Abstract
Warfarin inhibits vitamin-K dependent proteins involved in bone mineralization and the prevention of vascular calcification (bone Gla protein BGP, matrix Gla protein MGP). In this multicenter, cross-sectional study with 3-year follow-up, data from 387 patients on hemodialysis for ≥1 year at 18 dialysis units were analyzed. Patients on warfarin treatment for > 1 year (11.9% of the population) were compared with the remaining cohort for vertebral fractures, vascular calcifications and mortality. Vertebral fractures and vascular calcifications were sought in L-L vertebral X-rays (D5 to L4).
Compared with controls, warfarin-treated male patients had more vertebral fractures (77.8 vs. 57.7%, p<0.04), but not females (42.1% vs. 48.4%, p=0.6); total BGP was significantly reduced (82.35 vs. 202 μg/L, p<0.0001), with lower levels in treated men (69.5 vs. women 117.0 μg/L, p=0.03). In multivariate logistic regression analyses, the use of warfarin was associated with increased odds of aortic (OR 2.58, p<0.001) and iliac calcifications (OR 2.86, p<0.001); identified confounders were age, atrial fibrillation, angina, PPI use and total BGP. Seventy-seven patients died during a 2.7±0.5 year follow-up. In univariate Cox regression analysis, patients on warfarin had a higher risk of all-cause mortality (HR 2.42, 95% CI 1.42-4.16, p=0.001) when compared with those untreated and data adjustment for confounders attenuated but confirmed the significant warfarin-mortality link (HR: 1.97, 95% CI: 1.02-3.84, P=0.046).
In hemodialysis patients, additional studies are warranted to verify the risk/benefit ratio of warfarin, which appears to be associated with significant morbidity and increased mortality.
Keywords: Hemodialysis, matrix Gla protein, mortality, osteocalcin, vascular calcifications, vertebral fractures, warfarin.
Current Vascular Pharmacology
Title:Prevalence of Vertebral Fractures, Vascular Calcifications, and Mortality in Warfarin Treated Hemodialysis Patients
Volume: 13 Issue: 2
Author(s): Maria Fusaro, Giovanni Tripepi, Marianna Noale, Mario Plebani, Martina Zaninotto, Antonio Piccoli, Agostino Naso, Davide Miozzo, Sandro Giannini, Marco Avolio, Annalisa Foschi, Maria Antonietta Rizzo, Maurizio Gallieni and The Vertebral Fractures and Vascular Calcifications Study Group
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Keywords: Hemodialysis, matrix Gla protein, mortality, osteocalcin, vascular calcifications, vertebral fractures, warfarin.
Abstract: Warfarin inhibits vitamin-K dependent proteins involved in bone mineralization and the prevention of vascular calcification (bone Gla protein BGP, matrix Gla protein MGP). In this multicenter, cross-sectional study with 3-year follow-up, data from 387 patients on hemodialysis for ≥1 year at 18 dialysis units were analyzed. Patients on warfarin treatment for > 1 year (11.9% of the population) were compared with the remaining cohort for vertebral fractures, vascular calcifications and mortality. Vertebral fractures and vascular calcifications were sought in L-L vertebral X-rays (D5 to L4).
Compared with controls, warfarin-treated male patients had more vertebral fractures (77.8 vs. 57.7%, p<0.04), but not females (42.1% vs. 48.4%, p=0.6); total BGP was significantly reduced (82.35 vs. 202 μg/L, p<0.0001), with lower levels in treated men (69.5 vs. women 117.0 μg/L, p=0.03). In multivariate logistic regression analyses, the use of warfarin was associated with increased odds of aortic (OR 2.58, p<0.001) and iliac calcifications (OR 2.86, p<0.001); identified confounders were age, atrial fibrillation, angina, PPI use and total BGP. Seventy-seven patients died during a 2.7±0.5 year follow-up. In univariate Cox regression analysis, patients on warfarin had a higher risk of all-cause mortality (HR 2.42, 95% CI 1.42-4.16, p=0.001) when compared with those untreated and data adjustment for confounders attenuated but confirmed the significant warfarin-mortality link (HR: 1.97, 95% CI: 1.02-3.84, P=0.046).
In hemodialysis patients, additional studies are warranted to verify the risk/benefit ratio of warfarin, which appears to be associated with significant morbidity and increased mortality.
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Fusaro Maria, Tripepi Giovanni, Noale Marianna, Plebani Mario, Zaninotto Martina, Piccoli Antonio, Naso Agostino, Miozzo Davide, Giannini Sandro, Avolio Marco, Foschi Annalisa, Rizzo Antonietta Maria, Gallieni Maurizio and The Vertebral Fractures and Vascular Calcifications Study Group , Prevalence of Vertebral Fractures, Vascular Calcifications, and Mortality in Warfarin Treated Hemodialysis Patients, Current Vascular Pharmacology 2015; 13 (2) . https://dx.doi.org/10.2174/15701611113119990146
DOI https://dx.doi.org/10.2174/15701611113119990146 |
Print ISSN 1570-1611 |
Publisher Name Bentham Science Publisher |
Online ISSN 1875-6212 |
Call for Papers in Thematic Issues
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Ischemic cardiovascular disease includes myocardial infarction, coronary atherosclerotic heart disease, angina pectoris, etc., constitute the leading cause of patient mortality by preventing tissues from getting sufficient oxygen and nutrients. Ischemic heart disease, as a clinical condition, is characterized by myocardial ischemia, causing an imbalance between myocardial blood supply and demand, ...read more
TREATMENT OF CARDIOVASCULAR DISEASE IN CHRONIC AND END STAGE KIDNEY DISEASE
Cardiovascular disease still remains the leading cause of death in Chronic and End Stage Kidney Disease, accounting for more than half of all deaths in dialysis patients. During the past decade, research has been focused on novel therapeutic agents that might delay or even reverse cardiovascular disease and vascular calcification, ...read more
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