Exploring the Complex Interplay: Fatty Liver Severity, Epicardial Fat Volume, and Coronary Artery Calcification

EXTENDED ABSTRACT

Background

Nonalcoholic fatty liver disease (NAFLD) is characterized by hepatic steatosis in the absence of secondary causes of hepatic fat accumulation, including clinically important alcohol exposure [1]. It is common worldwide [2, 3]; a cited meta-analysis estimated an overall prevalence of 25.24%, with the highest rates in the Middle East and South America [4], while Iranian studies have reported prevalence estimates of approximately 27.88%-33% [5, 6]. NAFLD spans a spectrum from simple steatosis to nonalcoholic steatohepatitis, with a proportion of affected patients progressing to fibrosis, cirrhosis, or hepatic failure [7, 8].

NAFLD is also closely associated with metabolic syndrome; major recognized risk factors include age, sex, obesity, and insulin resistance [2,9]. Although liver biopsy is the most accurate diagnostic method, its invasive nature limits routine use. Clinical assessment therefore commonly integrates ultrasonographic and laboratory findings, and ultrasonographic grading can correlate with the degree of hepatic fatty infiltration [10-13]. The article further describes growing interest in the cardiovascular implications of NAFLD because patients frequently have traditional cardiovascular risk factors and may have increased atherosclerotic risk [13-15].

Epicardial adipose tissue is a metabolically active visceral fat depot located directly on the epicardial surface and surrounding the coronary arteries. Because of its shared developmental origin and metabolic behavior with visceral adipose tissue, it can release inflammatory mediators and may participate in local paracrine interactions with the myocardium and coronary circulation [16-18]. Coronary artery calcium (CAC) is likewise used as an imaging marker of subclinical coronary atherosclerosis and future cardiovascular risk [19]. However, prior findings regarding the relationship of fatty liver with CAC have been inconsistent [20]. The present study therefore evaluated whether ultrasonographic fatty liver severity was associated with epicardial fat volume and coronary artery calcium score in patients undergoing coronary CT angiography.

Methods

This cross-sectional study enrolled 136 consecutive patients referred to the coronary CT angiography unit of Farshchian Cardiovascular Hospital in Hamadan, Iran. Eligible participants had low-to-moderate risk of coronary artery disease and provided written informed consent. Exclusion criteria were a history of coronary artery bypass grafting, percutaneous coronary intervention, pericardial effusion, hypothyroidism, Cushing syndrome, or corticosteroid use. Before CT angiography, contrast allergy history was assessed and glomerular filtration rate was calculated. The sample size of 136 was calculated using an assumed adult fatty liver prevalence of 35%, alpha=0.05, and an error of 0.08, following the prevalence estimate cited by the authors [21].

Cardiac CT was performed using a 128-slice Siemens multidetector scanner. Before contrast administration, prospective ECG-triggered 3-mm axial images were obtained from the carina to the inferior cardiac border. CAC was measured semi-automatically with Syngo.via software according to the Agatston method; coronary plaques with density greater than 130 Hounsfield units were included. Epicardial fat volume was also measured semi-automatically. Adipose tissue was defined using a density range of -250 to -50 Hounsfield units, and the epicardial fat region was manually traced from the origin of the left main coronary artery to the cardiac apex before software-based volume calculation.

A single sonologist performed liver ultrasonography using a GE Voluson E6 system with a 3-5 MHz probe. Fatty liver severity was categorized according to hepatic echogenicity as normal, mild (grade I), moderate (grade II), or severe (grade III). Data were analyzed in SPSS version 26. Because epicardial fat volume and CAC score were not normally distributed, Kruskal-Wallis testing was used for comparisons by fatty liver grade, sex, and age group. Chi-square testing evaluated fatty liver grade according to age group, sex, smoking, diabetes, hypertension, dyslipidemia, and family history of cardiovascular disease. Statistical significance was defined as P<0.05. The Ethics Committee of Hamadan University of Medical Sciences approved the study (IR.UMSHA.REC.1400.208), and written informed consent was obtained from all participants.

Results

The mean age of the 136 participants was 52.12±10.90 years, with an age range of 22-83 years. There were 69 men (50.5%) and 67 women (49.5%). Smoking was reported in 30.1%, a family history of cardiovascular disease in 39.7%, hypertension in 45.6%, and diabetes in 21.3%. Ultrasonography classified 64 patients (47.1%) as having no fatty liver, 48 (35.3%) as grade I, 21 (15.4%) as grade II, and 3 (2.2%) as grade III. CAC was zero in 65.4% of participants and minimal in 9.6%; mild, moderate, and severe CAC categories accounted for 11.8%, 12.5%, and 0.7%, respectively. The overall reported mean CAC score was 30.76±35.40, and mean epicardial fat volume was 86.84±36.56.

Table 1. Mean and standard deviation of epicardial fat volume and coronary artery calcium score according to fatty liver severity.

Because of the small numbers in grades II and III, the investigators combined grades I-III for the principal comparison with the normal group. No statistically significant association was detected between fatty liver status and epicardial fat volume (P=0.625) or CAC score (P=0.096), although the article states that CAC was higher among patients with fatty liver than among those with normal liver ultrasonography. Stratified analyses similarly showed no significant differences in CAC according to fatty liver grade among men (P=0.108), women (P=0.968), patients younger than 50 years (P=0.130), or those aged 50 years and older (P=0.374). Epicardial fat volume also did not differ significantly by fatty liver grade after stratification by sex or age; reported P values were 0.451 for men, 0.771 for women, 0.798 for participants younger than 50 years, and 0.710 for those aged 50 years or older.

Fatty liver grade was not significantly associated with age group (P=0.705), sex (P=0.389), smoking (P=0.257), or hypertension (P=0.331). In contrast, NAFLD was significantly more frequent among participants with diabetes (P=0.001), dyslipidemia (P=0.015), and a family history of cardiovascular disease (P=0.001). Among participants with diabetes, 9 (31.0%) had normal liver ultrasonography, 8 (27.6%) had grade I fatty liver, and 12 (41.4%) had grades II-III. Among those with dyslipidemia, the corresponding distributions were 16 (31.4%), 22 (43.1%), and 13 (25.5%). For participants reporting a family history of cardiovascular disease, the respective frequencies were 15 (27.8%), 24 (44.4%), and 15 (27.8%).

Table 4. Fatty liver grade according to family history of cardiovascular disease, dyslipidemia, and diabetes.

Conclusion

In this cohort of patients referred for coronary CT angiography, ultrasonographic fatty liver severity was not significantly related to epicardial fat volume or coronary artery calcium score, including after analyses stratified by sex and age. Fatty liver was, however, significantly more common in participants with diabetes, dyslipidemia, and a family history of cardiovascular disease. These findings support the article's conclusion that fatty liver severity was not associated with these two coronary imaging markers. The authors noted that the absence of a healthy control group and the relatively small sample, particularly in higher fatty liver grades, may have limited detection of associations, and they recommended evaluation in larger cardiac and noncardiac populations.

Keywords: Calcium Score, Epicardial Fat, Fatty Liver

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