title: Fetuin-A, glycemic status, and risk of cardiovascular disease: The Multi-Ethnic Study of Atherosclerosis.
abstract: OBJECTIVE
  Fetuin-A is a hepatic secretory protein that both promotes insulin resistance and inhibits arterial calcification. Previous studies have suggested that the association of fetuin-A with incident cardiovascular disease (CVD) might be modified by glycemic status.
  
  
  RESULTS
  We conducted a case-cohort study of fetuin-A and incident non-fatal CVD nested in the Multi-Ethnic Study of Atherosclerosis with follow-up from 2000 to 2007. Fetuin-A concentrations were measured from baseline serum samples among 2505 randomly selected subcohort members and 142 incident cases. In weighted multivariable Cox regression models, no association was observed between fetuin-A and incident CVD in the total study population (HR per SD = 1.01; 95% CI: 0.84, 1.23). Although associations with CVD events were not statistically significant within categories of glycemic status, our results tended to support the interaction with glycemic status observed in other studies, with a positive trend restricted to participants with impaired fasting glucose or diabetes (HR per SD = 1.20; 95% CI: 0.89, 1.63) and an inverse trend among normoglycemic individuals (HR = 0.89; 95% CI: 0.69-1.13) (p-interaction = 0.04). In addition, we observed significant interaction between fasting glucose and fetuin-A when both were treated continuously in the subset of participants not using diabetes medication (p-interaction = 0.006).
  
  
  CONCLUSIONS
  Our results suggest that fetuin-A is not associated with an overall risk of CVD, but support prior evidence indicating that the association might be modified by glycemic status.
authors.affiliation: Department of Nutrition, Harvard T.H. Chan School of Public Health, Boston, MA, USA.
authors.forename: Sarah A
authors.initials: SA
authors.lastname: Aroner
authors.affiliation: Department of Nutrition, Harvard T.H. Chan School of Public Health, Boston, MA, USA.
authors.forename: David E
authors.initials: DE
authors.lastname: St-Jules
authors.affiliation: Division of General Medicine and Primary Care, Beth Israel Deaconess Medical Center, Boston, MA, USA.
authors.forename: Kenneth J
authors.initials: KJ
authors.lastname: Mukamal
authors.affiliation: Division of Nephrology and Kidney Research Institute, Department of Medicine, University of Washington, USA.
authors.forename: Ronit
authors.initials: R
authors.lastname: Katz
authors.affiliation: Division of General Internal Medicine, University of California, San Francisco, USA.
authors.forename: Michael G
authors.initials: MG
authors.lastname: Shlipak
authors.affiliation: Department of Family and Preventive Medicine, University of California, San Diego, USA.
authors.forename: Michael H
authors.initials: MH
authors.lastname: Criqui
authors.affiliation: Division of Nephrology and Kidney Research Institute, Department of Medicine, University of Washington, USA.
authors.forename: Bryan
authors.initials: B
authors.lastname: Kestenbaum
authors.affiliation: The New York Academy of Medicine, New York, NY, USA.
authors.forename: David S
authors.initials: DS
authors.lastname: Siscovick
authors.affiliation: Division of Nephrology and Kidney Research Institute, Department of Medicine, University of Washington, USA.
authors.forename: Ian H
authors.initials: IH
authors.lastname: de Boer
authors.affiliation: Department of Pathology and Laboratory Medicine, University of Vermont College of Medicine, USA.
authors.forename: Nancy S
authors.initials: NS
authors.lastname: Jenny
authors.affiliation: Los Angeles Biomedical Research Institute at Harbor-UCLA Medical Center, USA.
authors.forename: Matthew J
authors.initials: MJ
authors.lastname: Budoff
authors.affiliation: Division of Nephrology-Hypertension, Department of Medicine, University of California, San Diego, CA, USA; Nephrology Section, Veterans Affairs San Diego Healthcare System, San Diego, CA, USA.
authors.forename: Joachim H
authors.initials: JH
authors.lastname: Ix
authors.affiliation: Department of Nutrition, Harvard T.H. Chan School of Public Health, Boston, MA, USA. Electronic address: mkjensen@hsph.harvard.edu.
authors.forename: Majken K
authors.initials: MK
authors.lastname: Jensen
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D050197:Atherosclerosis / Q000097:blood* / Q000453:epidemiology*; D001786:Blood Glucose / Q000378:metabolism; D002318:Cardiovascular Diseases / Q000097:blood* / Q000453:epidemiology*; D016022:Case-Control Studies; D015331:Cohort Studies; D003920:Diabetes Mellitus / Q000097:blood / Q000453:epidemiology; D005006:Ethnicity; D005260:Female; D006801:Humans; D006943:Hyperglycemia / Q000097:blood / Q000453:epidemiology; D007333:Insulin Resistance; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D016016:Proportional Hazards Models; D011446:Prospective Studies; D012307:Risk Factors; D014481:United States; D060749:alpha-2-HS-Glycoprotein / Q000378:metabolism*
chemical_list: C556354:AHSG protein, human; D001786:Blood Glucose; D060749:alpha-2-HS-Glycoprotein
keywords: Blood glucose; Cardiovascular disease; Fetuin-A