Associations of Antibodies Targeting Periodontal Pathogens With Subclinical Coronary, Carotid, and Peripheral Arterial Atherosclerosis in Rheumatoid Arthritis

Arthritis Rheumatol. 2021 Apr;73(4):568-575. doi: 10.1002/art.41572. Epub 2021 Mar 3.

Abstract

Objective: Both periodontal disease and cardiovascular disease (CVD) are overrepresented in rheumatoid arthritis (RA). This study was undertaken to investigate the contribution of periodontal pathogens to CVD in RA.

Methods: RA patients underwent assessments of coronary artery calcification (CAC), carotid intima-media thickness and plaque, and ankle-brachial index via computed tomography, ultrasound, and Doppler ultrasound, respectively. Sera were assayed for antibodies targeting Porphyromonas gingivalis (Pg), Aggregatibacter actinomycetemcomitans serotype B (Aa), and Aa-derived leukotoxin A (LtxA). Associations of antibodies against these periodontal pathogens with measures of atherosclerosis were explored using generalized linear models.

Results: Among 197 RA patients, anti-Pg was detected in 72 patients (37%), anti-Aa in 41 patients (21%), and anti-LtxA in 84 patients (43%). Adjusting for relevant confounders and reported tooth loss, the mean CAC score was 90% higher in those with anti-Aa and/or anti-LtxA compared with those without either antibody (19 units versus 10 units; P = 0.033). The adjusted odds of CAC ≥100 units were 2.23-fold higher in those with anti-Aa and/or anti-LtxA compared with those without either antibody (P = 0.040). Anti-Aa and/or anti-LtxA seropositivity was significantly associated with all other assessed measures of atherosclerosis except carotid plaque. Anti-Pg was not associated with any measure of atherosclerosis. Higher swollen joint count was associated with CAC exclusively in the group with anti-Aa and/or anti-LtxA.

Conclusion: Immunoreactivity against Aa and/or its major virulence factor LtxA was associated with atherosclerosis in multiple vascular beds of RA patients and amplified the effect of swollen joints on coronary atherosclerosis, suggesting a role for treatment/prevention of periodontal disease in the prevention of CVD in RA.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Aggregatibacter actinomycetemcomitans / immunology*
  • Antibodies, Bacterial / immunology*
  • Arthritis, Rheumatoid / complications
  • Arthritis, Rheumatoid / diagnostic imaging
  • Arthritis, Rheumatoid / immunology*
  • Atherosclerosis / complications
  • Atherosclerosis / diagnostic imaging
  • Atherosclerosis / immunology*
  • Carotid Intima-Media Thickness
  • Case-Control Studies
  • Coronary Artery Disease / complications
  • Coronary Artery Disease / diagnostic imaging
  • Coronary Artery Disease / immunology*
  • Female
  • Humans
  • Male
  • Middle Aged
  • Porphyromonas gingivalis / immunology*
  • Risk Factors
  • Severity of Illness Index
  • Tomography, X-Ray Computed
  • Ultrasonography, Doppler
  • Vascular Calcification / complications
  • Vascular Calcification / diagnostic imaging
  • Vascular Calcification / immunology*

Substances

  • Antibodies, Bacterial