Prevalence of vertebral fractures, vascular calcifications, and mortality in warfarin treated hemodialysis patients.
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.
CNR, Institute of Neuroscience - Padova, Italy. dante.lucia@libero.it.
Maria
M
Fusaro
Giovanni
G
Tripepi
Marianna
M
Noale
Mario
M
Plebani
Martina
M
Zaninotto
Antonio
A
Piccoli
Agostino
A
Naso
Davide
D
Miozzo
Sandro
S
Giannini
Marco
M
Avolio
Annalisa
A
Foschi
Maria Antonietta
MA
Rizzo
Maurizio
M
Gallieni
D000368:Aged; D000369:Aged, 80 and over; D000925:Anticoagulants / Q000009:adverse effects*; D016022:Case-Control Studies; D003430:Cross-Sectional Studies; D005260:Female; D006801:Humans; D007558:Italy / Q000453:epidemiology; D053208:Kaplan-Meier Estimate; D007674:Kidney Diseases / Q000175:diagnosis / Q000401:mortality / Q000628:therapy*; D016015:Logistic Models; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D016017:Odds Ratio; D015995:Prevalence; D016016:Proportional Hazards Models; D006435:Renal Dialysis / Q000009:adverse effects / Q000401:mortality; D012307:Risk Factors; D012737:Sex Factors; D016103:Spinal Fractures / Q000175:diagnosis / Q000453:epidemiology* / Q000401:mortality; D013997:Time Factors; D061205:Vascular Calcification / Q000175:diagnosis / Q000453:epidemiology* / Q000401:mortality; D014859:Warfarin / Q000009:adverse effects*
D000925:Anticoagulants; D014859:Warfarin