title: Homocysteine levels are inversely associated with capillary density in men, not in premenopausal women.
abstract: BACKGROUND
  Homocysteine is an independent predictor of cardiovascular risk. The mechanisms underlying this link are not fully elucidated. Whereas the role of vascular dysfunction in conduit arteries is extensively studied, the role of the microcirculation in this relationship is largely unexplored. We assessed the relationship between homocysteine levels and microvascular structure and function in a healthy, population-based cohort.
  
  
  METHODS
  We cross-sectionally studied 260 participants (aged 42 years, 47% men) of the Amsterdam Growth and Health Longitudinal Study. Nailfold videocapillaroscopy was used to assess capillary density at baseline, during venous occlusion and during peak reactive hyperaemia. The relationship between tertiles of homocysteine and microvascular outcomes was evaluated using linear regression analyses, with adjustment for BMI and blood pressure. Stratified analyses were performed for men and women.
  
  
  RESULTS
  In men, we observed a negative, nonlinear relationship between homocysteine and baseline capillary density, showing a lower capillary density in the highest tertile of homocysteine [adjusted B -8.65 capillaries/mm(2) (95%-CI: -16.05 to -1.25); P = 0.02]. In women, no significant associations were found between homocysteine and microvascular outcomes.
  
  
  CONCLUSIONS
  In men, higher homocysteine levels are associated with a reduction in basal perfusion of skin capillaries. This finding provides a novel potential explanation for how homocysteine influences cardiovascular disease risk.
authors.affiliation: Department of Internal and Vascular Medicine, Institute for Cardiovascular Research (IcaR-VU), VU University Medical Centre, Amsterdam, the Netherlands.
authors.forename: Jacqueline M
authors.initials: JM
authors.lastname: Hornstra
authors.forename: Trynke
authors.initials: T
authors.lastname: Hoekstra
authors.forename: Erik H
authors.initials: EH
authors.lastname: Serné
authors.forename: Ed C
authors.initials: EC
authors.lastname: Eringa
authors.forename: Nienke J
authors.initials: NJ
authors.lastname: Wijnstok
authors.forename: Henk J
authors.initials: HJ
authors.lastname: Blom
authors.forename: Jos W R
authors.initials: JW
authors.lastname: Twisk
authors.forename: Yvo M
authors.initials: YM
authors.lastname: Smulders
mesh_terms: D000328:Adult; D001794:Blood Pressure; D015992:Body Mass Index; D002196:Capillaries / Q000502:physiology*; D015331:Cohort Studies; D003430:Cross-Sectional Studies; D005260:Female; D005385:Fingers / Q000098:blood supply*; D006710:Homocysteine / Q000097:blood*; D006801:Humans; D016014:Linear Models; D008297:Male; D008833:Microcirculation / Q000502:physiology*; D020678:Microscopic Angioscopy; D017697:Premenopause / Q000097:blood* / Q000502:physiology; D012737:Sex Factors
chemical_list: D006710:Homocysteine
keywords: Capillaroscopy; cardiovascular diseases; homocysteine; microcirculation