Assessment of Subclinical Manifestations of Atherosclerosis of Coronary and Peripheral Arteries and Bone Strength Parameters in Women

Aim. To study associations between calcification of the coronary arteries (CA), the state of the peripheral vascular wall and bone strength indices.
Material and methods. In a cross-sectional study were included 200 women at the age 45-69 y.o. who were observed on an outpatient basis and signed informed consent. A survey was conducted on the presence of cardiovascular risk factors and the risk of fractures. The intima-media thickness (IMT), the presence and number of atherosclerotic plaques (AP) were studied using duplex scanning. Pulse wave velocity (PWV), augmentation index (AI) were measured by applanation tonometry. The presence of calcium deposits in coronary vessels was determined by multispiral computed tomography (MSCT) using the Agatston index. The bone mineral density (BMD) of the spine, hip neck (HN) and proximal hip (PH) was measured using double energy x-ray absorptiometry. The marker of bone resorption C-terminal telopeptide of type-1 collagen (СТх) was determined in blood serum by the β-crosslaps method.
Results. There was a positive correlation between the parameters of vascular stiffness, subclinical atherosclerosis of peripheral vessels and CA calcification: AI and calcium index (r=0.25, p<0.05), IMT and calcium index (r=0.23, p<0.05), presence of AP and calcium index (r=0.26, p<0.05). The PWV increased as the calcium index increased, but the correlation remained at the trend level. Women with low bone mass had higher PWV (p<0.05), AI (p<0.01), IMT (p<0.02), CTx level (p<0.001) and a higher number of AP than those with normal BMD. CTx was inversely correlated with PWV and calcium index (p<0.05). Based on multivariate linear regression analysis (adjusted for age, menopause duration, low body weight, smoking factor and total cholesterol) the independent nature of the relationship between the Agatstone index and BMD in all the measured parts of the skeleton, between AI and BMD of HN, and between IMT and BMD of HN was confirmed. The relationship between the marker of bone resorption CTx and BMD of the spine and PH remained highly reliable.
Conclusion. The correlation of stiffness indices and subclinical atherosclerosis of peripheral arteries, which is a predictor of high risk of cardiovascular events, allows to suggest an important role of changes in the peripheral vascular wall in increasing cardiovascular risk. A decrease in BMD and an increase in the marker of bone resorption, associated with an increase in indices of vascular stiffness and subclinical atherosclerosis and, especially, CA calcification, allows us to think about the common mechanisms of development and progression of atherosclerosis and osteoporosis. Therefore, early examination of women with a high cardiovascular risk, assessed by the SCORE scale, after 45 years and before menopause to detect vascular rigidity and the presence of subclinical atherosclerosis, and performing x-ray densitometry for individuals with changes in these indices will allow stratify the risks of atherosclerosis and osteoporosis complications and recommend preventive use of drugs that reduce vascular rigidity and increase BMD.

1. Lampropolos C.E., Papaioannou I., D'Cruz D.P. Osteoporosis-a risk factor for cardiovascular disease? Nat Rev Rheumatol. 2012;8:587-98. DOI:10.1038/nrrheum.2012.120.

2. den Uyl D., Nurmohamed M.T., van Tuyl L..H, et al. (Sub)clinical cardiovascular disease is associated with increased bone loss and fracture risk: a systematic review of the association between cardiovascular disease and osteoporosis. Arthritis Res Ther. 2011;13(1):R5. DOI:10.1186/ar3224.

3. Khan Z.A., Janssen I., Mazzarelli J.K., et al. Aortic stiffness changes indicator of vascular aging during, after menopause. Am J Cardiol. 2018;12(7):1161-8. DOI:10.1016/j.amjcard.2018.06.039.

4. Zhaleh S.S., Rezaie E.H., Milani N., at al. Evaluation of Bone Mineral Density in Perimenopausal Period. Arch Bone Jt Surg. 2018; 6 (1): 57-62.

5. Schulz E., Arfai K., Liu X., et al. Aortic calcification and the risk of osteoporosis and fractures. J Clin Endocrinol Metab. 2004;89:4246-53.

6. Mangiafico R.A., Alagona C., Pennisi P. Increased augmentation index and central aortic blood pressure in osteoporotic postmenopausal women. Osteoporos Int. 2008;19:49-56. DOI:10.1007/s00198-007-0438-5.

7. Boytsov S.A., Kukharchuk V.V., Karpov Yu.A., et al. Subclinical atherosclerosis as a risk factor for cardiovascular complications. Cardiovascular Therapy and Prevention. 2012;11(3):82-6 (In Russ.). DOI:10.15829/1728-8800-2012-3-82-86.

8. Laurent S., Cockcroft J., van Bortel L., et al. European Network for Non-invasive Investigation of Large Arteries Expert consensus document on arterial stiffness: methodological issues and clinical applications. Eur Heart J. 2006;27(21):2588-605. DOI:10.1093/eurheartj/ehl254.

9. Rajamannan N.M. Osteocardiology. Cardiac bone formation. London: Springer; 2018. DOI:10.1007/978-3-319-64994-8.

10. Li S., Yin L., Li K., et al. Relationship of volumetric bone mineral density by quantitative computed tomography with abdominal aortic calcification. Bone. 2020;133:115226. DOI:10.1016/j.bone.2020.115226.

11. Filgueira A., Carvalho A.B., Tomiyama C. Is Coronary Artery Calcification Associated with Vertebral Bone Density in Nondialyzed Chronic Kidney Disease Patients? Clin J Am Soc Nephrol. 2011;6(6):1456-62. DOI:10.2215/CJN.10061110.

12. Campos-Staffico A.M., Freitas W.M., Carvalho L.S., et al. Lower bone mass is associated with sub-clinical atherosclerosis, endothelial dysfunction and carotid thickness in the very elderly. Atherosclerosis. 2020;292:70-4. DOI:10.1016/j.atherosclerosis.2019.11.007.

13. Reid I.R., Evans M.C., Ames R., et al. The influence of osteophytes and aortic calcification on spinal mineral density in postmenopausal women. J Clin Endocrinol Metab. 1991;72:1372-4. DOI:10.1210/jcem-72-6-1372.

14. Vogt M.T., San Valentin R., Forrest K.Y., et al. Bone mineral density and aortic calcification: the Study of Osteoporotic Fractures. J Am Geriatr Soc. 1997;45:140-5. DOI:10.1111/j.1532-5415.1997.tb04498.x.

15. Zhu J., Guo F., Zhang J., et al. Relationship between carotid or coronary artery calcification and osteoporosis in the elderly. Minerva Med. 2019;110:12-7. DOI:10.23736/S0026-4806.18.05632-X.

16. Veronese N., Stubbs B., Crepaldi G., et al. Relationship between low bone mineral density and fractures with incident cardiovascular disease: a systematic review and meta-analysis. J Bone Miner Res. 2017;32:1126-35. DOI:10.1002/jbmr.3089.

17. Jargensen L., Joakimsen O., Rosvold Berntsen G.K., et al. Low bone mineral density is related to echogenic carotid artery plaques: a population-based study. Am J Epidemiol. 2004;160:549-56. DOI:10.1093/aje/kwh252.

18. Kim S.H., Kim Y.M., Cho M.A., et al. Echogenic carotid artery plaques are associated with vertebral fractures in postmenopausal women with low bone mass. Calcif Tissue Int. 2008;82:411-7. DOI:10.1007/s00223-008-9141-6.

19. Sumino H., Ichikawa S., Kasama S., et al. Elevated arterial stiffness in postmenopausal women with ostoporosis. Maturitas. 2006;55:212-8. DOI:10.1016/j.maturitas.2006.02.008.

20. Alikhanova N.A., Skripnikova I.A., Tkacheva O.N., et al. Association of parameters of vascular stiffness and subclinical atherosclerosis with bone mass in postmenopausal women. Cardiovascular Therapy and Prevention. 2016;2:51-6 (In Russ.) DOI:10.15829/1728-8800-2016-2-51-56.

21. Schulz E., Arfai K., Lui X., et al. Aortic Calcification and the Risk of Osteoporosis and Fractures. The Journal of Clinical Endocrinology & Metabolism. 2004;89(9)4246-53. DOI:10.1210/jc.2003-030964.

22. Kiel D.P., Kauppila L.I., Cupples L.A., et al. Bone loss and the progression of abdominal aortic calcification over a 25year period: the Framingham Heart Study. Calcif Tissue Int. 2001;68(5):271-6. DOI:10.1007/BF02390833.

23. Marcovitz P.A., Tran H.H., Franklin B.A., et al. Usefulness of bone mineral density to predict significant coronary artery disease. Am J Cardiol. 2005;96(8):1059-63. DOI:10.1016/j.amjcard.2005.06.034.

24. Campos-Obando N., Kavousi M., Roeters H.E., et al. Bone health and coronary artery calcification: The Rotterdam Study. Atherosclerosis. 2015;241:278-83. DOI:10.1016/j.atherosclerosis.2015.02.013.

25. Pereira T, Maldonado J., Pereira L., е1 al. Aortic stiffness is an independent predictor of stroke in hypertensive patients. Arq Bras Cardiol. 2013;100(5):437-43. DOI:10.5935/abc.20130079.

26. Tamaki J., Iki M., Hirano Y., et al. Low bone mass is associated with carotid atherosclerosis in postmenopausal women: the Japanese Population-based Osteoporosis (JPOS) Cohort Study. Osteoporosis Int. 2009;20:53-60. DOI:10.1007/s00198-008-0633-z.

27. Jaalkhorol M., Fujita Y., Kouda K., et al. Low bone mineral density is associated with an elevated risk of developing increased arterial stiffness: a 10-year follow-up of Japanese women from the Japanese population-based Osteoporosis (JPOS) cohort study. Maturitas. 2019;119:39-45. DOI:10.1016/j.maturitas.2018.11.001.

28. Song S.O., Park K.W., Yoo S.H., et al. Association of coronary artery disease and osteoporotic vertebral fracture in Korean men and women. Endocrinol Metab. 2012;27(1):39-44.

29. Qu X., Huang X., Jin F., et al. Bone mineral density and all-cause, cardiovascular and stroke mortality: a meta-analysis of prospective cohort studies. Int J Cardiol. 2013;166:385-93. DOI:10.1016/j.ij-card.2011.10.114.

30. Raskina T.A., Letaeva M.V., Voronkina A.V. Relationship between indicators of bone remodeling, bone mineral density, and severity of coronary atherosclerosis in men with stable coronary heart disease. Modern Rheumatology. 2018;12(1):26-32 (In Russ.)