title: S-adenosylhomocysteine is associated with subclinical atherosclerosis and renal function in a cardiovascular low-risk population.
abstract: OBJECTIVE
  Although homocysteine has been proposed as a cardiovascular risk factor, interventional trials lowering homocysteine have not consistently demonstrated clinical benefit. Recent evidence proposed the homocysteine metabolite S-adenosylhomocysteine (SAH) rather than homocysteine itself as the real culprit in cardiovascular disease. Of note, SAH is predominantly excreted by the kidneys, and cannot be lowered by vitamin supplementation. Due to its cumbersome measurement, data from large studies on the association between SAH, kidney function and cardiovascular disease are not available.
  
  
  METHODS
  We recruited 420 apparently healthy subjects into our I Like HOMe FU study. Among all study participants, we assessed parameters of C1 metabolism (homocysteine, SAH and S-adenosylmethionine), renal function (estimated glomerular filtration rate [eGFR]) and subclinical atherosclerosis (common carotid intima-media-thickness [IMT]). eGFR was estimated by the CKD-EPIcreat-cys equation.
  
  
  RESULTS
  Traditional cardiovascular risk factors and subclinical atherosclerosis were associated with SAH, but not with homocysteine (IMT vs SAH: r = 0.129; p = 0.010; IMT vs homocysteine: r = 0.009; p = 0.853). Moreover, renal function was more closely correlated with SAH than with homocysteine (eGFR vs SAH: r = -0.335; p < 0.001; eGFR vs homocysteine: r = -0.250; p < 0.001). The association between eGFR and SAH remained significant after adjustment for traditional cardiovascular risk factors.
  
  
  CONCLUSIONS
  In summary, cardiovascular risk factors, subclinical atherosclerosis and eGFR are more strongly associated with SAH than with homocysteine in apparently healthy subjects. Thus, SAH might represent a more promising target to prevent cardiovascular disease than homocysteine.
authors.affiliation: Department of Internal Medicine IV, Saarland University Medical Center, Homburg, Germany. Electronic address: adam.zawada@uks.eu.
authors.forename: Adam M
authors.initials: AM
authors.lastname: Zawada
authors.affiliation: Department of Internal Medicine IV, Saarland University Medical Center, Homburg, Germany. Electronic address: kyrill.rogacev@uks.eu.
authors.forename: Kyrill S
authors.initials: KS
authors.lastname: Rogacev
authors.affiliation: Department of Clinical Hemostaseology and Transfusion Medicine, Saarland University Medical Center, Homburg, Germany; Clinical Chemistry and Laboratory Medicine/Central Laboratory, Saarland University Medical Center, Homburg, Germany. Electronic address: bjoern.hummel@uks.eu.
authors.forename: Björn
authors.initials: B
authors.lastname: Hummel
authors.affiliation: Department of Internal Medicine IV, Saarland University Medical Center, Homburg, Germany. Electronic address: judith_berg@hotmail.de.
authors.forename: Judith T
authors.initials: JT
authors.lastname: Berg
authors.affiliation: Department of Internal Medicine IV, Saarland University Medical Center, Homburg, Germany. Electronic address: annika.friedrich@nexgo.de.
authors.forename: Annika
authors.initials: A
authors.lastname: Friedrich
authors.affiliation: Labor Dr. Limbach und Kollegen, Medizinisches Versorgungszentrum, Heidelberg, Germany. Electronic address: roth@labor-limbach.de.
authors.forename: Heinz J
authors.initials: HJ
authors.lastname: Roth
authors.affiliation: Clinical Chemistry and Laboratory Medicine/Central Laboratory, Saarland University Medical Center, Homburg, Germany. Electronic address: rima.obeid@uks.eu.
authors.forename: Rima
authors.initials: R
authors.lastname: Obeid
authors.affiliation: Clinical Chemistry and Laboratory Medicine/Central Laboratory, Saarland University Medical Center, Homburg, Germany. Electronic address: juergen.geisel@uks.eu.
authors.forename: Jürgen
authors.initials: J
authors.lastname: Geisel
authors.affiliation: Department of Internal Medicine IV, Saarland University Medical Center, Homburg, Germany. Electronic address: danilo.fliser@uks.eu.
authors.forename: Danilo
authors.initials: D
authors.lastname: Fliser
authors.affiliation: Department of Internal Medicine IV, Saarland University Medical Center, Homburg, Germany. Electronic address: gunnar.heine@uks.eu.
authors.forename: Gunnar H
authors.initials: GH
authors.lastname: Heine
mesh_terms: D058070:Asymptomatic Diseases; D050197:Atherosclerosis / Q000150:complications / Q000209:etiology* / Q000378:metabolism / Q000503:physiopathology*; D002318:Cardiovascular Diseases / Q000453:epidemiology / Q000209:etiology; D005260:Female; D005919:Glomerular Filtration Rate; D006710:Homocysteine / Q000378:metabolism; D006801:Humans; D008297:Male; D008875:Middle Aged; D012307:Risk Factors; D012435:S-Adenosylhomocysteine / Q000378:metabolism*; D012436:S-Adenosylmethionine / Q000378:metabolism
chemical_list: D006710:Homocysteine; D012436:S-Adenosylmethionine; D012435:S-Adenosylhomocysteine
keywords: Arteriosclerosis; Homocysteine; Kidney; S-adenosylhomocysteine; S-adenosylmethionine