Coronary calcium associated with changes in instrumental and humoral markers of sympathetic activity in patients with non-obstructive coronary atherosclerosis

Aim. To study the associations between sequential factors of the 10-year coronary heart disease (CHD) risk index MESA, heart rate variability (HRV), molecular markers of sympathetic activity and the presence or absence of calcium in the coronary arteries (CA) in patients with non-occlusive coronary atherosclerosis.
Materials and methods. A total of 30 patients with suspected CHD, as a result of which at least one CA stenosis < 70% with a left ventricular ejection fraction ≥ 50% according to transthoracic echocardiography was identified using coronary computed tomography angiography. HRV was studied by means of daily monitoring of electrocardiograms, analyzing the parameters of time and spectral analysis. All patients had blood samples taken to measure copeptin, catestatin, high-sensitivity C-reactive protein (hsCRP) and amino-terminal pro-brain natriuretic peptide (NT-proBNP). Statistical analysis was performed after dividing the distribution into two subgroups depending on the value of the coronary calcium index (coronary calcium Agatston score; CCI): group 1 (CCI 0, n = 11) and group 2 (CCI > 0, n = 19).
Results. Statistically significant (p < 0.05) correlations of CCI with lipid damage indices were established regarding total cholesterol and low-density lipoprotein cholesterol (LDL-C) (r = –0.36 and r = –0.40, respectively), coronary artery age (r = 0.77), 10-year coronary heart disease risk index MESA (r = 0.78) and 10-year prognosis of adverse cardiovascular events (r = 0.39). Multivariate regression analysis showed that the presence of coronary artery indices (CCI > 0) in patients with non-obstructive coronary artery lesions is independently associated with a family history of coronary heart disease [odds ratio (OR) 1.92, p = 0.0011]; HRV indices [NN (OR 1.75, p = 0.0001); SDANN (OR 1.43, p = 0.0136); pNN50 (OR 1.34; p = 0.0153); rMSSD (OR 1.88; p = 0.0793)] and high-density lipoprotein cholesterol (OR 1.09; p = 0.0111) were determined. The study determined threshold values of LDL-C (≤ 1.82 mmol/L; AUC = 0.72; p = 0.002) and copeptin (≤ 0.485 ngm/L; AUS = 0.672; p = 0.021) and hsCRP with catestatin (hsCRP ≤ 1.21 g/L and catestatin ≤ 138.1 μg/ml; AUC = 0.674; sensitivity 56.2%; p = 0.021), which in such patients can be used as markers associated with the presence of coronary calcium.
Conclusion. The presence of calcium in the coronary arteries in patients with non-obstructive lesions of the coronary arteries associated with an aggravated family history of CHD, disintegration of the autonomic heart regulation, which is expressed in the suppression of the activity of the parasympathetic division of the autonomic nervous system and the levels of reduction of LDL-C.

1. Бойцов С.А., Шальнова С.А., Деев А.Д., Калинина А.М. Моделирование риска развития сердечно-сосудистых заболеваний и их осложнений на индивидуальном и групповом уровнях. Терапевтический архив. 2013;85(9):4–10.

2. Hecht H.S. Coronary artery calcium scanning: past, present, and future. JACC Cardiovasc. Imaging. 2015;8(5):579–596. DOI: 10.1016/j.jcmg.2015.02.006.

3. Vonder M., van der Aalst C.M., de Koning H.J. Coronary artery calcium scoring in individuals at risk for coronary artery disease: current status and future perspectives. British Journal of Radiology. 2020;93(1113):20190880. DOI: 10.1259/bjr.20190880.

4. Yamaoka∙T., Watanabe S. Artificial intelligence in coronary artery calcium measurement: barriers and solutions for implementation into daily practice. European Journal of Radiology. 2023;164:110855. DOI: 10.1016/j.ejrad.2023.110855.

5. Воробьева Е.Н., Усолкин К.М., Мух Е.А., Воробьев Р.И., Насонов В.А. Гавриленко Н.М. Автоматизированное прогнозирование инфаркта миокарда и инсульта. Успехи современного естествознания. 2005;4:48–49.

6. Пушкарев Г.С., Мацкеплишвили С.Т., Кузнецов В.А., Акимова Е.В. Алгоритм оценки суммарного десятилетнего риска смерти от сердечно-сосудистых заболеваний у женщин 25-64 лет г. Тюмени (Тюменская шкала риска). Евразийский кардиологический журнал. 2021;(3):14–21. DOI: 10.38109/2225-1685-2021-3-14-21.

7. Knuuti J., Wijns W., Saraste A., Capodanno D., Barbato E., Funck-Brentano C. et al. 2019 ESC Guidelines for the diagnosis and management of chronic coronary syndromes: The Task Force for the diagnosis and management of chronic coronary syndromes of the European Society of Cardiology (ESC). European Heart Journal. 2020;41(3):407–477. DOI: 10.1093/eurheartj/ehz425.

8. Curry S.J., Krist A.H., Owens D.K., Barry M.J., Caughey A.B., Davidson K.W. et al. Risk assessment for cardiovascular disease with nontraditional risk factors: US preventive services task force recommendation statement. JAMA. 2018;320(3):272–280. DOI: 10.1001/jama.2018.8359.

9. Groen R.A., Jukema J.W., van Dijkman P.R.M., Bax J.J., Lamb H.J., Antoni M.L. et al. The clear value of coronary artery calcification evaluation on non-gated chest computed tomography for cardiac risk stratification. Cardiol. Ther. 2024;13(1):69–87. DOI: 10.1007/s40119-024-00354-9.

10. Hoshi R.A., Santos I.S., Bittencourt M.S., Dantas E.M., Andreão R.V., Mill J.G. et al. Association of coronary artery calcium with heart rate variability in the Brazilian longitudinal study of adult health – ELSA-Brasil. Braz. J. Med. Biol. Res. 2023;56:e12364. DOI: 10.1590/1414-431X2023e12364.

11. Vaseghi M., Shivkumar K. The role of the autonomic nervous system in sudden cardiac death. Prog. Cardiovasc. Dis. 2008;50(6):404–419. DOI: 10.1016/j.pcad.2008.01.003.

12. Borovac J.A., D’Amario D., Bozic J., Glavas D. Sympathetic nervous system activation and heart failure: current state of evidence and the pathophysiology in the light of novel biomarkers. World J. Cardiol. 2020;12(8):373–408. DOI: 10.4330/wjc.v12.i8.373.

13. Копьева К.В., Мальцева А.Н., Мочула А.В., Гракова Е.В., Завадовский К.В. Роль микроваскулярной дисфункции в патогенезе сердечной недостаточности с сохраненной фракцией выброса. Казанский медицинский журнал. 2022;103(6):918–927. DOI: 10.17816/KMJ109034.

14. Гракова Е.В., Копьева К.В., Гусакова А.М., Сморгон А.В., Ахмедов Ш.Д., Калюжин В.В. и др. Сердечная недостаточность с сохраненной фракцией выброса левого желудочка при неокклюзирующем коронарном атеросклерозе: клиническая полезность оценки вариабельности сердечного ритма. Бюллетень сибирской медицины. 2023;22(2):28–38. DOI: 10.20538/1682-0363-2023-2-28-38.

15. Agatston A.S., Janowitz W.R., Hildner F.J., Zusmer N.R., Viamonte M.Jr., Detrano R. Quantification of coronary artery calcium using ultrafast computed tomography. J. Am. Coll. Cardiol. 1990;15(4):827–832. DOI: 10.1016/0735-1097(90)90282-t.

16. Мочула А.В., Мочула О.В., Мальцева А.Н., Сулейманова А.С., Капилевич Н.А., Рябов В.В. и др. Количественная оценка миокардиального кровотока методом динамической однофотонной эмиссионной компьютерной томографии миокарда: взаимосвязь с электрокардиографическими изменениями и биохимическими маркерами повреждения у пациентов с острым инфарктом миокарда. Сибирский журнал клинической и экспериментальной медицины. 2023;39(3):66–74. DOI: 10.29001/2073-8552-2023-38-3-6674.

17. McClelland R.L., Jorgensen N.W., Budoff M., Blaha M.J., Post W.S., Kronmal R.A. et al. 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. DOI: 10.1016/j.jacc.2015.08.035.

18. Blaha M.J., Naazie I.N., Cainzos-Achirica M., Dardari Z.A., DeFilippis A.P., McClelland R.L., et al. Derivation of a Coronary Age Calculator Using Traditional Risk Factors and Coronary Artery Calcium: The Multi-Ethnic Study of Atherosclerosis. J. Am. Heart Assoc. 2021;10(6):e019351. DOI: 10.1161/JAHA.120.019351.

19. Алиева А.М, Булаева Н.И., Громова О.И., Голухова Е.З. Вариабельность сердечного ритма в оценке клинико-функционального состояния и прогноза при хронической сердечной недостаточности. Креативная кардиология. 2015;3:42–55. DOI: 10.15275/kreatkard.2015.03.04.

20. Graby J., Soto-Hernaez J., Murphy D., Oldman J., Burnett T.A., Charters P.F-P. et al. Coronary artery calcification on routine CT has prognostic and treatment implications for all ages. Clin. Radiol. 2023;78:412–420. DOI: 10.1016/j.crad.2023.02.00.

21. McClelland R.L., Chung H., Detrano R., Post W., Kronmal R.A. Distribution of coronary artery calcium by race, gender, and age: results from the Multi-Ethnic Study of Atherosclerosis (MESA). Circulation. 2006;113(1):30–37. DOI: 10.1161/CIRCULATIONAHA.105.580696.

22. Gottlieb I., Miller J.M., Arbab-Zadeh A., Dewey M., Clouse M.E., Sara L. et al. The absence of coronary calcification does not exclude obstructive coronary artery disease or the need for revascularization in patients referred for conventional coronary angiography. J. Am. Coll. Cardiol. 2010;55(7):627–634. DOI: 10.1016/j.jacc.2009.07.072.

23. Freeman A.M., Raman S.V., Aggarwal M., Maron D.J., Bhatt D.L., Parwani P. et al. Integrating coronary atherosclerosis burden and progression with coronary artery disease risk factors to guide therapeutic decision making. Am. J. Med. 2023;136(3):260–269.e7. DOI: 10.1016/j.amjmed.2022.10.021.

24. Mézquita A.J.V., Biavati F., Falk V., Alkadhi H., Hajhosseiny R., Maurovich-Horvat P. et al. Clinical quantitative coronary artery stenosis and coronary atherosclerosis imaging: a Consensus Statement from the Quantitative Cardiovascular Imaging Study Group. Nat. Rev. Cardiol. 2023;20(10):696–714. DOI: 10.1038/s41569-023-00880-4.

25. Neves P.O., Andrade J., Monção H. Coronary artery calcium score: current status. Radiol. Bras. 2017;50(3):182–189. DOI: 10.1590/0100-3984.2015.0235.

26. Villines T.C., Hulten E.A., Shaw L.J., Goyal M., Dunning A., Achenbach S. et al. CONFIRM Registry Investigators. Prevalence and severity of coronary artery disease and adverse events among symptomatic patients with coronary artery calcification scores of zero undergoing coronary computed tomography angiography: results from the CONFIRM (Coronary CT Angiography Evaluation for Clinical Outcomes: An International Multicenter) registry. J. Am. Coll. Cardiol. 2011;58(24):2533–2540. DOI: 10.1016/j.jacc.2011.10.851.

27. Curillova Z., Yaman B.F., Dorbala S., Kwong R.Y., Sitek A., El Fakhri G. et al. Quantitative relationship between coronary calcium content and coronary flow reserve as assessed by integrated PET/CT imaging. Eur. J. Nucl. Med. Mol. Imaging. 2009;36(10):1603–1610. DOI: 10.1007/s00259-009-1121-1.

28. Лысенкова Н.О., Румянцев М.И., Кратнов А.Е. Роль вегетативной нервной системы в развитии фатальных нарушений ритма сердца у пациентов с ишемической болезнью сердца. Доктор.Ру. 2016;11(128):33–35.

29. Lee S.E., Chang H.J., Sung J.M., Park H.B., Heo R., Rizvi A. et al. Effects of Statins on Coronary Atherosclerotic Plaques: The PARADIGM Study. JACC Cardiovasc. Imaging. 2018;11(10):1475–1484. DOI: 10.1016/j.jcmg.2018.04.015.

30. Lee S.E., Sung J.M., Andreini D., Budoff M.J., Cademartiri F., Chinnaiyan K. et al. Differential association between the progression of coronary artery calcium score and coronary plaque volume progression according to statins: the Progression of AtheRosclerotic PlAque DetermIned by Computed TomoGraphic Angiography Imaging (PARADIGM) study. Eur. Heart J. Cardiovasc. Imaging. 2019;20(11):1307–1314. DOI: 10.1093/ehjci/jez022.

31. Sandhu A.T., Rodriguez F., Ngo S., Patel B.N., Mastrodicasa D., Eng D. et al. Incidental Coronary Artery Calcium: Opportunistic Screening of Previous Nongated Chest Computed Tomography Scans to Improve Statin Rates (NOTIFY-1 Project). Circulation. 2023;147(9):703–714. DOI: 10.1161/CIRCULATIONAHA.