| Title: | Sex- and menopause-specific inverse associations between metabolic dysfunction-associated steatotic liver disease and serum lipoprotein(a) concentrations: evidence from SHIP and UK Biobank |
| Journal: | Cardiovascular Diabetology |
| Published: | 12 Jul 2026 |
| Pubmed: | https://pubmed.ncbi.nlm.nih.gov/42437923/ |
| DOI: | https://doi.org/10.1186/s12933-026-03289-8 |
Publication 20304
WARNING: the interactive features of this website use CSS3, which your browser does not support. To use the full features of this website, please update your browser.
Abstract
BackgroundThe association between metabolic dysfunction-associated steatotic liver disease (MASLD) and serum lipoprotein(a) (Lp[a]) levels remains controversial, with no sex- or menopausal status-stratified analyses. We aimed to analyse the associations between MASLD, liver fat content (LFC) and transaminases with Lp(a) concentrations stratified by sex and menopausal status.MethodsWe analysed data from 3825 individuals (1961 females; 51.3%) aged 32 to 70 years from the SHIP-START-0 cohort, and from 28,504 individuals (14,926 females; 52.4%) aged 38 to 72 years from the UK Biobank cohort. MASLD was determined by liver ultrasound examinations in SHIP-STAR-0 and by magnetic resonance imaging in UK Biobank. We examined sex- and menopausal status-specific associations of MASLD, LFC, alanine aminotransferase (ALT), aspartate aminotransferase (AST), and gamma-glutamyltransferase (GGT) with lipoprotein(a) [Lp(a)] concentrations, after adjustment for age, body mass index, haemoglobin A1c, glucose-lowering medication use, hypertension, smoking, and alcohol consumption.ResultsIn SHIP-START-0, MASLD, higher ALT, AST, and GGT levels were independently associated with lower Lp(a) concentrations only in males but not in females. However, after stratification by menopausal status, higher ALT levels were associated with lower Lp(a) concentrations in postmenopausal females, but not in premenopausal females. In UK Biobank, MASLD severity (moderate and severe), higher LFC, and higher serum transaminase levels were independently associated with lower Lp(a) concentrations in males. Higher LFC was also associated with lower Lp(a) concentrations in females, but serum liver enzymes were not. After stratification by menopausal status, MASLD severity and higher LFC were associated with lower Lp(a) concentrations in postmenopausal females, but not in premenopausal females. Males with MASLD had 24% and 9% lower Lp(a) concentrations than those without MASLD in SHIP-START-0 and UK Biobank.ConclusionsOur findings from two large community-based studies show that MASLD and higher LFC and ALT values were independently associated with lower Lp(a) concentrations in postmenopausal females and males. Future studies are needed to determine whether the cardiovascular risk in patients with MASLD remains elevated even when Lp(a) concentrations are reduced and whether these patients require more intensive treatment to further reduce Lp(a) concentrations below the currently recommended cut-off values.Graphical abstract</p>
18 Keywords
- Adult
- Aged
- Biological Specimen Banks
- Biomarkers
- Fatty Liver
- Female
- Humans
- Lipoprotein(a)
- Liver
- Male
- Menopause
- Middle Aged
- Non-alcoholic Fatty Liver Disease
- Risk Assessment
- Risk Factors
- Sex Factors
- UK Biobank
- United Kingdom
17 Authors
- Júlia Galbiati de Souza
- Till Ittermann
- Nicole Werner
- Sabine Schipf
- Nele Friedrich
- Matthias Nauck
- Marcio Hiroshi Miname
- Fábio Fernandes
- Raul Dias Santos
- Jelena-Rima Ghadri
- Davide Di Vece
- Martin Bahls
- Giovanni Targher
- Elisabeth Steinhagen-Thiessen
- Christian Templin
- Nágila Raquel Teixeira Damasceno
- Marcello Ricardo Paulista Markus
1 Application
| Application ID | Title |
|---|---|
| 1002466 | Description of multiple risk factors for end-organ diseases in the UK Biobank population. |
Enabling scientific discoveries that improve human health