Predictors of progression of coronary calcification in patients after coronary artery bypass grafting

Aim: To assess predictors of progression of coronary artery calcification (CAC) in men with stable coronary heart disease (CHD) after coronary artery bypass graft surgery (CABG) based on longterm (5 years) follow-up.

Materials and methods. The prospective study included 111 men who were hospitalized for planned CABG using cardiopulmonary bypass. All patients in the preoperative period underwent the following procedures: color duplex scanning (CDS) of the brachiocephalic arteries (BCA), multi-slice computed tomography (MSCT) coronary angiography to assess the degree of CAC using the Agatson method (calculation of the coronary artery calcium score – CAC) and estimation of femoral neck bone mineral density with the T-score calculation. The vital status of patients was ascertained after 3-5 years of follow-up after CABG, CDS of the BCA and MSCT-coronary angiography were repeated. To identify the most significant clinical and anamnestic risk factors and form a model of predictors of CAC progression, patients were divided into two groups depending on the high increase in CAC score (an increase in the score of more than 100 Agatston units (AU).

Results. 16 (14.4 %) out of 111 patients failed to establish contact for the next stage of the study. In 4 (3.6%) cases death was registered (3 – fatal myocardial infarction, 1 – fatal stroke). The CAC progression was assessed in 91 patients (81.9 %). Patients who showed signs of CAC progression comprised a group of 60 (65.9 %) patients; without CAC progression – 31 (34.1 %) patients. The “end points” in the groups were comparable and were detected in 18 cases (19.7 %): recurrent angina in 16 patients (p = 0.368), non-fatal myocardial infarction in 1 (p = 0.162) and 1 emergency stenting (р = 0,162) of the coronary artery that was not subjected to CABG. The five-year risk model for CAC progression included an initial decrease in femoral neck bone mineral density and nonadherence to statins for 5 years after CABG (p = 0.001).

Conclusions. 65.9 % of men with stable CHD showed the signs of CAC progression for 5 years after CABG, according to MSCT. The main predictors were: nonadherence to statins after CABG and initial low femoral neck bone mineral density.

1. Sousa-Uva M., Ahlsson A., Neumann F.J., lfonso F., Banning A.P., Benedetto U., Byrne R.A., Collet J.P., Falk V., Head S.J., Jüni P., Kastrati A., Koller A., Kristensen S.D., Niebauer J., Richter D.J., Seferovic P.M., Sibbing D., Stefanini G.G., Windecker S., Yadav R., Zembala M.O. ESC/EACTS Guidelines on myocardial revascularization Eur. J. Cardiothorac. Surg. 2018; 55: 4–90. doi: 10.1093/ejcts/ezy289

2. Gaifulin R.A., Sumin A.N., Ivanov S.V., Barbarash L.S. Survival after surgical treatment of patients with multifocal atherosclerosis in different age groups. Complex Problems of Cardiovascular Diseases. 2017; 6 (2): 618. (in Russian). doi: 10.17802/2306127820172618.

3. Lutai M.I., Golikova I.P. Calcification of the coronary arteries and aorta in patients with chronic ischemic heart disease: age and gender characteristics, relationship with risk factors. Ukrainian J. Cardiol. 2017; 1: 25– 31. (in Russian).

4. Barbarash O.L., Semenov V.Yu., Samorodskaya I.V., Evseeva M.V., Rozhkov N.A., Sumin A.N., Barbarash L.S. Comorbid pathology in patients with coronary artery disease with coronary artery bypass grafting: the experience of two cardiac surgery centers. Rus. J. Cardiol. 2017; 22 (3): 613. doi: 10.15829/1560407120173613 (in Russian).

5. Zykov M.V., Khryachkova O.N., Kashtalap V.V., Bykova I.S., Kokov A.N., Shibanova I.A., Barbarash O.L. Dynamics of coronary calcification and its relationship with the clinical course of coronary heart disease and osteopenic syndrome. Cardiology. 2019; 59 (4): 12–20. doi: 10.18087/cardio.2019.4.10247 (in Russian).

6. Kelkar A.A., Schultz W.M., Khosa F., SchulmanMarcus J., O'Hartaigh B.W., Gransar H., Blaha M.J., Knapper J.T., Berman D.S., Quyyumi A., Budoff M.J., Callister T.Q., Min J.K., Shaw L.J. Long-Term Prognosis After Coronary Artery Calcium Scoring Among Low-Intermediate Risk Women and Men. Circulation: Cardiovasc. Imaging. 2016; 9 (4). doi: 10.1161/CIRCIMAGING.115.003742

7. Kokov A.N., Masenko V.L., Tarasov R.S., Malyuta E.B., Sigareva A.A., Fanaskov V.B. Assessment of coronary artery disease in men with osteopenic syndrome and coronary artery disease. Therapeutic Archive. 2014; 86 (3): 65–70 (in Russian)

8. Bourantas C.V., Zhang Y.J., Garg S., Iqbal J., Valgimigli M., Windecker S., Mohr F.W., Silber S., Vries Td., Onuma Y., Garcia-Garcia H.M., Morel M.A., Serruys P.W. Prognostic implications of severe coronary calcification in patients undergoing coronary artery bypass surgery: An analysis of the SYNTAX Study: Coronary Calcification and Prognosis in CABG. Catheterization and Cardiovascular Interventions. 2015; 85 (2): 199–206. doi: 10.1002/ccd.25545

9. Barbarash O.L., Lebedeva N.B., Kokov A.N., Novitskaya A.A., Khryachkova O.N., Voronkina A.V. Relationship between biochemical markers of bone metabolism, osteopenic syndrome and coronary atherosclerosis in men with stable coronary artery disease. Atherosclerosis. 2015; 11 (2): 5–13 (in Russian).

10. Kashtalap V.V., Khryachkova O.N., Barbarash O.L. «New» pathological continuum: hypogonadism, osteoporosis and calcifying atherosclerosis. General factors of formation and progression. Atherosclerosis. 2016; 12 (4): 68–78 (in Russian).

11. Kashtalap V.V., Khryachkova O.N., Barbarash O.L. The clinical relevance of coronary calcification for the assessment of cardiovascular risk. Atherosclerosis and Dyslipidemia. 2016; 1 (22): 5–14 (in Russian).

12. Shaw L.J., Narula J., Chandrashekhar Y. The neverending story on coronary calcium: is it predictive, punitive, or protective? Am. Coll. Cardiol. 2015; 65: 1283–1285. doi: 10.1016/j.jacc.2015.02.024

13. Vancheri F., Longo G., Vancheri S., Danial J.S., Henein M.Y. Coronary Artery Microcalcification: Imaging and Clinical Implications. Diagnostics (Basel). 2019; 9 (4): 125. Published 2019 Sep 23. doi:10.3390/diagnostics9040125

14. Budoff M.J., Hokanson J.E., Nasir K., Shaw L.J., Kinney G.L., Chow D., Demoss D., Nuguri V., Nabavi V., Ratakonda R., Berman D.S., Raggi P. Progression of Coronary Artery Calcium Predicts All-Cause Mortality. JACC: Cardiovascular Imaging. 2010; 3 (12): 1229–1236. doi: 10.1016/j.jcmg.2010.08.018

15. de Maria G.L., Scarsini R., Adrian P., Banning A.P. Management of Calcific Coronary Artery Lesions Is it Time to Change Our Interventional Therapeutic Approach? Am. Coll. Cardiol. Intv. 2019; 12: 1465–1478. doi: 10.1016/j.jcin.2019.03.038

16. John R., Choudhri A.F., Weinberg A.D. Multicenter review of preoperative risk factors for stroke after coronary artery bypass grafting. Ann. Thorac. Surg. 2000; 69 (1): 30–36. doi:10.1016/s0003-4975(99)01309-0

17. Barbarash O.L., Kashtalap V.V., Zykov M.V., Khryachkova O.N., Novitskaya A.A., Kokov A.N., Shibanova I.A., Raskina T.A. Relationship between lipid and phosphorus-calcium metabolism disorders, the degree of coronary artery disease and osteopenia in elderly patients with ischemic heart disease. Creative Cardiology. 2016; 10 (2): 117–127. doi: 10.15275/kreatkard.2016.02.02 (in Russian).]

18. Barbarash O.A., Kashtalap V.V., Zykov M.V., Novitskaya A.A., Khryachkova O.N., Kokov A.N., Voronkina A.V., Shibanova I.A., Raskina T.A. Relationship between osteopontin concentration and the severity of coronary atherosclerosis and osteopenic syndrome in men with stable coronary artery disease. Atherosclerosis and Dyslipidemia. 2016; 4 (25) (in Russian).

19. Serrano C.V., Oranges M., Brunaldi V., de M. Soeiro A., Torres T.A., Nicolau J.C., Ramires J.A. Skeletonized coronary arteries: pathophysiological and clinical aspects of vascular calcification. Vasc. Health Risk. Manag. 2011; 7: 143–151. doi: 10.2147/VHRM.S16328

20. Barbarash O.L., Zhidkova I.I., Shibanova I.A., Ivanov S.V., Sumin A.N., Samorodskaya I.V., Barbarash L.S. The effect of comorbid pathology and age on hospital outcomes in patients undergoing coronary artery bypass grafting. Cardiovascular Therapy and Prevention. 2019; 18 (2): 58–64. doi: 10.15829/1728-8800-2019-2-58-64 (in Russian).

21. Nakama C., Kadowaki T., Choo J., Yang H.M., Jae S.Y., Kim H.J., You J., Lee J. Cross-sectional association of bone mineral density with coronary artery calcification in an international multi-ethnic population-based cohort of men aged 40–49: ERA JUMP study. IJC Heart & Vasculature 2020; 30: 100618. doi: 10.1016/j.ijcha.2020.100618

22. Hyder J.A., Allison M.A., Wong N., Papa A., Lang T.F., Sirlin C., Gapstur S.M., Ouyang P., Carr J.J., Criqui M.H. Association of Coronary Artery and Aortic Calcium With Lumbar Bone Density: The MESA Abdominal Aortic Calcium Study. Am. J. Epidemiol. 2008; 169 (2): 186–194. doi: 10.1093/aje/kwn303

23. Lee H.T., Shin J., Lim Y.H., Kim B.K., Kim Y.T., Lee J.U., Hong S., Song S.Y., Cho S.H. The Relationship Between Coronary Artery Calcification and Bone Mineral Density in Patients According to Their Metabolic Syndrome Status. Korean Circulat. J. 2011; 41 (2): 76. doi: 10.4070/kcj.2011.41.2.76

24. Chan J.J., Cupples L.A., Kiel D.P., O'Donnell C.J., Hoffmann U., Samelson E.J. QCT Volumetric Bone Mineral Density and Vascular and Valvular Calcification: The Framingham Study: Bone density and vascular and valvular calcification. J. Bone and Mineral. Res. 2015; 30 (10): 1767–1774. doi: 10.1002/jbmr.2530

25. Divers J., Register T.C., Langefeld C.D., Wagenknecht L.E., Bowden D.W., Carr J.J., Hightower R.C., Xu J., Hruska K.A., Freedman B.I. Relationships between calcified atherosclerotic plaque and bone mineral density in African Americans with type 2 diabetes. J. Bone and Mineral. Res. 2011; 26 (7): 1554–1560. doi: 10.1002/jbmr.389

26. Tsubaki M., Satou T., Itoh T., Imano M., Yanae M., Kato C., Takagoshi R., Komai M., Nishida S. Bisphosphonate-and statin-induced enhancement of OPG expression and inhibition of CD9, M-CSF, and RANKL expressions via inhibition of the Ras/MEK/ERK pathway and activation of p38MAPK in mouse bone marrow stromal cell line ST2. Mol. Cell Endocrinol. 2012; 361 (2): 219–231. doi: 10.1016/j.mce.2012.05.002

27. Puri R., Nicholls S.J., Shao M., Kataoka Y., Uno K., Kapadia S.R., Tuzcu E.M., Nissen S.E. Impact of statins on serial coronary calcification during atheroma progression and regression. J. Am. Coll. Cardiol. 2015; 65 (13): 1273–1282. doi: 10.1016/j.jacc.2015.01.036

28. Zhao X.Q., Yuan C., Hatsukami T.S., Frechette E.H., Kang X.J., Maravilla K.R., Brown B.G. Effects of prolonged intensive lipid-lowering therapy on the characteristics of carotid atherosclerotic plaques in vivo by MRI: a case-control study. Arterioscler. Thromb. Vasc. Biol. 2001; 21: 1623–1629. doi: 10.1161/hq1001.098463

29. Elshazly M.B., Stegman B., Puri R. Regression of coronary atheroma with statin therapy. Curr. Opin. Endocrinol. Diabetes Obes. 2016; 23 (2): 131–137. doi: 10.1097/MED.0000000000000234

30. Tian J., Gu X., Sun Y., Ban X., Xiao Y., Hu S., Yu B. Effect of statin therapy on the progression of coronary atherosclerosis. BMC Cardiovasc. Disord. 2012; 12: 70. Published 2012 Sep 1. doi: 10.1186/1471-2261-12-70

31. Hernández J.L., Olmos J.M., Romana G., Llorca J., Martínez J., Castillo J., de Juan J., Pérez-Pajares I., Ruiz S., González-Macías J. Influence of vitamin D status on the effect of statins on bone mineral density and bone turnover markers in postmenopausal women. J. Clin. Endocrinol. Metab. 2014; 99 (9): 3304–3309. doi: 10.1210/jc.2014-1102

32. An T., Hao J., Sun S., Li R., Yang M., Cheng G., Zou M. Efficacy of statins for osteoporosis: a systematic review and meta-analysis. Osteoporos Int. 2017; 28 (1): 47–57. doi: 10.1007/s00198-016-3844-8

33. Uzzan B., Cohen R., Nicolas P., Cucherat M., Perret G.Y. Effects of statins on bone mineral density: a meta-analysis of clinical studies. Bone. 2007; 40: 1581–1587. doi: 10.1016/j.bone.2007.02.019

34. Yue J., Zhang X., Dong B., Yang M. Statins and bone health in postmenopausal women: a systematic review of randomized controlled trials. Menopause. 2010; 17: 1071–1079. doi: 10.1097/gme.0b013e3181d3e036

35. Liu J., Zhu L.P., Yang X.L., Huang H.L., Ye D.Q. HMG-CoA reductase inhibitors (statins) and bone mineral density: a meta-analysis. Bone. 2013; 54: 151–156. doi: 10.1016/j.bone.2013.01.044