Abstract 15535: Protein Biomarkers of New-Onset Atherosclerotic Cardiovascular Disease
Current methods of identifying individuals at high risk for cardiovascular disease (CVD) that are based on levels of clinical risk factors (RF) are imperfect. Incorporating novel biomarkers into CVD risk assessment algorithms may improve their performance and allow clinicians to better match the intensity of treatment to a patient’s risk of disease.
Methods: We employed discovery and targeted strategies to measure plasma proteins in Framingham Heart Study participants. Multivariable models to predict new-onset CVD incorporated protein biomarkers alongside clinical RFs. Mass spectrometry (iTRAQ and MRM) was used to measure plasma proteins (861 by iTRAQ; 32 by MRM) using a case-control design (135 MI cases/135 controls, 336 CVD cases/336 controls; mean age 65 yrs, 30% women). Controls were matched to cases on age, sex, and smoking status. Targeted immunoassays for 44 candidate proteins used Luminex assays in 7500 individuals. Plasma samples were obtained at an examination that preceded the occurrence of clinical CVD.
Results: We identified 19 protein biomarkers that predicted new-onset CVD after adjustment for a) clinical CVD RFs and b) all other proteins from a given platform. 8 protein biomarkers came from iTRAQ, 6 from MRM, and 8 from immunoassay. These proteins represent platform-specific multimarker panels. About half the biomarkers have not previously been reported to be associated with CVD and represent novel findings.
Conclusions: Protein biomarkers, in combination with established CVD RF, may improve CVD risk prediction. If that improvement is substantial, future CVD risk assessment algorithms that incorporate plasma protein biomarkers may aid in the identification of high risk individuals early in the course of atherosclerosis progression when preventive strategies can be initiated to delay or prevent the onset of clinical CVD events. Validation of these protein biomarkers and resultant risk assessment algorithms in external cohorts is needed.
- © 2013 by American Heart Association, Inc.