MON-293 - ASCVD Risk Scores May Underestimate Cardiovascular Risk in Postmenopausal Women with Metabolic Dysfunction-Associated Steatotic Liver Disease

Background: Metabolic dysfunction-associated steatotic liver disease (MASLD), defined as increased intrahepatic lipid content in the setting of additional cardiometabolic risk factors such as overweight/obesity, hypertension, and type 2 diabetes, is an independent risk factor for atherosclerotic cardiovascular disease (ASCVD), with ASCVD representing the principal cause of death in patients with MASLD. However, little is known about whether ASCVD risk scores can predict cardiovascular risk in postmenopausal women with MASLD, independent of other risk factors.

Methods: This was a cross-sectional study of 49 postmenopausal women: 36 with and 13 without MASLD. Women underwent either liver MR spectroscopy (MRS) and/or FibroScan for evaluation of MASLD and were classified as having MASLD if liver fat on MRS ≥5% (N=36), and as not having MASLD if liver fat on MRS < 5% (N=11) or CAP on FibroScan < 250dB/m (N=2). ASCVD risk scores were calculated with the American Heart Association (AHA) pooled cohort and PREVENT equations. Primary analysis was comparison of ASCVD risk score between post-menopausal women with and without MASLD by Wilcoxon Rank Sum Test. Secondary endpoints were number of known cardiometabolic risk factors per person: overweight/obesity, history of hypertension, dyslipidemia, history of type 2 diabetes mellitus, and smoking status.

Results: MR liver fat was higher in women with MASLD (18.7% [10.7, 22.7] vs those without MASLD 3.8 [2.9, 4.0], p< 0.001). ASCVD risk scores were significantly higher in women with MASLD (AHA pooled cohort: median 5.88 [3.73, 8.41]; PREVENT median 3.65 [2.65, 4.9]), compared to those without MASLD (AHA pooled cohort: median 2.71 [1.64, 5.95], p=0.022; PREVENT median 1.85 [1.52, 2.38], p=0.009). Six (16.7%) women with MASLD had an ASCVD risk score >10% (high risk) while no woman without MASLD had a high ASCVD risk score. The median number of cardiometabolic risk factors was similar in women with MASLD (median 2 [2, 3]) compared to women without MASLD (median 2 [1, 3]; p=0.096). Twelve (33.3%) women with MASLD smoked tobacco whereas there were no women without MASLD who smoked (p=0.043). The difference in risk scores was no longer significant after adjusting for smoking status (pooled cohort: p=0.45; PREVENT: p=0.45).

Conclusion: In this well phenotyped cohort of postmenopausal women, both the AHA pooled cohort and PREVENT equations may underestimate the higher cardiovascular risk that has been documented among women with MASLD. Although women with MASLD had higher unadjusted predicted ASCVD risk, this difference was no longer significant after adjustment for smoking. This discrepancy may reflect a limitation of ASCVD risk scores in capturing MASLD-related cardiometabolic risk and underscore the need for future studies evaluating whether incorporating MASLD status improves cardiovascular risk stratification, particularly in postmenopausal women.

*Unless otherwise noted, all abstracts presented at ENDO must not be released to the press or the public until the date and time of presentation. For oral presentations, the abstracts are embargoed until the session begins. The Endocrine Society reserves the right to lift the embargo on specific abstracts that are selected for promotion prior to or during ENDO.*