Neal S. Parikh, MD
Tu W, Liu Q, Cao J, Zhao S, Zeng X, Deng A. γ-Glutamyl Transferase as a Risk Factor for All-Cause or Cardiovascular Disease Mortality Among 5912 Ischemic Stroke. Stroke. 2017
In light of an increasing interest in and understanding of the association between liver disease and cerebrovascular disease, Wen-Jun Tu and colleagues sought to explore the association between serum γ-glutamyl transferase (GGT) and post-stroke mortality.
In their well-designed and well-powered prospective, multicenter cohort observational study, the authors enrolled 5,912 patients within 24 hours of acute ischemic stroke. The study was conducted in China. They excluded patients with known hepatobiliary disease and alcohol abuse. Serum GGT level at baseline was the exposure of interest, and patients were followed for a median of 1 year with regular telephone interviews and review of death certificates. The primary outcome was all-cause mortality, and cardiovascular death (including fatal stroke) was separately adjudicated. Men and women were analyzed differently because normative values for GGT are sex-specific.
Univariate associations revealed the intriguing finding that baseline GGT was also associated with NIHSS and infarct volume. Baseline GGT was also associated with C – reactive protein, smoking, and other vascular risk factors.
In their primary model, they created a Cox proportional hazards model adjusted for age, conventional stroke risk factors, stroke severity (NIHSS and infarct volume), laboratory data for vascular risk factors, and lifestyle factors. Relative to the lowest quintile, subsequent quintiles of GGT values were associated with an increased risk of subsequent all-cause mortality, in a dose-dependent fashion. The risk of all-cause mortality was increased by 3.58 fold (95% confidence interval, 1.46-6.15) per log unit of GGT. Although recurrent stroke was not an outcome, elevated GGT values were also similarly associated with fatal stroke and other cardiovascular death.
In patients without overt liver disease or alcoholism, laboratory evidence of hepatic dysfunction was associated with an increased risk of all-cause death and recurrent, fatal stroke. These findings, together with reports of an association between serum alkaline phosphatase and outcomes after stroke,1,2 support the hypothesis that subclinical liver dysfunction is associated with adverse cerebrovascular outcomes. Future studies should assess the relationship between pre-stroke liver function and post-stroke outcomes. Otherwise, it remains possible that abnormal liver function lab values are a reflection of stroke severity rather than an independent risk factor for stroke outcomes.
1 Ryu WS, Lee SH, Kim CK, Kim BJ, Yoon BW. Increased serum alkaline phosphatase as a predictor of long-term mortality after stroke. Neurology. 2010:75;1995-2002.
2 Kim J, Song TJ, Song D, Lee HS, Nam CM, Nam HS, et al. Serum alkaline phosphatase and phosphate in cerebral atherosclerosis and functional outcomes after cerebral infarction. Stroke. 2013:44;3547-9.