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Increased vascular calcification in patients receiving warfarin.

Ekamol Tantisattamo1, Kum Hyun Han1, W Charles O'Neill2

  • 1From the Renal Division, Department of Medicine, Emory University School of Medicine, Atlanta, GA (E.T., K.H.H., C.O.N.); and Department of Internal Medicine, Inje University College of Medicine, Ilsan Paik Hospital, Goyang, Korea (K.H.H).

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Warfarin use significantly increases breast arterial calcification in women, with the risk rising with treatment duration. This effect appears cumulative and potentially irreversible, highlighting a critical consideration for long-term warfarin therapy.

Keywords:
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Area of Science:

  • Cardiovascular Medicine
  • Pharmacology
  • Radiology

Background:

  • Matrix Gla Protein (MGP) is a vitamin K-dependent inhibitor of medial arterial calcification.
  • Warfarin, an anticoagulant, inhibits MGP synthesis and activity, potentially promoting arterial calcification.
  • Previous studies indicated warfarin induces arterial calcification in experimental models, but human data were lacking.

Purpose of the Study:

  • To investigate the association between warfarin use and medial arterial calcification in humans.
  • To examine breast arterial calcification, a medial calcification easily identifiable on mammograms, as a surrogate marker.
  • To determine if warfarin-induced arterial calcification occurs in women and its relationship with treatment duration.

Main Methods:

  • Retrospective analysis of screening mammograms from women with current, past, or future warfarin use.
  • Comparison of arterial calcification prevalence between warfarin-exposed and age- and diabetes-matched untreated women.
  • Exclusion of women with severe renal impairment (serum creatinine >2.0 mg/dL) or end-stage renal disease.

Main Results:

  • Women on warfarin therapy for ≥1 month showed a 50% greater prevalence of arterial calcification (39.0%) compared to untreated women (25.9%; P<0.0001).
  • No increased prevalence of arterial calcification was observed in mammograms taken before warfarin therapy (26.4% vs. 25.8%).
  • The prevalence of arterial calcification increased with the duration of warfarin treatment, ranging from 25.0% for <1 year to 74.4% for >5 years.

Conclusions:

  • Breast arterial calcification prevalence is elevated in women with current or past warfarin use, independent of other risk factors.
  • The observed arterial calcification is likely cumulative and may be irreversible, suggesting a long-term consequence of warfarin therapy.
  • Duration of warfarin therapy is a significant determinant of arterial calcification, emphasizing the importance of treatment duration in risk assessment.