Liver Enzymes and Risk of Stroke: The Atherosclerosis Risk in Communities (ARIC) Study
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Background and Purpose Liver enzymes (aspartate aminotransferase [AST], alanine aminotransferase [ALT], and gamma-glutamyl transpeptidase [GGT]) are glutamate-regulatory enzymes, and higher glutamate levels correlated with worse prognosis of patients with neurotrauma. However, less is known about the association between liver enzymes and incidence of stroke. We evaluated the association between serum levels of AST, ALT, and GGT and incidence of stroke in the Atherosclerosis Risk in Communities (ARIC) study cohort from 1990 to 1992 through December 31, 2016. Methods We included 12,588 ARIC participants without prevalent stroke and with data on liver enzymes ALT, AST, and GGT at baseline. We used multivariable Cox regression models to examine the associations between liver enzymes levels at baseline and stroke risk (overall, ischemic stroke, and intracerebral hemorrhage [ICH]) through December 31, 2016, adjusting for potential confounders. Results During a median follow-up time of 24.2 years, we observed 1,012 incident strokes (922 ischemic strokes and 90 ICH). In age, sex, and race-center adjusted models, the hazard ratios (HRs; 95% confidence intervals [CIs]) for the highest compared to lowest GGT quartile were 1.94 (95% CI, 1.64 to 2.30) for all incident stroke and 2.01 (95% CI, 1.68 to 2.41) for ischemic stroke, with the results supporting a dose-response association (P for linear trend <0.001). Levels of AST were associated with increased risk of ICH, but the association was significant only when comparing the third quartile with the lowest quartile (adjusted HR, 1.82; 95% CI, 1.06 to 3.13). Conclusions Elevated levels of GGT (within normal levels), independent of liver disease, are associated with higher risk of incident stroke overall and ischemic stroke, but not ICH.
Abstract
Background and Purpose Liver enzymes (aspartate aminotransferase [AST], alanine aminotransferase [ALT], and gamma-glutamyl transpeptidase [GGT]) are glutamate-regulatory enzymes, and higher glutamate levels correlated with worse prognosis of patients with neurotrauma. However, less is known about the association between liver enzymes and incidence of stroke. We evaluated the association between serum levels of AST, ALT, and GGT and incidence of stroke in the Atherosclerosis Risk in Communities (ARIC) study cohort from 1990 to 1992 through December 31, 2016. Methods We included 12,588 ARIC participants without prevalent stroke and with data on liver enzymes ALT, AST, and GGT at baseline. We used multivariable Cox regression models to examine the associations between liver enzymes levels at baseline and stroke risk (overall, ischemic stroke, and intracerebral hemorrhage [ICH]) through December 31, 2016, adjusting for potential confounders. Results During a median follow-up time of 24.2 years, we observed 1,012 incident strokes (922 ischemic strokes and 90 ICH). In age, sex, and race-center adjusted models, the hazard ratios (HRs; 95% confidence intervals [CIs]) for the highest compared to lowest GGT quartile were 1.94 (95% CI, 1.64 to 2.30) for all incident stroke and 2.01 (95% CI, 1.68 to 2.41) for ischemic stroke, with the results supporting a dose-response association (P for linear trend <0.001). Levels of AST were associated with increased risk of ICH, but the association was significant only when comparing the third quartile with the lowest quartile (adjusted HR, 1.82; 95% CI, 1.06 to 3.13). Conclusions Elevated levels of GGT (within normal levels), independent of liver disease, are associated with higher risk of incident stroke overall and ischemic stroke, but not ICH.
참고문헌 (29)
- Benjamin EJ, "Heart disease and stroke statistics-2019update : a report from the American Heart Association", Circulation, 139, pp.e56~e528 (2019)
- Jung CS, "CSF and serum biomarkers focusing on cerebral vasospasm and ischemia after subarachnoid hemorrhage", Stroke Res Treat, 2013, pp.560305~ (2013)
- Lai TW, "Excitotoxicity and stroke : identifying novel targets for neuroprotection", Prog Neurobiol, 115, pp.157~188 (2014)
- Zheng Y, "Metabolites of glutamate metabolism are associated with incident cardiovascular events in the PREDIMED PREvención con DIeta MEDiterránea(PREDIMED)Trial", J Am Heart Assoc, 5, pp.e003755~ (2016)
- Weikert C, "Liver enzymes and stroke risk in middleaged German adults", Atherosclerosis, 228, pp.508~514 (2013)
- Kim HC, "Elevated serum aminotransferase level as a predictor of intracerebral hemorrhage : Korea Medical Insurance Corporation study", Stroke, 36, pp.1642~1647 (2005)
- Eckel RH, "The metabolic syndrome", Lancet, 365, pp.1415~1428 (2005)
- Pratt DS, "Evaluation of abnormal liver-enzyme results in asymptomatic patients", N Engl J Med, 342, pp.1266~1271 (2000)
- Campos F, "Blood levels of glutamate oxaloacetate transaminase are more strongly associated with good outcome in acute ischaemic stroke than glutamate pyruvate transaminase levels", Clin Sci(Lond), 121, pp.11~17 (2011)
- Khanna S, "Inducible glutamate oxaloacetate transaminase as a therapeutic target against ischemic stroke", Antioxid Redox Signal, 22, pp.175~186 (2015)
- Boyko M, "Pharmacokinetics of glutamateoxaloacetate transaminase and glutamate-pyruvate transaminase and their blood glutamate-lowering activity in naïve rats", Neurochem Res, 37, pp.2198~2205 (2012)
- Ndrepepa G, "Gamma-glutamyl transferase and cardiovascular disease", Ann Transl Med, 4, pp.481~ (2016)
- Tate SS, "Gamma-glutamyl transpeptidase: catalytic, structural and functional aspects", Mol Cell Biochem, 39, pp.357~368 (1981)
- Hanigan MH, "Gamma-glutamyl transpeptidase : redox regulation and drug resistance", Adv Cancer Res, 122, pp.103~141 (2014)
- Loomba R, "Serum γ-glutamyltranspeptidase predicts all-cause, cardiovascular and liver mortality in older adults", J Clin Exp Hepatol, 3, pp.4~11 (2013)
- Kunutsor SK, "Liver enzymes and risk of cardiovascular disease in the general population : a metaanalysis of prospective cohort studies", Atherosclerosis, 236, pp.7~17 (2014)
- Koga M, "Glutathione is a physiologic reservoir of neuronal glutamate", Biochem Biophys Res Commun, 409, pp.596~602 (2011)
- van der Stel AX, "The Campylobacter jejuni RacRS two-component system activates the glutamate synthesis by directly upregulating γ-glutamyltranspeptidase(GGT)", Front Microbiol, 6, pp.567~ (2015)
- Jousilahti P, "Serum gamma-glutamyl transferase, self-reported alcohol drinking, and the risk of stroke", Stroke, 31, pp.1851~1855 (2000)
- Shimizu Y, "Gamma-glutamyltranspeptidase and incident stroke among Japanese men and women : the Circulatory Risk in Communities Study(CIRCS)", Stroke, 41, pp.385~388 (2010)
- The ARIC investigators, "The Atherosclerosis Risk in Communities(ARIC)Study : design and objectives", Am J Epidemiol, 129, pp.687~702 (1989)
- Rosamond WD, "Stroke incidence and survival among middle-aged adults : 9-year follow-up of the Atherosclerosis Risk in Communities(ARIC)cohort", Stroke, 30, pp.736~743 (1999)
- Harrell FE, "Regression Modeling Strategies : With Applications to Linear Models, Logistic Regression, and Survival Analysis" (2001), Springer
- Yang W, "Gamma-glutamyl transferase predicts future stroke : a Korean nationwide study", Ann Neurol, 83, pp.375~386 (2018)
- Chandra A, "The cerebral circulation and cerebrovascular disease III : stroke", Brain Circ, 3, pp.66~77 (2017)
- Campos F, "High blood glutamate oxaloacetate transaminase levels are associated with good functional outcome in acute ischemic stroke", J Cereb Blood Flow Metab, 31, pp.1387~1393 (2011)
- da Silva-Candal A, "Clinical validation of blood", brain glutamate grabbing in acute ischemic stroke, 2018, pp.84, 260~273
- Dufour DR, "Diagnosis and monitoring of hepatic injury. I. Performance characteristics of laboratory tests", Clin Chem, 46, pp.2027~2049 (2000)
- Lazo M, "Brief communication : clinical implications of short-term variability in liver function test results", Ann Intern Med, 148, pp.348~352 (2008)