Crosstalk between periodontitis and cardiovascular risk

Abstract

Recent demographic developments resulted in an aged society with a rising disease burden of systemic and non-communicable diseases (NCDs). In cardiovascular disease (CVD), a NCD with high morbidity and mortality, recent preventive strategies include the investigation of comorbidities to reduce its significant economic burden. Periodontal disease, an oral bacterial-induced inflammatory disease of tooth-supporting tissue, is regulated in its prevalence and severity by the individual host response to a dysbiotic oral microbiota. Clinically, both NCDs are highly associated; however, shared risk factors such as smoking, obesity, type II diabetes mellitus and chronic stress represent only an insufficient explanation for the multifaceted interactions of both disease entities. Specifically, the crosstalk between both diseases is not yet fully understood. This review summarizes current knowledge on the clinical association of periodontitis and CVD, and elaborates on how periodontitis-induced pathophysiological mechanisms in patients may contribute to increased cardiovascular risk with focus on atherosclerosis. Clinical implications as well as current and future therapy considerations are discussed. Overall, this review supports novel scientific endeavors aiming at improving the quality of life with a comprehensive and integrated approach to improve well-being of the aging populations worldwide.

Keywords: cardiovascular disease; dysbiosis; inflammation; innate immunity; periodontitis.

Figure 1

Development and pathophysiology of periodontitis. Plaque deposited on our teeth provides a substrate for a variety of bacterial species. A lack in oral hygiene and insufficient plaque removal from the tooth surfaces and their surrounding junctional gingival tissue can trigger the development of gingivitis. Inflammation can then further progress towards the development of mild to severe periodontitis paralleled by establishment of a dysbiotic biofilm of inflammophilic bacteria. Initially, the periodontal tissue is infiltrated by neutrophils, T-lymphocytes and mononuclear cells such as macrophages, followed by mainly plasma cells in a later stage. These plaques can potentially expand into a destructive advanced lesion inducing loss of periodontal ligament and alveolar bone and thus causing the characteristic clinical symptoms of periodontitis.

Figure 2

Development and pathophysiology of atherosclerosis. Atherosclerosis is a progressive disease driven by lipid deposition and inflammation into the arterial wall. Initial endothelial dysfunction triggers LDL leakage in the vessel, where it is oxidized to oxLDL. Also, it induces the recruitment and adhesion of leukocytes (neutrophils, monocytes, T-lymphocytes) and their migration into the vascular intima. Here, oxLDL drives monocyte-derived macrophages to lipid uptake and foam cell formation, triggering a pro-inflammatory profile and ultimately, lipid overload and cell death. Neutrophils elucidate inflammatory responses by secreting pro-inflammatory mediators as MPO, produce ROS and contribute to the recruitment and activation of monocytes/macrophages by secreting chemotactic granule proteins as well as the production of NETs. Vascular SMCs migrate from the vessel wall into the developing atherosclerotic lesion, where they form a protective fibrous cap. Upon plaque progression and increasing inflammation, the fibrous cap thins, which makes the atherosclerotic plaque prone to rupture and trigger thrombus formation. LDL, low-density lipoprotein; MPO, myeloperoxidase; NETs, neutrophil extracellular traps; oxLDL, oxidized LDL; ROS, reactive oxygen species; SMCs, smooth muscle cells.

Figure 3

From shared risk factors to periodontitis-induced pathophysiological effects contributing to atherosclerotic risk. The co-existence of periodontitis and atherosclerosis may be triggered by shared risk factors such as smoking, obesity, T2DM and chronic stress. However, the pathogenesis of periodontitis could also by itself be responsible for the detected associations since the oral dysbiosis could influence cardiovascular health and existing atherosclerotic lesions directly and indirectly. Involved mechanisms include bacteraemia, systemic inflammation and leukocytosis, innate immune cell activation, hyperlipidemia, endothelial dysfunction and reduced vascular elasticity, thrombocyte activation as well as the formation of neutrophil extracellular traps (NETs). For more details, see text.