Construction and Verification of a Predictive Model for the Progression of Aortic Valve Calcification

Zhen Guo; Zhenyu Xiong; Chaoguang Xu; Jingjing He; Shaozhao Zhang; Rihua Huang; Menghui Liu; Jiaying Li; Xinxue Liao; Xiaodong Zhuang

doi:10.5334/gh.1473

Construction and Verification of a Predictive Model for the Progression of Aortic Valve Calcification

Volume 20 (2025): Issue 1

By: Zhen Guo , Zhenyu Xiong , Chaoguang Xu, Jingjing He, Shaozhao Zhang, Rihua Huang, Menghui Liu, Jiaying Li, Xinxue Liao and Xiaodong Zhuang

Open Access

|Sep 2025

Abstract

Background: The primary objective of this study is to develop and validate a predictive model assessing the likelihood of disease progression in individuals with aortic valve calcification (AVC).

Methods: For the second and third visits, 2,533 patients were followed up. They were randomly assigned to a train set and a validation set at a ratio of 7:3. After employing the Least Absolute Shrinkage and Selection Operator (LASSO) and multiple Cox regression to filter predictors, the selected variables were input into the Cox proportional risk model for model construction. Calibration curve, Consistency Index (C-index), Receiver Operating Characteristic (ROC) curve, and Decision Curve Analysis (DCA) were employed to validate the model. Patients were categorized into low- and high-risk groups based on the model’s predicted risk score, and survival analysis was conducted using Kaplan-Meier (K-M) plots. An online platform was used to enhance the clinical utility.

Results: The incidence of AVC progression was 9.63%. LASSO-Cox regression analysis identified seven variables significantly correlated with AVC progression. In both the training and validation sets, the Area Under the Curve (AUC) and C-index of the prediction model exceeded 0.8. The calibration curve aligned closely with the diagonal line. Decision Curve Analysis (DCA) underscored the clinical application value of the model. Survival analysis demonstrated a significantly higher progression rate in the high-risk group compared to the low-risk group. The online platform visualized the probability of progression.

Conclusion: The developed predictive model has proven reliability and accuracy in forecasting the 2-, 3-, and 4-year progression rates of patients with AVC. It offers a dependable framework for estimating progression and facilitating individualized comprehensive prevention strategies for individuals with AVC.

References

Bertazzo S, Gentleman E. Aortic valve calcification: a bone of contention. Eur Heart J. 2017;38(16):1189–1193. DOI: 10.1093/eurheartj/ehw071
Open DOI Search in Google Scholar Back to article
Bortnick AE, Xu S, Kim RS, Kestenbaum B, Ix JH, Jenny NS, et al. Biomarkers of mineral metabolism and progression of aortic valve and mitral annular calcification: the Multi-Ethnic Study of Atherosclerosis. Atherosclerosis. 2019;285:79–86. DOI: 10.1016/j.atherosclerosis.2019.04.215
Open DOI Search in Google Scholar Back to article
Généreux P, Sharma RP, Cubeddu RJ, Aaron L, Abdelfattah OM, Koulogiannis KP, et al. The mortality burden of untreated aortic stenosis. J Am Coll Cardiol. 2023;82(22):2101–2109. DOI: 10.1016/j.jacc.2023.09.796
Open DOI Search in Google Scholar Back to article
Willemink MJ, Maret E, Moneghetti KJ, Kim JB, Haddad F, Kobayashi Y, et al. Incremental value of aortomitral continuity calcification for risk assessment after Transcatheter Aortic Valve Replacement. Radiol Cardiothorac Imaging. 2019;1(5):e190067. DOI: 10.1148/ryct.2019190067
Open DOI Search in Google Scholar Back to article
Ludwig S, Goßling A, Waldschmidt L, Linder M, Bhadra OD, Voigtländer L, et al. TAVR for low-flow, low-gradient aortic stenosis: prognostic impact of aortic valve calcification. Am Heart J. 2020;225:138–148. DOI: 10.1016/j.ahj.2020.03.013
Open DOI Search in Google Scholar Back to article
Owens DS, Budoff MJ, Katz R, Takasu J, Shavelle DM, Carr JJ, et al. Aortic valve calcium independently predicts coronary and cardiovascular events in a primary prevention population. JACC Cardiovasc Imaging. 2012;5(6):619–25. DOI: 10.1016/j.jcmg.2011.12.023
Open DOI Search in Google Scholar Back to article
Chan KL, Teo K, Dumesnil JG, Ni A, Tam J. Effect of lipid lowering with rosuvastatin on progression of aortic stenosis: results of the aortic stenosis progression observation: measuring effects of rosuvastatin (ASTRONOMER) trial. Circulation. 2010;121(2):306–14. DOI: 10.1161/CIRCULATIONAHA.109.900027
Open DOI Search in Google Scholar Back to article
Cowell SJ, Newby DE, Prescott RJ, Bloomfield P, Reid J, Northridge DB, et al. A randomized trial of intensive lipid-lowering therapy in calcific aortic stenosis. N Engl J Med. 2005;352(23):2389–97. DOI: 10.1056/NEJMoa043876
Open DOI Search in Google Scholar Back to article
Rossebø AB, Pedersen TR, Boman K, Brudi P, Chambers JB, Egstrup K, et al. Intensive lipid lowering with simvastatin and ezetimibe in aortic stenosis. N Engl J Med. 2008;359(13):1343–56. DOI: 10.1056/NEJMoa0804602
Open DOI Search in Google Scholar Back to article
Dichtl W, Alber HF, Feuchtner GM, Hintringer F, Reinthaler M, Bartel T, et al. Prognosis and risk factors in patients with asymptomatic aortic stenosis and their modulation by atorvastatin (20 mg). Am J Cardiol. 2008;102(6):743–8. DOI: 10.1016/j.amjcard.2008.04.060
Open DOI Search in Google Scholar Back to article
Burgess S, Ference BA, Staley JR, Freitag DF, Mason AM, Nielsen SF, et al. Association of LPA variants with risk of coronary disease and the implications for lipoprotein(a)-lowering therapies: a Mendelian randomization analysis. JAMA Cardiol. 2018;3(7):619–627. DOI: 10.1001/jamacardio.2018.1470
Open DOI Search in Google Scholar Back to article
Welsh P, Welsh C, Celis-Morales CA, Brown R, Ho FK, Ferguson LD, et al. Lipoprotein(a) and cardiovascular disease: prediction, attributable risk fraction, and estimating benefits from novel interventions. Eur J Prev Cardiol. 2022;28(18):1991–2000. DOI: 10.1093/eurjpc/zwaa063
Open DOI Search in Google Scholar Back to article
Brandenburg VM, Reinartz S, Kaesler N, Krüger T, Dirrichs T, Kramann R, et al. Slower progress of aortic valve calcification with vitamin K supplementation: results from a prospective interventional proof-of-concept study. Circulation. 2017;135(21):2081–2083. DOI: 10.1161/CIRCULATIONAHA.116.027011
Open DOI Search in Google Scholar Back to article
O’Brien KD, Probstfield JL, Caulfield MT, Nasir K, Takasu J, Shavelle DM, et al. Angiotensin-converting enzyme inhibitors and change in aortic valve calcium. Arch Intern Med. 2005;165(8):858–62. DOI: 10.1001/archinte.165.8.858
Open DOI Search in Google Scholar Back to article
Capoulade R, Clavel M-A, Mathieu P, Côté N, Dumesnil JG, Arsenault M, et al. Impact of hypertension and renin-angiotensin system inhibitors in aortic stenosis. Eur J Clin Invest. 2013;43(12):1262–72. DOI: 10.1111/eci.12169
Open DOI Search in Google Scholar Back to article
Poggianti E, Venneri L, Chubuchny V, Jambrik Z, Baroncini LA, Picano E. Aortic valve sclerosis is associated with systemic endothelial dysfunction. J Am Coll Cardiol. 2003;41(1):136–41. DOI: 10.1016/S0735-1097(02)02622-0
Open DOI Search in Google Scholar Back to article
Choi B, Lee S, Kim S-M, Lee E-J, Lee SR, Kim D-H, et al. Dipeptidyl peptidase-4 induces aortic valve calcification by inhibiting insulin-like growth factor-1 signaling in valvular interstitial cells. Circulation. 2017;135(20):1935–1950. DOI: 10.1161/CIRCULATIONAHA.116.024270
Open DOI Search in Google Scholar Back to article
Bäck M, Michel J-B. From organic and inorganic phosphates to valvular and vascular calcifications. Cardiovasc Res. 2021;117(9):2016–2029. DOI: 10.1093/cvr/cvab038
Open DOI Search in Google Scholar Back to article
Bild DE, Bluemke DA, Burke GL, Detrano R, Roux AVD, Folsom AR, et al. Multi-Ethnic Study of Atherosclerosis: objectives and design. Am J Epidemiol. 2002;156(9):871–81. DOI: 10.1093/aje/kwf113
Open DOI Search in Google Scholar Back to article
Elmariah S, Delaney JAC, O’Brien KD, Budoff MJ, Vogel-Claussen J, Fuster V, et al. Bisphosphonate use and prevalence of valvular and vascular calcification in women MESA (the Multi-Ethnic Study of Atherosclerosis). J Am Coll Cardiol. 2010;56(21):1752–9. DOI: 10.1016/j.jacc.2010.05.050
Open DOI Search in Google Scholar Back to article
Li Z-H, Hao Q-Y, Zeng Y-H, Guo J-B, Li S-C, Gao J-W, et al. Remnant cholesterol and the risk of aortic valve calcium progression: insights from the MESA study. Cardiovasc Diabetol. 2024;23(1):20. DOI: 10.1186/s12933-023-02081-2
Open DOI Search in Google Scholar Back to article
Cheng FW, Ford NA, Wood AC, Tracy R. Avocado consumption and markers of inflammation: results from the Multi-Ethnic Study of Atherosclerosis (MESA). Eur J Nutr. 2023;62(5):2105–2113. DOI: 10.1007/s00394-023-03134-8
Open DOI Search in Google Scholar Back to article
Ambale-Venkatesh B, Yang X, Wu CO, Liu K, Hundley WG, McClelland R, et al. Cardiovascular event prediction by machine learning: the Multi-Ethnic Study of Atherosclerosis. Circ Res. 2017;121(9):1092–1101. DOI: 10.1161/CIRCRESAHA.117.311312
Open DOI Search in Google Scholar Back to article
Yamamoto H, Shavelle D, Takasu J, Lu B, Mao SS, Fischer H, et al. Valvular and thoracic aortic calcium as a marker of the extent and severity of angiographic coronary artery disease. Am Heart J. 2003;146(1):153–9. DOI: 10.1016/S0002-8703(03)00105-4
Open DOI Search in Google Scholar Back to article
Bortnick AE, Buzkova P, Otvos JD, Jensen MK, Tsai MY, Budoff MJ, et al. High-density lipoprotein and long-term incidence and progression of Aortic Valve Calcification: the Multi-Ethnic Study of Atherosclerosis. Arterioscler Thromb Vasc Biol. 2022;42(10):1272–1282. DOI: 10.1161/ATVBAHA.122.318004
Open DOI Search in Google Scholar Back to article
Fashanu OE, Bizanti A, Al-Abdouh A, Zhao D, Budoff MJ, Thomas IC, et al. Progression of valvular calcification and risk of incident stroke: the Multi-Ethnic Study of Atherosclerosis (MESA). Atherosclerosis. 2020;307:32–38. DOI: 10.1016/j.atherosclerosis.2020.06.009
Open DOI Search in Google Scholar Back to article
Rutkovskiy A, Malashicheva A, Sullivan G, Bogdanova M, Kostareva A, Stensløkken K-O, et al. Valve interstitial cells: the key to understanding the pathophysiology of heart valve calcification. J Am Heart Assoc. 2017;6(9). DOI: 10.1161/JAHA.117.006339
Open DOI Search in Google Scholar Back to article
Zheng KH, Tsimikas S, Pawade T, Kroon J, Jenkins WSA, Doris MK, et al. Lipoprotein(a) and oxidized phospholipids promote valve calcification in patients with aortic stenosis. J Am Coll Cardiol. 2019;73(17):2150–2162. DOI: 10.1016/j.jacc.2019.01.070
Open DOI Search in Google Scholar Back to article
Kaiser Y, van der Toorn JE, Singh SS, Zheng KH, Kavousi M, Sijbrands EJG, et al. Lipoprotein(a) is associated with the onset but not the progression of aortic valve calcification. Eur Heart J. 2022;43(39):3960–3967. DOI: 10.1093/eurheartj/ehac377
Open DOI Search in Google Scholar Back to article
Amoakwa K, Fashanu OE, Tibuakuu M, Zhao D, Guallar E, Whelton SP, et al. Resting heart rate and the incidence and progression of valvular calcium: the Multi-Ethnic Study of Atherosclerosis (MESA). Atherosclerosis. 2018;273:45–52. DOI: 10.1016/j.atherosclerosis.2018.04.004
Open DOI Search in Google Scholar Back to article
Rogge BP, Cramariuc D, Lønnebakken MT, Gohlke-Bärwolf C, Chambers JB, Boman K, et al. Effect of overweight and obesity on cardiovascular events in asymptomatic aortic stenosis: a SEAS substudy (Simvastatin Ezetimibe in Aortic Stenosis). J Am Coll Cardiol. 2013;62(18):1683–1690. DOI: 10.1016/j.jacc.2013.04.081
Open DOI Search in Google Scholar Back to article
Briand M, Lemieux I, Dumesnil JG, Mathieu P, Cartier A, Després J-P, et al. Metabolic syndrome negatively influences disease progression and prognosis in aortic stenosis. J Am Coll Cardiol. 2006;47(11):2229–36. DOI: 10.1016/j.jacc.2005.12.073
Open DOI Search in Google Scholar Back to article
Kaltoft M, Langsted A, Nordestgaard BG. Obesity as a causal risk factor for aortic valve stenosis. J Am Coll Cardiol. 2020;75(2):163–176. DOI: 10.1016/j.jacc.2019.10.050
Open DOI Search in Google Scholar Back to article
Kopytek M, Mazur P, Ząbczyk M, Undas A, Natorska J. Diabetes concomitant to aortic stenosis is associated with increased expression of NF-κB and more pronounced valve calcification. Diabetologia. 2021;64(11):2562–2574. DOI: 10.1007/s00125-021-05545-w
Open DOI Search in Google Scholar Back to article
Natorska J. Diabetes mellitus as a risk factor for aortic stenosis: from new mechanisms to clinical implications. Kardiol Pol. 2021;79(10):1060–1067. DOI: 10.33963/KP.a2021.0137
Open DOI Search in Google Scholar Back to article
Kamalesh M, Ng C, El Masry H, Eckert G, Sawada S. Does diabetes accelerate progression of calcific aortic stenosis? Eur J Echocardiogr. 2009;10(6):723–5. DOI: 10.1093/ejechocard/jep048
Open DOI Search in Google Scholar Back to article
Larsson SC, Wallin A, Håkansson N, Stackelberg O, Bäck M, Wolk A. Type 1 and type 2 diabetes mellitus and incidence of seven cardiovascular diseases. Int J Cardiol. 2018;262:66–70. DOI: 10.1016/j.ijcard.2018.03.099
Open DOI Search in Google Scholar Back to article
Owens DS, Katz R, Takasu J, Kronmal R, Budoff MJ, O’Brien KD. Incidence and progression of aortic valve calcium in the Multi-Ethnic Study of Atherosclerosis (MESA). Am J Cardiol. 2010;105(5):701–8. DOI: 10.1016/j.amjcard.2009.10.071
Open DOI Search in Google Scholar Back to article

Articles in this issue

DOI: https://doi.org/10.5334/gh.1473 | Journal eISSN: 2211-8179

Journal RSS Feed

Language: English

Submitted on: Jul 10, 2024

Accepted on: Sep 11, 2025

Published on: Sep 24, 2025

Published by: Ubiquity Press

In partnership with: Paradigm Publishing Services

Publication frequency: 1 issue per year

Keywords:

Aortic valve calcification,

progression,

predictive model,

online platform

© 2025 Zhen Guo, Zhenyu Xiong, Chaoguang Xu, Jingjing He, Shaozhao Zhang, Rihua Huang, Menghui Liu, Jiaying Li, Xinxue Liao, Xiaodong Zhuang, published by Ubiquity Press
This work is licensed under the Creative Commons Attribution 4.0 License.

Volume 20 (2025): Issue 1