes of atherosclerosis and ischemic heart disease. Ukrainskyi kardiolohichnyi zhurnal [Ukrainian Journal of Cardiology].2017;2:85–98 (in Russ.).

Abedin M, Tintut Y, Demer L. Vascular calcification: mechanisms and clinical ramifications. Arterioscler. Thromb. Vasе. Biol. 2004;24(7):1161–1170.

Aghagolzadeh P, Bachtler M, Bijarnia R, Jackson C, Smith ER, Odermatt A, Radpour R, Pasch A. Calcification of vascular smooth muscle cells is induced by secondary calciprotein particles and enhanced by tumor necrosis factor-α. Atherosclerosis. 2016;251:404–414.

Aikawa E1, Nahrendorf M, Figueiredo JL, Swirski FK, Shtatland T, Kohler RH, Jaffer FA, Aikawa M, Weissleder R. Osteogenesis associates with inflammation in early-stage atherosclerosis evaluated by molecular imaging in vivo. Circulation. 2007;116:2841–2850.

Arad Y, Goodman KJ, Roth M, Newstein D, Guerci AD. Coronary calcification, coronary disease risk factors, C-reactive protein, and atherosclerotic cardiovascular disease events: the St. Francis Heart Study. J. Am. Coll. Cardiol. 2005;46:158–165.

Bielinski SJ, Pankow JS, Li N, Hsu FC, Adar SD, Jenny NS, Bowden DW, Wasserman BA, Arnett D. ICAM1 and VCAM1 polymorphisms, coronary artery calcium, and circulating levels of soluble ICAM-1: The multi-ethnic study of atherosclerosis (MESA). Atherosclerosis. 2008;201(Issue 2):339–344.

Boström K, Watson KE, Horn S, Wortham C, Herman IM, Demer LL Bone morphogenetic protein expression in human atherosclerotic lesions. J. Clin. Invest. 1993;9(4):1800–1809.

Boström KI, Yao J, Guihard PJ, Blazquez-Medela AM, Yao Y. Endothelial-mesenchymal transition in atherosclerotic lesion calcification. Atherosclerosis. 2016;253:124–127.

Budoff MJ, Shaw LJ, Liu ST, Weinstein SR, Mosler TP, Tseng PH, Flores FR, Callister TQ, Raggi P, Berman DS. Long-term prognosis associated with coronary calcification: observations from a registry of 25,253 patients. J. Am. Coll. Cardiol. 2007;49:1860–1870.

Campos-Obando N, Kavousi M, Roeters van Lennep JE. Bone health and coronary artery calcification: The Rotterdam Study. Atherosclerosis 2015;241(Issue 1):278–283.

Cho I, Chang HJ, Ó Hartaigh B, Shin S, Sung JM, Lin FY, Achenbach S, Heo R, Berman DS, Budoff MJ, Callister TQ, Al-Mallah MH, Cademartiri F, Chinnaiyan K, Chow BJ, Dunning AM, DeLago A, Villines TC, Hadamitzky M, Hausleiter J, Leipsic J, Shaw LJ, Kaufmann PA, Cury RC, Feuchtner G, Kim YJ, Maffei E, Raff G, Pontone G, Andreini D, Min JK. Incremental prognostic utility of coronary CT angiography for asymptomatic patients based upon extent and severity of coronary artery calcium: results from the COronary CT Angiography EvaluatioN For Clinical Outcomes InteRnational Multicenter (CONFIRM) Study. Eur. Heart J. 2015;36(8):501–508.

Cho JH, Lee DY, Lee ES, Kim J, Park SE, Park CY, Lee WY, Oh KW, Park SW, Rhee EJ. Increased risk of coronary artery calcification progression in subjects with high baseline Lp(a) levels: The Kangbuk Samsung Health Study. International Journal of Cardiology. 2016;222:233–237.

Collin J, Gössl M, Matsuo Y, Cilluffo RR, Flammer AJ, Loeffler D, Lennon RJ, Simari RD, Spoon DB, Erbel R, Lerman LO, Khosla S, Lerman A. Osteogenic monocytes within the coronary circulation and their association with plaque vulnerability in patients with early atherosclerosis. International Journal of Cardiology. 2015;181:57–64.

Criqui MH, Denenberg JO, Ix JH, McClelland RL, Wassel CL, Rifkin DE, Carr JJ, Budoff MJ, Allison MA. Calcium density of coronary artery plaque and risk of Incident cardiovascular events. JAMA. 2014;311:271–278.

Demer L.L., Yin T. Inflammatory, Metabolic, and Genetic Mechanisms of Vascular Calcification // Arterioscler. Thromb. Vasc. Biol. - 2014. - Vol. 34. - Р.715-723.

Demer LL, Tintut Y. Vascular calcification. Pathobiology of a multifaceted disease. Circulation. 2008;117:2938–2948.

Detrano R, Guerci AD, Carr JJ, Bild DE, Burke G, Folsom AR, Liu K, Shea S, Szklo M, Bluemke DA, O'Leary DH, Tracy R, Watson K, Wong ND, Kronmal RA. Coronary calcium as a predictor of coronary events in four racial or ethnic groups. N. Engl. J. Med. 2008;358:1336–1345.

Doherty T.M., Asotra K., Fitzpatrick L.A. Qiao J-H, Wilkin DJ, Detrano RC, Dunstan CR, Shah PK, Rajavashisth TB. Calcification in atherosclerosis: Bone biology and chronic inflammation at the arterial crossroads. PNAS 2003;100(20):11201–11206.

Engbers EM, Timmer JR, Ottervanger JP, Mouden M, Knollema S, Jager PL. Impact of Gender on the Prognostic Value of Coronary Artery Calcium in Symptomatic Patients With Normal Single-Photon Emission Computed Tomography Myocardial Perfusion. The American Journal of Cardiology. 2016;118(Issue 11):1611–1615.

Fantus D, Awan Z, Seidah NG, Genest J. Aortic calcifica¬tion: Novel insights from familial hypercholesterolemia and potential role for the low-density lipoprotein receptor. Atherosclerosis. 2013;226:9–15.

Geisel MH, Bauer M, Hennig F, Hoffmann B, Lehmann N, Möhlenkamp S, Kröger K, Kara K, Müller T, Moebus S, Erbel R, Scherag A, Jöckel KH, Mahabadi AA; Heinz Nixdorf Recall study. Comparison of coronary artery calcification, carotid intima-media thickness and ankle-brachial index for predicting 10-year incident cardiovascular events in the general population. Eur. Heart J. 2017;38(23):1815–1822.

Gidding SS, Rana JS, Prendergast C, McGill H, Carr JJ, Liu K, Colangelo LA, Loria CM, Lima J, Terry JG, Reis JP, McMahan CA. Pathobiological Determinants of Atherosclerosis in Youth (PDAY) Risk Score in Young Adults Predicts Coronary Artery and Abdominal Aorta Calcium in Middle Age: The CARDIA Study / CLINICAL PERSPECTIVE. Circulation. 2016;133(2):139–146.

Gourgas O, Marulanda J, Zhang P, Murshed M, Cerruti M. Multidisciplinary Approach to Understand Medial Arterial CalcificationHighlights. Arteriosclerosis, Thrombosis, and Vascular Biology. 2018;38:363–372.

Grossman C, Ehrlich S, Shemesh J, Koren-Morag N, Grossman E. Coronary Artery Calcium and Exercise Electrocardiogram as Predictors of Coronary Events in Asymptomatic Adults. The American Journal of Cardiology. 2015;115(Issue 6):745–750.

Hamirani YS, Pandey S, Rivera JJ, Ndumele C, Budoff MJ, Blumenthal RS, Nasir K. Markers of inflam¬mation and coronary artery calcification: A systematic review. Atherosclerosis.2008;17:1–7.

Hamirani YS, Pandey S, Rivera JJ, Ndumele C, Budoff MJ, Blumenthal RS, Nasir K. Markers of inflammation and coronary artery calcification: A systematic review. Atherosclerosis. 2008;201(Issue 1):1–7.

Houslay ES, Cowell SJ, Prescott RJ, Reid J, Burton J, Northridge DB, Boon NA, Newby DE; Scottish Aortic Stenosis and Lipid Lowering Therapy, Impact on Regression trial Investigators. Progressive coronary calcification despite intensive lipid-lowering treatment: a randomised controlled trial. Heart 2006;92:1207–1212

Ibebuogu UN, Ahmadi N, Hajsadeghi F, Ramirez J, Flores F, Young E, Gopal A, Wong ND, Budoff MJ. Measures of Coronary Artery Calcification and Association With the Metabolic Syndrome and Diabetes. J. Cardiometab. Syndr. 2009;4(1):6–11.

Ikeda K, Souma Y, Akakabe Y, Kitamura Y, Matsuo K, Shimoda Y, Ueyama T, Matoba S, Yamada H, Okigaki M, Matsubara H. Macrophages play a unique role in the plaque calcification by enhancing the osteogenic signals exerted by vascular smooth muscle cells. Biochem. Biophys. Res. Commun. 2012;425:39–44.

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;283:2810–2815.

Joshi FR, Rajani NK, Abt M, Woodward M, Bucerius J, Mani V, Tawakol A, Kallend D, Fayad ZA, Rudd JH. Does Vascular Calcification Accelerate Inflammation?: A Substudy of the dal-PLAQUE Trial. J. Am. Coll. Cardiol. 2016;67(1):69–78.

Joshi NV, Vesey AT, Williams MC, Shah AS, Calvert PA, Craighead FH, Yeoh SE, Wallace W, Salter D, Fletcher AM, van Beek EJ, Flapan AD, Uren NG, Behan MW, Cruden NL, Mills NL, Fox KA, Rudd JH, Dweck MR, Newby DE. 18F-fluoride positron emission tomography for identification of ruptured and high-risk coronary atherosclerotic plaques: a prospective clinical trial. Lancet. 2014;383:705–713.

Joshi PH, Patel B, Blaha MJ, Berry JD, Blankstein R, Budoff MJ, Wong N, Agatston A, Blumenthal RS, Nasir K. Coronary artery Calcium predicts Cardiovascular events in participants with a low lifetime risk of Cardiovascular disease: The Multi-Ethnic Study of Atherosclerosis (MESA). Atherosclerosis. 2016;246:367–373.

Lee HL, Woo KM, Ryoo HM, Baek JH. Tumor necrosis factor-alpha increases alkaline phosphatase expression in vascular smooth muscle cells via MSX2 induction. Biochem. Biophys. Res. Commun. 2010;391:1087–1092.

Libby P. How does lipid lowering prevent coronary events? New insights from human imaging trials. Eur. Heart J. 2015;36:472–474.

Martinez LR, Miname MH, Bortolotto LA, Chacra AP, Rochitte CE, Sposito AC, Santos RD. No correlation and low agreement of imaging and inflammatory atherosclerosis’ markers in familial hypercholesterolemia. Atherosclerosis. 2008;200(Issue 1):83–88.

McClelland RL, Jorgensen NW, Budoff M, Blaha MJ, Post WS, Kronmal RA, Bild DE, Shea S, Liu K, Watson KE, Folsom AR, Khera A, Ayers C, Mahabadi AA, Lehmann N, Jöckel KH, Moebus S, Carr JJ, Erbel R, Burke GL. 10-Year Coronary Heart Disease Risk Prediction Using Coronary Artery Calcium and Traditional Risk Factors: Derivation in the MESA (Multi-Ethnic Study of Atherosclerosis) With Validation in the HNR (Heinz Nixdorf Recall) Study and the DHS (Dallas Heart Study). J. Am. Coll. Cardiol. 2015;66(15):1643–1653.

McEvoy JW, Blaha MJ, DeFilippis AP, Lima JA, Bluemke DA, Hundley WG, Min JK, Shaw LJ, Lloyd-Jones DM, Barr RG, Budoff MJ, Blumenthal RS, Nasir K. Cigarette Smoking and Cardiovascular Events. Role of Inflammation and Subclinical Atherosclerosis From the Multiethnic Study of Atherosclerosis. Arterioscler. Thromb. Vasc. Biol. 2015;35(3):7000–709.

McEvoy JW, Blaha MJ, Defilippis AP, Budoff MJ, Nasir K, Blumenthal RS, Jones SR. Coronary artery calcium progression: an important clinical measurement? A review of published reports. J. Am. Coll. Cardiol. 2010;56:1613–1622.

Menegazzo L, Poncina N, Albiero M, Menegolo M, Grego F, Avogaro A, Fadini GP. Diabetes modifies the relationships among carotid plaque calcification, composition and inflammation. Atherosclerosis 2015;241(Issue 2):533–538.

Möhlenkamp S1, Lehmann N, Moebus S, Schmermund A, Dragano N, Stang A, Siegrist J, Mann K, Jöckel KH, Erbel R; Heinz Nixdorf Recall Study Investigators. Quantification of Coronary Atherosclerosis and Inflammation to Predict Coronary Events and All-Cause Mortality. J. Am. Coll. Cardiol. 2011;57(13):1455–1464.

Mulders TA, Taraboanta C, Franken LC, van Heel E, Klass G, Forster BB, Arad Y, Boekholdt SM, Groenink M, Fröhlich J, Guerci AD, Stroes ES, Pinto-Sietsma SJ. Coronary artery calcification score as tool for risk assessment among families with premature coronary artery disease. Atherosclerosis. 2016;245:155–160.

Nakahara T, Narula J, Strauss HW. Calcification and Inflammation in Atherosclerosis : Which Is the Chicken, and Which Is the Egg? J. Am. Coll. Cardiol. 2016;67(1):79–80.

Nakanishi R, Li D, Blaha MJ, Whelton SP, Matsumoto S, Alani A, Rezaeian P, Blumenthal RS, Budoff MJ. The relationship between coronary artery calcium score and the long-term mortality among patients with minimal or absent coronary artery risk factors. International Journal of Cardiology 2015;185:275–281.

Nasir K, Bittencourt MS, Blaha MJ, Blankstein R, Agatson AS, Rivera JJ, Miedema MD, Sibley CT, Shaw LJ, Blumenthal RS, Budoff MJ, Krumholz HM. 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):1657–1668.

Nicoll R, Henein M. Arterial calcification: A new perspective? International Journal of Cardiology. 2017;228:11–22.

Nicoll R, Wiklund U, Zhao Y, Diederichsen A, Mickley H, Ovrehus K, Zamorano P, Gueret P, Schmermund A, Maffei E, Cademartiri F, Budoff M, Henein M. The coronary calcium score is a more accurate predictor of significant coronary stenosis than conventional risk factors in symptomatic patients: Euro-CCAD study. International Journal of Cardiology. 2016;207:13–19.

Hartaigh BÓ, Valenti V, Cho I, Schulman-Marcus J, Gransar H, Knapper J, Kelkar AA, Xie JX, Chang HJ, Shaw LJ, Callister TQ, Min JK. 15-Year prognostic utility of coronary artery calcium scoring for all-cause mortality in the elderly. Atherosclerosis. 2016;246:361–366.

Osawa K, Nakanishi R, Budoff MJ. Is there a role for coronary artery calcification scoring in primary prevention of cerebrovascular disease? Atherosclerosis. 2017;257:279–287.

Otsuka F, Sakakura K, Yahagi K, Joner M. Has our understanding of calcification in human coronary atherosclerosis progressed? Arterioscler. Thromb. Vasc. Biol. 2014;34:724–36.

Mehta A, Patel J, Al Rifai M, Ayers CR, Neeland IJ, Kanaya AM, Kandula N, Blaha MJ, Nasir K, Blumenthal RS, Joshi PH. Inflammation and Coro¬nary Artery Calcification in South Asians: The Mediators of Atherosclerosis in South Asians Living in America (MASALA) Study. Circulation. 2016;134:173–186.

Polonsky TS, McClelland RL, Jorgensen NW, Bild DE, Burke GL, Guerci AD, Greenland P. Coronary artery calcium score and risk classification for coronary heart disease prediction. JAMA 2010;303(16):1610–1616.

Puri R, Nicholls SJ, Shao M, Kataoka Y, Uno K, Kapadia SR, Tuzcu EM, Nissen SE. Impact of statins on serial coronary calcification during atheroma progression and regression. J. Am. Coll. Cardiol. 2015;65:1273–1282.

Raggi P, Khan A, Arepali C, Stillman AE. Coronary artery calcium scoring in the age of ct angiography: what is its role? Curr. Atheroscler. Rep. 2008;10:438–443.

Raggi Р, Callister TQ, Shaw U. Progression of coronary artery calcium and risk of first myocardial infarction in patients receiving cholesterol-lowering therapy. Arterioscler. Thromb. Vase Biol. 2004;24:1272–1277.

Rohrmann S, Garmo H, Malmström H, Hammar N, Jungner I, Walldius G, Van Hemelrijck M. Association between serum calcium concentration and risk of incident and fatal cardiovascular disease in the prospective AMORIS study. Atherosclerosis. 2016;251:85–93.

Sallam T, Cheng H, Demer LL, Tintut Y. Regulatory circuits controlling vascular cell calcification. Cell Mol. Life Sci. 2013;70:3187–3197.

Sangiorgi G, Rumberger JA, Severson A, Edwards WD. Arterial calcification and not lumen stenosis is highly correlated with atherosclerotic plaque burden in humans: a histologic study of 723 coronary artery segments using nondecalcifying methodology. J. Am. Coll. Cardiol. 1998;31:126–133.

Sanz J. Coronary Calcium Score and the New Guidelines: Back to Square One? J. Am. Coll. Cardiol. 2015;66(15):1669–1671.

Schmermund A, Achenbach S, Budde T, Buziashvili Y, Förster A, Friedrich G, Henein M, Kerkhoff G, Knollmann F, Kukharchuk V, Lahiri A, Leischik R, Moshage W, Schartl M, Siffert W, Steinhagen-Thiessen E, Sinitsyn V, Vogt A, Wiedeking B, Erbel R. Effect of intensive versus standard lipid-lowering treatment with atorvastatin on the progression of calcified coronary atherosclerosis over 12 months: a multicenter, randomized, double-blind trial. Circulation. 2006;113(3):427–437

Shanahan CM. Inflammation ushers in calcification: a cycle of damage and protection? Circulation. 2007;116:2782–2785.

Sharma RK, Sharma RK, Voelker DJ, Singh VN, Pahuja D, Nash T, Reddy HK. Cardiac risk stratification: Role of the coronary calcium score. Vascular Health and Risk Management 2010;6:603–610.

Shaw LJ, Narula J, Chandrashekhar Y. The Never Ending Story on Coronary Calcium: Is it Predictive, Punitive, or Protective? J. Am. Coll. Cardiol. 2015; 65(13):1283–1285.

Stary HC. The sequence of cell and matrix changes in atherosclerotic lesions of coronary arteries in the first forty years of life. Eur. Heart J.1990;11(E):3–19.

Swardfager W, Black SE. Coronary Artery Calcification: A Canary in the Cognitive Coalmine. J. Am. Coll. Cardiol. 2016;67(9):1023–1026.

Ten Kate GR, Bos S, Dedic A, Neefjes LA, Kurata A, Langendonk JG, Liem A, Moelker A, Krestin GP, de Feyter PJ, Roeters van Lennep JE, Nieman K, Sijbrands EJ. Increased Aortic Valve Calcification in Familial Hypercholesterolemia: Prevalence, Extent, and Associated Risk Factors. J. Am. Coll. Cardiol. 2015;66(24):2687–2695.

Terry JG, Carr JJ, Kouba EO, Davis DH, Menon L, Bender K, Chandler ET, Morgan T, Crouse JR 3rd. Effect of simvastatin (80 mg) on coronary and abdominal aortic arterial calcium (from the Coronary Artery calcification Treatment with Zocor [CATZ] study). Am J Cardiol. 2007;99:1714–1717

Tintut Y, Morony S, Demer LL. Hyperlipidemia promotes osteoclastic potential of bone marrow cells ex vivo. ATVB. 2004;24:e6–e10.

Tintut Y, Patel J, Territo M, Saini T, Parhami F, Demer LL. Monocyte/macrophage regulation of vascular calcification in vitro. Circulation 2002;105:650–655.

Uretsky S, Chokshi N, Kobrinski T, Agarwal SK, Po JR, Awan H, Jagarlamudi A, Gudiwada SP, D'Avino RC, Rozanski A. The Interplay of Physician Awareness and Reporting of Incidentally Found Coronary Artery Calcium on the Clinical Management of Patients Who Underwent Noncontrast Chest Computed Tomography. The American Journal of Cardiology. 2015;115(Issue 11):1513–1517.

Wang J, Aikawa E, Aikawa M. Leukocyte-Derived Microparticles as Proinflammatory Mediators in Atherosclerosis. J. Am. Coll. Cardiol. 2013;62(16):1442–1445.

Wang NC, Matthews KA, Barinas-Mitchell EJ, Chang CC, El Khoudary SR. Inflammatory/Hemostatic Biomarkers and Coronary Artery Calcium Progression in Women at Midlife (from the Study of Women's Health Across the Nation, Heart Study). The American Journal of Cardiology. 2016;118(Issue 3):311–318.

Wayhs R, Zelinger A, Raggi P. High coronary artery calcium scores pose an extremely elevated risk for hard events. J. Am. Coll. Cardiol. 2002;39:225–230.

Wilkins JT, Li RC, Sniderman A, Chan C, Lloyd-Jones DM. Discordance Between Apolipoprotein B and LDL-Cholesterol in Young Adults Predicts Coronary Artery Calcification: The CARDIA Study. J. Am. Coll. Cardiol. 2016;67(2):193–201.

Wu M, Rementer C, Giachelli CM. Vascular calcification: an update on mechanisms and challenges in treatment. Calcif. Tissue Int. 2013;93:365–373.

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