Research
Hormonal
Mendelian randomization studies suggest that genetic predisposition to MASLD via impaired VLDL secretion (PNPLA3, TM6SF2) may lower plasma lipids and potentially reduce coronary artery disease risk, whereas other MASLD genes show weak or no association with CAD.
This is a mechanistic insight rather than a direct intervention. It suggests that the way some people develop liver fat (by not secreting VLDL efficiently) might paradoxically protect them from heart disease. This highlights the complexity of the liver-heart axis.
ModerateQualifiesMEDIUM confidence
Clustering the four excluded genes [PNPLA3, TM6SF2, MTTP, and PEMT] showed a negative association (OR 0.97, 95% CI: 0.96, 0.99)... The entire cluster of MASLD genes was not associated with coronary artery disease, but when excluding the genes relating to MASLD through impaired VLDL secretion... a significant (but weak) association was found (OR 1.01, 95% CI: 1.00, 1.02).
Why this rating
Based on genetic association studies and Mendelian randomization, which are robust for causality but complex to interpret due to pleiotropy.
Source
Metabolic dysfunction-associated steatotic liver disease and the heart
Stan Driessen et al. · Hepatology · 2023
DOI 10.1097/hep.0000000000000735
narrative_reviewCited 94×
Read the paper DOI resolved against Crossref · corpus check 2026-06-10
More from this paper
- Metabolic dysfunction-associated steatotic liver disease (MASLD) is strongly associated with increased subclinical atherosclerosis (measured by carotid intima-media thickness and coronary artery calcification) and incident cardiovascular events, but does not independently increase cardiovascular mortality risk after adjusting for confounders.Good
- Advanced stages of MASLD (fibrosis/MASH) causally contribute to heart failure with preserved ejection fraction (HFpEF) through mechanical impediments to hepatic blood flow, reducing right ventricular preload.Moderate
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