The baseline demographics of the community care and protocol treatment groups appear in . The baseline characteristics for both groups have similar distributions of race, gender, hypertension, diabetes, smoking history, BMI, mean age, level of education, marital status, employment, and type of CVD event that qualified them for the study. There were a significantly greater number of subjects on cholesterol-lowering drugs in the community care group with 96.7% of subjects (147 of 152) taking these medications compared to 88.7% of subjects in the protocol treatment group. Further analyses of this difference showed that this variation in medication-usage patterns was not a significant modifier of any of the periodontal or inflammatory outcomes in this study, and no post hoc adjustments were indicated.
Demographic Characteristics at Baseline by Group Assignment: The PAVE Study
In , the baseline periodontal measurements for the community care and the protocol treatment groups show that they were well matched in terms of disease severity at baseline as indicated by measures of extent PD ≥4 mm, mean PD, mean AL, and extent BOP. Plaque indices and gingival indices were also similar for both groups (data not shown). The meanGCF-IL-1β levels were not significantly different at baseline comparing the two groups. Similarly, the baseline mean serum hs-CRP levels and the percentage of subjects with high hs-CRP were not different. Equal distribution of baseline characteristics between the two comparison groups suggested that randomization was effective.
Baseline Periodontal and Serum hs-CRP Measures by Treatment Group
The effects of periodontal therapy are shown at 6months in and at 1 year in . The treatment protocol had a significant effect on improving periodontal status at 6 months compared to community care (). The P values are statistically significant for extent PD ≥4 mm (P = 0.001) and mean PD(P = 0.0009)without significant effects on mean AL(borderline at P= 0.052) or extent BOP scores (P = 0.16)adjusting for baseline values for each patient using ANCOVA. Overall, there was an improvement in pocket reduction and a trend for slightly lower bleeding scores and less AL at 6 months comparing the protocol intervention group to the community care group. The GCF-IL-1β levels showed no significant differences between groups at 6months. The effects of periodontal intervention on serum hs-CRP show that there were no effects of protocol therapy on serum hs-CRP levels () at 6months.
Six-Month Follow-Up of Periodontal Assessments, GCF-IL-1β Levels, and Serum Measures of hs-CRP by Treatment Group
One-Year Follow-Up of Periodontal Assessments, GCF-IL-1β Levels, and Serum Measures of hs-CRP by Treatment Group
Compared to baseline, both groups showed a trend toward higher values at 6 months, but there were no significant differences in mean CRP values at 6 months adjusting for baseline values for each subject by ANCOVA. Thus, using intent-to-treat principles, the intervention resulted in an improvement in periodontal health but did not result in a significant change in GCF-IL-1β or serum hs-CRP levels at 6 months. As shown in , the clinical improvement seen among those treated under protocol was not significantly different from baseline at the 1-year follow-up. At the 1-year visit, GCF and serum data were available for 37 subjects. demonstrates that, at 1 year, there were no significant differences, using ANCOVA, in any of the clinical parameters or biomarker values comparing the community care group to the protocol treatment group after adjusting for baseline values, except for the extent subgingival calculus scores (values ≥2), which were significantly lower among those subjects receiving protocol-mandated care (P = 0.009). Furthermore, the clinical status for these 37 subjects was not significantly different from baseline at 1 year, except for lower subgingival calculus scores. However, because relatively few subjects were seen at 1 year, detailed secondary analyses were limited to the baseline and 6-month data.
Secondary Analyses of hs-CRP
One design issue of the trial that concerned us from the beginning was that subjects assigned to the community care group might receive periodontal care during the study period, an intervention that could potentially diminish any possible differences between the two study groups. At the onset before randomization, we also extracted hopeless teeth and provided home care instructions, thereby instituting some level of infection control among those who were ultimately assigned to the community care group. Furthermore, subjects who were identified as having periodontal disease and were randomized to the community care group were also provided with referral letters to seek additional care.
shows the dental care–use patterns for all study participants. Overall, 48% of the community care control group received one or more preventive or periodontal therapies during the 6-month study period, including prophylaxis, scaling and root planing, and periodontal surgery. Some of this information regarding scaling and root planing was previously published. 19
In , those subjects assigned to the community care group received significantly higher levels of non-study-care than those receiving therapy on protocol, including total number of dental visits, numbers of prophylaxis, and subgingival scaling and root planing. These use differences suggest that perhaps many who received care as part of the PAVE protocol chose to substitute study-provided care for normal community care dental visits, although they were advised to continue to seek routine dental care during the study. The protocol treatment provided a net change (SD) of −0.30 (0.45) mm (6-month baseline value) which was more improvement than that seen among the community care group (−0.13 [0.34] mm; P
= 0.001). However, both groups demonstrated a significant improvement in PD at 6 months relative to baseline ( and ). These findings suggested that secondary analyses to explore the effects of periodontal care provided to subjects randomized to the community care group appeared warranted.
Dental Use During First 6 Months of the Study
As secondary analyses, subjects were regrouped into those who received any periodontal treatment and those who received no treatment, irrespective of group assignment. Also, subjects were stratified based upon obesity. The community no treatment group was defined as those subjects assigned to the community care group who did not report having any periodontal care during the study period (6 months; n = 79). The community care group was further subdivided into those that received a prophylaxis only or a prophylaxis plus scaling and root planing. Three individuals in the community care group received periodontal surgery and were combined into the community scaling and root planing group. The any treatment group (n = 224) included protocol treatment plus those in the community care group that had either prophylaxis, scaling and root planing, or periodontal surgery. In , the percentage of subjects with high hs-CRP (hs-CRP >3mg/l) are shown for obese and non-obese individuals at 6 months for the community care group, stratified upon type of care provided within the community setting, the protocol treatment group, and the pooled any treatment group. There were two striking findings. First, there was no difference in the proportion of subjects who have elevated hs-CRP irrespective of treatment among those 73 obese individuals (BMI >30). It appears that periodontal treatment of obese individuals with high hs-CRP had no effect in the prevalence of elevated hs-CRP levels at 6months. Secondly, there was a marked lower proportion of subjects with hs-CRP ≥3 mg/l at 6 months among those non-obese subjects who received either a community prophylaxis or scaling and root planing, whether assigned to community care or protocol. Among non-obese individuals in the community who received no treatment, 43.5% had high hs-CRP at 6 months. In contrast, there was a strikingly lower proportion of subjects with high hs-CRP among those subjects who received a prophylaxis (6.25%; P = 0.009), scaling and root planing (8.3%; P = 0.03), and protocol therapy (22.2%; P = 0.04). It is noteworthy that these two community treatment groups also demonstrated clinical improvements at 6 months relative to baseline. For example, the mean (SE) PD change in millimeters for the four groups was: no treatment (−0.07 [0.06]), prophylaxis (−1.17 [0.06]), scaling and root planing (−0.20 [0.08]), and protocol treatment (−0.30 [0.03]). Combining all treated, non-obese subjects into the any treatment group showed, with statistical significance, a lower proportion of subjects with high hs-CRP from43.5% in the no treatment group to 17.6% (P = 0.006) in the any treatment group.
Figure 2 Percent of subjects with hs-CRP >3 mg/l at 6 months by treatment group and stratified by obesity. *P = 0.009; †P = 0.03; ‡P = 0.04; §P = 0.006. Tx = treatment; Prophy = prophylaxis; SRP = scaling and root planing. Vertical (more ...)
Logistic regression models were used to compute the ORs shown in for having high hs-CRP (>3 mg/l) at 6 months based upon periodontal treatment provided either in the community setting or on protocol compared to the community no treatment group as the referent population stratifying by obesity or using all treated subjects. As illustrated in , there were no significant findings regarding the risk for high hs-CRP among obese individuals irrespective of treatment category. However, any treatment among all subjects resulted in a statistically significant 2.38-fold lower odds for high hs-CRP (OR = 0.42 [95% CI = 0.18 to 0.995]). The effects were even stronger among the non-obese subjects, with a 3.85-fold lower odds for having high hs-CRP at 6 months with any treatment (OR = 0.26 [95% CI = 0.09 to 0.72]). The community-provided prophylaxis showed a significant reduction in OR among non-obese subjects, whereas the lower OR (0.09) seen with community scaling and root planing was not statistically significant among non-obese individuals. The protocol treatment had no effect among the obese individuals but significantly lowered the OR to 0.34 (95% CI = 0.12 to 0.98) among the non-obese subjects, representing a statistically significant 2.9-fold reduction in the number of subjects with high hs-CRP at 6 months compared to those non-treated individuals in the community setting.
OR (95% CI) for hs-CRP >3 mg/l at 6 Months