The effect of diabetes mellitus on aortic valve stenosis and its treatment outcome: A meta-analysis review

Document Type : Review Article

Authors

1 Department of Cardiovascular Surgery, Isfahan University of Medical Sciences, Isfahan, Iran

2 Department of Statistics, Cardiac Rehabilitation Research Center, Cardiovascular Research Institute, Isfahan University of Medical Sciences, Isfahan, Iran

10.48305/arya.2026.45869.3119
Abstract
BACKGROUND: Given the importance of diabetes mellitus (DM) and its role in the development of aortic valve stenosis (AVS), as well as its association with adverse outcomes after aortic valve replacement (AVR), the present meta analysis aimed to provide a comprehensive review of previous studies in this field.
METHODS: To achieve this objective, a thorough literature search was conducted in PUBMED/MEDLINE, ScienceDirect, CINAHL, EMBASE/SCOPUS, PsycINFO, ClinicalKey, the Cochrane Central Register of Controlled Trials (CENTRAL), ProQuest, Web of Science, and Persian databases such as SID and Magiran. The number of patients, gender ratio, mean age, prevalence of T2DM, AVS, and treatment outcomes after TAVI, TAVR, and SAVR (stroke, early and late mortality) were recorded.
RESULTS: This meta‑analysis comprised 22 studies involving a total of 760,287 patients with AVS. The pooled prevalence of DM was approximately 31% (95% CI: 26–36%). DM was associated with a significantly higher risk of early mortality, including both in‑hospital mortality (OR: 2.399) and 30‑day mortality (OR: 1.45), compared with non‑DM patients (p<0.05). However, the increase in late mortality (one year or longer) among DM patients was not statistically significant. Additionally, DM patients showed a significantly elevated risk of stroke compared with non‑DM patients (OR: 1.15; 95% CI: 1.03–1.28; p=0.009).
CONCLUSION: Overall, DM appears to play a significant role in the development of AVS and is associated with adverse outcomes including mortality and stroke after AVR.

Keywords


1. Bloomgarden ZT. Diabetes and cardiovascular disease. Diabetes Care. 2011;34(3):e24–30. https://doi.org/10.2337/dc11-0007
2. Falcão-Pires I, Hamdani N, Borbély A, Gavina C, Schalkwijk CG, van der Velden J, et al. Diabetes mellitus worsens diastolic left ventricular dysfunction in aortic stenosis through altered myocardial structure and cardiomyocyte stiffness. Circulation. 2011 Sep 6;124(10):1151-9. https://doi.org/10.1161/circulationaha.111.025270
3. Thaden JJ, Nkomo VT, Enriquez-Sarano M. The global burden of aortic stenosis. Prog Cardiovasc Dis. 2014 May-Jun;56(6):565-71. https://doi.org/10.1016/j.pcad.2014.02.006
4. Driscoll K, Cruz AD, Butcher JT. Inflammatory and Biomechanical Drivers of Endothelial-Interstitial Interactions in Calcific Aortic Valve Disease. Circ Res. 2021 Apr 30;128(9):1344-70. https://doi.org/10.1161/circresaha.121.318011
5. Mendez-Bailon M, Lorenzo-Villalba N, Muñoz-Rivas N, de Miguel-Yanes JM, De Miguel-Diez J, Comín-Colet J, et al. Transcatheter aortic valve implantation and surgical aortic valve replacement among hospitalized patients with and without type 2 diabetes mellitus in Spain (2014-2015). Cardiovasc Diabetol. 2017 Nov 9;16(1):144. https://doi.org/10.1186/s12933-017-0631-6
6. Mosch J, Gleissner CA, Body S, Aikawa E. Histopathological assessment of calcification and inflammation of calcific aortic valves from patients with and without diabetes mellitus. Histol Histopathol. 2017 Mar;32(3):293-306. https://doi.org/10.14670/hh-11-797
7. Simionescu M, Popov D, Sima A, Hasu M, Costache G, Faitar S, Vulpanovici A, Stancu C, Stern D, Simionescu N. Pathobiochemistry of combined diabetes and atherosclerosis studied on a novel animal model. The hyperlipemic-hyperglycemic hamster. Am J Pathol. 1996 Mar;148(3):997-1014.
8. Testuz A, Nguyen V, Mathieu T, Kerneis C, Arangalage D, Kubota N, et al. Influence of metabolic syndrome and diabetes on progression of calcific aortic valve stenosis. Int J Cardiol. 2017 Oct 1;244:248-53. https://doi.org/10.1016/j.ijcard.2017.06.104
9. Le Quang K, Bouchareb R, Lachance D, Laplante MA, El Husseini D, Boulanger MC, et al. Early development of calcific aortic valve disease and left ventricular hypertrophy in a mouse model of combined dyslipidemia and type 2 diabetes mellitus. Arterioscler Thromb Vasc Biol. 2014 Oct;34(10):2283-91. https://doi.org/10.1161/atvbaha.114.304205
10. Mazzone T, Chait A, Plutzky J. Cardiovascular disease risk in type 2 diabetes mellitus: insights from mechanistic studies. Lancet. 2008 May 24;371(9626):1800-9. https://doi.org/10.1016/s0140-6736(08)60768-0
11. Katz R, Budoff MJ, Takasu J, Shavelle DM, Bertoni A, Blumenthal RS, et al. Relationship of metabolic syndrome with incident aortic valve calcium and aortic valve calcium progression: the Multi-Ethnic Study of Atherosclerosis (MESA). Diabetes. 2009 Apr;58(4):813-9. https://doi.org/10.2337/db08-1515
12. Banovic M, Athithan L, McCann GP. Aortic stenosis and diabetes mellitus: An ominous combination. Diab Vasc Dis Res. 2019 Jul;16(4):310-23. https://doi.org/10.1177/1479164118820657
13. Rossebø AB, Pedersen TR, Allen C, Boman K, Chambers J, Egstrup K, et al. Design and baseline characteristics of the simvastatin and ezetimibe in aortic stenosis (SEAS) study. Am J Cardiol. 2007 Apr 1;99(7):970-3. https://doi.org/10.1016/j.amjcard.2006.10.064
14. Rossebø AB, Pedersen TR. Hyperlipidaemia and aortic valve disease. Curr Opin Lipidol. 2004 Aug;15(4):447-51. https://doi.org/10.1097/01.mol.0000137229.00020.fe
15. Teo KK, Corsi DJ, Tam JW, Dumesnil JG, Chan KL. Lipid lowering on progression of mild to moderate aortic stenosis: meta-analysis of the randomized placebo-controlled clinical trials on 2344 patients. Can J Cardiol. 2011 Nov-Dec;27(6):800-8. https://doi.org/10.1016/j.cjca.2011.03.012
16. Agmon Y, Khandheria BK, Meissner I, Sicks JR, O’Fallon WM, Wiebers DO, et al. Aortic valve sclerosis and aortic atherosclerosis: different manifestations of the same disease? Insights from a population-based study. J Am Coll Cardiol. 2001 Sep;38(3):827-34. https://doi.org/10.1016/s0735-1097(01)01422-x
17. Aronow WS. Indications for surgical aortic valve replacement. J Cardiovasc Dis Diagn. 2013;4(1):1-4. https://doi.org/10.4172/2329-9517.1000e103
18. Giritharan S, Cagampang F, Torrens C, Salhiyyah K, Duggan S, Ohri S. Aortic Stenosis Prognostication in Patients With Type 2 Diabetes: Protocol for Testing and Validation of a Biomarker-Derived Scoring System. JMIR Res Protoc. 2019 Aug 12;8(8):e13186. https://doi.org/10.2196/13186
19. 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 Jul 1;262:66-70. https://doi.org/10.1016/j.ijcard.2018.03.099
20. Mosch J, Gleissner CA, Body S, Aikawa E. Histopathological assessment of calcification and inflammation of calcific aortic valves from patients with and without diabetes mellitus. Histol Histopathol. 2017 Mar;32(3):293-306. https://doi.org/10.14670/hh-11-797
21. Halkos ME, Kilgo P, Lattouf OM, Puskas JD, Cooper WA, Guyton RA, et al. The effect of diabetes mellitus on in-hospital and long-term outcomes after heart valve operations. Ann Thorac Surg. 2010 Jul;90(1):124-30. https://doi.org/10.1016/j.athoracsur.2010.03.111
22. Smith RL 2nd, Herbert MA, Dewey TM, Brinkman WT, Prince SL, Ryan WH, et al. Does body mass index affect outcomes for aortic valve replacement surgery for aortic stenosis? Ann Thorac Surg. 2012 Mar;93(3):742-6; discussion 746-7. https://doi.org/10.1016/j.athoracsur.2011.11.027
23. Mendez-Bailon M, Lorenzo-Villalba N, Muñoz-Rivas N, de Miguel-Yanes JM, De Miguel-Diez J, Comín-Colet J, et al. Transcatheter aortic valve implantation and surgical aortic valve replacement among hospitalized patients with and without type 2 diabetes mellitus in Spain (2014-2015). Cardiovasc Diabetol. 2017 Nov 9;16(1):144. https://doi.org/10.1186/s12933-017-0631-6
24. Page MJ, McKenzie JE, Bossuyt PM, Boutron I, Hoffmann TC, Mulrow CD, et al. The PRISMA 2020 statement: an updated guideline for reporting systematic reviews. BMJ. 2021;372:n71. https://doi.org/10.1136/bmj.n71
25. Cuschieri S. The STROBE guidelines. Saudi J Anaesth. 2019 Apr;13(Suppl 1):S31-34. https://doi.org/10.4103/sja.sja_543_18
26. Hajibandeh S, Hajibandeh S, Antoniou GA, Green PA, Maden M, Torella F. Reporting and Methodological Quality of Randomised Controlled Trials in Vascular and Endovascular Surgery. Eur J Vasc Endovasc Surg. 2015 Nov;50(5):664-70. https://doi.org/10.1016/j.ejvs.2015.06.114
27. Martín-Núñez E, Goñi-Olóriz M, Matilla L, Garaikoetxea M, Mourino-Alvarez L, Navarro A, et al. Influence of diabetes mellitus on the pathological profile of aortic stenosis: a sex-based approach. Cardiovasc Diabetol. 2023 Oct 17;22(1):280. https://doi.org/10.1186/s12933-023-02009-w
28-. Jex N, Greenwood JP, Cubbon RM, Rider OJ, Chowdhary A, Thirunavukarasu S, et al. Association between type 2 diabetes and changes in myocardial structure, contractile function, energetics, and blood flow before and after aortic valve replacement in patients with severe aortic stenosis. Circulation. 2023;148(15):1138-53. https://doi.org/10.1161/circulationaha.122.063444
29. Roderburg C, Loosen SH, Luedde T, Kostev K, Luedde M. Diabetes mellitus is associated with an increased incidence of aortic valve stenosis. Diab Vasc Dis Res. 2021 Sep-Oct;18(5):14791641211033819. https://doi.org/10.1177/14791641211033819
30. 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 Nov;64(11):2562-74. https://doi.org/10.1007/s00125-021-05545-w
31. Berkovitch A, Segev A, Barbash I, Grossman Y, Maor E, Erez A, et al. Clinical impact of diabetes mellitus in patients undergoing transcatheter aortic valve replacement. Cardiovasc Diabetol. 2015 Oct 1;14:131. https://doi.org/10.1186/s12933-015-0291-3
32. Nieuwkerk AC, Santos RB, Mata RB, Tchétché D, de Brito Jr FS, Barbanti M, et al. Diabetes mellitus in transfemoral transcatheter aortic valve implantation: a propensity matched analysis. Cardiovasc Diabetol. 2022 Nov 16;21(1):246. https://doi.org/10.1186/s12933-022-01654-x
33. Ram E, Kogan A, Levin S, Fisman EZ, Tenenbaum A, Raanani E, et al. Type 2 diabetes mellitus increases long-term mortality risk after isolated surgical aortic valve replacement. Cardiovasc Diabetol. 2019 Mar 15;18(1):31. https://doi.org/10.1186/s12933-019-0836-y
34. López-de-Andrés A, Perez-Farinos N, de Miguel-Díez J, Hernández-Barrera V, Méndez-Bailón M, de Miguel-Yanes JM, et al. Impact of type 2 diabetes mellitus in the utilization and in-hospital outcomes of surgical aortic valve replacement in Spain (2001-2015). Cardiovasc Diabetol. 2018 Oct 16;17(1):135. https://doi.org/10.1186/s12933-018-0780-2
35. Natorska J, Wypasek E, Grudzień G, Sobczyk D, Marek G, Filip G, et al. Does diabetes accelerate the progression of aortic stenosis through enhanced inflammatory response within aortic valves? Inflammation. 2012 Jun;35(3):834-40. https://doi.org/10.1007/s10753-011-9384-7
36. Khan S, Dargham S, Al Suwaidi J, Jneid H, Abi Khalil C. Trends and Outcomes of Aortic Valve Replacement in Patients With Diabetes in the US. Front Cardiovasc Med. 2022 Mar 18;9:844068. https://doi.org/10.3389/fcvm.2022.844068
37. Lorusso R, Gelsomino S, Lucà F, De Cicco G, Billè G, Carella R, et al. Type 2 diabetes mellitus is associated with faster degeneration of bioprosthetic valve: results from a propensity score-matched Italian multicenter study. Circulation. 2012 Jan 31;125(4):604-14. https://doi.org/10.1161/circulationaha.111.025064
38. Abramowitz Y, Jilaihawi H, Chakravarty T, Mangat G, Maeno Y, Kazuno Y, et al. Impact of Diabetes Mellitus on Outcomes After Transcatheter Aortic Valve Implantation. Am J Cardiol. 2016 May 15;117(10):1636-42. https://doi.org/10.1016/j.amjcard.2016.02.040
39. Banovic M, Brkovic V, Nedeljkovic I, Nedeljkovic M, Popovic D, Djordjevic-Dikic A, et al. Diabetes mellitus and coronary microvascular function in asymptomatic patients with severe aortic stenosis and nonobstructed coronary arteries. Diab Vasc Dis Res. 2016 May;13(3):220-7. https://doi.org/10.1177/1479164115627107
40. Nakamura T, Toda K, Kuratani T, Miyagawa S, Yoshikawa Y, Fukushima S, et al. Diabetes Mellitus Impairs Left Ventricular Mass Regression after Surgical or Transcatheter Aortic Valve Replacement for Severe Aortic Stenosis. Heart Lung Circ. 2016 Jan;25(1):68-74. https://doi.org/10.1016/j.hlc.2015.05.019
41. Ayhan H, Güney MC, Keleş T, Bozkurt E. Outcomes of Transcatheter Aortic Valve Implantation in Patients with and without Diabetes Mellitus. Braz J Cardiovasc Surg. 2024 Jul 22;39(4):e20230088. https://doi.org/10.21470/1678-9741-2023-0088
42. Wang C, Jiang L, Feng S, Shi Y, Shen H, Shi X, et al. Risk factor analysis of calcification in aortic and mitral valves in maintenance peritoneal dialysis patients. Kidney Blood Press Res. 2013;37(4-5):488-95. https://doi.org/10.1159/000355729
43. Lindman BR, Arnold SV, Madrazo JA, Zajarias A, Johnson SN, Pérez JE, et al. The adverse impact of diabetes mellitus on left ventricular remodeling and function in patients with severe aortic stenosis. Circ Heart Fail. 2011 May;4(3):286-92. https://doi.org/10.1161/circheartfailure.110.960039
44. Tzamalis P, Herzberger V, Bergmann J, Wuerth A, Bramlage P, Schroefel H, et al. The association of diabetes mellitus treated with oral antidiabetic drugs and insulin with mortality after transcatheter valve implantation: a 3-year follow-up of the TAVIK registry. Cardiovasc Diabetol. 2019 May 28;18(1):63. https://doi.org/10.1186/s12933-019-0873-6
45. Tokarek T, Dziewierz A, Wiktorowicz A, Bagienski M, Rzeszutko L, Sorysz D, et al. Effect of diabetes mellitus on clinical outcomes and quality of life after transcatheter aortic valve implantation for severe aortic valve stenosis. Hellenic J Cardiol. 2018 Mar-Apr;59(2):100-7. https://doi.org/10.1016/j.hjc.2017.08.002
46. Conrotto F, D’Ascenzo F, Giordana F, Salizzoni S, Tamburino C, Tarantini G, et al. Impact of diabetes mellitus on early and midterm outcomes after transcatheter aortic valve implantation (from a multicenter registry). Am J Cardiol. 2014 Feb 1;113(3):529-34. https://doi.org/10.1016/j.amjcard.2013.10.025
47. Katz R, Wong ND, Kronmal R, Takasu J, Shavelle DM, Probstfield JL, et al. Features of the metabolic syndrome and diabetes mellitus as predictors of aortic valve calcification in the Multi-Ethnic Study of Atherosclerosis. Circulation. 2006 May 2;113(17):2113-9. https://doi.org/10.1161/circulationaha.105.598086
48. Culler SD, Cohen DJ, Brown PP, Kugelmass AD, Reynolds MR, Ambrose K, et al. Trends in Aortic Valve Replacement Procedures Between 2009 and 2015: Has Transcatheter Aortic Valve Replacement Made a Difference? Ann Thorac Surg. 2018 Apr;105(4):1137-43. https://doi.org/10.1016/j.athoracsur.2017.10.057
49. Puls M, Bleckmann A, Jacobshagen C, Danner BC, Hasenfuß G, Seipelt R, et al. Diabetes increases short- and long-term mortality after transcatheter aortic valve implantation (TAVI). Dtsch Med Wochenschr. 2014 Apr;139(16):822-8. https://doi.org/10.1055/s-0034-1369863
50. Minha SA, Magalhaes MA, Barbash IM, Ben-Dor I, Escarcega RO, Okubagzi PG, et al. The impact of diabetes mellitus on outcome of patients undergoing transcatheter aortic valve replacement. IJC Metabolic & Endocrine. 2015;9:54-60. https://doi.org/10.1016/j.ijcme.2015.05.023
51. Bjursten H, Norrving B, Ragnarsson S. Bjursten H, Norrving B, Ragnarsson S. Late stroke after transcatheter aortic valve replacement: a nationwide study. Sci Rep. 2021 May 5;11(1):9593. https://doi.org/10.1038/s41598-021-89217-0