Department of Medicine, Larner College of Medicine at the University of Vermont, Burlington, Vermont, United States of America.
Department of Pathology and Laboratory Medicine, Larner College of Medicine at the University of Vermont, Burlington, Vermont, United States of America.
PLoS One. 2018 Mar 12;13(3):e0194153. doi: 10.1371/journal.pone.0194153. eCollection 2018.
Liver disease, particularly non-alcoholic fatty liver disease (NAFLD), is a risk factor for cardiovascular disease, but little is known about its relationship with ischemic stroke.
In the Reasons for Geographic and Racial Differences in Stroke (REGARDS) cohort of 30,239 American black and white adults, we assessed baseline NAFLD as fatty liver index (FLI) >60, and assessed liver biomarkers aspartate aminotransferase (AST), alanine aminotransferase (ALT), γ-glutamyl transpeptidase (GGT), and the AST/ALT ratio and risk of incident ischemic stroke over 5.8 years using a case-cohort study design.
Considering 572 strokes and a 1,017-person cohort sample, NAFLD was inversely associated with stroke risk in men (HR: 0.50; 95% CI: 0.26, 0.96), as was being in the highest ALT quintile versus the lowest (HR: 0.39; 95% CI: 0.19, 0.78) and the highest versus lowest GGT quintile (HR: 0.45, 95% CI: 0.24, 0.85), but not in women. Conversely, FLI score above the 90th percentile was associated with increased stroke risk among women (HR: 2.26; 95% CI: 1.14-4.47), but not men. AST was not associated with stroke risk in either sex. AST/ALT ratio >2 was strongly associated with increased stroke risk in whites, but not blacks (HRs: 3.64; 95% CI: 1.42-9.35 and 0.97; 95% CI: 0.45-1.99, respectively; p for interaction = 0.03).
The relationships between NAFLD, liver biomarkers, and ischemic stroke are complex, and sex and race differences we observed require further study and confirmation.
肝脏疾病,尤其是非酒精性脂肪肝(NAFLD),是心血管疾病的一个危险因素,但人们对其与缺血性卒中的关系知之甚少。
在 Reasons for Geographic and Racial Differences in Stroke(REGARDS)队列中,纳入了 30239 名美国黑人和白人成年人,我们评估了基线时的 NAFLD,即脂肪肝指数(FLI)>60,并评估了肝生物标志物天冬氨酸氨基转移酶(AST)、丙氨酸氨基转移酶(ALT)、γ-谷氨酰转肽酶(GGT)以及 AST/ALT 比值,采用病例-队列研究设计,随访 5.8 年评估其与缺血性卒中发病的关系。
考虑到 572 例卒中事件和 1017 人的队列样本,NAFLD 与男性卒中风险呈负相关(HR:0.50;95%CI:0.26,0.96),ALT 五分位最高组与最低组(HR:0.39;95%CI:0.19,0.78)和 GGT 五分位最高组与最低组(HR:0.45,95%CI:0.24,0.85)也呈负相关,但在女性中无此相关性。相反,FLI 评分位于第 90 百分位数以上与女性卒中风险增加相关(HR:2.26;95%CI:1.14-4.47),但在男性中则无此相关性。AST 在两性中均与卒中风险无关。AST/ALT 比值>2 与白人卒中风险增加密切相关,但在黑人中则无此相关性(HRs:3.64;95%CI:1.42-9.35 和 0.97;95%CI:0.45-1.99;交互作用 P 值=0.03)。
NAFLD、肝生物标志物与缺血性卒中之间的关系较为复杂,我们观察到的性别和种族差异需要进一步研究和证实。