Salivary biomarkers associated with myocardial necrosis: results from an alcohol septal ablation model

Saliva is an oral fluid, composed mainly of water, produced and secreted in large part from the acinar and ductal cells of the major and minor salivary glands. Whole saliva derives additional constituents from serum, gingival crevicular fluid and oral mucosal transudate, making it appealing as a potential diagnostic fluid reflective of circulating levels in blood.1 Several studies report systemic biomarkers appearing in saliva including electrolytes,2, 3 blood products,4 enzymes and tissue destruction molecules,5–9 inflammatory markers,10–16 as well as proteins putatively associated with deadly diseases.17–21 However, the clinical utility of salivary diagnostics for the assessment of systemic disease remains elusive.20, 22–27 Cardiovascular disease (CVD) is a major cause of mortality in the U.S. and worldwide. More than 17 million people died from CVD in 2008, with the majority due to atherosclerotic events including myocardial infarction.28, 29 With the extend and importance of this disease, easy, noninvasive and low cost screening methods for the detection of myocardial infarction continue to be sought. One such potential screening fluid is saliva.30 Support for the use of saliva for the detection of CVD and myocardial infarction is built upon the framework that many serum biomarkers associated with inflammation, atherosclerosis, plaque stability and myocardial damage are known and appear in oral fluids.4, 9, 31–35 However, only a limited number of studies have demonstrated correlations between serum and salivary biomarkers of CVD.14, 33, 36 Thus, additional research is required if we are to gain a greater understanding of the clinical utility of saliva compared to serum with respect to CVD and myocardial infarction assessment. This is particularly important for finding new diagnostics for situations where acquisition, processing or analysis of blood is problematic. In this research investigation, we hypothesized that select salivary biomarkers would correlate with serum biomarkers of CVD in patients with pre-existing heart disease and could yield important diagnostic information regarding the evolution and progression of myocardial necrosis. To test this hypothesis we employed a unique model of myocardial infarction in patients with a pre-existing CVD (i.e., hypertrophic cardiomyopathy [HCM]) who were scheduled to undergo alcohol septal ablation (ASA). This procedure results in a controlled myocardial infarction and subsequent remodeling processes that permit improved hemodynamics and improved patient outcomes.37, 38 Together, the pre-existing CVD and subsequent kinetic course of myocardial necrosis allowed us to predict that a spectrum of myocardial damage, inflammation and tissue remodeling biomarkers would appear in serum and saliva at baseline, and significant spikes would occur in these biomarker levels during the post-operative phase consistent with myocardial infarction.39–43 Here this unique study design permitted us to report the novel findings that salivary levels of troponin (Tn)I and C-reactive protein (CRP) reflected changes in serum consistent with myocardial damage, and select salivary biomarkers correlate with serum biomarkers of CVD.