Associations of blood-based biomarkers of neurodegenerative diseases with mortality, cardio- and cerebrovascular events in persons with chronic coronary syndrome

Background

In light of growing evidence highlighting interactions between cardiac and brain health, we investigated associations of biomarkers of neurodegenerative diseases with adverse outcomes (all-cause and cardiovascular mortality, major cardiovascular events, and stroke) in persons with chronic coronary syndrome (CCS).

Methods

We used data from a cohort of persons with CCS for whom major adverse events were recorded over a follow-up of 20 years. We measured biomarkers of neurodegenerative diseases in baseline blood samples, using the Single-Molecule Array Technology on a HD-1 Analyzer. These include biomarkers of neuronal (neurofilament light chain (NfL) (n = 379)) and glial neurodegeneration (glial fibrillary acidic protein (GFAP) (n = 379)), and Alzheimer's disease pathology (phosphorylated tau181 (n = 379), total tau (n = 377), and amyloid β (Aβ₄₀, Aβ₄₂, Aβ₄₂/Aβ₄₀) (n = 377)). We applied Cox-proportional hazards models to evaluate associations of these biomarkers with adverse outcomes, adjusting for covariates and exploring interactions with apolipoprotein E (ApoE) ε4 genotype.

Results

Participants with higher NfL levels had increased rates of all-cause and cardiovascular mortality (Hazard ratio per increase by one standard deviation (95 % confidence interval): all-cause mortality: 1.36 (1.10–1.68); cardiovascular mortality: 1.42 (1.05–1.93)). The Aβ₄₀/Aβ₄₂-ratio was linked to incident stroke (0.72 (0.52–1.00)). Associations of GFAP with all-cause mortality and incident stroke were depending on ApoE ε4 genotype. The other biomarkers were not significantly associated with the studied outcomes.

Conclusions

In persons with CSS, NfL and the Aβ₄₀/Aβ₄₂-ratio were related to mortality and incident stroke, respectively, whereas associations of GFAP with adverse outcomes varied by ApoE genotype. These biomarkers might play a role in linking aging, cardiovascular and neurodegenerative diseases.