title: Serum thiols and cardiovascular risk scores: a combined assessment of transsulfuration pathway components and substrate/product ratios.
abstract: BACKGROUND
  Serum thiols have shown associations with surrogate markers of cardiovascular disease. However, little information is available on their combined association with validated cardiovascular risk scores for primary prevention at population level. We sought to determine whether individual serum thiol concentrations and substrate/product ratios within the transsulfuration pathway are independently associated with such scores.
  
  
  METHODS
  Data on clinical and demographic characteristics, serum thiols (homocysteine, cysteine, taurine, glutamylcysteine, total glutathione and cysteinylglycine) and high-sensitivity C-reactive protein (CRP) were collected from a sample of the Hunter Community Study without previous cardiovascular events [n=350, median age (IQR) = 62 (59-66) years]. Five-year absolute cardiovascular risk score for each subject was calculated using the Framingham Risk Equation.
  
  
  RESULTS
  Median risk score was 7% (IQR 4-10). After adjusting for body mass index, estimated glomerular filtration rate and physical activity regression analysis showed independent associations between cardiovascular risk scores and a) higher serum homocysteine (B 0.066, 95% CI 0.040 to 0.091, P<0.001) and lower cysteine (B -0.003, 95% CI -0.005 to -0.001, P=0.003) and glutathione (B -0.029, 95% CI -0.056 to -0.003, P=0.03) concentrations; and b) higher homocysteine/cysteine (B 0.114, 95% CI 0.066 to 0.161, P<0.001) and lower glutathione/cysteinylglycine (B -1.145, 95% CI -2.030 to -0.260, P=0.011) ratios. No significant associations were observed between cardiovascular risk scores, taurine and CRP.
  
  
  CONCLUSIONS
  Serum homocysteine, cysteine and glutathione are independently associated with cardiovascular risk scores at population level. Enzymatic pathways involved in reduced bioconversion of homocysteine into cysteine and increased glutathione degradation might play an important role in such associations.
authors.affiliation: Division of Applied Medicine, Section of Translational Medical Sciences, School of Medicine and Dentistry, University of Aberdeen, Polwarth Building, Foresterhill, Aberdeen AB25 2ZD, UK. a.a.mangoni@abdn.ac.uk
authors.forename: Arduino A
authors.initials: AA
authors.lastname: Mangoni
authors.forename: Angelo
authors.initials: A
authors.lastname: Zinellu
authors.forename: Ciriaco
authors.initials: C
authors.lastname: Carru
authors.forename: John R
authors.initials: JR
authors.lastname: Attia
authors.forename: Marc
authors.initials: M
authors.lastname: McEvoy
mesh_terms: D000368:Aged; D015415:Biomarkers / Q000097:blood; D015992:Body Mass Index; D002097:C-Reactive Protein / Q000032:analysis; D002318:Cardiovascular Diseases / Q000097:blood / Q000175:diagnosis*; D003545:Cysteine / Q000097:blood; D004151:Dipeptides / Q000097:blood; D005260:Female; D005919:Glomerular Filtration Rate; D005978:Glutathione / Q000097:blood; D006710:Homocysteine / Q000097:blood; D006801:Humans; D008297:Male; D008875:Middle Aged; D012044:Regression Analysis; D018570:Risk Assessment; D013438:Sulfhydryl Compounds / Q000097:blood*; D013455:Sulfur / Q000737:chemistry; D013654:Taurine / Q000097:blood
chemical_list: D015415:Biomarkers; D004151:Dipeptides; D013438:Sulfhydryl Compounds; D006710:Homocysteine; D013654:Taurine; C028505:cysteinylglycine; D013455:Sulfur; D002097:C-Reactive Protein; D005978:Glutathione; D003545:Cysteine