臺灣侵入性牙齒治療後發生心肌梗塞、缺血性腦中風、以及心內膜炎之風險:唯病例法研究

Abstract

背景： 侵入性牙齒治療可能會引起短暫的菌血症，因此被認為是心內膜炎、心肌梗塞、以及缺血性腦中風潛在的危險因子，可能的致病機轉為細菌透過侵入性牙齒治療所造成的傷口進入血液裡，細菌可能附著在功能不正常的心臟瓣膜或受損的心臟組織、抑或是進入到循環系統內，因此誘發心內膜炎，若細菌跑到血液中並附著在血管上，即可能引起系統性發炎症，進一步造成動脈硬化，誘發急性血管功能障礙，然而在過去的研究中，侵入性牙齒治療與心內膜炎、心肌梗塞、以及缺血性腦中風之間的關係還沒有一個定論，所以本研究的目的為探討侵入性牙齒治療與心內膜炎、心肌梗塞、以及缺血性腦中風的相關性。 方法： 本研究使用臺灣全民健康保險資料庫，我們應用兩種唯病例法研究設計來驗證假說，其中包含病例交叉(case-crossover)研究設計以及病例自我對照(self-controlled case series)研究設計，唯病例法研究設計的優點為不隨時間改變的干擾因子會自我校正，因此我們估計的相對風險可以避免干擾因子造成偏差。在病例交叉研究設計，我們使用條件式邏輯思迴歸模型來估計侵入性牙齒治療後發生心內膜炎、心肌梗塞、以及缺血性腦中風的風險，根據不同的併發症我們估計的暴露區間有所不同，針對心內膜炎，我們估計的暴露區間長度分別為ㄧ週、兩週、三週、和四週，而心肌梗塞以及缺血性腦中風的部分，我們估計的暴露區間長度分別為三天、七天、兩週、四週、八週、十二週、十六週、二十週、以及二十四週。在病例自我對照研究設計，我們使用條件式卜瓦松迴歸模型來估計侵入性牙齒治療後發生心內膜炎、心肌梗塞、以及缺血性腦中風的風險，我們分別估計侵入性牙齒治療後一至四週、五至八週、九至十二週、以及十三至十六週發生心內膜炎的風險，以及侵入性牙齒治療後一至三天、四至七天、八至十四天、三至四週、五至八週、九至十二週、十三至十六週、十七至二十週、和二十ㄧ至二十四週發生心肌梗塞與缺血性腦中風的風險。 結果: 在病例交叉研究設計中，我們總共納入9120位心內膜炎的個案、123819位心肌梗塞的個案、以及327179位缺血性腦中風的個案，而在病例自我對照研究設計中，我們總共納入 8181 位心內膜炎的個案、117655位心肌梗塞的個案、以及298757位缺血性腦中風的個案。心內膜炎風險估計的部分，在病例交叉研究設計中，當暴露區間長度為四週，其接受侵入性牙齒治療相對於沒有接受侵入性牙齒治療發生心內膜炎的勝算比為1.12 (95% 信賴區間:0.94-1.34)，而在病例自我對照研究設計中，侵入性牙齒治療後四週相較於對照區間，其年齡校正的發生率比為1.14 (95% 信賴區間:1.02-1.26)；心肌梗塞的部分，不論是病例交叉研究設計或是病例自我對照研究設計，我們有一致的結果：侵入性牙齒治療後24週相對於沒有接受侵入性牙齒治療，發生心肌梗塞的相對風險非常接近於1，或是風險未達統計上顯著差異；缺血性腦中風的部分，兩種研究設計估計的相對風險有一致的結果，侵入性牙齒治療後24週相對於沒有接受侵入性牙齒治療，發生缺血性腦中風的相對風險非常接近於1。 結論: 不論是病例交叉研究設計或是病例自我對照研究設計，我們的研究結果發現，侵入性牙齒治療後短期內不會增加心內膜炎、心肌梗塞、以及缺血性腦中風的風險，除此之外，針對高危險族群的部分，像是風濕性心臟病或是換過瓣膜的個案，研究結果顯示侵入性牙齒治療與心內膜炎無相關性，以及在年齡較大的個案中，侵入性牙齒治療與心肌梗塞及缺血性腦中風無相關性，因此，在臺灣族群使用預防性抗生素來降低心內膜炎的風險是不必要的，但是針對長期風險的部分，我們仍無法排除侵入性牙齒治療後會增加心肌梗塞以及缺血性腦中風風險之可能性。

BACKGROUND: Invasive dental treatments (IDTs) can yield temporary bacteremia and has therefore been considered a potential risk factor of infective endocarditis (IE), myocardial infarction (MI) and ischemic stroke (IS). It is hypothesized that, through the trauma caused by IDTs, bacteria gain entry to the bloodstream and may attach to abnormal heart valves, attach to damaged heart tissue, or travel through the circulation, giving rise to IE. Bacterial dissemination from the oral cavity and systemic inflammation linked to IDT may induce a state of acute vascular dysfunction. However, the association between IDTs and IE, MI. and IS remains controversial. The aim of this study is to estimate the association between IDTs and IE, MI, and IS. METHODS: The data in this study were obtained from the Health Insurance Database in Taiwan. We selected two case-only study designs, case-crossover and self-controlled case series, to analyze the data. The advantage of these methods is that confounding factors which do not vary with time are adjusted for implicitly. In the case-crossover design, conditional logistic regression model with exposure to IDTs was used to estimate the risks of IE following an IDT with 4, 8, 12, and 16 weeks delay and the risk of MI/IS following an IDT with 3 days, 7 days, 2 weeks, 4 weeks, 8 weeks, 12 weeks, 16 weeks, 20 weeks, and 24 weeks delay, respectively. In the self-controlled case series design, conditional Poisson regression model was used to estimate the risk of IE for the risk periods of 1-4, 5-8, 9-12, and 13-16 weeks following an IDT and the risk of MI/IS for the risk periods of 1-3 days, 4-7 days, 8-14 days, 3-4 weeks, 5-8weeks, 9-12 weeks, 13-16 weeks, 17-20 weeks, and 21-24weeks following an IDT. RESULTS: In total, 9120 IE patients, 123,819 MI patients and 327,179 IS patients in the case-crossover design, and 8181 IE patients, 117,655 MI patients and 298,757 IS patients were included in the self-controlled case-series. The odds ratio of IE was 1.12 (95% Confidence Interval (CI): 0.94-1.34) for 4 weeks in the case-crossover design, and the age-adjusted incidence rate ratio of IE was 1.14 (95% CI: 1.02-1.26) for 1-4 weeks after IDTs in self-controlled case series design. Results from both study designs showed that the risk of MI within the first 24 weeks was no significantly different or very close to unity. For IS, we observed no association between IDTs and IS or the risk is very close to unity. We also did not find any association between high risk IDTs and a larger risk of IE, MI and IS. CONCLUSIONS: In both study designs, we did not observe a clinically larger risk for IE, MI and IS in the short periods after IDTs. We also found no association between IDTs and IE among high-risk patients, such as those with rheumatic heart disease or valve replacement, and no association between IDTs and MI and IS among older patients. Therefore, antibiotic prophylaxis for prevention of IE is not required for the Taiwanese population. However, we cannot exclude that dental infections and diseases may yield a long-term effect on MI and IS.