Maria Fusaro 1, M.D., Ph.D., Marianna Noale 1, M.S.C., Giovanni Tripepi 2, M.S.C., Amgela D’Angelo 3, M.D., Davide Miozzo 3,M.D., Maurizio Gallieni 4, M.D., for the VC (Vascular Calcification) Study Group 1 CNR Aging Section, Institute of Neuroscience, Padua, Italy; 2 CNR-IBIM, Clinical Epidemiology and Physiopathology of Renal Diseases Hypertension of Reggio Calabria,Reggio Calabria, Italy; 3 Nephrology Unit, University of Padua, Italy; 4 Nephrology and Dialysis Unit, San Carlo Borromeo Hospital, Milan, Italy INTRODUCTION and AIMSMETHODS In addition to bleeding, other risks have been associated with use of Warfarin (W), including an increased susceptibility ti vascular calcifications and fractures caused by a reduction in the levels of vitamin K dependent carboxylated enzymes, matrix Gla-protein (MGP) and bone Gla-protein or osteocalcin (BGP), respectively. Indeed W acts as a vitamin K antagonist reducing vitamin K levels. The Aim was to evaluate prevalence Vertebral Fractures (VF), Vascular Calcifications (VC) and Mortality in relation to W. Use. Multicenter, cross-sectional study in hemodialysis patients, 18 hospital based dialysis centers in Northern Italy. We included 387 hemodialysis patients (11,9% on W treatment). We evaluated VF with a computerized analysis, of scanned L-L vertebral X- rays (D5 to L4). Reduction of > 20% of vertebral body height was considered a VF, while reduction between 15% and 20% were considered borderline F (BF). The severity of the vertebral fractures was estimated as mild, moderate or severe (reduction:20-25%, 25-40% or > 40% respectively) (Fig. 1) (1). VC assessments were centralized. Witteman’s method (2) was used for blinded assessments in duplicate. VC were quantified by measuring the length of calcific deposits along the anterior and posterior wall of the aorta (mild cm, moderate cm and severe > 10 cm). They also evaluated the presence or absence of calcifications of the iliac arteries in the same radiograph (mild cm, moderate cm and severe > 5 cm). Any differences were resolved by consensus. Follow up 2.7 ±0.5 years. Hemodialysis patients in treatment with W. are associated with higher Prevalence VF in men, VC and increased Mortality. Additional studies are warranted to explore the association among W. treatment, VF, VC and Mortality. REFERENCES: Bone markers were: Ca 9.15 ±0.68 mg/dL, P 4.8 ±1.28 mg/dL, median ALP 83 U/L, median PTH 244 pg/mL, mediana 25(OH)D 28.9 nmol/L, median BGP 175 cmg/L, median ucBGP mcg/L, median MGP nmol/L, median PCR 1.6 mg/L. We found that 55% of patients had VF and 30.9% of patients had BF. Prevalence of VC was 80.6% (mild 20.1%, moderate 30.8%, severe 29.7%) in the aorta and 55.1% in the iliac arteries We found were significantly associated W. use in Male (6.1% vs 14.4%, p=0.044) (Fig. 2) but not in female (3); Severe Aortic calcifications appeared to be significantly related to age, male gender, hypertriglyceridemia, PPI treatment and also W. treatment, the latter with an odd ratio of 3.04 (95% CI , p=0.0016). Also Severe Iliac calcifications were significantly related to Age, PTH and W., the latter with an odd ratio of 3.30 (95% CI , p=0.0013): Further during follow-up (2.7±0.5 years) mortality was of 19.9% (on 387 total patients) with significative increase in patients users W. (Log rank test p=0.0009) (Fig 3) RESULTS CONCLUSIONS WARFARIN USE IS ASSOCIATED WITH HIGHER PREVALENCE VERTEBRAL FRACTURES, VASCULAR CALCIFICATIONS AND INCREASED MORTALITY IN CHRONIC KIDNEY DISEASE Fig.1 Types of vertebral fractures Figure 3. Warfarin treatment and mortality 1.Genant HK, Wu CY, Van Kuijk C et al. Vertebral fracture assessment using a semiquantitative technique. J Bone Miner Res 1993; 8: 1137– Witterman JC, Grobbee DE, Valkenburg HA et al. J-shaped relation between change in diastolic blood pressure and progression of aortic atherosclerosis. Lancet 343: , Gage BF, Birman E, Radford MJ: Risk of osteoporotic fracture in elderly patients taking warfarin: results from National Registry of Atrial Fibrillation 2. Arch Intern Med 23: 241-6, 2006 Corresponding Author Maria Fusaro, M.D., Ph.D. CNR Aging Section, Institute of Neuroscience, Padua, Italy Via Giustiniani, 2, Padova, Italy. Telephone: FAX: Participating centers: Adria (Dott. Stoppa F; Dott.ssa Bernardi AM); Bassano del Grappa (Dott.ssa Pellanda V; Dott. Dell’Aquila R); Belluno (Dott. Tarroni G; Dott. De Paoli Vitali); Bolzano (Dott. Corradini R; Dott. Avolio M; Dott.Giacon B); Castelfranco V.to (Dott. Ferraro A; Dott. De Luca M); Dolo (Dott. Lucatello S; Dott.ssa Meneghel G); Feltre (Dott. Vianello A; Dott. Antonucci F); Firenze (Dott.ssa Grimaldi C; Dott. Mannarino A); Lodi (Dott. Barbisoni F; Dott. Elli A); Mestre (Dott. Morachiello P; Dott. Feriani M); Padova (Dott.ssa Rebeshini M; Dott. Naso A); Piove di Sacco-Chioggia (Dott.ssa Spinello M; Dott. Urso M); Rovigo (Dott.ssa Pati T; Dott. Gemelli A; Dott.ssa Bernardi AM); Schio (Dott.ssa Magonara FM; Dott. Axia M); Sesto SG (Dott. Ciurlino D; Dott. Bertoli S); Trento (Dott. Pica A; Dott.ssa Venturelli C; Dott. Brunori G); Treviso (Dott.ssa Puggia R; Dott.ssa Caberlotto A; Dott.ssa Mastrosimone S; Dott. Cascone C); Voghera (Dott.ssa Foschi A; Dott Milanesi F) Figure 2. Vertebral fractures and Gender in hemodialysis patients