Relationship between Peri-implantitis and Cardiovascular Diseases

Abstract

Objectives: The purpose of this study was to assess the relationship between peri-implantitis and cardiovascular diseases. Methods: A case-control design, cross-sectional study was conducted to evaluate the prevalence of peri-implantitis among individuals diagnosed with cardiovascular diseases (CVD). Health and CVD history were obtained through structured questionnaire. Participants who had at least one implant in function for more than 6 months were recruited. Individuals without CVD were grouped as "Control', and participants in the "Case" CVD group were recruited only when the dental implants were placed prior to CVD diagnosis. Among the "Case" group, individuals with peri-implantitis were included in the final analysis only when the per-implantitis onset was evidenced radiographically prior to the diagnosis of the CVD. Clinical and radiographic examinations were performed; samples of serum, peri-implant crevicular fluid (PICF), and gingival crevicular fluid (GCF) at the most severe diseased sites were collected to evaluate the pro-inflammatory cytokine profile. Subgingival plaque from the peri-implantitis sulci were analyzed using 16S rRNA next-generation sequencing and real-time qPCR technologies. Results: A higher prevalence of peri-implantitis (with detectable radiographic bone loss) in the CVD group (OR= 1.48, 95% CI= 0.71 to 3.11, p= 0.30) was found. Furthermore, moderate to severe peri-implantitis (radiographic bone loss ≥ 2mm) was significantly associated with cardiovascular diseases (OR= 2.18, 95% CI= 1.02 to 4.67, p=0.04), but was no longer observed after controlling for multiple significant confounding factors. The microbial community among the CVD group and peri-implantitis group demonstrated a more divergent profile compared to the control and healthy implant group. Predominantly anaerobic microorganisms at the peri-implantitis niche were associated with deeper pockets and severe bone loss. A higher bacterial counts (gene copies) of Prophylomonas gingivalis (P. gingivalis) was observed in the CVD group. Secondly, peri-implantitis pockets appeared to harbor higher Fusobacterium nucleatum (F. nucleatum) DNA in a dose-responsive relationship with the severity of peri-implant disease. Tannerella forsythia (T. forsythia) was significantly higher only in the severe peri-implantitis (radiographic bone loss> 4 mm). Serum fibrinogen was significantly higher in the CVD group and moderate to severe peri-implantitis (radiographic bone loss≥ 2mm) sites when compared to the control or healthy implant groups. A similar trend was observed in the serum interleukin (IL)-6, tumor necrosis factor (TNF-𝛼), and osteoprotegerin (OPG). PICF TNF-𝛼 was predominantly higher in the CVD group. This coincided with the local peri-implant inflammation. Matrix metalloproteinase (MMP)-8, IL-1𝛽, and tissue inhibited metalloproteinase (TIMP)-2 displayed fair accuracy in predicting peri-implant disease. The sensitivity increased when combined with the bacterial concentration of T. forsythia and F. nucleatum. Finally, OPG appeared to be the only GCF biomarker correlated with peri-implant disease. Conclusions: Moderate to severe peri-implantitis (radiographic bone loss ≥ 2mm) was observed to be a mild associative positive risk factor for the development of cardiovascular disease. However, a significant association was not observed after multivariable adjustment. Low-grade chronic inflammation around diseased dental implants, especially when the disease severity and tissue destruction was increased, may be linked to atherosclerosis and cardiovascular disease by increasing the overall inflammation burden on patients at risk for CVD.