Introduction
Metabolic dysfunction-associated steatohepatitis (MASH) is linked to increased risk of cardiovascular (CV) disease (CVD), but many aspects of CVD burden in patients with MASH remain unknown. Particularly, data on the clinical burden of CVD and specific CV events in patients with non-cirrhotic MASH vs those without non-cirrhotic MASH are limited.
Aims & Methods
The aim of this real-world study was to assess CVD burden in patients with and without non-cirrhotic MASH. Patients with MASH were identified using the International Classification of Diseases code for non-alcoholic steatohepatitis (K75.81) from October 2015–June 2022, using data from a federated network (TriNetX). The index date was defined as the date of first MASH diagnosis. Exclusion criteria were viral hepatitis, alcohol use disorder, chronic liver diseases other than MASH or metabolic dysfunction-associated steatotic liver disease, cirrhosis, decompensated MASH, hepatocellular carcinoma and human immunodeficiency virus. Patients with MASH were matched 1:1 to patients without MASH based on demographics (sex, age, year of start/end of insurance enrolment, and insurance scheme). Outcomes were CVD prevalence (assessed up to 1 year prior to index) and risk of CV events(s) during follow-up (index date to end of enrolment, death or study end) amongst patients with no history of respective CV event(s) at baseline. For CV risk, cumulative incidence was plotted using Aalen-Johansen curves after adjusting for competing risk of non-CV death. Incidence rate (IR) was calculated per 100 person-years (PY) and hazard ratios (HR) were calculated using Cox proportional hazard models (crude and adjusted for CV risk factors [age, sex, type 2 diabetes (T2D), chronic kidney disease (CKD), obesity, hyperlipidaemia and hypertension]).
Results
In total, 9,642 patients (4,821 with MASH; 4,821 without MASH) were included. In both groups, mean (standard deviation) age was 50.8 (13.2) years and 58.5% were women. Compared with those without MASH, more patients with MASH had hypertension (58% vs 31%), hyperlipidaemia (57% vs 30%), obesity (45% vs 17%), T2D (41% vs 14%) and CKD (6% vs 3%) at baseline. Prevalence of any CVD was higher in patients with MASH than without MASH (23% vs 12%), as was risk of any CV event (IR: 11.1 vs 4.5 per 100 PY; crude HR [95% confidence interval]: 2.72 [2.30, 3.22], p < 0.0001; adjusted HR: 2.27 [1.95, 2.66], p < 0.0001). Similar results were seen for individual CV events, namely ischaemic heart disease (IR: 5.3 vs 2.3), cerebrovascular disease (IR: 4.4 vs 2.1), atherosclerosis (IR: 3.9 vs 1.8), and heart failure (IR: 3.2 vs 1.5).
Conclusion
CVD prevalence at baseline and risk of CV events during follow-up were significantly higher in patients with non-cirrhotic MASH compared with matched controls without MASH in a real-world cohort. These data provide additional evidence of the association between MASH and CVD and complement a previous analysis of the unCoVer-MASH study.
Disclosure
EB has acted as a consultant for AstraZeneca, Boehringer Ingelheim, Bristol Myers Squibb, Gilead Sciences, Intercept Pharmaceuticals, Inventiva SA, Merck Sharp & Dohme (UK) limited, Novo Nordisk and Pfizer.
AM has no conflicts of interest.
KKM, ASC, KG, NK and ASP are employees of Novo Nordisk A/S and own employee shares/stocks.
KEC has acted as a consultant for Theratechnologies and Novo Nordisk, and has received grants from Bristol Myers Squibb and Novartis.