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.


RESULTS
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 90th percentile (25.2 micromol/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.
Girelli
Domenico
D
Department of Clinical and Experimental Medicine, University of Verona, Italy. domenico.girelli@univr.it
Martinelli
Nicola
N
Olivieri
Oliviero
O
Pizzolo
Francesca
F
Friso
Simonetta
S
Faccini
Giovanni
G
Bozzini
Claudia
C
Tenuti
Ilaria
I
Lotto
Valentina
V
Villa
Giuliano
G
Guarini
Patrizia
P
Trabetti
Elisabetta
E
Pignatti
Pier Franco
PF
Mazzucco
Alessandro
A
Corrocher
Roberto
R
D000368:Aged; D001026:Coronary Artery Bypass / Q000401:mortality*; D003324:Coronary Artery Disease / Q000150:complications* / Q000401:mortality / Q000601:surgery*; D005260:Female; D005838:Genotype; D006710:Homocysteine / Q000097:blood; D006801:Humans; D020138:Hyperhomocysteinemia / Q000097:blood / Q000150:complications* / Q000201:enzymology / Q000235:genetics; D007558:Italy / Q000453:epidemiology; D008297:Male; D042965:Methylenetetrahydrofolate Reductase (NADPH2) / Q000235:genetics; D008875:Middle Aged; D015999:Multivariate Analysis; D011379:Prognosis; D016016:Proportional Hazards Models; D011446:Prospective Studies; D012307:Risk Factors
D006710:Homocysteine; D042965:Methylenetetrahydrofolate Reductase (NADPH2)