title: Homocysteine is a determinant of ApoA-I and both are associated with ankle brachial index, in an ambulatory elderly population.
abstract: OBJECTIVE
  The ankle brachial index (ABI) is an indicator of lower extremity peripheral arterial disease (PAD) and a predictor of atherothrombosis. ApoA-I and HDL are associated with PAD, in humans. Homocysteine influences the liver expression of ApoA-I and decreases its blood level and HDL in genetic mice models. We aimed therefore to evaluate whether homocysteine and its nutritional determinants, folate and vitamin B12 are associated with ABI by influencing HDL metabolism, in an ambulatory elderly population.
  
  
  METHODS
  667 elderly volunteers from rural Sicily were assessed for ABI, homocysteine and its determinants, lipid markers and other predictors of PAD. HDL size was assessed in 15 sera in upper and lower quartiles of Hcy distribution.
  
  
  RESULTS
  In multivariate analysis, ApoA-I and homocysteine were two predictors of ABI (β-coefficient = 2.86, P<0.004 and β-coefficient = -3.41, P<0.001, respectively). Homocysteine correlated negatively with ApoA-I (R = -0.147, P<0.001) and with HDL-Cholesterol (R = -0.113, P = 0.003). The associations of homocysteine, vitamin B12 and methylmalonic acid with ApoA-I and HDL2a particles and that of homocysteine with increased small size HDL3c suggested mechanisms related with impaired synthesis of ApoA-I and HDL and abnormal maturation of HDL particles.
  
  
  CONCLUSIONS
  The influence of homocysteine on ApoA-I and HDL metabolism provides new insights on its role on vascular diseases, at a cross-point between atherosclerosis and atherothrombosis.
authors.affiliation: Inserm U954, Medical Faculty and CHU of Nancy, University Henri Poincaré, Nancy, France. rm.rodriguez@chu-nancy.fr
authors.forename: Rosa Maria
authors.initials: RM
authors.lastname: Guéant-Rodriguez
authors.forename: Rosario
authors.initials: R
authors.lastname: Spada
authors.forename: Maira
authors.initials: M
authors.lastname: Moreno-Garcia
authors.forename: Guido
authors.initials: G
authors.lastname: Anello
authors.forename: Paolo
authors.initials: P
authors.lastname: Bosco
authors.forename: Laurent
authors.initials: L
authors.lastname: Lagrost
authors.forename: Antonino
authors.initials: A
authors.lastname: Romano
authors.forename: Maurizio
authors.initials: M
authors.lastname: Elia
authors.forename: Jean-Louis
authors.initials: JL
authors.lastname: Guéant
mesh_terms: D000367:Age Factors; D000368:Aged; D000369:Aged, 80 and over; D055109:Ankle Brachial Index; D016632:Apolipoprotein A-I / Q000097:blood*; D015415:Biomarkers / Q000097:blood; D008076:Cholesterol, HDL / Q000097:blood; D005260:Female; D005492:Folic Acid / Q000097:blood; D006710:Homocysteine / Q000097:blood*; D006801:Humans; D057187:Independent Living; D008297:Male; D008764:Methylmalonic Acid / Q000097:blood; D008875:Middle Aged; D010316:Particle Size; D058729:Peripheral Arterial Disease / Q000097:blood* / Q000175:diagnosis / Q000503:physiopathology; D012044:Regression Analysis; D018570:Risk Assessment; D012307:Risk Factors; D012802:Sicily; D014805:Vitamin B 12 / Q000097:blood; D016138:Walking
chemical_list: C505693:APOA1 protein, human; D016632:Apolipoprotein A-I; D015415:Biomarkers; D008076:Cholesterol, HDL; D006710:Homocysteine; D008764:Methylmalonic Acid; D005492:Folic Acid; D014805:Vitamin B 12