Author:
Björnson Elias,Samaras Dimitrios,Adiels Martin,Kullberg Joel,Bäckhed Fredrik,Bergström Göran,Gummesson Anders
Abstract
AbstractNon-alcoholic fatty liver disease (NAFLD) is associated with increased secretion of apoB-containing lipoproteins and increased risk of coronary heart disease (CHD). ApoB-containing lipoproteins include low-density lipoproteins (LDLs) and triglyceride-rich lipoproteins (TRLs); and since both LDLs and TRLs are causally related to CHD, they may mediate a portion of the increased risk of atherosclerosis seen in people with NAFLD. In a cohort of 4161 middle aged men and women, we performed mediation analysis in order to quantify the mediating effect of apoB-containing lipoproteins in the relationship between liver fat and atherosclerosis—as measured by coronary artery calcium score (CACS). We found plasma apoB to mediate 17.6% (95% CI 11–24) of the association between liver fat and CACS. Plasma triglycerides and TRL-cholesterol (both proximate measures of TRL particles) mediated 22.3% (95% CI 11–34) and 21.6% (95% CI 10–33) of the association respectively; whereas LDL-cholesterol mediated 5.4% (95% CI 2.0–9.4). In multivariable models, the mediating effect of TRL-cholesterol and plasma triglycerides showed, again, a higher degree of mediation than LDL-cholesterol, corroborating the results seen in the univariable models. In summary, we find around 20% of the association between liver fat and CACS to be mediated by apoB-containing lipoproteins. In addition, we find that TRLs mediate the majority of this effect whereas LDLs mediate a smaller effect. These results explain part of the observed CAD-risk burden for people with NAFLD and further suggest that TRL-lowering may be particularly beneficial to mitigate NAFLD-associated coronary artery disease risk.
Funder
AFA Försäkring
Knut och Alice Wallenbergs Stiftelse
Hjärt-Lungfonden
ALF
Forskningsrådet om Hälsa, Arbetsliv och Välfärd
Vetenskapsrådet
LUA/ALF
VINNOVA
Sahlgrenska University Hospitals Research Foundations
University of Gothenburg
Publisher
Springer Science and Business Media LLC
Cited by
2 articles.
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