The Efficacy of Statin on Coronary Artery Calcification based on Agatston Score: An Updated Meta-analysis of Randomized Control Trials

Authors

Sony Hilal Wicaksono , Yusra Pintaningrum , Ketut Angga Aditya Putra Pramana

DOI:

10.29303/jppipa.v11i2.10221

Published:

2025-02-28

Issue:

Vol. 11 No. 2 (2025): February

Keywords:

Agatston Score, Coronary Artery Calcification, Statin

Review

Downloads

How to Cite

Wicaksono, S. H., Pintaningrum, Y., & Pramana, K. A. A. P. (2025). The Efficacy of Statin on Coronary Artery Calcification based on Agatston Score: An Updated Meta-analysis of Randomized Control Trials. Jurnal Penelitian Pendidikan IPA, 11(2), 30–37. https://doi.org/10.29303/jppipa.v11i2.10221

Downloads

Download data is not yet available.

Metrics

Metrics Loading ...

Abstract

The purpose of this study is to assess the efficacy of statin treatment on coronary artery calcifcation (CAC) in patients with asymptomatic coronary artery disease (CAD). For randomized controlled trials (RCTs) that assess the efficacy of statin treatment on CAC in patients with asymptomatic CAD, we searched in PubMed, ScienceDirect, and Cochrane. The included publications were subjected to meta-analyses using Review Manager v5.4. In comparison to control, patients with statistically significant had a lower Agatston score (MD -46.25; 95% CI -56.37 - -36.12; p < 0.00001) and had lower CAC volume (MD -24.36; 95% CI -38.21 - -10.51; p = 0.0006). Statin treatment was also linked to a decreased risk of atherosclerotic cardiovascular disease (ASCVD) events (OR 0.60, 95% CI 0.43-0.83; p = 0.002). According to our meta-analysis, the statin treatment was significant to lowering the Agatston score and CAC volume in patients with aysmptomatic CAD. Statin was also linked to a decreased risk of ASCVD events compared to control

References

Adelhoefer, S., Uddin, S. M. I., Osei, A. D., Obisesan, O. H., Blaha, M. J., & Dzaye, O. (2020). Coronary Artery Calcium Scoring: New Insights into Clinical Interpretation-Lessons from the CAC Consortium. Radiology. Cardiothoracic Imaging, 2(6), e200281. https://doi.org/10.1148/ryct.2020200281

Agatston, A. S., Janowitz, W. R., Hildner, F. J., Zusmer, N. R., Viamonte, M., & Detrano, R. (1990). Quantification of coronary artery calcium using ultrafast computed tomography. Journal of the American College of Cardiology, 15(4), 827–832. https://doi.org/https://doi.org/10.1016/0735-1097(90)90282-T

Ahmed, W., de Graaf, M. A., Broersen, A., Kitslaar, P. H., Oost, E., Dijkstra, J., Bax, J. J., Reiber, J. H. C., & Scholte, A. J. (2015). Automatic detection and quantification of the Agatston coronary artery calcium score on contrast computed tomography angiography. The International Journal of Cardiovascular Imaging, 31(1), 151–161. https://doi.org/10.1007/s10554-014-0519-4

Arad, Y., Goodman, K. J., Roth, M., Newstein, D., & Guerci, A. D. (2005). Coronary calcification, coronary disease risk factors, C-reactive protein, and atherosclerotic cardiovascular disease events: the St. Francis Heart Study. Journal of the American College of Cardiology, 46(1), 158–165. https://doi.org/10.1016/j.jacc.2005.02.088

Bauersachs, R., Zeymer, U., Brière, J.-B., Marre, C., Bowrin, K., & Huelsebeck, M. (2019). Burden of Coronary Artery Disease and Peripheral Artery Disease: A Literature Review. Cardiovascular Therapeutics, 2019, 8295054. https://doi.org/10.1155/2019/8295054

Criqui, M. H., Denenberg, J. O., Ix, J. H., McClelland, R. L., Wassel, C. L., Rifkin, D. E., Carr, J. J., Budoff, M. J., & Allison, M. A. (2014). Calcium density of coronary artery plaque and risk of incident cardiovascular events. JAMA, 311(3), 271–278. https://doi.org/10.1001/jama.2013.282535

Ferencik, M., & Chatzizisis, Y. S. (2015). Statins and the coronary plaque calcium “paradox”: Insights from non-invasive and invasive imaging. Atherosclerosis, 241(2), 783–785. https://doi.org/10.1016/j.atherosclerosis.2015.05.021

Ferreira-González, I. (2014). The Epidemiology of Coronary Heart Disease. Revista Española de Cardiología (English Edition), 67(2), 77–162. https://doi.org/10.1016/j.rec.2013.10.002

Goff, D. C. J., Lloyd-Jones, D. M., Bennett, G., Coady, S., D’Agostino, R. B., Gibbons, R., Greenland, P., Lackland, D. T., Levy, D., O’Donnell, C. J., Robinson, J. G., Schwartz, J. S., Shero, S. T., Smith, S. C. J., Sorlie, P., Stone, N. J., Wilson, P. W. F., Jordan, H. S., Nevo, L., … Tomaselli, G. F. (2014). 2013 ACC/AHA guideline on the assessment of cardiovascular risk: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines. Circulation, 129(25 Suppl 2), S49-73. https://doi.org/10.1161/01.cir.0000437741.48606.98

Grandhi, G. R., Mirbolouk, M., Dardari, Z. A., Al-Mallah, M. H., Rumberger, J. A., Shaw, L. J., Blankstein, R., Miedema, M. D., Berman, D. S., Budoff, M. J., Krumholz, H. M., Blaha, M. J., & Nasir, K. (2020). Interplay of Coronary Artery Calcium and Risk Factors for Predicting CVD/CHD Mortality: The CAC Consortium. JACC. Cardiovascular Imaging, 13(5), 1175–1186. https://doi.org/10.1016/j.jcmg.2019.08.024

Greenland, P., Blaha, M. J., Budoff, M. J., Erbel, R., & Watson, K. E. (2018). Coronary Calcium Score and Cardiovascular Risk. Journal of the American College of Cardiology, 72(4), 434–447. https://doi.org/10.1016/j.jacc.2018.05.027

Grundy, S. M., Stone, N. J., Bailey, A. L., Beam, C., Birtcher, K. K., Blumenthal, R. S., Braun, L. T., de Ferranti, S., Faiella-Tommasino, J., Forman, D. E., Goldberg, R., Heidenreich, P. A., Hlatky, M. A., Jones, D. W., Lloyd-Jones, D., Lopez-Pajares, N., Ndumele, C. E., Orringer, C. E., Peralta, C. A., … Yeboah, J. (2019). 2018 AHA/ACC/AACVPR/AAPA/ABC/ACPM/ADA/AGS/APhA/ASPC/NLA/PCNA Guideline on the Management of Blood Cholesterol: A Report of the American College of Cardiology/American Heart Association Task Force on Clinical Practice Guidelines. Circulation, 139(25), e1082–e1143. https://doi.org/10.1161/CIR.0000000000000625

Hoffmann, U., Massaro, J. M., D’Agostino, R. B. S., Kathiresan, S., Fox, C. S., & O’Donnell, C. J. (2016). Cardiovascular Event Prediction and Risk Reclassification by Coronary, Aortic, and Valvular Calcification in the Framingham Heart Study. Journal of the American Heart Association, 5(2). https://doi.org/10.1161/JAHA.115.003144

Houslay, E. S., Cowell, S. J., Prescott, R. J., Reid, J., Burton, J., Northridge, D. B., Boon, N. A., & Newby, D. E. (2006). Progressive coronary calcification despite intensive lipid-lowering treatment: a randomised controlled trial. Heart (British Cardiac Society), 92(9), 1207–1212. https://doi.org/10.1136/hrt.2005.080929

Knuuti, J., Wijns, W., Saraste, A., Capodanno, D., Barbato, E., Funck-Brentano, C., Prescott, E., Storey, R. F., Deaton, C., Cuisset, T., Agewall, S., Dickstein, K., Edvardsen, T., Escaned, J., Gersh, B. J., Svitil, P., Gilard, M., Hasdai, D., Hatala, R., … Bax, J. J. (2020). 2019 ESC Guidelines for the diagnosis and management of chronic coronary syndromes. European Heart Journal, 41(3), 407–477. https://doi.org/10.1093/eurheartj/ehz425

Kronmal, R. A., McClelland, R. L., Detrano, R., Shea, S., Lima, J. A., Cushman, M., Bild, D. E., & Burke, G. L. (2007). Risk factors for the progression of coronary artery calcification in asymptomatic subjects: results from the Multi-Ethnic Study of Atherosclerosis (MESA). Circulation, 115(21), 2722–2730. https://doi.org/10.1161/CIRCULATIONAHA.106.674143

Mahabadi, A. A., Lehmann, N., Dykun, I., Müller, T., Kälsch, H., & Erbel, R. (2015). Progression of coronary artery calcification by cardiac computed tomography. Herz, 40(6), 863–868. https://doi.org/10.1007/s00059-015-4342-z

Malguria, N., Zimmerman, S., & Fishman, E. K. (2018). Coronary Artery Calcium Scoring: Current Status and Review of Literature. Journal of Computer Assisted Tomography, 42(6), 887–897. https://doi.org/10.1097/RCT.0000000000000825

Mensah, G. A., Roth, G. A., & Fuster, V. (2019). The Global Burden of Cardiovascular Diseases and Risk Factors: 2020 and Beyond. In Journal of the American College of Cardiology (Vol. 74, Issue 20, pp. 2529–2532). https://doi.org/10.1016/j.jacc.2019.10.009

Mitchell, J. D., Fergestrom, N., Gage, B. F., Paisley, R., Moon, P., Novak, E., Cheezum, M., Shaw, L. J., & Villines, T. C. (2018). Impact of Statins on Cardiovascular Outcomes Following Coronary Artery Calcium Scoring. Journal of the American College of Cardiology, 72(25), 3233–3242. https://doi.org/10.1016/j.jacc.2018.09.051

Miyoshi, T., Kohno, K., Asonuma, H., Sakuragi, S., Nakahama, M., Kawai, Y., Uesugi, T., Oka, T., Munemasa, M., Takahashi, N., Mukohara, N., Habara, S., Koyama, Y., Nakamura, K., & Ito, H. (2018). Effect of Intensive and Standard Pitavastatin Treatment With or Without Eicosapentaenoic Acid on Progression of Coronary Artery Calcification Over 12 Months - Prospective Multicenter Study. Circulation Journal : Official Journal of the Japanese Circulation Society, 82(2), 532–540. https://doi.org/10.1253/circj.CJ-17-0419

Mori, H., Torii, S., Kutyna, M., Sakamoto, A., Finn, A. V, & Virmani, R. (2018). Coronary Artery Calcification and its Progression: What Does it Really Mean? JACC. Cardiovascular Imaging, 11(1), 127–142. https://doi.org/10.1016/j.jcmg.2017.10.012

Mortensen, M. B., Falk, E., Li, D., Nasir, K., Blaha, M. J., Sandfort, V., Rodriguez, C. J., Ouyang, P., & Budoff, M. (2018). Statin Trials, Cardiovascular Events, and Coronary Artery Calcification: Implications for a Trial-Based Approach to Statin Therapy in MESA. JACC. Cardiovascular Imaging, 11(2 Pt 1), 221–230. https://doi.org/10.1016/j.jcmg.2017.01.029

Mulders, T. A., Sivapalaratnam, S., Stroes, E. S. G., Kastelein, J. J. P., Guerci, A. D., & Pinto-Sietsma, S.-J. (2012). Asymptomatic individuals with a positive family history for premature coronary artery disease and elevated coronary calcium scores benefit from statin treatment: a post hoc analysis from the St. Francis Heart Study. JACC. Cardiovascular Imaging, 5(3), 252–260. https://doi.org/10.1016/j.jcmg.2011.11.014

Pescatore, L. A., Gamarra, L. F., & Liberman, M. (2019). Multifaceted Mechanisms of Vascular Calcification in Aging. Arteriosclerosis, Thrombosis, and Vascular Biology, 39(7), 1307–1316. https://doi.org/10.1161/ATVBAHA.118.311576

Raggi, P., Cooil, B., Shaw, L. J., Aboulhson, J., Takasu, J., Budoff, M., & Callister, T. Q. (2003). Progression of coronary calcium on serial electron beam tomographic scanning is greater in patients with future myocardial infarction. The American Journal of Cardiology, 92(7), 827–829. https://doi.org/10.1016/s0002-9149(03)00892-0

Ralapanawa, U., & Sivakanesan, R. (2021). Epidemiology and the Magnitude of Coronary Artery Disease and Acute Coronary Syndrome: A Narrative Review. Journal of Epidemiology and Global Health, 11(2), 169–177. https://doi.org/10.2991/jegh.k.201217.001

Rifai, M. Al, Blaha, M. J., Patel, J., Xiaoming, J., Cainzos-Achirica, M., Greenland, P., Budoff, M., Yeboah, J., Nasir, K., Al-Mallah, M. H., & Virani, S. S. (2020). Coronary Artery Calcification, Statin Use and Long-Term Risk of Atherosclerotic Cardiovascular Disease Events (from the Multi-Ethnic Study of Atherosclerosis). The American Journal of Cardiology, 125(6), 835–839. https://doi.org/10.1016/j.amjcard.2019.12.031

Rodriguez Garcia, M., Naves Diaz, M., & Cannata Andia, J. B. (2005). Bone metabolism, vascular calcifications and mortality: associations beyond mere coincidence. Journal of Nephrology, 18(4), 458–463.

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. (2006). 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, 113(3), 427–437. https://doi.org/10.1161/CIRCULATIONAHA.105.568147

Shioi, A., & Ikari, Y. (2018). Plaque Calcification During Atherosclerosis Progression and Regression. Journal of Atherosclerosis and Thrombosis, 25(4), 294–303. https://doi.org/10.5551/jat.RV17020

Singh, P., Emami, H., Subramanian, S., Maurovich-Horvat, P., Marincheva-Savcheva, G., Medina, H. M., Abdelbaky, A., Alon, A., Shankar, S. S., Rudd, J. H. F., Fayad, Z. A., Hoffmann, U., & Tawakol, A. (2016). Coronary Plaque Morphology and the Anti-Inflammatory Impact of Atorvastatin: A Multicenter 18F-Fluorodeoxyglucose Positron Emission Tomographic/Computed Tomographic Study. Circulation. Cardiovascular Imaging, 9(12), e004195. https://doi.org/10.1161/CIRCIMAGING.115.004195

Stone, N. J., Robinson, J. G., Lichtenstein, A. H., Bairey Merz, C. N., Blum, C. B., Eckel, R. H., Goldberg, A. C., Gordon, D., Levy, D., Lloyd-Jones, D. M., McBride, P., Schwartz, J. S., Shero, S. T., Smith, S. C. J., Watson, K., & Wilson, P. W. F. (2014). 2013 ACC/AHA guideline on the treatment of blood cholesterol to reduce atherosclerotic cardiovascular risk in adults: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines. Journal of the American College of Cardiology, 63(25 Pt B), 2889–2934. https://doi.org/10.1016/j.jacc.2013.11.002

Terry, J. G., Carr, J. J., Kouba, E. O., Davis, D. H., Menon, L., Bender, K., Chandler, E. T., Morgan, T., & Crouse, J. R. 3rd. (2007). Effect of simvastatin (80 mg) on coronary and abdominal aortic arterial calcium (from the coronary artery calcification treatment with zocor [CATZ] study). The American Journal of Cardiology, 99(12), 1714–1717. https://doi.org/10.1016/j.amjcard.2007.01.060

Vedanthan, R., Seligman, B., & Fuster, V. (2014). Global perspective on acute coronary syndrome: a burden on the young and poor. Circulation Research, 114(12), 1959–1975. https://doi.org/10.1161/CIRCRESAHA.114.302782

Villines, T. C., Hulten, E. A., Shaw, L. J., Goyal, M., Dunning, A., Achenbach, S., Al-Mallah, M., Berman, D. S., Budoff, M. J., Cademartiri, F., Callister, T. Q., Chang, H.-J., Cheng, V. Y., Chinnaiyan, K., Chow, B. J. W., Delago, A., Hadamitzky, M., Hausleiter, J., Kaufmann, P., … Min, J. K. (2011). 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. Journal of the American College of Cardiology, 58(24), 2533–2540. https://doi.org/10.1016/j.jacc.2011.10.851

Zhu, D., Mackenzie, N. C. W., Farquharson, C., & Macrae, V. E. (2012). Mechanisms and clinical consequences of vascular calcification. Frontiers in Endocrinology, 3, 95. https://doi.org/10.3389/fendo.2012.00095

Author Biographies

Sony Hilal Wicaksono, Universitas Indonesia

Yusra Pintaningrum, Mataram University

Ketut Angga Aditya Putra Pramana, General Practitioner of North Lombok General Hospital

License

Copyright (c) 2025 Sony Hilal Wicaksono, Yusra Pintaningrum, Ketut Angga Aditya Putra Pramana

Creative Commons License

This work is licensed under a Creative Commons Attribution 4.0 International License.

Authors who publish with Jurnal Penelitian Pendidikan IPA, agree to the following terms:

  1. Authors retain copyright and grant the journal right of first publication with the work simultaneously licensed under a Creative Commons Attribution 4.0 International License (CC-BY License). This license allows authors to use all articles, data sets, graphics, and appendices in data mining applications, search engines, web sites, blogs, and other platforms by providing an appropriate reference. The journal allows the author(s) to hold the copyright without restrictions and will retain publishing rights without restrictions.
  2. Authors are able to enter into separate, additional contractual arrangements for the non-exclusive distribution of the journal's published version of the work (e.g., post it to an institutional repository or publish it in a book), with an acknowledgment of its initial publication in Jurnal Penelitian Pendidikan IPA.
  3. Authors are permitted and encouraged to post their work online (e.g., in institutional repositories or on their website) prior to and during the submission process, as it can lead to productive exchanges, as well as earlier and greater citation of published work (See The Effect of Open Access).