Simon Tracey G, Roelstraete Bjorn, Hagström Hannes, Sundström Johan, Ludvigsson Jonas F
Department of Medicine, Massachusetts General Hospital, Boston, MA, USA
Harvard Medical School, Boston, MA, USA.
Gut. 2022 Sep;71(9):1867-1875. doi: 10.1136/gutjnl-2021-325724. Epub 2021 Sep 6.
Some data suggest a positive association between non-alcoholic fatty liver disease (NAFLD) and incident major adverse cardiovascular events (MACEs). However, data are lacking from large cohorts with liver histology, which remains the gold standard for staging NAFLD severity.
This population-based cohort included all Swedish adults with histologically confirmed NAFLD and without cardiovascular disease (CVD) at baseline (1966-2016, n=10 422). NAFLD was defined from prospectively recorded histopathology and categorised as simple steatosis, non-fibrotic steatohepatitis, non-cirrhotic fibrosis and cirrhosis. Patients with NAFLD were matched to ≤5 population controls without NAFLD or CVD, by age, sex, calendar year and county (n=46 517). Using Cox proportional hazards modelling, we calculated multivariable adjusted HRs (aHRs) and 95% CIs for MACE outcomes (ie, ischaemic heart disease (IHD), stroke, congestive heart failure (CHF) or cardiovascular (CV) mortality).
Over a median of 13.6 years, incident MACE was confirmed in 2850 patients with NAFLD and 10 648 controls. Patients with NAFLD had higher incidence of MACE than controls (24.3 vs 16.0/1000 person-years (PY); difference=8.3/1000 PY; aHR 1.63, 95% CI 1.56 to 1.70), including higher rates of IHD (difference=4.2/1000 PY; aHR 1.64, 95% CI 1.54 to 1.75), CHF (difference=3.3/1000 PY; aHR 1.75, 95% CI 1.63 to 1.87), stroke (difference=2.4/1000 PY; aHR 1.58, 95% CI 1.46 to 1.71) and CV mortality (difference=1.2/1000 PY; aHR 1.37, 95% CI 1.27 to 1.48). Rates of incident MACE increased progressively with worsening NAFLD severity (p=0.02), with the highest incidence observed with cirrhosis (difference vs controls=27.2/1000 PY; aHR 2.15, 95% CI 1.77 to 2.61).
Compared with matched population controls, patients with biopsy-proven NAFLD had significantly higher incidence of MACE, including IHD, stroke, CHF and CV mortality. Excess risk was evident across all stages of NAFLD and increased with worsening disease severity.
一些数据表明非酒精性脂肪性肝病（NAFLD）与主要不良心血管事件（MACE）的发生之间存在正相关。然而，缺乏来自有肝脏组织学检查的大型队列的数据，而肝脏组织学检查仍是NAFLD严重程度分期的金标准。
该基于人群的队列包括所有在基线时（1966 - 2016年，n = 10422）经组织学确诊为NAFLD且无心血管疾病（CVD）的瑞典成年人。NAFLD由前瞻性记录的组织病理学定义，并分类为单纯性脂肪变性、非纤维化性脂肪性肝炎、非肝硬化性纤维化和肝硬化。NAFLD患者按年龄、性别、日历年和郡县与≤5名无NAFLD或CVD的人群对照进行匹配（n = 46517）。使用Cox比例风险模型，我们计算了MACE结局（即缺血性心脏病（IHD）、中风、充血性心力衰竭（CHF）或心血管（CV）死亡）的多变量调整后风险比（aHRs）和95%置信区间（CIs）。
在中位13.6年的时间里，2850例NAFLD患者和10648例对照确诊发生了MACE。NAFLD患者的MACE发生率高于对照（24.3对16.0/1000人年（PY）；差异 = 8.3/1000 PY；aHR 1.63，95% CI 1.56至1.70），包括IHD发生率更高（差异 = 4.2/1000 PY；aHR 1.64，95% CI 1.54至1.75）、CHF发生率更高（差异 = 3.3/1000 PY；aHR 1.75，95% CI 1.63至1.87）、中风发生率更高（差异 = 2.4/1000 PY；aHR 1.58，95% CI 1.46至1.71）和CV死亡率更高（差异 = 1.2/1000 PY；aHR 1.37，95% CI 1.27至1.48）。MACE的发生率随着NAFLD严重程度的加重而逐渐增加（p = 0.02），肝硬化患者的发生率最高（与对照相比差异 = 27.2/1000 PY；aHR 2.15，95% CI 1.77至2.61）。
与匹配的人群对照相比，经活检证实的NAFLD患者发生MACE的发生率显著更高，包括IHD、中风、CHF和CV死亡。在NAFLD的所有阶段都存在额外风险，且随着疾病严重程度的加重而增加。
