Abstract P005: Traditional Cardiovascular Risk Factors Explain the Association Between GGT and Incident Cardiovascular Events, but not Total Mortality
Authors: Ndumele Chiadi E , Christman Andrea L , Lazo Mariana , Clark Jeanne M , Blumenthal Roger S , Hoogeveen Ron C , Coresh Josef , Selvin Elizabeth 
Published: July 2021

Background:
Elevated levels of the liver enzyme gamma glutamyl transpeptidase (GGT) are associated with incident diabetes and the metabolic syndrome, but there is conflicting evidence regarding the association between GGT and cardiovascular risk.
Hypothesis:
GGT is positively associated with risk of coronary heart disease (CHD), congestive heart failure (CHF), and total mortality, independently of metabolic factors.

Methods:
We analyzed data from 9,104 participants in the Atherosclerosis Risk in Communities (ARIC) Study without cardiovascular disease or high alcohol consumption (>2 drinks per day for women and > 1 drink per day for men) at baseline (Visit 4, 1996-1999). GGT was measured from thawed plasma samples from Visit 4. The primary outcome was incident CHD (non-fatal MI, coronary revascularizations, or CHD death). Secondary outcomes were CHF and total mortality. We estimated the hazard ratios from Cox models for the risks associated with quartiles of GGT and ln-transformed GGT.

Results:
During a median of 10 years of follow-up, there were 925 CHD events, 654 CHF events, and 1,084 deaths. Male gender, diabetes, and components of the metabolic syndrome were associated with higher GGT levels at baseline. GGT was positively associated with risk of CHD and CHF in age-adjusted models, but not after adjustment for components of the metabolic syndrome and diabetes (
Table
). In contrast, the highest quartile of GGT remained associated with total mortality even after adjustment for all metabolic factors. Similar findings were seen for analyses of ln-GTT.

Conclusion:
The association between GGT and incident cardiovascular events was largely explained by metabolic risk factors. However, elevated GGT was associated with total mortality independent of the metabolic syndrome and diabetes, suggesting a potential alternative mechanism of risk.

Table

Hazard Ratios of Incident CHD, CHF and Total Mortality Associated with Quartiles
*
of GGT

GGT Q1 (≤14 U/L)n=2,039)
GGT Q2 (15-20 U/L)n=2,301
GGT Q3 (21-30 U/L)n=2,385
GGT Q4 (≥31 U/L)n=2,379

CHD

Model 1

Ref
1.16(0.93-1.44)
1.28(1.04-1.58)
1.62(1.32-1.99)

Model 2

Ref
1.10(0.89-1.37)
1.18(0.95-1.47)
1.47(1.19-1.82)

Model 3

Ref
1.03(0.82-1.28)
1.06(0.85-1.32)
1.30(1.04-.1.61)

Model 4

Ref
1.00(0.80-1.24)
1.00(0.80-1.24)
1.17(0.94-1.46)

CHF

Model 1

Ref
1.12(0.86-1.45)
1.36(1.06-1.74)
1.97(1.55-2.51)

Model 2

Ref
1.00(0.77-1.29)
1.12(0.87-1.45)
1.59(1.24-2.02)

Model 3

Ref
0.96(0.74-1.24)
1.04(0.80-1.35)
1.41(1.09-1.81)

Model 4

Ref
0.90(0.70-1.18)
0.93(0.71-1.20)
1.17(0.91-1.51)

TOTAL MORTALITY

Ref
0.90(0.69-1.17)
0.94(0.72-1.22)
1.13(0.87-1.46)

Model 1

Ref
1.14(0.94-1.38)
1.16(0.96-1.41)
1.52(1.26-1.83)

Model 2

Ref
1.14(0.94-1.39)
1.15(0.94-1.40)
1.50(1.24-1.83)

Model 3

Ref
1.16(0.95-1.41)
1.16(0.95-1.42)
1.48(1.21-1.80)

Model 4

Ref
1.13(0.93-1.38)
1.10(0.90-1.35)
1.34(1.09-1.64)

*

Quartiles defined on the entire study population Model 1: Adjusted for age, race, and sex Model 2: Adjusted for Model 1 + BMI and smoking Model 3: Adjusted for Model 2 + metabolic syndrome components (fasting hyperglycemia (BS>100), hypertension (SBP>130, DBP>85 or anti-hypertension medications), hypertriglyceridemia (>150 mg/dl), low HDL (<40 mg/dl for men and <50 mg/dl for women) and abdominal obesity (waist circumference > 102 cm for men and >88 cm for women))Model 4: Adjusted for Model 3 + diabetes mellitus