Warfarin Use May Be Associated with Increase Prevalence of Valvular Calcification.

Warfarin affects the synthesis and function of the matrix Gla protein, a vitamin K–dependent protein, which is a potent inhibitor of tissue calcification. We aimed to study the association of use of warfarin with calcification of the mitral valve, mitral annulus, and aortic valve.

We reviewed 1155 patient's charts with a diagnosis of nonvalvular atrial fibrillation. Based on the chart review, patients were grouped into the warfarin group and the no warfarin group. The following parameters were recorded in both groups: age, ethnicity, glomerular filtration rate, calcium-phosphate product, lipid profile, coronary artery disease, diabetes, hypertension and intake of medications including aspirin, angiotensin converting enzyme inhibitors, angiotensin receptor blockers, statins, and beta blockers. All the echocardiograms were analyzed by two cardiologists blinded to the clinical details of subjects but alerted to evaluate for the presence of mitral valve calcium (MVC), mitral annular calcium (MAC), aortic valve calcium (AVC), or any of the three. Stepwise logistic regression analysis was used to identify significant independent risk factors associated with any calcification using twenty five variables.

Out of 1155 patient records reviewed, 725(63%) were in the warfarin group and 430(37%) were in the no warfarin group. MVC, MAC, or AVC was present in 473 of 725 patients (65%) on warfarin versus 225 of 430 patients (52%) not on warfarin (p<0.0001). Stepwise logistic regression analysis showed significant independent risk factors for any valve calcification were use of warfarin (Odds ratio 1.972, p-value< 0.001), age (Odds ratio 1.078 per one year increase, p-value <0.001), dyslipidemia (Odds ratio 0.235,p-value <0.001), calcium-phosphate product (Odds ratio 1.015, p-value 0.024), and coronary artery disease ( Odds ratio 13.563, p-value <0.0001).

Warfarin intake is associated with a significantly higher prevalence of MVC, MAC or AVC. Further studies are needed to confirm this association and the duration of warfarin intake for development of calcification. A pilot study has been started to study the effect of oral vitamin K on valvular calcification.

Off Label Use: Oral Vitamin K in preventing calcification.