冠動脈バイパス術（CABG）を受けた患者におけるAdvanced Glycation End Product（AGE）および Soluble Receptor of AGE（sRAGE）レベルと歯周炎の重症度との関係および3年間の予後予測因子として

Advanced Glycation End Product (AGE) and Soluble Receptor of AGE (sRAGE) Levels in Relation to Periodontitis Severity and as Putative 3-Year Outcome Predictors in Patients Undergoing Coronary Artery Bypass Grafting (CABG).

抄録

Advanced glycation end product（AGE）の組織濃度および末梢のsoluble receptor of AGE（sRAGE）濃度は、歯周炎の重症度と関連する可能性がある。これらのパラメータと歯周炎は，冠動脈バイパス術（CABG）を受ける患者の転帰予測因子となる可能性がある．本研究は、歯周炎とAGE/sRAGEとの関連性を検討することを目的とした。最終的には、AGE、sRAGE、重度の歯周炎が、CABG後3年以内の新たな心血管イベントの発生と関連するかどうかを検討したいと考えた。CABG手術を必要とする冠動脈血管疾患（CVD）患者95名（年齢69歳，男性88.3%）を対象とした．歯周病診断は「米国疾病管理予防センター（CDC）」のガイドライン（2007年）に従い、歯周病の新分類（2018年）に従って病期分類を行った。AGE組織濃度は皮膚自発蛍光（sAF）として評価し、sRAGE濃度は市販の酵素結合免疫吸着測定法（ELISA）キットを用いて測定した。一変量および多変量ベースライン解析および生存率解析は，Mann-Whitney U test， Chi² test， Kaplan-Meier curve with Log-Rank test， Logistic and Cox regressionにより行った．sAFは，年齢，性別，プラーク指数および糖尿病を共因とする重症歯周炎の独立リスク指標として特定された（修正オッズ比［OR］ = 2.9， = 0.028 ）．歯肉縁下の炎症の程度は，プロービング時出血（BOP）のある部位の割合で評価し，sRAGE濃度と逆相関を示した（r = -0.189, = 0.034）．sAF（Hazard Ratio [HR] = 2.4, = 0.004）とsRAGE（HR = 1.9, = 0.031）はともにCABG後の新しい有害事象の粗リスクを増加させた。重度の歯周炎の発生は、新たな心血管イベントのリスクを高める傾向にある（HR = 1.8, = 0.115）。多変量Cox回帰を適用すると、末梢動脈疾患（調整後HR = 2.7, = 0.006）と心筋梗塞の既往（調整後HR = 2.8, = 0.010）のみが、心血管予後の独立危険因子であることが証明された。このことから，sAFは重度歯周炎の新たな独立したリスク指標となる可能性があると結論づけた．一方，CABGを受けた患者では，sAF，sRAGE，重度歯周炎は術後予後の独立した要因とはならなかった．

Tissue concentrations of advanced glycation end product (AGE) and peripheral soluble receptor of AGE (sRAGE) levels may be associated with periodontitis severity. Both parameters and periodontitis might serve as outcome predictors for patients undergoing coronary artery bypass grafting (CABG). This study aimed to investigate possible associations between periodontitis and AGE/sRAGE. Ultimately, we wanted to examine whether AGE, sRAGE, and severe periodontitis are associated with the incidence of new cardiovascular events within 3 years of follow-up after CABG. Ninety-five patients with coronary vascular disease (CVD) (age 69 years, 88.3% males) needing CABG surgery were included. Periodontal diagnosis was made according to the guidelines of the "Centers for Disease Control and Prevention (CDC)" (2007) and staged according to the new classification of periodontal diseases (2018). AGE tissue concentrations were assessed as skin autofluorescence (sAF). sRAGE levels were determined by using a commercially available enzyme-linked immunoabsorbance assay (ELISA) kit. Univariate and multivariate baseline and survival analyses were carried out with Mann-Whitney U test, Chi² test, Kaplan-Meier curves with Log-Rank test, and logistic and Cox regression. sAF was identified as an independent risk indicator for severe periodontitis with respect to the cofactors age, gender, plaque index, and diabetes (adjusted odds ratio [OR] = 2.9, = 0.028). The degree of subgingival inflammation assessed as a percentage of sites with bleeding on probing (BOP) was inversely correlated with sRAGE concentration (r = -0.189, = 0.034). Both sAF (Hazard Ratio [HR] = 2.4, = 0.004) and sRAGE (HR = 1.9, = 0.031) increased the crude risk for new adverse events after CABG. The occurrence of severe periodontitis trends towards a higher risk for new cardiovascular events (HR = 1.8, = 0.115). Applying multivariate Cox regression, only peripheral arterial disease (adjusted HR = 2.7, = 0.006) and history of myocardial infarction (adjusted HR = 2.8, = 0.010) proved to be independent risk factors for cardiovascular outcome. We conclude that sAF may represent a new, independent risk indicator for severe periodontitis. In contrast, sAF, sRAGE, and severe periodontitis were not independent prognostic factors for postoperative outcome in patients undergoing CABG.