The association between proteomically derived cardiovascular risk and incident dementia in a community cohort

Abstract

Introduction: A connection exists between peripheral disease such as cardiovascular (CV) disease and the risk for dementia potentially through shared vascular biological underpinnings. Large-scale proteomic phenotyping can be useful to establish associations and elucidate mechanisms and etiology of disease. We applied previously developed and validated plasma proteomic tests that predict domains of CV risks to characterize the association between CV risk profiles and 20-year dementia risk in an observational cohort. Methods: We used data and samples obtained from Atherosclerosis Risk in Communities study (ARIC) visit 3 (n = 11,701) to assess the association between the SomaScan® assay CV risk tests (secondary cardiovascular risk, primary cardiovascular risk, heart failure with preserved ejection fraction, and heart failure with reduced ejection fraction) and incident dementia. Survival analysis was used to estimate 20-year Kaplan-Meier (KM) dementia rates and hazard ratios by tertile of CV risk scores. Results: Increasing risks of all four CV-related risk tests were positively associated with the risk for dementia (P< 0.0001) and the tertiles for each of these tests stratified dementia risk 20 years from sample collection (figure). The table shows the KM dementia 20-year event rates and hazard ratios for the associations between CV risk domains and dementia. For example, compared to the lowest risk tertile, there was a 59% increased risk for dementia in the middle secondary CV risk tertile and more than 2-fold increased dementia risk in the highest risk tertile. Discussion: These findings demonstrate an association between CV risk and the development of dementia and may capture pathophysiology of dementia that is below the threshold to detect disease. In addition, the use of proteomic phenotypes can be a tool for monitoring to characterize the multi-organ disease processes and vascular association with the development of dementia.