Warfarin use and the risk of valvular calcification.
BACKGROUND
Warfarin affects the synthesis and function of the matrix Gla-protein, a vitamin K-dependent protein, which is a potent inhibitor of tissue calcification.


OBJECTIVE
To investigate the incidence of mitral valve calcium (MVC), mitral annular calcium (MAC) and aortic valve calcium (AVC) in patients with non-valvular atrial fibrillation (AF) treated with warfarin vs. no warfarin.


METHODS
Of 1155 patients, mean age 74 years, with AF, 725 (63%) were treated with warfarin and 430 (37%) without warfarin. The incidence of MVC, MAC and AVC was investigated in these 1155 patients with two-dimensional echocardiograms. Unadjusted logistic regression analysis was conducted to examine the association between the use of warfarin and the incidence of MVC, MAC or AVC. Logistic regression analyses were also conducted to investigate whether the relationship stands after adjustment for confounding risk factors such as age, sex, race, ejection fraction, smoking, hypertension, diabetes, dyslipidemia, coronary artery disease (CAD), glomerular filtration rate, calcium, phosphorus, calcium-phosphorus product, alkaline phosphatase, use of aspirin, beta blockers, angiotensin-converting enzyme inhibitors or angiotensin receptor blockers, and statins.


RESULTS
There was a significant association between the use of warfarin and the risk of calcification [unadjusted odds ratio = 1.71, 95% CI = (1.34-2.18)]. The association still stands after adjustment for confounding risk factors. MVC, MAC or AVC was present in 473 of 725 patients (65%) on warfarin vs. 225 of 430 patients (52%) not on warfarin (P < 0.0001). Whether this is a causal relationship remains unknown.


CONCLUSIONS
Use of warfarin in patients with AF is associated with an increased prevalence of MVC, MAC or AVC.
Division of Cardiology, Department of Medicine, New York Medical College, Valhalla, NY 10595, USA. ROBERT_LERNER@nymc.edu
R G
RG
Lerner
W S
WS
Aronow
A
A
Sekhri
C
C
Palaniswamy
C
C
Ahn
T
T
Singh
R
R
Sandhu
J A
JA
McClung
D000368:Aged; D000369:Aged, 80 and over; D001021:Aortic Valve / Q000473:pathology*; D001281:Atrial Fibrillation / Q000150:complications / Q000188:drug therapy; D002114:Calcinosis / Q000139:chemically induced*; D002135:Calcium-Binding Proteins / Q000096:biosynthesis / Q000502:physiology; D016326:Extracellular Matrix Proteins / Q000096:biosynthesis / Q000502:physiology; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D008943:Mitral Valve / Q000473:pathology*; D012044:Regression Analysis; D012189:Retrospective Studies; D012306:Risk; D012307:Risk Factors; D014859:Warfarin / Q000009:adverse effects* / Q000627:therapeutic use; D000097568:Matrix Gla Protein
D002135:Calcium-Binding Proteins; D016326:Extracellular Matrix Proteins; D014859:Warfarin; D000097568:Matrix Gla Protein