Hepatic fat as a novel marker for high-risk coronary atherosclerotic plaque features in familial hypercholesterolaemia

Gavin Huangfu, Biyanka Jaltotage, Jing Pang, Nick S. R. Lan, Arun Abraham, Jacobus Otto, Abdul Ihdayhid, James M. Rankin, Benjamin J.W. Chow, Gerald Watts, Oyekoya T. Ayonrinde, Girish Dwivedi

Research output: Contribution to journalArticlepeer-review

4 Citations (Web of Science)


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 mm 3 vs Q1: 414 mm 3, 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.


Original languageEnglish
Pages (from-to)155370
JournalMetabolism: clinical and experimental
Early online date1 Dec 2022
Publication statusPublished - Feb 2023


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