Abstract

Background: Hepatic steatosis (HS) and a 10-year atherosclerotic cardiovascular disease (ASCVD) risk of ≥7.5% are associated with increased risk for future cardiovascular events. However, cardiovascular risk of patients with HS at ASCVD<7.5% is not clearly understood.

Methods: We studied adults with suspected stable angina and no history of coronary artery disease (CAD) who underwent coronary CT imaging in the PROMISE trial. HS, coronary artery calcium (CAC) score, obstructive CAD (stenosis ≥50%) and vulnerable plaques (plaques with low attenuation, positive remodeling, and napkin-ring sign) were defined by using coronary CT datasets. Major adverse cardiovascular event (MACE) was defined as hospitalization for unstable angina, non-fatal myocardial infarction, and all-cause death. Multivariable Cox regression analysis adjusting for CAC, obstructive CAD and vulnerable plaques assessed whether HS independently predicts MACE among patients at <7.5% ASCVD risk.

Results: Among ASCVD<7.5% risk patients, individuals with HS were younger (54.3±5.2 vs 55.8±5.2; p<0.001), more likely to be males (40.2% [98/244] vs 27.1% [260/960]; p<0.001), had more risk factors (mean number of risk factors: 2.06±0.89 vs 1.93±0.91; p=0.047) and had higher triglycerides (138.0 vs 115.0 mg/dL, p=0.014) and alanine transaminase (30.0 vs 19.0 mg/dL; p<0.001) than those without HS. These features similarly differed among patients with ASCVD≥7.5% risk with and without HS. CAD characteristics, (CAC, obstructive CAD, vulnerable plaques) did not differ between HS vs no HS patients independent of ASCVD risk (all p>0.05). Patients with HS had higher MACE rate in the ASCVD<7.5% (1.5% [14/960] vs 3.75 [9/244]; p=0.027) and ASCVD≥7.5% groups (3.1% [56/1,802] vs 4.7% [33/696]; p=0.043) compared to patients without HS. Among patients without HS ASCVD≥7.5% had higher MACE rate compared to ASCVD<7.5% (3.1% [56/1,802] vs 1.5% [14/960]; p=0.011). In patients with HS MACE rates were similar (ASCVD≥7.5% vs <7.5%: 4.7% [33/696] vs 3.7% [9/244], p=0.484). The cumulative event rate was significantly lower for patients without HS and ASCVD<7.5% compared to the other groups (figure). In patients with ASCVD<7.5%, HS predicted MACE (aHR:2.34, 95%CI:1.01-5.43; p=0.048), independent of CAD characteristics.

Conclusion: Individuals with radiographic HS and <7.5% ASCVD risk have similar CAD severity and burden as patients without HS at <7.5% ASCVD but experience similar MACE rates as individuals at ≥7.5% ASCVD risk.