Highlights
- •Hepatic fat independently predicts high-risk coronary artery plaque features in FH.
- •Hepatic fat associates with higher low attenuation and non-calcified plaque volumes.
- •CT assessment of hepatic fat may add incremental value to CVD risk stratification.
Abstract
Background & aims
Hepatic steatosis has been associated with increased risk of coronary artery disease.
Individuals with familial hypercholesterolaemia have accelerated but variable progression
of coronary artery disease. We investigated whether hepatic steatosis is associated
with novel coronary atherosclerosis biomarkers in adults with heterozygous familial
hypercholesterolaemia, using comprehensive coronary computed tomographic angiography.
Methods
We conducted a cross-sectional study of 213 asymptomatic patients with familial hypercholesterolaemia
(median age 54.0 years, 59 % female) who underwent coronary computed tomographic angiography
for cardiovascular risk assessment in an outpatient clinic. High-risk plaque features,
plaque volume and pericoronary adipose tissue attenuation were assessed. From concurrently
captured upper abdominal images, severity of hepatic steatosis was computed, as liver
minus spleen computed tomography attenuation and stratified into quartiles.
Results
Of 213 familial hypercholesterolaemia patients, 59 % had coronary artery calcium,
36 % obstructive coronary artery disease (≥50 % stenosis) and 77 % high-risk plaque
features. Increasing hepatic steatosis was associated with higher calcium scores,
more high-risk plaque features and presence of obstructive coronary artery disease.
Hepatic steatosis was associated with the presence of high-risk plaque features (OR:
1.48; 95 % CI: 1.09–2.00; p = 0.01), particularly in the proximal coronary segments
(OR: 1.52; 95 % CI: 1.18–1.96; p = 0.001). Associations persisted on multivariable
logistic regression analysis adjusting for cardiometabolic factors, obstructive coronary
artery disease and calcium score. Hepatic steatosis was associated with higher plaque
volumes (Q4: 499 mm3 vs Q1: 414 mm3, p = 0.02), involving mainly low attenuation and noncalcified plaques (both p = 0.03).
No differences in pericoronary adipose tissue attenuation were observed.
Conclusions
Hepatic steatosis is associated with multiple indices of advanced coronary atherosclerosis
in familial hypercholesterolaemia patients, particularly high-risk plaque features,
independent of conventional cardiovascular risk factors and markers. This may involve
specific mechanisms related to hepatic steatosis.
Clinical trial number: N/A.
Graphical abstract
Graphical Abstract
Abbreviations:
ACS (acute coronary syndrome), ASCVD (atherosclerotic cardiovascular disease), BMI (body mass index), CAC (coronary artery calcium), CAD (coronary artery disease), CCTA (computed coronary tomographic angiography), CT (computed tomography), FH (familial hypercholesterolaemia), HDL (high-density lipoprotein), HRP (high-risk plaque), HS (hepatic steatosis), HU (Hounsfield unit), HUL-S (liver attenuation index), IQR (interquartile range), LAD (left anterior descending), LAP (low-attenuation plaque), LDL (low-density lipoprotein), NAFLD (non-alcoholic fatty liver disease), PCAT (pericoronary adipose tissue attenuation), PR (positive remodelling), PV (plaque volume), RCA (right coronary artery), RLP (remnant lipoprotein), SC (spotty calcification)Keywords
To read this article in full you will need to make a payment
Purchase one-time access:
Academic & Personal: 24 hour online accessCorporate R&D Professionals: 24 hour online accessOne-time access price info
- For academic or personal research use, select 'Academic and Personal'
- For corporate R&D use, select 'Corporate R&D Professionals'
Subscribe:
Subscribe to Metabolism - Clinical and ExperimentalAlready a print subscriber? Claim online access
Already an online subscriber? Sign in
Register: Create an account
Institutional Access: Sign in to ScienceDirect
References
- Metabolically healthy obesity.Endocr Rev. 2020; 41bnaa004
- Metabolic inflammation—a role for hepatic inflammatory pathways as drivers of comorbidities in nonalcoholic fatty liver disease?.Gastroenterology. 2020; 158e6
- Non-alcoholic fatty liver disease and risk of cardiovascular disease.Metabolism. 2016; 65: 1136-1150
- Non-alcoholic fatty liver disease and risk of fatal and non-fatal cardiovascular events: an updated systematic review and meta-analysis.Lancet Gastroenterol Hepatol. 2021; 6: 903-913
- Nonalcoholic fatty liver disease and cardiovascular risk: a scientific statement from the American Heart Association.Arterioscler Thromb Vasc Biol. 2022; https://doi.org/10.1161/ATV. 0000000000000153
- The diagnosis and management of nonalcoholic fatty liver disease: practice guidance from the American Association for the Study of Liver Diseases.Hepatology. 2018; 67: 328-357
- Non-alcoholic fatty liver disease, insulin resistance, metabolic syndrome and their association with vascular risk.Metabolism. 2021; 119154770
- Integrated guidance on the care of familial hypercholesterolaemia from the International FH Foundation.Int J Cardiol. 2014; 171: 309-325
- An age-matched computed tomography angiographic study of coronary atherosclerotic plaques in patients with familial hypercholesterolaemia.Atherosclerosis. 2020; 298: 52-57
- Postprandial lipoprotein metabolism in familial hypercholesterolemia: thinking outside the box.Metabolism. 2012; 61: 3-11
- Elevated lipoprotein (a), hypertension and renal insufficiency as predictors of coronary artery disease in patients with genetically confirmed heterozygous familial hypercholesterolemia.Int J Cardiol. 2015; 201: 633-638
- Heterozygous familial hypercholesterolaemia in specialist centres in South Africa, Australia and Brazil: importance of early detection and lifestyle advice.Atherosclerosis. 2018; 277: 470-476
- Prevalence of non-coronary heart disease in patients with familial hypercholesterolemia: an analysis from the HELLAS-FH.Atherosclerosis. 2021; 331: e185-e186
- Coronary artery plaque characteristics associated with adverse outcomes in the SCOT-HEART study.J Am Coll Cardiol. 2019; 73: 291-301
- Low-attenuation noncalcified plaque on coronary computed tomography angiography predicts myocardial infarction: results from the multicenter SCOT-HEART trial (Scottish Computed Tomography of the HEART).Circulation. 2020; 141: 1452-1462
- Non-invasive detection of coronary inflammation using computed tomography and prediction of residual cardiovascular risk (the CRISP CT study): a post-hoc analysis of prospective outcome data.Lancet. 2018; 392: 929-939
- Coronary computed tomographic angiography findings and their therapeutic implications in asymptomatic patients with familial hypercholesterolemia. Lessons from the SAFEHEART study.J Clin Lipidol. 2018; 12: 948-957
- High-risk plaque detected on coronary CT angiography predicts acute coronary syndromes independent of significant stenosis in acute chest pain: results from the ROMICAT-II trial.J Am Coll Cardiol. 2014; 64: 684-692
- Prognostic value of coronary CT angiography and calcium score for major adverse cardiac events in outpatients.JACC Cardiovasc Imaging. 2012; 5: 990-999
- A comparative analysis of phenotypic predictors of mutations in familial hypercholesterolemia.J Clin Endocrinol Metabol. 2018; 103: 1704-1714
- SCCT guidelines for the interpretation and reporting of coronary CT angiography: a report of the Society of Cardiovascular Computed Tomography Guidelines Committee.J Cardiovasc Comput Tomogr. 2014; 8: 342-358
- Quantification of coronary artery calcium using ultrafast computed tomography.J Am Coll Cardiol. 1990; 15: 827-832
- Incremental prognostic value of quantified vulnerable plaque by cardiac computed tomography.J Thorac Imaging. 2016; 31: 373-379
- High-risk coronary plaque at coronary CT angiography is associated with nonalcoholic fatty liver disease, independent of coronary plaque and stenosis burden: results from the ROMICAT II trial.Radiology. 2015; 274: 693-701
- Macrovesicular hepatic steatosis in living related liver donors: correlation between CT and histologic findings.Radiology. 2004; 230: 276-280
- Pericardial, but not hepatic, fat by CT is associated with CV outcomes and structure: the multi-ethnic study of atherosclerosis.JACC Cardiovasc Imaging. 2017; 10: 1016-1027
- The metabolic syndrome—a new worldwide definition.Lancet. 2005; 366: 1059-1062
- Obesity-induced changes in adipose tissue microenvironment and their impact on cardiovascular disease.Circ Res. 2016; 118: 1786-1807
- Nonalcoholic fatty liver disease and the heart: JACC state-of-the-art review.J Am Coll Cardiol. 2019; 73: 948-963
- Non-alcoholic fatty liver disease (NAFLD) and its connection with insulin resistance, dyslipidemia, atherosclerosis and coronary heart disease.Nutrients. 2013; 5: 1544-1560
- The liver as an endocrine organ—linking NAFLD and insulin resistance.Endocr Rev. 2019; 40: 1367-1393
- Pericoronary adipose tissue computed tomography attenuation and high-risk plaque characteristics in acute coronary syndrome compared with stable coronary artery disease.JAMA Cardiol. 2018; 3: 858-863
- Determinants of pericoronary adipose tissue attenuation on computed tomography angiography in coronary artery disease.J Am Heart Assoc. 2020; 9e016202
- Pathologic assessment of the vulnerable human coronary plaque.Heart. 2004; 90: 1385-1391
- Coronary artery spatial distribution of acute myocardial infarction occlusions.Circulation. 2004; 110: 278-284
- Distance from the coronary ostium to the culprit lesion in acute ST-elevation myocardial infarction and its implications regarding the potential prevention of proximal plaque rupture.J Thromb Thrombolysis. 2003; 15: 189-196
- Heritability of coronary artery disease: insights from a classical twin study.<sb:contribution><sb:title>Circ</sb:title></sb:contribution><sb:host><sb:issue><sb:series><sb:title>Cardiovasc Imaging</sb:title></sb:series></sb:issue></sb:host>. 2022; 15e013348
- Plaque progression at coronary CT angiography links non-alcoholic fatty liver disease and cardiovascular events: a prospective single-center study.Eur Radiol. 2022; 1–11
- Incremental prognostic value of non-alcoholic fatty liver disease over coronary computed tomography angiography findings in patients with suspected coronary artery disease.Eur J Prev Cardiol. 2021; 28: 2059-2066
- The correlation between hepatic fat fraction evaluated by dual-energy computed tomography and high-risk coronary plaques in patients with non-alcoholic fatty liver disease.Jpn J Radiol. 2021; 39: 763-773
- Severe, but not mild to moderate, non-alcoholic fatty liver disease associated with increased risk of subclinical coronary atherosclerosis.BMC Cardiovasc Disord. 2021; 21: 1-9
- Fibrosis stage is the strongest predictor for disease-specific mortality in NAFLD after up to 33 years of follow-up.Hepatology. 2015; 61: 1547-1554
- Cardiovascular risk factors in non-alcoholic fatty liver disease.Liver Int. 2019; 39: 197-204
- Non-alcoholic fatty liver disease and incident major adverse cardiovascular events: results from a nationwide histology cohort.Gut. 2022; 71: 1867-1875
- A meta-analysis of the effects of glucagon-like-peptide 1 receptor agonist (GLP1-RA) in nonalcoholic fatty liver disease (NAFLD) with type 2 diabetes (T2D).Sci Rep. 2021; 11: 1-8
- Recent guidelines for non-alcoholic fatty liver disease (NAFLD): are they already outdated and in need of supplementation? Elsevier, 2022: 155248
- Tirzepatide versus semaglutide once weekly in patients with type 2 diabetes.NEnglJMed. 2021; 385: 503-515
- Effects of cotadutide on metabolic and hepatic parameters in adults with overweight or obesity and type 2 diabetes: a 54-week randomized phase 2b study.Diabetes Care. 2021; 44: 1433-1442
- EASL-EASD-EASO clinical practice guidelines for the management of non-alcoholic fatty liver disease.Obesity Facts. 2016; 9: 65-90
- Potential of electron beam computed tomography for coronary artery calcium screening to evaluate fatty liver: comparison with 1H magnetic resonance spectroscopy in the Dallas Heart Study.J Invest Med. 2011; 59: 780-786
- Current status of imaging in nonalcoholic fatty liver disease.World J Hepatol. 2018; 10: 530
- Coronary calcium score and cardiovascular risk.J Am Coll Cardiol. 2018; 72: 434-447
- Analysis of steatosis biomarkers and inflammatory profile after adding on PCSK9 inhibitor treatment in familial hypercholesterolemia subjects with nonalcoholic fatty liver disease: a single lipid center real-world experience.Nutr Metab Cardiovasc Dis. 2021; 31: 869-879
- Cardiovascular disease in patients with genotyped familial hypercholesterolemia in Norway during 1994–2009, a registry study.Eur J Prev Cardiol. 2016; 23: 1962-1969
- Familial hypercholesterolaemia: evolving knowledge for designing adaptive models of care.Nat Rev Cardiol. 2020; 17: 360-377
Article info
Publication history
Published online: November 30, 2022
Accepted:
November 25,
2022
Received:
June 4,
2022
Identification
Copyright
© 2022 Elsevier Inc. All rights reserved.
