Fabrice Mac-Way1, Aurélie Poulin1, Mihai Silviu Utescu1, Sacha A De Serres1, Karine Marquis2, Pierre Douville3, Simon Desmeules1, Richard Larivière1, Marcel Lebel4, Mohsen Agharazii1. 1. CHU de Québec Research Center, L'Hôtel-Dieu de Québec Hospital, Québec, QC, Canada Division of Nephrology, Faculty of Medicine, Université Laval, Québec, QC, Canada. 2. CHU de Québec Research Center, L'Hôtel-Dieu de Québec Hospital, Québec, QC, Canada. 3. Département de biologie moléculaire, de biochimie médicale et de pathologie, Faculty of Medicine, Université Laval, Québec, QC, Canada Département de biologie médicale, L'Hôtel-Dieu de Québec Hospital, CHU de Québec, Québec, QC, Canada. 4. Division of Nephrology, Faculty of Medicine, Université Laval, Québec, QC, Canada.
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.
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 HDpatients 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 HDpatients. These findings suggest that the net cardiovascular benefit of long-term warfarin therapy may need to be reevaluated in this population.
Authors: Lisa Eggebrecht; Jürgen H Prochaska; Andreas Schulz; Natalie Arnold; Claus Jünger; Sebastian Göbel; Dagmar Laubert-Reh; Harald Binder; Manfred E Beutel; Nobert Pfeiffer; Stefan Blankenberg; Karl J Lackner; Henri M Spronk; Hugo Ten Cate; Thomas Münzel; Philipp S Wild Journal: J Am Heart Assoc Date: 2018-09-04 Impact factor: 5.501