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. 2018 Aug 22;13(8):e0202666.
doi: 10.1371/journal.pone.0202666. eCollection 2018.

Non-alcoholic fatty liver disease is a strong predictor of coronary artery calcification in metabolically healthy subjects: A cross-sectional, population-based study in middle-aged subjects

Anders Gummesson  1   2 , Ulf Strömberg  3 , Caroline Schmidt  2 , Joel Kullberg  4   5 , Oskar Angerås  2   6 , Stefan Lindgren  7 , Ola Hjelmgren  2   8 , Kjell Torén  9 , Annika Rosengren  2 , Björn Fagerberg  2 , John Brandberg  10 , Göran Bergström  2   8
Affiliations

Non-alcoholic fatty liver disease is a strong predictor of coronary artery calcification in metabolically healthy subjects: A cross-sectional, population-based study in middle-aged subjects

Anders Gummesson et al. PLoS One. .

Abstract

Objectives: This study aims to estimate the relationship between non-alcoholic fatty liver disease (NAFLD) and measures of atherosclerotic cardiovascular disease (ASCVD), and to determine to what extent such relationships are modified by metabolic risk factors.

Methods: The study was conducted in the population-based Swedish CArdioPulmonary bioImage Study (SCAPIS) pilot cohort (n = 1015, age 50-64 years, 51.2% women). NAFLD was defined as computed tomography liver attenuation ≤40 Hounsfield Units, excluding other causes of liver fat. Coronary artery calcification score (CACS) was assessed using the Agatston method. Carotid plaques and intima media thickness (IMT) were measured by ultrasound. Metabolic status was based on assessments of glucose homeostasis, serum lipids, blood pressure and inflammation. A propensity score model was used to balance NAFLD and non NAFLD groups with regards to potential confounders and associations between NAFLD status and ASCVD variables in relation to metabolic status were examined by logistic and generalized linear regression models.

Results: NAFLD was present in 106 (10.4%) of the subjects and strongly associated with obesity-related traits. NAFLD was significantly associated with CACS after adjustment for confounders and metabolic risk factors (OR 1.77, 95% CI 1.07-2.94), but not with carotid plaques and IMT. The strongest association between NAFLD and CACS was observed in subjects with few metabolic risk factors (n = 612 [60% of all] subjects with 0-1 out of 7 predefined metabolic risk factors; OR 5.94, 95% CI 2.13-16.6).

Conclusions: NAFLD was independently associated with coronary artery calcification but not with measures of carotid atherosclerosis in this cohort. The association between NAFLD and CACS was most prominent in the metabolically healthy subjects.

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Conflict of interest statement

J.K. is cofounder and employee of Antaros Medical, Sweden. S.L. has received fees from Intercept Pharmaceuticals for lecturing and advisory board participation. A.G. is a part time employee at Antaros Medical, Sweden. All other authors declared they do not have anything to disclose regarding conflict of interest with respect to this manuscript. This does not alter our adherence to PLOS ONE policies on sharing data and materials.

Figures

Fig 1
Fig 1. Reasons for excluding SCAPIS pilot participants in the present study.
Fig 2
Fig 2. Schematic illustration of an underlying, hypothetical causal model framework considered when modelling cross-sectional relationships between NAFLD, confounders, metabolic risk factors, and outcome measures of atherosclerotic cardiovascular disease.
NAFLD is the risk factor studied. The potential confounders may influence NAFLD but not vice versa. By contrast, the metabolic risk factors may be influenced or modified by NAFLD, i.e. some of these factors may act as intermediates in the potential causal pathways between NAFLD and the outcomes.
Fig 3
Fig 3. Proportions (in percent) of subjects with CACS = 0, 1–99, and ≥100 according to NAFLD and metabolic status. Numbers within bars depict the number of subjects within each category.
See this image and copyright information in PMC

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