Hyperhomocysteinemia and Mortality after Coronary Artery Bypass Grafting

Abstract

BackgroundThe independent prognostic impact, as well as the possible causal role, of hyperhomocysteinemia (HHcy) in coronary artery disease (CAD) is controversial. No previous study specifically has addressed the relationship between HHcy and mortality after coronary artery bypass grafting (CABG) surgery. The aim of this study is to evaluate the prognostic impact of HHcy after CABG surgery.Methodology and Principal FindingsWe prospectively followed 350 patients who underwent elective CABG between May 1996 and May 1999. At baseline, fasting total homocysteine (tHcy) levels were measured in all participants, and a post-methionine loading (PML) test was performed in 77.7% of them (n = 272). After a median follow-up of 58 months, 33 patients (9.4%) had died, 25 because of cardiovascular events. HHcy, defined by levels higher than the 90th percentile (25.2 µmol/L) of the population's distribution, was significantly associated to total and cardiovascular mortality (P = 0.018 [log-rank test 5.57]; P = 0.002 [log-rank test 9.76], respectively). The PML test had no prognostic value. After multiple adjustment for other univariate predictors by Cox regression, including statin therapy (the most powerful predictor in uni-/multivariate analyses), high-sensitivity C Reactive Protein (hs-CRP) levels, and all known major genetic (MTHFR 677C→T polymorphism) and non-genetic (B-group vitamin status and renal function) tHcy determinants, HHcy remained an independent prognostic factor for mortality (HRs: 5.02, 95% CIs 1.88 to 13.42, P = 0.001).ConclusionsHHcy is an important prognostic marker after CABG, independent of modern drug therapy and biomarkers.

Plasma homocysteine levels are related to medium-term venous graft degeneration in coronary artery bypass graft patients

“…Contrary to Rodionov’s ( 28 ) observation that Hcy is only a bystander in CAD, our results support the opinion that Hcy plays an active role in SVG progression. Girelli et al ( 29 ) observed similar results in 350 CAD patients after a mean follow-up of 4.8 years; Hcy was an important and independent prognostic factor of mortality after CABG. Furthermore, fasting Hcy level correlated positively with CRP.…”

S-adenosylmethionine mediates inhibition of inflammatory response and changes in DNA methylation in human macrophages

“…Methylcytosine-enriched samples were then fluorescently labeled (Cy5), and input control samples (not methylcytosine-enriched) were fluorescently labeled (Cy3), followed by competitive hybridization to a high throughput 3ϫ750k NimbleGen array containing CpG islands and all annotated gene promoters in the human genome. Signals were detected with the NimbleGen microarray scanner MS 200 (16). The Comprehensive High-throughput Array for Relative Methylation (CHARM) method in R Studio previously described (3) was modified to analyze the meDIP DNA methylation arrays for control and 500 mol/l SAMtreated cells (3,27).…”

Role of hydrogen sulfide in endothelial dysfunction: Pathophysiology and therapeutic approaches

“…Accordingly, many studies demonstrate a clear association between HHcy and coronary artery disease, atherosclerosis, hypertension and neurodegenerative diseases [131] . Indeed, HHcy can be considered as a predictive biomarker of cardiovascular mortality in patients affected by coronary artery disease, and plasma levels of Hcy correlate with the severity of atherosclerosis [132] .…”