TY - JOUR
T1 - Liver enzymes and risk of stroke
T2 - The atherosclerosis risk in communities (aric) study
AU - Ruban, Angela
AU - Daya, Natalie
AU - Schneider, Andrea L.C.
AU - Gottesman, Rebecca
AU - Selvin, Elizabeth
AU - Coresh, Josef
AU - Lazo, Mariana
AU - Koton, Silvia
N1 - Funding Information:
The authors thank the staff and participants of the ARIC study for their important contributions. This work was supported by NIH/NIDDK grant R01DK089174 to Dr. Elizabeth Selvin. Reagents for the ALT, AST, and GGT assays were donated by Roche Diagnostics.
Funding Information:
The Atherosclerosis Risk in Communities study has been funded in whole or in part with Federal funds from the National Heart, Lung, and Blood Institute, National Institutes of Health, Department of Health and Human Services, under Contract nos. (HHSN268201700001I, HHSN268201700003I, HHS-N268201700005I, HHSN268201700004I, HH-SN2682017000021). Neurocognitive data is collected by U01 2U01HL096812, 2U01HL096814, 2U01HL096899, 2U01HL096902, 2U01HL096917 from the NIH (NHLBI, NINDS, NIA and NIDCD), and with previous brain MRI examinations funded by R01-HL70825 from the NHLBI. Dr. Selvin was supported by NIH/NIDDK K24DK106414 and R01DK089174 grants. Dr. Lazo was supported by NIH/NIDDK grant R01DK089174.
Publisher Copyright:
© 2020 Korean Stroke Society OpenAccess article distributed under the t.
PY - 2020/9
Y1 - 2020/9
N2 - Background and Purpose Liver enzymes (aspartate aminotransferase [AST], alanine aminotrans-ferase [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 con-founders. 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 compar-ing 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.
AB - Background and Purpose Liver enzymes (aspartate aminotransferase [AST], alanine aminotrans-ferase [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 con-founders. 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 compar-ing 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.
KW - Alanine transaminase
KW - Aspartate aminotransferases
KW - Atherosclerosis risk in communities
KW - Gamma-glu-tamyltransferase
KW - Incidence
KW - Liver enzymes
KW - Stroke
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U2 - 10.5853/jos.2020.00290
DO - 10.5853/jos.2020.00290
M3 - Article
C2 - 33053951
AN - SCOPUS:85092135966
SN - 2287-6391
VL - 22
SP - 357
EP - 368
JO - Journal of Stroke
JF - Journal of Stroke
IS - 3
ER -