Progression of coronary artery calcification (CAC) may be more predictive of future coronary heart disease events than a baseline CAC score. We determined whether serum gamma-glutamyltransferase (GGT) activity can independently predict the progression of CAC in adults with type 2 diabetes mellitus (T2DM). Patients (n = 326) without symptomatic cardiovascular (CV) disease were evaluated by CAC imaging. The CAC scores were assessed at baseline and after 20 ± 4 months. Serum GGT activities were significantly higher in progressors compared with nonprogressors (39 ± 16 vs 27 ± 11 U/L, P < .001). Multivariable analyses demonstrated that GGT activity retained a strong association with CAC progression after adjustment for CV risk factors. Additionally, there was a graded association between GGT activity quartile and annualized CAC progression. In asymptomatic patients with T2DM, we prospectively found that serum GGT activity may be an independent predictor of CAC progression but not a predictor of CAC incidence.
NemesanszkyELottJA. Gamma-glutamyltransferase and its isoenzymes: progress and problems. Clin Chem. 1985;31
(6):797–803.
2.
LeeDHSilventoinenKJacobsDRJousilahtiPTuomiletoJ. γ-Glutamyltransferase, obesity, and the risk of type 2 diabetes: observational cohort study among 20,158 middle-aged men and women. J Clin Endocrinol Metab. 2004;9
(11):5410–5414.
3.
LeeDSEvansJCRobinsSJ. Gamma-glutamyltransferase and metabolic syndrome, cardiovascular disease, and mortality risk: the Framingham heart study. Arterioscler Thromb Vasc Biol. 2007;27
(1):127–133.
4.
LeeDHJacobsDRJrGrossM. γ-Glutamyltransferase is a predictor of incident diabetes and hypertension: the coronary artery risk development in young adults (CARDIA) study. Clin Chem. 2003;(8):49.
5.
EmdinMPassinoCMichelassiCDonatoLPompellaAPaolicchiA. Additive prognostic value of gamma-glutamyltransferase in coronary artery disease. Int Cardiol. 2009;136
(1):80–85.
6.
MasonJEStarkeRDVan KirkJE. Gamma-glutamyltransferase: a novel cardiovascular risk. Bio Marker Prev Cardiol. 2010;13
(1):36–41.
7.
RuttmannEBrantLJConcinHDiemGRappKUlmerH. γ-Glutamyltransferase as a risk factor for cardiovascular disease mortality: an epidemiological investigation in a cohort of 163 944 Austrian adults. Circulation. 2005;112
(14):2130–2137.
EmdinMPompellaAPaolicchiA. Gamma-glutamyltransferase, atherosclerosis, and cardiovascular disease triggering oxidative stress within the plaque. Circulation. 2005;112
(14):2078–2080.
10.
FranziniMCortiAMartinelliB. γ-Glutamyltransferase activity in human atherosclerotic plaques—biochemical similarities with the circulating enzyme. Atherosclerosis. 2009;202
(1):119–127.
11.
HyoEPSuYCMinKKByung-HeeOh. Cardio-ankle vascular index reflects coronary atherosclerosis in patients with abnormal glucose metabolism: assessment with 256 slice multi-detector computed tomography. J Cardiol. 2012;60
(5):372–376.
WexlerLBrundageBCrouseJ. Coronary artery calcification: pathophysiology, epidemiology, imaging methods, and clinical implications. A statement for health professionals from the American Heart Association writing group. Circulation. 1996;94
(5):1175–1192.
14.
AnandDVLimEDarkoD. Determinants of progression of coronary artery calcification in type 2 diabetes role of glycemic control and inflammatory/vascular calcification markers. J Am Coll Cardiol. 2007;50
(23):2218–2225.
15.
AtarAIYilmazOCAkinKSelcokiYErOEryonucuB. Association between gamma-glutamyltransferase and coronary artery calcification. Int J Cardiol. 2013;167
(4):1264–1267.
16.
BianLQZhangZYKimSJZhouCCChoiYH. Gamma glutamyltransferase as a novel marker of coronary artery calcification in women. J Cardiovasc Med (Hagerstown). 2012;13
(11):684–690.
17.
LeeWRyooJHSuhBSLeeJKimJ. Association of coronary artery calcification and serum gamma-glutamyl transferase in Korean. Atherosclerosis. 2013;226
(1):269–274.
18.
StevensRJKothariVAdlerAIStrattonIM, United Kingdom Prospective Diabetes Study (UKPDS) Group. The UKPDS risk engine: a model for the risk of coronary heart disease in type 2 diabetes (UKPDS 56). Clin Sci (Lond). 2001;101
(6):671–679.
19.
KomatsuSKamataTImaiAOharaT. Controlling intracoronary CT number for coronary CT angiography. J Cardiol. 2013;61(2)155–161.
20.
HokansonJEMacKenzieTKinneyG. Evaluating changes in coronary artery calcium: an analytic method that accounts for interscan variability. Am J Roentgenol. 2004;182
(5):1327–1332.
21.
ShawLJRaggiPSchistermanEBermanDSCallisterTQ. Prognostic value of cardiac risk factors and coronary artery calcium screening for all-cause mortality. Radiology. 2003;228
(3):826–833.
FujitaMUenoKHataA. Association of gamma-glutamyltransferase with incidence of type 2 diabetes in Japan. Exp Bio Med. 2010;235
(3):335–341.
24.
AndréPBalkauBVolSCharlesMAEschwègeE; DESIR Study Group. γ-Glutamyltransferase activity and development of the metabolic syndrome (International Diabetes Federation Definition) in middle-aged men and women. Diabetes Care. 2007;30
(9):2355–2361.
25.
SluikDBeulensJWWeikertC. Gamma-glutamyltransferase, cardiovascular disease and mortality in individuals with diabetes mellitus. Diabetes Metab Res Rev. 2012;28
(3):284–288.
26.
SabanayagamCShankarALiJPollardCDucatmanA. Serum gamma-glutamyl transferase level and diabetes mellitus among US adults. Eur J Epidemiol. 2009;24
(7):369–373.
27.
BonnetFDucluzeauPHGastaldelliA. Liver enzymes are associated with hepatic insulin resistance, insulin secretion, and glucagon concentration in healthy men and women. Diabetes. 2011;60
(6):1660–1667.
28.
BianchiCPennoGCrisciI. Serum gamma-glutamyltransferase levels are related to insulin sensitivity and secretion in subjects with abnormal glucose regulation. Diabetes Metab Res Rev. 2010;26
(3):181–186.
29.
GiralPJacobNDourmapC. Elevated gamma-glutamyltransferase activity and perturbed thiol profile are associated with features of metabolic syndrome. Arterioscler Thromb Vasc Biol. 2008;28
(3):587–593.
30.
LeeDHSteffesMWJacobsDR. Can persistent organic pollutants explain the association between serum γ-glutamyltransferase and type 2 diabetes?Diabetologia. 2008;51
(3):402–407.
31.
LeeDHGrossMDSteffesMWJacobsDR. Is serum gamma-glutamyltransferase a biomarker of xenobiotics, which are conjugated by glutathione?Arterioscler Thromb Vasc Biol. 2008;28
(4):26–28.
32.
ZaineffBDJorgeEEvangelinaGGabrielaLMCenobioRJGuadalupeCM. γ-Glutamyl transferase: a marker of nonalcoholic fatty liver disease in patients with the metabolic syndrome. Eur J Gastroenterol Hepatol. 2012;24
(7):805–810.
33.
NdumeleCENasirKConceiçaoRDCarvalhoJBlumenthalRSSantosRD. Hepatic steatosis, obesity, and the metabolic syndrome are independently and additively associated with increased systemic inflammation. Arterioscler Thromb Vasc Biol. 2011;31
(8):1927–1932.
34.
SimãoANDichiJBBarbosaDSCecchiniRDichiI. Influence of uric acid and γ-glutamyltransferase on total antioxidant capacity and oxidative stress in patients with metabolic syndrome. Nutrition. 2008;24
(7-8):675–681.
35.
GiralPRatziuVCouvertP. Plasma bilirubin and gamma-glutamyltransferase activity are inversely related in dyslipidemic patients with metabolic syndrome: relevance to oxidative stress. Atherosclerosis. 2010;210
(2):607–613.
36.
DemircanSYaziciMDurnaK. The importance of gamma-glutamyltransferase activity in patients with coronary artery disease. Clin Cardiol. 2009;32
(4):220–225.
37.
AksakalETanbogaIHKurtM. The relation of serum gamma-glutamyl transferase levels with coronary lesion complexity and long-term outcome in patients with stable coronary artery disease. Atherosclerosis. 2012;221
(2):596–601.
38.
ErogluSSadeLEPolatEBozbasHUlusTMuderrisogluH. Association between serum gamma-glutamyltransferase activity and carotid intima–media thickness. Angiology. 2011;62
(2):107-110.
39.
ChirumamillaAPMaeharaAMintzGS. High platelet reactivity on clopidogrel therapy correlates with increased coronary atherosclerosis and calcification: a volumetric intravascular ultrasound study. JACC Cardiovasc Imaging. 2012;5
(5):540–549.
40.
BolodeokuJAGanotakisESMikhailidisDPWinderAF. Correlation between serum gamma-glutamyl transferase activity and the platelet count. Platelets. 1997;8
(5):333–335.
41.
GürdölFNwoseOMMikhailidisDP. Gamma-glutamyl transferase activity in human platelets: quantification of activity, isoenzyme characterization and potential clinical relevance. Platelets. 1995;6
(4):200–203.
42.
ChoSYLeeHJParkTS. Mean platelet volume in patients with increased γ-glutamyl transferase [published online February 10, 2014]. Platelets. 2014.
43.
JungDHLeeHRLeeYJKimJKParkBJShimJY. The association between coronary artery calcification and mean platelet volume in the general population. Platelets. 2011;22
(8):567–571.
44.
CappelliSEpistolatoMCVianelloA. Aortic valve disease and gamma-glutamyltransferase: accumulation in tissue and relationships with calcific degeneration. Atherosclerosis. 2010;213
(2):385–391.
45.
BudoffMJHokansonJENasirK. Progression of coronary artery calcium predicts all-cause mortality. J Am Coll Cardiol Img. 2010;3
(12):1229–1236.
46.
MotroMShemeshJ. Calcium channel blocker nifedipine slows down progression of coronary calcification in hypertensive patients compared with diuretics. Hypertension. 2001;37
(6):1410–1413.
