Scholarlink

Background <p>Metabolic dysfunction-associated steatotic liver disease (MASLD) is associated with increased cardiovascular disease (CVD) risk. Lipoprotein(a) [Lp(a)] and insulin resistance (IR) are established cardiovascular risk factors, yet their joint associations with cardiovascular outcomes in MASLD remain poorly understood.</p> Methods <p>We analyzed data from the UK Biobank and included 101,348 adults with MASLD for CVD mortality analyses and 94,089 individuals without baseline CVD for incident CVD analyses. IR was assessed using the triglyceride-glucose (TyG) index. Participants were categorized according to Lp(a) levels (&lt; 125 vs. ≥ 125&#xa0;nmol/L) and TyG index (low vs. high, defined by the 75th percentile) and further classified into four joint Lp(a)/IR groups, with low Lp(a)/low IR serving as the reference group. Cox proportional hazards models were used to evaluate associations of Lp(a), TyG, and their combined categories with incident CVD and CVD mortality.</p> Results <p>During a median follow-up of 15.7&#xa0;years, elevated Lp(a) and higher TyG levels were each independently associated with increased risks of incident CVD and CVD mortality, regardless of each other’s status. In the fully adjusted model, each SD increase in Lp(a) was associated with a 14% higher risk of CVD mortality (HR, 1.14; 95% CI 1.10–1.19; <i>P</i> &lt; 0.001) and a 9% higher risk of incident CVD (HR, 1.09; 95% CI, 1.07–1.11; <i>P</i> &lt; 0.001). Similarly, each SD increase in TyG was associated with a 27% higher risk of CVD mortality (HR, 1.27; 95% CI 1.21–1.34; <i>P</i> &lt; 0.001) and a 9% higher risk of incident CVD (HR, 1.09; 95% CI 1.07–1.12; <i>P</i> &lt; 0.001). Compared with participants in the reference group with Lp(a) &lt; 125&#xa0;nmol/L and low IR, those with concomitantly elevated Lp(a) and high IR exhibited the highest cardiovascular risk, with adjusted HRs of 2.04 (95% CI 1.63–2.55) for CVD mortality and 1.49 (95% CI 1.35–1.64) for incident CVD (both <i>P</i> &lt; 0.001), with a significant dose-response trend across groups (<i>P</i> for trend &lt; 0.001). These associations remained consistent across subgroups stratified by age, sex, obesity, diabetes, and hypertension.</p> Conclusions <p>Elevated Lp(a) and IR were independently associated with adverse cardiovascular outcomes in MASLD, with the highest risk observed among individuals with concomitant elevations in both markers.</p> Graphical abstract <p></p>

错误：搜索内容不能为空，请输入英文关键词
错误：关键词超出字数限制，请精简
高级检索

Lipoprotein(a), insulin resistance, and cardiovascular outcomes in metabolic dysfunction-associated steatotic liver disease

  • 期刊论文

  • 出版模式：

    开放获取

  • 发表日期：

    2026年7月17日

查看全文
  • Bingtian Dong,
  • Yuping Chen,
  • Fang He,
  • Biao Li,
  • Biao Wu,
  • Zhengdong Chen,
  • Enfa Zhao,
  • Yongjian Chen,
  • Chaoxue Zhang

摘要

Background

Metabolic dysfunction-associated steatotic liver disease (MASLD) is associated with increased cardiovascular disease (CVD) risk. Lipoprotein(a) [Lp(a)] and insulin resistance (IR) are established cardiovascular risk factors, yet their joint associations with cardiovascular outcomes in MASLD remain poorly understood.

Methods

We analyzed data from the UK Biobank and included 101,348 adults with MASLD for CVD mortality analyses and 94,089 individuals without baseline CVD for incident CVD analyses. IR was assessed using the triglyceride-glucose (TyG) index. Participants were categorized according to Lp(a) levels (< 125 vs. ≥ 125 nmol/L) and TyG index (low vs. high, defined by the 75th percentile) and further classified into four joint Lp(a)/IR groups, with low Lp(a)/low IR serving as the reference group. Cox proportional hazards models were used to evaluate associations of Lp(a), TyG, and their combined categories with incident CVD and CVD mortality.

Results

During a median follow-up of 15.7 years, elevated Lp(a) and higher TyG levels were each independently associated with increased risks of incident CVD and CVD mortality, regardless of each other’s status. In the fully adjusted model, each SD increase in Lp(a) was associated with a 14% higher risk of CVD mortality (HR, 1.14; 95% CI 1.10–1.19; P < 0.001) and a 9% higher risk of incident CVD (HR, 1.09; 95% CI, 1.07–1.11; P < 0.001). Similarly, each SD increase in TyG was associated with a 27% higher risk of CVD mortality (HR, 1.27; 95% CI 1.21–1.34; P < 0.001) and a 9% higher risk of incident CVD (HR, 1.09; 95% CI 1.07–1.12; P < 0.001). Compared with participants in the reference group with Lp(a) < 125 nmol/L and low IR, those with concomitantly elevated Lp(a) and high IR exhibited the highest cardiovascular risk, with adjusted HRs of 2.04 (95% CI 1.63–2.55) for CVD mortality and 1.49 (95% CI 1.35–1.64) for incident CVD (both P < 0.001), with a significant dose-response trend across groups (P for trend < 0.001). These associations remained consistent across subgroups stratified by age, sex, obesity, diabetes, and hypertension.

Conclusions

Elevated Lp(a) and IR were independently associated with adverse cardiovascular outcomes in MASLD, with the highest risk observed among individuals with concomitant elevations in both markers.

Graphical abstract