Gamma-Glutamyltransferase as a Risk Factor for Cardiovascular Disease Mortality
Ruttmann E, Brant LJ, Concin H, et al. • Circulation
Key Finding
Upper-normal GGT increases cardiovascular mortality by 64% in men
Original title: “Gamma-glutamyltransferase as a risk factor for cardiovascular disease mortality”
Plain English Summary
This landmark Austrian study of 163,944 adults followed for 17 years found GGT in the highest quartile was associated with 64% higher cardiovascular mortality in men and 51% higher in women. The association was independent of alcohol consumption, suggesting GGT reflects systemic oxidative stress. GGT predicted mortality even within the "normal" range.
In-Depth Analysis
Background
Dr. Elfriede Ruttmann and colleagues from the Vorarlberg Health Monitoring and Promotion Program published this landmark study in Circulation (PMID: 16186419, DOI: 10.1161/CIRCULATIONAHA.105.533778), examining GGT as a cardiovascular mortality risk factor.
Study Design
Design: Prospective population-based cohort Population: 163,944 Austrian adults (76,113 men, 87,831 women) Follow-up: Mean 17 years Outcome: Cardiovascular mortality (fatal CHD, stroke, heart failure) Analysis: Cox regression by GGT quartiles with extensive adjustment
Key Findings
GGT quartiles and cardiovascular mortality:
| GGT Quartile | Men HR (95% CI) | Women HR (95% CI) |
|---|---|---|
| Q1 | 1.0 (reference) | 1.0 (reference) |
| Q2 | 1.23 (1.07-1.41) | 1.19 (1.01-1.40) |
| Q3 | 1.38 (1.21-1.58) | 1.24 (1.05-1.46) |
| Q4 | 1.64 (1.43-1.87) | 1.51 (1.28-1.78) |
Critical finding: Risk began increasing in Q2—within the "normal" laboratory range.
Independence: Association persisted after adjusting for:
- •Age, BMI, blood pressure, cholesterol
- •Smoking, alcohol consumption
- •Diabetes, physical activity
Mechanistic Insights
The authors proposed GGT directly participates in atherosclerosis:
- •Found within coronary plaques
- •Pro-oxidant activity promotes LDL oxidation
- •Marker of glutathione metabolism/oxidative stress
- •Correlates with metabolic syndrome components
Clinical Implications
This massive study established GGT as an independent cardiovascular risk factor. "Normal" GGT above the population median still confers elevated risk.
Metabolic Health Perspective
GGT is a valuable early warning marker. For metabolic optimization, targeting GGT in the lower half of the normal range (<20 U/L in men, <15 U/L in women) may indicate better metabolic health.
Paradigm Relevance
How this study applies to different clinical perspectives:
Standard Medical
Conventional clinical guidelines used by most doctors
Not directly relevant to this paradigm
Research Consensus
Current scientific understanding, often ahead of guidelines
Not directly relevant to this paradigm
Metabolic Optimization
Proactive targets for optimal health, not just disease absence
Not directly relevant to this paradigm
Study Details
- Type
- research.studyTypes.observational
Related Biomarkers
Calculate & Evaluate on Metabolicum
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