Cardiovascular Biomarker Index in Saliva of Cardiac Patients

Objectives: Our objective was to apply the CARDIOvascular BIOmarker INDEX (cardiobioindex) method to assess the cardiac classification content of various biomarkers of cardiovascular disease (CVD) in serum and saliva.

Methods: Advanced detection methodologies Luminex®, proteomic microarrays, Enzyme Linked ImmunoSorbent Assay and lab-on-a-chip (LOC) methods were employed for the detection and measurement of 28 protein biomarkers in serum and saliva of healthy control and cardiac disease patients. The cardiobioindex method, which utilizes the area under the receiver operating characteristic curve and logistic regression, was applied here to elucidate the performance of single biomarkers and biomarker combinations for classifying cardiac disease patients.

Results: The cardiobioindex method was validated through its capacity to replicate some of the major associations previously identified for serum lipids and C-reactive protein (CRP) levels. Here, CRP and lipid cardiobioindex inputs in classifying control and cardiac patients were consistent with the reported relative value of the biomarkers as risk factors for CVD. The cardiobioindex method demonstrated strong diagnostic utility of a number of single biomarkers in saliva and improved classification with respect to a panel of biomarkers CRP, interleukin (IL)-1β, IL-13, B-natriuretic peptide, IL-6, tumor necrosis factor-α, IL-10, IL-4, soluble CD40 ligand, IL-8 and IL-5.

Conclusions: The development of practical measurement methods and improved strategies of biomarker validation are likely to have a profound impact on accelerating the translation of biomarkers of CVD to patient care. The cardiobioindex method has the potential to overcome current time-consuming biomarker validation approach and, when utilized in conjunction with a point-of-care device, such as LOC system, promises to substantially augment cardiac diagnostics. These initial studies reveal that saliva shows strong promise as diagnostic medium for this purpose, and is worthy of more detailed studies in the future.

Supported by National Institute of Dental and Craniofacial Research Division of NIH (#U01 DE017793-01).