Subclinical cardiac dysfunction and circulating markers of brain injury in older adults: The cardiovascular health study

INTRODUCTION: Dementia has been strongly linked with cardiovascular disease, but the relationships between cardiovascular disease and brain health at subclinical stages have not been fully explored. We investigated the associations between subclinical cardiac dysfunction, defined by cardiac biomarkers and echocardiography, and novel neurobiomarkers associated with the brain injury in older adults. METHODS: We included 962 participants from the Cardiovascular Health Study who had no history of stroke, transient ischemic attack, atrial fibrillation, heart failure, or myocardial infarction. We analyzed cross-sectional associations using linear regression. Outcomes variables were serum neurofilament light chain (NfL) and glial fibrillary acidic protein (GFAP), two markers of subclinical brain injury. Exposure variables were serum N-terminal pro-brain-type natriuretic peptide (NT-proBNP) and high-sensitivity cardiac troponin T (hs-cTnT) and subclinical cardiac measures including echocardiographic left atrial reservoir strain, left ventricular average longitudinal strain, early diastolic strain rate of the left ventricle, decreased left ventricular ejection fraction, average E/e', percent predicted left ventricular mass, and left atrial diameter. RESULTS: Among 844 participants with serum biomarkers, hs-cTnT was significantly associated with NfL (β = 1.881, 95 % CI: (0.729, 3.032), p = 0.001), and this association remained significant even after mutual adjustment for NT-proBNP (β = 1.781, 95 % CI: (0.626, 2.937), p = 0.003). NT-proBNP was also associated with NfL (β = 1.170, 95 % CI: (0.047, 2.293), p = 0.041), although this association was slightly attenuated and not statistically significant after adjustment for hs-cTnT (β = 1.004, 95 % CI: (-0.119, 2.126), p = 0.08). There were no significant associations observed for either circulating marker with GFAP, nor were echocardiographic variables associated with NfL or GFAP. CONCLUSIONS: In older adults without clinically identified cardiovascular disease, subclinical cardiac dysfunction identified through hs-cTnT and, to a lesser extent, NT-proBNP, was associated with higher levels of NfL, a marker of brain injury. This novel insight suggests that even subclinical cardiac disease is linked to brain health.