Cognitive Decline Over Time in Patients With Systolic Heart Failure: Insights From WARCEF

Abstract

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).

Keywords: Mini-Mental State Examination; cognitive function; comorbidities; dementia; longitudinal analysis.

Conflict of interest statement

Conflict of Interest:

Dr. Anker reports being a consultant for Bayer, Boehringer Ingelheim, Novartis, Stealth Peptides, Servier, Vifor, Janssen (all for trial/registry steering committee work), and he has received research grants from Abbott Vascular and Vifor. Dr. Homma reports being a consultant for St. Jude Medical, Daiichi-Sankyo, Bristol Meyers Squibb, Pfizer. Dr. Labovitz has received a research grant from Bristol-Myers Squibb/Pfizer for the AREST trial. Dr. Lip has served as a consultant for Bayer/Janssen, BMS/Pfizer, Biotronik, Medtronic, Boehringer Ingelheim, Novartis, Verseon and Daiichi-Sankyo; speaker for Bayer, BMS/Pfizer, Medtronic, Boehringer Ingelheim, and Daiichi-Sankyo. No fees are directly received personally. Dr. Sacco has received research grants from NINDS, NCATS, AHA, Evelyn McKnight Brain Foundation and Boehringer Ingelheim. Dr. Teerlink has received consulting fees/research grants from Actelion, Amgen, Bayer, Cytokinetics, Medtronic, Novartis, St. Jude, Trevena. The other authors have no relations to report.

Copyright © 2019 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.

Figures

Figure 1.

Kaplan-Meier plot of all-cause death according to the change of MMSE score from baseline (N=1846) MMSE, Mini-Mental State Examination The outcome of the Kaplan-Meier plot was the time to death from any cause. Kaplan-Meier estimates of mortality rate with an MMSE score change of ≥2, 1, and non-drop (labeled as moderate-severe, mild, and none in the figure) were 33.4%, 32.1%, and 27.2% (p =0.051), respectively.

Central Illustration.. Predictors of cognitive decline in systolic heart failure

NYHA, New York Heart Association; HF, heart failure; CV, cardiovascular. Demographic and clinical variables (green circles) associated with cognitive decline during follow-up