Epidemiology
Lp(a) falls as liver fibrosis worsens in fatty liver disease, but cardiovascular risk stays high regardless, 56,168-patient study finds (Liver Int 2025)
Original title: Association of Plasma Lipoprotein(a) With Major Adverse Cardiovascular Events in MASLD With or Without Advanced Liver Fibrosis
This two-centre study enrolled 56,168 patients with metabolic dysfunction-associated steatotic liver disease (MASLD), followed for a median 5.0 years (IQR 2.0-8.5), to clarify Lp(a)'s uncertain role in predicting major adverse cardiovascular events (MACE) once liver fibrosis severity is considered; advanced fibrosis was defined as FIB-4 index above 2.67. Overall, 6,136 patients developed incident MACE. Higher Lp(a) percentile was inversely associated with advanced liver fibrosis (91st-100th percentile, adjusted OR 0.65, 95% CI 0.59-0.72, P < 0.001), and patients with advanced fibrosis were less likely to have high Lp(a). Yet among patients with advanced fibrosis, those who did have high Lp(a) had substantially higher MACE risk than those with low Lp(a) (adjusted HR 1.56, 95% CI 1.27-1.91, P < 0.001), and overall MACE incidence stayed high in the advanced-fibrosis group regardless of Lp(a) level. The authors conclude that relying on Lp(a) alone could underestimate cardiovascular risk in MASLD patients with advanced liver fibrosis, since low Lp(a) in this subgroup does not signal low cardiovascular risk.
Original abstract
Background And Aims: 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.
Methods: 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.
Results: 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.
Conclusions: 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.
Summary written by lp-a.org from the published abstract; figures as published. Page updated 17 August 2026. Methods.