Antibodies to periodontal pathogens are associated with coronary plaque remodeling but not with vulnerability or burden
Introduction
Periodontitis is a bacterially induced chronic inflammatory disease of tissues supporting the teeth and is highly prevalent (20–50%) in the adult population [1]. In the past decades, several epidemiological studies have suggested positive associations between clinically established periodontal and cardiovascular disease [2], [3], [4], and several small experimental studies have proposed potential mechanisms underlying these associations [2], [5]. The mechanism that has been most advocated is bacteremia followed by vascular contamination by periodontal pathogens [2], [6]. On the other hand, there have also been many studies that failed to demonstrate such associations between periodontal infection and atherosclerosis, particularly after adjusting for confounding variables [2]. Furthermore, evidence that periodontal interventions or systemic antibiotic treatment result in improved cardiovascular outcomes is currently lacking [2], [7]. Therefore, the proposed independent association between periodontal disease and atherosclerosis may still be considered as controversial.
This controversy is further underscored by the nature of the measures that have been used for periodontal infection (i.e. exposure) and atherosclerotic disease (i.e. outcome) in previous studies. The measures for periodontal infection were mostly subjective or based on clinical findings, usually in studies with limited sample size [2]. However, circulating immunoglobulin G (IgG) and immunoglobulin A (IgA) levels against periodontal pathogens may be more accurate measures of periodontal infection and its severity [8], [9]. Furthermore, they may be used in large epidemiological studies. Major periodontal pathogens include Porphyromonas gingivalis, Aggregatibacter actinomycetemcomitans, Tannerella forsythia and Prevotella intermedia [2]. The outcome measures that have been used in previous studies mostly consisted of clinical diagnosis of coronary heart disease (such as history of myocardial infarction), which is a clinical manifestation of the underlying atherosclerosis, but may not be an accurately measure of the extent of atherosclerosis. Conversely, intravascular ultrasound (IVUS) imaging of the coronary arteries allows for accurate measurement of coronary plaque burden, as well as measurement of remodeling of coronary lesions [10], [11], [12]. Additionally, IVUS virtual histology (IVUS-VH) (i.e. analysis of IVUS radiofrequency backscatter), allows for tissue characterization and for identification of virtual histology-derived thin-cap fibroatheroma (VH-TCFA) lesions, which have previously been shown to be predictive for future coronary events [10], [11], [12], [13], [14], [15].
This study aims to investigate whether there are positive associations between plasma IgG and IgA-class immunoglobulin levels against four major periodontal pathogens (i.e. P. gingivalis, A. actinomycetemcomitans, T. forsythia and P. intermedia) and the extent of coronary atherosclerosis, coronary plaque vulnerability and coronary remodeling as measured by IVUS, as well as 1-year cardiovascular outcome.
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Study population
The design of The European Collaborative Project on Inflammation and Vascular Wall Remodeling in Atherosclerosis – Intravascular Ultrasound (ATHEROREMO-IVUS) study has been described in detail elsewhere [12], [16]. In brief, 581 patients who underwent diagnostic coronary angiography or percutaneous coronary intervention (PCI) for acute coronary syndrome (ACS) (n = 318) or stable coronary artery disease (n = 263) have been included between 2008 and 2011 in the Erasmus MC, Rotterdam, the
Baseline characteristics
Mean age of the patients was 61.5 ± 11.3 years and 76% were men (Table 1). Coronary angiography was performed for various indications: 46% of patients had stable coronary artery disease, 26% of the patients had unstable angina pectoris and 28% of the patients had an acute myocardial infarction. ACS patients had slightly lower IgG-class antibody levels against A. actinomycetemcomitans compared to patients with stable coronary artery disease (Supplemental Table 1). Antibody levels were similar in
Discussion
This study investigated the associations between antibodies to major periodontal pathogens and coronary atherosclerosis on IVUS-VH. We found that IgG and IgA against P. gingivalis, A. actinomycetemcomitans, T. forsythia and P. intermedia were not associated with coronary plaque burden or VH-TCFA lesion morphology in the overall study population. High levels of IgA against A. actinomycetemcomitans, T. forsythia and P. intermedia, however, were associated with lower extent of positive lesion
Sources of funding
This work was supported by the European Commission, Seventh Framework Programme (grant number FP7-HEALTH-2007-2.4.2-1), the Netherlands Heart Foundation (grant number NHS2009B091 to J.M.C.), and the Academy of Finland (grant number 1266053 to P.J.P.).
Disclosures
None.
Conflict of interest
None.
Acknowledgments
We would like to thank the following interventional cardiologists and technical staff for their contribution to this study: Eric Duckers, MD, PhD; Willem van der Giessen, MD, PhD; Peter P.T. de Jaegere, MD, PhD; Jurgen M.R. Ligthart; Nicolas van Mieghem, MD; Carl Schultz, MD, PhD; Karen T. Witberg and Felix Zijlstra, MD, PhD. We are indebted to Professor Willem van der Giessen, who had a valuable contribution to the design and completion of the study, but passed away before finalization of this
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2020, Clinica Chimica ActaCitation Excerpt :Most findings [11,12] are consistent with those of Hosomi. However, de Boer et al. [13] found no positive association between the levels of serum IgG and IgA against major periodontal pathogens and coronary atherosclerosis. The epidemiological studies described above indicated that oral periodontal infection is a crucial independent risk factor for atherosclerotic cardiovascular disease.
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These authors contributed equally to this work.