The Value of Gamma-Glutamyltransferase in Cardiovascular Risk Prediction

Background

Wannamethee SG, Lennon L, Shaper AG. Arterioscler Thromb Vasc Biol. 2008;28(3):540-545. PMID: 18096825

This prospective cohort study from the British Regional Heart Study examined whether gamma-glutamyltransferase (GGT) adds predictive value for cardiovascular events beyond traditional risk factors.

Study Design

Parameter	Details
Design	Prospective cohort study
Population	6,997 British men aged 40-59
Follow-up	24 years
Primary Endpoint	CVD mortality and coronary heart disease events
Analysis	Cox proportional hazards with Framingham risk factors

Key Findings

GGT Quartile	Relative Risk CVD Death	Relative Risk CHD
Q1 (lowest)	1.0 (reference)	1.0 (reference)
Q2	1.15	1.12
Q3	1.34	1.25
Q4 (highest)	1.68	1.52

Risk remained significant after adjustment for alcohol, BMI, triglycerides, HDL, and diabetes.

Mechanistic Insights

GGT reflects oxidative stress, glutathione metabolism, and hepatic steatosis—all mechanistically linked to atherosclerosis development. The study supports GGT as a biomarker of underlying metabolic dysfunction rather than simply a liver enzyme.

Clinical Implications

Elevated GGT within "normal" range identifies individuals at increased cardiovascular risk not captured by traditional risk assessment. The authors suggest GGT deserves consideration in comprehensive CVD risk evaluation.

Metabolic Health Perspective

GGT elevations often precede overt metabolic syndrome diagnosis, making it a valuable early warning marker. An "optimal" GGT (<20 U/L) rather than simply "normal" may be a more appropriate target for metabolic health.