Page 88 - Read Online

Page 2 of 18 Kozarov et al. Vessel Plus 2020;4:10 I http://dx.doi.org/10.20517/2574-1209.2019.31

INTRODUCTION
[1,2]
Cardiovascular disease (CVD) is the commonest cause of mortality and morbidity globally . Compared
with the past, global progress in extending life expectancy is forecasted to be slower from 2016 to
2040. This trend resulted from predicted slowed advances on key drivers including stagnated gains on
[3]
cardiovascular diseases, which was a major factor in historical improvements in life expectancy .
Atherosclerosis is a chronic vascular inflammation associated with hypercholesterolemia, accumulation
of lipids, hypertension, diabetes, smoking, smooth muscle cell proliferation, cell apoptosis, necrosis,
fibrosis, and genetic factors. Atherosclerosis causes plaque accumulation, obstructing blood flow and
contributes to acute ischemic events such as myocardial infarction or stroke. In these events, the arterial
wall inflammatory lesion becomes destabilized, leading to plaque rupture and discharge of its necrotic core
in the circulation, triggering coagulation and thrombosis. Such vulnerable plaques present the highest risk
of acute events. The risk of atherosclerotic disease has been observed to be significantly higher in patients
with periodontal disease, independently of other established risk factors.

Many CVD patients do not present any of the classical risk factors. Between 60%-70% of individuals with
[4]
multiple cardiovascular disease risk factors have not experienced a cardiovascular event and only 50% of
[5]
the CVD patients have been shown to have elevated serum cholesterol . While major statin trials report
an average 28% reduction in low-density lipoprotein (LDL) cholesterol and a 31% reduction in relative
[6]
risk, patients still have significant residual risk . Likewise, myocardial infarction and stroke continue to
occur in up to two-thirds of all patients, even after many of these factors are addressed . This “forgotten”
[7]
majority of patients leave wide open the door for exploration of risk factors that have not been adequately
addressed to date.

While the importance of the traditional risk factors is well established, the data indicate additional factors
contributing to atherogenesis. Infectious processes and products of the endogenous microbiome are
capable to modulate atherosclerosis and its complications either directly, or indirectly, by eliciting local and
systemic responses that potentiate atherogenesis. Here we will focus on bacterial infections as potential
contributors to vascular inflammation, with an emphasis on periodontal pathogens as an established
component of the atherosclerosis microbiome.

CURRENT VIEW OF THE INFECTIOUS COMPONENT OF ATHEROSCLEROSIS. ASSOCIATION

OF PERIODONTITIS WITH CVD
The initiation of atherogenic process is typical for a chronic inflammatory disease. This process starts with
recruitment of leukocytes from blood flow, mediated by a range of endothelial surface-expressed adhesins
(more details in the study by Libby ). The endothelial activation and subsequent leukocyte recruitment/
[8]
transmigration in tissue is in response to an activating stimulus, which includes microbial constituents.

Gingivitis and its advanced stage, chronic periodontitis, are the most prevalent microbial infections in
man. Only in recent decades has the association between periodontal diseases and systemic conditions
such as coronary heart disease and stroke became subject to investigation [9-16] .

The largest genome network analysis (63,746 cases and 130,681 controls) identified lipid metabolism and
inflammation as main pathways involved in the genetic predisposition to coronary artery disease (CAD).
Specifically, the four most significant pathways mapping to putative genes involved in CAD are linked to
lipid metabolism and inflammation, underscoring the causal role of these activities in the genetic etiology
of CAD. However, the genetic variants strongly associated with CAD explain approximately only at most
10.6% of CAD heritability [17-19] .