The impact of warfarin on the rate of progression of aortic stiffness in hemodialysis patients: a longitudinal study.

Abstract

BACKGROUND:

Accelerated progression of aortic stiffness in patients with advanced chronic kidney disease is not well explained by the traditional cardiovascular risk factors. We hypothesized that vitamin K deficiency may result in an accelerated progression of aortic stiffness in the pro-calcifying uremic milieu.

METHOD:

Eighteen hemodialysis (HD) patients on warfarin were matched to 54 HD patients without warfarin (control). Aortic stiffness was determined by carotid-femoral pulse wave velocity (cf-PWV) at baseline and after a mean follow-up of 1.2 years. In the control group, spontaneous vitamin K deficiency was defined as proteins induced by vitamin K deficiency/absence-II >median.

RESULTS:

At baseline, clinical characteristics and cf-PWV were similar. Adjusted cf-PWV increased by 0.86 ± 1.87 m/s in control and by 2.24 ± 2.68 m/s in warfarin group (P = 0.024). After adjustments for confounders, warfarin therapy was independently associated with progression of aortic stiffness (P = 0.016). The rate of progression of aortic stiffness showed a linear trend in response to vitamin K status and warfarin therapy, suggesting that at least part of the effects are mediated through reduced availability of vitamin K. The unadjusted and adjusted hazard ratio (HR) of warfarin therapy on mortality were, respectively, 2.40 (P = 0.006) and 2.53 (P = 0.006). In a forward conditional Cox regression analysis, age, albumin, augmentation index (AIx) and a cf-PWV > 13.8 m/s at the time of follow-up (HR: 2.11, P = 0.05) were independent determinants of mortality, whereas warfarin use was not retained as an independent factor. Finally, control patients with poor vitamin K status had an intermediate survival as compared with controls with better vitamin K status and patients with warfarin (P = 0.01).

CONCLUSION:

This is the first study to show a temporal association between warfarin, functional vitamin K deficiency and progression of aortic stiffness in HD patients. These findings suggest that the net cardiovascular benefit of long-term warfarin therapy may need to be reevaluated in this population.

• Authors: Fabrice Mac-Way, Aurélie Poulin, Mihai Silviu Utescu, Sacha A De Serres, Karine Marquis, Pierre Douville, Simon Desmeules, Richard Larivière, Marcel Lebel, Mohsen Agharazii
• Journal: Nephrology, dialysis, transplantation : official publication of the European Dialysis and Transplant Association - European Renal Association (Nephrol Dial Transplant) Vol. 29 Issue 11 Pg. 2113-20 (Nov 2014) ISSN: 1460-2385 [Electronic] England
• PMID: 24944209 (Publication Type: Journal Article, Observational Study, Research Support, Non-U.S. Gov't)
• Copyright: © The Author 2014. Published by Oxford University Press on behalf of ERA-EDTA. All rights reserved.

Chemical References

• Anticoagulants
• Warfarin

Topics

• Aged
• Anticoagulants (pharmacology)
• Aorta, Thoracic (drug effects, physiopathology)
• Cardiovascular Diseases (epidemiology, etiology, prevention & control)
• Disease Progression
• Female
• Follow-Up Studies
• Humans
• Incidence
• Kidney Failure, Chronic (complications, mortality, therapy)
• Male
• Middle Aged
• Pulse Wave Analysis
• Quebec (epidemiology)
• Renal Dialysis
• Risk Factors
• Survival Rate (trends)
• Time Factors
• Vascular Stiffness (drug effects)
• Warfarin (pharmacology)