title: Vitamin K-Dependent Protein Activity and Incident Ischemic Cardiovascular Disease: The Multi-Ethnic Study of Atherosclerosis.
abstract: Vitamin K-dependent proteins (VKDPs), which require post-translational modification to achieve biological activity, seem to contribute to thrombus formation, vascular calcification, and vessel stiffness. Whether VKDP activity is prospectively associated with incident cardiovascular disease has not been studied.
  
  
  
  VKDP activity was determined by measuring circulating des-γ-carboxy prothrombin concentrations in a random sample of 709 multiethnic adults free of cardiovascular disease drawn from the Multi-Ethnic Study of Atherosclerosis (MESA). Lower des-γ-carboxy prothrombin concentrations reflect greater VKDP activity. Subjects were followed up for the risk of ischemic cardiovascular disease (coronary heart disease, stroke, and fatal cardiovascular disease) for 11.0 years of follow-up. A total of 75 first ischemic CVD events occurred during follow-up. The incidence of ischemic cardiovascular disease increased progressively across des-γ-carboxy prothrombin quartiles, with event rates of 5.9 and 11.7 per 1000 person-years in the lowest and highest quartiles. In analyses adjusted for traditional cardiovascular risk factors and measures of vitamin K intake, a doubling of des-γ-carboxy prothrombin concentration was associated with a 1.53 (95% confidence interval, 1.09-2.13; P=0.008) higher risk of incident ischemic cardiovascular disease. The association was consistent across strata of participants with diabetes mellitus, hypertension, renal impairment, and low vitamin K nutritional intake.
  
  
  
  In this sample of middle-aged and older adults, VKDP activity was associated with incident ischemic cardiovascular events. Further studies to understand the role of this large class of proteins in cardiovascular disease are warranted.
authors.affiliation: From the Department of Medicine, Beth Israel Deaconess Medical Center, Boston, MA (J.D., K.J.M.); Department of Biostatistics, University of Washington, Seattle (R.L.Y.); Human Nutrition Research Center on Aging, Tufts University, Boston, MA (K.M.S.); College of Medicine (R.P.T.) and Department of Pathology (N.S.J.), University of Vermont, Burlington; and Nephrology Section, Veterans Affairs San Diego Healthcare System, CA (J.H.I.). jdanzige@bidmc.harvard.edu.
authors.forename: John
authors.initials: J
authors.lastname: Danziger
authors.affiliation: From the Department of Medicine, Beth Israel Deaconess Medical Center, Boston, MA (J.D., K.J.M.); Department of Biostatistics, University of Washington, Seattle (R.L.Y.); Human Nutrition Research Center on Aging, Tufts University, Boston, MA (K.M.S.); College of Medicine (R.P.T.) and Department of Pathology (N.S.J.), University of Vermont, Burlington; and Nephrology Section, Veterans Affairs San Diego Healthcare System, CA (J.H.I.).
authors.forename: Rebekah L
authors.initials: RL
authors.lastname: Young
authors.affiliation: From the Department of Medicine, Beth Israel Deaconess Medical Center, Boston, MA (J.D., K.J.M.); Department of Biostatistics, University of Washington, Seattle (R.L.Y.); Human Nutrition Research Center on Aging, Tufts University, Boston, MA (K.M.S.); College of Medicine (R.P.T.) and Department of Pathology (N.S.J.), University of Vermont, Burlington; and Nephrology Section, Veterans Affairs San Diego Healthcare System, CA (J.H.I.).
authors.forename: M Kyla
authors.initials: MK
authors.lastname: Shea
authors.affiliation: From the Department of Medicine, Beth Israel Deaconess Medical Center, Boston, MA (J.D., K.J.M.); Department of Biostatistics, University of Washington, Seattle (R.L.Y.); Human Nutrition Research Center on Aging, Tufts University, Boston, MA (K.M.S.); College of Medicine (R.P.T.) and Department of Pathology (N.S.J.), University of Vermont, Burlington; and Nephrology Section, Veterans Affairs San Diego Healthcare System, CA (J.H.I.).
authors.forename: Russell P
authors.initials: RP
authors.lastname: Tracy
authors.affiliation: From the Department of Medicine, Beth Israel Deaconess Medical Center, Boston, MA (J.D., K.J.M.); Department of Biostatistics, University of Washington, Seattle (R.L.Y.); Human Nutrition Research Center on Aging, Tufts University, Boston, MA (K.M.S.); College of Medicine (R.P.T.) and Department of Pathology (N.S.J.), University of Vermont, Burlington; and Nephrology Section, Veterans Affairs San Diego Healthcare System, CA (J.H.I.).
authors.forename: Joachim H
authors.initials: JH
authors.lastname: Ix
authors.affiliation: From the Department of Medicine, Beth Israel Deaconess Medical Center, Boston, MA (J.D., K.J.M.); Department of Biostatistics, University of Washington, Seattle (R.L.Y.); Human Nutrition Research Center on Aging, Tufts University, Boston, MA (K.M.S.); College of Medicine (R.P.T.) and Department of Pathology (N.S.J.), University of Vermont, Burlington; and Nephrology Section, Veterans Affairs San Diego Healthcare System, CA (J.H.I.).
authors.forename: Nancy S
authors.initials: NS
authors.lastname: Jenny
authors.affiliation: From the Department of Medicine, Beth Israel Deaconess Medical Center, Boston, MA (J.D., K.J.M.); Department of Biostatistics, University of Washington, Seattle (R.L.Y.); Human Nutrition Research Center on Aging, Tufts University, Boston, MA (K.M.S.); College of Medicine (R.P.T.) and Department of Pathology (N.S.J.), University of Vermont, Burlington; and Nephrology Section, Veterans Affairs San Diego Healthcare System, CA (J.H.I.).
authors.forename: Kenneth J
authors.initials: KJ
authors.lastname: Mukamal
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D050197:Atherosclerosis / Q000097:blood* / Q000175:diagnosis / Q000208:ethnology* / Q000401:mortality; D015415:Biomarkers / Q000097:blood*; D005260:Female; D006801:Humans; D015994:Incidence; D053208:Kaplan-Meier Estimate; D008297:Male; D008875:Middle Aged; D017202:Myocardial Ischemia / Q000097:blood* / Q000175:diagnosis / Q000208:ethnology* / Q000401:mortality; D011237:Predictive Value of Tests; D011379:Prognosis; D016016:Proportional Hazards Models; D011446:Prospective Studies; D011498:Protein Precursors / Q000097:blood*; D011516:Prothrombin; D018570:Risk Assessment; D012307:Risk Factors; D020521:Stroke / Q000097:blood* / Q000175:diagnosis / Q000208:ethnology* / Q000401:mortality; D013997:Time Factors; D014481:United States / Q000453:epidemiology; D014812:Vitamin K / Q000097:blood*; D014813:Vitamin K Deficiency / Q000097:blood / Q000208:ethnology
chemical_list: D015415:Biomarkers; D011498:Protein Precursors; D014812:Vitamin K; C008208:acarboxyprothrombin; D011516:Prothrombin
keywords: cardiovascular diseases; prothrombin; risk factors; vitamin K