A cluster of blood-based protein biomarkers associated with decreased cerebral blood flow relates to future cardiovascular events in patients with cardiovascular disease

Abstract

Abstract Introduction Biological processes underlying decreased cerebral blood flow (CBF) in patients with cardiovascular disease (CVD) are largely unknown. We hypothesized that identification of protein clusters associated with lower CBF in patients with CVD may explain underlying processes. Methods In 428 participants (74% cardiovascular diseases; 26% reference participants) from the Heart-Brain Connection Study, CBF was measured with MRI in normal-appearing grey matter with pseudo-continuous arterial spin labeling. We assessed the relation between 92 plasma proteins from the Olink® cardiovascular III panel and CBF using cluster-based analyses and generated a Biomarker Compound Score (BCS). The BCS was related to cardiovascular risk and observed cardiovascular events within 2-year follow-up. Results Thirteen proteins were associated with CBF (ρSpearman range: -0.10 to -0.19, pFDR-corrected <0.05), and formed one cluster. The cluster primarily reflected extracellular matrix organization processes. The BCS was higher in patients with CVD compared to reference participants (pFDR-corrected <0.05) and was associated with cardiovascular risk (p <0.001) and cardiovascular events (OR 2.05, p <0.01). Conclusions We identified a cluster of plasma biomarkers related to CBF, which is related to future cardiovascular events in patients with CVD. The cluster primarily reflected extracellular matrix organization processes, which represent potential targets to preserve CBF in patients with CVD.