Hyperuricemia and Elevated Uric Acid/Creatinine Ratio are Associated with a Higher Risk of Periodontitis: A Population- based Cross-Sectional Study

Hyperuricemia and Elevated Uric Acid/Creatinine Ratio are Associated with a Higher Risk of Periodontitis: A Population- based Cross-Sectional 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 Hyperuricemia and Elevated Uric Acid/Creatinine Ratio are Associated with a Higher Risk of Periodontitis: A Population- based Cross-Sectional Study Yueqi Chen, Peipei Lu, Chuyin Lin, Song Li, Yufan Zhu, Jiaying Tan, and 2 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-4675086/v1 This work is licensed under a CC BY 4.0 License Status: Published Journal Publication published 15 Nov, 2024 Read the published version in BMC Oral Health → Version 1 posted 15 You are reading this latest preprint version Abstract Objectives To explore the relationship between hyperuricemia and the risk of developing periodontitis. Materials and Methods A representative dataset of 10,158 adults was extracted from the National Health and Nutrition Examination Survey (NHANES) 2009–2014. The relationship between hyperuricemia (the primary exposure) and the risk of periodontitis (outcome) were evaluated using weighted logistic regression models. Serum uric acid (UA) levels and the UA to creatinine (UA/Cr) ratio were used as secondary exposures. Their associations with the risk of periodontitis were analyzed using weighted logistic regression or restricted cubic spline regression. Results The prevalence of moderate/severe periodontitis was 56.7% among individuals with hyperuricemia and 44.8% among those without. After adjustment, individuals with hyperuricemia had a 26.9% higher risk of developing moderate/severe periodontitis compared to those without hyperuricemia (adjusted OR = 1.269, 95% CI = 1.080 to 1.492, P = 0.006). This increased risk could be explained by a linear relationship with the serum UA/Cr ratio and a U-shaped relationship with serum UA levels. Each unit increase in the serum UA/Cr ratio was associated with a 4.6% higher risk of developing moderate/severe periodontitis (adjusted OR = 1.046, 95% CI = 1.008 to 1.086, P = 0.021). Additionally, each 1 mg/dL increase in serum UA was associated with a 10.2% higher risk (adjusted OR = 1.102, 95% CI = 1.008 to 1.206, P = 0.035) of developing moderate/severe periodontitis when UA levels were greater than 5.5 mg/dL, but a 10.6% lower risk when UA levels were 5.5 mg/dL or lower (adjusted OR = 0.894, 95% CI = 0.800 to 0.998, P = 0.046). Sensitivity analyses validated the robustness of the findings. Conclusions This study provides the first direct evidence that hyperuricemia is associated with an increased risk of developing periodontitis, especially the moderate and severe forms. Clinical Relevance Individuals with hyperuricemia may represent a subgroup of the population susceptible to periodontitis. It may be prudent to initiate timely systemic and periodontal interventions in patients with hyperuricemia to halt the progression of periodontitis. Hyperuricemia uric acid uric acid to creatinine ratio periodontal diseases urate-lowering therapy Figures Figure 1 Figure 2 Figure 3 1 INTRODUCTION Periodontitis is a multifactorial inflammatory condition characterized by progressive destruction of the periodontal supporting apparatus. It arises from the interplay between oral dysbiosis and dysregulated host inflammatory responses. Severe periodontitis affects approximately 24% of the global population, leading to significant risks of tooth loss and reduced quality of life [ 1 ]. Periodontitis is linked to numerous systemic inflammatory and metabolic comorbidities, such as metabolic syndrome and cardiovascular diseases. The co-occurrence and reciprocal impacts of periodontitis and systemic disorders significantly contribute to the global disease burden and present substantial public health challenges. Previous studies have indicated strong associations between periodontitis and the “triple H” conditions: hyperglycemia, hyperlipidemia, and hypertension [ 2 ]. However, there has been limited investigation into the potential connection between periodontitis and the emerging “fourth H”, hyperuricemia, which is increasingly recognized as another component of metabolic syndrome. Hyperuricemia is a prevalent metabolic disorder caused by disturbances in uric acid (UA) metabolism, affecting around 20% the US population according to the National Health and Nutrition Examination Survey (NHANES) 2007–2016 [ 3 ]. Besides triggering gout and kidney stones, hyperuricemia has recently been identified as a potential risk factor for cardiovascular diseases, osteoporosis, and chronic kidney diseases.[ 4 ]. Individuals with hyperuricemia exhibit systemic impairments in innate and adaptive immune responses [ 5 , 6 ]. UA appears to be a primary trigger for these impaired host responses, displaying pro-inflammatory and pro-oxidative properties under pathological conditions. Given the shared systemic comorbidities and impaired host responses in both hyperuricemia and periodontitis, it is plausible to hypothesize that hyperuricemia might be a susceptibility factor for periodontitis. By 2020, several studies had explored the relationship between periodontitis and hyperuricemia [ 7 ]. However, positive associations found in earlier studies were limited to normal serum UA levels, with UA previously considered an antioxidant in periodontal medicine. In 2020, our group hypothesized that hyperuricemia could be a potential risk factor for periodontitis and proposed serval plausible mechanisms [ 8 ]. Subsequent studies provided direct evidence exploring this relationship, but their conclusions were controversial. A cross-sectional study based on Taiwan population concluded that UA adversely effects periodontal condition [ 9 ]. Conversely, a cross-sectional study based on Korean population suggested that hyperuricemia might protect against periodontitis [ 10 ], while another study found no significant relationship between hyperuricemia and periodontitis [ 11 ]. Consequently, the existence and magnitude of hyperuricemia’s effect on periodontitis remain uncertain. To investigate the relationship between hyperuricemia and the risk of developing periodontitis, the present study aims to conduct a cross-sectional analysis of the US population using the NHANES database. 2 MATERIALS AND METHODS Ethic Statement and Reporting Guideline The NHANES project was approved by the Ethics Review Committee of the National Center for Health Statistics of the US. All participants provided their informed consent. This study adhered to the STROBE guidelines for reporting cross-sectional studies [ 12 ]. PECOS Participants = Community population of US adults Exposure = Hyperuricemia Comparison = Free from hyperuricemia Outcome = Developing moderate/severe periodontitis S = Cross-sectional study Research Question Compared with individuals without hyperuricemia, do those with hyperuricemia carry a higher risk of developing moderate/severe periodontitis? 2.1 Study Population This study combined data from three waves of NHANES data were combined (2009 to 2010, 2011 to 2012 and 2013 to 2014). A full-mouth, six-site per tooth periodontal examination was conducted by well-trained examiners, assessing attachment loss and pocket probing depth. Participants aged over 30 with at least one existing tooth were included in the periodontal examination. A total of 10,683 qualified individuals were initially considered for further analysis. After excluding 525 participants due to missing serum UA data, 10,158 participants remained for statistical analysis (Fig. 1 ). 2.2 Measurement of Serum UA and Definition of Hyperuricemia In the NHANES cycles from 2009 and 2014, serum UA and creatinine levels were measured using the Beckman UniCel DxC800 Synchron. Serum UA was assessed using the timed endpoint method, and creatine was measured using the Jaffe rate method [ 13 ]. The UA to creatinine ratio (serum UA/Cr ratio) was calculated to provide a surrogate for the net production of serum UA [ 14 ]. Hyperuricemia was defined as serum UA levels ≥ 7.0 mg/dL, regardless of sex in the present study [ 3 ]. During the NHANES home interview, participants were asked, “Has a doctor or other health professional ever told you that you had gout?” Those who answered “Yes” were diagnosed with gout for the purposes of this study. 2.3 Diagnosis and Classification of Periodontitis To identify individuals with periodontitis, the criteria established by the Centers for Disease Control and Prevention (CDC) and the American Academy of Periodontology (AAP) were applied [ 15 ]. Mild periodontitis was defined by the presence of at least two interproximal sites with attachment loss (AL) ≥ 3 mm, and at least two interproximal sites with probing depth (PD) ≥ 4 mm (not on the same tooth), or one site with PD ≥ 5 mm. Moderate periodontitis was diagnosed when there were at least two interproximal sites with AL ≥ 4 mm (not on the same tooth), or at least two interproximal sites with PD ≥ 5 mm (also not on the same tooth). Severe periodontitis was diagnosed by the presence of at least two interproximal sites with AL ≥ 6 mm (not on the same tooth) and at least one interproximal site with PD ≥ 4 mm. Individuals were identified as having no periodontitis if none of these conditions were met. Further classifications were performed based on the initial diagnosis. 2.4 Assessment of covariates Information on sex, age, ethnicity, poverty to income ratio (PIR), and educational attainment was extracted from the demographic section of NHANES. Participants were categorized based on smoking status as non-smokers (consumed less than 100 cigarettes in their lifetime), former smokers (consumed more than 100 cigarettes but currently quit) and current smokers (have ongoing smoking habit). Alcohol consumption was categorized into non-drinkers, 1 to 5 drinks per month, 5 to 10 drinks per month, or more than 10 drinks per month. Body mass index (BMI) data were obtained from the physical examinations section. Participants were identified as having certain medical conditions based on their responses to questions about whether a doctor or other health professional has ever diagnosed them with diabetes, high cholesterol, cancer, weak or failing kidneys, or cerebra-cardiovascular diseases (including congestive heart failure, coronary heart disease, angina, heart attack, stroke or hypertension). Participants were considered to have received periodontal treatment if they answered “Yes” to the question, “Have you ever had treatment for gum disease such as scaling and root planning, sometimes called "deep cleaning"?”. Additionally, participants were asked, “In the past month, have you used or taken medication for which a prescription is needed?” (excluding vitamins or minerals). Participants were identified as receiving urate-lowering therapy (ULT) if they reported currently taking allopurinol, febuxostat, or probenecid [ 3 ]. 2.5 Statistical Analysis All statistical analysis were conducted using the noncommercial software R (version 4.1.0). Data from three NHANES cycles (2009 to 2010, 2011 to 2012 and 2013 to 2014) were combined, and 6-year sampling weights were constructed according to NHANES recommendations [ 13 ]. Multiple imputation was applied to complete missing covariate data before conducting statistical analysis. Differences in categorical and continuous variables between individuals with moderate/severe periodontitis and controls were compared using Chi -square tests and Student’s t tests, respectively. Continuous were presented as means (± standard deviations, SDs), and categorical variables as corresponding proportions. Weighted multivariable logistic regression was employed to estimate the odds ratio ( OR ) and confidence interval ( CI ) for the associations between hyperuricemia (as well as serum UA and serum UA/Cr ratio) and periodontitis. Model 1 adjusted for demographic factors, including sex, age groups, ethnicity, PIR and educational attainment. Model 2 further adjusted for BMI and lifestyle factors such as smoking status and alcohol consumption. Model 3 additionally adjusted for systemic conditions (including a history of cerebra-cardiovascular diseases, diabetes, hyperlipidemia, cancer and kidney conditions), periodontal treatment and ULT based on Model 2. Nonlinear relationships between serum UA and periodontitis were evaluated using restricted cubic spline regression, and the inflection point was calculated using the two-piecewise linear regression model. The receiver operating characteristic curve was used to evaluate the predictive competence of the serum UA/Cr ratio for moderate/severe periodontitis. The significance level was set at P < 0.05. 2.6 Sensitivity Analysis To enhance the robustness of the findings, alternative definitions of hyperuricemia and classifications of periodontitis were used for validation analysis. The alternative definition of hyperuricemia identified subjects as having hyperuricemia if serum UA levels were ≥ 7.0 mg/dL in males or ≥ 6.0 mg/dL in females [ 3 ]. Two alternative classifications of periodontitis were applied: 1. Participants were divided into those with periodontitis and healthy controls. 2. Two separate statistical analysis were performed: one comparing severe periodontitis to healthy controls, and another comparing mild and moderate periodontitis to healthy controls. Subgroup analysis stratified by sex, age, ethnicity, diabetes, hyperlipidemia, gout, periodontal treatment, and ULT were performed to verify the findings within specific populations. Interaction effects between hyperuricemia and serval characteristics were tested to examine the distinctions among specific subgroups. 3 RESULTS 3.1 Characteristics of the Study Population In the US population, the overall prevalence of periodontitis was 42.1%, consisting of 4.3% mild, 30.0% moderate and 7.8% severe forms. Nineteen percent of the study population were diagnosed with hyperuricemia, and 3.9% reported a history of gout diagnosis. Hyperuricemia prevalence was 6.6% in females and 22.1% in males. Among different ethnicities, Non-Hispanic Whites accounted for 70.0% of all cases of hyperuricemia. Among participants with hyperuricemia, 47.2% had moderate/severe periodontitis (11.6% moderate, 35.6% severe), while among those without hyperuricemia, the corresponding proportion was 36.2% (7.2% moderate, 29.0% severe) (Table 1 ). Table 1 Baseline characteristics of the study population stratified by periodontitis Characteristics Overall Non-hyperuricemia Hyperuricemia P value Frequency 138,117,868 119,221,910 18,895,959 / Sex < 0.001*** Female 5,136 (50.9%) 4,799 (55.6%) 337 (21.2%) Male 5,022 (49.1%) 3,911 (44.4%) 1,111 (78.8%) Age 0.063 30-44-year-old 3,418 (34.6%) 2,993 (34.8%) 425 (32.8%) 45-64-year-old 4,146 (43.5%) 3,557 (43.7%) 589 (42.3%) > 65-year-old 2,594 (21.9%) 2,160 (21.5%) 434 (24.9%) PIR 0.200 ≤ 1 1,983 (12.1%) 1,721 (12.4%) 262 (10.8%) ≥ 3 4,139 (54.4%) 3,559 (54.4%) 580 (54.1%) 1–3 4,036 (33.5%) 3,430 (33.2%) 606 (35.1%) Educational attainment 0.200 Less than high school 2,355 (15.2%) 2,017 (15.2%) 338 (14.9%) High school graduate 2,199 (20.9%) 1,864 (20.6%) 335 (22.7%) College graduate or above 5,604 (63.9%) 4,829 (64.2%) 775 (62.3%) Ethnicity < 0.001*** Non-Hispanic White 4,438 (69.2%) 3,796 (69.0%) 642 (70.3%) Non-Hispanic Black 2,021 (10.1%) 1,647 (9.8%) 374 (12.3%) Mexican American 1,467 (8.1%) 1,311 (8.4%) 156 (6.1%) Others 1,217 (7.2%) 1,047 (7.2%) 170 (7.2%) Other Hispanic 1,015 (5.4%) 909 (5.6%) 106 (4.0%) BMI < 0.001*** normal weight 2,639 (26.3%) 2,448 (28.7%) 191 (10.6%) underweight 118 (1.1%) 110 (1.2%) 8 (0.5%) overweight 3,534 (35.6%) 3,070 (35.7%) 464 (34.9%) obesity 3,867 (37.1%) 3,082 (34.4%) 785 (54.0%) Smoking status 0.036* Current smoker 1,906 (17.3%) 1,651 (17.4%) 255 (17.0%) Former smoker 2,554 (26.4%) 2,106 (25.8%) 448 (30.2%) Non-smoker 5,698 (56.3%) 4,953 (56.9%) 745 (52.8%) Alcohol consumption < 0.001*** 1–5 drinks/month 4,993 (49.6%) 4,306 (50.0%) 687 (46.9%) 10 + drinks/month 1,651 (20.1%) 1,319 (19.1%) 332 (27.0%) 5–10 drinks/month 768 (9.3%) 647 (9.1%) 121 (9.9%) Non-drinker 2,746 (21.0%) 2,438 (21.8%) 308 (16.2%) Hypertension < 0.001*** No 6,355 (65.9%) 5,696 (68.6%) 659 (48.5%) Yes 3,803 (34.1%) 3,014 (31.4%) 789 (51.5%) Hyperlipidemia 0.003** No 6,109 (60.5%) 5,343 (61.4%) 766 (54.4%) Yes 4,049 (39.5%) 3,367 (38.6%) 682 (45.6%) Diabetes < 0.001*** No 8,631 (88.0%) 7,468 (88.7%) 1,163 (84.0%) Yes 1,527 (12.0%) 1,242 (11.3%) 285 (16.0%) Cerebra-cardiovascular diseases < 0.001*** No 9,266 (92.7%) 8,026 (93.5%) 1,240 (87.5%) Yes 892 (7.3%) 684 (6.5%) 208 (12.5%) Cancer 0.300 No 9,217 (89.5%) 7,907 (89.6%) 1,310 (88.5%) Yes 941 (10.5%) 803 (10.4%) 138 (11.5%) Kidney diseases < 0.001*** No 9,884 (97.9%) 8,516 (98.3%) 1,368 (95.4%) Yes 274 (2.1%) 194 (1.7%) 80 (4.6%) Gout < 0.001*** No 9,743 (96.1%) 8,468 (97.2%) 1,275 (89.2%) Yes 415 (3.9%) 242 (2.8%) 173 (10.8%) ULT 0.013* No 10,030 (98.7%) 8,609 (98.8%) 1,421 (98.2%) Yes 128 (1.3%) 101 (1.2%) 27 (1.8%) Periodontal treatment 0.600 No 7,751 (78.0%) 6,637 (78.1%) 1,114 (77.3%) Yes 2,407 (22.0%) 2,073 (21.9%) 334 (22.7%) Serum UA 5.42 ± 1.40 5.04 ± 1.06 7.81 ± 0.81 < 0.001*** Serum UA/Cr ratio 6.30 ± 1.60 6.07 ± 1.45 7.72 ± 1.76 < 0.001*** Periodontal conditions < 0.001*** Healthy 4,960 (58.0%) 4,394 (59.5%) 566 (48.6%) Mild periodontitis 475 (4.3%) 414 (4.3%) 61 (4.2%) Moderate periodontitis 3,598 (29.9%) 2,995 (29.0%) 603 (35.6%) Severe periodontitis 1,125 (7.8%) 907 (7.2%) 218 (11.6%) ***, P < 0.001; **, P < 0.01; *, P < 0.05; BMI, body mass index; PIR, poverty to income ratio; UA, uric acid; UA/Cr ratio, uric acid to creatinine ratio; ULT, urate-lowering therapy. 3.2 Associations Between Hyperuricemia and Risk of Periodontitis The crude model demonstrated that individuals with hyperuricemia had a 57.3% increased risk ( OR = 1.573, 95% CI = 1.350 to 1.832, P < 0.001) of developing moderate/severe periodontitis compared to controls without hyperuricemia. After adjusting for demographic factors including sex, age, ethnicity, educational attainment and PIR, the periodontal risk declined to 28.2%. Further adjustment for lifestyle, BMI, systemic conditions (including cerebra-cardiovascular diseases, diabetes, hyperlipidemia, cancers and kidney diseases), periodontal treatment and ULT revealed that hyperuricemia remained significantly associated with a ~ 30% increased risk of developing moderate/severe periodontitis (Table 2 ). Table 2 Effects of hyperuricemia, serum UA and serum UA/Cr ratio on risk of periodontitis assessed by logistic regression Exposure Model OR 95% CI P value Hyperuricemia Crude model 1.573 1.350, 1.832 < 0.001*** Model 1 1.282 1.096, 1.498 0.003** Model 2 1.300 1.105, 1.529 0.002** Model 3 1.269 1.080, 1.492 0.006** Serum UA Crude model 1.150 1.109, 1.191 < 0.001*** Model 1 1.017 0.978, 1.058 0.389 Model 2 1.030 0.987, 1.074 0.165 Model 3 1.021 0.977, 1.068 0.338 UA/Cr ratio Crude model 1.034 1.001, 1.069 0.045* Model 1 1.045 1.010, 1.080 0.013* Model 2 1.048 1.010, 1.088 0.015* Model 3 1.046 1.008, 1.086 0.021* CI , confidence interval; OR , odds ratio; UA, uric acid; UA/Cr ratio, uric acid to creatinine ratio; ***, P < 0.001; **, P < 0.01; *, P < 0.05; Model 1, adjusted for demographic factors, including sex, age, ethnicity, poverty to income ratio, educational attainment; Model 2, adjusted for smoking status, alcohol consumption, body mass index and the aforementioned demographic factors; Model 3, adjusted for cerebra-cardiovascular conditions (including congestive heart failure, coronary heart disease, angina, heart attack, stroke and hypertension), hyperlipidemia, diabetes, cancer, kidney conditions, periodontal treatment and urate-lowering therapy on the basis of model 2. 3.3 Associations Between Serum UA Level and Risk of Periodontitis The crude model demonstrated a linear positive relationship between serum UA level and the risk of developing moderate/severe periodontitis ( OR = 1.150, 95% CI = 1.109 to 1.191, P < 0.001). However, after adjusting for demographic factors, lifestyle, BMI, systemic conditions, periodontal treatment and ULT, the statistical significance of this linear relationship was lost (Table 2 ). Restricted cubic spline regression, conducted with the adjusted model, identified a significant U-shaped (i.e., non-linear) relationship between serum UA level and the risk of developing moderate/severe periodontitis ( P = 0.0417) (Fig. 2 ). Threshold effect analysis further estimated an inflection point at 5.5 mg/dL. Above 5.5 mg/dL, every 1 mg/dL increase in serum UA was associated with a 10.2% higher risk (adjusted OR = 1.102, 95% CI = 1.008 to 1.206, P = 0.035) of developing moderate/severe periodontitis (Table 3 ). Conversely, below 5.5 mg/dL, every 1 mg/dL increase in serum UA was associated with a 10.6% lower periodontal risk (adjusted OR = 0.894, 95% CI = 0.800 to 0.998, P = 0.046). Table 3 Threshold effect analyses of the effects of serum UA on the risk of periodontitis Adjusted OR (95% CI ), P value Inflection point 5.5 mg/dL P for log likelihood ratio P = 0.006 Serum UA ≤ 5.5 mg/dL 0.894 (0.800, 0.998), 0.046 Serum UA > 5.5 mg/dL 1.102 (1.008, 1.206), 0.035 Sex, age, ethnicity, educational attainment, poverty to income ratio, body mass index, smoking status, alcohol consumption, cerebra-cardiovascular conditions, hyperlipidemia, diabetes, cancer, kidney conditions, periodontal treatment and ULT were adjusted for; CI , confidence interval; serum UA, serum uric acid; OR , odds ratio; 3.4 Associations Between Serum UA/Cr Ratio and Risk of Periodontitis Given the potential influence of renal function on serum UA levels, an emerging index, serum UA/Cr ratio, was utilized to reflect the net production of serum UA. Exploration of the correlation between serum UA/Cr ratio and the risk of developing moderate/severe periodontitis was conducted. Generally, the serum UA/Cr ratio in individuals with and without hyperuricemia was 6.07 ± 1.45 and 7.72 ± 1.76, respectively. The crude model indicated that each unit increase in serum UA/Cr ratio was associated with a 3.4% elevated risk of developing moderate/severe periodontitis ( OR = 1.034, 95% CI = 1.001 to 1.069). After adjusting for demographic factors, lifestyle, BMI, systemic conditions, periodontal treatment and ULT, the increased periodontal risk was 4.6% (adjusted OR = 1.046, 95% CI = 1.008 to 1.086, P = 0.021) (Table 2 ). However, the receiver operating characteristic curve demonstrated that the serum UA/Cr ratio lacked the competence to predict moderate/severe periodontitis (Fig. 3 ). 3.5 Sensitivity analysis To examine the robustness of the findings, an alternate definition of hyperuricemia (i.e., male > 7.0 mg/dL, or female > 6.0 mg/dL) was applied for sensitivity analysis. Initially, the crude model demonstrated that individuals with hyperuricemia exhibited a 40.1% elevated risk of developing moderate/severe periodontitis compared to those without hyperuricemia ( OR = 1.401, 95% CI = 1.223 to 1.605, P < 0.001). The increased periodontal risks ranged from 24.0–27.9% after adjusting for demographic and systemic factors. Furthermore, diverse grouping maneuvers over periodontal conditions were performed while maintaining the primary definition of hyperuricemia r (i.e., > 7.0 mg/dL regardless of sex). The crude model demonstrated that individuals with hyperuricemia carried a 55.3% increased risk ( OR = 1.553, 95% CI = 1.319 to 1.829, P < 0.001) of developing any type of periodontitis compared to those without, with adjusted risks ranging from 19.0–23.8%. Compared to those without hyperuricemia, individuals with it carried a 46.3% increased risk ( OR = 1.463, 95% CI = 1.236 to 1.730, P < 0.001) of developing mild/moderate periodontitis (vs. no periodontitis). However, the significance was lost after adjusting for demographic and systemic factors ( OR = 1.162, 95% CI = 0.982 to 1.375, P = 0.078). Individuals with hyperuricemia carried a 97.4% higher risk ( OR = 1.974, 95% CI = 1.524 to 2.556, P < 0.001) of developing severe periodontitis compared to those without, with adjusted risks ranging from 42.7–47.2%. Even after altering the definition of hyperuricemia and grouping tactics for periodontal conditions in sensitivity analysis, the results remained robust (see Supplementary Materials). Interaction analysis revealed a significant interaction between hyperuricemia and ULT ( P for interaction < 0.001). Subgroup analysis showed that the increased periodontal risk in the ULT subgroup (adjusted OR = 19.488, 95% CI = 3.898 to 97.444) was much higher than that in the non-ULT subgroup (adjusted OR = 1.209, 95% CI = 1.017,1.437, P = 0.0318). No significant interactions were found ( P for interaction > 0.05) between hyperuricemia and specific covariates, including sex, age, ethnicities, periodontal treatment and history of diabetes, hyperlipidemia or gout (see Figure S5 in Supplementary Materials), suggesting that these factors did not influence the impact of hyperuricemia on the risk of developing periodontitis. 4 DISCUSSIONS Several studies have examined the associations between hyperuricemia and periodontitis, yet the results have been inconclusive. The present cross-sectional study, conducted on the US population, is the first of its kind to definitively link hyperuricemia with a 30% increased risk of developing moderate/severe periodontitis, even after adjusting for potential confounders including demographic factors, lifestyles and systemic diseases. Specifically, when focusing solely on the risk of developing severe periodontitis, the increase jumps to 97.4% ( OR = 1.974, 95% CI = 1.524 to 2.556). Sensitivity analysis based on varied definitions of hyperuricemia and classifications of periodontal conditions reaffirmed the robustness of the primary findings, with the increased periodontal risks consistently above 20%, regardless of alternations in hyperuricemia definitions and periodontitis classifications. The increase in periodontal risk appears to be linked to a linear relationship with the serum UA/Cr ratio and a U-shaped relationship with serum UA levels. Taken together, the present study provides the first direct evidence suggesting that hyperuricemia may indeed be associated with a higher risk of periodontitis progression. Numerous observational studies with small sample sizes have noted elevated blood UA levels in individuals with periodontitis compared to those without [ 16 , 17 ]. However, these increases in blood UA levels have often fallen within the normal range, as indicated in the latest systematic review conducted by our research group [ 7 ]. A cross-sectional study in 2018, involving 1,123 individuals (295 with stage Ⅱ/Ⅲ periodontitis vs. 828 with a healthy periodontium), suggested that increased serum UA levels may have adverse effects on periodontitis ( OR = 1.100, 95% CI = 1.001 to 1.209). However, this significant association disappeared in the adjusted model ( OR = 1.097, 95% CI = 0.998 to 1.206), and hyperuricemia diagnosis was not conducted in this study [ 9 ]. Two subsequent cross-sectional studies, conducted in 2020 and 2023 respectively and based on the Korean population, attempted to explore the associations between hyperuricemia and periodontitis. However, these two studies either failed to find any significant association between hyperuricemia and periodontitis or suggested hyperuricemia as a protective factor against periodontitis [ 10 , 11 ]. Several reasons may account for these discrepancies. Firstly, the two cross-sectional studies identified periodontitis cases using Community Periodontal Index of limited examined teeth or self-reported diagnosis history, which could lead to a significant proportion of misdiagnosis [ 1 ]. Secondly, one of the cross-sectional studies excluded numerous individuals with missing covariates, potentially introducing biases into the results. Another cross-sectional study based on NHANES data of 2009 to 2011, explored the relationships between hyperuricemia and periodontitis [ 18 ]. However, incorrect reporting of periodontitis prevalence in this study has raised concerns about its conclusions [ 19 ]. In contrast, the present study, involving over 10,000 individuals from the US population, rigorously diagnosed periodontal conditions and hyperuricemia using quantitative criteria. Moreover, the robustness of the findings was verified by multiple covariate adjustments and sensitivity analysis. In this context, the present study provides the first evidence of a positive association between hyperuricemia and the risk of periodontitis. Specifically, individuals with hyperuricemia were found to be more susceptible to periodontitis, particularly the severe form, compared to those without hyperuricemia. These findings suggest that hyperuricemia may be a novel risk factor for periodontitis. Notably, the positive association between hyperuricemia and periodontitis differed from the relationship between serum UA levels and periodontitis. Existing studies have yielded conflicting conclusions regarding the correlation between serum UA levels and periodontitis. For instance, a cross-sectional study based of a Taiwan military population found a positive association between serum UA levels and periodontitis risk ( OR = 1.100, 95% CI = 1.001 to 1.209). In contrast, a similar study in a Korean population implied that hyperuricemia was negatively associated with periodontitis risk ( OR = 0.89, 95% CI = 0.81 to 0.96). The present study, based on a US community population, did not find a linear relationship between serum UA levels and periodontitis after adjusting for covariates. Instead, a U-shaped relationship emerged, a pattern also seen between serum UA levels and other diseases such as chronic kidney diseases and cardiovascular diseases. [ 20 , 21 ]. The inflection point was determined to be 5.5 mg/dL through threshold effect analysis. Below this threshold, increasing serum UA levels were significantly associated with a decreased risk of periodontitis, while levels above 5.5 mg/dL were positively associated with periodontitis. Hence, within a certain range, serum UA may have a protective role against periodontitis due to its potential antioxidative effects under physiological conditions [ 22 ]. However, this protective effect appears to be limited. The use of higher thresholds (either 7.0 or 6.0 mg/dL) to define hyperuricemia might obscure the statistically significant protective effects of serum UA on periodontitis. Gout is commonly recognized as symptomatic hyperuricemia. A retrospective cohort study with an average follow-up period of 6 years (gout vs. controls, N = 31,759 vs. N = 63,517) indicated that individuals with gout had a higher incidence of periodontitis (adjusted hazard ratio = 1.13, 95% CI = 1.10 to 1.16). The study also suggested that the use of colchicine, a treatment for gout flare-ups and chronic gout, could reduce the incidence of periodontitis in gout patients (adjusted hazard ratio = 0.85, 95% CI = 0.79 to 0.91), compared to those not receiving ULT. Interestingly, gout patients were found to have an increased abundance of Prevotella intermedia in their saliva [ 23 ]. Another study reported that tophus (gout nodules) could be found in the gingiva [ 24 ]. These studies support a positive correlation between gout and periodontitis. In the present study, the prevalence of gout was approximately 20.5% among individuals with hyperuricemia. Subgroup analysis stratified by gout indicated that the effect of hyperuricemia on periodontitis was independent of gout. Besides, gout was not significantly associated with periodontitis when included in logistic regression models. This study did not observe any association between gout and periodontitis, possibly due to the complex relationship between hyperuricemia and gout. It is known that most individuals with hyperuricemia, whose serum UA levels exceed the threshold for urate crystallization, do not have a history of gout [ 25 ]. Conversely, patients experiencing gout flare-ups can exhibit normal UA level [ 26 ]. In the present study, 58.3% of individuals with a history of gout had normal UA levels at the time of examination, a proportion far exceeding that of those receiving ULT (28.9% of gouty individuals). The observation that most gout patients had normalized their serum UA levels made it difficult to identify a potential relationship between gout and periodontitis. Notably, the present study found that the impact of hyperuricemia on periodontal risk was influenced by ULT. The increased periodontal risk associated with hyperuricemia in the ULT subgroup was much greater than that in the non-ULT subgroup. However, this does not necessarily mean that ULT amplifies the adverse effect of hyperuricemia on periodontitis. Instead, the higher proportions of hyperuricemia (18.6% vs. 13.6%), gout (91.8% vs. 2.7%) and self-reported kidney diseases (10.0% vs. 2.0%) in the ULT subgroup suggest that these individuals had more refractory hyperuricemia compared to those not receiving ULT (see the proportion of hyperuricemia in the subgroups with/without ULT in the Table 1 ). Several studies have used the UA/Cr ratio as a surrogate for UA levels, considering kidney clearance function thus providing a better marker for net serum UA production [ 27 ]. Evidence shows that the serum UA/Cr ratio is positively associated with various diseases, including metabolic syndrome, non-alcoholic fatty liver disease, and cardiovascular events [ 28 – 30 ]. In the present study, the serum UA/Cr ratio exhibited a positive linear relationship with periodontitis, unlike serum UA levels. This suggests that the monotonic correlation between the serum UA/Cr ratio and periodontitis might be more predictable. However, the receiver operating characteristic curve indicated that the serum UA/Cr ratio was not effective in distinguishing individuals with moderate/severe periodontitis (Area under the curve = 0.502), likely due to the weak effect of the serum UA/Cr ratio on periodontitis ( OR = 1.046) or confounding effects from other systemic conditions. Nonetheless, the relationship between the serum UA/Cr ratio and periodontitis might reflect the systemic metabolic responses of patients with periodontitis or the effects of systemic metabolic disorders on periodontitis. Among individuals with hyperuricemia, the risk of developing severe periodontitis was significantly higher than the risk of developing mild/moderate forms, even after adjusting for multiple systemic conditions. Patients with severe periodontitis are generally exposed to specific inherited or multiple environmental factors. It is possible that hyperuricemia and periodontitis share some unknown hereditary basis. Other covariates not included in the current study, such as dietary factors, might also strengthen the association between hyperuricemia and severe periodontitis. The underlying mechanisms by which hyperuricemia exacerbates periodontitis remain unclear. Our recent review article hypothesized that hyperuricemia might worsen periodontitis by aggravating periodontal dysbiosis, inflammation and oxidative stress [ 8 ]. Therefore, combined animal models of these two conditions should be developed to explore the underlying mechanisms. The findings of the present study also suggest the toned for prompt systemic and periodontal intervention in patients with hyperuricemia to prevent the progression of periodontitis. Serval limitations exist in the current study. Firstly, the cross-sectional design limits the ability to determine causal associations. Prospective cohort and interventional studies are warranted to validate these findings. Secondly, serum UA levels can exhibit circadian rhythms. Pacheco et al. reported that the estimated amplitudes of circannual variation for serum UA were 0.20 mg/dL in males and 0.17 mg/dL in females [ 31 ]. This variability could introduce some unpredictable but limited bias. Thirdly, the findings were derived from survey data collected in the US population between 2009 and 2014. The epidemiological features of hyperuricemia and periodontitis might vary over time and across regions. The prevalence of hyperuricemia has varied over the last decade and across different regions [ 3 , 32 , 33 ]. Treatment coverage rates and regimens might also differ globally. Therefore, caution should be exercised when generalizing these findings to other populations or regions. 5. CONCLUSION In conclusion, despite the study’s limitations, this research provides the first direct evidence supporting a positive association between hyperuricemia and the risk of periodontitis, particularly the moderate and severe forms. Prospective cohort and interventional studies are warranted to validate these findings. Declarations FUNDING INFORMATION This work was supported by Guangdong Basic and Applied Basic Research Foundation (Grants 2023A1515030037 and 2022A1515010497); The Basic Research Program of Guangzhou Science and Technology Bureau (2023A03J0324 and 202201020203); The Fundings of Guangzhou Medical University for Improving Innovation Capability of Undergraduates (Guangyifa [2024]61 and Guangkouyixue [2022]3); and The Teaching Fundings of Guangzhou Medical University (Guangyidafa [2021]28-2 and [2021]159-48). ACKNOWLEDGEMENT All authors acknowledge the investigators and participants of the National Health and Nutrition Examination Survey (NHANES). CONFLICT OF INTEREST STATEMENT The authors in this study declare no conflict of interest. AUTHOR CONTRIBUTIONS Ting Yu, Yueqi Chen, Peipei Lu, Chuyin Lin and Yinghong Zhou participated in the study design; Yueqi Chen, Peipei Lu, Chuyin Lin, Song Li, Yufan Zhu and Jiaying Tan performed the statistical analyses; Yueqi Chen, Peipei Lu, Chuyin Lin, Ting Yu and Yinghong Zhou wrote the manuscript; and Ting Yu and Yinghong Zhou revised the manuscript. DATA AVAILABILITY STATEMENT The data that support the findings of this study are openly available in [National Health and Nutrition Examination survey] at NHANES-National Health and Nutrition Examination Survey Homepage (cdc.gov). References Trindade, D., Carvalho, R., Machado, V., Chambrone, L., Mendes, J.J., Botelho, J.: Prevalence of periodontitis in dentate people between 2011 and 2020: A systematic review and meta-analysis of epidemiological studies. 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Sci Rep. 7, 42818 (2017). https://doi.org/10.1038/srep42818 Xu, J., Jia, Y., Mao, Z., Wei, X., Qiu, T., Hu, M.: Association between serum uric acid, hyperuricemia and periodontitis: a cross-sectional study using NHANES data. BMC Oral Health. 23, 610 (2023). https://doi.org/10.1186/s12903-023-03320-4 O’Dwyer, M.C., Furgal, A., Furst, W., Ramakrishnan, M., Capizzano, N., Sen, A., Klinkman, M.: The Prevalence of Periodontitis Among US Adults with Multimorbidity Using NHANES Data 2011-2014. J Am Board Fam Med. 36, 313–324 (2023). https://doi.org/10.3122/jabfm.2022.220207R1 Mori, K., Furuhashi, M., Tanaka, M., Numata, K., Hisasue, T., Hanawa, N., Koyama, M., Osanami, A., Higashiura, Y., Inyaku, M., Matsumoto, M., Moniwa, N., Ohnishi, H., Miura, T.: U-shaped relationship between serum uric acid level and decline in renal function during a 10-year period in female subjects: BOREAS-CKD2. Hypertens Res. 44, 107–116 (2021). https://doi.org/10.1038/s41440-020-0532-z Konta, T., Ichikawa, K., Kawasaki, R., Fujimoto, S., Iseki, K., Moriyama, T., Yamagata, K., Tsuruya, K., Narita, I., Kondo, M., Shibagaki, Y., Kasahara, M., Asahi, K., Watanabe, T.: Association between serum uric acid levels and mortality: a nationwide community-based cohort study. Sci Rep. 10, 6066 (2020). https://doi.org/10.1038/s41598-020-63134-0 Lin, K.-M., Lu, C.-L., Hung, K.-C., Wu, P.-C., Pan, C.-F., Wu, C.-J., Syu, R.-S., Chen, J.-S., Hsiao, P.-J., Lu, K.-C.: The Paradoxical Role of Uric Acid in Osteoporosis. Nutrients. 11, 2111 (2019). https://doi.org/10.3390/nu11092111 Liu, J., Cui, L., Yan, X., Zhao, X., Cheng, J., Zhou, L., Gao, J., Cao, Z., Ye, X., Hu, S.: Analysis of Oral Microbiota Revealed High Abundance of Prevotella Intermedia in Gout Patients. Cell Physiol Biochem. 49, 1804–1812 (2018). https://doi.org/10.1159/000493626 Xu, Q., Lin, C.-S.: An interesting tophus in gingiva. Int J Rheum Dis. 26, 401–402 (2023). https://doi.org/10.1111/1756-185X.14522 Dehlin, M., Jacobsson, L., Roddy, E.: Global epidemiology of gout: prevalence, incidence, treatment patterns and risk factors. Nat Rev Rheumatol. 16, 380–390 (2020). https://doi.org/10.1038/s41584-020-0441-1 Zhang, J., Sun, W., Gao, F., Lu, J., Li, K., Xu, Y., Li, Y., Li, C., Chen, Y.: Changes of serum uric acid level during acute gout flare and related factors. Front Endocrinol (Lausanne). 14, 1077059 (2023). https://doi.org/10.3389/fendo.2023.1077059 Borghi, C., Piani, F.: Uric acid and estimate of renal function. Let’s stick together. Int J Cardiol. 310, 157–158 (2020). https://doi.org/10.1016/j.ijcard.2020.01.046 Cao, T., Tong, C., Halengbieke, A., Ni, X., Tang, J., Zheng, D., Guo, X., Yang, X.: Serum uric acid to creatinine ratio and metabolic syndrome in middle-aged and elderly population: Based on the 2015 CHARLS. Nutr Metab Cardiovasc Dis. 33, 1339–1348 (2023). https://doi.org/10.1016/j.numecd.2023.05.004 Choi, J., Joe, H., Oh, J.-E., Cho, Y.-J., Shin, H.-S., Heo, N.H.: Correction: The Correlation Between NAFLD and Serum Uric Acid to Serum Creatinine Ratio. PLoS One. 18, e0294801 (2023). https://doi.org/10.1371/journal.pone.0294801 Casiglia, E., Tikhonoff, V., Virdis, A., Grassi, G., Angeli, F., Barbagallo, C.M., Bombelli, M., Cicero, A.F.G., Cirillo, M., Cirillo, P., Dell’Oro, R., D’elia, L., Desideri, G., Ferri, C., Galletti, F., Gesualdo, L., Giannattasio, C., Iaccarino, G., Lippa, L., Mallamaci, F., Masi, S., Maloberti, A., Masulli, M., Mazza, A., Mengozzi, A., Muiesan, M.L., Nazzaro, P., Palatini, P., Parati, G., Pontremoli, R., Quarti-Trevano, F., Rattazzi, M., Reboldi, G., Rivasi, G., Salvetti, M., Tocci, G., Ungar, A., Verdecchia, P., Viazzi, F., Volpe, M., Borghi, C., Working Group on Uric Acid and Cardiovascular Risk of the Italian Society of Hypertension (SIIA): Serum uric acid / serum creatinine ratio as a predictor of cardiovascular events. Detection of prognostic cardiovascular cut-off values. J Hypertens. 41, 180–186 (2023). https://doi.org/10.1097/HJH.0000000000003319 Pacheco de Andrade, M., Hirata, R.D.C., Sandrini, F., Largura, A., Hirata, M.H.: Uric acid biorhythm, a feature of long-term variation in a clinical laboratory database. Clin Chem Lab Med. 50, 853–859 (2012). https://doi.org/10.1515/cclm-2011-0150 Zhang, M., Zhu, X., Wu, J., Huang, Z., Zhao, Z., Zhang, X., Xue, Y., Wan, W., Li, C., Zhang, W., Wang, L., Zhou, M., Zou, H., Wang, L.: Prevalence of Hyperuricemia Among Chinese Adults: Findings From Two Nationally Representative Cross-Sectional Surveys in 2015-16 and 2018-19. Front Immunol. 12, 791983 (2021). https://doi.org/10.3389/fimmu.2021.791983 Al Shanableh, Y., Hussein, Y.Y., Saidwali, A.H., Al-Mohannadi, M., Aljalham, B., Nurulhoque, H., Robelah, F., Al-Mansoori, A., Zughaier, S.M.: Prevalence of asymptomatic hyperuricemia and its association with prediabetes, dyslipidemia and subclinical inflammation markers among young healthy adults in Qatar. BMC Endocr Disord. 22, 21 (2022). https://doi.org/10.1186/s12902-022-00937-4 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-4675086","acceptedTermsAndConditions":true,"allowDirectSubmit":false,"archivedVersions":[],"articleType":"Research Article","associatedPublications":[],"authors":[{"id":333682773,"identity":"8cfa3b88-e8dd-4a0f-bf36-8849fe58b164","order_by":0,"name":"Yueqi Chen","email":"","orcid":"","institution":"Guangzhou Medical University","correspondingAuthor":false,"prefix":"","firstName":"Yueqi","middleName":"","lastName":"Chen","suffix":""},{"id":333682774,"identity":"6afe6ffc-d2e0-47ac-a3bc-7565ec2cf379","order_by":1,"name":"Peipei Lu","email":"","orcid":"","institution":"Guangzhou Medical University","correspondingAuthor":false,"prefix":"","firstName":"Peipei","middleName":"","lastName":"Lu","suffix":""},{"id":333682775,"identity":"7308db2f-190d-4527-be87-b8d98b928f76","order_by":2,"name":"Chuyin Lin","email":"","orcid":"","institution":"Guangzhou Medical University","correspondingAuthor":false,"prefix":"","firstName":"Chuyin","middleName":"","lastName":"Lin","suffix":""},{"id":333682776,"identity":"d2dd7023-6854-4483-bb15-0738e132a3e6","order_by":3,"name":"Song Li","email":"","orcid":"","institution":"Guangzhou Medical University","correspondingAuthor":false,"prefix":"","firstName":"Song","middleName":"","lastName":"Li","suffix":""},{"id":333682777,"identity":"088c5bc5-7548-44dc-ae09-fef888371571","order_by":4,"name":"Yufan Zhu","email":"","orcid":"","institution":"Guangzhou Medical University","correspondingAuthor":false,"prefix":"","firstName":"Yufan","middleName":"","lastName":"Zhu","suffix":""},{"id":333682778,"identity":"bb01f908-d696-4b29-ad74-a611a9516eae","order_by":5,"name":"Jiaying Tan","email":"","orcid":"","institution":"Guangzhou Medical University","correspondingAuthor":false,"prefix":"","firstName":"Jiaying","middleName":"","lastName":"Tan","suffix":""},{"id":333682779,"identity":"7240532a-90c7-4eda-abc5-366836d6171b","order_by":6,"name":"Yinghong Zhou","email":"","orcid":"","institution":"The University of Queensland","correspondingAuthor":false,"prefix":"","firstName":"Yinghong","middleName":"","lastName":"Zhou","suffix":""},{"id":333682780,"identity":"ab1132cb-0537-42de-bb02-54d31650d38b","order_by":7,"name":"Ting Yu","email":"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAAAsElEQVRIiWNgGAWjYDCCAxBKjo29/QDRWhgbgJQxH8+ZBNK0JM6TcDAgTgff8d7jDxjbDqe3STAkMPyo2EZYi+SZc4kNQC25bdKNBxh7ztwmrMXgRo4hRIvMgQRmxjZitNx/A9aSziaRYECklhs8YC0JxGuRPJNjOIPhXLphGzCQDxLlF77jZww+MJRZy8u3tx988KOCCC0gwPyXDcI4QJx6MPhDgtpRMApGwSgYeQAA2No+hw8BHU0AAAAASUVORK5CYII=","orcid":"","institution":"Guangzhou Medical University","correspondingAuthor":true,"prefix":"","firstName":"Ting","middleName":"","lastName":"Yu","suffix":""}],"badges":[],"createdAt":"2024-07-02 14:48:44","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-4675086/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-4675086/v1","draftVersion":[],"editorialEvents":[{"content":"https://doi.org/10.1186/s12903-024-05173-x","type":"published","date":"2024-11-15T15:57:03+00:00"}],"editorialNote":"","failedWorkflow":false,"files":[{"id":62137389,"identity":"3c32c824-b95c-4ff2-b784-1759c1f1235d","added_by":"auto","created_at":"2024-08-09 16:32:48","extension":"png","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":140372,"visible":true,"origin":"","legend":"\u003cp\u003eWorkflow of inclusion criteria.\u003c/p\u003e","description":"","filename":"Figure1.png","url":"https://assets-eu.researchsquare.com/files/rs-4675086/v1/1f2301407f263ed088693571.png"},{"id":62137391,"identity":"035f2f00-15d9-4b6f-b6d8-a71e0b92f31f","added_by":"auto","created_at":"2024-08-09 16:32:48","extension":"png","order_by":2,"title":"Figure 2","display":"","copyAsset":false,"role":"figure","size":311899,"visible":true,"origin":"","legend":"\u003cp\u003eDose-response relationship between serum UA level and risk of periodontitis. A nonlinear association between serum UA and risk of developing moderate/severe periodontitis was found. The solid and dashed line denoted the estimated values and their corresponding 95% confidence interval, respectively. The adjusted factors involved demography, life styles and systemic conditions.\u003c/p\u003e","description":"","filename":"Figure2.png","url":"https://assets-eu.researchsquare.com/files/rs-4675086/v1/26f5b166f3a0ff9f6a5e39fe.png"},{"id":62137390,"identity":"d7640985-3e47-4650-a5f0-14a4d42cb3e1","added_by":"auto","created_at":"2024-08-09 16:32:48","extension":"png","order_by":3,"title":"Figure 3","display":"","copyAsset":false,"role":"figure","size":118702,"visible":true,"origin":"","legend":"\u003cp\u003eThe predictive performance of serum UA/Cr ratio in identifying moderate/severe periodontitis. AUC, area under the curve; UA/Cr ratio, uric acid to creatinine ratio.\u003c/p\u003e","description":"","filename":"Figure3.png","url":"https://assets-eu.researchsquare.com/files/rs-4675086/v1/332d7f9cf1e4db2d45a4f162.png"},{"id":69274809,"identity":"e6a00b61-55f8-41c3-b623-e4e6878a6728","added_by":"auto","created_at":"2024-11-18 16:32:42","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":1489836,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-4675086/v1/2a2ef2eb-dc56-4467-8ac2-d9de45381a03.pdf"},{"id":62137388,"identity":"5bcf7f9c-c4ee-4974-a84c-00c99da4085c","added_by":"auto","created_at":"2024-08-09 16:32:48","extension":"docx","order_by":1,"title":"","display":"","copyAsset":false,"role":"supplement","size":221857,"visible":true,"origin":"","legend":"","description":"","filename":"Supplementarymaterials.docx","url":"https://assets-eu.researchsquare.com/files/rs-4675086/v1/afea59a7c4060e165d3d5c77.docx"}],"financialInterests":"No competing interests reported.","formattedTitle":"Hyperuricemia and Elevated Uric Acid/Creatinine Ratio are Associated with a Higher Risk of Periodontitis: A Population- based Cross-Sectional Study","fulltext":[{"header":"1 INTRODUCTION","content":"\u003cp\u003ePeriodontitis is a multifactorial inflammatory condition characterized by progressive destruction of the periodontal supporting apparatus. It arises from the interplay between oral dysbiosis and dysregulated host inflammatory responses. Severe periodontitis affects approximately 24% of the global population, leading to significant risks of tooth loss and reduced quality of life [\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e]. Periodontitis is linked to numerous systemic inflammatory and metabolic comorbidities, such as metabolic syndrome and cardiovascular diseases. The co-occurrence and reciprocal impacts of periodontitis and systemic disorders significantly contribute to the global disease burden and present substantial public health challenges. Previous studies have indicated strong associations between periodontitis and the \u0026ldquo;triple H\u0026rdquo; conditions: hyperglycemia, hyperlipidemia, and hypertension [\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e]. However, there has been limited investigation into the potential connection between periodontitis and the emerging \u0026ldquo;fourth H\u0026rdquo;, hyperuricemia, which is increasingly recognized as another component of metabolic syndrome.\u003c/p\u003e \u003cp\u003eHyperuricemia is a prevalent metabolic disorder caused by disturbances in uric acid (UA) metabolism, affecting around 20% the US population according to the National Health and Nutrition Examination Survey (NHANES) 2007\u0026ndash;2016 [\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e]. Besides triggering gout and kidney stones, hyperuricemia has recently been identified as a potential risk factor for cardiovascular diseases, osteoporosis, and chronic kidney diseases.[\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e]. Individuals with hyperuricemia exhibit systemic impairments in innate and adaptive immune responses [\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e, \u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e]. UA appears to be a primary trigger for these impaired host responses, displaying pro-inflammatory and pro-oxidative properties under pathological conditions. Given the shared systemic comorbidities and impaired host responses in both hyperuricemia and periodontitis, it is plausible to hypothesize that hyperuricemia might be a susceptibility factor for periodontitis.\u003c/p\u003e \u003cp\u003eBy 2020, several studies had explored the relationship between periodontitis and hyperuricemia [\u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e]. However, positive associations found in earlier studies were limited to normal serum UA levels, with UA previously considered an antioxidant in periodontal medicine. In 2020, our group hypothesized that hyperuricemia could be a potential risk factor for periodontitis and proposed serval plausible mechanisms [\u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e]. Subsequent studies provided direct evidence exploring this relationship, but their conclusions were controversial. A cross-sectional study based on Taiwan population concluded that UA adversely effects periodontal condition [\u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e]. Conversely, a cross-sectional study based on Korean population suggested that hyperuricemia might protect against periodontitis [\u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e], while another study found no significant relationship between hyperuricemia and periodontitis [\u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e]. Consequently, the existence and magnitude of hyperuricemia\u0026rsquo;s effect on periodontitis remain uncertain.\u003c/p\u003e \u003cp\u003eTo investigate the relationship between hyperuricemia and the risk of developing periodontitis, the present study aims to conduct a cross-sectional analysis of the US population using the NHANES database.\u003c/p\u003e"},{"header":"2 MATERIALS AND METHODS","content":"\u003cp\u003e\u003cb\u003e Ethic Statement and Reporting Guideline\u003c/b\u003e\u003c/p\u003e \u003cp\u003e The NHANES project was approved by the Ethics Review Committee of the National Center for Health Statistics of the US. All participants provided their informed consent. This study adhered to the STROBE guidelines for reporting cross-sectional studies [\u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e].\u003c/p\u003e \u003cp\u003e \u003cb\u003ePECOS\u003c/b\u003e \u003c/p\u003e \u003cp\u003eParticipants\u0026thinsp;=\u0026thinsp;Community population of US adults\u003c/p\u003e \u003cp\u003eExposure\u0026thinsp;=\u0026thinsp;Hyperuricemia\u003c/p\u003e \u003cp\u003eComparison\u0026thinsp;=\u0026thinsp;Free from hyperuricemia\u003c/p\u003e \u003cp\u003eOutcome\u0026thinsp;=\u0026thinsp;Developing moderate/severe periodontitis\u003c/p\u003e \u003cp\u003eS\u0026thinsp;=\u0026thinsp;Cross-sectional study\u003c/p\u003e \u003cp\u003e \u003cb\u003eResearch Question\u003c/b\u003e \u003c/p\u003e \u003cp\u003eCompared with individuals without hyperuricemia, do those with hyperuricemia carry a higher risk of developing moderate/severe periodontitis?\u003c/p\u003e \u003cdiv id=\"Sec3\" class=\"Section2\"\u003e \u003ch2\u003e2.1 Study Population\u003c/h2\u003e \u003cp\u003eThis study combined data from three waves of NHANES data were combined (2009 to 2010, 2011 to 2012 and 2013 to 2014). A full-mouth, six-site per tooth periodontal examination was conducted by well-trained examiners, assessing attachment loss and pocket probing depth. Participants aged over 30 with at least one existing tooth were included in the periodontal examination. A total of 10,683 qualified individuals were initially considered for further analysis. After excluding 525 participants due to missing serum UA data, 10,158 participants remained for statistical analysis (Fig.\u0026nbsp;\u003cspan refid=\"Fig1\" class=\"InternalRef\"\u003e1\u003c/span\u003e).\u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec4\" class=\"Section2\"\u003e \u003ch2\u003e2.2 Measurement of Serum UA and Definition of Hyperuricemia\u003c/h2\u003e \u003cp\u003eIn the NHANES cycles from 2009 and 2014, serum UA and creatinine levels were measured using the Beckman UniCel DxC800 Synchron. Serum UA was assessed using the timed endpoint method, and creatine was measured using the Jaffe rate method [\u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e]. The UA to creatinine ratio (serum UA/Cr ratio) was calculated to provide a surrogate for the net production of serum UA [\u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e]. Hyperuricemia was defined as serum UA levels\u0026thinsp;\u0026ge;\u0026thinsp;7.0 mg/dL, regardless of sex in the present study [\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e]. During the NHANES home interview, participants were asked, \u0026ldquo;Has a doctor or other health professional ever told you that you had gout?\u0026rdquo; Those who answered \u0026ldquo;Yes\u0026rdquo; were diagnosed with gout for the purposes of this study.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec5\" class=\"Section2\"\u003e \u003ch2\u003e2.3 Diagnosis and Classification of Periodontitis\u003c/h2\u003e \u003cp\u003eTo identify individuals with periodontitis, the criteria established by the Centers for Disease Control and Prevention (CDC) and the American Academy of Periodontology (AAP) were applied [\u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e]. Mild periodontitis was defined by the presence of at least two interproximal sites with attachment loss (AL)\u0026thinsp;\u0026ge;\u0026thinsp;3 mm, and at least two interproximal sites with probing depth (PD)\u0026thinsp;\u0026ge;\u0026thinsp;4 mm (not on the same tooth), or one site with PD\u0026thinsp;\u0026ge;\u0026thinsp;5 mm. Moderate periodontitis was diagnosed when there were at least two interproximal sites with AL\u0026thinsp;\u0026ge;\u0026thinsp;4 mm (not on the same tooth), or at least two interproximal sites with PD\u0026thinsp;\u0026ge;\u0026thinsp;5 mm (also not on the same tooth). Severe periodontitis was diagnosed by the presence of at least two interproximal sites with AL\u0026thinsp;\u0026ge;\u0026thinsp;6 mm (not on the same tooth) and at least one interproximal site with PD\u0026thinsp;\u0026ge;\u0026thinsp;4 mm. Individuals were identified as having no periodontitis if none of these conditions were met. Further classifications were performed based on the initial diagnosis.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec6\" class=\"Section2\"\u003e \u003ch2\u003e2.4 Assessment of covariates\u003c/h2\u003e \u003cp\u003eInformation on sex, age, ethnicity, poverty to income ratio (PIR), and educational attainment was extracted from the demographic section of NHANES. Participants were categorized based on smoking status as non-smokers (consumed less than 100 cigarettes in their lifetime), former smokers (consumed more than 100 cigarettes but currently quit) and current smokers (have ongoing smoking habit). Alcohol consumption was categorized into non-drinkers, 1 to 5 drinks per month, 5 to 10 drinks per month, or more than 10 drinks per month.\u003c/p\u003e \u003cp\u003eBody mass index (BMI) data were obtained from the physical examinations section. Participants were identified as having certain medical conditions based on their responses to questions about whether a doctor or other health professional has ever diagnosed them with diabetes, high cholesterol, cancer, weak or failing kidneys, or cerebra-cardiovascular diseases (including congestive heart failure, coronary heart disease, angina, heart attack, stroke or hypertension).\u003c/p\u003e \u003cp\u003e Participants were considered to have received periodontal treatment if they answered \u0026ldquo;Yes\u0026rdquo; to the question, \u0026ldquo;Have you ever had treatment for gum disease such as scaling and root planning, sometimes called \"deep cleaning\"?\u0026rdquo;. Additionally, participants were asked, \u0026ldquo;In the past month, have you used or taken medication for which a prescription is needed?\u0026rdquo; (excluding vitamins or minerals). Participants were identified as receiving urate-lowering therapy (ULT) if they reported currently taking allopurinol, febuxostat, or probenecid [\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e].\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec7\" class=\"Section2\"\u003e \u003ch2\u003e2.5 Statistical Analysis\u003c/h2\u003e \u003cp\u003eAll statistical analysis were conducted using the noncommercial software R (version 4.1.0). Data from three NHANES cycles (2009 to 2010, 2011 to 2012 and 2013 to 2014) were combined, and 6-year sampling weights were constructed according to NHANES recommendations [\u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e]. Multiple imputation was applied to complete missing covariate data before conducting statistical analysis.\u003c/p\u003e \u003cp\u003eDifferences in categorical and continuous variables between individuals with moderate/severe periodontitis and controls were compared using \u003cem\u003eChi\u003c/em\u003e-square tests and Student\u0026rsquo;s \u003cem\u003et\u003c/em\u003e tests, respectively. Continuous were presented as means (\u0026plusmn;\u0026thinsp;standard deviations, SDs), and categorical variables as corresponding proportions.\u003c/p\u003e \u003cp\u003eWeighted multivariable logistic regression was employed to estimate the odds ratio (\u003cem\u003eOR\u003c/em\u003e) and confidence interval (\u003cem\u003eCI\u003c/em\u003e) for the associations between hyperuricemia (as well as serum UA and serum UA/Cr ratio) and periodontitis. Model 1 adjusted for demographic factors, including sex, age groups, ethnicity, PIR and educational attainment. Model 2 further adjusted for BMI and lifestyle factors such as smoking status and alcohol consumption. Model 3 additionally adjusted for systemic conditions (including a history of cerebra-cardiovascular diseases, diabetes, hyperlipidemia, cancer and kidney conditions), periodontal treatment and ULT based on Model 2.\u003c/p\u003e \u003cp\u003eNonlinear relationships between serum UA and periodontitis were evaluated using restricted cubic spline regression, and the inflection point was calculated using the two-piecewise linear regression model. The receiver operating characteristic curve was used to evaluate the predictive competence of the serum UA/Cr ratio for moderate/severe periodontitis. The significance level was set at \u003cem\u003eP\u003c/em\u003e\u0026thinsp;\u0026lt;\u0026thinsp;0.05.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec8\" class=\"Section2\"\u003e \u003ch2\u003e2.6 Sensitivity Analysis\u003c/h2\u003e \u003cp\u003eTo enhance the robustness of the findings, alternative definitions of hyperuricemia and classifications of periodontitis were used for validation analysis. The alternative definition of hyperuricemia identified subjects as having hyperuricemia if serum UA levels were \u0026ge;\u0026thinsp;7.0 mg/dL in males or \u0026ge;\u0026thinsp;6.0 mg/dL in females [\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eTwo alternative classifications of periodontitis were applied:\u003c/p\u003e \u003c/div\u003e\n\u003cp\u003e1. Participants were divided into those with periodontitis and healthy controls.\u003c/p\u003e\n\u003cp\u003e2. Two separate statistical analysis were performed: one comparing severe periodontitis to healthy controls, and another comparing mild and moderate periodontitis to healthy controls.\u003c/p\u003e \u003cp\u003eSubgroup analysis stratified by sex, age, ethnicity, diabetes, hyperlipidemia, gout, periodontal treatment, and ULT were performed to verify the findings within specific populations. Interaction effects between hyperuricemia and serval characteristics were tested to examine the distinctions among specific subgroups.\u003c/p\u003e"},{"header":"3 RESULTS","content":"\u003cdiv id=\"Sec11\" class=\"Section2\"\u003e \u003ch2\u003e3.1 Characteristics of the Study Population\u003c/h2\u003e \u003cp\u003eIn the US population, the overall prevalence of periodontitis was 42.1%, consisting of 4.3% mild, 30.0% moderate and 7.8% severe forms. Nineteen percent of the study population were diagnosed with hyperuricemia, and 3.9% reported a history of gout diagnosis. Hyperuricemia prevalence was 6.6% in females and 22.1% in males. Among different ethnicities, Non-Hispanic Whites accounted for 70.0% of all cases of hyperuricemia.\u003c/p\u003e \u003cp\u003eAmong participants with hyperuricemia, 47.2% had moderate/severe periodontitis (11.6% moderate, 35.6% severe), while among those without hyperuricemia, the corresponding proportion was 36.2% (7.2% moderate, 29.0% severe) (Table\u0026nbsp;\u003cspan refid=\"Tab1\" class=\"InternalRef\"\u003e1\u003c/span\u003e).\u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab1\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 1\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003eBaseline characteristics of the study population stratified by periodontitis\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"5\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c5\" colnum=\"5\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e \u003cp\u003eCharacteristics\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003eOverall\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003eNon-hyperuricemia\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c4\"\u003e \u003cp\u003eHyperuricemia\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c5\"\u003e \u003cp\u003e\u003cem\u003eP\u003c/em\u003e value\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eFrequency\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e138,117,868\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e119,221,910\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e18,895,959\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e/\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eSex\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;0.001***\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eFemale\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e5,136 (50.9%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e4,799 (55.6%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e337 (21.2%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eMale\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e5,022 (49.1%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e3,911 (44.4%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e1,111 (78.8%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eAge\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.063\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e30-44-year-old\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e3,418 (34.6%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e2,993 (34.8%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e425 (32.8%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e45-64-year-old\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e4,146 (43.5%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e3,557 (43.7%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e589 (42.3%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u0026gt;\u0026thinsp;65-year-old\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e2,594 (21.9%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e2,160 (21.5%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e434 (24.9%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePIR\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.200\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u0026le;\u0026thinsp;1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e1,983 (12.1%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e1,721 (12.4%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e262 (10.8%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u0026ge;\u0026thinsp;3\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e4,139 (54.4%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e3,559 (54.4%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e580 (54.1%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e1\u0026ndash;3\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e4,036 (33.5%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e3,430 (33.2%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e606 (35.1%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eEducational attainment\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.200\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eLess than high school\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e2,355 (15.2%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e2,017 (15.2%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e338 (14.9%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eHigh school graduate\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e2,199 (20.9%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e1,864 (20.6%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e335 (22.7%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eCollege graduate or above\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e5,604 (63.9%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e4,829 (64.2%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e775 (62.3%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eEthnicity\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;0.001***\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eNon-Hispanic White\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e4,438 (69.2%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e3,796 (69.0%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e642 (70.3%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eNon-Hispanic Black\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e2,021 (10.1%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e1,647 (9.8%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e374 (12.3%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eMexican American\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e1,467 (8.1%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e1,311 (8.4%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e156 (6.1%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eOthers\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e1,217 (7.2%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e1,047 (7.2%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e170 (7.2%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eOther Hispanic\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e1,015 (5.4%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e909 (5.6%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e106 (4.0%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eBMI\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;0.001***\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003enormal weight\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e2,639 (26.3%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e2,448 (28.7%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e191 (10.6%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eunderweight\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e118 (1.1%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e110 (1.2%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e8 (0.5%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eoverweight\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e3,534 (35.6%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e3,070 (35.7%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e464 (34.9%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eobesity\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e3,867 (37.1%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e3,082 (34.4%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e785 (54.0%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eSmoking status\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.036*\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eCurrent smoker\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e1,906 (17.3%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e1,651 (17.4%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e255 (17.0%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eFormer smoker\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e2,554 (26.4%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e2,106 (25.8%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e448 (30.2%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eNon-smoker\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e5,698 (56.3%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e4,953 (56.9%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e745 (52.8%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eAlcohol consumption\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;0.001***\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e1\u0026ndash;5 drinks/month\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e4,993 (49.6%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e4,306 (50.0%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e687 (46.9%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e10\u0026thinsp;+\u0026thinsp;drinks/month\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e1,651 (20.1%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e1,319 (19.1%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e332 (27.0%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e5\u0026ndash;10 drinks/month\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e768 (9.3%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e647 (9.1%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e121 (9.9%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eNon-drinker\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e2,746 (21.0%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e2,438 (21.8%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e308 (16.2%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eHypertension\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;0.001***\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eNo\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e6,355 (65.9%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e5,696 (68.6%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e659 (48.5%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eYes\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e3,803 (34.1%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e3,014 (31.4%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e789 (51.5%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eHyperlipidemia\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.003**\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eNo\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e6,109 (60.5%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e5,343 (61.4%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e766 (54.4%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eYes\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e4,049 (39.5%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e3,367 (38.6%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e682 (45.6%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eDiabetes\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;0.001***\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eNo\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e8,631 (88.0%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e7,468 (88.7%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e1,163 (84.0%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eYes\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e1,527 (12.0%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e1,242 (11.3%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e285 (16.0%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eCerebra-cardiovascular diseases\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;0.001***\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eNo\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e9,266 (92.7%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e8,026 (93.5%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e1,240 (87.5%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eYes\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e892 (7.3%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e684 (6.5%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e208 (12.5%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eCancer\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.300\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eNo\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e9,217 (89.5%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e7,907 (89.6%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e1,310 (88.5%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eYes\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e941 (10.5%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e803 (10.4%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e138 (11.5%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eKidney diseases\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;0.001***\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eNo\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e9,884 (97.9%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e8,516 (98.3%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e1,368 (95.4%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eYes\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e274 (2.1%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e194 (1.7%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e80 (4.6%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eGout\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;0.001***\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eNo\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e9,743 (96.1%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e8,468 (97.2%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e1,275 (89.2%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eYes\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e415 (3.9%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e242 (2.8%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e173 (10.8%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eULT\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.013*\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eNo\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e10,030 (98.7%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e8,609 (98.8%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e1,421 (98.2%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eYes\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e128 (1.3%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e101 (1.2%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e27 (1.8%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePeriodontal treatment\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.600\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eNo\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e7,751 (78.0%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e6,637 (78.1%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e1,114 (77.3%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eYes\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e2,407 (22.0%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e2,073 (21.9%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e334 (22.7%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eSerum UA\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e5.42\u0026thinsp;\u0026plusmn;\u0026thinsp;1.40\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e5.04\u0026thinsp;\u0026plusmn;\u0026thinsp;1.06\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e7.81\u0026thinsp;\u0026plusmn;\u0026thinsp;0.81\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;0.001***\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eSerum UA/Cr ratio\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e6.30\u0026thinsp;\u0026plusmn;\u0026thinsp;1.60\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e6.07\u0026thinsp;\u0026plusmn;\u0026thinsp;1.45\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e7.72\u0026thinsp;\u0026plusmn;\u0026thinsp;1.76\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;0.001***\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePeriodontal conditions\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;0.001***\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eHealthy\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e4,960 (58.0%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e4,394 (59.5%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e566 (48.6%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eMild periodontitis\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e475 (4.3%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e414 (4.3%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e61 (4.2%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eModerate\u003c/p\u003e \u003cp\u003eperiodontitis\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e3,598 (29.9%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e2,995 (29.0%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e603 (35.6%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eSevere\u003c/p\u003e \u003cp\u003eperiodontitis\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e1,125 (7.8%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e907 (7.2%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e218 (11.6%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003ctfoot\u003e \u003ctr\u003e\u003ctd colspan=\"5\"\u003e***, \u003cem\u003eP\u003c/em\u003e\u0026thinsp;\u0026lt;\u0026thinsp;0.001; **, \u003cem\u003eP\u003c/em\u003e\u0026thinsp;\u0026lt;\u0026thinsp;0.01; *, \u003cem\u003eP\u003c/em\u003e\u0026thinsp;\u0026lt;\u0026thinsp;0.05; BMI, body mass index; PIR, poverty to income ratio; UA, uric acid; UA/Cr ratio, uric acid to creatinine ratio; ULT, urate-lowering therapy.\u003c/td\u003e\u003c/tr\u003e \u003c/tfoot\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec12\" class=\"Section2\"\u003e \u003ch2\u003e3.2 Associations Between Hyperuricemia and Risk of Periodontitis\u003c/h2\u003e \u003cp\u003eThe crude model demonstrated that individuals with hyperuricemia had a 57.3% increased risk (\u003cem\u003eOR\u003c/em\u003e\u0026thinsp;=\u0026thinsp;1.573, 95% \u003cem\u003eCI\u003c/em\u003e\u0026thinsp;=\u0026thinsp;1.350 to 1.832, \u003cem\u003eP\u003c/em\u003e\u0026thinsp;\u0026lt;\u0026thinsp;0.001) of developing moderate/severe periodontitis compared to controls without hyperuricemia. After adjusting for demographic factors including sex, age, ethnicity, educational attainment and PIR, the periodontal risk declined to 28.2%. Further adjustment for lifestyle, BMI, systemic conditions (including cerebra-cardiovascular diseases, diabetes, hyperlipidemia, cancers and kidney diseases), periodontal treatment and ULT revealed that hyperuricemia remained significantly associated with a\u0026thinsp;~\u0026thinsp;30% increased risk of developing moderate/severe periodontitis (Table\u0026nbsp;\u003cspan refid=\"Tab2\" class=\"InternalRef\"\u003e2\u003c/span\u003e).\u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab2\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 2\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003eEffects of hyperuricemia, serum UA and serum UA/Cr ratio on risk of periodontitis assessed by logistic regression\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"5\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c5\" colnum=\"5\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e \u003cp\u003eExposure\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003eModel\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003e\u003cem\u003eOR\u003c/em\u003e\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c4\"\u003e \u003cp\u003e95% \u003cem\u003eCI\u003c/em\u003e\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c5\"\u003e \u003cp\u003e\u003cem\u003eP\u003c/em\u003e value\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eHyperuricemia\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eCrude model\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e1.573\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e1.350, 1.832\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;0.001***\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eModel 1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e1.282\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e1.096, 1.498\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e0.003**\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eModel 2\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e1.300\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e1.105, 1.529\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e0.002**\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eModel 3\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e1.269\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e1.080, 1.492\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e0.006**\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eSerum UA\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eCrude model\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e1.150\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e1.109, 1.191\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;0.001***\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eModel 1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e1.017\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.978, 1.058\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e0.389\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eModel 2\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e1.030\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.987, 1.074\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e0.165\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eModel 3\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e1.021\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.977, 1.068\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e0.338\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eUA/Cr ratio\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eCrude model\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e1.034\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e1.001, 1.069\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e0.045*\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eModel 1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e1.045\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e1.010, 1.080\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e0.013*\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eModel 2\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e1.048\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e1.010, 1.088\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e0.015*\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eModel 3\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e1.046\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e1.008, 1.086\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e0.021*\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003ctfoot\u003e \u003ctr\u003e\u003ctd colspan=\"5\"\u003e\u003cem\u003eCI\u003c/em\u003e, confidence interval; \u003cem\u003eOR\u003c/em\u003e, odds ratio; UA, uric acid; UA/Cr ratio, uric acid to creatinine ratio; ***, \u003cem\u003eP\u003c/em\u003e\u0026thinsp;\u0026lt;\u0026thinsp;0.001; **, \u003cem\u003eP\u003c/em\u003e\u0026thinsp;\u0026lt;\u0026thinsp;0.01; *, \u003cem\u003eP\u003c/em\u003e\u0026thinsp;\u0026lt;\u0026thinsp;0.05; Model 1, adjusted for demographic factors, including sex, age, ethnicity, poverty to income ratio, educational attainment; Model 2, adjusted for smoking status, alcohol consumption, body mass index and the aforementioned demographic factors; Model 3, adjusted for cerebra-cardiovascular conditions (including congestive heart failure, coronary heart disease, angina, heart attack, stroke and hypertension), hyperlipidemia, diabetes, cancer, kidney conditions, periodontal treatment and urate-lowering therapy on the basis of model 2.\u003c/td\u003e\u003c/tr\u003e \u003c/tfoot\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec13\" class=\"Section2\"\u003e \u003ch2\u003e3.3 Associations Between Serum UA Level and Risk of Periodontitis\u003c/h2\u003e \u003cp\u003eThe crude model demonstrated a linear positive relationship between serum UA level and the risk of developing moderate/severe periodontitis (\u003cem\u003eOR\u003c/em\u003e\u0026thinsp;=\u0026thinsp;1.150, 95% \u003cem\u003eCI\u003c/em\u003e\u0026thinsp;=\u0026thinsp;1.109 to 1.191, \u003cem\u003eP\u003c/em\u003e\u0026thinsp;\u0026lt;\u0026thinsp;0.001). However, after adjusting for demographic factors, lifestyle, BMI, systemic conditions, periodontal treatment and ULT, the statistical significance of this linear relationship was lost (Table\u0026nbsp;\u003cspan refid=\"Tab2\" class=\"InternalRef\"\u003e2\u003c/span\u003e).\u003c/p\u003e \u003cp\u003eRestricted cubic spline regression, conducted with the adjusted model, identified a significant U-shaped (i.e., non-linear) relationship between serum UA level and the risk of developing moderate/severe periodontitis (\u003cem\u003eP\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.0417) (Fig.\u0026nbsp;\u003cspan refid=\"Fig2\" class=\"InternalRef\"\u003e2\u003c/span\u003e). Threshold effect analysis further estimated an inflection point at 5.5 mg/dL. Above 5.5 mg/dL, every 1 mg/dL increase in serum UA was associated with a 10.2% higher risk (adjusted \u003cem\u003eOR\u003c/em\u003e\u0026thinsp;=\u0026thinsp;1.102, 95% \u003cem\u003eCI\u003c/em\u003e\u0026thinsp;=\u0026thinsp;1.008 to 1.206, \u003cem\u003eP\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.035) of developing moderate/severe periodontitis (Table\u0026nbsp;\u003cspan refid=\"Tab3\" class=\"InternalRef\"\u003e3\u003c/span\u003e). Conversely, below 5.5 mg/dL, every 1 mg/dL increase in serum UA was associated with a 10.6% lower periodontal risk (adjusted \u003cem\u003eOR\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.894, 95% \u003cem\u003eCI\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.800 to 0.998, \u003cem\u003eP\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.046).\u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab3\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 3\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003eThreshold effect analyses of the effects of serum UA on the risk of periodontitis\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"2\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003eAdjusted \u003cem\u003eOR\u003c/em\u003e (95% \u003cem\u003eCI\u003c/em\u003e), \u003cem\u003eP\u003c/em\u003e value\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eInflection point\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e5.5 mg/dL\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cem\u003eP\u003c/em\u003e for log likelihood ratio\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e\u003cem\u003eP\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.006\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eSerum UA\u0026thinsp;\u0026le;\u0026thinsp;5.5 mg/dL\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e0.894 (0.800, 0.998), 0.046\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eSerum UA\u0026thinsp;\u0026gt;\u0026thinsp;5.5 mg/dL\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e1.102 (1.008, 1.206), 0.035\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003ctfoot\u003e \u003ctr\u003e\u003ctd colspan=\"2\"\u003eSex, age, ethnicity, educational attainment, poverty to income ratio, body mass index, smoking status, alcohol consumption, cerebra-cardiovascular conditions, hyperlipidemia, diabetes, cancer, kidney conditions, periodontal treatment and ULT were adjusted for; \u003cem\u003eCI\u003c/em\u003e, confidence interval; serum UA, serum uric acid; \u003cem\u003eOR\u003c/em\u003e, odds ratio;\u003c/td\u003e\u003c/tr\u003e \u003c/tfoot\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec14\" class=\"Section2\"\u003e \u003ch2\u003e3.4 Associations Between Serum UA/Cr Ratio and Risk of Periodontitis\u003c/h2\u003e \u003cp\u003eGiven the potential influence of renal function on serum UA levels, an emerging index, serum UA/Cr ratio, was utilized to reflect the net production of serum UA. Exploration of the correlation between serum UA/Cr ratio and the risk of developing moderate/severe periodontitis was conducted.\u003c/p\u003e \u003cp\u003eGenerally, the serum UA/Cr ratio in individuals with and without hyperuricemia was 6.07\u0026thinsp;\u0026plusmn;\u0026thinsp;1.45 and 7.72\u0026thinsp;\u0026plusmn;\u0026thinsp;1.76, respectively. The crude model indicated that each unit increase in serum UA/Cr ratio was associated with a 3.4% elevated risk of developing moderate/severe periodontitis (\u003cem\u003eOR\u003c/em\u003e\u0026thinsp;=\u0026thinsp;1.034, 95% \u003cem\u003eCI\u003c/em\u003e\u0026thinsp;=\u0026thinsp;1.001 to 1.069). After adjusting for demographic factors, lifestyle, BMI, systemic conditions, periodontal treatment and ULT, the increased periodontal risk was 4.6% (adjusted \u003cem\u003eOR\u003c/em\u003e\u0026thinsp;=\u0026thinsp;1.046, 95% \u003cem\u003eCI\u003c/em\u003e\u0026thinsp;=\u0026thinsp;1.008 to 1.086, \u003cem\u003eP\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.021) (Table\u0026nbsp;\u003cspan refid=\"Tab2\" class=\"InternalRef\"\u003e2\u003c/span\u003e). However, the receiver operating characteristic curve demonstrated that the serum UA/Cr ratio lacked the competence to predict moderate/severe periodontitis (Fig.\u0026nbsp;\u003cspan refid=\"Fig3\" class=\"InternalRef\"\u003e3\u003c/span\u003e).\u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec15\" class=\"Section2\"\u003e \u003ch2\u003e3.5 Sensitivity analysis\u003c/h2\u003e \u003cp\u003eTo examine the robustness of the findings, an alternate definition of hyperuricemia (i.e., male\u0026thinsp;\u0026gt;\u0026thinsp;7.0 mg/dL, or female\u0026thinsp;\u0026gt;\u0026thinsp;6.0 mg/dL) was applied for sensitivity analysis. Initially, the crude model demonstrated that individuals with hyperuricemia exhibited a 40.1% elevated risk of developing moderate/severe periodontitis compared to those without hyperuricemia (\u003cem\u003eOR\u003c/em\u003e\u0026thinsp;=\u0026thinsp;1.401, 95% \u003cem\u003eCI\u003c/em\u003e\u0026thinsp;=\u0026thinsp;1.223 to 1.605, \u003cem\u003eP\u003c/em\u003e\u0026thinsp;\u0026lt;\u0026thinsp;0.001). The increased periodontal risks ranged from 24.0\u0026ndash;27.9% after adjusting for demographic and systemic factors.\u003c/p\u003e \u003cp\u003eFurthermore, diverse grouping maneuvers over periodontal conditions were performed while maintaining the primary definition of hyperuricemia r (i.e., \u0026gt;\u0026thinsp;7.0 mg/dL regardless of sex). The crude model demonstrated that individuals with hyperuricemia carried a 55.3% increased risk (\u003cem\u003eOR\u003c/em\u003e\u0026thinsp;=\u0026thinsp;1.553, 95% \u003cem\u003eCI\u003c/em\u003e\u0026thinsp;=\u0026thinsp;1.319 to 1.829, \u003cem\u003eP\u003c/em\u003e\u0026thinsp;\u0026lt;\u0026thinsp;0.001) of developing any type of periodontitis compared to those without, with adjusted risks ranging from 19.0\u0026ndash;23.8%.\u003c/p\u003e \u003cp\u003eCompared to those without hyperuricemia, individuals with it carried a 46.3% increased risk (\u003cem\u003eOR\u003c/em\u003e\u0026thinsp;=\u0026thinsp;1.463, 95% \u003cem\u003eCI\u003c/em\u003e\u0026thinsp;=\u0026thinsp;1.236 to 1.730, \u003cem\u003eP\u003c/em\u003e\u0026thinsp;\u0026lt;\u0026thinsp;0.001) of developing mild/moderate periodontitis (vs. no periodontitis). However, the significance was lost after adjusting for demographic and systemic factors (\u003cem\u003eOR\u003c/em\u003e\u0026thinsp;=\u0026thinsp;1.162, 95% \u003cem\u003eCI\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.982 to 1.375, \u003cem\u003eP\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.078).\u003c/p\u003e \u003cp\u003eIndividuals with hyperuricemia carried a 97.4% higher risk (\u003cem\u003eOR\u003c/em\u003e\u0026thinsp;=\u0026thinsp;1.974, 95% \u003cem\u003eCI\u003c/em\u003e\u0026thinsp;=\u0026thinsp;1.524 to 2.556, \u003cem\u003eP\u003c/em\u003e\u0026thinsp;\u0026lt;\u0026thinsp;0.001) of developing severe periodontitis compared to those without, with adjusted risks ranging from 42.7\u0026ndash;47.2%.\u003c/p\u003e \u003cp\u003eEven after altering the definition of hyperuricemia and grouping tactics for periodontal conditions in sensitivity analysis, the results remained robust (see Supplementary Materials).\u003c/p\u003e \u003cp\u003eInteraction analysis revealed a significant interaction between hyperuricemia and ULT (\u003cem\u003eP\u003c/em\u003e for interaction\u0026thinsp;\u0026lt;\u0026thinsp;0.001). Subgroup analysis showed that the increased periodontal risk in the ULT subgroup (adjusted \u003cem\u003eOR\u003c/em\u003e\u0026thinsp;=\u0026thinsp;19.488, 95% \u003cem\u003eCI\u003c/em\u003e\u0026thinsp;=\u0026thinsp;3.898 to 97.444) was much higher than that in the non-ULT subgroup (adjusted \u003cem\u003eOR\u003c/em\u003e\u0026thinsp;=\u0026thinsp;1.209, 95% \u003cem\u003eCI\u003c/em\u003e\u0026thinsp;=\u0026thinsp;1.017,1.437, \u003cem\u003eP\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.0318). No significant interactions were found (\u003cem\u003eP\u003c/em\u003e for interaction\u0026thinsp;\u0026gt;\u0026thinsp;0.05) between hyperuricemia and specific covariates, including sex, age, ethnicities, periodontal treatment and history of diabetes, hyperlipidemia or gout (see Figure S5 in Supplementary Materials), suggesting that these factors did not influence the impact of hyperuricemia on the risk of developing periodontitis.\u003c/p\u003e \u003c/div\u003e"},{"header":"4 DISCUSSIONS","content":"\u003cp\u003eSeveral studies have examined the associations between hyperuricemia and periodontitis, yet the results have been inconclusive. The present cross-sectional study, conducted on the US population, is the first of its kind to definitively link hyperuricemia with a 30% increased risk of developing moderate/severe periodontitis, even after adjusting for potential confounders including demographic factors, lifestyles and systemic diseases. Specifically, when focusing solely on the risk of developing severe periodontitis, the increase jumps to 97.4% (\u003cem\u003eOR\u003c/em\u003e\u0026thinsp;=\u0026thinsp;1.974, 95% \u003cem\u003eCI\u003c/em\u003e\u0026thinsp;=\u0026thinsp;1.524 to 2.556).\u003c/p\u003e \u003cp\u003eSensitivity analysis based on varied definitions of hyperuricemia and classifications of periodontal conditions reaffirmed the robustness of the primary findings, with the increased periodontal risks consistently above 20%, regardless of alternations in hyperuricemia definitions and periodontitis classifications. The increase in periodontal risk appears to be linked to a linear relationship with the serum UA/Cr ratio and a U-shaped relationship with serum UA levels. Taken together, the present study provides the first direct evidence suggesting that hyperuricemia may indeed be associated with a higher risk of periodontitis progression.\u003c/p\u003e \u003cp\u003eNumerous observational studies with small sample sizes have noted elevated blood UA levels in individuals with periodontitis compared to those without [\u003cspan citationid=\"CR16\" class=\"CitationRef\"\u003e16\u003c/span\u003e, \u003cspan citationid=\"CR17\" class=\"CitationRef\"\u003e17\u003c/span\u003e]. However, these increases in blood UA levels have often fallen within the normal range, as indicated in the latest systematic review conducted by our research group [\u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eA cross-sectional study in 2018, involving 1,123 individuals (295 with stage Ⅱ/Ⅲ periodontitis vs. 828 with a healthy periodontium), suggested that increased serum UA levels may have adverse effects on periodontitis (\u003cem\u003eOR\u003c/em\u003e\u0026thinsp;=\u0026thinsp;1.100, 95% \u003cem\u003eCI\u003c/em\u003e\u0026thinsp;=\u0026thinsp;1.001 to 1.209). However, this significant association disappeared in the adjusted model (\u003cem\u003eOR\u003c/em\u003e\u0026thinsp;=\u0026thinsp;1.097, 95% \u003cem\u003eCI\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.998 to 1.206), and hyperuricemia diagnosis was not conducted in this study [\u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e]. Two subsequent cross-sectional studies, conducted in 2020 and 2023 respectively and based on the Korean population, attempted to explore the associations between hyperuricemia and periodontitis. However, these two studies either failed to find any significant association between hyperuricemia and periodontitis or suggested hyperuricemia as a protective factor against periodontitis [\u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e, \u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e]. Several reasons may account for these discrepancies. Firstly, the two cross-sectional studies identified periodontitis cases using Community Periodontal Index of limited examined teeth or self-reported diagnosis history, which could lead to a significant proportion of misdiagnosis [\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e]. Secondly, one of the cross-sectional studies excluded numerous individuals with missing covariates, potentially introducing biases into the results.\u003c/p\u003e \u003cp\u003eAnother cross-sectional study based on NHANES data of 2009 to 2011, explored the relationships between hyperuricemia and periodontitis [\u003cspan citationid=\"CR18\" class=\"CitationRef\"\u003e18\u003c/span\u003e]. However, incorrect reporting of periodontitis prevalence in this study has raised concerns about its conclusions [\u003cspan citationid=\"CR19\" class=\"CitationRef\"\u003e19\u003c/span\u003e]. In contrast, the present study, involving over 10,000 individuals from the US population, rigorously diagnosed periodontal conditions and hyperuricemia using quantitative criteria. Moreover, the robustness of the findings was verified by multiple covariate adjustments and sensitivity analysis. In this context, the present study provides the first evidence of a positive association between hyperuricemia and the risk of periodontitis. Specifically, individuals with hyperuricemia were found to be more susceptible to periodontitis, particularly the severe form, compared to those without hyperuricemia. These findings suggest that hyperuricemia may be a novel risk factor for periodontitis.\u003c/p\u003e \u003cp\u003eNotably, the positive association between hyperuricemia and periodontitis differed from the relationship between serum UA levels and periodontitis. Existing studies have yielded conflicting conclusions regarding the correlation between serum UA levels and periodontitis. For instance, a cross-sectional study based of a Taiwan military population found a positive association between serum UA levels and periodontitis risk (\u003cem\u003eOR\u003c/em\u003e\u0026thinsp;=\u0026thinsp;1.100, 95% \u003cem\u003eCI\u003c/em\u003e\u0026thinsp;=\u0026thinsp;1.001 to 1.209). In contrast, a similar study in a Korean population implied that hyperuricemia was negatively associated with periodontitis risk (\u003cem\u003eOR\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.89, 95% \u003cem\u003eCI\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.81 to 0.96).\u003c/p\u003e \u003cp\u003eThe present study, based on a US community population, did not find a linear relationship between serum UA levels and periodontitis after adjusting for covariates. Instead, a U-shaped relationship emerged, a pattern also seen between serum UA levels and other diseases such as chronic kidney diseases and cardiovascular diseases. [\u003cspan citationid=\"CR20\" class=\"CitationRef\"\u003e20\u003c/span\u003e, \u003cspan citationid=\"CR21\" class=\"CitationRef\"\u003e21\u003c/span\u003e]. The inflection point was determined to be 5.5 mg/dL through threshold effect analysis. Below this threshold, increasing serum UA levels were significantly associated with a decreased risk of periodontitis, while levels above 5.5 mg/dL were positively associated with periodontitis. Hence, within a certain range, serum UA may have a protective role against periodontitis due to its potential antioxidative effects under physiological conditions [\u003cspan citationid=\"CR22\" class=\"CitationRef\"\u003e22\u003c/span\u003e]. However, this protective effect appears to be limited. The use of higher thresholds (either 7.0 or 6.0 mg/dL) to define hyperuricemia might obscure the statistically significant protective effects of serum UA on periodontitis.\u003c/p\u003e \u003cp\u003eGout is commonly recognized as symptomatic hyperuricemia. A retrospective cohort study with an average follow-up period of 6 years (gout vs. controls, N\u0026thinsp;=\u0026thinsp;31,759 vs. N\u0026thinsp;=\u0026thinsp;63,517) indicated that individuals with gout had a higher incidence of periodontitis (adjusted hazard ratio\u0026thinsp;=\u0026thinsp;1.13, 95% \u003cem\u003eCI\u003c/em\u003e\u0026thinsp;=\u0026thinsp;1.10 to 1.16). The study also suggested that the use of colchicine, a treatment for gout flare-ups and chronic gout, could reduce the incidence of periodontitis in gout patients (adjusted hazard ratio\u0026thinsp;=\u0026thinsp;0.85, 95% \u003cem\u003eCI\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.79 to 0.91), compared to those not receiving ULT. Interestingly, gout patients were found to have an increased abundance of \u003cem\u003ePrevotella intermedia\u003c/em\u003e in their saliva [\u003cspan citationid=\"CR23\" class=\"CitationRef\"\u003e23\u003c/span\u003e]. Another study reported that tophus (gout nodules) could be found in the gingiva [\u003cspan citationid=\"CR24\" class=\"CitationRef\"\u003e24\u003c/span\u003e]. These studies support a positive correlation between gout and periodontitis.\u003c/p\u003e \u003cp\u003eIn the present study, the prevalence of gout was approximately 20.5% among individuals with hyperuricemia. Subgroup analysis stratified by gout indicated that the effect of hyperuricemia on periodontitis was independent of gout. Besides, gout was not significantly associated with periodontitis when included in logistic regression models. This study did not observe any association between gout and periodontitis, possibly due to the complex relationship between hyperuricemia and gout. It is known that most individuals with hyperuricemia, whose serum UA levels exceed the threshold for urate crystallization, do not have a history of gout [\u003cspan citationid=\"CR25\" class=\"CitationRef\"\u003e25\u003c/span\u003e]. Conversely, patients experiencing gout flare-ups can exhibit normal UA level [\u003cspan citationid=\"CR26\" class=\"CitationRef\"\u003e26\u003c/span\u003e]. In the present study, 58.3% of individuals with a history of gout had normal UA levels at the time of examination, a proportion far exceeding that of those receiving ULT (28.9% of gouty individuals). The observation that most gout patients had normalized their serum UA levels made it difficult to identify a potential relationship between gout and periodontitis.\u003c/p\u003e \u003cp\u003eNotably, the present study found that the impact of hyperuricemia on periodontal risk was influenced by ULT. The increased periodontal risk associated with hyperuricemia in the ULT subgroup was much greater than that in the non-ULT subgroup. However, this does not necessarily mean that ULT amplifies the adverse effect of hyperuricemia on periodontitis. Instead, the higher proportions of hyperuricemia (18.6% vs. 13.6%), gout (91.8% vs. 2.7%) and self-reported kidney diseases (10.0% vs. 2.0%) in the ULT subgroup suggest that these individuals had more refractory hyperuricemia compared to those not receiving ULT (see the proportion of hyperuricemia in the subgroups with/without ULT in the Table\u0026nbsp;\u003cspan refid=\"Tab1\" class=\"InternalRef\"\u003e1\u003c/span\u003e).\u003c/p\u003e \u003cp\u003eSeveral studies have used the UA/Cr ratio as a surrogate for UA levels, considering kidney clearance function thus providing a better marker for net serum UA production [\u003cspan citationid=\"CR27\" class=\"CitationRef\"\u003e27\u003c/span\u003e]. Evidence shows that the serum UA/Cr ratio is positively associated with various diseases, including metabolic syndrome, non-alcoholic fatty liver disease, and cardiovascular events [\u003cspan additionalcitationids=\"CR29\" citationid=\"CR28\" class=\"CitationRef\"\u003e28\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR30\" class=\"CitationRef\"\u003e30\u003c/span\u003e]. In the present study, the serum UA/Cr ratio exhibited a positive linear relationship with periodontitis, unlike serum UA levels. This suggests that the monotonic correlation between the serum UA/Cr ratio and periodontitis might be more predictable. However, the receiver operating characteristic curve indicated that the serum UA/Cr ratio was not effective in distinguishing individuals with moderate/severe periodontitis (Area under the curve\u0026thinsp;=\u0026thinsp;0.502), likely due to the weak effect of the serum UA/Cr ratio on periodontitis (\u003cem\u003eOR\u003c/em\u003e\u0026thinsp;=\u0026thinsp;1.046) or confounding effects from other systemic conditions. Nonetheless, the relationship between the serum UA/Cr ratio and periodontitis might reflect the systemic metabolic responses of patients with periodontitis or the effects of systemic metabolic disorders on periodontitis.\u003c/p\u003e \u003cp\u003eAmong individuals with hyperuricemia, the risk of developing severe periodontitis was significantly higher than the risk of developing mild/moderate forms, even after adjusting for multiple systemic conditions. Patients with severe periodontitis are generally exposed to specific inherited or multiple environmental factors. It is possible that hyperuricemia and periodontitis share some unknown hereditary basis. Other covariates not included in the current study, such as dietary factors, might also strengthen the association between hyperuricemia and severe periodontitis. The underlying mechanisms by which hyperuricemia exacerbates periodontitis remain unclear. Our recent review article hypothesized that hyperuricemia might worsen periodontitis by aggravating periodontal dysbiosis, inflammation and oxidative stress [\u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e]. Therefore, combined animal models of these two conditions should be developed to explore the underlying mechanisms. The findings of the present study also suggest the toned for prompt systemic and periodontal intervention in patients with hyperuricemia to prevent the progression of periodontitis.\u003c/p\u003e \u003cp\u003eServal limitations exist in the current study. Firstly, the cross-sectional design limits the ability to determine causal associations. Prospective cohort and interventional studies are warranted to validate these findings. Secondly, serum UA levels can exhibit circadian rhythms. Pacheco et al. reported that the estimated amplitudes of circannual variation for serum UA were 0.20 mg/dL in males and 0.17 mg/dL in females [\u003cspan citationid=\"CR31\" class=\"CitationRef\"\u003e31\u003c/span\u003e]. This variability could introduce some unpredictable but limited bias. Thirdly, the findings were derived from survey data collected in the US population between 2009 and 2014. The epidemiological features of hyperuricemia and periodontitis might vary over time and across regions. The prevalence of hyperuricemia has varied over the last decade and across different regions [\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e, \u003cspan citationid=\"CR32\" class=\"CitationRef\"\u003e32\u003c/span\u003e, \u003cspan citationid=\"CR33\" class=\"CitationRef\"\u003e33\u003c/span\u003e]. Treatment coverage rates and regimens might also differ globally. Therefore, caution should be exercised when generalizing these findings to other populations or regions.\u003c/p\u003e"},{"header":"5. CONCLUSION","content":"\u003cp\u003eIn conclusion, despite the study\u0026rsquo;s limitations, this research provides the first direct evidence supporting a positive association between hyperuricemia and the risk of periodontitis, particularly the moderate and severe forms. Prospective cohort and interventional studies are warranted to validate these findings.\u003c/p\u003e"},{"header":"Declarations","content":"\u003cp\u003e\u003cstrong\u003eFUNDING INFORMATION\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThis work was supported by Guangdong Basic and Applied Basic Research Foundation (Grants 2023A1515030037 and 2022A1515010497); The Basic Research Program of Guangzhou Science and Technology Bureau (2023A03J0324 and 202201020203); The Fundings of Guangzhou Medical University for Improving Innovation Capability of Undergraduates (Guangyifa [2024]61 and Guangkouyixue [2022]3); and The Teaching Fundings of Guangzhou Medical University (Guangyidafa [2021]28-2 and [2021]159-48).\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eACKNOWLEDGEMENT\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eAll authors acknowledge the investigators and participants of the National Health and Nutrition Examination Survey (NHANES).\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eCONFLICT OF INTEREST STATEMENT\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe authors in this study declare no conflict of interest.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAUTHOR CONTRIBUTIONS\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eTing Yu, Yueqi Chen, Peipei Lu, Chuyin Lin and Yinghong Zhou participated in the study design; Yueqi Chen, Peipei Lu, Chuyin Lin, Song Li, Yufan Zhu and Jiaying Tan performed the statistical analyses; Yueqi Chen, Peipei Lu, Chuyin Lin, Ting Yu and Yinghong Zhou wrote the manuscript; and Ting Yu and Yinghong Zhou revised the manuscript.\u0026nbsp;\u003c/p\u003e\u003cp\u003e\u003cstrong\u003eDATA AVAILABILITY STATEMENT\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe data that support the findings of this study are openly available in [National Health and Nutrition Examination survey] at NHANES-National Health and Nutrition Examination Survey Homepage (cdc.gov).\u0026nbsp;\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\n\u003cli\u003eTrindade, D., Carvalho, R., Machado, V., Chambrone, L., Mendes, J.J., Botelho, J.: Prevalence of periodontitis in dentate people between 2011 and 2020: A systematic review and meta-analysis of epidemiological studies. 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Med Hypotheses. 137, 109591 (2020). https://doi.org/10.1016/j.mehy.2020.109591\u003c/li\u003e\n\u003cli\u003eTsai, K.-Z., Su, F.-Y., Cheng, W.-C., Huang, R.-Y., Lin, Y.-P., Lin, G.-M.: Associations between metabolic biomarkers and localized stage II/III periodontitis in young adults: The CHIEF Oral Health study. J Clin Periodontol. 48, 1549\u0026ndash;1558 (2021). https://doi.org/10.1111/jcpe.13555\u003c/li\u003e\n\u003cli\u003eByun, S.-H., Yoo, D.-M., Lee, J.-W., Choi, H.-G.: Analyzing the Association between Hyperuricemia and Periodontitis: A Cross-Sectional Study Using KoGES HEXA Data. Int J Environ Res Public Health. 17, 4777 (2020). https://doi.org/10.3390/ijerph17134777\u003c/li\u003e\n\u003cli\u003eJoo, J.-Y., Park, H.R., Cho, Y., Noh, Y., Lee, C.H., Lee, S.-G.: Increased prevalence of periodontitis with hypouricemic status: findings from the Korean National Health and Nutrition Examination Survey, 2016-2018. J Periodontal Implant Sci. 53, 283\u0026ndash;294 (2023). https://doi.org/10.5051/jpis.2202220111\u003c/li\u003e\n\u003cli\u003evon Elm, E., Altman, D.G., Egger, M., Pocock, S.J., G\u0026oslash;tzsche, P.C., Vandenbroucke, J.P., STROBE Initiative: The Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) statement: guidelines for reporting observational studies. Lancet. 370, 1453\u0026ndash;1457 (2007). https://doi.org/10.1016/S0140-6736(07)61602-X\u003c/li\u003e\n\u003cli\u003eNHANES Survey Methods and Analytic Guidelines, https://wwwn.cdc.gov/nchs/nhanes/analyticguidelines.aspx#sample-design\u003c/li\u003e\n\u003cli\u003eMandal, A.K., Mount, D.B.: The molecular physiology of uric acid homeostasis. Annu Rev Physiol. 77, 323\u0026ndash;345 (2015). https://doi.org/10.1146/annurev-physiol-021113-170343\u003c/li\u003e\n\u003cli\u003eEke, P.I., Page, R.C., Wei, L., Thornton-Evans, G., Genco, R.J.: Update of the case definitions for population-based surveillance of periodontitis. J Periodontol. 83, 1449\u0026ndash;1454 (2012). https://doi.org/10.1902/jop.2012.110664\u003c/li\u003e\n\u003cli\u003eGharbi, A., Hamila, A., Bouguezzi, A., Dandana, A., Ferchichi, S., Chandad, F., Guezguez, L., Miled, A.: Biochemical parameters and oxidative stress markers in Tunisian patients with periodontal disease. BMC Oral Health. 19, 225 (2019). https://doi.org/10.1186/s12903-019-0912-4\u003c/li\u003e\n\u003cli\u003eSakanaka, A., Kuboniwa, M., Hashino, E., Bamba, T., Fukusaki, E., Amano, A.: Distinct signatures of dental plaque metabolic byproducts dictated by periodontal inflammatory status. Sci Rep. 7, 42818 (2017). https://doi.org/10.1038/srep42818\u003c/li\u003e\n\u003cli\u003eXu, J., Jia, Y., Mao, Z., Wei, X., Qiu, T., Hu, M.: Association between serum uric acid, hyperuricemia and periodontitis: a cross-sectional study using NHANES data. BMC Oral Health. 23, 610 (2023). https://doi.org/10.1186/s12903-023-03320-4\u003c/li\u003e\n\u003cli\u003eO\u0026rsquo;Dwyer, M.C., Furgal, A., Furst, W., Ramakrishnan, M., Capizzano, N., Sen, A., Klinkman, M.: The Prevalence of Periodontitis Among US Adults with Multimorbidity Using NHANES Data 2011-2014. J Am Board Fam Med. 36, 313\u0026ndash;324 (2023). https://doi.org/10.3122/jabfm.2022.220207R1\u003c/li\u003e\n\u003cli\u003eMori, K., Furuhashi, M., Tanaka, M., Numata, K., Hisasue, T., Hanawa, N., Koyama, M., Osanami, A., Higashiura, Y., Inyaku, M., Matsumoto, M., Moniwa, N., Ohnishi, H., Miura, T.: U-shaped relationship between serum uric acid level and decline in renal function during a 10-year period in female subjects: BOREAS-CKD2. Hypertens Res. 44, 107\u0026ndash;116 (2021). https://doi.org/10.1038/s41440-020-0532-z\u003c/li\u003e\n\u003cli\u003eKonta, T., Ichikawa, K., Kawasaki, R., Fujimoto, S., Iseki, K., Moriyama, T., Yamagata, K., Tsuruya, K., Narita, I., Kondo, M., Shibagaki, Y., Kasahara, M., Asahi, K., Watanabe, T.: Association between serum uric acid levels and mortality: a nationwide community-based cohort study. 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Nat Rev Rheumatol. 16, 380\u0026ndash;390 (2020). https://doi.org/10.1038/s41584-020-0441-1\u003c/li\u003e\n\u003cli\u003eZhang, J., Sun, W., Gao, F., Lu, J., Li, K., Xu, Y., Li, Y., Li, C., Chen, Y.: Changes of serum uric acid level during acute gout flare and related factors. Front Endocrinol (Lausanne). 14, 1077059 (2023). https://doi.org/10.3389/fendo.2023.1077059\u003c/li\u003e\n\u003cli\u003eBorghi, C., Piani, F.: Uric acid and estimate of renal function. Let\u0026rsquo;s stick together. Int J Cardiol. 310, 157\u0026ndash;158 (2020). https://doi.org/10.1016/j.ijcard.2020.01.046\u003c/li\u003e\n\u003cli\u003eCao, T., Tong, C., Halengbieke, A., Ni, X., Tang, J., Zheng, D., Guo, X., Yang, X.: Serum uric acid to creatinine ratio and metabolic syndrome in middle-aged and elderly population: Based on the 2015 CHARLS. Nutr Metab Cardiovasc Dis. 33, 1339\u0026ndash;1348 (2023). https://doi.org/10.1016/j.numecd.2023.05.004\u003c/li\u003e\n\u003cli\u003eChoi, J., Joe, H., Oh, J.-E., Cho, Y.-J., Shin, H.-S., Heo, N.H.: Correction: The Correlation Between NAFLD and Serum Uric Acid to Serum Creatinine Ratio. PLoS One. 18, e0294801 (2023). https://doi.org/10.1371/journal.pone.0294801\u003c/li\u003e\n\u003cli\u003eCasiglia, E., Tikhonoff, V., Virdis, A., Grassi, G., Angeli, F., Barbagallo, C.M., Bombelli, M., Cicero, A.F.G., Cirillo, M., Cirillo, P., Dell\u0026rsquo;Oro, R., D\u0026rsquo;elia, L., Desideri, G., Ferri, C., Galletti, F., Gesualdo, L., Giannattasio, C., Iaccarino, G., Lippa, L., Mallamaci, F., Masi, S., Maloberti, A., Masulli, M., Mazza, A., Mengozzi, A., Muiesan, M.L., Nazzaro, P., Palatini, P., Parati, G., Pontremoli, R., Quarti-Trevano, F., Rattazzi, M., Reboldi, G., Rivasi, G., Salvetti, M., Tocci, G., Ungar, A., Verdecchia, P., Viazzi, F., Volpe, M., Borghi, C., Working Group on Uric Acid and Cardiovascular Risk of the Italian Society of Hypertension (SIIA): Serum uric acid / serum creatinine ratio as a predictor of cardiovascular events. Detection of prognostic cardiovascular cut-off values. J Hypertens. 41, 180\u0026ndash;186 (2023). https://doi.org/10.1097/HJH.0000000000003319\u003c/li\u003e\n\u003cli\u003ePacheco de Andrade, M., Hirata, R.D.C., Sandrini, F., Largura, A., Hirata, M.H.: Uric acid biorhythm, a feature of long-term variation in a clinical laboratory database. Clin Chem Lab Med. 50, 853\u0026ndash;859 (2012). https://doi.org/10.1515/cclm-2011-0150\u003c/li\u003e\n\u003cli\u003eZhang, M., Zhu, X., Wu, J., Huang, Z., Zhao, Z., Zhang, X., Xue, Y., Wan, W., Li, C., Zhang, W., Wang, L., Zhou, M., Zou, H., Wang, L.: Prevalence of Hyperuricemia Among Chinese Adults: Findings From Two Nationally Representative Cross-Sectional Surveys in 2015-16 and 2018-19. Front Immunol. 12, 791983 (2021). https://doi.org/10.3389/fimmu.2021.791983\u003c/li\u003e\n\u003cli\u003eAl Shanableh, Y., Hussein, Y.Y., Saidwali, A.H., Al-Mohannadi, M., Aljalham, B., Nurulhoque, H., Robelah, F., Al-Mansoori, A., Zughaier, S.M.: Prevalence of asymptomatic hyperuricemia and its association with prediabetes, dyslipidemia and subclinical inflammation markers among young healthy adults in Qatar. BMC Endocr Disord. 22, 21 (2022). https://doi.org/10.1186/s12902-022-00937-4\u003c/li\u003e\n\u003c/ol\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":false,"highlight":"","institution":"","isAcceptedByJournal":true,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"bmc-oral-health","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"ohea","sideBox":"Learn more about [BMC Oral Health](http://bmcoralhealth.biomedcentral.com/)","snPcode":"","submissionUrl":"https://www.editorialmanager.com/ohea/default.aspx","title":"BMC Oral Health","twitterHandle":"BMC_series","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"em","reportingPortfolio":"BMC Series","inReviewEnabled":true,"inReviewRevisionsEnabled":true},"keywords":"Hyperuricemia, uric acid, uric acid to creatinine ratio, periodontal diseases, urate-lowering therapy","lastPublishedDoi":"10.21203/rs.3.rs-4675086/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-4675086/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003ch2\u003eObjectives\u003c/h2\u003e \u003cp\u003eTo explore the relationship between hyperuricemia and the risk of developing periodontitis.\u003c/p\u003e\u003ch2\u003eMaterials and Methods\u003c/h2\u003e \u003cp\u003eA representative dataset of 10,158 adults was extracted from the National Health and Nutrition Examination Survey (NHANES) 2009\u0026ndash;2014. The relationship between hyperuricemia (the primary exposure) and the risk of periodontitis (outcome) were evaluated using weighted logistic regression models. Serum uric acid (UA) levels and the UA to creatinine (UA/Cr) ratio were used as secondary exposures. Their associations with the risk of periodontitis were analyzed using weighted logistic regression or restricted cubic spline regression.\u003c/p\u003e\u003ch2\u003eResults\u003c/h2\u003e \u003cp\u003eThe prevalence of moderate/severe periodontitis was 56.7% among individuals with hyperuricemia and 44.8% among those without. After adjustment, individuals with hyperuricemia had a 26.9% higher risk of developing moderate/severe periodontitis compared to those without hyperuricemia (adjusted \u003cem\u003eOR\u003c/em\u003e\u0026thinsp;=\u0026thinsp;1.269, 95% \u003cem\u003eCI\u003c/em\u003e\u0026thinsp;=\u0026thinsp;1.080 to 1.492, \u003cem\u003eP\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.006). This increased risk could be explained by a linear relationship with the serum UA/Cr ratio and a U-shaped relationship with serum UA levels. Each unit increase in the serum UA/Cr ratio was associated with a 4.6% higher risk of developing moderate/severe periodontitis (adjusted \u003cem\u003eOR\u003c/em\u003e\u0026thinsp;=\u0026thinsp;1.046, 95% \u003cem\u003eCI\u003c/em\u003e\u0026thinsp;=\u0026thinsp;1.008 to 1.086, \u003cem\u003eP\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.021). Additionally, each 1 mg/dL increase in serum UA was associated with a 10.2% higher risk (adjusted \u003cem\u003eOR\u003c/em\u003e\u0026thinsp;=\u0026thinsp;1.102, 95% \u003cem\u003eCI\u003c/em\u003e\u0026thinsp;=\u0026thinsp;1.008 to 1.206, \u003cem\u003eP\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.035) of developing moderate/severe periodontitis when UA levels were greater than 5.5 mg/dL, but a 10.6% lower risk when UA levels were 5.5 mg/dL or lower (adjusted \u003cem\u003eOR\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.894, 95% \u003cem\u003eCI\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.800 to 0.998, \u003cem\u003eP\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.046). Sensitivity analyses validated the robustness of the findings.\u003c/p\u003e\u003ch2\u003eConclusions\u003c/h2\u003e \u003cp\u003eThis study provides the first direct evidence that hyperuricemia is associated with an increased risk of developing periodontitis, especially the moderate and severe forms.\u003c/p\u003e\u003ch2\u003eClinical Relevance\u003c/h2\u003e \u003cp\u003eIndividuals with hyperuricemia may represent a subgroup of the population susceptible to periodontitis. It may be prudent to initiate timely systemic and periodontal interventions in patients with hyperuricemia to halt the progression of periodontitis.\u003c/p\u003e","manuscriptTitle":"Hyperuricemia and Elevated Uric Acid/Creatinine Ratio are Associated with a Higher Risk of Periodontitis: A Population- based Cross-Sectional Study","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2024-08-09 16:32:43","doi":"10.21203/rs.3.rs-4675086/v1","editorialEvents":[{"type":"communityComments","content":0},{"type":"decision","content":"Revision requested","date":"2024-08-09T15:16:37+00:00","index":"","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2024-08-08T12:22:13+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"96552252996137478947655188432056649082","date":"2024-08-03T12:44:16+00:00","index":"hide","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2024-08-02T07:58:40+00:00","index":"hide","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2024-08-01T18:08:56+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"322142054168207705034433344490834377097","date":"2024-08-01T05:40:01+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"285842515528020677958378061367075898840","date":"2024-07-29T22:42:31+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"69820150896898517210434455209235403290","date":"2024-07-28T06:57:34+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"116843163792700387774070915654388594698","date":"2024-07-23T03:20:24+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"109870137743252772472522953525964329879","date":"2024-07-16T08:03:23+00:00","index":"hide","fulltext":""},{"type":"reviewersInvited","content":"","date":"2024-07-09T15:06:34+00:00","index":"","fulltext":""},{"type":"editorInvited","content":"","date":"2024-07-09T13:54:29+00:00","index":"","fulltext":""},{"type":"editorAssigned","content":"","date":"2024-07-08T09:18:16+00:00","index":"","fulltext":""},{"type":"checksComplete","content":"","date":"2024-07-08T09:17:09+00:00","index":"","fulltext":""},{"type":"submitted","content":"BMC Oral Health","date":"2024-07-02T14:47:27+00:00","index":"","fulltext":""}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"bmc-oral-health","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"ohea","sideBox":"Learn more about [BMC Oral Health](http://bmcoralhealth.biomedcentral.com/)","snPcode":"","submissionUrl":"https://www.editorialmanager.com/ohea/default.aspx","title":"BMC Oral Health","twitterHandle":"BMC_series","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"em","reportingPortfolio":"BMC Series","inReviewEnabled":true,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"419469e7-d00a-4c8f-adf6-23f4fc8ee583","owner":[],"postedDate":"August 9th, 2024","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"published-in-journal","subjectAreas":[],"tags":[],"updatedAt":"2024-11-18T15:59:51+00:00","versionOfRecord":{"articleIdentity":"rs-4675086","link":"https://doi.org/10.1186/s12903-024-05173-x","journal":{"identity":"bmc-oral-health","isVorOnly":false,"title":"BMC Oral Health"},"publishedOn":"2024-11-15 15:57:03","publishedOnDateReadable":"November 15th, 2024"},"versionCreatedAt":"2024-08-09 16:32:43","video":"","vorDoi":"10.1186/s12903-024-05173-x","vorDoiUrl":"https://doi.org/10.1186/s12903-024-05173-x","workflowStages":[]},"version":"v1","identity":"rs-4675086","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-4675086","identity":"rs-4675086","version":["v1"]},"buildId":"qtupq5eGEP_6zYnWcrvyt","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}