Periodontitis and the risk of all-cause and cause-specific mortality among individuals with osteoarthritis in U.S.: A population-based cohort study

Periodontitis and the risk of all-cause and cause-specific mortality among individuals with osteoarthritis in U.S.: A population-based cohort study | Research Square window.SnipcartSettings = { analytics: { enabled: false } }; (function() { var accessVector = localStorage.getItem('access_vector') || ''; window.dataLayer = window.dataLayer || []; if (accessVector) { window.dataLayer.push({ user: { profile: { profileInfo: { snid: accessVector } } } }); } })(); (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start':new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0],j=d.createElement(s),dl=l!='dataLayer'?'&l='+l:'';j.async=true;j.src='https://www.googletagmanager.com/gtm.js?id='+i+dl;f.parentNode.insertBefore(j,f);})(window,document,'script','dataLayer','GTM-K279D39R'); Browse Preprints In Review Journals COVID-19 Preprints AJE Video Bytes Research Tools Research Promotion AJE Professional Editing AJE Rubriq About Preprint Platform In Review Editorial Policies Our Team Advisory Board Help Center Sign In Submit a Preprint Cite Share Download PDF Research Article Periodontitis and the risk of all-cause and cause-specific mortality among individuals with osteoarthritis in U.S.: A population-based cohort study Yuhan He, Ziyi Wang, Shanfeng Lin, Mika Ikegame, Yaxin Qu, Yao Weng, and 4 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-6746901/v1 This work is licensed under a CC BY 4.0 License Status: Posted Version 1 posted You are reading this latest preprint version Abstract Background: The potential association between periodontitis and osteoarthritis (OA) has been widely reported in recent years, but the effect of periodontitis on the mortality of OA participants has yet to be determined. This study was designed to clarify the association between periodontitis and mortality in OA individuals. Methods: This study includes 1,248 OA participants who aged ≥ 30 years from NHANES in the baseline period of 1988-2014. Cox and Weibull models were utilized to calculate hazard ratios (HRs), time ratios (TRs), and 95% confidence intervals (CIs) to examine the correlation between periodontitis and mortality in participants with OA. Results: Over a span of 14.38 years median follow-up, 542 deaths were observed. Moderate-to-severe periodontitis was correlated with all-cause mortality among individuals with OA after adjusting for covariates. (Cox: HR: 1.31, 95% CI: 1.01 – 1.71, P = 0.041; AFT: TR: 0.87, 95% CI: 0.76 - 0.99, P = 0.039). Notably, moderate-to-severe periodontitis increased the risk of CVD-related mortality among female participants (HR: 1.89, 95% CI: 1.18 – 3.02, P = 0.008). However, no significant connection was found between periodontitis and other mortality. Conclusions: This study revealed a higher all-cause mortality in OA participants with moderate-to-severe periodontitis than in those with no/mild periodontitis and also a higher mortality in female participants with moderate-to-severe periodontitis. osteoarthritis periodontitis mortality cardiovascular disease Figures Figure 1 1 INTRODUCTION Osteoarthritis (OA) is a complex degenerative joint disease with pain, socioeconomic disadvantage and disability, causing approximately 2.5 million adults in the U.S. and 250 million worldwide to suffer [1-3] . Primary OA results from the malfunctioning of hyaline cartilage while secondary OA arises from underlying conditions such as diabetes mellitus (DM) and rheumatoid arthritis (RA) [4] . In recent years, studies have highlighted that OA is associated with reduced survival and increased mortality [5] and that individuals with OA are at elevated risk of other systemic diseases that may further impact survival, such as cardiovascular disease (CVD) [6] , which may further compromise longevity and underscore the need for future longitudinal studies. Extending lifespan in individuals with OA remains a key focus of current research. Periodontitis ranks as the second most common oral disease, impacting over 40% of adults in the US, causing tooth mobility and loss [7] . Periodontium (periodontal ligament and alveolar bone) defect caused by dental plaque/biofilm is the main character of this chronic inflammatory oral condition [8] . Major pathogens including Porphyromonas gingivalis and Tannerella forsythia contributes to the disruption of local microbial homeostasis, leading to a microbiota where circulating oral microbial toxins may lead to systemic metastatic damage [9, 10] . Numerous studies revealed periodontitis has a close relation with multiple systemic disease, such as rheumatoid arthritis [11] , cardiovascular disease [12] , diabetes [13] and its effect on oncology, immunology, and neurology have also been gradually demonstrated [14-18] . From the recent report of Kim, J.W. et al, the association between periodontitis and OA was indicated [19, 20] . To further understand this correlation, prognosis and long-term survival of OA individuals remains to be investigated. Under the fact that OA constitutes a serious global disease burden, comprehending the relevant clues is vital for both individuals afflicted with OA and healthcare providers involved in their treatment. To provide insights that are more representative of the U.S. population, we utilized the NHANES database to investigate the correlation between periodontitis and mortality among individuals with OA, insights that are more representative of the U.S. population. 2 METHODS Ethical approval statement The study was conducted in accordance with the Declaration of Helsinki and approved by the National Center for Health Statistics (NCHS) Research Ethics Review Board (ERB) Approval. (https://www.cdc.gov/nchs/nhanes/irba98.htm) Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) reporting guidelines for cohort studies were adhered in this cohort study. Clinical trial number Not applicable . 2.1 Study population In this study, we collected data from NHANES program which provides physical condition and nutrition profile of the U.S. population [21] . This survey obtains a sample that mirrors the characteristics of the population by employing a stratified, multistage probability design. Available periodontal data was sourced from three durations [22] ( Supplementary File 1 ). Participants aged over 30 years with self-reported OA (Individuals who have been diagnosed by a doctor or healthcare expert that they have OA or OA-related symptoms, or they completed a standardized medical status questionnaire concerning about OA) and simultaneously with provided periodontal measurement data were included in this study. Follow-up discontinuation (n=4), expectant and nursing participants (n=3) were excluded. Overall 1,248 participants qualified for the enrollment criteria for this study ( Supplementary Fig. 1 ).We adhered to the STROBE guidelines for cohort studies. Detailed information could be found in Supplementary file 2 . 2.2 Assessment of periodontal status Participants were categorized into moderate-to-severe periodontitis and no/mild periodontitis as previously described [23] . Detailed periodontal estimation was in Supplementary file 1 . Briefly, individuals recorded ≥ 2 interproximal sites with a clinical attachment loss (CAL) ≥ 4 mm or periodontal probing depth (PPD) ≥ 5 mm on the same/ different sites were defined as moderate-to-severe periodontitis. 2.3 Ascertainment of participants mortality outcomes Endpoint outcome (death event) of participants were gained from National Center for Health Statistics (NCHS). Initial time point was set when participants receive periodontal check. The calculation of person-years was from the day of the oral examination and ends at the earliest death event, follow-up discontinuation, or to the date of December 31, 2019. Disease-specific mortality was identified based on the International Statistical Classification of Diseases, 10th Revision (ICD-10) with appropriate ICD-10 codes selected for calculating mortality, including CVD (00-09, 11, 13, 20-51, 60-69), cancer (00-97). 2.4 Assessment of covariates Briefly, directed acyclic graph (DAG) was used to determine the covariates which could be potentially affect the mortality between periodontitis and OA were selected as follows: age, gender, race, socioeconomic status (SES), smoking habit, alcohol consumption, physical activity, and obesity (BMI status) ( Supplementary Fig. 2 ). Associated health disorders such as diabetic condition and hypertension were also considered. SES were performed by income, educational attainment, profession, and medical coverage into a categorical variable with three levels representing ( Supplementary file 1 ). 2.5 Statistical analysis Statistical analyses adhered to NHANES guidelines, considering the complex sampling framework that included the use of weighted samples, cluster grouping, and stratified analysis [24] . Student's t-tests were used for continuous variables and chi-squared tests for categorical variables to compare baseline characteristics between different periodontal states. Kaplan-Meier survival curves were generated to assess differences in mortality between no/mild and moderate-to-severe periodontitis, while cumulative incidence functions (CIF) were used to illustrate changes in mortality over time. The relationship between periodontitis and all-cause mortality was evaluated through Cox models, while competing risk models were employed to evaluate associations with cause-specific mortality [25] . The Weibull model was used to examine the impact of periodontal status on overall lifespan. The study implemented four statistical models to account for confounding variables: Model 0 involved univariate regression analysis; Model 1 accounted for adjustments based on age, gender, and race/ethnicity, while Model 2 additionally included smoking habits, alcohol consumption, and physical activity, and obesity (BMI status); Model 3 included additional covariates such as socioeconomic status (SES), comorbidities and study intervals. Schoenfeld's remainder is used to test the proportional hazard hypothesis. Trend tests were conducted to evaluate the relationship between these quartiles and various mortality outcomes. Restricted cubic spline (RCS) models were employed to investigate potential dose-response relationships, with nonlinear associations assessed using likelihood ratio tests. Stratified analyses based on age and gender were also performed to investigate potential subgroup effects. Further sensitivity analyses were performed to strengthen the data reliability, including: 1). Exclueded participants with less than 2 years of follow-up; 2). Exclueded those with pre-existing cardiovascular disease or cancer; 3). Exclueded those with missing covariate data; 4). Additional analyses without multiple imputation were also conducted. P -value below 0.05 was deemed statistically significant, and all analyses were carried out utilizing R software (version 4.3.1). 3 Results 3.1 Characteristics of osteoarthritis participants A representative data of a total 1248 participants with osteoarthritis in NHANES were collected in this study. Over 18,277 person-years of follow-up (median follow-up of 14.38) of unweighted 1,248 participants, 574 all-cause deaths 192 CVD-related and 108 cancer related was recorded. Among these individuals identified with moderate-to-severe periodontitis are approximately 15 years older than no/mild periodontitis group (mean age 62.9 ± 0.7 vs 58 ± 0.5, P < 0.001) and female is less likely to get moderate-to-severe periodontitis (52.9% vs 71.8%, P < 0.001). Smokers no matter they are a former smoker (41.3% vs 33.9%) or a current smoker (17.3% vs 12.5%, P = 0.018), Light/moderate drinkers (72.9% vs 64.5, P = 0.048), individuals with hypertension (64.3% vs 52.3%, P = 0.002) are more likely to be suffering moderate-to-severe periodontitis. However, we found no significant difference in ethnicity, socioeconomic status (SES), physical status and obesity. Except for hypertension, no differences were observed in comorbidities such as hyperlipidemia and diabetes mellitus ( Table 1 and Supplementary Table 2 ). 3.2 Association between moderate-to-severe periodontitis and all kinds of mortality The CIF analysis suggested CVD-related mortality was significantly higher ( P = 0.039) in the moderate-to-severe periodontitis. However, no significant differences were detected in cancer-related mortality ( P = 0.321) and other mortality rates ( P = 0.058) ( Fig. 1. A ). Moderate-to-severe periodontitis was significantly associated with all-cause ( P < 0.001) and CVD-related ( P < 0.001) mortality among participants with OA according to the crude Kaplan-Meier (KM) analysis ( Fig. 1. B-D ). The absolute rates of all kinds of mortality for moderate-to-severe periodontitis were 32.02% ( all-cause, 95% CI: 31.97 – 32.06), 9.21% (CVD-related, 95% CI: 9.19-9.24), and 3.97% (cancer-related, 95% CI: 6.24 – 6.28). Following adjustment for all covariates, moderate-to-severe periodontitis remained significantly associated with an increasing risk of cancer-related mortality (hazard ratio [HR]: 1.31, 95% CI: 1.01 – 1.71, P = 0.041). Although CVD-related and cancer-related mortality was significantly related to moderate-to-severe periodontitis from crude model, no significant differences were found in their mortality outcomes after covariate adjustment ( Table 2 ). Weibull model showed that OA participants with moderate-to-severe periodontitis had shorter anticipated lifespan for all-cause mortality than those with no/mild periodontitis. (Time ratio: 0.87, 95% CI: 0.76 - 0.99, P = 0.039), while no significant change was observed in CVD or cancer related mortality ( Table 3 ). 3.3 Trend test of periodontitis and stratified analyses In the trend test, no significant association was observed between increasing severity of periodontitis and mortality from any cause, including all-cause, CVD-related, and cancer-related mortality in patients with osteoarthritis. (Table 4 ). Stratified analysis was performed to evaluate the influence of different clinical phenotypes on the outcomes ( Table 4 ). Most HR results demonstrated a positive association between periodontitis and all-cause mortality in participants with OA. ( Supplementary Table 4 ). Notably, among female participants, moderate-to-severe periodontitis increased the risk of CVD-related mortality (HR: 1.89, 95% CI: 1.18 – 3.02, P = 0.008). 3.4 Sensitivity analyses The exclusion of participants whose monitoring period less than 2 years (Supplementary Table 5) had no effect on the results or those diagnosed with cancer or CVD (Supplementary Table 6) . Similarly, when multiple imputations were not performed (Supplementary Tables 7-8) , or when participants with incomplete covariate data were removed ( Supplementary Tables 9-10 ), the findings remained consistent. Supplementary Table 11 also yielded results consistent with the primary analysis. 4 DISCUSSION This nationally population-based cohort study utilized data from the NHANES database to systematically investigate the relation between periodontitis and all-cause along with cause-specific mortality among adults with OA in the United States. The results indicated that periodontitis has a strong correlation with all-cause mortality among OA participants, with the risk escalating alongside the severity of periodontitis. Specifically, individuals with moderate-to-severe periodontitis faced a 31% increased risk of all-cause mortality compared to those with no or mild periodontitis, however, no significant mortality relation was found in CVD and cancer subgroup. Furthermore, moderate-to-severe periodontitis shortens the anticipated lifespan for all-cause mortality by 13% among individuals with OA. Additional covariate adjustments, stratified analyses and various sensitivity analyses confirmed the consistency and stability of these results. Regarding the outcome of the stratified analysis, age-stratified subgroup analysis showed a trend consistent with the overall study findings. Notably, in male participants with periodontitis and OA, a significant association was found with reduced CVD mortality and female subgroup showed periodontitis was associated with an increase in CVD mortality among OA individuals. This finding further supports the previous study that female individuals with periodontitis are more likely to develop osteoarthritis [26] . A variety of studies have assessed the correlation between periodontitis and OA [27] but few studies investigated the correlation between periodontitis and prognosis and long-term survival of OA individuals. A 15-year follow-up cohort study involving a large sample size demonstrated that individuals with periodontitis exhibited an increased risk of developing OA (hazard ratio [HR] = 1.15, 95% confidence interval [CI] = 1.12–1.17, P < 0.001) [26] . Additionally, a significant association was observed between periodontitis and the progression to severe OA, necessitating total knee or hip replacement (TKR/THR). In this study, our findings indicate that periodontitis not only elevates the mortality risk but also substantially reduces the survival time of OA individuals. Notably, female participants reached statistical significance that moderate-to-severe periodontitis increased the risk of CVD-related mortality. Based on our understanding, this is the initial cohort study to establish the correlation between the severity of periodontitis and mortality among OA individuals in U.S. adults. Pathogens associated with periodontitis could be shed into the salivary secretions and have been implicated in the exacerbation of systemic diseases including OA [28, 29] . This may be explained by mechanisms similar to those observed in odontogenic infections, where metastatic inflammation arises from bacterial dissemination. Periodontal pathogens from the subgingival dental plaque/biofilm involves their ability to break the tight junctions of the gingiva [30] . This disruption allows the toxic molecules including outer membrane vesicles (OMVs) secreted from those pathogens to enter the blood vessels and spread to distant joints which could potentially induce secondary OA [31] . Previously, Moen et al. demonstrated this possibility by detecting a higher amount of bacterial genetic material in synovial fluid compared to plasma [32] . Furthermore, DNA from Porphyromonas gingivalis ( Pg ), a major pathogen of periodontitis, was further detected in joint compartments [33] , supporting the hypothesis that oral bacteria or their genetic material can disseminate to distant sites such as the joints. Additionally, periodontitis induces a long-term of low-grade systemic inflammation by increasing serum pro-inflammatory mediators or influences systemic inflammation through changes in the lipid profiles, or thrombotic and hemostatic markers that would thus exacerbate the condition of OA participants [34] . Despite the significant insights gained from our study, certain limitations must be considered carefully. Firstly, only 131 cause-specific death outcomes were recorded in this study. The insufficient sample group diminish the robustness of our conclusions and restrict the scope of further correlation analyses. Secondly, the concurrent collection of periodontitis and related data at baseline might not fully capture the temporal relationship needed to establish causality. Thirdly, differences in periodontal examination methods over the years may have introduced inconsistencies and reduced the reliability of our findings. Finally, comparing with the updating periodontal recording standard, the limited oral quadrant selection and specific tooth examinations could have led to measurement bias and an underestimation of both the occurrence and seriousness of moderate-to-severe periodontitis. In conclusion, this study revealed a higher all-cause mortality in OA participants with moderate-to-severe periodontitis than in those with no/mild periodontitis and also a higher mortality in female participants with moderate-to-severe periodontitis. These insights underscore the importance of integrating periodontal health management into the overall care plan for OA individuals to potentially improve their long-term outcomes. 5 CONCLUSIONS In this study, we found that participants with OA who had moderate-to-severe periodontitis experienced higher overall mortality rates compared to those with no or mild periodontitis. Additionally, female participants with moderate-to-severe periodontitis showed an increased risk of mortality. Abbreviations OA: Osteoarthritis NHANES: National Health and Nutrition Examination Survey HR: Hazard Ratio TR: Time Ratio CI: Confidence Interval CVD: Cardiovascular Disease DM: Diabetes Mellitus RA: Rheumatoid Arthritis CAL: Clinical Attachment Loss PP D: Periodontal Probing Depth ICD-10: International Statistical Classification of Diseases, 10th Revision DAG: Directed Acyclic Graph SES: Socioeconomic Status BMI: Body Mass Index STROBE: Strengthening the Reporting of Observational Studies in Epidemiology CIF: Cumulative Incidence Function RCS: Restricted Cubic Spline AFT: Accelerated Failure Time SE: Standard Error HTN: Hypertension HPL: Hyperlipidemia Pg: Porphyromonas gingivalis OMVs: Outer Membrane Vesicles Declarations Acknowledgments We are grateful for the data provided by National Health and Nutrition Examination Survey. Funding: This work was supported by Chinese Scholarship Council (Grant No. 202208210086) The present work was supported by Grant-in-Aid for Scientific Research (to Ziyi Wang [24K23623 and 25K20204] and to Hiroshi Kamioka [23K2780406]) from the Japan Society for the Promotion of Science, Japan. Conflicts of Interest The authors declare no conflict of interest. Authorship YH. H.: Data curation, formal analysis, investigation, methodology, software, visualization, and writing; ZY. W.: Resources, project administration, and review & editing, SF. L: Data curation, formal analysis, M.I., YX, Q, Y.W, H,S, YL. Z, H.K. H.O: Data curation, formal analysis, review & editing. Ethics approval and consent to participate The NHANES database was approved by the National Center for Health Statistics (NCHS) Institutional Review Board in accordance with the revised Declaration of Helsinki. Informed consent was obtained from all participants prior to data collection and health examinations. 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Baseline characteristics of participants with osteoarthritis according to periodontal status Periodontal status Over all No/ Mild periodontitis Moderate/ Severe periodontitis Characteristics Mean/ % * SE * Mean/ % SE Mean/ % SE P † No.(Unweighted) 1248 740 508 No.(Weighted) 13,643,072 4,926,496 8,716,576 Age (years), mean 59.8 0.4 58 0.5 62.9 0.7 <0.001 Age status, % <0.001 <45 11.8 1.2 14.2 1.7 7.4 1.6 [45, 65) 51.5 2 55.5 2.4 44.5 2.8 ≥65 36.7 1.7 30.3 2 48.1 3 Gender, Female 65 1.8 71.8 2.1 52.9 3.2 <0.001 Race/ ethnicity, % 0.315 Non-Hispanic white 86.1 1.4 87.4 1.4 83.9 2.3 Non-Hispanic black 6.3 0.7 5.9 0.8 7.1 1.2 Hispanic 4.8 0.8 4.5 0.8 5.3 1.3 Other race/ ethnicity 2.8 0.9 2.3 0.9 3.6 1.5 Socioeconomic Status, % 0.140 Low 11.6 1.3 10.5 1.3 13.5 2.2 Medium 55.4 1.9 54.2 2.3 57.3 3 High 33.1 1.9 35.3 2.3 29.2 3.1 Smoking habits , % 0.018 Never smoker 49.2 1.7 53.6 2.6 41.4 3.4 Former smoker 36.6 1.8 33.9 2.6 41.3 3.2 Current smoker 14.2 1.4 12.5 1.5 17.3 2.7 Alcohol consumption, % 0.048 Nondrinker 12.1 1.4 13.8 1.9 9.2 1.7 Light/ moderate drinker 67.5 1.4 64.5 1.9 72.9 2.6 Heavier drinker 20.3 1.5 21.7 2.1 17.9 2.3 Physical status, % 0.187 Inactive 18.5 1.5 18.9 2.1 17.8 2.1 Insufficient 48.9 2 50.9 2.4 45.4 3.5 Recommended 32.6 2 30.2 2.3 36.7 3.2 BMI, Mean 29.6 0.2 29.8 0.3 29.2 0.4 0.281 BMI status (kg/m2), % 0.426 <25 25.4 1.6 24.9 2.1 26.1 2.6 [25.0 -30) 34.4 2.3 33.2 2.5 36.4 3.1 ≥30 40.3 2 41.8 2.5 37.5 3 Comorbidities, % Hypertension 56.6 1.9 52.3 2.4 64.3 3 0.002 Hyperlipidemia 69.9 2 68 2.4 73.1 3.2 0.157 Diabetes mellitus 16.7 1.6 14.9 2 19.9 2.4 0.086 Cohort period, % <0.001 NHANES III 12.4 1.1 12.8 1.4 11.8 1.6 NHANES 1999-2004 56 2.9 61.8 2.9 45.8 4.4 NHANES 2009-2014 31.6 3.1 25.5 2.7 42.4 4.7 No.(Unweighted) 1248 740 508 No.(Weighted) 13,643,072 4,926,496 8,716,576 Age (years), mean 59.8 0.4 58 0.5 62.9 0.7 <0.001 Age status, % <0.001 *Normally distributed continuous variables are described as means ± SEs; Categorical variables are presented as numbers (percentages). All estimates accounted for complex survey designs. †The t test was used for continuous variables and the χ test for categorical variables. Table 2. HR (95% CIs) for All-cause and cause-specific mortality according to periodontitis Periodontal status No/ Mild periodontitis Moderate/ Severe periodontitis P All cause* Deaths/total (Unweighted) 270/740 272/508 Deaths/total (Weighted) 1,994,296/4,926,496 2,356,381/8,716,576 Model 1† 1.00 [Reference] 1.93 (1.53, 2.45) <0.001 Model 2‡ 1.00 [Reference] 1.31 (1.02, 1.68) 0.034 Model 3§ 1.00 [Reference] 1.30 (1.01, 1.68) 0.044 Model 4¶ 1.00 [Reference] 1.31 (1.01, 1.71) 0.041 CVD cause Deaths/total (Unweighted) 99/740 93/508 Deaths/total (Weighted) 573,816/4,926,496 723,876/8,716,576 Model 1 1.00 [Reference] 1.80 (1.25, 2.59) 0.002 Model 2 1.00 [Reference] 1.14 (0.77, 1.69) 0.513 Model 3 1.00 [Reference] 1.16 (0.78, 1.72) 0.466 Model 4 1.00 [Reference] 1.07 (0.73, 1.57) 0.740 Cancer cause Deaths/total (Unweighted) 57/740 51/508 Deaths/total (Weighted) 389,829/4,926,496 514,286/8,716,576 Model 1 1.00 [Reference] 1.71 (1.05, 2.77) 0.031 Model 2 1.00 [Reference] 1.24 (0.76, 2.03) 0.381 Model 3 1.00 [Reference] 1.19 (0.70, 2.02) 0.516 Model 4 1.00 [Reference] 1.36 (0.78, 2.38) 0.280 * All-cause mortality used Cox proportional hazards model, and cause-specific mortality used competing risk model. † Model 1 was univariate analysis. ‡ Model 2 included age (30-44, 45-64 or ≥65 years old), gender, race/ethnicity (non-Hispanic white, non-Hispanic black, Hispanic or other races), § Model 3 additionally included smoking habit (never smokers, former or current smokers), alcohol consumption (nondrinker, heavier drinker, or light/ moderate drinker), physical activity status (inactive, insufficient, recommended) and BMI status (body measure index, normal (≤24.9 [kg/m2]), overweight (25.0-29.9 [kg/m2]), and obesity (≥30.0 [kg/m2]) based on Model 2. ¶ Model 4 was further adjusted for SES (Socioeconomic Status, low, middle, high),，HTN status (hypertension, yes or no) , HPL (hyperlipidemia, yes or no), and diabetes status (yes or no) based on Model 3. Table 3. Time Ratio (95% CIs) for All-cause and cause-specific mortality according to periodontitis by Weibull model. Periodontal status No/ Mild periodontitis Moderate/ Severe periodontitis P All cause* Deaths/total (Unweighted) 270/740 272/508 Deaths/total (Weighted) 1,994,296/4,926,496 2,356,381/8,716,576 Model 1† 1.00 [Reference] 0.67 (0.58, 0.77) <0.001 Model 2‡ 1.00 [Reference] 0.87 (0.76, 0.99) 0.034 Model 3§ 1.00 [Reference] 0.87 (0.77, 1000) 0.047 Model 4¶ 1.00 [Reference] 0.87 (0.76, 0.99) 0.039 CVD cause Deaths/total (Unweighted) 99/740 93/508 Deaths/total (Weighted) 573,816/4,926,496 723,876/8,716,576 Model 1 1.00 [Reference] 0.67 (0.52, 0.88) 0.004 Model 2 1.00 [Reference] 0.94 (0.73, 1.20) 0.602 Model 3 1.00 [Reference] 0.94 (0.73, 1.19) 0.590 Model 4 1.00 [Reference] 0.97 (0.77, 1.24) 0.830 Cancer cause Deaths/total (Unweighted) 57/740 51/508 Deaths/total (Weighted) 389,829/4,926,496 514,286/8,716,576 Model 1 1.00 [Reference] 0.85 (0.63, 1.16) 0.313 Model 2 1.00 [Reference] 0.88 (0.66, 1.18) 0.401 Model 3 1.00 [Reference] 0.91 (0.66, 1.24) 0.544 Model 4 1.00 [Reference] 0.83 (0.59, 1.18) 0.296 *All-cause and Cause-specific mortality used Weibull accelerated failure time model. † Model 1 was univariate analysis. ‡ Model 2 included age (30-44, 45-64 or ≥65 years old), gender, race/ethnicity (non-Hispanic white, non-Hispanic black, Hispanic or other races), § Model 3 additionally included smoking habit (never smokers, former or current smokers), alcohol consumption (nondrinker, heavier drinker, or light/ moderate drinker), physical activity status (inactive, insufficient, recommended) and BMI status (body measure index, normal (≤24.9 [kg/m2]), overweight (25.0-29.9 [kg/m2]), and obesity (≥30.0 [kg/m2]) based on Model 2. ¶ Model 4 was further adjusted for SES (Socioeconomic Status, low, middle, high),，HTN status (hypertension, yes or no) , HPL (hyperlipidemia, yes or no), and diabetes status (yes or no) based on Model 3. Table 4. HR (95% CIs) for All-cause and cause-specific mortality according to status of periodontitis Outcomes Events (Weighted), n/N HR (95% CI) P All cause No/Mild periodontitis 2,356,381/8,716,576 1.00 [Reference] Moderate periodontitis* 1,882,381/4,661,903 1.35 (1.05, 1.73) 0.018 Severe periodontitis 111,915/264,593 0.86 (0.36, 2.06) 0.743 P for trend 1.20 (0.93, 1.55) 0.161 CVD cause* No/Mild periodontitis 723,876/8,716,576 1.00 [Reference] Moderate periodontitis 530,431/4,661,903 1.08 (0.74, 1.60) 0.679 Severe periodontitis 43,385/264,593 0.89 (0.30, 2.64) 0.830 P for trend 1.03 (0.73, 1.45) 0.854 Cancer cause* No/Mild periodontitis 514,286/8,716,576 1.00 [Reference] Moderate periodontitis 352,641/4,661,903 1.33 (0.75, 2.36) 0.332 Severe periodontitis 37,188/264,593 1.95 (0.76, 5.02) 0.164 P for trend 1.35 (0.85, 2.16) 0.205 * All-cause mortality used Cox proportional hazards model, and cause-specific mortality used competing risk model. All the models were adjusted for age (30-44, 45-64 or ≥65 years old), gender (male and female), race/ethnicity (non-Hispanic white, non-Hispanic black, Hispanic, and other races), SES (high, medium, and low level), smoking habit (current smokers, former smokers, and never smokers), alcohol consumption (nondrinkers, heavier drinkers, and light/moderate drinkers), physical activity status (inactive, insufficient, recommended), BMI status (body mass index, normal, overweight, and obesity), HTN status (hypertension, yes or no), HPL (hyperlipidemia status, yes or no), diabetes status (yes or no) and cohort period. Additional Declarations No competing interests reported. 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Also discoverable on Platform About Our Team In Review Editorial Policies Advisory Board Help Center Resources Author Services Accessibility API Access RSS feed Manage Cookie Preferences © Research Square 2026 | ISSN 2693-5015 (online) Privacy Policy Terms of Service Do Not Sell My Personal Information {"props":{"pageProps":{"initialData":{"identity":"rs-6746901","acceptedTermsAndConditions":true,"allowDirectSubmit":true,"archivedVersions":[],"articleType":"Research Article","associatedPublications":[],"authors":[{"id":485438567,"identity":"118f4108-c2cf-47d0-ae3f-9af919d9ff58","order_by":0,"name":"Yuhan He","email":"","orcid":"","institution":"Okayama University","correspondingAuthor":false,"prefix":"","firstName":"Yuhan","middleName":"","lastName":"He","suffix":""},{"id":485438568,"identity":"b24bb796-5edd-4a4f-9f83-fe4d0b29e512","order_by":1,"name":"Ziyi Wang","email":"data:image/png;base64,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","orcid":"","institution":"Okayama University","correspondingAuthor":true,"prefix":"","firstName":"Ziyi","middleName":"","lastName":"Wang","suffix":""},{"id":485438569,"identity":"469bef6c-f7c2-4316-8839-f1f546b3aa11","order_by":2,"name":"Shanfeng Lin","email":"","orcid":"","institution":"China Medical University","correspondingAuthor":false,"prefix":"","firstName":"Shanfeng","middleName":"","lastName":"Lin","suffix":""},{"id":485438570,"identity":"a3c1ee3c-3b96-4f1d-8c68-dd4a7d5fc705","order_by":3,"name":"Mika Ikegame","email":"","orcid":"","institution":"Okayama University","correspondingAuthor":false,"prefix":"","firstName":"Mika","middleName":"","lastName":"Ikegame","suffix":""},{"id":485438574,"identity":"8b29c94c-6fca-4d8f-9ada-5ee6d37f78ba","order_by":4,"name":"Yaxin Qu","email":"","orcid":"","institution":"Okayama University","correspondingAuthor":false,"prefix":"","firstName":"Yaxin","middleName":"","lastName":"Qu","suffix":""},{"id":485438575,"identity":"3d45adf0-616d-423a-9307-2017e226ed10","order_by":5,"name":"Yao Weng","email":"","orcid":"","institution":"Okayama University","correspondingAuthor":false,"prefix":"","firstName":"Yao","middleName":"","lastName":"Weng","suffix":""},{"id":485438576,"identity":"2d2003bb-7746-4eda-9a8b-2b624b684646","order_by":6,"name":"Heriati Sitosari","email":"","orcid":"","institution":"Universitas Gadjah Mada","correspondingAuthor":false,"prefix":"","firstName":"Heriati","middleName":"","lastName":"Sitosari","suffix":""},{"id":485438577,"identity":"93876f4d-e75f-463a-90cd-8135a31b77f3","order_by":7,"name":"Yilin Zheng","email":"","orcid":"","institution":"Okayama University","correspondingAuthor":false,"prefix":"","firstName":"Yilin","middleName":"","lastName":"Zheng","suffix":""},{"id":485438578,"identity":"8d4b3198-7e5b-4e97-a18b-d2fcc95e4fd2","order_by":8,"name":"Hiroshi Kamioka","email":"","orcid":"","institution":"Okayama University","correspondingAuthor":false,"prefix":"","firstName":"Hiroshi","middleName":"","lastName":"Kamioka","suffix":""},{"id":485438579,"identity":"3b869dc9-d992-4680-9406-a9e93e5a3915","order_by":9,"name":"Hirohiko Okamura","email":"","orcid":"","institution":"Okayama University","correspondingAuthor":false,"prefix":"","firstName":"Hirohiko","middleName":"","lastName":"Okamura","suffix":""}],"badges":[],"createdAt":"2025-05-26 04:23:41","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-6746901/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-6746901/v1","draftVersion":[],"editorialEvents":[],"editorialNote":"","failedWorkflow":false,"files":[{"id":87047345,"identity":"f5c99e0c-ae46-43a7-9b76-7a592e38405d","added_by":"auto","created_at":"2025-07-18 14:42:11","extension":"png","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":126759,"visible":true,"origin":"","legend":"\u003cp\u003eAssociation between moderate-to-severe periodontitis and all kinds of mortality. \u003cstrong\u003eA\u003c/strong\u003e. Cumulative incidence of different cause-specific mortality. \u003cstrong\u003eB\u003c/strong\u003e. The weighted Kaplan-Meier analysis of periodontitis with all-cause survival. \u003cstrong\u003eC\u003c/strong\u003e. The weighted Kaplan-Meier analysis of periodontitis with CVD- related survival; \u003cstrong\u003eD\u003c/strong\u003e: The weighted Kaplan-Meier analysis of periodontitis with cancer-related survival.\u003c/p\u003e","description":"","filename":"1.png","url":"https://assets-eu.researchsquare.com/files/rs-6746901/v1/f81125dc1d976e5d5b122115.png"},{"id":91551033,"identity":"bb2c560a-b56f-48a3-b6ca-dd8aa32cac94","added_by":"auto","created_at":"2025-09-17 15:53:26","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":1572322,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-6746901/v1/86aaf77d-bc62-4554-9abe-05547e15fb08.pdf"},{"id":87047344,"identity":"319bbd1e-ed6c-4373-aacb-27e0604be992","added_by":"auto","created_at":"2025-07-18 14:42:11","extension":"docx","order_by":0,"title":"","display":"","copyAsset":false,"role":"supplement","size":34542,"visible":true,"origin":"","legend":"","description":"","filename":"Supplementaryfile1.docx","url":"https://assets-eu.researchsquare.com/files/rs-6746901/v1/9d9d6f943ab9614bec13f723.docx"},{"id":87047347,"identity":"3c5d168e-049a-469a-86f7-d1a74482bf17","added_by":"auto","created_at":"2025-07-18 14:42:11","extension":"docx","order_by":1,"title":"","display":"","copyAsset":false,"role":"supplement","size":660425,"visible":true,"origin":"","legend":"","description":"","filename":"Supplementaryfile2.docx","url":"https://assets-eu.researchsquare.com/files/rs-6746901/v1/1330baff52beafb6997a09dc.docx"}],"financialInterests":"No competing interests reported.","formattedTitle":"Periodontitis and the risk of all-cause and cause-specific mortality among individuals with osteoarthritis in U.S.: A population-based cohort study","fulltext":[{"header":"1 INTRODUCTION","content":"\u003cp\u003eOsteoarthritis (OA) is a complex degenerative joint disease with pain, socioeconomic disadvantage and disability, causing approximately 2.5 million adults in the U.S. and 250 million worldwide to suffer\u003csup\u003e[1-3]\u003c/sup\u003e. Primary OA results from the malfunctioning of hyaline cartilage while secondary OA arises from underlying conditions such as diabetes mellitus (DM) and rheumatoid arthritis (RA)\u003csup\u003e[4]\u003c/sup\u003e. In recent years, studies have highlighted that OA is associated with reduced survival and increased mortality\u003csup\u003e[5]\u003c/sup\u003e and that individuals with OA are at elevated risk of other systemic diseases that may further impact survival, such as cardiovascular disease (CVD)\u003csup\u003e[6]\u003c/sup\u003e, which may further compromise longevity and underscore the need for future longitudinal studies. Extending lifespan in individuals with OA remains a key focus of current research.\u003c/p\u003e\n\u003cp\u003ePeriodontitis ranks as the second most common oral disease, impacting over 40% of adults in the US, causing tooth mobility and loss\u003csup\u003e[7]\u003c/sup\u003e. Periodontium (periodontal ligament and alveolar bone) defect caused by dental plaque/biofilm is the main character of this chronic inflammatory oral condition\u003csup\u003e[8]\u003c/sup\u003e. Major pathogens including \u003cem\u003ePorphyromonas gingivalis\u003c/em\u003e and \u003cem\u003eTannerella forsythia\u003c/em\u003e contributes to the disruption of local microbial homeostasis, leading to a\u0026nbsp;microbiota\u0026nbsp;where circulating oral microbial toxins may lead to systemic metastatic damage\u003csup\u003e[9, 10]\u003c/sup\u003e. Numerous studies revealed periodontitis has a close relation with multiple systemic disease, such as\u0026nbsp;rheumatoid arthritis\u003csup\u003e[11]\u003c/sup\u003e,\u0026nbsp;cardiovascular disease\u003csup\u003e[12]\u003c/sup\u003e,\u0026nbsp;diabetes\u003csup\u003e[13]\u003c/sup\u003e and its effect on oncology, immunology, and neurology have also been gradually demonstrated\u0026nbsp;\u003csup\u003e[14-18]\u003c/sup\u003e.\u003c/p\u003e\n\u003cp\u003eFrom the recent report of Kim, J.W. et al, the association between periodontitis and OA was indicated\u003csup\u003e[19, 20]\u003c/sup\u003e. To further understand this correlation, prognosis and long-term survival of OA individuals remains to be investigated. Under the fact that OA constitutes a serious global disease burden, comprehending the relevant clues is vital for both individuals afflicted with OA and healthcare providers involved in their treatment. To provide insights that are more representative of the U.S. population, we utilized the NHANES database to investigate the correlation between periodontitis and mortality among individuals with OA, insights that are more representative of the U.S. population.\u003c/p\u003e"},{"header":"2 METHODS","content":"\u003cp\u003e\u003cstrong\u003e\u003cem\u003eEthical approval statement\u003c/em\u003e\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe study was conducted in accordance with the Declaration of Helsinki and approved by the National Center for Health Statistics (NCHS) Research Ethics Review Board (ERB) Approval. (https://www.cdc.gov/nchs/nhanes/irba98.htm)\u003c/p\u003e\n\u003cp\u003eStrengthening the Reporting of Observational Studies in Epidemiology (STROBE) reporting guidelines for cohort studies were adhered in this cohort study.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003e\u003cem\u003eClinical trial number\u003c/em\u003e\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eNot applicable\u003cem\u003e.\u003c/em\u003e\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003e\u003cem\u003e2.1 Study population\u003c/em\u003e\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eIn this study, we collected data from NHANES program which provides physical condition and nutrition profile of the U.S. population\u003csup\u003e[21]\u003c/sup\u003e. This survey obtains a sample that mirrors the characteristics of the population by employing a stratified, multistage probability design. Available periodontal data was sourced from three durations\u003csup\u003e[22]\u003c/sup\u003e (\u003cstrong\u003eSupplementary File 1\u003c/strong\u003e). Participants aged over 30 years with self-reported OA (Individuals who have been diagnosed by a doctor or healthcare expert that they have OA or OA-related symptoms, or they completed a standardized medical status questionnaire concerning about OA) and simultaneously with provided periodontal measurement data were included in this study. Follow-up discontinuation (n=4), expectant and nursing participants (n=3) were excluded. Overall 1,248 participants qualified for the enrollment criteria for this study (\u003cstrong\u003eSupplementary Fig. 1\u003c/strong\u003e).We adhered to the STROBE guidelines for cohort studies. Detailed information could be found in \u003cstrong\u003eSupplementary file 2\u003c/strong\u003e.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003e\u003cem\u003e2.2\u0026nbsp;\u003c/em\u003e\u003c/strong\u003e\u003cstrong\u003e\u003cem\u003eAssessment of periodontal status\u0026nbsp;\u003c/em\u003e\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eParticipants were categorized into moderate-to-severe periodontitis and no/mild periodontitis as previously described\u003csup\u003e[23]\u003c/sup\u003e. Detailed periodontal estimation was in \u003cstrong\u003eSupplementary file 1\u003c/strong\u003e. Briefly, individuals recorded \u0026ge; 2 interproximal sites with a clinical attachment loss (CAL) \u0026ge; 4 mm or periodontal probing depth (PPD) \u0026ge; 5 mm on the same/ different sites were defined as moderate-to-severe periodontitis.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003e\u003cem\u003e2.3 Ascertainment of participants mortality outcomes\u003c/em\u003e\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eEndpoint outcome (death event) of participants were gained from National Center for Health Statistics (NCHS).\u0026nbsp;Initial time point was set when participants receive periodontal check. The calculation of person-years was from the day of the oral examination and ends at the earliest death event, follow-up discontinuation, or to the date of December 31, 2019. Disease-specific mortality was identified based on the International Statistical Classification of Diseases, 10th Revision (ICD-10) with appropriate ICD-10 codes selected for calculating mortality, including CVD (00-09, 11, 13, 20-51, 60-69), cancer (00-97).\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003e\u003cem\u003e2.4 Assessment of covariates\u003c/em\u003e\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eBriefly, directed acyclic graph (DAG) was used to determine the covariates which could be potentially affect the mortality between periodontitis and OA were selected as follows: age, gender, race, socioeconomic status (SES), smoking habit, alcohol consumption, physical activity, and obesity (BMI status) (\u003cstrong\u003eSupplementary Fig. 2\u003c/strong\u003e). Associated health disorders such as diabetic condition and hypertension were also considered. SES were performed by income, educational attainment, profession, and medical coverage into a categorical variable with three levels representing (\u003cstrong\u003eSupplementary file 1\u003c/strong\u003e).\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003e\u003cem\u003e2.5 Statistical analysis\u003c/em\u003e\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eStatistical analyses adhered to NHANES guidelines, considering the complex sampling framework that included the use of weighted samples, cluster grouping, and stratified analysis\u003csup\u003e[24]\u003c/sup\u003e. Student\u0026apos;s t-tests were used for continuous variables and chi-squared tests for categorical variables to compare baseline characteristics between different periodontal states. Kaplan-Meier survival curves were generated to assess differences in mortality between no/mild and moderate-to-severe periodontitis, while cumulative incidence functions (CIF) were used to illustrate changes in mortality over time.\u003c/p\u003e\n\u003cp\u003eThe relationship between periodontitis and all-cause mortality was evaluated through Cox models, while competing risk models were employed to evaluate associations with cause-specific mortality\u003csup\u003e[25]\u003c/sup\u003e. The Weibull model was used to examine the impact of periodontal status on overall lifespan. The study implemented four statistical models to account for confounding variables: Model 0 involved univariate regression analysis; Model 1 accounted for adjustments based on age, gender, and race/ethnicity, while Model 2 additionally included smoking habits, alcohol consumption, and physical activity, and obesity (BMI status); Model 3 included additional covariates such as socioeconomic status (SES), comorbidities and study intervals.\u0026nbsp;Schoenfeld\u0026apos;s remainder is used to test the proportional hazard hypothesis.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eTrend tests were conducted to evaluate the relationship between these quartiles and various mortality outcomes. Restricted cubic spline (RCS) models were employed to investigate potential dose-response relationships, with nonlinear associations assessed using likelihood ratio tests. Stratified analyses based on age and gender were also performed to investigate potential subgroup effects.\u003c/p\u003e\n\u003cp\u003eFurther sensitivity analyses were performed to strengthen the data reliability, including: 1). Exclueded participants with less than 2 years of follow-up; 2). Exclueded those with pre-existing cardiovascular disease or cancer; 3). Exclueded those with missing covariate data; 4). Additional analyses without multiple imputation were also conducted.\u0026nbsp;\u003cem\u003eP\u003c/em\u003e-value below 0.05 was deemed statistically significant, and all analyses were carried out utilizing R software (version 4.3.1).\u003c/p\u003e"},{"header":"3 Results","content":"\u003cp\u003e\u003cstrong\u003e\u003cem\u003e3.1 Characteristics of osteoarthritis participants\u003c/em\u003e\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eA representative data of a total 1248 participants with osteoarthritis in NHANES were collected in this study. Over 18,277 person-years of follow-up (median follow-up of 14.38) of unweighted 1,248 participants, 574 all-cause deaths 192 CVD-related and 108 cancer related was recorded.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eAmong these individuals identified with moderate-to-severe periodontitis are approximately 15 years older than no/mild periodontitis group (mean age 62.9 \u0026plusmn; 0.7 vs 58 \u0026plusmn; 0.5, \u003cem\u003eP\u003c/em\u003e \u0026lt; 0.001) and female is less likely to get moderate-to-severe periodontitis (52.9% vs 71.8%,\u003cem\u003e\u0026nbsp;P\u003c/em\u003e \u0026lt; 0.001). Smokers no matter they are a former smoker (41.3% vs 33.9%) or a current smoker (17.3% vs 12.5%,\u003cem\u003e\u0026nbsp;P\u003c/em\u003e = 0.018), Light/moderate drinkers (72.9% vs 64.5, \u003cem\u003eP\u003c/em\u003e = 0.048), individuals with hypertension (64.3% vs 52.3%,\u003cem\u003e\u0026nbsp;P\u003c/em\u003e = 0.002) are more likely to be suffering moderate-to-severe periodontitis. However, we found no significant difference in ethnicity, socioeconomic status (SES), physical status and obesity. Except for hypertension, no differences were observed in comorbidities such as hyperlipidemia and diabetes mellitus (\u003cstrong\u003eTable 1\u0026nbsp;\u003c/strong\u003eand\u003cstrong\u003e\u0026nbsp;Supplementary Table 2\u003c/strong\u003e).\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003e\u003cem\u003e3.2 Association between moderate-to-severe periodontitis and all kinds of mortality\u003c/em\u003e\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe CIF analysis suggested CVD-related mortality was significantly higher (\u003cem\u003eP\u003c/em\u003e = 0.039) in the moderate-to-severe periodontitis. However, no significant differences were detected in cancer-related mortality (\u003cem\u003eP\u003c/em\u003e = 0.321) and other mortality rates (\u003cem\u003eP\u003c/em\u003e = 0.058) (\u003cstrong\u003eFig. 1. A\u003c/strong\u003e). Moderate-to-severe periodontitis was significantly associated with all-cause (\u003cem\u003eP\u003c/em\u003e \u0026lt; 0.001) and CVD-related (\u003cem\u003eP\u003c/em\u003e \u0026lt; 0.001) mortality among participants with OA according to the crude Kaplan-Meier (KM) analysis (\u003cstrong\u003eFig. 1. B-D\u003c/strong\u003e). The absolute rates of all kinds of mortality for moderate-to-severe periodontitis were 32.02%\u003cstrong\u003e\u0026nbsp;(\u003c/strong\u003eall-cause, 95% CI: 31.97 \u0026ndash; 32.06), 9.21% (CVD-related, 95% CI: 9.19-9.24), and 3.97% (cancer-related, 95% CI: 6.24 \u0026ndash; 6.28).\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eFollowing adjustment for all covariates, moderate-to-severe periodontitis remained significantly associated with an increasing risk of cancer-related mortality (hazard ratio [HR]: 1.31, 95% CI: 1.01 \u0026ndash; 1.71, \u003cem\u003eP\u003c/em\u003e = 0.041). Although CVD-related and cancer-related mortality was significantly related to moderate-to-severe periodontitis from crude model, no significant differences were found in their mortality outcomes after covariate adjustment (\u003cstrong\u003eTable 2\u003c/strong\u003e). Weibull model showed that OA participants with moderate-to-severe periodontitis had shorter anticipated lifespan for all-cause mortality than those with no/mild periodontitis. (Time ratio: 0.87, 95% CI: 0.76 - 0.99, \u003cem\u003eP\u003c/em\u003e = 0.039), while no significant change was observed in CVD or cancer related mortality (\u003cstrong\u003eTable 3\u003c/strong\u003e).\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003e\u003cem\u003e3.3 Trend test of periodontitis and stratified analyses\u0026nbsp;\u003c/em\u003e\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eIn the trend test, no significant association was observed between increasing severity of periodontitis and mortality from any cause, including all-cause, CVD-related, and cancer-related mortality in patients with osteoarthritis.\u003cstrong\u003e\u0026nbsp;(Table 4\u003c/strong\u003e).\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eStratified analysis was performed to evaluate the influence of different clinical phenotypes on the outcomes (\u003cstrong\u003eTable 4\u003c/strong\u003e).\u0026nbsp;Most HR results demonstrated a positive association between periodontitis and all-cause mortality in participants with OA. (\u003cstrong\u003eSupplementary Table 4\u003c/strong\u003e). Notably, among female participants, moderate-to-severe periodontitis increased the risk of CVD-related mortality (HR: 1.89, 95% CI: 1.18 \u0026ndash; 3.02, \u003cem\u003eP\u003c/em\u003e = 0.008).\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003e\u003cem\u003e3.4 Sensitivity analyses\u003c/em\u003e\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe exclusion of participants whose monitoring period less than 2 years\u003cstrong\u003e\u0026nbsp;(Supplementary Table 5)\u003c/strong\u003e had no effect on the results or those diagnosed with cancer or CVD \u003cstrong\u003e(Supplementary Table 6)\u003c/strong\u003e. Similarly, when multiple imputations were not performed \u003cstrong\u003e(Supplementary Tables 7-8)\u003c/strong\u003e, or when participants with incomplete covariate data were removed (\u003cstrong\u003eSupplementary Tables 9-10\u003c/strong\u003e), the findings remained consistent. \u003cstrong\u003eSupplementary Table 11\u003c/strong\u003e also yielded results consistent with the primary analysis.\u003c/p\u003e"},{"header":"4 DISCUSSION","content":"\u003cp\u003eThis nationally population-based cohort study utilized data from the NHANES database to systematically investigate the relation between periodontitis and all-cause along with cause-specific mortality among adults with OA in the United States. The results indicated that periodontitis has a strong correlation with all-cause mortality among OA participants, with the risk escalating alongside the severity of periodontitis. Specifically, individuals with moderate-to-severe periodontitis faced a 31% increased risk of all-cause mortality compared to those with no or mild periodontitis, however, no significant mortality relation was found in CVD and cancer subgroup. Furthermore, moderate-to-severe periodontitis shortens the anticipated lifespan for all-cause mortality by 13% among individuals with OA. Additional covariate adjustments, stratified analyses and various sensitivity analyses confirmed the consistency and stability of these results.\u003c/p\u003e\u003cp\u003eRegarding the outcome of the stratified analysis, age-stratified subgroup analysis showed a trend consistent with the overall study findings. Notably, in male participants with periodontitis and OA, a significant association was found with reduced CVD mortality and female subgroup showed periodontitis was associated with an increase in CVD mortality among OA individuals. This finding further supports the previous study that female individuals with periodontitis are more likely to develop osteoarthritis\u003csup\u003e[26]\u003c/sup\u003e.\u003c/p\u003e\u003cp\u003eA variety of studies have assessed the correlation between periodontitis and OA\u003csup\u003e[27]\u003c/sup\u003e but few studies investigated the correlation between periodontitis and prognosis and long-term survival of OA individuals. A 15-year follow-up cohort study involving a large sample size demonstrated that individuals with periodontitis exhibited an increased risk of developing OA (hazard ratio [HR]\u0026thinsp;=\u0026thinsp;1.15, 95% confidence interval [CI]\u0026thinsp;=\u0026thinsp;1.12\u0026ndash;1.17, \u003cem\u003eP\u003c/em\u003e\u0026thinsp;\u0026lt;\u0026thinsp;0.001)\u003csup\u003e[26]\u003c/sup\u003e. Additionally, a significant association was observed between periodontitis and the progression to severe OA, necessitating total knee or hip replacement (TKR/THR).\u003c/p\u003e\u003cp\u003eIn this study, our findings indicate that periodontitis not only elevates the mortality risk but also substantially reduces the survival time of OA individuals. Notably, female participants reached statistical significance that moderate-to-severe periodontitis increased the risk of CVD-related mortality. Based on our understanding, this is the initial cohort study to establish the correlation between the severity of periodontitis and mortality among OA individuals in U.S. adults.\u003c/p\u003e\u003cp\u003ePathogens associated with periodontitis could be shed into the salivary secretions and have been implicated in the exacerbation of systemic diseases including OA\u003csup\u003e[28, 29]\u003c/sup\u003e. This may be explained by mechanisms similar to those observed in odontogenic infections, where metastatic inflammation arises from bacterial dissemination. Periodontal pathogens from the subgingival dental plaque/biofilm involves their ability to break the tight junctions of the gingiva\u003csup\u003e[30]\u003c/sup\u003e. This disruption allows the toxic molecules including outer membrane vesicles (OMVs) secreted from those pathogens to enter the blood vessels and spread to distant joints which could potentially induce secondary OA\u003csup\u003e[31]\u003c/sup\u003e. Previously, Moen et al. demonstrated this possibility by detecting a higher amount of bacterial genetic material in synovial fluid compared to plasma\u003csup\u003e[32]\u003c/sup\u003e. Furthermore, DNA from Porphyromonas gingivalis (\u003cem\u003ePg\u003c/em\u003e), a major pathogen of periodontitis, was further detected in joint compartments\u003csup\u003e[33]\u003c/sup\u003e, supporting the hypothesis that oral bacteria or their genetic material can disseminate to distant sites such as the joints. Additionally, periodontitis induces a long-term of low-grade systemic inflammation by increasing serum pro-inflammatory mediators or influences systemic inflammation through changes in the lipid profiles, or thrombotic and hemostatic markers that would thus exacerbate the condition of OA participants\u003csup\u003e[34]\u003c/sup\u003e.\u003c/p\u003e\u003cp\u003eDespite the significant insights gained from our study, certain limitations must be considered carefully. Firstly, only 131 cause-specific death outcomes were recorded in this study. The insufficient sample group diminish the robustness of our conclusions and restrict the scope of further correlation analyses. Secondly, the concurrent collection of periodontitis and related data at baseline might not fully capture the temporal relationship needed to establish causality. Thirdly, differences in periodontal examination methods over the years may have introduced inconsistencies and reduced the reliability of our findings. Finally, comparing with the updating periodontal recording standard, the limited oral quadrant selection and specific tooth examinations could have led to measurement bias and an underestimation of both the occurrence and seriousness of moderate-to-severe periodontitis.\u003c/p\u003e\u003cp\u003eIn conclusion, this study revealed a higher all-cause mortality in OA participants with moderate-to-severe periodontitis than in those with no/mild periodontitis and also a higher mortality in female participants with moderate-to-severe periodontitis. These insights underscore the importance of integrating periodontal health management into the overall care plan for OA individuals to potentially improve their long-term outcomes.\u003c/p\u003e"},{"header":"5 CONCLUSIONS","content":"\u003cp\u003eIn this study, we found that participants with OA who had moderate-to-severe periodontitis experienced higher overall mortality rates compared to those with no or mild periodontitis. Additionally, female participants with moderate-to-severe periodontitis showed an increased risk of mortality.\u003c/p\u003e"},{"header":"Abbreviations","content":"\u003cp\u003e\u003cstrong\u003eOA:\u0026nbsp;\u003c/strong\u003eOsteoarthritis\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eNHANES:\u0026nbsp;\u003c/strong\u003eNational Health and Nutrition Examination Survey\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eHR:\u0026nbsp;\u003c/strong\u003eHazard Ratio\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eTR:\u0026nbsp;\u003c/strong\u003eTime Ratio\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eCI:\u0026nbsp;\u003c/strong\u003eConfidence Interval\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eCVD:\u003c/strong\u003e Cardiovascular Disease\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eDM:\u0026nbsp;\u003c/strong\u003eDiabetes Mellitus\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eRA:\u0026nbsp;\u003c/strong\u003eRheumatoid Arthritis\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eCAL:\u0026nbsp;\u003c/strong\u003eClinical Attachment Loss\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003ePP\u003c/strong\u003eD: Periodontal Probing Depth\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eICD-10:\u0026nbsp;\u003c/strong\u003eInternational Statistical Classification of Diseases, 10th Revision\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eDAG:\u0026nbsp;\u003c/strong\u003eDirected Acyclic Graph\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eSES:\u0026nbsp;\u003c/strong\u003eSocioeconomic Status\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eBMI:\u0026nbsp;\u003c/strong\u003eBody Mass Index\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eSTROBE:\u0026nbsp;\u003c/strong\u003eStrengthening the Reporting of Observational Studies in Epidemiology\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eCIF:\u0026nbsp;\u003c/strong\u003eCumulative Incidence Function\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eRCS:\u003c/strong\u003e Restricted Cubic Spline\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAFT:\u0026nbsp;\u003c/strong\u003eAccelerated Failure Time\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eSE:\u0026nbsp;\u003c/strong\u003eStandard Error\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eHTN:\u0026nbsp;\u003c/strong\u003eHypertension\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eHPL:\u0026nbsp;\u003c/strong\u003eHyperlipidemia\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003ePg:\u003c/strong\u003e Porphyromonas gingivalis\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eOMVs:\u0026nbsp;\u003c/strong\u003eOuter Membrane Vesicles\u003c/p\u003e"},{"header":"Declarations","content":"\u003cp\u003e\u003cstrong\u003e\u003cem\u003eAcknowledgments\u003c/em\u003e\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eWe are grateful for the data provided by National Health and Nutrition Examination Survey.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003e\u003cem\u003eFunding:\u003c/em\u003e\u003c/strong\u003e This work was supported by Chinese Scholarship Council (Grant No. 202208210086)\u003c/p\u003e\n\u003cp\u003eThe present work was supported by Grant-in-Aid for Scientific Research (to Ziyi Wang [24K23623 and 25K20204] and to Hiroshi Kamioka [23K2780406]) from the Japan Society for the Promotion of Science, Japan.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003e\u003cem\u003eConflicts of Interest\u003c/em\u003e\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe authors declare no conflict of interest.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003e\u003cem\u003eAuthorship\u003c/em\u003e\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eYH. H.: Data curation, formal analysis, investigation, methodology, software, visualization, and writing; ZY. W.: Resources, project administration, and review \u0026amp; editing, SF. L: Data curation, formal analysis, M.I., YX, Q, Y.W, H,S, YL. Z, H.K. H.O: Data curation, formal analysis, review \u0026amp; editing.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003e\u003cem\u003eEthics approval and consent to participate\u003c/em\u003e\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe NHANES database was approved by the National Center for Health Statistics (NCHS) Institutional Review Board in accordance with the revised Declaration of Helsinki. Informed consent was obtained from all participants prior to data collection and health examinations. This secondary data analysis was exempt from review by Okayama University, as the dataset used is de-identified and publicly available.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003e\u003cem\u003eData statement\u003c/em\u003e\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe data and code that support the findings of this study are available from https://github.com/He-Yuhan.\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\n \u003cli\u003eHunter, D.J. and S. Bierma-Zeinstra, \u003cem\u003eOsteoarthritis.\u003c/em\u003e The Lancet, 2019. \u003cstrong\u003e393\u003c/strong\u003e(10182): p. 1745-1759.\u003c/li\u003e\n \u003cli\u003eMendy, A., J. Park, and E.R. Vieira, \u003cem\u003eOsteoarthritis and risk of mortality in the USA: a population-based cohort study.\u003c/em\u003e International journal of epidemiology, 2018. \u003cstrong\u003e47\u003c/strong\u003e(6): p. 1821-1829.\u003c/li\u003e\n \u003cli\u003eMa, K., E. Thota, and T. 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Sima, and A. Pandya, \u003cem\u003eImpact of treating oral disease on preventing vascular diseases: a model-based cost-effectiveness analysis of periodontal treatment among patients with type 2 diabetes.\u003c/em\u003e Diabetes Care, 2020. \u003cstrong\u003e43\u003c/strong\u003e(3): p. 563-571.\u003c/li\u003e\n \u003cli\u003eDizdar, O., et al., \u003cem\u003eIncreased cancer risk in patients with periodontitis.\u003c/em\u003e Current Medical Research and Opinion, 2017. \u003cstrong\u003e33\u003c/strong\u003e(12): p. 2195-2200.\u003c/li\u003e\n \u003cli\u003eHashioka, S., et al., \u003cem\u003eThe possible causal link of periodontitis to neuropsychiatric disorders: more than psychosocial mechanisms.\u003c/em\u003e International journal of molecular sciences, 2019. \u003cstrong\u003e20\u003c/strong\u003e(15): p. 3723.\u003c/li\u003e\n \u003cli\u003eKim, J.W., et al., \u003cem\u003eAssociation of periodontitis with radiographic knee osteoarthritis.\u003c/em\u003e Journal of Periodontology, 2020. \u003cstrong\u003e91\u003c/strong\u003e(3): p. 369-376.\u003c/li\u003e\n \u003cli\u003eDisale, P.R., et al., \u003cem\u003ePrevalence and severity of periodontitis in patients with established rheumatoid arthritis and osteoarthritis.\u003c/em\u003e Journal of family medicine and primary care, 2020. \u003cstrong\u003e9\u003c/strong\u003e(6): p. 2919-2925.\u003c/li\u003e\n \u003cli\u003e\u003cem\u003eIntroduction of National Health and Nutrition Examination Survey\u003c/em\u003e. June 2022; Available from: https://www.cdc.gov/nchs/nhanes/index.htm.\u003c/li\u003e\n \u003cli\u003e\u003cem\u003eNHANES questionnaires, datasets, and related documentation.\u003c/em\u003e June 2022; Available from: https://wwwn.cdc.gov/nchs/nhanes/.\u003c/li\u003e\n \u003cli\u003eTran, D.T., et al., \u003cem\u003eAssessment of partial‐mouth periodontal examination protocols for periodontitis surveillance.\u003c/em\u003e Journal of clinical periodontology, 2014. \u003cstrong\u003e41\u003c/strong\u003e(9): p. 846-852.\u003c/li\u003e\n \u003cli\u003eChen, F., et al., \u003cem\u003eAssociation between periodontitis and mortality of patients with cardiovascular diseases: a cohort study based on NHANES.\u003c/em\u003e Journal of Periodontology, 2024. \u003cstrong\u003e95\u003c/strong\u003e(2): p. 175-184.\u003c/li\u003e\n \u003cli\u003eWolbers, M., et al., \u003cem\u003eCompeting risks analyses: objectives and approaches.\u003c/em\u003e European heart journal, 2014. \u003cstrong\u003e35\u003c/strong\u003e(42): p. 2936-2941.\u003c/li\u003e\n \u003cli\u003eMa, K.S.-K., et al., \u003cem\u003eBidirectional relationship between osteoarthritis and periodontitis: a population-based cohort study over a 15-year follow-up.\u003c/em\u003e Frontiers in immunology, 2022. \u003cstrong\u003e13\u003c/strong\u003e: p. 909783.\u003c/li\u003e\n \u003cli\u003eCoburn, B.W., et al., \u003cem\u003ePerformance of self‐reported measures for periodontitis in rheumatoid arthritis and osteoarthritis.\u003c/em\u003e Journal of periodontology, 2015. \u003cstrong\u003e86\u003c/strong\u003e(1): p. 16-26.\u003c/li\u003e\n \u003cli\u003eChen, B., et al., \u003cem\u003eVariations in oral microbiome profiles in rheumatoid arthritis and osteoarthritis with potential biomarkers for arthritis screening.\u003c/em\u003e Scientific reports, 2018. \u003cstrong\u003e8\u003c/strong\u003e(1): p. 17126.\u003c/li\u003e\n \u003cli\u003eMarchesan, J.T., et al., \u003cem\u003ePorphyromonas gingivalis oral infection exacerbates the development and severity of collagen-induced arthritis.\u003c/em\u003e Arthritis research \u0026amp; therapy, 2013. \u003cstrong\u003e15\u003c/strong\u003e: p. 1-13.\u003c/li\u003e\n \u003cli\u003eHe, Y., et al., \u003cem\u003eOuter membrane vesicles derived from Porphyromonas gingivalis induced cell death with disruption of tight junctions in human lung epithelial cells.\u003c/em\u003e Archives of Oral Biology, 2020. \u003cstrong\u003e118\u003c/strong\u003e: p. 104841.\u003c/li\u003e\n \u003cli\u003eRo\u0026scaron;kar, S. and I. Hafner-Bratkovič, \u003cem\u003eThe role of inflammasomes in osteoarthritis and secondary joint degeneration diseases.\u003c/em\u003e Life, 2022. \u003cstrong\u003e12\u003c/strong\u003e(5): p. 731.\u003c/li\u003e\n \u003cli\u003eMoen, K., et al., \u003cem\u003eSynovial inflammation in active rheumatoid arthritis and psoriatic arthritis facilitates trapping of a variety of oral bacterial DNAs.\u003c/em\u003e Clin Exp Rheumatol, 2006. \u003cstrong\u003e24\u003c/strong\u003e(6): p. 656-63.\u003c/li\u003e\n \u003cli\u003eTotaro, M.C., et al., \u003cem\u003ePorphyromonas gingivalis and the pathogenesis of rheumatoid arthritis: analysis of various compartments including the synovial tissue.\u003c/em\u003e Arthritis Research \u0026amp; Therapy, 2013. \u003cstrong\u003e15\u003c/strong\u003e(3): p. R66.\u003c/li\u003e\n \u003cli\u003eHajishengallis, G., \u003cem\u003ePeriodontitis: from microbial immune subversion to systemic inflammation.\u003c/em\u003e Nature reviews immunology, 2015. \u003cstrong\u003e15\u003c/strong\u003e(1): p. 30-44.\u003c/li\u003e\n\u003c/ol\u003e"},{"header":"Tables","content":"\u003ctable border=\"0\" cellspacing=\"0\" cellpadding=\"0\" width=\"589\"\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd colspan=\"8\" style=\"width: 589px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eTable 1. Baseline characteristics of participants with osteoarthritis according to periodontal status\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 172px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 67px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 41px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"4\" style=\"width: 252px;\"\u003e\n \u003cp\u003ePeriodontal status\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 57px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 172px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"2\" style=\"width: 108px;\"\u003e\n \u003cp\u003eOver all\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"2\" style=\"width: 119px;\"\u003e\n \u003cp\u003eNo/ Mild periodontitis\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"2\" style=\"width: 133px;\"\u003e\n \u003cp\u003eModerate/ Severe periodontitis\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 57px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 172px;\"\u003e\n \u003cp\u003eCharacteristics\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 67px;\"\u003e\n \u003cp\u003eMean/ %\u003csup\u003e*\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 41px;\"\u003e\n \u003cp\u003eSE\u003csup\u003e*\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 78px;\"\u003e\n \u003cp\u003eMean/ %\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 41px;\"\u003e\n \u003cp\u003eSE\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 64px;\"\u003e\n \u003cp\u003eMean/ %\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 69px;\"\u003e\n \u003cp\u003eSE\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 57px;\"\u003e\n \u003cp\u003e\u003cem\u003eP\u003c/em\u003e\u003csup\u003e\u0026dagger;\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 172px;\"\u003e\n \u003cp\u003eNo.(Unweighted)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"2\" valign=\"top\" style=\"width: 108px;\"\u003e\n \u003cp\u003e1248\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"2\" valign=\"top\" style=\"width: 119px;\"\u003e\n \u003cp\u003e740\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"2\" valign=\"top\" style=\"width: 133px;\"\u003e\n \u003cp\u003e508\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 57px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 172px;\"\u003e\n \u003cp\u003eNo.(Weighted)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"2\" valign=\"top\" style=\"width: 108px;\"\u003e\n \u003cp\u003e13,643,072\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"2\" valign=\"top\" style=\"width: 119px;\"\u003e\n \u003cp\u003e4,926,496\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"2\" valign=\"top\" style=\"width: 133px;\"\u003e\n \u003cp\u003e8,716,576\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 57px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 172px;\"\u003e\n \u003cp\u003eAge (years), mean\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 67px;\"\u003e\n \u003cp\u003e59.8\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 41px;\"\u003e\n \u003cp\u003e0.4\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 78px;\"\u003e\n \u003cp\u003e58\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 41px;\"\u003e\n \u003cp\u003e0.5\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 64px;\"\u003e\n \u003cp\u003e62.9\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 69px;\"\u003e\n \u003cp\u003e0.7\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 57px;\"\u003e\n \u003cp\u003e\u0026lt;0.001\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 172px;\"\u003e\n \u003cp\u003eAge status, %\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 67px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 41px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 78px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 41px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 64px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 69px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 57px;\"\u003e\n \u003cp\u003e\u0026lt;0.001\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 172px;\"\u003e\n \u003cp\u003e\u0026lt;45\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 67px;\"\u003e\n \u003cp\u003e11.8\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 41px;\"\u003e\n \u003cp\u003e1.2\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 78px;\"\u003e\n \u003cp\u003e14.2\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 41px;\"\u003e\n \u003cp\u003e1.7\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 64px;\"\u003e\n \u003cp\u003e7.4\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 69px;\"\u003e\n \u003cp\u003e1.6\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 57px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 172px;\"\u003e\n \u003cp\u003e[45, 65)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 67px;\"\u003e\n \u003cp\u003e51.5\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 41px;\"\u003e\n \u003cp\u003e2\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 78px;\"\u003e\n \u003cp\u003e55.5\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 41px;\"\u003e\n \u003cp\u003e2.4\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 64px;\"\u003e\n \u003cp\u003e44.5\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 69px;\"\u003e\n \u003cp\u003e2.8\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 57px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 172px;\"\u003e\n \u003cp\u003e\u0026ge;65\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 67px;\"\u003e\n \u003cp\u003e36.7\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 41px;\"\u003e\n \u003cp\u003e1.7\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 78px;\"\u003e\n \u003cp\u003e30.3\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 41px;\"\u003e\n \u003cp\u003e2\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 64px;\"\u003e\n \u003cp\u003e48.1\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 69px;\"\u003e\n \u003cp\u003e3\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 57px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 172px;\"\u003e\n \u003cp\u003eGender, Female\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 67px;\"\u003e\n \u003cp\u003e65\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 41px;\"\u003e\n \u003cp\u003e1.8\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 78px;\"\u003e\n \u003cp\u003e71.8\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 41px;\"\u003e\n \u003cp\u003e2.1\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 64px;\"\u003e\n \u003cp\u003e52.9\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 69px;\"\u003e\n \u003cp\u003e3.2\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 57px;\"\u003e\n \u003cp\u003e\u0026lt;0.001\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 172px;\"\u003e\n \u003cp\u003eRace/ ethnicity, %\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 67px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 41px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 78px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 41px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 64px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 69px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 57px;\"\u003e\n \u003cp\u003e0.315\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 172px;\"\u003e\n \u003cp\u003eNon-Hispanic white\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 67px;\"\u003e\n \u003cp\u003e86.1\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 41px;\"\u003e\n \u003cp\u003e1.4\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 78px;\"\u003e\n \u003cp\u003e87.4\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 41px;\"\u003e\n \u003cp\u003e1.4\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 64px;\"\u003e\n \u003cp\u003e83.9\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 69px;\"\u003e\n \u003cp\u003e2.3\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 57px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 172px;\"\u003e\n \u003cp\u003eNon-Hispanic black\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 67px;\"\u003e\n \u003cp\u003e6.3\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 41px;\"\u003e\n \u003cp\u003e0.7\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 78px;\"\u003e\n \u003cp\u003e5.9\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 41px;\"\u003e\n \u003cp\u003e0.8\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 64px;\"\u003e\n \u003cp\u003e7.1\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 69px;\"\u003e\n \u003cp\u003e1.2\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 57px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 172px;\"\u003e\n \u003cp\u003eHispanic\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 67px;\"\u003e\n \u003cp\u003e4.8\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 41px;\"\u003e\n \u003cp\u003e0.8\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 78px;\"\u003e\n \u003cp\u003e4.5\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 41px;\"\u003e\n \u003cp\u003e0.8\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 64px;\"\u003e\n \u003cp\u003e5.3\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 69px;\"\u003e\n \u003cp\u003e1.3\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 57px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 172px;\"\u003e\n \u003cp\u003eOther race/ ethnicity\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 67px;\"\u003e\n \u003cp\u003e2.8\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 41px;\"\u003e\n \u003cp\u003e0.9\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 78px;\"\u003e\n \u003cp\u003e2.3\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 41px;\"\u003e\n \u003cp\u003e0.9\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 64px;\"\u003e\n \u003cp\u003e3.6\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 69px;\"\u003e\n \u003cp\u003e1.5\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 57px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 172px;\"\u003e\n \u003cp\u003eSocioeconomic Status, %\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 67px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 41px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 78px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 41px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 64px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 69px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 57px;\"\u003e\n \u003cp\u003e0.140\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 172px;\"\u003e\n \u003cp\u003eLow\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 67px;\"\u003e\n \u003cp\u003e11.6\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 41px;\"\u003e\n \u003cp\u003e1.3\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 78px;\"\u003e\n \u003cp\u003e10.5\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 41px;\"\u003e\n \u003cp\u003e1.3\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 64px;\"\u003e\n \u003cp\u003e13.5\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 69px;\"\u003e\n \u003cp\u003e2.2\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 57px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 172px;\"\u003e\n \u003cp\u003eMedium\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 67px;\"\u003e\n \u003cp\u003e55.4\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 41px;\"\u003e\n \u003cp\u003e1.9\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 78px;\"\u003e\n \u003cp\u003e54.2\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 41px;\"\u003e\n \u003cp\u003e2.3\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 64px;\"\u003e\n \u003cp\u003e57.3\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 69px;\"\u003e\n \u003cp\u003e3\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 57px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 172px;\"\u003e\n \u003cp\u003eHigh\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 67px;\"\u003e\n \u003cp\u003e33.1\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 41px;\"\u003e\n \u003cp\u003e1.9\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 78px;\"\u003e\n \u003cp\u003e35.3\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 41px;\"\u003e\n \u003cp\u003e2.3\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 64px;\"\u003e\n \u003cp\u003e29.2\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 69px;\"\u003e\n \u003cp\u003e3.1\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 57px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 172px;\"\u003e\n \u003cp\u003eSmoking habits\u003c/p\u003e\n \u003cp\u003e, %\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 67px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 41px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 78px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 41px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 64px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 69px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 57px;\"\u003e\n \u003cp\u003e0.018\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 172px;\"\u003e\n \u003cp\u003eNever smoker\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 67px;\"\u003e\n \u003cp\u003e49.2\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 41px;\"\u003e\n \u003cp\u003e1.7\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 78px;\"\u003e\n \u003cp\u003e53.6\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 41px;\"\u003e\n \u003cp\u003e2.6\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 64px;\"\u003e\n \u003cp\u003e41.4\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 69px;\"\u003e\n \u003cp\u003e3.4\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 57px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 172px;\"\u003e\n \u003cp\u003eFormer smoker\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 67px;\"\u003e\n \u003cp\u003e36.6\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 41px;\"\u003e\n \u003cp\u003e1.8\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 78px;\"\u003e\n \u003cp\u003e33.9\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 41px;\"\u003e\n \u003cp\u003e2.6\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 64px;\"\u003e\n \u003cp\u003e41.3\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 69px;\"\u003e\n \u003cp\u003e3.2\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 57px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 172px;\"\u003e\n \u003cp\u003eCurrent smoker\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 67px;\"\u003e\n \u003cp\u003e14.2\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 41px;\"\u003e\n \u003cp\u003e1.4\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 78px;\"\u003e\n \u003cp\u003e12.5\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 41px;\"\u003e\n \u003cp\u003e1.5\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 64px;\"\u003e\n \u003cp\u003e17.3\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 69px;\"\u003e\n \u003cp\u003e2.7\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 57px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 172px;\"\u003e\n \u003cp\u003eAlcohol consumption, %\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 67px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 41px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 78px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 41px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 64px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 69px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 57px;\"\u003e\n \u003cp\u003e0.048\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 172px;\"\u003e\n \u003cp\u003eNondrinker\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 67px;\"\u003e\n \u003cp\u003e12.1\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 41px;\"\u003e\n \u003cp\u003e1.4\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 78px;\"\u003e\n \u003cp\u003e13.8\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 41px;\"\u003e\n \u003cp\u003e1.9\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 64px;\"\u003e\n \u003cp\u003e9.2\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 69px;\"\u003e\n \u003cp\u003e1.7\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 57px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 172px;\"\u003e\n \u003cp\u003eLight/ moderate drinker\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 67px;\"\u003e\n \u003cp\u003e67.5\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 41px;\"\u003e\n \u003cp\u003e1.4\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 78px;\"\u003e\n \u003cp\u003e64.5\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 41px;\"\u003e\n \u003cp\u003e1.9\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 64px;\"\u003e\n \u003cp\u003e72.9\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 69px;\"\u003e\n \u003cp\u003e2.6\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 57px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 172px;\"\u003e\n \u003cp\u003eHeavier drinker\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 67px;\"\u003e\n \u003cp\u003e20.3\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 41px;\"\u003e\n \u003cp\u003e1.5\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 78px;\"\u003e\n \u003cp\u003e21.7\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 41px;\"\u003e\n \u003cp\u003e2.1\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 64px;\"\u003e\n \u003cp\u003e17.9\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 69px;\"\u003e\n \u003cp\u003e2.3\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 57px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 172px;\"\u003e\n \u003cp\u003ePhysical status, %\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 67px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 41px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 78px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 41px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 64px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 69px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 57px;\"\u003e\n \u003cp\u003e0.187\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 172px;\"\u003e\n \u003cp\u003eInactive\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 67px;\"\u003e\n \u003cp\u003e18.5\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 41px;\"\u003e\n \u003cp\u003e1.5\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 78px;\"\u003e\n \u003cp\u003e18.9\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 41px;\"\u003e\n \u003cp\u003e2.1\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 64px;\"\u003e\n \u003cp\u003e17.8\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 69px;\"\u003e\n \u003cp\u003e2.1\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 57px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 172px;\"\u003e\n \u003cp\u003eInsufficient\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 67px;\"\u003e\n \u003cp\u003e48.9\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 41px;\"\u003e\n \u003cp\u003e2\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 78px;\"\u003e\n \u003cp\u003e50.9\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 41px;\"\u003e\n \u003cp\u003e2.4\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 64px;\"\u003e\n \u003cp\u003e45.4\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 69px;\"\u003e\n \u003cp\u003e3.5\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 57px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 172px;\"\u003e\n \u003cp\u003eRecommended\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 67px;\"\u003e\n \u003cp\u003e32.6\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 41px;\"\u003e\n \u003cp\u003e2\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 78px;\"\u003e\n \u003cp\u003e30.2\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 41px;\"\u003e\n \u003cp\u003e2.3\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 64px;\"\u003e\n \u003cp\u003e36.7\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 69px;\"\u003e\n \u003cp\u003e3.2\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 57px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 172px;\"\u003e\n \u003cp\u003eBMI, Mean\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 67px;\"\u003e\n \u003cp\u003e29.6\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 41px;\"\u003e\n \u003cp\u003e0.2\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 78px;\"\u003e\n \u003cp\u003e29.8\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 41px;\"\u003e\n \u003cp\u003e0.3\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 64px;\"\u003e\n \u003cp\u003e29.2\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 69px;\"\u003e\n \u003cp\u003e0.4\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 57px;\"\u003e\n \u003cp\u003e0.281\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 172px;\"\u003e\n \u003cp\u003eBMI status (kg/m2), %\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 67px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 41px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 78px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 41px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 64px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 69px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 57px;\"\u003e\n \u003cp\u003e0.426\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 172px;\"\u003e\n \u003cp\u003e\u0026lt;25\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 67px;\"\u003e\n \u003cp\u003e25.4\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 41px;\"\u003e\n \u003cp\u003e1.6\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 78px;\"\u003e\n \u003cp\u003e24.9\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 41px;\"\u003e\n \u003cp\u003e2.1\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 64px;\"\u003e\n \u003cp\u003e26.1\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 69px;\"\u003e\n \u003cp\u003e2.6\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 57px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 172px;\"\u003e\n \u003cp\u003e[25.0 -30)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 67px;\"\u003e\n \u003cp\u003e34.4\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 41px;\"\u003e\n \u003cp\u003e2.3\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 78px;\"\u003e\n \u003cp\u003e33.2\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 41px;\"\u003e\n \u003cp\u003e2.5\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 64px;\"\u003e\n \u003cp\u003e36.4\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 69px;\"\u003e\n \u003cp\u003e3.1\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 57px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 172px;\"\u003e\n \u003cp\u003e\u0026ge;30\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 67px;\"\u003e\n \u003cp\u003e40.3\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 41px;\"\u003e\n \u003cp\u003e2\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 78px;\"\u003e\n \u003cp\u003e41.8\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 41px;\"\u003e\n \u003cp\u003e2.5\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 64px;\"\u003e\n \u003cp\u003e37.5\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 69px;\"\u003e\n \u003cp\u003e3\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 57px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 172px;\"\u003e\n \u003cp\u003eComorbidities, %\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 67px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 41px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 78px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 41px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 64px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 69px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 57px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 172px;\"\u003e\n \u003cp\u003eHypertension\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 67px;\"\u003e\n \u003cp\u003e56.6\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 41px;\"\u003e\n \u003cp\u003e1.9\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 78px;\"\u003e\n \u003cp\u003e52.3\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 41px;\"\u003e\n \u003cp\u003e2.4\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 64px;\"\u003e\n \u003cp\u003e64.3\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 69px;\"\u003e\n \u003cp\u003e3\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 57px;\"\u003e\n \u003cp\u003e0.002\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 172px;\"\u003e\n \u003cp\u003eHyperlipidemia\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 67px;\"\u003e\n \u003cp\u003e69.9\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 41px;\"\u003e\n \u003cp\u003e2\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 78px;\"\u003e\n \u003cp\u003e68\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 41px;\"\u003e\n \u003cp\u003e2.4\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 64px;\"\u003e\n \u003cp\u003e73.1\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 69px;\"\u003e\n \u003cp\u003e3.2\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 57px;\"\u003e\n \u003cp\u003e0.157\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 172px;\"\u003e\n \u003cp\u003eDiabetes mellitus\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 67px;\"\u003e\n \u003cp\u003e16.7\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 41px;\"\u003e\n \u003cp\u003e1.6\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 78px;\"\u003e\n \u003cp\u003e14.9\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 41px;\"\u003e\n \u003cp\u003e2\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 64px;\"\u003e\n \u003cp\u003e19.9\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 69px;\"\u003e\n \u003cp\u003e2.4\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 57px;\"\u003e\n \u003cp\u003e0.086\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 172px;\"\u003e\n \u003cp\u003eCohort period, %\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 67px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 41px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 78px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 41px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 64px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 69px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 57px;\"\u003e\n \u003cp\u003e\u0026lt;0.001\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 172px;\"\u003e\n \u003cp\u003eNHANES III\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 67px;\"\u003e\n \u003cp\u003e12.4\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 41px;\"\u003e\n \u003cp\u003e1.1\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 78px;\"\u003e\n \u003cp\u003e12.8\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 41px;\"\u003e\n \u003cp\u003e1.4\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 64px;\"\u003e\n \u003cp\u003e11.8\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 69px;\"\u003e\n \u003cp\u003e1.6\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 57px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 172px;\"\u003e\n \u003cp\u003eNHANES 1999-2004\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 67px;\"\u003e\n \u003cp\u003e56\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 41px;\"\u003e\n \u003cp\u003e2.9\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 78px;\"\u003e\n \u003cp\u003e61.8\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 41px;\"\u003e\n \u003cp\u003e2.9\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 64px;\"\u003e\n \u003cp\u003e45.8\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 69px;\"\u003e\n \u003cp\u003e4.4\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 57px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 172px;\"\u003e\n \u003cp\u003eNHANES 2009-2014\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 67px;\"\u003e\n \u003cp\u003e31.6\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 41px;\"\u003e\n \u003cp\u003e3.1\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 78px;\"\u003e\n \u003cp\u003e25.5\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 41px;\"\u003e\n \u003cp\u003e2.7\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 64px;\"\u003e\n \u003cp\u003e42.4\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 69px;\"\u003e\n \u003cp\u003e4.7\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 57px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 172px;\"\u003e\n \u003cp\u003eNo.(Unweighted)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 67px;\"\u003e\n \u003cp\u003e1248\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 41px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 78px;\"\u003e\n \u003cp\u003e740\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 41px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 64px;\"\u003e\n \u003cp\u003e508\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 69px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 57px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 172px;\"\u003e\n \u003cp\u003eNo.(Weighted)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 67px;\"\u003e\n \u003cp\u003e13,643,072\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 41px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 78px;\"\u003e\n \u003cp\u003e4,926,496\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 41px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 64px;\"\u003e\n \u003cp\u003e8,716,576\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 69px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 57px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 172px;\"\u003e\n \u003cp\u003eAge (years), mean\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 67px;\"\u003e\n \u003cp\u003e59.8\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 41px;\"\u003e\n \u003cp\u003e0.4\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 78px;\"\u003e\n \u003cp\u003e58\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 41px;\"\u003e\n \u003cp\u003e0.5\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 64px;\"\u003e\n \u003cp\u003e62.9\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 69px;\"\u003e\n \u003cp\u003e0.7\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 57px;\"\u003e\n \u003cp\u003e\u0026lt;0.001\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 172px;\"\u003e\n \u003cp\u003eAge status, %\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 67px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 41px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 78px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 41px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 64px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 69px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 57px;\"\u003e\n \u003cp\u003e\u0026lt;0.001\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd colspan=\"8\" style=\"width: 589px;\"\u003e\n \u003cp\u003e*Normally distributed continuous variables are described as means \u0026plusmn; SEs; Categorical variables are presented as numbers (percentages). All estimates accounted for complex survey designs.\u003c/p\u003e\n \u003cp\u003e\u0026dagger;The t test was used for continuous variables and the \u0026chi; test for categorical variables.\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n\u003c/table\u003e\n\u003cp\u003e\u0026nbsp;\u003c/p\u003e\n\u003ctable border=\"0\" cellspacing=\"0\" cellpadding=\"0\" width=\"100%\"\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd colspan=\"4\" style=\"width: 100px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eTable 2. HR (95% CIs) for All-cause and cause-specific mortality according to periodontitis\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 33px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"2\" style=\"width: 56px;\"\u003e\n \u003cp\u003ePeriodontal status\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 10px;\"\u003e\n \u003cp\u003e\u003cem\u003e\u0026nbsp;\u003c/em\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 33px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 24px;\"\u003e\n \u003cp\u003eNo/ Mild periodontitis\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 32px;\"\u003e\n \u003cp\u003eModerate/ Severe periodontitis\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 10px;\"\u003e\n \u003cp\u003e\u003cem\u003eP\u003c/em\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 33px;\"\u003e\n \u003cp\u003eAll cause*\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 24px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 32px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 10px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 33px;\"\u003e\n \u003cp\u003eDeaths/total (Unweighted)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 24px;\"\u003e\n \u003cp\u003e270/740\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 32px;\"\u003e\n \u003cp\u003e272/508\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 10px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 33px;\"\u003e\n \u003cp\u003eDeaths/total (Weighted)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 24px;\"\u003e\n \u003cp\u003e1,994,296/4,926,496\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 32px;\"\u003e\n \u003cp\u003e2,356,381/8,716,576\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 10px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 33px;\"\u003e\n \u003cp\u003eModel 1\u0026dagger;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 24px;\"\u003e\n \u003cp\u003e1.00 [Reference]\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 32px;\"\u003e\n \u003cp\u003e1.93 (1.53, 2.45)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 10px;\"\u003e\n \u003cp\u003e\u0026lt;0.001\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 33px;\"\u003e\n \u003cp\u003eModel 2\u0026Dagger;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 24px;\"\u003e\n \u003cp\u003e1.00 [Reference]\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 32px;\"\u003e\n \u003cp\u003e1.31 (1.02, 1.68)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 10px;\"\u003e\n \u003cp\u003e0.034\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 33px;\"\u003e\n \u003cp\u003eModel 3\u0026sect;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 24px;\"\u003e\n \u003cp\u003e1.00 [Reference]\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 32px;\"\u003e\n \u003cp\u003e1.30 (1.01, 1.68)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 10px;\"\u003e\n \u003cp\u003e0.044\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 33px;\"\u003e\n \u003cp\u003eModel 4\u0026para;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 24px;\"\u003e\n \u003cp\u003e1.00 [Reference]\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 32px;\"\u003e\n \u003cp\u003e1.31 (1.01, 1.71)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 10px;\"\u003e\n \u003cp\u003e0.041\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 33px;\"\u003e\n \u003cp\u003eCVD cause\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 24px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 32px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 10px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 33px;\"\u003e\n \u003cp\u003eDeaths/total (Unweighted)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 24px;\"\u003e\n \u003cp\u003e99/740\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 32px;\"\u003e\n \u003cp\u003e93/508\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 10px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 33px;\"\u003e\n \u003cp\u003eDeaths/total (Weighted)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 24px;\"\u003e\n \u003cp\u003e573,816/4,926,496\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 32px;\"\u003e\n \u003cp\u003e723,876/8,716,576\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 10px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 33px;\"\u003e\n \u003cp\u003eModel 1\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 24px;\"\u003e\n \u003cp\u003e1.00 [Reference]\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 32px;\"\u003e\n \u003cp\u003e1.80 (1.25, 2.59)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 10px;\"\u003e\n \u003cp\u003e0.002\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 33px;\"\u003e\n \u003cp\u003eModel 2\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 24px;\"\u003e\n \u003cp\u003e1.00 [Reference]\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 32px;\"\u003e\n \u003cp\u003e1.14 (0.77, 1.69)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 10px;\"\u003e\n \u003cp\u003e0.513\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 33px;\"\u003e\n \u003cp\u003eModel 3\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 24px;\"\u003e\n \u003cp\u003e1.00 [Reference]\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 32px;\"\u003e\n \u003cp\u003e1.16 (0.78, 1.72)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 10px;\"\u003e\n \u003cp\u003e0.466\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 33px;\"\u003e\n \u003cp\u003eModel 4\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 24px;\"\u003e\n \u003cp\u003e1.00 [Reference]\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 32px;\"\u003e\n \u003cp\u003e1.07 (0.73, 1.57)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 10px;\"\u003e\n \u003cp\u003e0.740\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 33px;\"\u003e\n \u003cp\u003eCancer cause\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 24px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 32px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 10px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 33px;\"\u003e\n \u003cp\u003eDeaths/total (Unweighted)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 24px;\"\u003e\n \u003cp\u003e57/740\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 32px;\"\u003e\n \u003cp\u003e51/508\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 10px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 33px;\"\u003e\n \u003cp\u003eDeaths/total (Weighted)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 24px;\"\u003e\n \u003cp\u003e389,829/4,926,496\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 32px;\"\u003e\n \u003cp\u003e514,286/8,716,576\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 10px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 33px;\"\u003e\n \u003cp\u003eModel 1\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 24px;\"\u003e\n \u003cp\u003e1.00 [Reference]\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 32px;\"\u003e\n \u003cp\u003e1.71 (1.05, 2.77)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 10px;\"\u003e\n \u003cp\u003e0.031\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 33px;\"\u003e\n \u003cp\u003eModel 2\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 24px;\"\u003e\n \u003cp\u003e1.00 [Reference]\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 32px;\"\u003e\n \u003cp\u003e1.24 (0.76, 2.03)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 10px;\"\u003e\n \u003cp\u003e0.381\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 33px;\"\u003e\n \u003cp\u003eModel 3\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 24px;\"\u003e\n \u003cp\u003e1.00 [Reference]\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 32px;\"\u003e\n \u003cp\u003e1.19 (0.70, 2.02)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 10px;\"\u003e\n \u003cp\u003e0.516\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 33px;\"\u003e\n \u003cp\u003eModel 4\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 24px;\"\u003e\n \u003cp\u003e1.00 [Reference]\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 32px;\"\u003e\n \u003cp\u003e1.36 (0.78, 2.38)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 10px;\"\u003e\n \u003cp\u003e0.280\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd colspan=\"4\" style=\"width: 100px;\"\u003e\n \u003cp\u003e* All-cause mortality used Cox proportional hazards model, and cause-specific mortality used competing risk model.\u003c/p\u003e\n \u003cp\u003e\u0026dagger; Model 1 was univariate analysis. \u0026nbsp;\u003c/p\u003e\n \u003cp\u003e\u0026Dagger; Model 2 included age (30-44, 45-64 or \u0026ge;65 years old), gender, race/ethnicity (non-Hispanic white, non-Hispanic black, Hispanic or other races), \u0026sect; Model 3 additionally included smoking habit (never smokers, former or current smokers), alcohol consumption (nondrinker, heavier drinker, or light/ moderate drinker), physical activity status (inactive, insufficient, recommended) and BMI status (body measure index, normal (\u0026le;24.9 [kg/m2]), overweight (25.0-29.9 [kg/m2]), and obesity (\u0026ge;30.0 [kg/m2]) based on Model 2.\u003c/p\u003e\n \u003cp\u003e\u0026para; Model 4 was further adjusted for SES (Socioeconomic Status, low, middle, high),，HTN status (hypertension, yes or no) , HPL (hyperlipidemia, yes or no), and diabetes status (yes or no) based on Model 3.\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n\u003c/table\u003e\n\u003cp\u003e\u0026nbsp;\u003c/p\u003e\n\u003ctable border=\"0\" cellspacing=\"0\" cellpadding=\"0\" width=\"100%\"\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd colspan=\"4\" style=\"width: 100px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eTable 3. Time Ratio (95% CIs) for All-cause and cause-specific mortality according to periodontitis by Weibull model.\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 33px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"2\" style=\"width: 55px;\"\u003e\n \u003cp\u003ePeriodontal status\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 11px;\"\u003e\n \u003cp\u003e\u003cem\u003e\u0026nbsp;\u003c/em\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 33px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 24px;\"\u003e\n \u003cp\u003eNo/ Mild periodontitis\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 30px;\"\u003e\n \u003cp\u003eModerate/ Severe periodontitis\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 11px;\"\u003e\n \u003cp\u003e\u003cem\u003eP\u003c/em\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 33px;\"\u003e\n \u003cp\u003eAll cause*\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 24px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 30px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 11px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 33px;\"\u003e\n \u003cp\u003eDeaths/total (Unweighted)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 24px;\"\u003e\n \u003cp\u003e270/740\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 30px;\"\u003e\n \u003cp\u003e272/508\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 11px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 33px;\"\u003e\n \u003cp\u003eDeaths/total (Weighted)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 24px;\"\u003e\n \u003cp\u003e1,994,296/4,926,496\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 30px;\"\u003e\n \u003cp\u003e2,356,381/8,716,576\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 11px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 33px;\"\u003e\n \u003cp\u003eModel 1\u0026dagger;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 24px;\"\u003e\n \u003cp\u003e1.00 [Reference]\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 30px;\"\u003e\n \u003cp\u003e0.67 (0.58, 0.77)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 11px;\"\u003e\n \u003cp\u003e\u0026lt;0.001\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 33px;\"\u003e\n \u003cp\u003eModel 2\u0026Dagger;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 24px;\"\u003e\n \u003cp\u003e1.00 [Reference]\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 30px;\"\u003e\n \u003cp\u003e0.87 (0.76, 0.99)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 11px;\"\u003e\n \u003cp\u003e0.034\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 33px;\"\u003e\n \u003cp\u003eModel 3\u0026sect;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 24px;\"\u003e\n \u003cp\u003e1.00 [Reference]\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 30px;\"\u003e\n \u003cp\u003e0.87 (0.77, 1000)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 11px;\"\u003e\n \u003cp\u003e0.047\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 33px;\"\u003e\n \u003cp\u003eModel 4\u0026para;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 24px;\"\u003e\n \u003cp\u003e1.00 [Reference]\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 30px;\"\u003e\n \u003cp\u003e0.87 (0.76, 0.99)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 11px;\"\u003e\n \u003cp\u003e0.039\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 33px;\"\u003e\n \u003cp\u003eCVD cause\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 24px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 30px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 11px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 33px;\"\u003e\n \u003cp\u003eDeaths/total (Unweighted)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 24px;\"\u003e\n \u003cp\u003e99/740\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 30px;\"\u003e\n \u003cp\u003e93/508\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 11px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 33px;\"\u003e\n \u003cp\u003eDeaths/total (Weighted)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 24px;\"\u003e\n \u003cp\u003e573,816/4,926,496\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 30px;\"\u003e\n \u003cp\u003e723,876/8,716,576\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 11px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 33px;\"\u003e\n \u003cp\u003eModel 1\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 24px;\"\u003e\n \u003cp\u003e1.00 [Reference]\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 30px;\"\u003e\n \u003cp\u003e0.67 (0.52, 0.88)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 11px;\"\u003e\n \u003cp\u003e0.004\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 33px;\"\u003e\n \u003cp\u003eModel 2\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 24px;\"\u003e\n \u003cp\u003e1.00 [Reference]\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 30px;\"\u003e\n \u003cp\u003e0.94 (0.73, 1.20)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 11px;\"\u003e\n \u003cp\u003e0.602\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 33px;\"\u003e\n \u003cp\u003eModel 3\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 24px;\"\u003e\n \u003cp\u003e1.00 [Reference]\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 30px;\"\u003e\n \u003cp\u003e0.94 (0.73, 1.19)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 11px;\"\u003e\n \u003cp\u003e0.590\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 33px;\"\u003e\n \u003cp\u003eModel 4\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 24px;\"\u003e\n \u003cp\u003e1.00 [Reference]\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 30px;\"\u003e\n \u003cp\u003e0.97 (0.77, 1.24)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 11px;\"\u003e\n \u003cp\u003e0.830\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 33px;\"\u003e\n \u003cp\u003eCancer cause\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 24px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 30px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 11px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 33px;\"\u003e\n \u003cp\u003eDeaths/total (Unweighted)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 24px;\"\u003e\n \u003cp\u003e57/740\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 30px;\"\u003e\n \u003cp\u003e51/508\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 11px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 33px;\"\u003e\n \u003cp\u003eDeaths/total (Weighted)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 24px;\"\u003e\n \u003cp\u003e389,829/4,926,496\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 30px;\"\u003e\n \u003cp\u003e514,286/8,716,576\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 11px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 33px;\"\u003e\n \u003cp\u003eModel 1\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 24px;\"\u003e\n \u003cp\u003e1.00 [Reference]\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 30px;\"\u003e\n \u003cp\u003e0.85 (0.63, 1.16)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 11px;\"\u003e\n \u003cp\u003e0.313\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 33px;\"\u003e\n \u003cp\u003eModel 2\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 24px;\"\u003e\n \u003cp\u003e1.00 [Reference]\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 30px;\"\u003e\n \u003cp\u003e0.88 (0.66, 1.18)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 11px;\"\u003e\n \u003cp\u003e0.401\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 33px;\"\u003e\n \u003cp\u003eModel 3\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 24px;\"\u003e\n \u003cp\u003e1.00 [Reference]\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 30px;\"\u003e\n \u003cp\u003e0.91 (0.66, 1.24)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 11px;\"\u003e\n \u003cp\u003e0.544\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 33px;\"\u003e\n \u003cp\u003eModel 4\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 24px;\"\u003e\n \u003cp\u003e1.00 [Reference]\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 30px;\"\u003e\n \u003cp\u003e0.83 (0.59, 1.18)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 11px;\"\u003e\n \u003cp\u003e0.296\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd colspan=\"4\" style=\"width: 100px;\"\u003e\n \u003cp\u003e*All-cause and Cause-specific mortality used Weibull accelerated failure time model.\u003c/p\u003e\n \u003cp\u003e\u0026dagger; Model 1 was univariate analysis. \u0026nbsp;\u003c/p\u003e\n \u003cp\u003e\u0026Dagger;\u0026nbsp;Model 2 included age (30-44, 45-64 or\u0026nbsp;\u0026ge;65 years old), gender, race/ethnicity (non-Hispanic white, non-Hispanic black, Hispanic or other races),\u0026nbsp;\u0026sect;\u0026nbsp;Model 3 additionally included smoking habit (never smokers, former or current smokers), alcohol consumption (nondrinker, heavier drinker, or light/ moderate drinker), physical activity status (inactive, insufficient, recommended) and BMI status (body measure index, normal (\u0026le;24.9 [kg/m2]), overweight (25.0-29.9 [kg/m2]), and obesity (\u0026ge;30.0 [kg/m2]) based on Model 2.\u003c/p\u003e\n \u003cp\u003e\u0026para;\u0026nbsp;Model 4 was further adjusted for SES (Socioeconomic Status, low, middle, high),，HTN status (hypertension, yes or no) , HPL (hyperlipidemia, yes or no), and diabetes status (yes or no) based on Model 3.\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n\u003c/table\u003e\n\u003cp\u003e\u0026nbsp;\u003c/p\u003e\n\u003ctable border=\"0\" cellspacing=\"0\" cellpadding=\"0\" width=\"522\" class=\"fr-table-selection-hover\"\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd colspan=\"4\" style=\"width: 522px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eTable 4. HR (95% CIs) for All-cause and cause-specific mortality according to status of periodontitis\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 169px;\"\u003e\n \u003cp\u003eOutcomes\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 169px;\"\u003e\n \u003cp\u003eEvents (Weighted), n/N\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 131px;\"\u003e\n \u003cp\u003eHR (95% CI)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 54px;\"\u003e\n \u003cp\u003e\u003cem\u003eP\u003c/em\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 169px;\"\u003e\n \u003cp\u003eAll cause\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 169px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 131px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 54px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 169px;\"\u003e\n \u003cp\u003eNo/Mild periodontitis\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 169px;\"\u003e\n \u003cp\u003e2,356,381/8,716,576\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 131px;\"\u003e\n \u003cp\u003e1.00 [Reference]\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 54px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 169px;\"\u003e\n \u003cp\u003eModerate periodontitis*\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 169px;\"\u003e\n \u003cp\u003e1,882,381/4,661,903\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 131px;\"\u003e\n \u003cp\u003e1.35 (1.05, 1.73)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 54px;\"\u003e\n \u003cp\u003e0.018\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 169px;\"\u003e\n \u003cp\u003eSevere periodontitis\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 169px;\"\u003e\n \u003cp\u003e111,915/264,593\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 131px;\"\u003e\n \u003cp\u003e0.86 (0.36, 2.06)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 54px;\"\u003e\n \u003cp\u003e0.743\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 169px;\"\u003e\n \u003cp\u003e\u003cem\u003eP\u003c/em\u003e for trend\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 169px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 131px;\"\u003e\n \u003cp\u003e1.20 (0.93, 1.55)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 54px;\"\u003e\n \u003cp\u003e0.161\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 169px;\"\u003e\n \u003cp\u003eCVD cause*\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 169px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 131px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 54px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 169px;\"\u003e\n \u003cp\u003eNo/Mild periodontitis\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 169px;\"\u003e\n \u003cp\u003e723,876/8,716,576\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 131px;\"\u003e\n \u003cp\u003e1.00 [Reference]\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 54px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 169px;\"\u003e\n \u003cp\u003eModerate periodontitis\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 169px;\"\u003e\n \u003cp\u003e530,431/4,661,903\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 131px;\"\u003e\n \u003cp\u003e1.08 (0.74, 1.60)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 54px;\"\u003e\n \u003cp\u003e0.679\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 169px;\"\u003e\n \u003cp\u003eSevere periodontitis\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 169px;\"\u003e\n \u003cp\u003e43,385/264,593\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 131px;\"\u003e\n \u003cp\u003e0.89 (0.30, 2.64)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 54px;\"\u003e\n \u003cp\u003e0.830\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 169px;\"\u003e\n \u003cp\u003e\u003cem\u003eP\u003c/em\u003e for trend\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 169px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 131px;\"\u003e\n \u003cp\u003e1.03 (0.73, 1.45)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 54px;\"\u003e\n \u003cp\u003e0.854\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 169px;\"\u003e\n \u003cp\u003eCancer cause*\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 169px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 131px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 54px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 169px;\"\u003e\n \u003cp\u003eNo/Mild periodontitis\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 169px;\"\u003e\n \u003cp\u003e514,286/8,716,576\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 131px;\"\u003e\n \u003cp\u003e1.00 [Reference]\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 54px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 169px;\"\u003e\n \u003cp\u003eModerate periodontitis\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 169px;\"\u003e\n \u003cp\u003e352,641/4,661,903\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 131px;\"\u003e\n \u003cp\u003e1.33 (0.75, 2.36)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 54px;\"\u003e\n \u003cp\u003e0.332\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 169px;\"\u003e\n \u003cp\u003eSevere periodontitis\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 169px;\"\u003e\n \u003cp\u003e37,188/264,593\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 131px;\"\u003e\n \u003cp\u003e1.95 (0.76, 5.02)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 54px;\"\u003e\n \u003cp\u003e0.164\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 169px;\"\u003e\n \u003cp\u003eP for trend\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 169px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 131px;\"\u003e\n \u003cp\u003e1.35 (0.85, 2.16)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 54px;\"\u003e\n \u003cp\u003e0.205\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd colspan=\"4\" valign=\"top\" style=\"width: 522px;\"\u003e\n \u003cp\u003e* All-cause mortality used Cox proportional hazards model, and cause-specific mortality used competing risk model. All the models were adjusted for age (30-44, 45-64 or \u0026ge;65 years old), gender (male and female), race/ethnicity (non-Hispanic white, non-Hispanic black, Hispanic, and other races), SES (high, medium, and low level), smoking habit (current smokers, former smokers, and never smokers), alcohol consumption (nondrinkers, heavier drinkers, and light/moderate drinkers), physical activity status (inactive, insufficient, recommended), BMI status (body mass index, normal, overweight, and obesity), HTN status (hypertension, yes or no), HPL (hyperlipidemia status, yes or no), diabetes status (yes or no) and cohort period.\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n\u003c/table\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":true,"highlight":"","institution":"","isAcceptedByJournal":false,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true},"keywords":"osteoarthritis, periodontitis, mortality, cardiovascular disease","lastPublishedDoi":"10.21203/rs.3.rs-6746901/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-6746901/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003cp\u003e\u003cem\u003e\u003cstrong\u003eBackground:\u003c/strong\u003e\u003c/em\u003e The potential association between periodontitis and osteoarthritis (OA) has been widely reported in recent years, but the effect of periodontitis on the mortality of OA participants has yet to be determined. This study was designed to clarify the association between periodontitis and mortality in OA individuals.\u003c/p\u003e\n\u003cp\u003e\u003cem\u003e\u003cstrong\u003eMethods: \u003c/strong\u003e\u003c/em\u003eThis study includes 1,248 OA participants who aged ≥ 30 years from NHANES in the baseline period of 1988-2014. Cox and Weibull models were utilized to calculate hazard ratios (HRs), time ratios (TRs), and 95% confidence intervals (CIs) to examine the correlation between periodontitis and mortality in participants with OA.\u003c/p\u003e\n\u003cp\u003e\u003cem\u003e\u003cstrong\u003eResults: \u003c/strong\u003e\u003c/em\u003eOver a span of 14.38 years median follow-up, 542 deaths were observed. Moderate-to-severe periodontitis was correlated with all-cause mortality among individuals with OA after adjusting for covariates. (Cox: HR: 1.31, 95% CI: 1.01 – 1.71, \u003cem\u003eP\u003c/em\u003e = 0.041; AFT: TR: 0.87, 95% CI: 0.76 - 0.99, \u003cem\u003eP\u003c/em\u003e = 0.039). Notably, moderate-to-severe periodontitis increased the risk of CVD-related mortality among female participants (HR: 1.89, 95% CI: 1.18 – 3.02, \u003cem\u003eP\u003c/em\u003e = 0.008). However, no significant connection was found between periodontitis and other mortality.\u003c/p\u003e\n\u003cp\u003e\u003cem\u003e\u003cstrong\u003eConclusions: \u003c/strong\u003e\u003c/em\u003eThis study revealed a higher all-cause mortality in OA participants with moderate-to-severe periodontitis than in those with no/mild periodontitis and also a higher mortality in female participants with moderate-to-severe periodontitis.\u003c/p\u003e","manuscriptTitle":"Periodontitis and the risk of all-cause and cause-specific mortality among individuals with osteoarthritis in U.S.: A population-based cohort study","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2025-07-18 14:34:06","doi":"10.21203/rs.3.rs-6746901/v1","editorialEvents":[{"type":"communityComments","content":0}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"219a82fb-8457-4fd8-8281-18ac17205651","owner":[],"postedDate":"July 18th, 2025","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"posted","subjectAreas":[],"tags":[],"updatedAt":"2025-09-17T15:53:16+00:00","versionOfRecord":[],"versionCreatedAt":"2025-07-18 14:34:06","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-6746901","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-6746901","identity":"rs-6746901","version":["v1"]},"buildId":"8U1c8b4HqxoKbykW_rLl7","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}