Association Between Periodontitis and Blood Lipid Levels in a Korean Population

Received: 13 February 2017 Accepted: 20 July 2017

DOI: 10.1902/jop.2017.170111

ORIGINAL ARTICLE

Association between periodontitis and blood lipid levels in a Korean population

Seyoung Lee1 Aejung Im1 Eunae Burm2,3 Mina Ha2

1 Department of Public Health, Graduate Abstract School, Dankook University, Cheonan, Republic of Korea Background: Hyperlipidemia is a known risk factor for cardiovascular diseases. A 2Department of Preventive Medicine, common biologic mechanism between systemic diseases, such as cardiovascular dis- Dankook University College of Medicine, eases, and periodontal diseases has been suggested. The aim of this study is to examine Cheonan, Republic of Korea the association between blood lipid proﬁle and periodontitis. 3Department of Nursing, Munkyung College, Mungyeong, Republic of Korea Methods: The study included 6,905 Korean adults, aged ≥ 20 years. Individuals with Correspondence incomplete data on blood lipid levels, those who lacked results of periodontitis exam- Prof. Mina Ha, Department of Preventive Medicine, Dankook University College of ination using the Community Periodontal Index system in the Fifth Korean National Medicine, 119 Dandae-ro, Dongnam-gu, Health and Nutrition Examination Survey for 2010 and 2012 and those diagnosed with Cheoana-si, Chungnam-do 31116, Republic of diabetes mellitus, hypertension, and hyperlipidemia were excluded from the study. All Korea. Email: [email protected] analyses involved complex sampling design. The association was assessed using multiple logistic regression analysis adjusted for covariates.

Results: Women with low high-density lipoprotein (HDL) cholesterol levels showed a significantly higher risk of periodontitis (odds ratio (OR) [95% confidence inter- val (CI)]: 1.65 [1.03 to 2.66] for the lowest group) than those with high HDL levels. Women with high low-density lipoprotein (LDL) cholesterol levels showed a higher risk of the disease (OR [95% CI]: 2.38 [1.01 to 5.60] for the highest group) than those with low LDL levels. There were significant dose-response relationships between disease risk and levels of HDL and LDL (P trend of 0.001 and 0.04, respectively). There was no significant difference in the risk between pre- and postmenopausal women. Men did not show any significant association between blood lipid levels and periodontitis.

Conclusion: There was a signiﬁcant association between periodontitis and low HDL and high LDL cholesterol levels in women. J Periodontol 2018;89:000–000.

KEYWORDS Lipoproteins, HDL, hyperlipidemias, lipoproteins, LDL, periodontitis, women's health

Periodontal disease is a chronic inﬂammatory disease caused Prevalence of periodontal diseases among adults aged ≥30 by host reaction to microorganisms and bioﬁlms, leading to years in South Korea has declined from 42.4% in 2007 to the destruction of periodontal tissues surrounding the teeth 26.1% in 2012.4 Even so, one of three adults is estimated to and eventual loss of teeth.1 It was reported that 46% of have periodontal disease. adults aged 30 years or more have periodontal disease in the Periodontal disease is not limited to the oral cavity. Instead, United States,2 and 95% of those aged ≥35 years have clini- it is an exposure variable,5 as well as a dependent variable, cal attachment loss of > 3 mm at 12 index teeth in Germany.3 with respect to systemic diseases. In general, it relates to the

28 © 2017 American Academy of Periodontology wileyonlinelibrary.com/journal/jper J Periodontol. 2018;89:28–35. LEE ET AL. 29 cellular and humoral immunity system. In case of compro- study. The KNHANES protocol was approved by the Institu- mised immunity, host response to subgingival bacteria has tional Review Board of the Centers for Disease Control and the potential to cause severe periodontal tissue destruction.6 It Prevention, and written informed consent was obtained from can also result from drug therapy, diet, stress, hormonal disor- the participants prior to enrollment. ders, and hematologic disordors.7 In case of atherosclerosis, blood flow to periodontal tissue decreases, and its resistance to 1.2 Measuring blood lipid level anaerobic microorganisms is impaired, resulting in periodon- For blood lipid level measurement, fasting blood was drawn tal disease and/or tooth loss. Several studies have indicated from participants who responded to the questionnaire and that patients with periodontal disease may have a higher risk were found to be eligible after ensuring the absence of of cardiovascular disease.8–11 Therefore, coronary heart dis- rash; open cuts; weak, damaged, and closed blood vessels; ease may share its risk factors with periodontal disease.8,11 A paralysis; and shunt for hemodialysis. Lipid levels, with the recent study,12 based on the U.S. National Health and Nutri- exception of low-density lipoprotein (LDL) cholesterol, were tion Examination Survey,13 found a significant association measured using the enzymatic method.19 LDL level was between borderline to high levels of serum total cholesterol calculated using the Friedewald formula.20 and periodontitis. Furthermore, treatment for hyperlipidemia Based on the 2015 Korean Guidelines for Management of had a protective effect against periodontal attachment loss.14 Dyslipidemia,20 blood lipid levels for total cholesterol (TC), During puberty, pregnancy, and menopause, women expe- high-density lipoprotein (HDL) cholesterol, LDL cholesterol, rience significant hormonal changes that impact periodon- and triglycerides (TGs) were classified into three groups for tal tissues by altering the host response.15 The prevalence of statistical analysis. These groups were as follows: for TC: metabolic syndrome, a composite of high lipid levels, obesity, 1) < 200 mm/dL (normal), 2) 200 to 239 mm/dL (bor- and high blood pressure, increases with menopause.16 These derline), and 3) ≥ 240 mm/dL (high), for HDL choles- are also factors associated with increased risk of cardiovascu- terol: 1) ≤ 40 mm/dL (low), 2) 41 to 59 mm/dL (nor- lar disease. This suggests a potential difference between the mal), and 3) ≥ 60 mm/dL (high); for LDL cholesterol: sexes in the association between blood lipids and periodontal 1) < 100 mm/dL (low), 2) 100 to 159 mm/dL (normal to bor- disease. derline), and 3) ≥ 160 mm/dL (high to very high); and for Therefore, the aim of this study is to examine the associ- TGs: 1) < 150 mm/dL (normal), 2) 150 to 199 mm/dL (bor- ation between blood lipid levels and the risk of periodonti- derline), and 3) ≥ 200 mm/dL (high to very high). tis using a nationally representative sample while considering possible differences between men and women. 1.3 Examination of periodontitis Dental health examination was conducted by two dental epidemiologists (KY Han and YS Choi, Dentists, Korean 1 MATERIALS AND METHODS Centers for Disease Control and Prevention, Cheongju, Korea) and about 30 public health dentists sent from local 1.1 Study participants governments in each year. Internal and external quality Data from the fifth Korea National Health and Nutrition control programs, including training for examiners before Examination Survey (KNHANES, 2010 to 2012) were survey, field quality control, supervision of survey table, and used.17 The KNHANES is conducted every year across data cleaning were implemented. For generating the CPI the nation with samples from 192 survey districts, 3,840 score, participants were examined for subgingival dental households, and household members aged ≥1 year. For calculus and bleeding in the mandibular left incisors. Stan- sampling, survey areas were allocated considering adminis- dard test teeth (10 teeth) were checked using a World Health trative districts, regions, and distribution of residence types Organization (WHO)-recommended dental probe with a to ensure representativeness. For the fifth (2010 to 2012) 0.5-mm-diameter round ball tip. The probe was pressed with survey, the latest sampling frame was used to reflect changes ≈20 × g force to determine periodontal pocket depth. in the survey areas and households after the 2005 Population According to the WHO recommendations,18 periodontal and Housing Census. Data from 2011 were excluded from diseases are scored based on the periodontal health status: the analysis because periodontitis data were not available. Of healthy (score 0), gingival bleeding (score 1), calculus and 17,016 people surveyed in 2010 and 2012, 6,905 individuals bleeding (score 2), shallow periodontal pockets (score 3), (2,878 males, 4,027 females; aged 20 to 84 years; mean age: and deep periodontal pockets (score 4). When participants 39 years) who had received a blood test, been examined could not be scored unambiguously because of proximity to using the Community Periodontal Index (CPI),18 and had a boundary line between scores, the lower score was given. never been diagnosed with hypertension, diabetes mellitus, The maximum score of each tooth was regarded as the CPI or hyperlipidemia were selected for inclusion in the present for the individual. Participants were grouped into the healthy 30 LEE ET AL.

TABLE 1 Prevalence of periodontitis by general characteristics of study participants Number of participants With periodontitis Males Females Males Females n%n%n%Pvalue∗ n%Pvalue∗ All 2,878 100.0 4,027 100.0 782 27.2 583 14.5 Area Urban 2,382 82.4 3,409 84.5 583 20.5 <0.001 454 11.1 <0.001 Rural 496 17.6 618 15.0 199 36.1 129 18.1 Age (years) 19 to 44 1,699 68.1 2,473 66.6 286 14.9 <0.001 176 6.5 <0.001 44 to 64 950 28.7 1,354 30.5 390 40.5 334 23.2 >65 229 3.2 200 2.9 106 46.5 73 34.9 BMI (kg/m2) <18.5 62 2.4 293 8.6 19 24.0 0.89 18 4.8 <0.001 18.5 to 25 1,818 62.4 2,828 69.8 504 23.4 383 11.5 >25 991 35.2 856 21.6 258 22.9 178 18.3 Menopausal status Premenopause — — 2,745 74.9 — — 261 8.7 <0.001 Postmenopause — — 1,217 25.1 — — 308 24.0 Education (years) ≤6 236 5.8 473 9.8 117 46.3 <0.001 158 31.7 <0.001 6to9 223 6.7 318 8.0 116 48.2 93 26.1 10 to 12 1,104 45.3 1,559 42.2 300 22.2 194 10.7 ≥13 1,258 42.2 1,610 40.0 235 17.6 123 6.8 Household income† Low 290 9.8 361 9.6 115 29.5 <0.001 90 20.6 <0.001 Low middle 721 25.8 993 26.8 209 25.1 165 14.4 High middle 912 33.1 1,262 31.5 235 22.6 164 11.1 High 924 31.1 1,361 32.1 208 20.0 150 9.5 Cigarette smoking status Never smoker 603 22.3 3,475 84.6 107 14.8 <0.001 507 12.8 0.42 Ex-smoker 1,053 33.1 296 9.0 303 24.5 33 9.2 Current smoker 1,168 44.6 191 6.5 357 24.5 29 12.7 Current alcohol intake, yes 2,165 77.8 1,765 47.0 584 23.3 0.76 237 11.8 0.26 Use of oral hygienic tools Brushing before sleep, yes 957 36.1 1,503 39.3 200 17.2 <0.001 176 10.1 <0.001 Dental ﬂoss, yes 400 13.8 987 23.9 62 16.3 <0.001 84 7.6 <0.001 Interdental brush, yes 352 11.6 715 16.5 93 25.9 0.33 95 12.1 0.90 Oral health examination, yes 738 23.9 1,036 25.1 193 23.8 0.76 132 11.3 0.26 — = not applicable. ∗P value and percent calculated considering the complex sampling design. †Monthly household income categorized based on income distribution of whole Korean population. periodontal condition group (scores 0 to 2) or the periodontitis mass index (BMI) calculated from weight (kg)/height (m2); group (score 3 to 4). 4) cigarette smoking status (never smoked, ex-smoker [smoked earlier but quit], and current smoker); and 5) alcohol 1.4 Potential confounders and covariates consumption (“Yes”: respondents have been drinking more than a glass of liquor/month for the last 1 year, and “No”: the The following were considered as potential confounders or respondents drinking less than a glass of liquor/month for the covariates: 1) geographic regions (urban and rural); 2) edu- last 1 year). cation levels (≤ 6, 7 to 9, 10 to 12, ≥ 13 years); 3) body LEE ET AL. 31

TABLE 2 Levels of blood lipids in study participants All Without periodontitis With periodontitis Blood lipids (mg/dL) Mean 95% CI∗ Mean 95% CI∗ Mean 95% CI∗ P value† Males n = 2,878 n = 2,096 n = 782 TC 188.11 186.37 to 189.84 187.31 185.33 to 189.28 190.75 187.88 to 193.62 <0.001 HDL 47.03 46.50 to 47.56 47.36 46.76 to 47.96 45.96 45.07 to 46.85 <0.001 LDL 115.30 112.87 to 117.73 114.42 111.54 to 117.27 118.42 113.08 to 123.76 <0.001 TG 148.95 143.21 to 154.68 145.13 138.48 to 151.78 161.54 151.98 to 171.10 <0.001 Females n = 4,027 n = 3,444 n = 583 TC 184.83 183.38 to 186.28 182.92 181.42 to 184.43 198.22 194.44 to 202.00 <0.001 HDL 53.72 53.27 to 54.18 54.16 53.67 to 54.65 50.65 49.51 to 51.80 <0.001 LDL 110.50 108.85 to 113.78 108.12 105.12 to 111.12 126.33 119.40 to 133.27 <0.001 TG 99.45 97.02 to 101.87 96.78 94.22 to 99.35 118.23 109.84 to 126.61 <0.001 ∗Mean and 95% CIs of lipid levels were calculated considering the complex sampling design. †P value for the diﬀerence of mean values between participants without and participants with periodontitis calculated by t test considering the complex sampling design.

1.5 Statistical analyses significantly higher levels of TC, LDL cholesterol, and TGs and lower levels of HDL cholesterol than those without peri- As the KNHANES uses a two-step stratified cluster sampling, odontitis (Table 2). data analysis methods for complex sampling design were used After adjusting for various covariates, there was a signif- for all analyses to improve accuracy of the representative- icant association between lower HDL cholesterol levels and ness and estimation of the parameters. All analyses considered increased risk of periodontitis in women. ORs were 1.37 and three variables of complex sample design: 1) weight; 2) strata; 1.65 in the middle and lowest level groups, compared with the and 3) cluster, which were included in the raw database. 𝜒2 highest level group, with a strong inverse relationship to the test was performed to identify general characteristics of study HDL levels (P trend = 0.001). The higher the LDL level, the participants. t test was performed to determine the difference higher the risk of periodontitis in women (P = 0.04). The risk in lipid levels between people with and without periodonti- was significantly elevated in the highest LDL group (OR [95% tis. Logistic regression analysis was conducted to examine CI]: 2.38 [1.01 to 5.60]) (Table 3). However, in men, there the association between blood lipid levels and periodontitis. was no significant association between risk of periodontitis Odds ratios (ORs) and 95% confidence intervals (CIs) were and levels of any of the blood lipid types. estimated, after adjustment for age, region, education level, When analyses were repeated after stratification by BMI, drinking, and smoking as covariates. Analyses were per- menopausal status, results were not significantly different formed separately based on sex. A statistical software package between pre- and postmenopausal women (P for multiplica- (IBM Statistical Package for Social Sciences, version 19, IBM tive interaction > 0.05 for all blood lipid classes) (Table 4). Corporation, New York, NY, USA) was used for all statistical analyses. P < 0.05 was considered statistically significant.

3 DISCUSSION 2 RESULTS This study shows that, unlike in men, risk of periodontitis Prevalence of periodontitis was 27.2% (782 out of 2,878) and increased significantly in women with lower HDL and higher 14.5% (583 out of 4,027) in men and women, respectively. LDL cholesterol levels. People of both sexes were more likely to have periodonti- There have been a number of studies on the association tis if they: 1) were older; 2) lived in urban rather than in between blood lipid levels and periodontal diseases. Results rural regions; 3) were less educated; 4) had lower household are somewhat different with the different types of blood incomes; and 5) had poor dental hygiene habits, such as not lipids. Some studies with relatively small sample sizes of 52 brushing before sleeping or using dental floss. Women who to 261 participants did not find any association.21–23 A study had high BMIs and were postmenopausal were more likely to on 677 outpatients of multicenter hospitals in Columbia have periodontitis (Table 1). showed the association of periodontal diseases with high TG Means and 95% CIs of blood lipid levels are presented in and HDL levels.24 There are other studies showing an asso- Table 2. Both men and women with periodontitis exhibited ciation between TG and HDL and periodontal disease,25,26 32 LEE ET AL.

TABLE 3 Association between levels of blood lipids and periodontitis in the Korean population Men Women Periodontitis Periodontitis Blood Lipid Level (mg/dL) N n (%) OR∗ 95% CI OR† 95% CI N n (%) OR∗ 95% CI OR† 95% CI TC ≤ 199 1,830 482 (26.3) 1 Ref. 1 Ref. 2,704 298 (11.0) 1 Ref. 1 Ref. 200 to 239 837 244 (29.1) 1.27 1.02 to 1.59 1.09 0.85 to 1.40 1,020 213 (20.8) 2.22 1.76 to 2.82 1.36 1.03 to 1.78 ≥ 240 211 56 (26.5) 1.02 0.73 to 1.45 0.82 0.57 to 1.18 303 72 (23.7) 2.80 1.93 to 4.04 1.24 0.81 to 1.90 P trend‡ 0.73 0.11 HDL cholesterol ≤ 39 558 138 (26.9) 1.41 0.97 to 2.04 1.32 0.86 to 2.02 280 58 (20.7) 2.26 1.50 to 3.41 1.65 1.03 to 2.66 40 to 59 1,808 476 (26.3) 1.17 0.82 to 1.68 1.27 0.86 to 1.88 2,215 351 (15.8) 1.51 1.14 to 2.00 1.37 1.02 to 1.84 ≥ 60 512 168 (30.1) 1 Ref. 1 Ref. 1,532 174 (11.3) 1 Ref. 1 Ref. P trend‡ 0.05 0.001 LDL cholesterol ≤ 99 289 70 (24.2) 1 Ref. 1 Ref. 315 23 (7.3) 1 Ref. 1 Ref. 100 to 159 517 138 (26.7) 1.25 0.85 to 1.84 1.02 0.67 to 1.57 464 82 (17.6) 2.83 1.58 to 5.07 1.62 0.88 to 2.98 ≥ 160 75 19 (25.3) 1.37 0.68 to 2.75 0.88 0.44 to 1.76 69 25 (36.2) 5.63 2.64 to 12.01 2.38 1.01 to 5.60 P trend‡ 0.85 0.04 TG ≤ 149 1,854 474 (25.5) 1 Ref. 1 Ref. 3,431 465 (13.5) 1 Ref. 1 Ref. 150 to 199 450 136 (30.2) 1.49 1.17 to 1.92 1.16 0.89 to 1.52 323 54 (16.7) 1.38 0.94 to 2.04 0.75 0.48 to 1.17 ≥ 200 574 172 (29.9) 1.35 1.05 to 1.72 1.06 0.79 to 1.43 273 64 (23.4) 2.13 1.50 to 3.02 1.26 0.73 to 1.63 P trend‡ 0.51 0.46 ∗ORs and 95% CIs estimated using survey logistic regression model. †Adjusted OR and 95% CIs estimated using multiple survey logistic regression model adjusted for age, area, education, BMI, alcohol intake, menopausal status (in women), and smoking status. ‡P value for trend calculated using the continuous scale of blood lipid in the corresponding model. and between TC and TG with periodontal disease.27,28 and women. A study by Ahn35 used the KNHANES data of Another study reported that TC and LDL levels were higher 2010 and 2012, the same participants as in the present study, and HDL levels were lower in the group with periodontitis and found that the higher the level of HDL, the lower the compared with those in the gingivitis and periodontally prevalence of periodontal disease. The present study of the healthy groups.29 Different results regarding different blood general representative population found that the association lipid types among studies might be due to differences of study was limited to women. design, sample size, and characteristics of the participants. Tomofuji et al.36 conducted a study on animals and found Periodontal disease severity was associated with LDL lev- that a high cholesterol level leads to periodontal disease and els and LDL-particle sizes.30 Higher levels of serum TC and could increase the inflammatory reaction induced by bacterial LDL were observed in infection by Tannerella forsythia,a pathogens. Women experience various physical and physio- periodontopathogen, which may increase the atherosclerotic logic changes after menopause, such as a decrease in estro- potency of LDL and augment the risk for atherosclerosis in gen, and they face increased risk of abdominal obesity37 patients with periodontal disease.31 Clinical attachment level as well as increased blood pressure,38 decrease in HDL and probing depth had significant associations with serum lev- cholesterol level, and increase in LDL cholesterol and TG els of LDL and TC.32 High serum LDL cholesterol was shown levels.39 The concentration of LDL cholesterol increases to be associated with periodontitis.33,34 by 10% to 20% after menopause compared with before Association between blood lipid levels and periodontal dis- menopause.38 Lack of female hormones also increases risk ease also has been reported in representative populations. of osteoporosis, which could have an impact on periodon- A recent study,12 based on the 2011 to 2012 U.S. National tal disease via inflammation in periodontal tissues and loss Health and Nutrition Examination Survey,13 found a statisti- of alveolar bone.40 Although a statistically significant dif- cally significant association between borderline to high levels ference between pre- and postmenopausal women could not of serum TC and periodontitis in a combined sample of men be found in the association between blood lipid levels and LEE ET AL. 33

TABLE 4 Association between blood lipids and periodontitis by menopausal status in Korean women Premenopause (n = 2,745) Postmenopause (n = 1,217) Blood lipid level (mg/dL) No. of cases (%) OR∗ 95% CI No. of cases (%) OR∗ 95% CI P Interaction† TC ≤199 167 (7.2) 1 Ref. 124 (20.3) 1 Ref. 0.18 200 to 239 74 (13.3) 1.49 1.04 to 2.13 137 (26.9) 1.23 0.83 to 1.83 ≥240 21 (19.8) 1.68 0.90 to 3.16 50 (24.4) 1.01 0.56 to 1.71 Ptrend‡ 0.09 0.85 HDL cholesterol ≤39 26 (13.3) 1.83 1.03 to 3.27 39 (29.6) 1.76 0.88 to 3.53 0.08 40 to 59 153 (8.5) 1.13 0.78 to 1.63 198 (26.4) 1.99 1.28 to 3.10 ≥60 65 (7.7) 1 Ref. 45 (12.5) 1 Ref. Ptrend‡ 0.16 <0.001 LDL cholesterol ≤99 17 (5.6) 1 Ref. 6 (10.3) 1 Ref. 0.63 100 to 159 34 (10.4) 1.04 0.46 to 2.35 47 (29.1) 2.69 0.93 to 7.83 ≥160 8 (28.2) 2.74 0.83 to 9.05 17 (28.3) 2.81 0.75 to 10.51 Ptrend‡ 0.22 0.15 TG ≤149 229 (8.4) 1 Ref. 229 (23.0) 1 Ref. 0.46 150 to 199 15 (11.4) 0.97 0.48 to 1.94 36 (18.2) 0.64 0.32 to 1.11 ≥200 18 (13.1) 1.02 0.54 to 1.91 46 (31.2) 1.20 0.72 to 1.97 Ptrend‡ 0.33 0.79

∗ORs and 95% CIs estimated using multiple survey logistic regression model adjusted for age, area, education, BMI, alcohol intake, and smoking status. †P value for interaction calculated by input of interaction term (menopause × blood lipid) using the continuous scale of blood lipid in the corresponding model in all women. ‡P value for trend calculated using the continuous scale of blood lipid in the corresponding model. periodontitis in the present study (absence of multiplicative determine the causal association between dyslipidemia and interaction), the increasing trend of periodontitis in propor- periodontitis. tion to the decrease in HDL levels was more obvious in postmenopausal women. ACKNOWLEDGMENTS One of the major strengths of this study is that it used a large number of study participants and a nationally representative The authors did not receive any financial support for the sample. Thus, results could be generalized to the Korean pop- present study. The authors report no conflicts of interest ulation. However, the KNHANES comprises cross-sectional related to this study. data, making it hard to define the time order of blood lipid and periodontitis, resulting in a limitation in causal inference of the association. REFERENCES 1. Petersen PE, Ogawa H. Strengthening the prevention of periodontal disease: The WHO approach. J Periodontol. 2005;76:2187–2193. PubMed. 4 CONCLUSIONS 2. Eke PI, Dye BA, Wei L, et al. Update on prevalence of periodontitis in adults in the United States: NHANES 2009 to. J Periodontol. The present study finds that Korean women showed an 2012;86:611–622. PubMed. increase in periodontitis risk in association with lower HDL 3. Holtfreter B, Kocher T, Hoffmann T, Desvarieux M, Micheelis W. and higher LDL cholesterol levels. The fact that the dys- Prevalence of periodontal disease and treatment demands based on a lipidemia prevalence in the Korean population has been German dental survey (DMS IV). J Clin Periodontol. 2010;37:211– 41 increasing suggests its growing contribution to periodon- 219. PubMed. tal diseases among other risk factors and importance of its 4. Ministry of Health and Welfare. The Korea National Health and control to prevent periodontitis, particularly in women. In Nutrition Examination. Korea Centers for Disease Control and Pre- the future, a cohort study with follow-up will be helpful to vention. Available at: www.mohw.go.kr. Accessed 06 Dec 2015. 34 LEE ET AL.

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