Association between periodontitis and its treatment on mortality rates of end-stage renal disease: A systematic review and meta-analysis.

BACKGROUND: The association between periodontitis and systemic diseases is widely researched. Conflicting literature exists on the relationship between periodontitis and the outcomes of end-stage renal disease (ESRD) patients. We hereby reviewed evidence to examine if periodontitis and its management impact the mortality rates of ESRD patients. MATERIAL AND METHODS: Literature was searched on the databases of PubMed, Embase, CENTRAL, Web of Science, and Scopus till 27th April 2023. All cohort studies reporting adjusted effect size of the relationship between periodontitis or its management and mortality rates of ESRD patients were included. RESULTS: Eight studies were eligible of which six reported the association between periodontitis and mortality while two reported between periodontal treatment and mortality. Pooled analysis showed no association between the presence of periodontitis and all-cause mortality amongst ESRD patients (HR: 1.13 95% CI: 0.77, 1.65 I2=72%). Results were unchanged on sensitivity analysis. Pooled analysis of three studies showed no difference in the risk of cardiovascular mortality amongst ESRD patients with and without periodontitis (HR: 1.44 95% CI: 0.57, 3.60 I2=86%). A descriptive analysis of two studies showed that periodontal treatment could reduce the risk of mortality in ESRD patients with periodontitis. CONCLUSIONS: Limited evidence indicates that periodontitis does not impact all-cause and cardiovascular mortality in ESRD patients. Data on the role of periodontal therapy in improving outcomes is scarce. Further research is needed to generate high-quality evidence on this subject.

Performance evaluation of survival regression models in analysing Swedish dental implant complication data with frailty.

The use of inappropriate methods for estimating the effects of covariates in survival data with frailty leads to erroneous conclusions in medical research. This study evaluated the performance of 13 survival regression models in assessing the factors associated with the timing of complications in implant-supported dental restorations in a Swedish cohort. Data were obtained from randomly selected cohort (n = 596) of Swedish patients provided with dental restorations supported in 2003. Patients were evaluated over 9 years of implant loss, peri-implantitis or technical complications. Best Model was identified using goodness, AIC and BIC. The loglikelihood, the AIC and BIC were consistently lower in flexible parametric model with frailty (df = 2) than other models. Adjusted hazard of implant complications was 45% (adjusted Hazard Ratio (aHR) = 1.449; 95% Confidence Interval (CI): 1.153-1.821, p = 0.001) higher among patients with periodontitis. While controlling for other variables, the hazard of implant complications was about 5 times (aHR = 4.641; 95% CI: 2.911-7.401, p<0.001) and 2 times (aHR = 2.338; 95% CI: 1.553-3.519, p<0.001) higher among patients with full- and partial-jaw restorations than those with single crowns. Flexible parametric survival model with frailty are the most suitable for modelling implant complications among the studied patients.

Periodontitis is associated with incident chronic liver disease-A population-based cohort study.

BACKGROUND & AIMS: Chronic liver disease is a major health concern worldwide and the identification of novel modifiable risk factors may benefit subjects at risk. Few studies have analyzed periodontitis as a risk factor for liver complications. We studied whether periodontitis is associated with incident severe liver disease. METHODS: The study comprised 6165 individuals without baseline liver disease who participated in the Finnish population-based Health 2000 Survey (BRIF8901) during 2000-2001, a nationally representative cohort. Follow-up was until 2013 for liver-related admissions, liver cancer and mortality from National Hospital Discharge, Finnish Cancer Registry and Causes of Death Register, Statistics Finland. Mild to moderate periodontitis was defined as ≥1 tooth with periodontal pocket ≥4 mm deep, and advanced periodontitis as ≥5 teeth with such pockets. Multiple confounders were considered. RESULTS: A total of 79 subjects experienced a severe liver event during follow-up. When adjusted for age, sex and number of teeth, hazards ratios by Cox regression regarding incident severe liver disease were, for mild to moderate periodontitis, 2.12 (95% CI 0.98-4.58), and, for advanced periodontitis, 3.69 (95% CI 1.79-7.60). These risk estimates remained stable after additionally adjusting for alcohol use, smoking, metabolic risk, serum gamma-glutamyltransferase, dental-care habits, lifestyle and socioeconomic status. Periodontal disease-associated liver risk was accentuated among subjects with non-alcoholic fatty liver disease or heavy alcohol use at baseline. CONCLUSIONS: Periodontitis was associated with incident liver disease in the general population independently of various confounders. As a preventable disease, periodontal disease might present a modifiable risk factor for chronic liver disease.

Periodontitis and early mortality among adults treated with hemodialysis: a multinational propensity-matched cohort study.

BACKGROUND: Periodontitis is associated with cardiovascular mortality in the general population and adults with chronic diseases. However, it is unclear whether periodontitis predicts survival in the setting of kidney failure. METHODS: ORAL-D was a propensity matched analysis in 3338 dentate adults with end-stage kidney disease treated in a hemodialysis network in Europe and South America designed to examine the association between periodontitis and all-cause and cardiovascular-related mortality in people on long-term hemodialysis. Participants were matched 1:1 on their propensity score for moderate to severe periodontitis assessed using the World Health Organization Community Periodontal Index. A random-effects Cox proportional hazards model was fitted with shared frailty to account for clustering of mortality risk within countries. RESULTS: Among the 3338 dentate participants, 1355 (40.6%) had moderate to severe periodontitis at baseline. After using propensity score methods to generate a matched cohort of participants with periodontitis similar to those with none or mild periodontal disease, moderate to severe periodontitis was associated with a lower risk of all-cause (9.1 versus 13.0 per 100 person years, hazard ratio 0.74, 95% confidence interval 0.61 to 0.90) and cardiovascular (4.3 versus 6.9 per 100 person years, hazard ratio 0.67, 0.51 to 0.88) mortality. These associations were not changed substantially when participants were limited to those with 12 or more natural teeth and when accounting for competing causes of cardiovascular death. CONCLUSION: In contrast to the general population, periodontitis does not appear to be associated with an increased risk of early death in adults treated with hemodialysis.

Mortality is associated with inflammation, anemia, specific diseases and treatments, and molecular markers.

Lifespan is a complex trait, and longitudinal data for humans are naturally scarce. We report the results of Cox regression and Pearson correlation analyses using data of the Study of Health in Pomerania (SHIP), with mortality data of 1518 participants (113 of which died), over a time span of more than 10 years. We found that in the Cox regression model based on the Bayesian information criterion, apart from chronological age of the participant, six baseline variables were considerably associated with higher mortality rates: smoking, mean attachment loss (i.e. loss of tooth supporting tissue), fibrinogen concentration, albumin/creatinine ratio, treated gastritis, and medication during the last 7 days. Except for smoking, the causative contribution of these variables to mortality was deemed inconclusive. In turn, four variables were found to be associated with decreased mortality rates: treatment of benign prostatic hypertrophy, treatment of dyslipidemia, IGF-1 and being female. Here, being female was an undisputed causative variable, the causal role of IFG-1 was deemed inconclusive, and the treatment effects were deemed protective to the degree that treated subjects feature better survival than respective controls. Using Cox modeling based on the Akaike information criterion, diabetes, mean corpuscular hemoglobin concentration, red blood cell count and serum calcium were also associated with mortality. The latter two, together with albumin and fibrinogen, aligned with an"integrated albunemia" model of aging proposed recently.

Associations between Periodontal Microbiota and Death Rates.

It is conceived that specific combinations of periodontal bacteria are associated with risk for the various forms of periodontitis. We hypothesized that such specificity is also related to human cause-specific death rates. We tested this hypothesis in a representative sample of the US population followed for a mean duration of 11 years and found that two specific patterns of 21 serum antibodies against periodontal bacteria were significantly associated with increased all-cause and/or diabetes-related mortalities. These data suggested that specific combinations of periodontal bacteria, even without inducing clinically significant periodontitis, may have a significant impact on human cause-specific death rates. Our findings implied that increased disease and mortality risk could be transmittable via the transfer of oral microbiota, and that developing personalized strategies and maintaining healthy oral microbiota beyond protection against periodontitis would be important to manage the risk.

Non-linear association of periodontal pathogen antibodies with mortality.

BACKGROUND: Periodontal pathogens are associated with predisposition to chronic diseases and death. Antibody levels against them reflect flora burden, although high levels might indicate a protective response. We studied all-cause and cause specific mortality in relation to antibody levels in a representative US sample. METHODS: Adults ≥ 20 years (n=6993) from the second phase of the Third National Health and Nutrition Examination Survey (NHANES III) were followed for a median of 13.2 years. Serum antibodies against Porphyromonas gingivalis (antiPG) and Actinobacillus actinomycetemcomitans (antiAA) were quantified by ELISA at baseline (1991-1994). Mortality hazard ratios (HRs) were calculated across antibody quartiles using the quartile with highest mortality as reference. RESULTS: Median (25th, 75th percentiles) antiPG was 72 (63, 93) ELISA Units (EU) and median antiAA was 70 (64, 89) EU. After adjustment for potential confounders, mortality was highest for participants with antibodies in the third antiPG quartile (72-92 EU), with lower mortality risk for values not only below but also above this range [HR for the 1st to 4th quartiles: 0.81 (95% CI: 0.65, 1.01), 0.67 (95% CI: 0.55, 0.82), 1.00 (Reference), 0.79 (95% CI: 0.64, 0.97)]. In spline regression models the association had an inverted U-shape and mortality exhibited a peak at 84 EU (67th percentile). Mortality was not associated with antiAA. CONCLUSIONS: Mortality was highest for those just above the median antiPG and a reduced risk was present among those with low or high levels of the antibody. Future studies should confirm this downward trend in upper levels and investigate a potential protective role of immunity against P. gingivalis.

All-cause mortality and periodontitis in 60-70-year-old men: a prospective cohort study.

OBJECTIVE: To investigate the association between periodontitis and mortality from all causes in a prospective study in a homogenous group of 60- to 70-year-old West European men. METHODOLOGY: A representative sample of 1400 dentate men, (mean age 63.8, SD 3.0 years), drawn from the population of Northern Ireland, had a comprehensive periodontal examination between 2001 and 2003. Men were divided into thirds on the basis of their mean periodontal attachment loss (PAL). The primary endpoint, death from any cause, was analysed using Kaplan-Meier survival plots and Cox's proportional hazards model. RESULTS: In total, 152 (10.9%) of the men died during a mean follow-up of 8.9 (SD 0.7) years; 37 (7.9%) men in the third with the lowest PAL (<1.8 mm) died compared with 73 (15.7%) in the third with the highest PAL (>2.6 mm). The unadjusted hazard ratio (HR) for death in the men with the highest level of PAL compared with those with the lowest PAL was 2.11 (95% CI 1.42-3.14), p < 0.0001. After adjustment for confounding variables (age, smoking, hypertension, BMI, diabetes, cholesterol, education, marital status and previous history of a cardiovascular event) the HR was 1.57 (1.04-2.36), p = 0.03. CONCLUSION: The European men in this prospective cohort study with the most severe loss of periodontal attachment were at an increased risk of death compared with those with the lowest loss of periodontal attachment.

Mechanism of increased mortality in hemodialysed patients with periodontitis.

Periodontitis significantly decreases survival in hemodialysed patients with end stage renal disease (ESRD). Periodontitis-related microorganisms spreading into the bloodstream are thought to impair blood rheological parameters - for example, increasing whole blood viscosity, aggregating blood elements, and decreasing blood flow - and thereby significantly accelerate systemic or local diseases, impairing survival. We discuss the ability of a prototypical pathogenic anaerobic polybacterial consortium to modulate and interfere with host immune responses and to enzymatically degrade host proteins, to bind to and cleave extracellular matrix proteins, to invade intercellularly as well as intracellularly, to promote vascular permeability, to disrupt polymorphonuclear leukocyte function, to cleave complement, and to degrade IgG heavy chains. To further elucidate these phenomena, studies involving detecting microorganism byproducts and monitoring blood rheological parameters are necessary.

Effect of inflammation in the periodontium in early old age on mortality at 21-year follow-up.

OBJECTIVES: To analyze whether inflammatory processes in the periodontium in early old age are related to subsequent mortality during 21 years of follow-up in a nondisabled 70-year-old population. SETTING: Community-based population in Copenhagen. DESIGN: The study was based on the Glostrup Aging Study of the 1914 population, with baseline in 1984 when the participants were 70 years old and follow-up 21 years later. PARTICIPANTS: Three hundred thirty-five dentate men and women participated in the clinical oral health examination. MEASUREMENTS: Severe periodontal inflammation was measured for all teeth present as the number of teeth with inflammation and periodontal pockets 6 mm deep or more. Mortality data were obtained from the Danish Death Register at 21-year follow-up. The Cox proportional hazards regression model was used. Covariates were measured at baseline and included number of teeth, caries, sex, education, income, hypertension, diabetes mellitus, osteoarthritis, arteriostenosis, myocardial infarction, comorbidity, fatigue, and ability to brush teeth. RESULTS: The analyses showed that severe periodontal inflammation in at least three teeth at age 70 was marginally related to mortality during 21-year follow-up (crude hazard ratio (HR)=1.17, 95% confidence interval (CI)=0.91-1.78). The estimate increased slightly when adjusted for sex, income, fatigue, and smoking (adjusted HR=1.37, 95% CI=0.97-1.92). The estimates were attenuated when adjusted for the specific diseases, especially arteriostenosis and osteoarthritis. CONCLUSION: Inflammation in the periodontium in early old age tends to be associated with mortality in older age.

Evidencias científicas de la relación entre periodontitis y enfermedades cardiovasculares / Scientific evidence for the relationship between periodontitis and cardiovascular disease

Muchos estudios clínicos han investigado la posible asociación entre periodontitis y la enfermedad coronaria. Algunos mantienen una asociación epidemiológica entre ellas y confirman las investigaciones previas que han demostrado que la inflamación periodontal crónica, la infección bacteriana persistente con la presencia de patógenos periodontales, las bolsas periodontales profundas, el número de dientes perdidos y otros marcadores periodontales, parecen ser factores de riesgo importantes para las enfermedades cardiovasculares. Las enfermedades periodontales y cardiovasculares son comunes, y su asociación es muy importante en salud pública. Ambas enfermedades comparten factores de riesgo, tales como la edad, tabaco, stress, estatus socioeconómico y metabolismo de las grasas, por lo que las posibilidades de sesgo son altas (AU)

A lot of clinical studies have investigated the possible association between periodontitis and coronary heart disease (CHD). Some of them supports the existence of epidemiologic association between them and confirms previous investigations that have found that chronic periodontal inflammation, persistent bacterial infection with the presence of major periodontal pathogens, deep periodontal pockets, the number of missing teeth and other periodontal markers, seems to be important risk factors for cardiovascular diseases. But it will be required to do better controlled and larger studies to identify it this biological mechanism are responsible for this increased risk and provide a convincing support of a casual association and in this way periodontal treatments could prevent CHD. Since periodontal disease and cardiovascular disease are common, their association is of significant public health importance. They share common risk factors, such as increasing age, smoking, stress, socioeconomic status, and body fat metabolism, the potential for confounding is substantial (AU)

Periodontitis and premature death: a 16-year longitudinal study in a Swedish urban population.

BACKGROUND AND OBJECTIVE: Growing experimental evidence implicates chronic inflammation/infection due to periodontal diseases as a risk factor for death. The objective was to evaluate the role of periodontitis in premature death in a prospective study. METHODS: The causes of death in 3273 randomly-selected subjects, aged 30-40 years, from 1985 to 2001 were registered. At baseline, 1676 individuals underwent a clinical oral examination (Group A) and 1597 did not (Group B). Mortality and causes of death from 1985 to 2001 were recorded according to ICD-9-10. RESULTS: In Groups A (clinically examined group) and B, a total of 110 subjects had died: 40 subjects in Group A, and 70 in Group B. In Group A significant differences were present at baseline between survivors and persons who later died, with respect to dental plaque, calculus, gingival inflammation and number of missing molars in subjects with periodontitis (p < 0.001). The multiple logistic regression analysis results of the relationship between being dead (dependent variable) and several independent variables identified periodontitis with any missing molars as a principal independent predictor of death. CONCLUSIONS: Young individuals with periodontitis and missing molars seem to be at increased risk for premature death by life-threatening diseases, such as neoplasms, and diseases of the circulatory and digestive systems.

Periodontal disease and risk of subsequent cardiovascular disease in U.S. male physicians.

OBJECTIVES: We sought to prospectively assess whether self-reported periodontal disease is associated with subsequent risk of cardiovascular disease in a large population of male physicians. BACKGROUND: Periodontal disease, the result of a complex interplay of bacterial infection and chronic inflammation, has been suggested to be a predictor of cardiovascular disease. METHODS: Physicians' Health Study I was a randomized, double-blind, placebo-controlled trial of aspirin and beta-carotene in 22,071 U.S. male physicians. A total of 22,037 physicians provided self-reports of presence or absence of periodontal disease at study entry and were included in this analysis. RESULTS: A total of 2,653 physicians reported a personal history of periodontal disease at baseline. During an average of 12.3 years of follow-up, there were 797 nonfatal myocardial infarctions, 631 nonfatal strokes and 614 cardiovascular deaths. Thus, for each end point, the study had >90% power to detect a clinically important increased risk of 50%. In Cox proportional hazards regression analysis adjusted for age and treatment assignment, physicians who reported periodontal disease at baseline had slightly elevated, but statistically nonsignificant, relative risks (RR) of nonfatal myocardial infarction, (RR, 1.12; 95% confidence interval [CI], 0.92 to 1.36), nonfatal stroke (RR, 1.10; CI, 0.88 to 1.37) and cardiovascular death (RR, 1.20; CI, 0.97 to 1.49). Relative risk for a combined end point of all important cardiovascular events (first occurrence of nonfatal myocardial infarction, nonfatal stroke or cardiovascular death) was 1.13 (CI, 0.99 to 1.28). After adjustment for other cardiovascular risk factors, RRs were all attenuated and nonsignificant. CONCLUSIONS: These prospective data suggest that self-reported periodontal disease is not an independent predictor of subsequent cardiovascular disease in middle-aged to elderly men.

Aggressive periodontitis associated with Fanconi's anemia. A case report.

BACKGROUND: Fanconi's anemia is an autosomal recessive disease associated with chromosomal breakage as well as pancytopenia, skin pigmentation, renal hypoplasia, cardiac defects, microcephaly, congenital malformations of the skeleton, hypogonadism, and increased risk of leukemia. The present report describes the periodontal clinical and microbiological status of an 11-year old male having Fanconi's anemia. METHODS: Polymerase chain reaction analysis to detect human cytomegalovirus (HCMV), Epstein-Barr type 1 virus, and herpes simplex virus (HSV) was performed on paper-point samples pooled from either 3 periodontal sites with advanced attachment loss or 3 gingivitis sites with no clinical attachment loss. Anaerobic bacterial culture examination was performed on the pooled periodontitis sample. RESULTS: The patient suffered from pancytopenia, allergy, asthma, hearing impairment, and mental retardation. Dentition consisted of 7 primary teeth, 11 erupted permanent teeth, and 14 unerupted permanent teeth. Most erupted teeth showed severe gingival inflammation with some gingival overgrowth and various degrees of periodontal attachment loss. Genomes of HCMV and HSV were detected in the pooled periodontitis sample and HCMV in the pooled gingivitis sample. The periodontitis sample but not the gingivitis sample revealed HCMV mRNA of major capsid protein, suggestive of active viral infection. The periodontitis sample also yielded Actinobacillus actinomycetemcomitans (1.1% of total isolates), FusobActerium species (7.9%), Campylobacter species (2.2%), Peptostreptococcus micros (3.4%), and Candida albicans (0.3%). CONCLUSIONS: Oral features of Fanconi's anemia may include increased susceptibility to periodontitis. It is likely that underlying host defense impairment coupled with periodontal infection by HCMV and A. actinomycetemcomitans contribute to the severe type of periodontitis associated with Fanconi's anemia.

Periodontal disease and risk of cerebrovascular disease: the first national health and nutrition examination survey and its follow-up study.

BACKGROUND: Periodontal disease has been found to be a potential risk factor for coronary heart disease. However, its association with cerebrovascular accidents (CVAs) is much less studied. METHODS: This study examines the association between periodontal disease and CVA. The study cohort comprises 9962 adults aged 25 to 74 years who participated in the First National Health and Nutrition Examination Survey and its follow-up study. Baseline periodontal status was categorized into (1) no periodontal disease, (2) gingivitis, (3) periodontitis, and (4) edentulousness. All CVAs (International Classification of Diseases, Ninth Revision [ICD-9], codes 430-438) were ascertained by hospital records for nonfatal events and death certificates for fatal events. The first CVA, nonfatal or fatal, was used to define incidence. Relative risks were estimated by hazard ratios from the Cox proportional hazard model with adjustment for several demographic variables and well-established cardiovascular risk factors. Weights were used to generate risk estimates. RESULTS: Periodontitis is a significant risk factor for total CVA and, in particular, nonhemorrhagic stroke (ICD-9, 433-434 and 436-438). Compared with no periodontal disease, the relative risks (95% confidence intervals) for incident nonhemorrhagic stroke were 1.24 (0.74-2.08) for gingivitis, 2.11 (1.30-3.42) for periodontitis, and 1.41 (0.96-2.06) for edentulousness. For total CVA, the results were 1.02 (0.70-1.48) for gingivitis, 1.66 (1.15-2.39) for periodontitis, and 1.23 (0.91-1.66) for edentulousness. Increased relative risks for total CVA and nonhemorrhagic stroke associated with periodontitis were also seen in white men, white women, and African Americans. Similar results were found for fatal CVA. CONCLUSION: Periodontal disease is an important risk factor for total CVA and, in particular, nonhemorrhagic stroke.