Cross-sectional analysis of the association of periodontitis with carotid intima media thickness and atherosclerotic plaque in the Hamburg City health study.

BACKGROUND: Previous epidemiological studies regarding the association between chronic periodontitis (CP) and carotid intima-media thickness (cIMT) and subclinical atherosclerosis have been inconclusive. OBJECTIVE: The aim of this study was to determine whether CP is associated with subclinical atherosclerosis in a large population-based cohort study conducted in northern Germany (the Hamburg City Health study). METHODS: Baseline data from 5781 participants of the Hamburg City Health Study with complete oral health and carotid ultrasound data (50.7% female, mean age: 62.1 ± 8.4 years) were evaluated. A standardized duplex sonography of the carotid artery was performed with measurement of carotid intima-media thickness (cIMT) and atherosclerotic plaques. Oral health was assessed by recording the decayed, missing, and filled teeth (DMFT) index, clinical attachment loss (CAL), bleeding on probing (BOP), and the dental plaque index (PI). Correlations were tested for statistical significance by means of descriptive statistics and multivariate regression analyses. RESULTS: Moderate and severe CP were associated with the prevalence of cIMT ≥ 1 mm (none or mild CP: 5.1%, moderate CP: 6.1%, severe CP: 10%) and mean cIMT (none or mild CP: 0.72 mm, moderate CP: 0.75 mm, severe CP: 0.78 mm) in bivariate analyses (p < .001). Additionally, severe and moderate CP were associated with higher prevalence of carotid atherosclerotic plaques (plaque = yes: none or mild CP: 23.9%, moderate CP: 29%, severe CP: 40.2%,). After adjustment for age, sex, smoking, diabetes, hypertension, educational level, hypercholesterolemia, and hsCRP, severe CP still correlated significantly with cIMT and the prevalence of cIMT ≥1 mm and/or presence of carotid atherosclerotic plaques. CONCLUSION: In this study, severe CP was associated with increased cIMT and higher prevalence of carotid plaques independent of common risk factors.

Association between periodontitis and heart failure in the general population.

AIMS: Data on the association between periodontitis and preclinical cardiac alterations remain scarce. The aim of the current study is to determine if periodontitis is associated with morphological and functional cardiac changes measured by transthoracic echocardiography as well as different heart failure (HF) phenotypes. METHODS: Participants from the population-based Hamburg City Health Study [ClinicalTrial.gov (NCT03934957)], who underwent transthoracic echocardiography and periodontal screening were included. Periodontitis was classified according to Eke and Page (none/mild, moderate, severe). The 2021 ESC HF guidelines were applied and HF was classified into HF with preserved ejection fraction (HFpEF, ejection fraction ≥50%), HF with mid-range and reduced ejection fraction [HF(m)rEF, ejection fraction <50%], and HF in general [HFpEF and HF(m)rEF]. Due to limited size, all subjects with LVEF <50% and symptoms or signs of HF were classified as HF with reduced and mildly reduced ejection fraction [HF(m)rEF]. RESULTS: Within 6209 participants with full periodontal examination, we identified an overlap of n = 167 participants with periodontitis and HF. Participants with severe periodontitis showed a higher burden of cardiovascular risk factors (men at advanced age, diabetes mellitus, hypertension) when compared with participants with none/mild periodontitis. After adjustment for age, sex, body mass index, smoking, diabetes, hypertension, atrial fibrillation, and coronary artery disease, severe periodontitis was significantly associated with HF(m)rEF (odds ratio: 3.16; 95% CI: 1.21, 8.22; P = 0.019), although no association was found for HFpEF and HF in general. CONCLUSIONS: The current study demonstrated that severe periodontitis was significantly associated with HF(m)rEF, although no relevant associations were found with HFpEF and HF in general as well as echocardiographic variables. The results implicate a potential target group, who need special attention from cooperating physicians and dentists. Future studies are warranted to verify whether systemic inflammation could be the link between the two diseases.

Cross-sectional study on the association of periodontitis with arterial hypertension in the Hamburg City Health Study.

AIM: Aim of this study was to investigate the association between periodontitis and arterial hypertension, both of which show correlations with classical cardiovascular risk factors and inflammatory activity. MATERIALS AND METHODS: A cross-sectional analysis of data from a large population-based health survey (the Hamburg City Health Study, HCHS) including 5934 participants with complete periodontal examination and blood pressure data, of whom 5735 had medical records regarding anti-hypertensive medication, was performed. Probing depths, gingival recessions, bleeding on probing (BOP), dental plaque, and decayed-missing-filled teeth (DMFT) indices were recorded as measures of oral health. Clinical attachment loss (CAL) per tooth was calculated and periodontitis was staged into three groups (no/mild, moderate, severe). Arterial hypertension was diagnosed based on the participants' medication history and systolic and diastolic blood pressure values. Logistic regression models were constructed accounting for a set of potential confounders (age, sex, smoking, body mass index (BMI), diabetes, educational level, alcohol intake) and high sensitivity-C-reactive protein (hsCRP). RESULTS: The odds of arterial hypertension increased significantly along with periodontitis severity (OR for severe periodontitis: 2.19; 95% CI 1.85-2.59; p < 0.001; OR for moderate periodontitis: 1.65; 95% CI 1.45-1.87; p < 0.001). Participants with moderate or severe periodontitis also had significantly higher age- and sex-adjusted odds of arterial hypertension, which was slightly weakened when additionally adjusted for BMI, diabetes, smoking, educational level, and alcohol intake (OR for severe PD: 1.28, 95% CI 1.04-1.59, p = 0.02; OR for moderate PD: 1.30, 95% CI 1.11-1.52, p = 0.001). The fraction of participants with undertreated hypertension (untreated and poorly controlled hypertension) was considerably larger in participants with severe periodontitis than in those with no/mild periodontitis (50.1% vs. 37.4% for no/mild periodontitis). CONCLUSIONS: The study shows an association between periodontitis and arterial hypertension that is independent of age, sex, diabetes, BMI, smoking, educational level, and alcohol intake. In addition, undertreatment of hypertension was more common in people with severe periodontitis compared with periodontally more healthy people.

Periodontitis, dental plaque, and atrial fibrillation in the Hamburg City Health Study.

BACKGROUND/AIM: Atrial fibrillation (AF) is a major health problem and causes heart failure and stroke. Pathophysiological mechanisms indicate a link with oral health including periodontitis (PD), but supporting data are scarce. The aim was to investigate the link between features of oral health and the prevalence of AF. METHODS: This cross-sectional analysis of the Hamburg City Health Study included 5,634 participants with complete data on their PD and AF status. AF was assessed via self-reported questionnaire or medically diagnosed by standard 12-lead resting ECG. The oral health examination included full-mouth measurements of the dental plaque index (PI), the clinical attachment loss (CAL) at 6 sites per tooth, the bleeding on probing (BOP) and the decayed, missing and filled teeth (DMFT) index. Descriptive analyses for all variables stratified by the status of PD were performed. To test for an association between prevalent PD and prevalent AF, multivariable logistic regression models were used. Mediation analysis was used to test if interleukin-6 (IL-6) and/or C-reactive protein (CRP) mediated the association between PD and AF. RESULTS: Atrial fibrillation (prevalence: 5.6%) and the severity of PD (prevalence: moderate: 57.7%, severe: 18.9%) increased with age in men and women. Prevalent severe PD, CAL ≥3 mm, PI, and BOP were all associated with prevalent AF in unadjusted regression analysis. However, no association except for PI (odds ratio (OR): 1.22, 95% confidence interval (CI): 1.1-1.35, p<0.001) could be observed after adjusting for age, sex, high-sensitivity C-reactive protein (hs-CRP), interleukin-6 (IL-6), body mass index, diabetes, smoking, and educational level. Participants brushing their teeth at least twice daily had a lower AF prevalence compared with those brushing only once daily. Hs-CRP, IL-6, and the odds of AF increased as a function of PD severity grades in unadjusted analysis. However, neither the DMFT index nor IL-6 or CRP was associated with AF after adjusting for age and sex. Mediation analyses could not provide support for the hypothesis that IL-6 or CRP acted as mediator of the association between prevalent PD and prevalent AF. CONCLUSION: The study shows an association between prevalent AF and increased dental plaque levels indicated by a higher PI. In contrast, an association of prevalent PD with prevalent AF after adjustments for several confounders could not be demonstrated. Further studies are necessary to investigate the mechanisms underlying poor oral hygiene and AF as well as the influence of improved oral hygiene on AF onset.

Roles of the Chr.9p21.3 ANRIL Locus in Regulating Inflammation and Implications for Anti-Inflammatory Drug Target Identification.

Periodontitis (PD) is a common gingival infectious disease caused by an over-aggressive inflammatory reaction to dysbiosis of the oral microbiome. The disease induces a profound systemic inflammatory host response, that triggers endothelial dysfunction and pro-thrombosis and thus may aggravate atherosclerotic vascular disease and its clinical complications. Recently, a risk haplotype at the ANRIL/CDKN2B-AS1 locus on chromosome 9p21.3, that is not only associated with coronary artery disease / myocardial infarction (CAD/MI) but also with PD, could be identified by genome-wide association studies. The locus encodes ANRIL - a long non-coding RNA (lncRNA) which, like other lncRNAs, regulates genome methylation via interacting with specific DNA sequences and proteins, such as DNA methyltranferases and polycomb proteins, thereby affecting expression of multiple genes by cis and trans mechanisms. Here, we describe ANRIL regulated genes and metabolic pathways and discuss implications of the findings for target identification of drugs with potentially anti-inflammatory activity in general.