Serum glial fibrillary acidic protein indicates memory impairment in patients with chronic heart failure

Abstract

Aims: Cognitive dysfunction occurs frequently in patients with heart failure (HF), but early detection remains challenging. Serum glial fibrillary acidic protein (GFAP) is an emerging biomarker of cognitive decline in disorders of primary neurodegeneration such as Alzheimer's disease. We evaluated the utility of serum GFAP as a biomarker for cognitive dysfunction and structural brain damage in patients with stable chronic HF.

Methods and results: Using bead-based single molecule immunoassays, we quantified serum levels of GFAP in patients with HF participating in the prospective Cognition.Matters-HF study. Participants were extensively phenotyped, including cognitive testing of five separate domains and magnetic resonance imaging (MRI) of the brain. Univariable and multivariable models, also accounting for multiple testing, were run. One hundred and forty-six chronic HF patients with a mean age of 63.8 ± 10.8 years were included (15.1% women). Serum GFAP levels (median 246 pg/mL, quartiles 165, 384 pg/mL; range 66 to 1512 pg/mL) did not differ between sexes. In the multivariable adjusted model, independent predictors of GFAP levels were age (T = 5.5; P < 0.001), smoking (T = 3.2; P = 0.002), estimated glomerular filtration rate (T = -4.7; P < 0.001), alanine aminotransferase (T = -2.1; P = 0.036), and the left atrial end-systolic volume index (T = 3.4; P = 0.004). NT-proBNP but not serum GFAP explained global cerebral atrophy beyond ageing. However, serum GFAP levels were associated with the cognitive domain visual/verbal memory (T = -3.0; P = 0.003) along with focal hippocampal atrophy (T = 2.3; P = 0.025).

Conclusions: Serum GFAP levels are affected by age, smoking, and surrogates of the severity of HF. The association of GFAP with memory dysfunction suggests that astroglial pathologies, which evade detection by conventional MRI, may contribute to memory loss beyond ageing in patients with chronic HF.

Keywords: Brain atrophy; Chronic heart failure; Cognitive decline; GFAP; Glial fibrillary acidic protein; Memory dysfunction.

Figure 1

Scatter plot of natural log‐transformed GFAP and clinical parameters. Spearman's regression coefficient (ρ) is shown. AF, atrial fibrillation; eGFR, estimated glomerular filtration rate; GFAP, glial fibrillary acidic protein; LA, left atrium.

Figure 2

Scatter plot of natural log‐transformed GFAP and parameters of brain atrophy/memory. Spearman's regression coefficient (ρ), cerebral atrophy score (on a scale from 1 to 8) and age‐adjusted, gender‐adjusted, and education‐adjusted T scores of visual/verbal memory are shown. GFAP, glial fibrillary acidic protein.