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American Heart Association

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Final ID: MP1629

Associations of baseline and longitudinal changes in MASLD with risk of heart failure events in type 2 diabetes and overweight or obesity: the Look Action for Health in Diabetes (Look AHEAD) Trial Liver Ancillary Study

Abstract Body (Do not enter title and authors here): Introduction: Adults with type 2 diabetes (T2D) and overweight or obesity have a high prevalence of metabolic dysfunction-associated steatotic liver disease (MASLD). MASLD is associated with risk of atherosclerotic cardiovascular disease (ASCVD). However, the relationship between MASLD and risk of heart failure (HF), including HF subtypes, in T2D is less well-established.
Methods: We included participants with T2D and overweight/obesity from the Look AHEAD (Action for Health in Diabetes) trial who had available AST, ALT, and GGT data. The probability of MASLD was estimated using the Dallas Steatosis Index and classified as low, intermediate, or high based on probabilities <40%, ≥40 to <70%, and ≥70%, respectively. Adjusted Cox models were created to evaluate the associations of baseline and 1-year longitudinal changes in probability of MASLD with risk of overall HF, HF with preserved and reduced ejection fraction (HFpEF and HFrEF, respectively).
Results: The present study included 3,938 participants (mean age 59 years, 59% female, 67% White race). During follow-up, 211 HF events occurred (107 HFpEF, 84 HFrEF). Compared with a low probability of MASLD at baseline, high probability of MASLD at baseline was associated with overall HF risk (Table). In HF subtype analyses, higher probability of MASLD was significantly associated with higher risk of HFpEF but not HFrEF. In longitudinal analysis, 1-year increase in the probability of MASLD was significantly associated with higher risk of overall HF with a similar, non-significant pattern of association observed for both HF subtypes.
Conclusions: Among adults with T2D and overweight or obesity in the Look AHEAD trial, higher probability of MASLD at baseline and increase in MASLD probability over 1-year follow-up were associated with higher risk of overall HF. Baseline MASLD probability was significantly associated with risk of HFpEF but not HFrEF. These findings underscore the prognostic implications of MASLD and its importance in HF risk assessment in T2D.
  • Chunawala, Zainali  ( University of Texas Southwestern , Dallas , Texas , United States )
  • Butler, Javed  ( Baylor Scott and White , Dallas , Texas , United States )
  • Ballantyne, Christie  ( BAYLOR COLLEGE MEDICINE , Houston , Texas , United States )
  • Bertoni, Alain  ( WAKE FOREST UNIV SCHOOL MED , Pfafftown , North Carolina , United States )
  • Espeland, Mark  ( Wake Forest School of Medicine , Winston-Salem , North Carolina , United States )
  • De Lemos, James  ( UT SOUTHWESTERN MEDICAL CTR , Dallas , Texas , United States )
  • Pandey, Ambarish  ( UT Southwestern Medical Center , Dallas , Texas , United States )
  • Patel, Kershaw  ( Houston Methodist Hospital , Houston , Texas , United States )
  • Clark, Jeanne  ( Rutgers Robert Wood Johnson Med Sch , New Brunswick , New Jersey , United States )
  • Vanwagner, Lisa  ( University of Texas Southwestern , Dallas , Texas , United States )
  • Browning, Jeffrey  ( University of Texas Southwestern , Dallas , Texas , United States )
  • Garcia, Katelyn  ( Wake Forest Baptist Health , Winston-Salem , North Carolina , United States )
  • Zannad, Faiez  ( CVCT and Universite de Lorraine , Paris , France )
  • Maruthur, Nisa  ( John Hopkins , Dallas , Maryland , United States )
  • Sanyal, Arun  ( Virginia Commonwealth University , Richmond , Virginia , United States )
  • Author Disclosures:
    Zainali Chunawala: DO NOT have relevant financial relationships | Javed Butler: No Answer | Christie Ballantyne: DO have relevant financial relationships ; Researcher:merck:Active (exists now) ; Consultant:Novo Nordisk:Active (exists now) ; Researcher:Novo Nordisk:Active (exists now) ; Consultant:Arrowhead:Active (exists now) ; Researcher:Arrowhead:Active (exists now) ; Consultant:Ionis:Active (exists now) ; Researcher:Ionis:Active (exists now) ; Consultant:Amgen:Active (exists now) ; Researcher:Amgen:Active (exists now) ; Consultant:Eli Lilly:Active (exists now) ; Researcher:Eli Lilly:Active (exists now) ; Consultant:Novartis:Active (exists now) ; Researcher:Novartis:Active (exists now) ; Consultant:Merck:Active (exists now) | Alain Bertoni: DO NOT have relevant financial relationships | Mark Espeland: DO NOT have relevant financial relationships | James de Lemos: DO have relevant financial relationships ; Independent Contractor:Amgen, Inc.:Active (exists now) ; Independent Contractor:Verve:Active (exists now) ; Consultant:Siemen's:Past (completed) ; Independent Contractor:Jannsen:Active (exists now) ; Independent Contractor:Astra Zeneca:Past (completed) ; Independent Contractor:Merck:Active (exists now) ; Independent Contractor:Eli Lilli:Active (exists now) ; Independent Contractor:Varian:Active (exists now) ; Independent Contractor:Regerenon Pharmaceuticals:Active (exists now) | Ambarish Pandey: DO have relevant financial relationships ; Consultant:Tricog:Active (exists now) ; Consultant:Sarfez Therapeutics, Edwards Lifesciences, Merck, Bayer, Anumana, Alleviant, Pfizer, Abbott, Axon Therapies, Kilele Health, Acorai, Kardigan, Novartis, Idorsia Pharma, and Science37:Active (exists now) ; Consultant:Rivus:Active (exists now) ; Consultant:iRhythm:Active (exists now) ; Researcher:SQ innovations:Active (exists now) ; Research Funding (PI or named investigator):SC Pharma:Active (exists now) ; Consultant:Astra Zeneca:Active (exists now) ; Research Funding (PI or named investigator):Ultromics:Active (exists now) ; Research Funding (PI or named investigator):Roche:Active (exists now) ; Consultant:Ultromics:Active (exists now) ; Consultant:Roche:Active (exists now) ; Consultant:Lilly:Active (exists now) ; Consultant:Bayer:Active (exists now) ; Consultant:Novo Nordisk:Active (exists now) | Kershaw Patel: DO have relevant financial relationships ; Consultant:Novo Nordisk:Past (completed) ; Research Funding (PI or named investigator):NIH:Active (exists now) | Jeanne Clark: DO have relevant financial relationships ; Advisor:Novo Nordisk:Expected (by end of conference) ; Other (please indicate in the box next to the company name):Novo Nordisk - supported publication:Active (exists now) | Lisa VanWagner: DO have relevant financial relationships ; Consultant:Gerson Lehrman Group:Active (exists now) ; Independent Contractor:Medicolegal services:Active (exists now) ; Researcher:Madrigal Pharmaceuticals:Active (exists now) ; Advisor:Madrigal Pharmaceuticals:Past (completed) ; Consultant:Alpha Insights:Active (exists now) ; Consultant:Slingshot Insights:Active (exists now) | Jeffrey Browning: No Answer | Katelyn Garcia: DO NOT have relevant financial relationships | Faiez ZANNAD: DO have relevant financial relationships ; Advisor:Alnylam, Bayer, Biopeutics, Boehringer, Cellprothera, Centrix, Cereno, Centrix Corteria, CVRx, Lilly, Lupin, Merck, NovoNordisk, Opalia Recordati, Owkin, Polygon, Ribocure, Roche, Viatris,:Active (exists now) ; Ownership Interest:Polygon, Cereno pharmaceutical, CVCT:Active (exists now) | Nisa Maruthur: No Answer | Arun Sanyal: DO have relevant financial relationships ; Consultant:Eli Lilly, Echosens, Abbott:Active (exists now) ; Individual Stocks/Stock Options:Durect, Genfit, Tiziana, Inversago:Active (exists now) ; Royalties/Patent Beneficiary:Elsevier and UpToDate:Active (exists now) ; Other (please indicate in the box next to the company name):Institution has received Grant support from:Merck, Ocelot, Novartis, Salix:Active (exists now) ; Other (please indicate in the box next to the company name):Institution has received Grant support from: Gilead, Intercept, Mallinckrodt:Active (exists now) ; Other (please indicate in the box next to the company name):Institution has received Grant support from:Astra Zeneca, Bristol Myers Squibb:Active (exists now) ; Consultant:Takesa, Surrozen, Terns, Zydus:Active (exists now) ; Consultant:Salix, Myovent, Media Technologies, Sequana:Active (exists now) ; Consultant:Akero, Novo Nordisk, Path AI, Pfizer, Poxel:Active (exists now) ; Consultant:Lipocine, Madrigal, Merck, Glaxo Smith Kline, Novartis:Active (exists now) ; Consultant:Genetech, Gilead, Histoindex, Janssen:Active (exists now) ; Consultant:Boehringer Ingleheim, Bristol Myers Squibb:Active (exists now) ; Consultant:Astra Zeneca, Alnylam, Regeneron:Active (exists now) ; Consultant:Variant, Cascade, 89 Bio:Active (exists now) ; Consultant:Corcept, Arrowhead, Boston Pharmaceuticals:Active (exists now) ; Consultant:Promed, Genfit, Satellite Bio:Active (exists now)
Meeting Info:

Scientific Sessions 2025

2025

New Orleans, Louisiana

Session Info:

Drivers of Heart Failure: Environmental and Behavioral Factors

Sunday, 11/09/2025 , 09:15AM - 10:30AM

Moderated Digital Poster Session

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Intensive lifestyle intervention, MASLD, and cardiovascular outcomes in type 2 diabetes and overweight or obesity: the Look Action for Health in Diabetes (Look AHEAD) trial Liver Ancillary Study

Chunawala Zainali, Butler Javed, Ballantyne Christie, Bertoni Alain, Espeland Mark, De Lemos James, Pandey Ambarish, Patel Kershaw, Clark Jeanne, Vanwagner Lisa, Browning Jeffrey, Garcia Katelyn, Zannad Faiez, Maruthur Nisa, Sanyal Arun

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