Indu Dhar1, Gard F T Svingen2, Eva R Pedersen2, Barbara DeRatt3, Arve Ulvik4, Elin Strand5, Per M Ueland6, Kaare H Bønaa7, Jesse F Gregory3, Ottar K Nygård8. 1. Department of Clinical Science, University of Bergen, Bergen, Norway; KG Jebsen Centre for Diabetes Research, University of Bergen, Bergen, Norway. Electronic address: Indu.Dhar@uib.no. 2. Department of Heart Disease, Haukeland University Hospital, Bergen, Norway. 3. Food Science and Human Nutrition Department, University of Florida, Gainesville, FL. 4. Bevital AS, Bergen, Norway. 5. Department of Clinical Science, University of Bergen, Bergen, Norway. 6. Department of Clinical Science, University of Bergen, Bergen, Norway; Bevital AS, Bergen, Norway. 7. Department of Cancer Research and Molecular Medicine, Norwegian University of Science and Technology, Trondheim, Norway. 8. Department of Clinical Science, University of Bergen, Bergen, Norway; KG Jebsen Centre for Diabetes Research, University of Bergen, Bergen, Norway; Department of Heart Disease, Haukeland University Hospital, Bergen, Norway.
Abstract
BACKGROUND: Cystathionine is a thio-ether and a metabolite formed from homocysteine during transsulfuration. Elevated plasma cystathionine levels are reported in patients with cardiovascular disease; however prospective relationships with acute myocardial infarction (AMI) are unknown. We investigated associations between plasma cystathionine and AMI among patients with suspected and/or verified coronary heart disease (CHD). METHODS: Subjects from two independent cohort studies, the Western Norway Coronary Angiography Cohort (WECAC) (3033 patients with stable angina pectoris; 263 events within 4.8 years of median follow-up) and the Norwegian Vitamin Trial (NORVIT) (3670 patients with AMI; 683 events within 3.2 years of median follow-up) were included. RESULTS: In both cohorts, plasma cystathionine was associated with several traditional CHD risk factors (P < 0.001). Comparing the cystathionine quartile 4 to 1, age and gender adjusted hazard ratios (95% confidence intervals) for AMI were 2.08 (1.43-3.03) and 1.41 (1.12-1.76) in WECAC and NORVIT, respectively. Additional adjustment for traditional risk factors slightly attenuated the risk estimates, which were generally stronger in both cohorts among non-smokers, patients with higher age, and lower BMI or PLP status (P-interaction ≤ 0.04). Risk associations also tended to be stronger in patients not treated with B-vitamins. Additionally, in a subset of 80 WECAC patients, plasma cystathionine associated strongly negatively with glutathione, an important antioxidant and positively with lanthionine, a marker of H2S production (P < 0.001). CONCLUSIONS: Plasma cystathionine is associated with increased risk of AMI among patients with either suspected or verified coronary heart disease, and is possibly related to altered redox homeostasis.
BACKGROUND:Cystathionine is a thio-ether and a metabolite formed from homocysteine during transsulfuration. Elevated plasma cystathionine levels are reported in patients with cardiovascular disease; however prospective relationships with acute myocardial infarction (AMI) are unknown. We investigated associations between plasma cystathionine and AMI among patients with suspected and/or verified coronary heart disease (CHD). METHODS: Subjects from two independent cohort studies, the Western Norway Coronary Angiography Cohort (WECAC) (3033 patients with stable angina pectoris; 263 events within 4.8 years of median follow-up) and the Norwegian Vitamin Trial (NORVIT) (3670 patients with AMI; 683 events within 3.2 years of median follow-up) were included. RESULTS: In both cohorts, plasma cystathionine was associated with several traditional CHD risk factors (P < 0.001). Comparing the cystathionine quartile 4 to 1, age and gender adjusted hazard ratios (95% confidence intervals) for AMI were 2.08 (1.43-3.03) and 1.41 (1.12-1.76) in WECAC and NORVIT, respectively. Additional adjustment for traditional risk factors slightly attenuated the risk estimates, which were generally stronger in both cohorts among non-smokers, patients with higher age, and lower BMI or PLP status (P-interaction ≤ 0.04). Risk associations also tended to be stronger in patients not treated with B-vitamins. Additionally, in a subset of 80 WECAC patients, plasma cystathionine associated strongly negatively with glutathione, an important antioxidant and positively with lanthionine, a marker of H2S production (P < 0.001). CONCLUSIONS: Plasma cystathionine is associated with increased risk of AMI among patients with either suspected or verified coronary heart disease, and is possibly related to altered redox homeostasis.
Authors: Miranda J Spratlen; Maria Grau-Perez; Jason G Umans; Joseph Yracheta; Lyle G Best; Kevin Francesconi; Walter Goessler; Poojitha Balakrishnan; Shelley A Cole; Mary V Gamble; Barbara V Howard; Ana Navas-Acien Journal: Environ Int Date: 2018-10-12 Impact factor: 9.621