Lionel A. Mandell, Richard G. Wunderink, Antonio Anzueto, John G. Bartlett, G. Douglas Campbell, Nathan C. Dean, Scott F. Dowell, Thomas M. File, Jr. Daniel M. Musher, Michael S. Niederman, Antonio Torres, and Cynthia G. Whitney McMaster University Medical School, Hamilton, Ontario, Canada; Northwestern University Feinberg School of Medicine, Chicago, Illinois; University of Texas Health Science Center and South Texas Veterans Health Care System, San Antonio, and Michael E. DeBakey Veterans Affairs Medical Center and Baylor College of Medicine, Houston, Texas; Johns Hopkins University School of Medicine, Baltimore, Maryland; Division of Pulmonary, Critical Care, and Sleep Medicine, University of Mississippi School of Medicine, Jackson; Division of Pulmonary and Critical Care Medicine, LDS Hospital, and University of Utah, Salt Lake City, Utah; Centers for Disease Control and Prevention, Atlanta, Georgia; Northeastern Ohio Universities College of Medicine, Rootstown, and Summa Health System, Akron, Ohio; State University of New York at Stony Brook, Stony Brook, and Department of Medicine, Winthrop University Hospital, Mineola, New York; and Cap de Servei de Pneumologia i Allergia Respiratoria, Institut Clinic del Torax, Hospital Clinic de Barcelona, Facultat de Medicina, Universitat de Barcelona, Institut d’Investigacions Biomediques August Pi i Sunyer, CIBER CB06/06/0028, Barcelona, Spain.

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Infectious Diseases Society of America/American Thoracic Society Consensus Guidelines on the Management of Community-Acquired Pneumonia in Adults

It is our central hypothesis that periodontal diseases, which are chronic Gramnegative infections, represent a previously unrecognized risk factor for atherosclerosis and thromboembolic events. Previous studies have demonstrated an association between periodontal disease severity and risk of coronary heart disease and stroke. We hypothesize that this association may be due to an underlying inflammatory response trait, which places an individual at high risk for developing both periodontal disease and atherosclerosis. We further suggest that periodontal disease, once established, provides a biological burden of endotoxin (lipopolysaccharide) and inflammatory cytokines (especially TxA2 , IL-1β, PGE2 , and TNF-α) which serve to initiate and exacerbate atherogenesis' and thromboembolic events. A cohort study was conducted using combined data from the Normative Aging Study and the Dental Longitudinal Study sponsored by the United States Department of Veterans Affairs. Mean bone loss scores and worst probing pocket depth scores per tooth were measured on 1,147 men during 1968 to 1971. Information gathered during follow-up examinations showed that 207 men developed coronary heart disease (CHD), 59 died of CHD, and 40 had strokes. Incidence odds ratios adjusted for established cardiovascular risk factors were 1.5, 1.9, and 2.8 for bone loss and total CHD, fatal CHD, and stroke, respectively. Levels of bone loss and cumulative incidence of total CHD and fatal CHD indicated a biologic gradient between severity of exposure and occurrence of disease. J Periodontol 1996;67:1123-1137.

Periodontal Disease and Cardiovascular Disease

BACKGROUND: There is evidence that chronic inflammation may promote atherosclerotic disease. We tested the hypothesis that acute infection and vaccination increase the short-term risk of vascular events. METHODS: We undertook within-person comparisons, using the case-series method, to study the risks of myocardial infarction and stroke after common vaccinations and naturally occurring infections. The study was based on the United Kingdom General Practice Research Database, which contains computerized medical records of more than 5 million patients. RESULTS: A total of 20,486 persons with a first myocardial infarction and 19,063 persons with a first stroke who received influenza vaccine were included in the analysis. There was no increase in the risk of myocardial infarction or stroke in the period after influenza, tetanus, or pneumococcal vaccination. However, the risks of both events were substantially higher after a diagnosis of systemic respiratory tract infection and were highest during the first three days (incidence ratio for myocardial infarction, 4.95; 95 percent confidence interval, 4.43 to 5.53; incidence ratio for stroke, 3.19; 95 percent confidence interval, 2.81 to 3.62). The risks then gradually fell during the following weeks. The risks were raised significantly but to a lesser degree after a diagnosis of urinary tract infection. The findings for recurrent myocardial infarctions and stroke were similar to those for first events. CONCLUSIONS: Our findings provide support for the concept that acute infections are associated with a transient increase in the risk of vascular events. By contrast, influenza, tetanus, and pneumococcal vaccinations do not produce a detectable increase in the risk of vascular events.

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Risk of Myocardial Infarction and Stroke after Acute Infection or Vaccination

Background: Recent studies suggest that chronic infections including those associated with periodontitis increase the risk for coronary vascular disease (CVD) and stroke. We hypothesize that oral microorganisms including periodontal bacterial pathogens enter the blood stream during transient bacteremias where they may play a role in the development and progression of atherosclerosis leading to CVD. Methods: To test this hypothesis, 50 human specimens obtained during carotid endarterectomy were examined for the presence of Chlamydia pneumoniae, human cytomegalovirus, and bacterial 16S ribosomal RNA using specific oligonucleotide primers in polymerase chain reaction (PCR) assays. Approximately 100 ng of chromosomal DNA was extracted from each specimen and then amplified using standard conditions (30 cycles of 30 seconds at 95°C, 30 seconds at 55°C, and 30 seconds at 72°C). Bacterial 16S rDNA was amplified using 2 synthetic oligonucleotide primers specific for eubacteria. The PCR product generated with the e...

Identification of periodontal pathogens in atheromatous plaques.

There is a lack of consensus among studies on the possible risks of stroke from cigarette smoking; because of this a meta-analysis was conducted. All published data on the association were sought and the relative risk for each study obtained whenever possible. The pooled relative risks were calculated by using estimates of the precision of the individual relative risks to weight their contribution to the meta-analysis. Thirty two separate studies were analysed. The overall relative risk of stroke associated with cigarette smoking was 1.5 (95% confidence interval 1.4 to 1.6). Considerable differences were seen in relative risks among the subtypes: cerebral infarction 1.9, cerebral haemorrhage 0.7, and subarachnoid haemorrhage 2.9. An effect of age on the relative risk was also noted; less than 55 years 2.9, 55-74 years 1.8, and greater than or equal to 75 years 1.1. A dose response between the number of cigarettes smoked and relative risk was noted, and there was a small increased risk in women compared with men. Ex-smokers under the age of 75 seemed to retain an appreciably increased risk of stroke (1.5); for all ages the relative risk in ex-smokers was 1.2. The meta-analysis provides strong evidence of an excess risk of stroke among cigarette smokers. Stroke should therefore be added to the list of diseases related to smoking.

https://www.bmj.com/content/bmj/298/6676/789.full.pdf

Meta-analysis of relation between cigarette smoking and stroke.

The association between dental infections and cerebral infarction was investigated in a case-control study involving 40 patients with ischaemic cerebral infarction under the age of 50, and 40 randomly selected community controls matched for sex and age. Poor oral health, as assessed by two indices measuring the severity of infections of teeth and periodontium, or by the presence of subgingival calculus or the presence of suppuration in the gingival pockets, were more common in male patients than in male controls, but no difference was observed in females. If severe dental infections were combined with other probable bacterial infections there were altogether 16 patients (40%) but only two controls (5%) who had suffered from a probable bacterial infection within 1 month or at the time of the stroke or when examined as a control (P less than 0.01). Our results suggest an association between bacterial infection and ischaemic cerebrovascular disease in patients under 50 years of age. Severe chronic dental infection seems to be an important type of infection associated with cerebral infarction in males.

Dental infections in association with cerebral infarction in young and middle-aged men.

The role of preceding infection as a risk factor for ischaemic stroke was investigated in a case-control study of 54 consecutive patients under 50 years of age with brain infarction and 54 randomly selected controls from the community matched for sex and age. Information about previous illnesses, smoking, consumption of alcohol, and use of drugs was taken. A blood sample was analysed for standard biochemical variables and serum cholesterol, high density lipoprotein cholesterol, triglyceride, and fasting blood glucose concentrations determined. Titres of antimicrobial antibodies against various bacteria, including Staphylococcus, Streptococcus, Yersinia, and Salmonella and several viruses were determined. Febrile infection was found in patients during the month before the brain infarction significantly more often than in controls one month before their examination (19 patients v three controls; estimated relative risk 9.0 (95% confidence interval 2.2 to 80.0)). The most common preceding febrile infection was respiratory infection (80%). Infections preceding brain infarction were mostly of bacterial origin based on cultural, serological, and clinical data. In conditional logistic regression analysis for matched pairs the effect of preceding febrile infection remained significant (estimated relative risk 14.5 (95% confidence interval 1.9 to 112.3)) when tested with triglyceride concentration, hypertension, smoking, and preceding intoxication with alcohol. Although causality cannot be inferred from these data and plausible underlying mechanisms remain undetermined, preceding febrile infection may play an important part in the development of brain infarction in young and middle aged patients.

https://www.bmj.com/content/bmj/296/6630/1156.full.pdf

Preceding infection as an important risk factor for ischaemic brain infarction in young and middle aged patients.

. Vascular diseases are multifactorial, and several risk factors, such as increasing age, male sex, hypertension, diabetes, dyslipidemias and smoking, are well-known. In recent studies, associations have also been found between preceding infections and development of myocardial or cerebral infarction. Preceding acute respiratory infections are reported to be more common in patients with myocardial or cerebral infarction. Cerebral infarction may follow infective endocarditis, bacterial meningitis or any other bacteremic infection. Oral infections are common chronic bacterial infections. Although oral infections are local, they may lead to systemic infectious complications via stransient bacteremias, and there may also be other systemic effects, for instance, via immunologic or toxic mechanisms. Association between oral infections and vascular diseases has been studied in 2 Finnish case-control studies concerning myocardial and cerebral infarction. In these case-control studies, it was found that oral infections were more common in patients with myocardial or cerebral infarction than in their age- and sex-matched community controls. There are many factors, such as diabetes, smoking and alcohol abuse, which may predispose to both development of infarction and oral infections. Therefore, the observed association between oral infections and vascular diseases may result from these common predisposing factors, and causality between them cannot be inferred. There are, however, several possible links between oral infections and infarction. Although causality between oral infections and infarction cannot be proven, patients who have poor oral health need health education, paying attention to those common risk factors of oral infections and vascular diseases. Furthermore, their oral infections should be treated, because they may predispose to infectious complications, which may lead to infarction.

Vascular diseases and oral infections

Pneumococcal bacteraemia during a recent decade

The occurrence of central nervous system (CNS) complications was studied retrospectively in 150 patients with bacteremia caused by Staphylococcus aureus, Streptococcus pneumoniae, beta-hemolytic streptococci or Escherichia coli. The incidence and clinical manifestations of different CNS complications were noted during 1 month after the bacteremia. Special attention was paid to vascular complications (infarction or hemorrhage), infections (meningitis or brain abscess) and mental changes when they were the only signs of CNS origin (lowered level of consciousness, confusion or delirium). The risk of cerebral infarction was elevated in the patients with bacteremia during the first month after the positive blood culture as compared with the overall risk of stroke in the general population. 10/150 patients (7%) developed cerebral infarction during that month. Two of these cases were associated with bacterial meningitis and 1 with endocarditis. Mental changes as a main symptom of CNS origin occurred in 27% of patients with bacteremia. Increasing patient age predisposed to this complication. Mental changes were not associated with any bacterial species studied. Altogether 40% of the patients developed CNS complications, which were a significant risk factor for death during the first month after the bacteremia.

Jaana Syrjänen

Papers

Dental infections in association with cerebral infarction in young and middle-aged men.

Preceding infection as an important risk factor for ischaemic brain infarction in young and middle aged patients.

Vascular diseases and oral infections

Pneumococcal bacteraemia during a recent decade

Central Nervous System Complications in Patients with Bacteremia