on November 9, 2006
Published online before print November 9, 2006, doi: 10.1161/01.ATV.0000251993.20372.40
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Submitted on August 3, 2006
Accepted on October 25, 2006
Gamma Glutamyl Transferase and Metabolic Syndrome, Cardiovascular Disease, and Mortality Risk. The Framingham Heart Study
Douglas S. Lee *;
From the Institute for Clinical Evaluative Sciences and University Health Network (D.S.L.), University of Toronto, Canada; the National Heart, Lung, and Blood Institute’s Framingham Heart Study (J.C.E., S.J.R., C.S.F., T.J.W., E.J.B., R.B.D., R.S.V.), Framingham, Mass; the Department of Medicine (P.W.W.), Medical University of South Carolina, Charleston; the Mathematics Department (R.B.D.), Boston University, Boston, Mass; the Cardiology Division, Massachusetts General Hospital, Harvard Medical School, Boston, Mass; the Cardiology Section (E.J.B., R.S.V.) and the Department of Preventive Medicine and Epidemiology (R.S.V.), Boston University School of Medicine, Boston, Mass.
* To whom correspondence should be addressed. E-mail: dlee{at}ices.on.ca.
Objective--To determine whether serum 
-glutamyl transferase (GGT) predicts cardiovascular disease (CVD) morbidity and mortality, accounting for temporal changes in known CVD risk factors and C-reactive protein (CRP).
Methods and Results--In 3451 Framingham Study participants (mean age 44 years, 52% women) we examined the relations of GGT with CVD risk factors, and prospectively determined the risk of new-onset metabolic syndrome, incident CVD, and death. GGT was positively associated with body mass index, blood pressure, LDL cholesterol, triglycerides, and blood glucose in cross-sectional analysis (P<0.005). On follow-up (mean 19 years), 968 participants developed metabolic syndrome, 535 developed incident CVD, and 362 died. The risk of metabolic syndrome increased with higher GGT (multivariable-adjusted hazard ratio [HR] per SD increment log-GGT, 1.26 [95%CI; 1.18 to 1.35]). Adjusting for established CVD risk factors (as time-dependent covariates updated quadriennially) and baseline CRP, a 1-SD increase in log-GGT conferred a 13% increase in CVD risk (P=0.007) and 26% increased risk of death (P<0.001). Individuals in the highest GGT quartile experienced a 67% increase in CVD incidence (multivariable-adjusted HR 1.67, 95%CI; 1.25 to 2.22).
Conclusion--An increase in serum GGT predicts onset of metabolic syndrome, incident CVD, and death suggesting that GGT is a marker of metabolic and cardiovascular risk.
Key words: biomarkers • gamma glutamyl transferase • risk factor • cardiovascular disease • metabolic syndrome • mortality
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