Author + information
- Received April 12, 2019
- Revision received August 28, 2019
- Accepted September 10, 2019
- Published online November 25, 2019.
- Tetz C. Lee, MD, MPHa,
- Min Qian, PhDa,
- Yutong Liu, MSa,
- Susan Graham, MDb,
- Douglas L. Mann, MDc,
- Koki Nakanishi, MDa,
- John R. Teerlink, MDd,
- Gregory Y.H. Lip, MDe,f,
- Ronald S. Freudenberger, MDg,
- Ralph L. Sacco, MD, MSh,
- Jay P. Mohr, MDa,
- Arthur J. Labovitz, MDi,
- Piotr Ponikowski, MD, PhDj,
- Dirk J. Lok, MDk,
- Kenji Matsumoto, MDa,
- Conrado Estol, MDl,
- Stefan D. Anker, MD, PhDm,n,
- Patrick M. Pullicino, MDo,
- Richard Buchsbauma,
- Bruce Levin, PhDa,
- John L.P. Thompson, PhDa,
- Shunichi Homma, MDa,
- Marco R. Di Tullio, MDa,∗ (, )
- for the WARCEF Investigators
- aColumbia University Medical Center, New York, NY
- bDepartment of Medicine, State University of New York at Buffalo, Buffalo, New York
- cDepartment of Medicine, Washington University School of Medicine, St. Louis, Missouri
- dSection of Cardiology, San Francisco Veterans Affairs Medical Center and School of Medicine, University of California San Francisco, San Francisco, California
- eLiverpool Centre for Cardiovascular Science, University of Liverpool and Liverpool Heart and Chest Hospital, Liverpool, United Kingdom
- fAalborg Thrombosis Research Unit, Department of Clinical Medicine, Aalborg University, Aalborg, Denmark
- gLehigh Valley Hospital, Allentown, Pennsylvania
- hDepartment of Neurology, University of Miami, Miami, Florida
- iDepartment of Medicine, University of South Florida, Tampa, Florida
- jMilitary Hospital, Wroclaw, Poland
- kDeventer Hospital, Deventer, the Netherlands
- lStroke Unit, Sanatorio Guemes, Buenos Aires, Argentina
- mDivision of Cardiology and Metabolism, Department of Cardiology, and Berlin-Brandenburg Center for Regenerative Therapies, Deutsches Zentrum für Herz-Kreislauf-Forschung partner site Berlin; Charité Universitätsmedizin Berlin, Germany
- nDepartment of Cardiology and Pneumology, University Medicine Göttingen, Göttingen, Germany
- oKent Institute of Medicine and Health Science, Canterbury, United Kingdom
- ↵∗Address for correspondence:
Dr. Marco R. Di Tullio, Department of Medicine, Columbia University Irving Medical Center, 630 West 168th Street, New York, New York 10032.
Objectives This study sought to characterize cognitive decline (CD) over time and its predictors in patients with systolic heart failure (HF).
Background Despite the high prevalence of CD and its impact on mortality, predictors of CD in HF have not been established.
Methods This study investigated CD in the WARCEF (Warfarin versus Aspirin in Reduced Ejection Fraction) trial, which performed yearly Mini-Mental State Examinations (MMSE) (higher scores indicate better cognitive function; e.g., normal score: 24 or higher). A longitudinal time-varying analysis was performed among pertinent covariates, including baseline MMSE and MMSE scores during follow-up, analyzed both as a continuous variable and a 2-point decrease. To account for a loss to follow-up, data at the baseline and at the 12-month visit were analyzed separately (sensitivity analysis).
Results A total of 1,846 patients were included. In linear regression, MMSE decrease was independently associated with higher baseline MMSE score (p < 0.0001), older age (p < 0.0001), nonwhite race/ethnicity (p < 0.0001), and lower education (p < 0.0001). In logistic regression, CD was independently associated with higher baseline MMSE scores (odds ratio [OR]: 1.13; 95% confidence interval [CI]: 1.07 to 1.20]; p < 0.001), older age (OR: 1.37; 95% CI: 1.24 to 1.50; p < 0.001), nonwhite race/ethnicity (OR: 2.32; 95% CI: 1.72 to 3.13 for black; OR: 1.94; 95% CI: 1.40 to 2.69 for Hispanic vs. white; p < 0.001), lower education (p < 0.001), and New York Heart Association functional class II or higher (p = 0.03). Warfarin and other medications were not associated with CD. Similar trends were seen in the sensitivity analysis (n = 1,439).
Conclusions CD in HF is predicted by baseline cognitive status, demographic variables, and NYHA functional class. The possibility of intervening on some of its predictors suggests the need for the frequent assessment of cognitive function in patients with HF. (Warfarin versus Aspirin in Reduced Cardiac Ejection Fraction [WARCEF]; NCT00041938)
The WARCEF trial was supported by U.S. National Institute of Neurological Disorders and Stroke (NINDS) grants U01-NS-043975 (to Dr. Homma) and U01-NS-039143 (to Dr. Thompson). Dr. Anker is a consultant for Bayer, Boehringer Ingelheim, Novartis, Stealth Peptides, Servier, Vifor, and Janssen; and has received research support from Abbott Vascular and Vifor. Dr. Homma is a consultant for St. Jude Medical, Daiichi-Sankyo, Bristol-Myers Squibb, and Pfizer. Dr. Labovitz has received research support from Bristol-Myers Squibb/Pfizer. Dr. Lip is a consultant for Bayer/Janssen, Bristol-Myers Squibb/Pfizer, Biotronik, Medtronic, Boehringer Ingelheim, Novartis, Verseon, and Daiichi-Sankyo; and is a speaker for Bayer, Bristol-Myers Squibb/Pfizer, Medtronic, Boehringer Ingelheim, and Daiichi-Sankyo. Dr. Sacco has received research support from grants from NINDS, National Center for Advancing Translational Sciences, American Heart Association, the Evelyn McKnight Brain Foundation, and Boehringer Ingelheim. Dr. Teerlink is a consultant for and has received research support from Actelion, Amgen, Bayer, Cytokinetics, Medtronic, Novartis, St. Jude Medical, and Trevena. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose.
- Received April 12, 2019.
- Revision received August 28, 2019.
- Accepted September 10, 2019.
- 2019 American College of Cardiology Foundation
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