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 resultsUsing 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 = À4.7; P < 0.001), alanine aminotransferase (T = À2.1; 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 = À3.0; 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.

Sustained Increase in Serum Glial Fibrillary Acidic Protein after First ST-Elevation Myocardial Infarction

“…This implies that the differential and sustained increase in GFAP within the first 3 months of our study might not have been due to an acute hypoxic event, but rather caused by chronic processes within the central nervous system after MI. Recently published serum GFAP elevations in chronic heart failure patients and independent relations to memory impairment [ 13 ] further support the concept that the increased risk for AD after MI [ 2 ] might be triggered by chronic glial activation or damage.…”

“…Serum glial fibrillary acidic protein (GFAP), as an intermediate filament of mature astrocytes, associates with cognitive decline in neurological disorders such as Alzheimer’s disease, reflecting disease-related reactive astrogliosis [ 10 ] and astroglial damage in the brain [ 11 , 12 ]. Our group has recently shown that memory deficits in patients with chronic heart failure associate with elevated levels of serum GFAP [ 13 ]. Furthermore, neurofilament light chain (NfL) as a marker for neuronal damage has gained attention in predicting pre-clinical and clinical dementia [ 14 , 15 , 16 ].…”

Profiles of cognitive impairment in chronic heart failure—A cluster analytic approach

“…Slightly higher serum levels of GFAP were seen in our "global deficient" cluster. Previous publications have already shown that GFAP is associated with CI (especially memory function) not only in Alzheimer's disease but also in chronic HF (Cicognola et al, 2021;Traub et al, 2022). In this line, neuronal biomarkers such as GFAP might be better suitable for predicting CI in HF patients compared with established HF measures.…”

“…Examinations included cardiovascular and neurological clinical examination, neuropsychological test battery, electrocardiogram, echocardiography, 6-min walk testing, and brain magnetic resonance imaging (MRI). We measured routine blood parameters and the neurodegenerative serum biomarkers neurofilament light chain (NfL), glial fibrillary acidic protein (GFAP), and phosphorylated Tau protein (pTau) according to a prespecified protocol from venous blood (Traub et al, 2022 ).…”

Chronic Neuroinflammation and Cognitive Decline in Patients with Cardiac Disease: Evidence, Relevance, and Therapeutic Implications

“…A recent meta-analysis reported higher concentrations of CHI3L1, TREM2, MCP-1, and transforming growth factor-β in the CSF of AD patients compared to controls [ 115 ]. Along these lines, elevated neuronal serum biomarkers such as neurofilament light chain, phosphorylated tau protein and GFAP are associated with cognitive decline in chronic HF [ 116 , 117 ]. The recently observed increase in serum GFAP after MI might reflect the abovedescribed astroglial activation [ 118 ].…”