Sarkar, Souvik

ABSTRACT Background Metabolic dysfunction‐associated steatotic liver disease (MASLD) exhibits marked heterogeneity in fibrosis progression and liver‐related outcomes. Liver biopsy is not feasible for longitudinal risk stratification at scale, creating a need for validated non‐invasive biomarkers, particularly imaging biomarkers, that can predict clinically meaningful disease progression and liver‐related outcomes. Aims To describe the design and rationale of the GOLDMINE study, established to determine whether non‐invasive imaging biomarkers predict MASLD progression and liver‐related clinical outcomes. Methods GOLDMINE is an investigator‐initiated, multi‐centre, international longitudinal cohort enrolling up to 1000 adults with either biopsy‐proven MASLD or MASLD cirrhosis across the full fibrosis spectrum. Participants are recruited from 15 sites in the US and 4 international sites (Japan, Singapore and France). At baseline, participants undergo clinical phenotyping, vibration‐controlled transient elastography, and advanced magnetic resonance imaging (MRI), including proton‐density‐fat‐fraction and magnetic resonance elastography (MRE). MRI (and biospecimen banking) is repeated at 2‐year intervals (years 2 and 4), with annual follow‐up visits for up to 10 years. Baseline liver histology is centrally processed, digitized and reviewed by a single expert hepatopathologist; all MRI/MREs are centrally interpreted. Results The prespecified clinical outcomes include progression to cirrhosis, clinically significant portal hypertension, major adverse liver‐related outcomes (ascites, hepatic encephalopathy, portal hypertensive bleeding, liver transplantation/qualification), hepatocellular carcinoma, major adverse cardiovascular events, and all‐cause mortality, with independent central adjudication of all events. Conclusions GOLDMINE establishes a rigorously phenotyped MASLD cohort integrating centralized histology, advanced MRI‐based biomarkers, longitudinal biobanking, and adjudicated outcomes, providing a platform to validate imaging and blood‐based prognostic biomarkers in MASLD.

Abstract Background/Introduction Little is known about the prevalence of high-risk plaque features or cardiometabolic predictors in diverse patient populations with underrepresented minorities, in the setting of stable chest pain. Purpose The goals of our study are to 1) describe plaque characteristics in a diverse patient population with underrepresented minorities and 2) characterize cardiometabolic risk factors associated with high prevalence of high-risk quantitative low attenuation noncalcified plaque (LDNCP) burden. Methods Our study included patients with chest pain undergoing CCTA between June 2016 and October 2021 for stable chest pain, who had a complete cardiometabolic panel including lipoprotein(a) and lipid panel, and at least one blood pressure recording before CCTA. Patients with prior PCI or CABG where excluded. CACS was performed before CCTA as per Agatston method and quantified in Agatston Units (AU). Stenosis was graded as per SCCT guidelines by cardiologists and radiologists with level 3 cardiac CT expertise. Plaque measurements were performed using previously validated semiautomated software (AutoPlaque version 2.5) in all patients with CAD-RADS >0 by expert readers blinded from patients' characteristics. Coronary atherosclerotic plaque volumes were measured. Independent predictors for plaque on CCTA among patients were examined using Wilcox multivariate logistic regression. Results A total of 227 consecutive patients were included in our study (see table; age 55.00 [47.50–62.00] years, 63% female, 16% diabetes, 44% hypertension, 40% hyperlipidemia and 32% with current or previous smoking history). Majority of patients were Hispanic (64%) and the rest were Black (27%), White (6%) and Asian (3%). Patients with LDNCP burden >4% were older (60.00 [52.00–66.50] vs 53.00 [43.75–61.00]; p<0.001), more likely to be diabetic (27.7 vs 11.5%; p=0.005), hypertensive (67.7 vs 33.8%; p<0.001), hyperlipidemic (64.6 vs 29.9%; p<0.001) and present smokers (31.3 vs 13.9%; p=0.003). Almost all patients (63/67) with LDNCP burden >4% had non-obstructive disease (CAD-RADS<4). Patient with LDNCP burden >4% were more likely to be on statin therapy (46.0 vs 30.4%; p=0.041). There was no differences in ethnicity, hemoglobin A1C, TC, LDL-C, HLD-C, TGs, lipoprotein(a), SBP or DBP. By logistic regression analysis, age (OR [CI]: 1.06 [1.01–1.08]), hypertension (2.20, [1.06–4.63]) and hyperlipidemia (2.73 [1.37–5.47]) increased the likelihood of LDNCP burden >4%, but not Lipoprotein (a)>175 nmol/L (OR [CI]: 1.07 [0.48–2.31]. Conclusions In our cohort of patients with high number of unrepresented minorities presenting with stable chest pain, almost all patients (94%) with LDNCP burden >4% had non-obstructive CAD (CAD-RADS<4). There were no differences in prevalence of LDNCP or CAD-RADS among different ethnic groups. Age, hypertension and hyperlipidemia, were the cardiometabolic factors related to LDNCP burden >4%. Funding Acknowledgement Type of funding sources: None.