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(Stroke. 1997;28:1724-1729.)
© 1997 American Heart Association, Inc.

Articles

Association Between Acute Cerebrovascular Ischemia and Chronic and Recurrent Infection

Armin J. Grau, MD; Florian Buggle; Christoph Ziegler, DMD, MD; Wolfgang Schwarz; Jutta Meuser, MD; Abel-Jan Tasman, MD; Alexandra Bühler; Cand Med; Christoph Benesch, MD; Heiko Becher, PhD; Werner Hacke, MD

From the Department of Neurology (A.J.G., F.B., A.B., W.H.), Department of Oral and Maxillofacial Surgery (C.Z., W.S.), Department of Ear, Nose and Throat Medicine (J.M., A.-J.T.), Department of Neurosurgery (C.B.), University of Heidelberg, and Department of Epidemiology, German Cancer Research Center (H.B.), Heidelberg, Germany.

Correspondence to Armin J Grau, MD, Department of Neurology, University of Heidelberg, Im Neuenheimer Feld 400, D-69120 Heidelberg, Germany. E-mail Armin_Grau{at}krzmail.krz.uni-heidelberg.de

	Abstract

Top Abstract Introduction Subjects and Methods Results Discussion References

 
Background and Purpose We performed a case-control study to investigate whether chronic or recurrent respiratory, ear-nose-throat (ENT), and dental infections are risk factors for cerebrovascular ischemia.

Methods Using a standardized questionnaire we investigated past infectious diseases in 166 consecutive patients with acute cerebrovascular ischemia and in 166 age- and sex-matched nonstroke neurological patient controls. In subgroups, we performed standardized ENT (69 patients, 66 control subjects) and dental examinations including orthopantomography (66 patients, 60 control subjects). Dental status was determined by a total dental index (TDI) that reflects caries, periapical lesions, periodontitis, and other dental lesions and by an orthopantomography index (OPGI) that was assessed blinded.

Results Frequent (2 episodes in each of the 2 preceding years) or chronic bronchitis was associated with cerebrovascular ischemia in age-adjusted multiple logistic regression analysis (odds ratio, OR, 2.2; 95% confidence interval, CI, 1.04 to 4.6). Groups were not different in ENT examination. Patients tended to have a worse dental status (TDI: P=.070; OPGI: P=.062) and had more severe periodontitis (P=.047) and periapical lesions (P=.027) than control subjects. In age-adjusted multiple logistic regression analysis with social status and established vascular risk factors, poor dental status (TDI) was independently associated with cerebrovascular ischemia (OR, 2.6; 95% CI, 1.18 to 5.7).

Conclusion Recurrent or chronic bronchial infection and poor dental status, mainly resulting from chronic dental infection, may be associated with an increased risk for cerebrovascular ischemia.

Key Words: cerebral ischemia • risk factors • infection

	Introduction

Top Abstract Introduction Subjects and Methods Results Discussion References

 
Several studies unanimously showed that acute infection is a risk factor for cerebrovascular ischemia.^{1 2 3 4} In contrast, the role of chronic or recurrent infection as a potential stroke risk factor is mainly unknown.⁵ Presently, there is increasing evidence that chronic bronchitis⁶ and chronic infection with microbial agents such as Chlamydia pneumoniae,⁷ Helicobacter pylori,⁸ and cytomegalovirus⁹ may be associated with cardiovascular disease and atherogenesis. Furthermore, poor dental health was shown to increase the risk for coronary heart disease and acute myocardial infarction.^{10 11 12 13 14} Caries and periodontitis are the most important chronic dental diseases, and they both are bacterial infections.^{15 16} In a case-control study, poor dental status was a risk factor for myocardial infarction independent from age, social class, smoking, hyperlipidemia, and diabetes mellitus.¹⁰ Further results indicated a significant association between chronic dental infection and severity of coronary atherosclerosis.¹¹ Other studies found the number of missing teeth¹² and poor oral hygiene and periodontitis but not caries¹³ to be independently associated with coronary heart disease. Few studies addressed the role of dental infection in cerebrovascular disease. In a case-control study with 40 ischemic stroke patients under the age of 50 years, male but not female patients had more severe dental infection than respective control subjects from the community.¹⁷ A recently published cohort study with 1147 men followed for more than 18 years found periodontal disease to be associated with coronary heart disease (relative risk, 1.5; 95% CI, 1.04 to 2.1) and stroke (relative risk, 2.8; 95% CI, 1.45 to 5.5) independent from other risk factors and education.¹⁴

We investigated whether chronic or recurrent bronchial, ENT, and dental infections may be associated with acute cerebrovascular ischemia. Furthermore, we tested the hypothesis that chronic or recurrent infection is primarily correlated with cerebrovascular ischemia from large artery atherosclerosis.

	Subjects and Methods

Top Abstract Introduction Subjects and Methods Results Discussion References

 
We performed a case-control study of patients with acute cerebrovascular ischemia and age- and sex-matched hospitalized control subjects in order to study the role of acute and chronic infectious diseases as stroke risk factors. Here we report results from the analysis of past infectious diseases and from standardized dental and ENT examinations that were performed in subgroups of patients.

We examined 166 consecutive patients who were admitted to the Neurology Department for acute cerebrovascular ischemia between August 1995 and January 1996. The patients, 56 women and 110 men, were 61.2±13.8 (mean±SD; range, 22 to 85) years of age. Patients suffered from either brain infarction, as evidenced by CT or MRI (n=130), or from transient cerebral ischemia (n=36; symptoms lasting <24 hours and no infarction on neuroimaging). All patients received a cranial CT scan, with those with primary cerebral hemorrhage excluded. Follow-up neuroimaging studies were done in 93 patients; 66 patients were examined by digital subtraction, CT, or MR angiography. Extracranial and transcranial Doppler ultrasound studies were done in 155 and 150 patients, respectively. An electrocardiogram was available in 152 patients and echocardiography (transthoracic and/or transesophageal) was performed in 99 patients. In the absence of other potential causes, cerebrovascular ischemia was diagnosed to be caused by large artery atherosclerosis in case of arterial occlusions or stenoses 50% diameter reduction at a site and with a morphology typical of atherosclerotic lesions on Doppler ultrasound or angiography. Further etiological diagnoses included cardioembolism, based on the criteria of the Trial of ORG 10172 in Acute Stroke Treatment (TOAST) investigators,¹⁸ other (eg, microangiopathy, dissection, and vasculitis), and unknown including multiple possible causes.

The control group consisted of hospitalized patients from the Departments of Neurology or Neurosurgery. From the control group we excluded patients who had cerebrovascular (eg, intracranial hematoma, migraine, spinal cord ischemia), inflammatory (eg, meningitis, encephalitis, multiple sclerosis, Guillain-Barré syndrome), alcohol-derived (eg, Wernicke encephalopathy), or paraneoplastic neurological disorders and patients with central nervous system metastases. Patients and control subjects were individually matched for sex and age (±10 years). The first control subject was admitted after a respective patient was entered into the study. The age restriction was abandoned when no control subject could be identified within 2 weeks after admission of a patient with cerebrovascular ischemia. All 166 control patients who were asked agreed to participate. The control subjects (56 women and 110 men) had an age of 57.9±15.3 (range, 19 to 87) years (difference between groups: P=.065). Control patients suffered from primary brain tumors (n=47), neurodegenerative and movement disorders (n=40), peripheral neuropathy including diseases of the cranial nerves (n=24), disorders of the vertebral column (n=22), epileptic seizures (n=15), and other diseases (n=18).

We took a detailed history from all participating subjects using a standardized questionnaire that focuses on previous vascular diseases and risk factors and on inflammatory diseases. We asked all subjects whether they had ever been diagnosed to suffer from bronchitis, sinusitis, tonsillitis, or urinary tract infection. Recurrent infection (eg, recurrent bronchitis) was acknowledged when the respective diagnosis had been made two or more times. We also asked for the number of episodes with cough and phlegm during the last 2 years; subjects who mentioned at least two such episodes or cough with phlegm during as much as 3 months in each of 2 years were diagnosed as suffering from "frequent or chronic bronchitis." Acute infection was considered as a potential confounder in multivariate analysis; it was defined as reported previously.² We interviewed a next of kin when information was not available from the patient. In a few cases of missing information the respective parameter was qualified as being negative. In 10 patients no history was available and in 18 patients information was based on a next-of-kin interview. In the control group, medical history was taken from the subjects themselves. The social status was based on the subject's occupation or when people did not work on their highest school degree. The occupation of subjects in class I typically required academic or similar training, subjects in class II were specialized workers and employees without academic or similar training, and class III consisted of nonspecialized workers. On follow-up examination 3 or more months after ischemia, fibrinogen (turbidimetric assay; Baxter) and leukocyte count (Coulter counter analyzer) were evaluated. Patients with acute inflammatory diseases within the week before follow-up examination were excluded from these analyses.

Dental and ENT Examination
Subgroups of patients from both groups were asked to participate in standardized dental and ENT examinations. For ethical and legal reasons, we excluded those patients who were not able to give informed consent, patients who could not be transported to the Dental or ENT Department due to severe illness, and pregnant women and subjects with professional exposure to ionizing radiation.

Among the 166 patients, 44 had one of the above exclusion criteria and 36 patients were referred to other hospitals or discharged early after stroke and could therefore not be examined in this part of the study. Among the 86 patients we asked, 66 patients (20 women, 46 men; age, 54.3±13.6 years) agreed to the dental examination. Eighty-eight control subjects were asked and 60 (19 women, 41 men; age, 56.6±15.4 years) took part in the dental examination. Sixty-nine patients (20 women, 49 men; age, 56.2±14.2 years) and 66 subjects from the control group (20 women, 46 men; age, 54.4±16.1 years) gave their consent to an ENT examination.

The dental examination consisted of a standardized clinical evaluation of all teeth and the periodontium and a radiograph of jaws and teeth (OPG). Dental status was graded by using two indexes, one of which was assessed blind. We used a modified TDI,^{11 14} which is based on clinical and radiological examination and included assessment of caries, periodontitis, periapical lesions, nonvital teeth without periapical lesions, and pericoronitis. The index ranged from 0 to 14, increasing with the severity of the disease (Table 1). Six or more points in the TDI were considered as poor dental status. Almost all dental examinations were done by two dentists (C.Z. and W.S.). At the end of the study, OPGs were reexamined by one dentist (C.Z.) who was blinded to the status of the respective subject. The number of periapical lesions, vertical bone pockets, lesions caused by third-degree caries or by pericoronitis, and radiolucent areas at the furcation were added and formed the OPGI.¹¹

View this table: [in this window] [in a new window]   Table 1. The Total Dental Index

On ENT examination, chronic otitis media with otorrhea was assessed by otoscopy. Endoscopy of the middle nasal meatus served to identify purulent discharge from the paranasal sinus ostia (purulent sinusitis). A-mode sonography was used to evaluate mucosal thickening or retention of secretion in maxillar and frontal sinuses. Tonsils were inspected and purulent discharge was discerned by expression of tonsillar crypt content.

The local ethics committee approved the study protocol and the office in charge, the Regierungspräsidium Karlsruhe, agreed to the use of OPG for scientific purposes. All subjects investigated gave informed consent.

Statistical Methods
We used the nonparametric Mann-Whitney U test for the comparison of dental indexes and calculated Spearman's rank correlation coefficient to express the correlation of different variables. The ² test and Fisher's exact test were applied to compare sample proportions; the McNemar test was used for analyzing data based on individually matched case-control pairs. Odds ratios were estimated with a univariate or multiple conditional logistic regression model. For the analysis of dental and ENT parameters the individual matching was released and new strata were formed according to a frequency matching by age and sex. To study the influence of various factors on a parameter, we used an ANOVA model. All analyses were performed using the statistical software package by SAS Inc.

	Results

Top Abstract Introduction Subjects and Methods Results Discussion References

 
We first present results for the total study group, regardless of whether subjects participated in the dental and ENT examinations. Patients suffered more often than control subjects from recurrent bronchitis (OR, 1.90; 95% CI, 1.11 to 3.3) and from frequent or chronic bronchitis (OR, 2.09; 95% CI, 1.02 to 4.3) (Table 2). In age-adjusted multiple logistic regression analysis with arterial hypertension, diabetes mellitus, current smoking, acute respiratory infection within 1 week, and previous stroke or transient cerebral ischemia as covariates, frequent or chronic bronchitis remained significantly associated with acute cerebrovascular ischemia (OR, 2.19; 95% CI, 1.04 to 4.6) (Table 3). Patients with cerebrovascular ischemia due to large artery atherosclerosis (n=40) did not suffer from frequent or chronic bronchitis (7/40; 17.5%) more often than patients with other etiologies (22/102; 21.6%). Similarly, the prevalence of frequent or chronic bronchitis was not different between patients with (14/75; 18.7%) and without (15/67; 22.4%) atherosclerotic vascular disease (history of coronary heart disease or peripheral arterial disease, atherosclerotic stenoses, or occlusions of brain-supplying arteries). Recurrent sinusitis, recurrent tonsillitis, and recurrent urinary tract infection were not more common among patients than control subjects (Table 2). The prevalence of hypertension, diabetes mellitus, smoking, and previous vascular disorders in our control group was comparable to the prevalence in population controls from our area in a previous study² (data not shown).

View this table: [in this window] [in a new window]   Table 2. History of Recurrent or Chronic Infection in Patients and Control Subjects

View this table: [in this window] [in a new window]   Table 3. Age-Adjusted Multiple Logistic Regression Analysis With Frequent or Chronic Bronchitis and Other Factors

On ENT examination, none of the parameters assessed by clinical or ultrasound examination had a higher prevalence in the patient group than in the control group. In contrast, chronic purulent tonsillitis was more prevalent in control subjects than in patients (Table 4).

View this table: [in this window] [in a new window]   Table 4. Results of the ENT Examination

On the basis of both TDI and OPGI, patients with cerebrovascular ischemia tended to have a worse dental status than the control group (P=.070 and P=.062, respectively) (Table 5). Both scores were significantly correlated with each other (r=.62; P<.001). We will now focus on the TDI. Male patients and patients over the age of 50 years had a significantly worse dental status than the respective control group, whereas no difference existed in women and in younger subjects. Patients with cerebrovascular ischemia had significantly more severe periodontitis and periapical lesions than the control group. No differences existed with respect to other parameters assessed (Table 5). None of the subjects had typical drug-induced periodontal disease, eg, gingival hyperplasia.

View this table: [in this window] [in a new window]   Table 5. Results of the Dental Examination

In univariate analysis, poor dental status (TDI 6) was associated with an increased risk for cerebrovascular ischemia (OR, 2.51; 95% CI, 1.20 to 5.2). In multiple logistic regression analysis, the association of poor dental status and cerebrovascular ischemia was found to be independent of current smoking, diabetes mellitus, low social status, and preexisting vascular diseases with an almost unchanged OR of 2.60 (95% CI, 1.18 to 5.7) (Table 6). In univariate analysis, patients with large artery atherosclerosis (n=17) had a worse dental status (median TDI, 7.5; 25% to 75% quartile, 4 to 9) than patients with cerebrovascular ischemia of other or unknown origin (n=49; median TDI, 4.5; 25% to 75% quartile, 3 to 7; P=.041). This difference was more pronounced when patients with known atherosclerotic vascular disease of the brain, heart or legs (n=27; median TDI, 7; 25% to 75% quartile, 4 to 9) were compared with patients without such disease (n=39; median TDI, 4; 25% to 75% quartile, 3 to 7; P=.017). However, in an ANOVA model with current smoking, diabetes mellitus, social class, and age, atherosclerotic disease was not independently associated with poor dental status (P=.13).

View this table: [in this window] [in a new window]   Table 6. Age-Adjusted Multiple Logistic Regression Analysis With Poor Dental Status (TDI 6) and Other Factors

In measurements on follow-up examination 3 months or more after ischemia, patients with previously assessed poor dental status (TDI 6) tended to have higher leukocyte counts (n=28; 8.1±2.1 per nL) than the other patients (n=28; 7.1±1.6 per nL; P=.077). There was no difference between groups with respect to fibrinogen (n=27, 3.35±1.07 g/L versus n=25, 3.39±1.45 g/L; NS). Leukocyte count was correlated with TDI (r=.27; P=.048) and the periodontitis score (r=.31; P=.022) but not with other subscores of the TDI. TDI and fibrinogen were not associated with each other.

Patients and control subjects with dental examinations are selected groups. It is possible that risk factors or diseases may have influenced the participation in dental examination differentially in both groups. Therefore, we compared the prevalence of vascular risk factors and diseases in patients and control subjects who participated and those who did not participate in the dental examination. The participation rate of subjects with hypertension, diabetes mellitus, current smoking, previous vascular diseases, or low social status was not different between both groups (P>.1, ² test, respectively).

	Discussion

Top Abstract Introduction Subjects and Methods Results Discussion References

 
The results from this study suggest that independent from established vascular risk factors, symptoms of recurrent or chronic bronchitis and poor dental status may be associated with cerebrovascular ischemia. Periodontitis and periapical lesions appear as the main contributors in the role of chronic dental disease.

We examined patients with acute ischemia because stroke itself can lead to reduced oral hygiene and thus to an increased rate of dental infection. And we decided to investigate hospitalized control subjects because on the basis of previous experience, we could expect a low participation rate of community controls, especially in a study including ENT and dental examinations. In our hospitalized control group, 68% and 75% of the subjects asked took part in the dental and ENT examinations, respectively. From the control group we excluded neurological disorders that can be caused (eg, meningitis and encephalitis) or triggered (eg, multiple sclerosis or Guillain-Barré syndrome) by infectious diseases and that may be associated with increased susceptibility to infection (eg, metastasizing tumors). We cannot exclude that some of the neurological disorders of the control group were also associated with infectious disease and poor dental hygiene. Such presently unknown association would have resulted in an underestimation of the role of infection in cerebrovascular ischemia. The risk factor profile in our control group was similar to the one in a community control group in a recent study in our area,² indicating that the control group was representative with respect to conventional vascular risk factors.

Recently, a large cohort study from Finland reported that symptoms of chronic bronchitis were an independent predictor for coronary heart disease (relative risk, 1.52; 95% CI, 1.33 to 1.75).⁶ We found that a history of chronic or frequent bronchitis was significantly associated with acute cerebrovascular ischemia independent from recent acute respiratory infection, current smoking, and other potential confounders. From cohort studies, there is evidence that reduced ventilatory function (eg, resulting from chronic bronchitis) is associated with an increased risk for stroke.^{19 20} Presently, it is unknown whether the association between frequent or chronic bronchitis and cerebrovascular ischemia is causal and which pathogenetic pathways might eventually link both diseases. Our data do not support the hypothesis that chronic or frequent bronchitis may particularly contribute to the risk of stroke by promoting atherosclerosis. Chronic or frequently exacerbating bronchial infection may be associated with a procoagulant state; however, further studies are required to investigate such a hypothesis.

Older studies suggested that chronic infectious disease (eg, infection of the paranasal sinuses) could play a role in the pathogenesis of atherosclerotic lesions in large arteries.^{21 22} We found no association between cerebrovascular ischemia and chronic ENT infection. To avoid difficulties in interpretation of paranasal sinus opacifications on plain radiograph, we chose to assess the sinuses by a combination of endoscopical investigation of the middle meatus and A-mode sonography. We could not investigate the ethmoidal and sphenoidal sinuses because imaging of this region was not available from all control subjects. Future studies may address the question of whether infection of these sinuses is associated with cerebrovascular ischemia.

Using two methods to evaluate dental health, one of which was assessed blinded, we found an association between poor dental status and cerebrovascular ischemia in univariate analysis. Similar to a longitudinal study on dental health and coronary heart disease,¹³ periodontitis and periapical lesions but not caries contributed to the differences between groups. Smoking, diabetes mellitus, and social status are known to influence dental health, and immobility caused by preexisting vascular diseases may also have an impact.²³ However, the multivariate analysis showed that the association between cerebrovascular ischemia and dental status was independent from these factors. Poor oral hygiene may be combined with poor control of established vascular risk factors, but the idea of a health-neglecting lifestyle as a confounding factor would not explain the differences between caries and periodontitis as risk factors in our study. Diet may be a confounder that was not controlled for in our study. High sucrose intake increases the risk for caries,¹⁵ but it seems not to play an important role in periodontitis.²³ Low levels of antioxidants, particularly vitamin C, may be a risk factor for both atherosclerosis and infectious disease.²⁴ The role of vitamin intake in periodontal disease is insufficiently known, however.

The lesions assessed by the TDI are mostly but not always caused by infectious dental disease. Missing and nonvital teeth can be the sequel of a trauma, but periapical lesions and periodontitis, which were more severe in the patient group, are both infectious disorders. Periapical lesions result from chronic bacterial infection, originating from the pulpa and extending into the periapical tissue.²⁵ Periodontitis is primarily caused by anaerobic gram-negative bacteria and is episodic in nature with relatively short periods of exacerbation.¹⁴ Periodontal pathogens can evade local host defense mechanisms and even daily procedures such as toothbrushing and chewing can induce transient bacteremia.²⁶ Periodontitis frequently leads to substantial systemic antibody response to specific periodontal pathogenetic microbes and their endotoxins.²⁷ Such systemic effect of dental infection is also reflected by increased activity of von Willebrand factor,²⁸ a marker of endothelial activation, and elevated leukocyte count and fibrinogen, both risk factors for stroke and myocardial infarction.²⁹ In our study, TDI and the subscore of periodontitis were correlated with leukocyte count but not with fibrinogen.

Poor dental status was associated with atherosclerotic disease in univariate analysis, but this association was not significant when age and vascular risk factors were adjusted for. Larger studies are required to determine whether dental infection may be a risk factor for stroke due to large artery atherosclerosis. Monocytes and macrophages play an important pathogenetic role in both atherosclerosis and periodontitis.^{14 30} Beck and coworkers hypothesized that subjects with a genetically determined strong monocytic response to bacterial antigens could be at high risk for developing both periodontal disease and atherosclerosis.¹⁴ Once established, periodontitis represents a burden of bacteria, endotoxin, and proinflammatory cytokines that may contribute to atherogenesis and thromboembolic events.^{14 16} A systemic challenge with bacteria or endotoxin can induce inflammatory cell infiltration into large arteries, vascular smooth muscle proliferation, and other sequelae, which are also prominent features in the natural history of atherogenesis.^{31 32} Streptococcus sanguis, a microbe of the normal oral flora, can induce platelet aggregation and may thus be thrombogenic when allowed to enter the systemic circulation as in periodontitis.³³ Furthermore, acute—and possibly exacerbating chronic—infection can modify established vascular risk factors by reducing glucose tolerance³⁴ and moving serum lipids toward a profile that is more atherogenic.³⁵

Presently, it is unknown whether the association between chronic or recurrent infection and stroke is causal. Several pathogenetic pathways make a causal linkage plausible. However, it is also possible that genetic and environmental factors increase the susceptibility to both chronic infection and stroke. The decline in stroke mortality is insufficiently explained by improvements in established risk factors.^{36 37} If the observed association between chronic infection and cerebrovascular ischemia is causal, better control of infection and improved dental care may have contributed to the recent decline of stroke. Chronic infection is a treatable condition, and for preventive purposes, it appears important to further elucidate its role as a potential stroke risk factor.

	Selected Abbreviations and Acronyms

 

CI = confidence interval ENT = ear-nose-throat OPG = orthopantomography OPGI = orthopantomography index OR = odds ratio TDI = total dental index

Received April 18, 1997; revision received June 30, 1997; accepted July 2, 1997.

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				E. Lalla, D. B. Park, P. N. Papapanou, and I. B. Lamster Oral Disease Burden in Northern Manhattan Patients With Diabetes Mellitus Am J Public Health, September 1, 2008; 98(Supplement_1): S91 - S94. [Abstract] [Full Text] [PDF]

				P. S. Stein, M. Desrosiers, S. J. Donegan, J. F. Yepes, and R. J. Kryscio Tooth loss, dementia and neuropathology in the Nun Study J Am Dent Assoc, October 1, 2007; 138(10): 1314 - 1322. [Abstract] [Full Text] [PDF]

				P.J. Ford, E. Gemmell, P. Timms, A. Chan, F.M. Preston, and G.J. Seymour Anti-P. gingivalis Response Correlates with Atherosclerosis J. Dent. Res., January 1, 2007; 86(1): 35 - 40. [Abstract] [Full Text] [PDF]

				V. Ganesan, M. Prengler, A. Wade, and F. J. Kirkham Clinical and Radiological Recurrence After Childhood Arterial Ischemic Stroke Circulation, November 14, 2006; 114(20): 2170 - 2177. [Abstract] [Full Text] [PDF]

				L. B. Goldstein, R. Adams, M. J. Alberts, L. J. Appel, L. M. Brass, C. D. Bushnell, A. Culebras, T. J. DeGraba, P. B. Gorelick, J. R. Guyton, et al. Primary Prevention of Ischemic Stroke: A Guideline From the American Heart Association/American Stroke Association Stroke Council: Cosponsored by the Atherosclerotic Peripheral Vascular Disease Interdisciplinary Working Group; Cardiovascular Nursing Council; Clinical Cardiology Council; Nutrition, Physical Activity, and Metabolism Council; and the Quality of Care and Outcomes Research Interdisciplinary Working Group: The American Academy of Neurology affirms the value of this guideline. Circulation, June 20, 2006; 113(24): e873 - e923. [Abstract] [Full Text] [PDF]

				L. B. Goldstein, R. Adams, M. J. Alberts, L. J. Appel, L. M. Brass, C. D. Bushnell, A. Culebras, T. J. DeGraba, P. B. Gorelick, J. R. Guyton, et al. Primary Prevention of Ischemic Stroke: A Guideline From the American Heart Association/American Stroke Association Stroke Council: Cosponsored by the Atherosclerotic Peripheral Vascular Disease Interdisciplinary Working Group; Cardiovascular Nursing Council; Clinical Cardiology Council; Nutrition, Physical Activity, and Metabolism Council; and the Quality of Care and Outcomes Research Interdisciplinary Working Group: The American Academy of Neurology affirms the value of this guideline. Stroke, June 1, 2006; 37(6): 1583 - 1633. [Abstract] [Full Text] [PDF]

				M. L. Rufail, H. A. Schenkein, S. E. Barbour, J. G. Tew, and R. van Antwerpen Altered lipoprotein subclass distribution and PAF-AH activity in subjects with generalized aggressive periodontitis J. Lipid Res., December 1, 2005; 46(12): 2752 - 2760. [Abstract] [Full Text] [PDF]

				J. D. Beck, P. Eke, G. Heiss, P. Madianos, D. Couper, D. Lin, K. Moss, J. Elter, and S. Offenbacher Periodontal Disease and Coronary Heart Disease: A Reappraisal of the Exposure Circulation, July 5, 2005; 112(1): 19 - 24. [Abstract] [Full Text] [PDF]

				E. Kazanci, K. K. Oguz, A. Gurgey, and M. Topcu Streptococcus oralis as a Risk Factor for Middle Cerebral Artery Thrombosis J Child Neurol, July 1, 2005; 20(7): 611 - 613. [Abstract] [PDF]

				N. Brodala, E. P. Merricks, D. A. Bellinger, D. Damrongsri, S. Offenbacher, J. Beck, P. Madianos, D. Sotres, Y.-L. Chang, G. Koch, et al. Porphyromonas gingivalis Bacteremia Induces Coronary and Aortic Atherosclerosis in Normocholesterolemic and Hypercholesterolemic Pigs Arterioscler. Thromb. Vasc. Biol., July 1, 2005; 25(7): 1446 - 1451. [Abstract] [Full Text] [PDF]

				J.A. Zeller, A. Lenz, C.C. Eschenfelder, P. Zunker, and G. Deuschl Platelet-Leukocyte Interaction and Platelet Activation in Acute Stroke With and Without Preceding Infection Arterioscler. Thromb. Vasc. Biol., July 1, 2005; 25(7): 1519 - 1523. [Abstract] [Full Text] [PDF]

				P.-O. Soder, B. Soder, J. Nowak, and T. Jogestrand Early Carotid Atherosclerosis in Subjects With Periodontal Diseases Stroke, June 1, 2005; 36(6): 1195 - 1200. [Abstract] [Full Text] [PDF]

				S. P. Engebretson, I. B. Lamster, M. S.V. Elkind, T. Rundek, N. J. Serman, R. T. Demmer, R. L. Sacco, P. N. Papapanou, and M. Desvarieux Radiographic Measures of Chronic Periodontitis and Carotid Artery Plaque Stroke, March 1, 2005; 36(3): 561 - 566. [Abstract] [Full Text] [PDF]

				P. Ford, E. Gemmell, P. Walker, M. West, M. Cullinan, and G. Seymour Characterization of Heat Shock Protein-Specific T Cells in Atherosclerosis Clin. Vaccine Immunol., February 1, 2005; 12(2): 259 - 267. [Abstract] [Full Text] [PDF]

				P. J. Pussinen, G. Alfthan, H. Rissanen, A. Reunanen, S. Asikainen, and P. Knekt Antibodies to Periodontal Pathogens and Stroke Risk Stroke, September 1, 2004; 35(9): 2020 - 2023. [Abstract] [Full Text] [PDF]

				E. Lalla, D. B. Park, P. N. Papapanou, and I. B. Lamster Oral Disease Burden in Northern Manhattan Patients With Diabetes Mellitus Am J Public Health, May 1, 2004; 94(5): 755 - 758. [Abstract] [Full Text] [PDF]

				G. D.O. Lowe Dental Disease, Coronary Heart Disease and Stroke, and Inflammatory Markers: What Are the Associations, and What Do They Mean? Circulation, March 9, 2004; 109(9): 1076 - 1078. [Full Text] [PDF]

				A. J. Grau, H. Becher, C. M. Ziegler, C. Lichy, F. Buggle, C. Kaiser, R. Lutz, S. Bultmann, M. Preusch, and C. E. Dorfer Periodontal Disease as a Risk Factor for Ischemic Stroke Stroke, February 1, 2004; 35(2): 496 - 501. [Abstract] [Full Text] [PDF]

				J.R. Elter, S. Offenbacher, J.F. Toole, and J.D. Beck Relationship of Periodontal Disease and Edentulism to Stroke/TIA J. Dent. Res., December 1, 2003; 82(12): 998 - 1001. [Abstract] [Full Text]

				P. J. Lindsberg and A. J. Grau Inflammation and Infections as Risk Factors for Ischemic Stroke Stroke, October 1, 2003; 34(10): 2518 - 2532. [Abstract] [Full Text] [PDF]

				R. Tuominen, A. Reunanen, M. Paunio, I. Paunio, and A. Aromaa Oral Health Indicators Poorly Predict Coronary Heart Disease Deaths J. Dent. Res., September 1, 2003; 82(9): 713 - 718. [Abstract] [Full Text] [PDF]

				H.-C. HUNG, W. WILLETT, A. ASCHERIO, B. A. ROSNER, E. RIMM, and K. J. JOSHIPURA Tooth loss and dietary intake J Am Dent Assoc, September 1, 2003; 134(9): 1185 - 1192. [Abstract] [Full Text] [PDF]

				M. Desvarieux, R. T. Demmer, T. Rundek, B. Boden-Albala, D. R. Jacobs Jr, P. N. Papapanou, and R. L. Sacco Relationship Between Periodontal Disease, Tooth Loss, and Carotid Artery Plaque: The Oral Infections and Vascular Disease Epidemiology Study (INVEST) Stroke, September 1, 2003; 34(9): 2120 - 2125. [Abstract] [Full Text] [PDF]

				W. G. Haynes and C. Stanford Periodontal Disease and Atherosclerosis: From Dental to Arterial Plaque Arterioscler. Thromb. Vasc. Biol., August 1, 2003; 23(8): 1309 - 1311. [Full Text] [PDF]