Association between periodontal probing depth and PF4/heparin-complex antibodies in the Study of Health in Pomerania (SHIP)

Background: Platelet factor 4 (PF4), a chemokine released from platelets during activation, can complex with polyanions. The prototype reaction is the formation of PF4/heparin-complexes. Heparin treated patients can develop antibodies against these complexes, which activate platelets and provoke thrombotic complications. PF4/heparin-complex antibodies can also be observed in non-heparin treated patients. We have recently shown that PF4 can bind to bacteria. We hypothesized that periodontal inflammation may be involved in platelet activation, increased PF4 release, and binding of PF4 to bacteria with consecutive induction of PF4/heparin-complex antibodies. Material and Methods: The Study of Health in Pomerania (SHIP) is a population-based study (Western Pomerania, 1997–2001). Of 4308 participants (20–81years), 3500 subjects were included. Blood samples were screened for anti-PF4/heparin-IgM, -IgG, and -IgA. Probing depth (PD) was assessed on four sites per tooth, excluding third molars, half-mouth, alternating on right or left sides. Mean and extent PD (percentage of sites with PD≥3/4/5mm) were determined. Linear regression models evaluated the association between PD and PF4/heparin-complex antibodies. Effect modification was assessed using Likelihood ratio tests (p<0.10). Results: 49% were men and mean age was 47.7years. Mean anti-PF4/heparin-ELISA ODs for IgM, IgG, and IgA were 0.34±0.22, 0.24±0.17, and 0.10±0.10, respectively. After age and gender adjustment, mean IgM values increased by 0.006, -0.004, 0.020, and 0.058 OD compared to the reference quintile. The association was more pronounced in males (p interaction=0.05). Similarly, mean IgG and IgA values relevantly increased across mean PD quintiles (p trend=0.001). Findings were consistent if restricted to subjects without hospital stays within last 12 months; additionally adjusted for CRP, leucocytes, and fibrinogen; restricted to subjects with inhibition by high heparin of >40%; or if extent PD was evaluated. Conclusion: Periodontitis was associated with presence of natural PF4/heparin-complex antibodies. Potentially these antibodies are one explanation for the empirically observed association between periodontitis and the risk for cardiovascular disease.