Large-Scale Protein Assay Identifies Novel Protein Biomarkers Associated With Arterial Stiffness and Vascular Calcification Measures.

Abstract

Large-scale protein assays have the potential to identify novel biomarkers and improve prediction of cardiovascular disease (CVD) risk. The burden of atherosclerotic CVD and related risk factors is disproportionately high in Afro-Caribbean populations in whom novel risk prediction strategies may be warranted. Thus, we analyzed the association of early atherosclerosis markers with peripheral blood proteomic biomarkers quantified using the Olink Target 96 Cardiovascular III panel in 342 community-dwelling men from the Tobago Health Study. Atherosclerosis markers included pulse wave velocity (PWV), abdominal aortic calcification (AAC), and coronary artery calcification (CAC). Blood pressure, height, and weight were measured by trained clinic staff. Hypertension, dyslipidemia, and diabetes status were classified via clinical measures and the prescription of relevant medication. Statistical methods included differential expression analysis fully adjusted for assay batch, age, BMI, smoking, diabetes, dyslipidemia, and blood pressures. Men ranged from 53 to 89 years of age (mean ± SD = 63.3 ± 8.1 years). Average BMI was 27.7 ± 4.3 kg/m², 79.2% had hypertension, average LDL cholesterol was 129.4 ± 37.7 mg/dL, 24.6% had diabetes, and 5.9% were current smokers. In fully adjusted models, 18 proteins were associated with PWV and 1 was associated with CAC. There were no significant associations with AAC. Thirteen of these significant associations (12 PWV and 1 CAC) were novel, having never been identified as associated with these atherosclerosis measures in any previous study. While these proteins are involved in physiological processes known to contribute to CVD, such as inflammation, the strongest effects were seen for previously unreported protein associations. Our work is the first large-scale protein assay performed in an Afro-Caribbean population and adds to existing evidence that indicates that protein biomarker signatures of CVD may differ by racial/ethnic group. Further research is needed to understand the role of protein biomarkers in the prediction and progression of CVD among this high-risk group.