Literature has been published on the importance of salivary biomarkers in the diagnosis of CVDs, which includes Myoglobin (MYO), Cardiac troponin I (cTnI), Creatine phosphokinase MB (CK-MB), Myeloperoxidase (MPO), brain natriuretic peptide (NT-proBNP), Exosomal miRNA, C-Reactive Protein (CRP), Matrix metalloproteinase-8 (MMP-8), MMP-9 and tissue inhibitor of MMP-8 (TIMP-1) [
1,
2,
3,
15,
16,
17]. Myoglobin, which appears in both serum and saliva bio-fluids, can be used to detect AMI. Miller and his coworkers conducted research, and established that salivary myoglobin levels were greater within 48 h of the onset of angina in AMI patients [
4]. It was proved that the unstimulated saliva concentration of Cardiac troponin-I (cTnI) at the onset of 12 h and 24 h of Acute Myocardial Infection and creatine phosphokinase-MB (CK-MB) increased in patients with AMI compared to Non-AMI controls. This study also proved the strong link between levels of serum and salivary CK-MB and CPK, indicating that saliva-based tests may provide an easy and convenient way of providing point-of-care testing of CVDs [
3]. CRP is one of the inflammatory mediators of our body that is produced to trigger the complement cascade in response to acute injuries and infections. It also contributes and plays a vital role in atherogenesis [
4]. Studies proving a group of salivary biomarkers including CRP, MYO, and MPO as a diagnostic tool for AMI have shown a sensitivity of 90–100% [
5,
18], but BNP salivary levels, in contrast to serum BNP, were lower than the mean value of the control group [
3]. Many inflammatory components and adhesion molecules have also been identified as a salivary biomarker for the diagnosis of AMI, including IL-6, MMP-9, soluble intercellular adhesion molecule (sICAM-1), a soluble form of CD40 ligand (sCD40-L), CRP, cTnI and adiponectin [
16,
17]. Matrix metalloproteinase-8 has a well-established role in the repair and remodeling process of myocardial tissue after damage. Tissue inhibitor TIMP-1 inhibits MMP-8. So the ratio of MMP-8/TIMP-1 also projects the acceptable image of progression and severity of CVDs [
1]. Miller et al. elaborated that the concentrations of CRP, brain natriuretic peptide (NT-proBNP), matrix metallopeptidase 9 and tumor necrosis factor α in saliva were greater than in the AMI patients [
7].
Some research has been conducted to test and check the compatibility of salivary biomarkers with serum biomarkers [
4,
7]. Labat et al. investigated and found that there is a strong, positive and significant correlation between salivary and serum CRP levels among patients with ischemic heart disease (IHD). Through the collection of saliva and plasma samples from 250 individuals with a prior history of cardiovascular disease, salivary levels of CRP, prostaglandin E2 (PGE2), leukotriene B4 (LTB4), matrix metaaloproteinase 9 (MMP9), creatinine and lysozyme were measured, with the results indicating that saliva could be an alternative means for evaluation of cardiovascular risk [
18]. This indicates that CRP can be used to detect and monitor CVDs [
2]. Kossaify et al. studied certain specific cardiac biomarkers and a few non-specific inflammatory biomarkers that have significant roles in inflammation and plaque instability. They elaborated that levels of CRP, CK-MB, cardiac troponin I, cardiac troponin T, some interleukins (IL), tumor necrosis factor alpha (TNF-Alpha), MMPs, and MPO are associated with both saliva and serum [
3]. The conditions leading to increase or alteration in the levels of these biomarkers specifically related to cardiac tissues include myocardial injury, myocardial inflammation and myocardial stress. Other general conditions include neuroendocrine activation, plaque instability, atherosclerotic processes, platelet activation, endothelial dysfunction and oxidative stresses. Moreover, Thul et al. collected saliva from 254 individuals and took the ultrasound measurements of the thickness of the carotid artery’s intima media layer and analyzed the lipid mediator resolvin D1 by means of an enzyme-linked immunosorbent assay, and checked the association between leukotriene B4 and resolvin D1. Results depicted the independent prediction of intima media thickness, and both served as a biomarker of non-resolving inflammation [
19]. In addition to this, the presence and activity of inflammatory mediators in saliva suggests its constant low level in the oral cavity of healthy individuals in association with age [
20].
Folley et al. also assessed the utility of unstimulated whole saliva to determine cardiovascular health. Unstimulated whole saliva and serum was collected from 29 patients with CVD, at intervals of 0.8, 16, 24 and 48 h after invasive cardiac procedures, by using gingival and sublingual swabs. Results showed that the oral fluid reflected most of the biomarkers present in serum, which ultimately suggests that saliva serves as an essential tool for assessing cardiac ischemia or necrosis [
21]. Rahim et al. also reviewed the biomarkers in salivary proteome to predict acute myocardial infarction [
22]. A detailed description of identified salivary biomarkers for the detection of CVD biomarkers is presented in
Table 1 below.