Xiao Tie, Liu Hui-Hui, Tian Na, Lian Li-You, Miao Kai-Wen, Li Yu-Ting, Chen Li-Li, Yuan Hai-Yang, Du Mulong, Wu Shanshan, Sun Feng, Targher Giovanni, Byrne Christopher D, Shapiro Michael D, Lip Gregory Y H, Zhou Xiao-Dong, Li Jian-Jun, Zheng Ming-Hua
MAFLD Research Centre, Department of Hepatology, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, China.
Department of Cardiology, Cardiometabolic Centre, State Key Laboratory of Cardiovascular Diseases, Fu Wai Hospital, National Centre for Cardiovascular Diseases, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.
Liver Int. 2025 Aug;45(8):e70208. doi: 10.1111/liv.70208.
There is uncertainty regarding the role of plasma lipoprotein(a) [Lp(a)] in predicting cardiovascular events in patients with metabolic dysfunction-associated steatotic liver disease (MASLD). We examined the association between plasma Lp(a) concentrations and major adverse cardiovascular events (MACE) in MASLD, stratified by the severity of liver fibrosis.
This study enrolled patients with MASLD from two centres. Lp(a) percentile groups were generated with the reference group set at the 1st-50th Lp(a) percentiles. High Lp(a) levels correspond to the 91st-100th percentile. Advanced liver fibrosis was defined using the fibrosis (FIB)-4 index > 2.67. MACE was defined as myocardial infarction, ischemic stroke, or cardiovascular death. Cox regression was used to assess the association between the Lp(a) percentile groups and MACE.
A total of 56 168 patients with MASLD were followed for a median of 5.0 years (IQR: 2.0-8.5 years), and 6136 patients developed incident MACE. There was an inverse association between Lp(a) percentiles and advanced liver fibrosis (91st-100th percentile, adjusted OR = 0.65, 95% CI 0.59-0.72; p < 0.001). In patients with advanced liver fibrosis, there was a lower proportion in the high Lp(a) levels group (p < 0.001), although the incidence of MACE remained high. MASLD patients with advanced liver fibrosis and high Lp(a) levels had a higher risk of MACE (adjusted HR = 1.56, 95% CI 1.27-1.91; p < 0.001) than those with low Lp(a) levels.
Plasma Lp(a) levels are lower in MASLD patients with advanced fibrosis, yet their MACE risk remains high, suggesting that relying on Lp(a) alone may underestimate cardiovascular risk if advanced liver fibrosis is not considered.
血浆脂蛋白(a)[Lp(a)]在预测代谢功能障碍相关脂肪性肝病（MASLD）患者心血管事件中的作用尚不确定。我们研究了按肝纤维化严重程度分层的MASLD患者血浆Lp(a)浓度与主要不良心血管事件（MACE）之间的关联。
本研究纳入了来自两个中心的MASLD患者。Lp(a)百分位数分组以第1至50 Lp(a)百分位数的参考组设定。高Lp(a)水平对应第91至100百分位数。使用纤维化（FIB）-4指数>2.67定义晚期肝纤维化。MACE定义为心肌梗死、缺血性中风或心血管死亡。采用Cox回归评估Lp(a)百分位数分组与MACE之间的关联。
共对56168例MASLD患者进行了中位5.0年（四分位间距：2.0 - 8.5年）的随访，6136例患者发生了新发MACE。Lp(a)百分位数与晚期肝纤维化之间存在负相关（第91至100百分位数，校正OR = 0.65，95%CI 0.59 - 0.72；p < 0.001）。在晚期肝纤维化患者中，高Lp(a)水平组的比例较低（p < 0.001），尽管MACE的发生率仍然很高。与低Lp(a)水平的MASLD患者相比，晚期肝纤维化且Lp(a)水平高的MASLD患者发生MACE的风险更高（校正HR = 1.56，95%CI 1.27 - 1.91；p < 0.001）。
晚期纤维化的MASLD患者血浆Lp(a)水平较低，但其MACE风险仍然很高，这表明如果不考虑晚期肝纤维化，仅依靠Lp(a)可能会低估心血管风险。
