Adam M Zawada1, Kyrill S Rogacev2, Björn Hummel3, Judith T Berg4, Annika Friedrich5, Heinz J Roth6, Rima Obeid7, Jürgen Geisel8, Danilo Fliser9, Gunnar H Heine10. 1. Department of Internal Medicine IV, Saarland University Medical Center, Homburg, Germany. Electronic address: adam.zawada@uks.eu. 2. Department of Internal Medicine IV, Saarland University Medical Center, Homburg, Germany. Electronic address: kyrill.rogacev@uks.eu. 3. 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. 4. Department of Internal Medicine IV, Saarland University Medical Center, Homburg, Germany. Electronic address: judith_berg@hotmail.de. 5. Department of Internal Medicine IV, Saarland University Medical Center, Homburg, Germany. Electronic address: annika.friedrich@nexgo.de. 6. Labor Dr. Limbach und Kollegen, Medizinisches Versorgungszentrum, Heidelberg, Germany. Electronic address: roth@labor-limbach.de. 7. Clinical Chemistry and Laboratory Medicine/Central Laboratory, Saarland University Medical Center, Homburg, Germany. Electronic address: rima.obeid@uks.eu. 8. Clinical Chemistry and Laboratory Medicine/Central Laboratory, Saarland University Medical Center, Homburg, Germany. Electronic address: juergen.geisel@uks.eu. 9. Department of Internal Medicine IV, Saarland University Medical Center, Homburg, Germany. Electronic address: danilo.fliser@uks.eu. 10. Department of Internal Medicine IV, Saarland University Medical Center, Homburg, Germany. Electronic address: gunnar.heine@uks.eu.
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. CONCLUSION: 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.
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. CONCLUSION: 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: Adam M Zawada; Jenny S Schneider; Anne I Michel; Kyrill S Rogacev; Björn Hummel; Nicolas Krezdorn; Soeren Müller; Björn Rotter; Peter Winter; Rima Obeid; Jürgen Geisel; Danilo Fliser; Gunnar H Heine Journal: Epigenetics Date: 2016-03-28 Impact factor: 4.528
Authors: Courtney A Whalen; Floyd J Mattie; Cristina Florindo; Bertrand van Zelst; Neil K Huang; Isabel Tavares de Almeida; Sandra G Heil; Thomas Neuberger; A Catharine Ross; Rita Castro Journal: Nutrients Date: 2020-07-23 Impact factor: 5.717
Authors: Sammy Elmariah; Laurie A Farrell; Maureen Daher; Xu Shi; Michelle J Keyes; Carolyn H Cain; Eugene Pomerantsev; Gus J Vlahakes; Ignacio Inglessis; Jonathan J Passeri; Igor F Palacios; Caroline S Fox; Eugene P Rhee; Robert E Gerszten Journal: J Am Heart Assoc Date: 2016-03-15 Impact factor: 5.501