臺灣博碩士論文加值系統

背景：
牙周病是全世界的一個盛行率相當高的疾病；心血管疾病也是一個現代人常見且高致死率的疾病。心血管疾病包括心肌梗塞、中風、心臟衰竭、冠狀動脈疾病等等，且是造成高死亡率及高失能的主要原因。其中，急性心肌梗塞是心血管疾病的一種急性發作，在世界各國都屬死亡率很高的疾病，並會導致猝死及失能。心血管疾病的危險因子包括年齡、男性、高血壓、糖尿病、血酯異常、吸菸及發炎性疾病，如:牙周病等。
牙周病和心血管疾病的關聯性已被之前許多研究所探討，但至今尚未有研究針對不同的牙周病治療與心血管疾病的發生率之關聯性來作探討。
本論文兩個部分的研究，主要在於利用台灣的全民健保資料庫，來分析並探討台灣成年人的牙周病與心血管疾病，包括缺血性中風與急性心肌梗塞的發生率的關聯性。此研究並會調整年齡、性別、及其他共病症後再進行分析。

方法：
本論文中兩部分的研究均屬於族群導向回溯性的世代研究。我們使用全民健保資料庫2000年的百萬人抽樣檔。即從西元2000年全台灣的健保投保民眾中，隨機抽樣出一百萬人，並分析這一百萬人自2000年至2010年間的所有門診及住院就醫和承保資料以進行分析研究。
在第一個研究之中，我們先找出2000-2010年資料庫中20歲以上，無中風病史，所有被牙科醫師診斷為牙周病的病患，共有510762個病患，然後我們將所有有牙周病診斷的病人，再分為洗牙組、深度治療組及未接受牙周病治療組。另外對照組則為208674位從無牙周病診斷的病人。我們接著觀察這四組的病人，在這十年當中，其罹患缺血性中風的發生率是否有顯著差別? 並利用Cox迴歸模型來分析各項因子與缺血性中風發生率之間的關聯性。
在第二個研究中，我們則是分析了資料庫中牙周病與急性心肌梗塞發生率的關聯性。我們共找出2000-2010年資料庫中20歲以上，無心肌梗塞病史的牙周病病患，共有511 630個病患，對照組則有208 713位從無牙周病診斷的病人。我們也將牙周病病人依治療處置分為洗牙組、深度治療組及未接受牙周治療組三組，再與無牙周病的對照組一起觀察比較:其罹患急性心肌梗塞的發生率是否有顯著差別? 並利用Cox迴歸模型來分析各項因子與急性心肌梗塞發生率之間的關聯性。

結果：
第一部份的研究顯示:無牙周病的病人，其缺血性中風的發生率為0.32%/y的人年發生率，即平均發生率為每1萬人年中有32人；而牙周病族群中，洗牙組則有最低的發生率: 0.14%/y；接著是深度治療組，0.39%/y；有牙周病卻未治療的，則有最高的發生率: 0.48%/y，即平均發生率為每1萬人年中有48人，且均達統計上之顯著意義(p值<0.001)。在調整其他干擾因子後，Cox迴歸模型分析則顯示洗牙組及深度治療組比起無牙周病的對照組，有較低的機率發生中風，分別是0.78倍及0.95倍 (95%信賴區間分別為0.75-0.81；0.91-0.99）；然而有牙周病卻沒治療的，比起對照組，則有1.15倍的機率發生中風，特別是經年齡分層後發現，對20-44歲的族群，其機率甚至高達2.17倍(95%信賴區間為1.64-2.87）。
在有關牙周病與急性心肌梗塞發生率的研究結果則顯示:無牙周病的病人，其急性心肌梗塞的發生率為0.19%/y的人年發生率，即平均發生率為每1萬人年中有19人發生急性心肌梗塞；而牙周病族群中，洗牙組則有最低的發生率: 0.11%/y，即平均發生率為每1萬人年中有11人發生急性心肌梗塞；接著是深度治療組，0.28%/y；有牙周病卻未治療的，則有最高的人年發生率: 0.31%/y，且均達統計上之顯著意義(p值<0.001)。若依三個牙周治療組來看:可看到心肌梗塞發生率在所有年齡、性別及共病的分組中，均呈現有顯著的趨勢關係: 洗牙組<深度治療組<牙周病未治療組。在調整其他干擾因子後，Cox迴歸分析則顯示:洗牙組比起無牙周病組，有較低的機率發生心肌梗塞( 0.89倍； 95%信賴區間為0.81 -0.94）；然而有牙周病卻沒治療的，比起對照組，則有1.24倍的機率發生心肌梗塞(95%信賴區間為1.13-1.36）。

結論：
洗牙為缺血性中風及急性心肌梗塞的保護因子。維持牙周健康及接受洗牙和牙周病治療，均能降低發生缺血性中風及急性心肌梗塞的機率。

意義：
這個研究的結果，提出了有關牙周病與心血管疾病的關聯性之證明。我們希望能藉此對臨床牙醫師及衛生政策制定者，強調口腔健康的重要，更希望能因此降低因為牙周疾病影響而導致的缺血性中風及急性心肌梗塞的發生率。

Background:
The periodontal disease (PD) is a high prevalent disease around the world. The cardiovascular diseases (CVD) are the common diseases of modern people and result in high mortality rates. Cardiovascular disease included myocardial infarction, angina, stroke, transient ischemic attack, claudication, heart failure, coronary revascularization and peripheral arterial disease is the major death cause and leads severe disability. Acute myocardial infarction (AMI) is the leading cause of morbidity and mortality worldwide. AMI is one of the acute events of CHD and may result in sudden death or disability. The risk factors of CHD include age, male gender, hypertension, diabetes, dyslipidemia, smoking, as well as inflammatory disease such as periodontal disease (PD).
A correlation has been established between periodontal disease and cardiovascular diseases. However, no previous studies have discussed the relationship between different PD treatments and the incidence rate of cardiovascular diseases among different age groups.
The Longitudinal Health Insurance Database (LHID) from National Health Insurance Research Database (NHIRD) in Taiwan provided information of representative samples in Taiwan. Our research explores the association between PD and cardiovascular diseases including ischemic stroke and AMI after adjust the age, gender, and comorbidities through analyzing the registry data of the population in Taiwan. The observation focus on whether different PD treatments result in different incidence of stroke and AMI.

Methods:
Two parts of our research were both designed as population-based retrospective cohort studies. A million registered beneficiaries of the NHI program in Taiwan were randomly selected in 2000. All claims for reimbursements and registry files from 2000 to 2010 were used for analysis.
We identified 510 762 PD cases and 208 674 non-PD subjects from January 1, 2000 to December 31, 2010 from the Taiwanese NHIRD administrative data included in the study of PD and ischemic stroke. And of total 511 630 PD cases and 208 713 non-PD subjects were included in the study of PD and AMI. The PD cases were divided into dental prophylaxis, intensive treatment, and PD without treatment groups. The ischemic stroke incidence rates (stroke-IR) and AMI incidence rates (AMI-IR) were assessed among groups during follow-up in the two parts of our research. Cox regression analysis was used to determine the relationship between PD and incidence of ischemic stroke and AMI after adjustment for age, sex, and comorbidities in our research.

Results:
From the finding of our first part of research: the stroke- IR of the non-PD was 0.32%/y. In the PD group, subjects who received dental prophylaxis had the lowest stroke- IR (0.14%/y); subjects with intensive PD treatment or tooth extraction had a higher stroke- IR (0.39%/y); and subjects without PD treatment had the highest stroke- IR (0.48%/y) (p< 0.001). After adjustment for confounders, the dental prophylaxis and intensive treatment groups had a significant lower Hazard Ratio (HR) for ischemic stroke than non- PD group (HR=0.78 and 0.95, 95%CI =0.75-0.81 and 0.91-0.99, respectively), whereas the PD without treatment group had a significant higher HR for stroke (HR=1.15, 95%CI=1.07-1.24), especially among the youngest (20-44) age group (HR=2.17, 95%CI =1.64-2.87) after stratifying for age.
The results of our second part of research showed the AMI-IR for non-PD group was 0.19%/y. In contrast, for the PD group undergoing dental prophylaxis exhibited the lowest AMI-IR (0.11%/y) while subjects applied for intensive treatment and without PD treatment had higher AMI-IR with 0.28%/y and 0.31%/y, respectively (p<0.001). Interestingly, the significant trend relationship of AMI-IR among three PD treatment groups (dental prophylaxis< intensive treatment < without treatment group) was found among all age-, sex-, and comorbidity group. And the dental prophylaxis group had a lower HR for AMI compared to non-PD group (HR=0.89, 95%CI =0.85-0.94) whereas the PD without treatment group had the higherst HR (1.24, 95%CI=1.13-1.36) among all PD groups after adjustment for confounders.

Conclusion:
The dental prophylaxis is a protective factor for both ischemic stroke and AMI. Maintaining periodontal health by receiving dental prophylaxis and PD treatments could decrease the risk of ischemic stroke and AMI.

Significance:
The results of our research provide more information about the association between PD and cardiovascular diseases for clinicians and policy makers to emphasize the importance of oral hygiene and, hopefully, reduce the incidence rates of ischemic stroke and AMI result from PD of people.

Contents
CHAPTER I. INTRODUCTION 1
1.1 BACKGROUNDS 1
1.2 OBJECTIVE 4
1.3 SIGNIFICANCES 5
CHAPTER II. LITERATURE REVIEW 7
2.1 THE RELATIONSHIP BETWEEN PD AND CVD 7
2.2 RISK FACTORS AND COMORBIDITIES FOR CVD 12
CHAPTER III. MATERIALS AND METHODS 19
3.1 STUDY DESIGN 19
3.2 HYPOTHESIS 20
3.3 SUBJECTS 22
3.4 STUDY VARIABLES 32
3.5 STATISTICS 39
CHAPTER IV. RESULTS 42
4.1 THE ASSOCIATION BETWEEN PD AND ISCHEMIC STROKE 42
4.2 THE ASSOCIATION BETWEEN PD AND AMI 48
CHAPTER V. DISCUSSIONS 53
5.1 THE ASSOCIATION BETWEEN PD AND ISCHEMIC STROKE 53
5.2 THE ASSOCIATION BETWEEN PD AND AMI 57
5.3. STRENGTH OF OUR RESEARCH 59
5.4 LIMITATIONS OF OUR RESEARCH 60
CHAPTER VI. CONCLUSIONS 62
REFERENCES 63
Appendices
APPENDIX A : PUBLISHED PAPER
APPENDIX B: SUBMITTED MANUSCRIPT


List of Figures
FIGURE1. POTENTIAL RELATIONSHIPS BETWEEN INFECTIONS, CARDIOVASCULAR RISK FACTORS, CYTOKINE RELEASE, INFLAMMATORY REACTIONS, ATHEROTHROMBOSI 11
FIGURE2. SAMPLE SELECTION FOR “THE ASSOCIATION BETWEEN PD &; ISCHEMIC STROKE” 30
FIGURE3. SAMPLE SELECTION FOR “THE ASSOCIATION BETWEEN PD AND AMI” 31



List of Tables
TABLE1: ICD-9 CM &; PROCEDURE CODES OF “THE ASSOCIATION BETWEEN PD &; ISCHEMIC STROKE” 24
TABLE2: ICD-9CM &; PROCEDURE CODES OF “THE ASSOCIATION BETWEEN PD &; AMI” 25
TABLE 3. VARIABLES USED IN “THE ASSOCIATION BETWEEN PD AND ISCHEMIC STROKE” 40
TABLE 4. VARIABLES USED IN “THE ASSOCIATION BETWEEN PD AND AMI” 41
TABLE 5. BASELINE CHARACTERISTICS OF THE STUDY SUBJECTS 44
TABLE 6. THE STROKE PREVALENCE AMONG STUDY SUBJECTS BY PERIODONTAL DISEASE TYPES 45
TABLE 7. COX REGRESSION MODEL FOR PREDICTOR OF STROKE DEVELOPMENT 47
TABLE 8. BASELINE CHARACTERISTICS OF THE STUDY SUBJECTS 50
TABLE 9. COX REGRESSION MODEL FOR PREDICTOR OF AMI DEVELOPMENT 52

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