Elsevier

Atherosclerosis

Volume 237, Issue 1, November 2014, Pages 84-91
Atherosclerosis

Antibodies to periodontal pathogens are associated with coronary plaque remodeling but not with vulnerability or burden

https://doi.org/10.1016/j.atherosclerosis.2014.08.050Get rights and content

Highlights

  • Antibodies to periodontal pathogens are not associated with coronary plaque burden.

  • Antibodies to periodontal pathogens are not associated with plaque vulnerability.

  • Antibodies to periodontal pathogens are associated with coronary plaque remodeling.

Abstract

Objective

Previous studies have suggested positive associations between periodontal infection and cardiovascular disease. We aimed to investigate the associations of circulating antibodies against periodontal pathogens with 1-year cardiovascular outcome, as well as the extent of coronary atherosclerosis, plaque vulnerability and lesion remodeling on intravascular ultrasound (IVUS) imaging.

Methods

Between 2008 and 2011, radiofrequency IVUS imaging of a non-culprit coronary artery was performed in 581 patients who underwent coronary angiography. Immunoglobulin G (IgG) and A (IgA) against Porphyromonas gingivalis, Aggregatibacter actinomycetemcomitans, Tannerella forsythia and Prevotella intermedia were measured in plasma.

Results

None of the antibody levels were associated with coronary plaque burden, radiofreqeuncy-IVUS-derived thin-cap fibroatheroma lesion morphology or 1-year incidence of major adverse cardiac events (MACE), which included all-cause mortality, acute coronary syndrome and unplanned coronary revascularization. IgA against A. actinomycetemcomitans, T. forsythia and P. intermedia were inversely associated with extent of positive lesion remodeling (OR for highest versus lowest tertile 0.55, 95%CI 0.35–0.88, p = 0.012; 0.53, 95%CI 0.32–0.87, p = 0.012; and 0.64, 95%CI 0.40–1.02, p = 0.061, respectively). In diabetic patients specifically, IgG against P. gingivalis tended to be associated with coronary plaque burden (p = 0.080), while IgA against P. gingivalis tended to be associated with incident MACE (p = 0.060).

Conclusion

Plasma IgG and IgA against major periodontal pathogens were not associated with the extent of coronary atherosclerosis (with the exception of a trend in diabetics) nor with coronary plaque vulnerability. IgA against periodontal pathogens were inversely associated with extent of coronary remodeling. Altogether, these results do not add evidence for a substantial role of systemic exposure to periodontal pathogens in coronary artery disease.

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.

Section snippets

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

References (29)

  • P.J. Pussinen et al.

    Multiserotype enzyme-linked immunosorbent assay as a diagnostic aid for periodontitis in large-scale studies

    J Clin Microbiol

    (2002)
  • G.W. Stone et al.

    A prospective natural-history study of coronary atherosclerosis

    New Engl J Med

    (2011)
  • J.M. Cheng et al.

    In vivo detection of high-risk coronary plaques by radiofrequency intravascular ultrasound and cardiovascular outcome: results of the atheroremo-ivus study

    Eur Heart J

    (2014)
  • H.M. Garcia-Garcia et al.

    Tissue characterisation using intravascular radiofrequency data analysis: recommendations for acquisition, analysis, interpretation and reporting

    EuroIntervention

    (2009)
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