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Background <p>The relationship between plasma lipoprotein(a) [Lp(a)] levels and metabolic dysfunction-associated steatotic liver disease (MASLD) remains unclear. The aim of this study was to examine the combined effects of Lp(a) levels on liver and vascular damage.</p> Methods <p>The study was conducted using the Liver-Bible cohort of individuals with metabolic dysfunction (n = 859, 808 with genomic information) and the Milan Biobank (n = 6963). Genome-wide association studies (GWAS) and polygenic risk scores (PRS) were used to evaluate the inherited factors influencing plasma Lp(a) levels.</p> Results <p>In the Liver-Bible cohort, genetic variation in the <i>LPA</i> gene was the strongest determinant of Lp(a), followed by liver stiffness measurement (LSM). Additionally, circulating Lp(a) levels, but not genetic predisposition, were inversely related to LSM, suggesting that MASLD severity may affect Lp(a) secretion. Among participants with more severe insulin resistance (n = 250), Lp(a) levels (odds ratio 6.7, 95% CI 1.0–53.0, p = 0.046) and LSM (odds ratio 13.7, 95% CI 1.4–172.2, p = 0.023) were associated with greater prevalence of carotid atherosclerotic plaques, regardless of traditional cardiovascular risk factors. In the Milan Biobank, genetically predicted higher Lp(a) levels tended to increase the risk of liver-related outcomes, whereas genetically predicted MASLD was associated with lower circulating Lp(a) levels.</p> Conclusions <p>The results of this study suggest that liver damage is more likely the cause of reduced plasma Lp(a) levels rather than a consequence. Assessing plasma Lp(a) levels and the extent of liver damage could improve the prediction of vascular damage.</p>

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Interplay among lipoprotein(a), hepatic and vascular damage in individuals with metabolic dysfunction

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2025年11月26日

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  • Serena Pelusi,
  • Chiara Macchi,
  • Francesco Malvestiti,
  • Sara Margarita,
  • Irene De Matteis,
  • Giulia Periti,
  • Jessica Rondena,
  • Stefania Mira,
  • Francesca Iemma,
  • Martina Tranchina,
  • Barbara Nardi,
  • Carla Lucci,
  • Cesare R. Sirtori,
  • Oscar Millet,
  • Jose M. Mato,
  • Giovanni Targher,
  • Daniele Prati,
  • Massimiliano Ruscica,
  • Luca Valenti,
  • Serena Pelusi,
  • Giulia Periti,
  • Vittoria Moretti,
  • Stefania Mira,
  • Sara Margarita,
  • Luisa Ronzoni,
  • Daniele Marchelli,
  • Hadi Heidgah Torgabehei,
  • Alessandra Cazzaniga,
  • Elena Sinopoli,
  • Laura Cerami,
  • Elia Casirati,
  • Eniada Rrapaj,
  • Divya Akkaldev,
  • Francesco Malvestiti,
  • Martina Tranchina,
  • Francesca Ferrari,
  • Giuseppe Lamorte,
  • Valentina Vaira,
  • Daniele Prati,
  • Luca Valenti,
  • Roberta D’Ambrosio,
  • Giulia Tosetti,
  • Massimo Iavarone Pietro Lampertico,
  • Marco Maggioni,
  • Emanuela Orsi,
  • Annalisa Cespiati,
  • Paola Dongiovanni,
  • Anna Ludovica Fracanzani,
  • Chiara Rosso,
  • Angelo Armandi,
  • Gian Paolo Caviglia,
  • Elisabetta Bugianesi,
  • Grazia Pennisi,
  • Salvatore Petta,
  • Antonio Liguori,
  • Luca Miele,
  • Giorgio Soardo,
  • Francesco Paolo Russo,
  • Alessandro Federico,
  • Federica Tavaglione,
  • Umberto Vespasiani-Gentilucci,
  • Francesca Marchignoli,
  • Loris Pironi,
  • Teresa Pollicino

摘要

Background

The relationship between plasma lipoprotein(a) [Lp(a)] levels and metabolic dysfunction-associated steatotic liver disease (MASLD) remains unclear. The aim of this study was to examine the combined effects of Lp(a) levels on liver and vascular damage.

Methods

The study was conducted using the Liver-Bible cohort of individuals with metabolic dysfunction (n = 859, 808 with genomic information) and the Milan Biobank (n = 6963). Genome-wide association studies (GWAS) and polygenic risk scores (PRS) were used to evaluate the inherited factors influencing plasma Lp(a) levels.

Results

In the Liver-Bible cohort, genetic variation in the LPA gene was the strongest determinant of Lp(a), followed by liver stiffness measurement (LSM). Additionally, circulating Lp(a) levels, but not genetic predisposition, were inversely related to LSM, suggesting that MASLD severity may affect Lp(a) secretion. Among participants with more severe insulin resistance (n = 250), Lp(a) levels (odds ratio 6.7, 95% CI 1.0–53.0, p = 0.046) and LSM (odds ratio 13.7, 95% CI 1.4–172.2, p = 0.023) were associated with greater prevalence of carotid atherosclerotic plaques, regardless of traditional cardiovascular risk factors. In the Milan Biobank, genetically predicted higher Lp(a) levels tended to increase the risk of liver-related outcomes, whereas genetically predicted MASLD was associated with lower circulating Lp(a) levels.

Conclusions

The results of this study suggest that liver damage is more likely the cause of reduced plasma Lp(a) levels rather than a consequence. Assessing plasma Lp(a) levels and the extent of liver damage could improve the prediction of vascular damage.