Abstract 001: Proteomic Signatures of Cardiovascular Risk Factors: A Cross-sectional Analysis of the Plasma Proteome in the Framingham Heart Study

Abstract

Introduction: Proteomic biomarkers related to cardiovascular disease (CVD) risk factors may offer insights into the pathogenesis of subclinical and clinical CVD. Hypothesis: We hypothesized that 1) CVD risk factors may have distinctive proteomic signatures; and 2) select proteins are associated with multiple CVD risk factors indicating a central (pleiotropic) role in disease pathogenesis. Methods: We measured 1317 circulating plasma proteomic biomarkers (SomaScan; using the SomaLogic platform) in up to 897 Framingham Heart Study Generation 3 participants (mean age 46 years; 56% women) without hypertension, diabetes mellitus, or clinical CVD at the second examination (2008-2011). We used linear regression (or logistic for binary outcomes) to relate levels of each inverse-log transformed proteomic biomarker to age, sex, body mass index (BMI), waist circumference, systolic and diastolic blood pressure, blood lipid fractions, fasting blood sugar and insulin, coronary artery calcium (by computed tomography), left ventricular mass (by echocardiography), pre-hypertension, pre-diabetes, dyslipidemia, overweight, obesity, alcohol consumption, physical activity (by accelerometer), and smoking. All models adjusted for age, sex, and BMI. A Bonferroni-adjusted p-value <2.7E-5 indicated statistical significance. Results: Forty-one proteins were associated with ≥8 CVD risk factors and 13 proteins (Apo E, C5a, GHR, IGFBP-2, leptin, NG36, Notch-3, QORL1, RGMB, SHBG, TIG2, XTP3A, tPA) were associated with ≥10 risk factors. Illustrative volcano plots for proteomic signatures of smoking and physical activity show high representation of proteins related to tumor suppression, immunologic function, and cellular communication (Figure). Conclusions: Our cross-sectional data from a relatively healthy community-based sample elucidated distinctive proteomic signatures of CVD risk factors. A small group of proteins were associated with multiple risk factors, suggesting their potential pleiotropic role in CVD.