Skip to main content
SpringerLink
Log in

Long-term vitamin-K antagonist use and coronary artery calcification

Langzeittherapie mit Vitamin-K-Antagonisten und Koronarsklerose

  • Original articles
  • Published:
Herz Aims and scope Submit manuscript

Abstract

Background

The aim of this study was to investigate the impact of vitamin K antagonist (VKA) therapy on coronary artery calcification (CAC) by comparing long-term VKA users with metallic prosthetic valves (MPVs) and VKA-free patients undergoing coronary calcium scoring for cardiovascular (CV) risk stratification.

Methods

A total of 108 patients (43 VKA users with MPV and 65 gender-, age-, and risk-factor-matched VKA-free patients) were included in the study. CAC was determined via computed tomography (CT) and quantified on the basis of the Agatston score. The VKA group comprised patients who had an MPV for longer than 5 years, which entailed long-term VKA use.

Results

Long-term VKA users had more calcified coronary arteries compared with the control group (178.1 ± 278 vs. 61.1 ± 130.6, p = 0.01). There was no difference between groups in terms of traditional CV risk factors. The mean duration of VKA use was 15 ± 7 years for the patients with MPV. There was no correlation between the duration of VKA use and mean Agatston score (r = 0.2, p = 0.215).

Conclusion

With its unique selection of patient groups, our study extends the findings of previous research that long-term VKA use is related to CAC as detected via CT scanning. The longer and more potent VKA regimen required for MPV patients is the primary cause of CAC in this group.

Zusammenfassung

Hintergrund

Ziel der vorliegenden Studie war es, den Einfluss einer Therapie mit Vitamin-K-Antagonisten (VKA) auf die Kalzifikation der Koronararterien zu untersuchen, indem die Langzeit-VKA-Therapie bei Patienten mit Klappenprothesen aus Metall („metallic prosthetic valves“, MPV) und Patienten ohne VKA anhand des koronaren Kalziumscores zur kardiovaskulären Risikostratifizierung verglichen wurde.

Methoden

In die Studie wurden insgesamt 108 Patienten (43 mit VKA und MPV sowie 65 in Bezug auf Geschlecht, Alter und Risikofaktoren vergleichbare Patienten ohne VKA) einbezogen. Das Vorliegen einer Koronarsklerose wurde mittels Computertomographie (CT) untersucht und anhand des Agatston-Scores quantifiziert. Die VKA-Gruppe umfasste Patienten mit einer MPV seit mehr als 5 Jahren und daher mit einer Langzeit-VKA-Therapie.

Ergebnisse

Bei Patienten unter Langzeit-VKA wurden mehr kalzifizierte Koronarien als in der Kontrollgruppe festgestellt (178,1 ± 278 vs. 61,1 ± 130,6; p = 0,01). Hinsichtlich herkömmlicher kardiovaskulärer Risikofaktoren bestand kein Unterschied zwischen den Gruppen. Die mittlere Dauer der VKA-Therapie bei den Patienten mit MPV betrug 15 ± 7 Jahre. Es fand sich keine Korrelation zwischen der Dauer der VKA-Therapie und dem Agatston-Score im Mittel (r = 0,2; p = 0,215).

Schlussfolgerung

Mit der besonderen Auswahl der Patientengruppen trägt die vorliegende Studie zur Erweiterung der Ergebnisse früherer Untersuchungen bei, dass eine Langzeittherapie mit VKA in Zusammenhang mit in der CT diagnostizierter Koronarsklerose stehe. Die bei Patienten mit MPV erforderliche längere und stärkere VKA-Therapie stellt die primäre Ursache für Koronarsklerose in dieser Gruppe dar.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References

  1. Hohnloser SH (2016) Treatment safety of non-vitamin K oral anticoagulants in patients with atrial fibrillation. Herz 41(1):37–47

    Article  CAS  Google Scholar 

  2. Chatrou ML, Winckers K, Hackeng TM et al (2012) Vascular calcification: the price to pay for anticoagulation therapy with vitamin K‑antagonists. Blood Rev 26(4):155–166. https://doi.org/10.1016/j.blre.2012.03.002

    Article  CAS  PubMed  Google Scholar 

  3. Luo G, Ducy P, McKee MD et al (1997) Spontaneous calcification of arteries and cartilage in mice lacking matrix GLA protein. Nature 386(6620):78–81. https://doi.org/10.1038/386078a0

    Article  CAS  PubMed  Google Scholar 

  4. Weijs B, Blaauw Y, Rennenberg RJ et al (2011) Patients using vitamin K antagonists show increased levels of coronary calcification: an observational study in low-risk atrial fibrillation patients. Eur Heart J 32(20):2555–2562. https://doi.org/10.1093/eurheartj/ehr226

    Article  CAS  PubMed  Google Scholar 

  5. Agatston AS, Janowitz WR, Hildner FJ et al (1990) Quantification of coronary artery calcium using ultrafast computed tomography. J Am Coll Cardiol 15(4):827–832

    Article  CAS  Google Scholar 

  6. Budoff MJ, Nasir K, McClelland RL, Detrano R, Wong N, Blumenthal RS, Kondos G, Kronmal RA (2009) Coronary calcium predicts events better with absolute calcium scores than age-sex-race/ethnicity percentiles: MESA (Multi-Ethnic Study of Atherosclerosis). J Am Coll Cardiol 53(4):345–352. https://doi.org/10.1016/j.jacc.2008.07.072

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  7. Demer LL, Tintut Y (2008) Vascular calcification: pathobiology of a multifaceted disease. Circulation 117(22):2938–2948. https://doi.org/10.1161/CIRCULATIONAHA.107.743161

    Article  PubMed  PubMed Central  Google Scholar 

  8. Kataoka Y, Wolski K, Uno K et al (2012) Spotty calcification as a marker of accelerated progression of coronary atherosclerosis: insights from serial intravascular ultrasound. J Am Coll Cardiol 59(18):1592–1597. https://doi.org/10.1016/j.jacc.2012.03.012

    Article  PubMed  Google Scholar 

  9. Criqui MH, Denenberg JO, Ix JH et al (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

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  10. Criqui MH, Knox JB, Denenberg JO et al (2017) Coronary artery calcium volume and density: potential interactions and overall predictive value: the multi-ethnic study of atherosclerosis. JACC Cardiovasc Imaging 10(8):845–854. https://doi.org/10.1016/j.jcmg.2017.04.018

    Article  PubMed  Google Scholar 

  11. Rennenberg RJ, Kessels AG, Schurgers LJ et al (2009) Vascular calcifications as a marker of increased cardiovascular risk: a meta-analysis. Vasc Health Risk Manag 5(1):185–197

    Article  CAS  Google Scholar 

  12. Poterucha TJ, Goldhaber SZ (2016) Warfarin and vascular calcification. Am J Med 129(6):635e1–635e4. https://doi.org/10.1016/j.amjmed.2015.11.032

    Article  CAS  Google Scholar 

  13. Johnson RC, Leopold JA, Loscalzo J (2006) Vascular calcification: pathobiological mechanisms and clinical implications. Circ Res 99(10):1044–1059. https://doi.org/10.1161/01.RES.0000249379.55535.21

    Article  CAS  Google Scholar 

  14. Herrmann SM, Whatling C, Brand E et al (2000) Polymorphisms of the human matrix gla protein (MGP) gene, vascular calcification, and myocardial infarction. Arterioscler Thromb Vasc Biol 20(11):2386–2393

    Article  CAS  Google Scholar 

  15. Sheng K, Zhang P, Lin W et al (2017) Association of Matrix Gla protein gene (rs1800801, rs1800802, rs4236) polymorphism with vascular calcification and atherosclerotic disease: a meta-analysis. Sci Rep 7(1):8713. https://doi.org/10.1038/s41598-017-09328-5

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  16. Khosroshahi HE, Sahin SC, Akyuz Y et al (2014) Long term follow-up of four patients with Keutel syndrome. Am J Med Genet A 164 A(11):2849–2856. https://doi.org/10.1002/ajmg.a.36699

    Article  CAS  PubMed  Google Scholar 

  17. Munroe PB, Olgunturk RO, Fryns JP et al (1999) Mutations in the gene encoding the human matrix Gla protein cause Keutel syndrome. Nat Genet 21(1):142–144. https://doi.org/10.1038/5102

    Article  CAS  PubMed  Google Scholar 

  18. Kruger T, Oelenberg S, Kaesler N et al (2013) Warfarin induces cardiovascular damage in mice. Arterioscler Thromb Vasc Biol 33(11):2618–2624. https://doi.org/10.1161/ATVBAHA.113.302244

    Article  CAS  PubMed  Google Scholar 

  19. Lerner RG, Aronow WS, Sekhri A et al (2009) Warfarin use and the risk of valvular calcification. J Thromb Haemost 7(12):2023–2027. https://doi.org/10.1111/j.1538-7836.2009.03630.x

    Article  CAS  PubMed  Google Scholar 

  20. Andrews J, Psaltis PJ, Bayturan O et al (2017) Warfarin use is associated with progressive coronary arterial calcification: insights from serial Intravascular ultrasound. JACC Cardiovasc Imaging. https://doi.org/10.1016/j.jcmg.2017.04.010

    Article  PubMed  Google Scholar 

  21. Schurgers LJ, Joosen IA, Laufer EM et al (2012) Vitamin K‑antagonists accelerate atherosclerotic calcification and induce a vulnerable plaque phenotype. PLoS ONE 7(8):e43229. https://doi.org/10.1371/journal.pone.0043229

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  22. Schurgers LJ, Spronk HM, Skepper JN et al (2007) Post-translational modifications regulate matrix Gla protein function: importance for inhibition of vascular smooth muscle cell calcification. J Thromb Haemost 5(12):2503–2511. https://doi.org/10.1111/j.1538-7836.2007.02758.x

    Article  CAS  PubMed  Google Scholar 

  23. Zühlke L, Engel ME, Karthikeyan G et al (2015) Characteristics, complications, and gaps in evidence-based interventions in rheumatic heart disease: the Global Rheumatic Heart Disease Registry (the REMEDY study). Eur Heart J 36(18):1115–122a

    Article  Google Scholar 

  24. Nishimura RA, Otto CM, Bonow RO et al (2017) 2017 AHA/ACC Focused Update of the 2014 AHA/ACC guideline for the management of patients with valvular heart disease: a report of the American College of Cardiology/American Heart Association Task Force on clinical practice guidelines. Circulation 135(25):e1159–e1195. https://doi.org/10.1161/CIR.0000000000000503

    Article  PubMed  Google Scholar 

  25. Nicholls SJ, Tuzcu EM, Wolski K et al (2007) Coronary artery calcification and changes in atheroma burden in response to established medical therapies. J Am Coll Cardiol 49(2):263–270. https://doi.org/10.1016/j.jacc.2006.10.038

    Article  PubMed  Google Scholar 

  26. Loffredo L, Perri L, Violi F (2015) Myocardial infarction and atrial fibrillation: different impact of anti-IIa vs anti-Xa new oral anticoagulants: a meta-analysis of the interventional trials. Int J Cardiol 178:8–9. https://doi.org/10.1016/j.ijcard.2014.10.124

    Article  PubMed  Google Scholar 

  27. Villines TC, O’Malley PG, Feuerstein IM et al (2009) Does prolonged warfarin exposure potentiate coronary calcification in humans? Results of the warfarin and coronary calcification study. Calcif Tissue Int 85(6):494–500. https://doi.org/10.1007/s00223-009-9300-4

    Article  CAS  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Faculty of Medicine, Department of Cardiology, Gazi University, Ankara, Turkey

    S. Ünlü MD, MSc, A. Şahinarslan MD, G. Gökalp MD, B. Sezenöz MD & R. M. Yalçın MD

  2. Faculty of Medicine, Department of Radiology, Gazi University, Ankara, Turkey

    H. K. Kılıç MD, G. Erbaş MD & M. Araç MD

  3. Institute of Health Sciences, Department of Pharmacology, Gazi University, Ankara, Turkey

    S. Ünlü MD, MSc

  4. Cardiology Department, Atatürk Chest Diseases and Chest Surgery Education and Research Hospital, Ankara, Turkey

    S. Ünlü MD, MSc

Authors
  1. S. Ünlü MD, MSc
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. A. Şahinarslan MD
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. H. K. Kılıç MD
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. G. Gökalp MD
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. B. Sezenöz MD
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. G. Erbaş MD
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. R. M. Yalçın MD
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. M. Araç MD
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to S. Ünlü MD, MSc.

Ethics declarations

Conflict of interest

S. Ünlü, A. Şahinarslan, H.K. Kılıç, G. Gökalp, B. Sezenöz, G. Erbaş, R.M. Yalçın, and M. Araç declare that they have no competing interests.

This article does not contain any studies with human participants or animals performed by any of the authors.

Additional information

Preliminary results of the study were presented as a poster at the European Society of Cardiology Congress 2015.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Ünlü, S., Şahinarslan, A., Kılıç, H.K. et al. Long-term vitamin-K antagonist use and coronary artery calcification. Herz 45, 580–585 (2020). https://doi.org/10.1007/s00059-018-4760-9

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00059-018-4760-9

Keywords

Schlüsselwörter

Search

Navigation