The prevalence of subclinical atherosclerosis of carotid arteries in patients with calcium pyrophosphate crystal deposition disease and osteoarthritis (pilot study)

To this date there have been no studies of subclinical atherosclerosis in the patients with calcium pyrophosphate crystal deposition disease (CPPD); in osteoarthritis (OA) such works are rare.
Objective: to assess the prevalence of subclinical atherosclerosis of carotid arteries (CA) in patients with CPPD and OA.
Patients and methods. The case-control study included 26 patients with CPPD and OA. The diagnosis of CPPD was based on the criteria of D.J. McCarty, diagnosis of OA was based on national clinical practice guidelines. We recorded data on smoking, blood pressure level. Assessed blood lipid spectrum, serum levels of glucose, creatinine, uric acid, CRP. Obesity was diagnosed in accordance with the WHO recommendations. All patients underwent CA Doppler ultrasonography (DUS). An increase in intima-media thickness (IMT) >0.9 mm was considered a manifestation of subclinical atherosclerosis. The SCORE index was calculated for all patients.
Results and discussion. The median serum CRP level was comparable in CPPD and OA. The CRP level >5 mg/L was detected in 8 patients with CPPD and in 3 patients with OA (p=0.09). Initial signs of atherosclerosis were present in 11 (42%) patients with CPPD and in 8 (31%) patients with OA (p=0.39). In CPPD, an increase in IMT was associated with a CRP level of ≥5 mg/L in 19% of cases, and in OA – in 12.5% (p=0.08). An increase in IMT >1.3 mm was not found in patients of both groups.
Conclusion. In patients with CPPD and OA, subclinical atherosclerosis is often present according to the CA ultrasound. Early detection of uncomplicated subclinical atherosclerosis in CPPD and OA is necessary for timely initiation of treatment aimed to prevent the progression of atherosclerosis and the development of cardiovascular diseases.

1. Piepoli MF, Hoes AW, Agewall S, et al. 2016 European Guidelines on cardiovascular disease prevention in clinical practice. Eur Heart J. 2016;37(29):2315-81. doi: 10.1093/eurheartj/ehw106.

2. Lusis AJ. Atherosclerosis. Nature. 2000;407(6801):233-41. doi:10.1038/35025203.

3. Hall FC, Dalbeth N. Disease modification and cardiovascular risk reduction: two sides of the same coin?. Rheumatology (Oxford). 2005;44(12):1473-82. doi:10.1093/rheumatology/kei012.

4. Naranjo A, Sokka T, Descalzo MA, et al. Cardiovascular disease in patients with rheumatoid arthritis: results from the QUEST-RA study. Arthritis Res Ther.2008;10(2):R30. doi:10.1186/ar2383.

5. Agca R, Heslinga SC, Rollefstad S, et al. EULAR recommendations for cardiovascular disease risk management in patients with rheumatoid arthritis and other forms of inflammatory joint disorders: 2015/2016 update. Ann Rheum Dis. 2017;76(1):17-28. doi:10.1136/annrheumdis-2016-209775.

6. Bierma-Zeinstra SMA, Waarsing JH. The role of atherosclerosis in osteoarthritis. Best Pract Res Clin Rheumatol. 2017;31(5):613-33. doi:10.1016/j.berh.2018.08.006.

7. Eliseev MS, Zhelyabina OV, Chikina MN, Novikova AM. Risk factors for cardiovascular diseases in patients with calcium pyrophosphate crystal deposition disease. Nauchnoprakticheskaya revmatologiya. 2019;57(5): 545-52. (In Russ.).

8. Eliseev MS, Novikova AM, Zhelyabina OV, et al. Assessment of cardiovascular risk in patients with microcrystalline arthritis and rheumatoid arthritis using the ATP III and Reynolds Risk Score scales. Nauchno-prakticheskaya revmatologiya. 2020;58(5):512-9. (In Russ.).

9. Beck C, Morbach H, Richl P, et al. How can calcium pyrophosphate crystals induce inflammation in hypophosphatasia or chronic inflammatory joint diseases? Rheumatol Int. 2009;29(3):229-38. doi:10.1007/s00296-008-0710-9.

10. Hall AJ, Stubbs B, Mamas MA, et al. Association between osteoarthritis and cardiovascular disease: Systematic review and meta-analysis. Eur J Prev Cardiol. 2016; 23(9):938-46. doi:10.1177/2047487315610663.

11. Berenbaum F. Osteoarthritis as an inflammatory disease (osteoarthritis is not osteoarthrosis!). Osteoarthritis Cartilage. 2013;21(1): 16-21. doi:10.1016/j.joca.2012.11.012.

12. Hoeven TA, Leening MJ, Bindels PJ, et al. Disability and not osteoarthritis predicts cardiovascular disease: a prospective population- based cohort study. Ann Rheum Dis. 2015;74(4):752-6. doi:10.1136/annrheumdis-2013-204388.

13. Loef M, van der Geest RJ, Lamb HJ, et al. Mediation of the association between obesity and osteoarthritis by blood pressure, vessel wall stiffness and subclinical atherosclerosis. Rheumatology (Oxford). 2021 Jul 1;60(7): 3268-77. doi: 10.1093/rheumatology/keaa778.

14. Abhishek A, Doherty S, Maciewicz R, et al. Association between low cortical bone mineral density, soft-tissue calcification, vascular calcification and chondrocalcinosis: a case-control study. Ann Rheum Dis. 2014; 73(11):1997-2002. doi:10.1136/annrheumdis-2013-203400.

15. Hollander JL, Jessar RA, McCarty DJ. Synovianalysis: an aid in arthritis diagnosis. Bull Rheum Dis. 1961 Dec;12:263-4.

16. Nasonov EL, editor. Rossiiskie klinicheskie rekomendatsii. Revmatologiya [Russian clinical guidelines. Rheumatology]. Moscow: GEOTAR-Media; 2020. 340 p.

17. Zhang W, Doherty M, Peat G, et al. EULAR evidence-based recommendations for the diagnosis of knee osteoarthritis. Ann Rheum Dis. 2010 Mar;69(3):483-9. doi: 10.1136/ard.2009.113100. Epub 2009 Sep 17.

18. World Health Organization (WHO). Obesity: prevention and management of the global epidemic. Report of the WHO Consultation. World Health Organ Tech Rep Ser. 2000;894(i-xii):1-253.

19. Montalescot G, Sechtem U, Achenbach S, et al. 2013 ESC guidelines on the management of stable coronary artery disease: the Task Force on the management of stable coronary artery disease of the European Society of Cardiology. Eur Heart J. 2013; 34(38):2949-3003. doi: 10.1093/eurheartj/eht296.

20. Committee of experts of the Russian Cardiological Society. National recommendations for cardiovascular prophylaxis. Kardiovaskulyarnaya Terapiya i Profilaktika. 2011;10(6 Suppl 2):1-64. (In Russ.)

21. Fernandez-Friera L, Fuster V, Lopez-Melgar B, et al. Normal LDL-Cholesterol Levels Are Associated With Subclinical Atherosclerosis in the Absence of Risk Factors. J Am Coll Cardiol. 2017;70(24): 2979-91. doi:10.1016/j.jacc.2017.10.024.

22. Simon A, Megnien JL, Chironi G. The value of carotid intima-media thickness for predicting cardiovascular risk. Arterioscler Thromb Vasc Biol. 2010;30(2):182-5. doi:10.1161/ATVBAHA.109.196980

23. Qu B, Qu T. Causes of changes in carotid intima-media thickness: a literature review. Cardiovasc Ultrasound. 2015 Dec 15;13:46. doi: 10.1186/s12947-015-0041-4.

24. Kaveshnikov VS, Serebryakova VN, Trubacheva IA. Percentile distribution of the thickness of the «intima-media» complex in the general population of working age. Sibirskii meditsinskii zhurnal. 2019;34(1): 145-51. (In Russ.)

25. Baldassarre D, Hamsten A, Veglia F, et al. Measurements of carotid intima-media thickness and of interadventitia common carotid diameter improve prediction of cardiovascular events: results of the IMPROVE (Carotid Intima Media Thickness [IMT] and IMTProgression as Predictors of Vascular Events in a High Risk European Population) study. J Am Coll Cardiol. 2012;60(16):1489-99. doi:10.1016/j.jacc.2012.06.034.

26. Khot UN, Khot MB, Bajzer CT, et al. Prevalence of conventional risk factors in patients with coronary heart disease. JAMA. 2003;290(7):898-904. doi:10.1001/jama.290.7.898.

27. Kwon GP, Schroeder JL, Amar MJ, et al. Contribution of macromolecular structure to the retention of low-density lipoprotein at arterial branch points. Circulation. 2008; 117(22):2919-27. doi:10.1161/CIRCULATIONAHA.107.754614.

28. Perez-Ruiz F, Martinez-Indart L, Carmona L, et al. Tophaceous gout and high level of hyperuricaemia are both associated with increased risk of mortality in patients with gout. Ann Rheum Dis. 2014;73(1):177-82. doi:10.1136/annrheumdis-2012-202421.

29. Mathieu S, Couderc M, Tournadre A, Soubrier M. Cardiovascular profile in osteoarthritis: a meta-analysis of cardiovascular events and risk factors. Joint Bone Spine. 2019;86(6):679-84. doi:10.1016/j.jbspin.2019.06.013.

30. Perk J, De Backer G, Gohlke H, et al. European Association for Cardiovascular Prevention & Rehabilitation (EACPR); ESC Committee for Practice Guidelines (CPG). European Guidelines on cardiovascular disease prevention in clinical practice (version 2012). Eur Heart J. 2012;33(13):1635-701.doi: 10.1093/eurheartj/ehs092.