Associations between MASLD, atrial fibrillation, cardiovascular events, mortality and aspirin use in older adults

Daniel Clayton-Chubb; Stuart K Roberts; Ammar Majeed; Robyn L Woods; Andrew M Tonkin; Mark R Nelson; Andrew T Chan; Joanne Ryan; Cammie Tran; Alexander Hodge; John S Lubel; Hans G Schneider; Amy Brodtmann; Sharyn M Fitzgerald; Suzanne G Orchard; John J McNeil; William W Kemp

doi:10.1007/s11357-024-01435-2

Associations between MASLD, atrial fibrillation, cardiovascular events, mortality and aspirin use in older adults

Geroscience. 2024 Nov 28. doi: 10.1007/s11357-024-01435-2. Online ahead of print.

Authors

Daniel Clayton-Chubb^{1

2

3

4}, Stuart K Roberts^{5

6}, Ammar Majeed^{5

6}, Robyn L Woods⁷, Andrew M Tonkin⁷, Mark R Nelson^{7

8}, Andrew T Chan^{9

10

11}, Joanne Ryan⁷, Cammie Tran⁷, Alexander Hodge^{12

13

14}, John S Lubel^{5

6

15}, Hans G Schneider^{7

16}, Amy Brodtmann^{13

17}, Sharyn M Fitzgerald⁷, Suzanne G Orchard⁷, John J McNeil⁷, William W Kemp^{5

6}

Affiliations

¹ Department of Gastroenterology, The Alfred Hospital Health, 99 Commercial Road, Melbourne, VIC, 3004, Australia. dan.clayton-chubb@monash.edu.
² Department of Medicine, School of Translational Medicine, Monash University, Melbourne, Australia. dan.clayton-chubb@monash.edu.
³ Department of Gastroenterology, Eastern Health, Melbourne, Australia. dan.clayton-chubb@monash.edu.
⁴ Department of Gastroenterology, St Vincent's Hospital, Melbourne, Australia. dan.clayton-chubb@monash.edu.
⁵ Department of Gastroenterology, The Alfred Hospital Health, 99 Commercial Road, Melbourne, VIC, 3004, Australia.
⁶ Department of Medicine, School of Translational Medicine, Monash University, Melbourne, Australia.
⁷ School of Public Health and Preventive Medicine, Monash University, Melbourne, Australia.
⁸ Menzies Institute for Medical Research, University of Tasmania, Hobart, Australia.
⁹ Clinical and Translational Epidemiology Unit, Massachusetts General Hospital, Boston, MA, USA.
¹⁰ Division of Gastroenterology, Massachusetts General Hospital, Boston, MA, USA.
¹¹ Harvard Medical School, Boston, MA, USA.
¹² Department of Gastroenterology, Eastern Health, Melbourne, Australia.
¹³ School of Health and Biomedical Science, RMIT University, Melbourne, Australia.
¹⁴ Department of Medicine, Eastern Clinical School, Monash University, Melbourne, Australia.
¹⁵ Department of Gastroenterology, Northern Health, Melbourne, Australia.
¹⁶ Department of Pathology, Alfred Health, Melbourne, Australia.
¹⁷ Department of Neurosciences, School of Translational Medicine, Monash University, Melbourne, Australia.

PMID: 39607592
DOI: 10.1007/s11357-024-01435-2

Abstract

The impact of metabolic dysfunction-associated steatotic liver disease (MASLD), the preferred nomenclature for NAFLD, on cardiovascular health and mortality among older adults is uncertain. As such, we aimed to identify whether MASLD increases the risk of Major Adverse Cardiovascular Events (MACE) (a composite of fatal coronary heart disease [excluding heart failure], nonfatal myocardial infarction, or fatal or nonfatal ischemic stroke), Atrial Fibrillation (AF), or all-cause mortality in older adults, and whether aspirin attenuates these risks in individuals with MASLD. This is a non-prespecified post-hoc analysis of the ASPREE (ASPirin in Reducing Events in the Elderly) randomized trial. Participants were community dwelling well adults aged ≥ 70 years without a history of atherosclerotic cardiovascular disease or AF. Fatty Liver Index (FLI) was used to identify MASLD at baseline. FLI is a composite of anthropometric and biochemical markers used in epidemiologic studies to rule in and rule out hepatic steatosis. MACE and cause of death were adjudicated by clinical experts; AF was assessed by previously defined algorithm in ASPREE. 9,097 participants were stratified into groups according to FLI. In univariate analysis, prevalent MASLD (FLI ≥ 60 with evidence of metabolic dysfunction; n = 2,998 [33.0%]) was associated with an increased risk of MACE (HR 1.47 [95% CI 1.22-1.78]) and AF (HR 1.50 [95% CI 1.19-1.88] but not all-cause mortality (HR 1.04 [95% CI 0.91-1.19]). After adjusting for cardiovascular disease risk factors, only the association between MASLD and AF remained significant (HR 1.46 [95% CI 1.11-1.93]). Aspirin did not reduce the risk of MACE, death, or AF in the MASLD group. MASLD was associated with an increased hazard of incident AF, but not of MACE or all-cause mortality, in community dwelling older adults. Primary prevention with aspirin does not ameliorate these risks in older adults with MASLD.

Keywords: ASPREE; Aspirin; Death; Elderly; Epidemiology; Myocardial infarction; Non-alcoholic fatty liver disease.