The Association of the Steatosis Severity in Fatty Liver Disease With Coronary Plaque Pattern in General Population

Pai-Feng Hsu; Ying-Wen Wang; Chung-Chi Lin; Yuan-Jen Wang; Yaw-Zon Ding; Teh-Ling Liou; Shao-Sung Huang; Tse-Min Lu; Wan-Leong Chan; Shing-Jong Lin; Hsin-Bang Leu


Liver International. 2021;41(1):81-90. 

In This Article


Based on hepatic sonography and history of limited daily alcohol consumption (males <30 g/d and females <20 g/d), NAFLD steatosis was defined according to the presence of fat infiltration into the liver. In order to avoid any influence from underlying liver disorders, carriers of Hepatitis B and C viruses and those with chronic liver parenchymal disorders were also excluded from this study. A similar definition for NAFLD identification was used in our previous study.[2] Furthermore, subjects with prior history of major CVDs, including stroke, myocardial infarction, coronary artery disease (CAD) and/or peripheral artery disease (PAD) were excluded from the study.

All subjects underwent blood sampling for biochemical studies and abdominal ultrasonography examinations. Experienced gastroenterologists who were blinded to clinical presentation and laboratory findings performed the abdominal ultrasonography evaluations, and image results were compared between the two specialists. Examinations were performed using an Aloka Prosound α6 (Hitachi Aloka Medical Systems, Tokyo, Japan) equipped with an 8 MHz-wide bandwidth linear active matrix transducer (ranging from 1 to 15 MHz). The severity of fatty liver steatosis was graded according to three categories: (a) mild, defined as a slight diffuse increase in the hepatic parenchyma with normal visualization of the diaphragm and the portal veins; (b) moderate, defined as a moderately diffuse increase in hepatic echogenicity with a slightly impaired visualization of the diaphragm and the portal veins; and (c) severe, defined as a marked increase in hepatic echogenicity with poor or no visualization of the diaphragm and the portal veins.[2,13] The definition of NAFLD steatosis severity was used in our previous work.[2] This study was conducted in accordance with the Declaration of Helsinki, and the protocol was approved by the Ethics Committee and Independent Review Boards in Taipei Veterans General Hospital (2018-04-006AC).

CCTA Measurement

Routine coronary computed tomography angiography (CCTA) was performed using a multiple detector computed tomography scanner (Definition Flash, Siemens Healthineers, Erlangen, Germany). Clinical blood pressure and heart rate were measured before CCTA, and beta-blockers, usually propranolol with or without a calcium channel blocker, were given to patients with an initial heart rate >80 beats per minute. Prospective electrocardiography-gated axial scans for calcium scoring were recorded at 75% of the R-R interval with the collimation set to 3.0 mm. The initial scanning sequence began approximately 1 cm above the left main coronary artery. CCTA parameters were 120 kV and 60 mA. A temporal resolution of 230 msec was achieved using the half-scan reconstruction method with a 350-ms gantry rotation time. CCTA was performed using retrospective gated helical scanning with the parameters set at 64 × 0.5 mm–128 × 0.625 mm collimation, 270–350 msec gantry rotation time, and 80–135 kV adapted to body size. The bolus-tracking method was used after injecting 50–100 mL of iodinated contrast medium (Iopamiro370, Bracco Imaging SpA, Milan, Italy; Ultravist 370, Bayer Pharma AG, Berlin, Germany) at a rate of 4.5–5.0 mL per second followed by 50 mL of normal saline at a rate of 5.5 mL per second based on the patient's body size. The workstation automatically selected the best phase; if the image quality was suboptimal, a phase with the best possible image quality was manually reconstructed, which was reconstructed into images with slice thicknesses of 0.75 and 0.9 mm at 0.45-mm intervals. All images were transferred to an external workstation (EBW, Amsterdam, Netherlands) for analysis. Detailed plaque morphology and the degree of coronary luminal stenosis were assessed based on previous guidelines.[14] The plaques can be characterized as calcified, noncalcified, or mixed (containing both types of material) plaques as previous study clarified as shown in Figure 1. Different plaque pattern have distinct differences in prognostic outcomes. Mixed plaques are associated with the worst prognosis, whereas calcified plaques are associated with the best event-free survival, and noncalcified plaques have an associated risk in between the other two types.[15,16]

Figure 1.

Longitudinal views of significant (>50%) stenotic calcified (A), non-calcified (soft)(B) and partial calcified (mixed) (C) plaque morphology of coronary atherosclerosis by coronary CT scan

The severity of coronary atherosclerosis was scored as previously reported. The coronary artery calcium (CAC) score was calculated using the Agatston method and graded: (1) 0, (2) 1–99, (3) 100–399 and (4) ≥400. Several CCTA scores, including CAC, atheroma burden obstructive score (ABOS), segment involvement score (SIS) and segment stenosis score (SSS) were measured.[17,18] ABOS was defined as the number of plaques with >50% stenosis in the entire coronary artery tree. SIS was calculated as the total number of coronary artery segments that exhibited plaques, regardless of the degree of luminal stenosis within each segment (minimum = 0; maximum = 16). SSS was used to measure the overall extent of coronary artery plaques. Each individual coronary segment was graded as having no to severe plaques (scores ranging from 0 to 3 points) based on the extent of coronary artery luminal diameter obstruction. The scores from all 16 individual segments were added together to yield a total score that ranged from 0 to 48.[19]

Laboratory Measurements

Blood samples were collected from patients after overnight fasting. Serum biochemical parameters, including high- and low-density lipoprotein cholesterol (HDL-C and LDL-C, respectively), blood urea nitrogen (BUN), creatinine, aspartate aminotransferase (AST), alanine aminotransferase (ALT), uric acid, fasting blood glucose and glycosylated hemoglobin (HbA1c) levels were measured using a TBA-c16000 automatic analyzer (Toshiba Medical Systems, Tochigi, Japan). The measurement of biochemical parameters was performed as previously described.[20]

Statistical Analysis

All data were expressed as the frequency (percentage) or the mean ± standard deviation (SD). All participants were divided into groups based on NAFLD steatosis severity. Parametric continuous data between the participants were compared using a one-way analysis of variance. Categorical data between the NAFLD subgroups were compared using a chi-squared or Fisher's exact test. In order to analyse the contributors to specific plaque patterns, a multivariate analysis was performed using logistic regression to show the independent predictive value for the presence of overall, calcified, non-calcified (soft) and partial calcified (mixed) plaques after considering variables, including age, gender, history of hypertension, diabetes, smoking, waist circumference and serum LDL-cholesterol values. Subgroup analyses were also performed to determine the impact of the severity of NAFLD steatosis in the presence of coronary plaque patterns among genders, age ≥65 years old, smoking status, LDL-C >160 mg/dL, body mass index (BMI) >27 and the presence of metabolic syndrome. The p-value was two-sided, with P < .05 considered to be statistically significant. Statistical analyses were performed utilizing SPSS software (Version 15.0, SPSS Inc).