Hyperhomocysteinemia and Mortality after Coronary Artery Bypass Grafting

BACKGROUND: The 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 FINDINGS: We 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 90(th) 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). CONCLUSIONS: HHcy is an important prognostic marker after CABG, independent of modern drug therapy and biomarkers

Novel serum paraoxonase activity assays are associated with coronary artery disease

BACKGROUND: Serum paraoxonase (PON1) exerts antiatherogenic effects. Novel PON1 enzymatic tests have been recently developed: 5-thiobutyl butyrolactone (TBBL) estimates PON1 lactonase activity, whereas 7-O-diethylphosphoryl-3-cyano-4-methyl-7-hydroxycoumarin (DEPCyMC) is considered a surrogate marker of PON1 concentration. The TBBL to DEPCyMC ratio provides the normalized lactonase activity (NLA), which may reflect the degree of PON1 lactonase catalytic stimulation. The aim of this study was to evaluate for the first time TBBLase and DEPCyMCase activity in patients with coronary artery disease (CAD). METHODS: An angiography-based case-control study was conducted, including 300 sex- and age-matched subjects [100 CAD-free, 100 CAD without myocardial infarction (MI) and 100 CAD with MI]. RESULTS: A low DEPCyMCase activity (lowest vs. highest tertile: OR 2.96, 95\% CI 1.18-7.43) and a high NLA (highest vs. lowest tertile: OR 3.25, 95\% CI 1.28-8.26) were both associated with CAD, independent of classical atherosclerosis risk factors, lipid-lowering therapy and PON1 genotype. Total TBBLase activity was, however, not different in CAD compared to CAD-free subjects. CONCLUSIONS: Novel PON1 activity assays may be associated with CAD. In this study, CAD patients had low DEPCyMCase activity, a possible marker of low PON1 concentration, but showed a high stimulation of PON1 lactonase activity

Kaplan-Meier survival plots for total mortality (A–B) and cardiovascular death (C–D) in relation to tHcy levels.

<p>Cutoff points for tHcy strata at 25.2 µmol/l in plots A and C, at 15 and 25.2 µmol/l in plots B and D.</p