Internal Medicine Resident University of Calgary, Canada
Background: Heart failure (HF) and cognitive impairment (CI) frequently coexist. The objective of this review is to synthesize evidence on the association between circulating biomarkers of neurodegenerative diseases and (1) the incidence of HF (2) cognitive dysfunction in patients with HF and (3) adverse HF outcomes.
METHODS AND RESULTS: A comprehensive search of MEDLINE and EMBASE identified 18 studies, involving over 30,000 participants, assessing plasma levels of amyloid beta (Aβ), tau protein, neurofilament light chain (NfL), glial fibrillary acidic protein (GFAP), triggering receptor expressed on myeloid cells 2 (TREM2), ubiquitin C-terminal hydrolase L1 (UCHL1), and YKL-40 in relation to HF-related outcomes (Figure 1). Elevated Aβ40 and YKL-40 levels were significantly associated with all-cause mortality in HF, with respective pooled hazard ratios of 1.34 (95% CI: 1.01–1.79; p = 0.0434) and 1.081 (95% CI: 1.002–1.166; p = 0.0443). There was a positive, but not significant, trend between elevated plasma tau levels and HF hospitalization, with HR of 1.21 (95% CI: 0.94–1.55; p = 0.1383). A pooled analysis of all biomarkers across various adverse outcomes demonstrated a significant association, with a HR of 1.20 (95% CI: 1.10–1.13; p < 0.0001) (Figure 2). Six studies examined the relationship between neurodegenerative biomarkers and cognitive performance in HF populations. Elevated pTau-181, NfL, GFAP, and TREM2 levels were each significantly associated with impairments in memory function, with pTau-181 and GFAP also linked to poorer global cognition. Aβ40, pTau-181, NfL, and YKL-40 were linked to incident HF in individual studies.
Conclusion: Neurodegenerative biomarkers—especially Aβ40 and YKL-40—demonstrate prognostic value in HF populations, and are associated with both adverse HF outcomes and cognitive decline. These findings suggest shared pathophysiologic pathways linking neurodegeneration and HF. This evidence highlights the need to validate the clinical utility of these biomarkers and to elucidate shared, potentially causative mechanistic pathways linking HF and neurodegenerative conditions—ultimately defining a neurodegenerative cardiomyopathy.
