Oral Infections and Cardiovascular Disease


by

Lise L. Håheim

DOI: 10.2174/97816080523251110101
eISBN: 978-1-60805-232-5, 2011
ISBN: 978-1-60805-689-7

  
  


Indexed in: Scopus

This book provides a comprehensive overview of current knowledge about research in oral infections and their association with cardiova...[view complete introduction]
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Table of Contents

Foreword , Pp. i-ii (2)

Paul M. Ridker
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Preface , Pp. iii-iv (2)

Lise Lund Haheim
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List of Contributors , Pp. v-vii (3)

Lise Lund Haheim
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Dental Infections and Cardiovascular Disease - The Early Findings , Pp. 3-7 (5)

Kimmo Mattila
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Causality - When do we have Sufficient Evidence to Mark a Risk Factor for Prophylactic Purposes Against Cardiovascular Disease? , Pp. 8-16 (9)

Lise Lund Haheim
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Risk Factors for Periodontal Disease , Pp. 17-25 (9)

Morten Enersen
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Cardiovascular Risk Factors - An Aetiologically Oriented Epidemiologist’s Perspective , Pp. 26-34 (9)

Dag S. Thelle
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Oral Bacteria in Cardiovascular Diseases , Pp. 35-44 (10)

Ingar Olsen
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Biological Mechanisms: Platelets and Bacteria - Current Scientific Evidence and Methods of Analyses , Pp. 45-66 (22)

Steven W. Kerrigan and Dermot Cox
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Laboratory Methods for Analyzing Correlation between Periodontitis and Cardiovascular Disease , Pp. 67-81 (15)

Anne Karin Kristoffersen
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The Concept of Infection Control in Prevention and Treatment of Periodontal Disease , Pp. 82-90 (9)

Per Ramberg and Jan Wennstrom
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When Risk Factor Patterns Change Due to New Scientific Evidence - Ethical Dilemmas , Pp. 91-100 (10)

Bjørn Hofmann
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Linking the Evidence of Oral Infections as a Causal Factor for Cardiovascular Diseases , Pp. 101-110 (10)

Lise Lund Haheim
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Subject Index , Pp. 111-113 (3)

Lise Lund Haheim
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Foreword

In a major paradigm shift with profound implications for disease prevention as well as treatment, physician-scientists have come to realize that the root cause of atherosclerosis includes far more than simple cholesterol accumulation and “encrustation” within the arteries. Rather, following an elegant series of laboratory and clinical observations made over the past quarter-century, inflammation is now seen to play a pivotal role in all phases of atherogenesis. From a basic perspective, a host of cytokines and adhesion molecules involved in both adaptive and innate immunity influence the initial attachment of monocytes to the vessel wall that leads to foam cell creation, the intermediate stage cellular proliferation of the intima that results in arterial narrowing, and plays critical roles in the final rupture of mature plaque resulting in acute luminal occlusion. From an epidemiologic perspective, abundant evidence demonstrates that biomarkers of inflammation are increased among apparently healthy men and women at risk for future vascular disease even when cholesterol levels are low, and that the magnitude of these effects is at least as large as that of blood pressure and cholesterol.

The clinical expression this paradigm shift has been the introduction of screening for high-sensitivity C-reactive protein (hsCRP) as a simple and inexpensive method to both determine vascular risk and better target preventive therapies. In 2008, the JUPITER investigators demonstrated in an 18,000 patient randomized trial that statin therapy cuts in half the risk of heart attack and stroke among individuals with low cholesterol who were nonetheless at high risk due to increased levels of hsCRP. On the basis of that trial, in 2009 the first international guidelines appeared that endorsed use of hsCRP among “intermediate risk” patients in primary prevention, and in 2010 the United States Food and Drug Administration granted approval for the use of statin therapy among individuals with elevated hsCRP, even in the absence of hyperlipidemia.

Where, however, does this systemic inflammation come from and might there be simple non-pharmacologic methods for vascular disease prevention that capitalize on this new information? One enticing area of research has been in the arena of dental infection and chronic periodontal disease, both of which are increased in populations with atherosclerosis. Could it be that the systemic inflammation triggered by poor oral hygiene is among the root causes of atherosclerosis?

In this text entitled Oral Infections and Cardiovascular Disease, Lise Lund Håheim and her colleagues expertly address this hypothesis. In opening chapters describing initial observations and population studies, the core epidemiology linking oral disease, cardiovascular risk factors, and vascular event rates is outlined, as is the complex issue of whether such associations are a cause or a result of underlying vascular disease. In this section, the need for large-scale prospective cohort data to more clearly establish a causal association is appropriately noted and the recognition made that other disorders associated with systemic inflammation such as psoriasis and rheumatoid arthritis also place affected individuals at increased vascular risk. This section is followed by core descriptions of oral pathogens and their potential roles as initiators of both local and systemic inflammation. Here, the accumulating evidence linking severity of oral infection to alterations of hemostasis, thrombosis, and endothelial dysfunction are described, as are potential independent mechanisms by which dental infection might result in vascular disease. The final sections of the text deal with genetic predispositions to infection, research tools needed for the field to expand, a review of evidence suggesting vascular benefits in association with improved oral hygiene, and a call for future work to help define causal pathways.

Ultimately, the inflammatory hypothesis of atherosclerosis will need direct testing in a series of randomized trials seeking evidence as to whether or not targeted anti-inflammatory treatments can reduce vascular event rates. One such randomized trial should be clearly conducted within the context of improved oral hygiene. This expertly edited text with contributors widely known in the field provides a concise summary of the scientific rationale for such a trial and should lead to improved health both for periodontal disease patients and for those with and at risk for vascular disease.

Paul M. Ridker, MD, MPH
Eugene Braunwald Professor of Medicine
Harvard Medical School
Director, Center for Cardiovascular Disease Prevention
Brigham and Women's Hospital
900 Commonwealth Avenue East
Boston, MA 02215
USA


Preface

Is there sufficient evidence to conclude that chronic periodontal infections and dental infections are associated with cardiovascular diseases or are even important factors in the causal chain that leads to atherosclerosis, myocardial infarction, aneurysms, stroke or heart valve disease? Are they involved in the progression or even the initiation of the diseases making up the entity of cardiovascular diseases (CVD)?

This book aims to give a broad overview of current knowledge about the research in the field of oral infections and their association with cardiovascular diseases. Chronic periodontal and dental infections in many respects share the same bacterial profile and together increase the infectious burden of any individual. The chronic course, with often low-grade exposure in the circulation to the infections, causes a long-term exposure that contributes to systemic inflammation, endothelial dysfunction, development of atherosclerotic lesions, thromboses and emboli, to atherosclerotic plaque rupture, and invasion of the cardiovascular tissues.

The authors were invited to present their knowledge in the light of their particular research field. They were asked to focus on the range of the different aspects needed. Many epidemiological, clinical and other scientific aspects are covered. For Chapter 1, Mattila was invited to write about the early story from the first presentation of the infection hypothesis for an infectious aetiology of coronary heart disease, together with the later animal studies and early case–control studies up to publication of the breakthrough study that he and his colleagues did in 1989. Causality is discussed in the context of philosophy, epidemiology, statistics and evidence-based medicine in Chapter 2. Criteria of causality when investigating association, and cause and effect are presented, and the final chapter links the current evidence of whether oral infections cause cardiovascular diseases, in view of the different study designs which give evidence that has different strength and biases.

In Chapters 3 and 4, Enersen and Thelle write about the current status of periodontal disease and cardiovascular disease (CVD), respectively. This is important knowledge for basic under-standing of the relationship between the two distinct diseases. Advanced methods have been used in this research to provide, examine and establish evidence of relevant factors linking oral bacteria to the bacteria or bacterial products in cardiovascular tissues or blood; in Chapter 5 Kristoffersen gives a detailed update on genetics and bacterial identification.

The laboratory methods presented by Kristoffersen (Chapter 7) have helped Olsen and other researchers to map the bacteria involved and their presence in diseased CVD tissues (Chapter 5). Kerrigan and Cox describe the serious consequences of oral bacteria on the platelets in the circulation in Chapter 6. Intervention studies are important for assessing the effect of treatment of chronic periodontal disease in the prevention of CVD. Chapter 8 gives an overview of the recommended treatment and prevention of periodontitis, which is important to both prevent oral infections and improve oral health and to reduce the risk of CVD.

In view of the theory of science and philosophy, Hofmann discusses, in Chapter 9, how to relate to new risk factors being brought into an established research field such as CVD. He presents the notion of necessary and sufficient causes for a disease, and includes the risk of the evidence not being sufficiently strong to draw conclusions. The final chapter brings together the main evidence.

As the editor, I am indebted to the international panel of my distinguished co-authors who have so willingly shared their wealth of knowledge to give the readers an insight into the study of the causality of CVD, in view of the role played by chronic periodontal disease and dental infections. The detailed accounts in which they outline the major issues in their and their colleagues’ research are of great value to readers in the scientific community, practitioners, teachers and students in relevant fields, and health-care planners. The framework of this E-book puts the scientific evidence of these different topics into a comprehensive perspective.

Lise Lund Håheim
University of Oslo, Oslo, Norway

List of Contributors

Author(s):
Lise L. Håheim
University of Oslo
Norway




Contributor(s):
Dermot Cox M.Sc, Ph.D
Principal Investigator, Cardiovascular Infection Group
School of Pharmacy & Molecular and Cellular Therapeutics
Royal College of Surgeons in Ireland, 123 St. Stephens Green
Dublin 2
Ireland


Morten Enersen D.D.S., Ph.D
Postdoc, Institute of Oral Biology/Department of Periodontics
Faculty of Dentistry, University of Oslo
Postbox 1052 Blindern
Oslo, 0316
Norway


Bjørn Hofmann M.Sc, Ph.D
Professor of medical ethics, Center for Medical Ethics at the University of Oslo and University College of Gjøvik
Faculty of Health Care and Nursing, University College of Gjøvik, Gjøvik,
Gjøvik
N-2801
Norway


Steve W. Kerrigan M.Sc, Ph.D
Principal Investigator, Cardiovascular Infection Group
School of Pharmacy & Molecular and Cellular Therapeutics
Royal College of Surgeons in Ireland 123 St. Stephens Green
Dublin 2
Ireland


Anne Karin Kristoffersen Ph.D
Research fellow, Institute of Oral Biology
University of Oslo
PO Box 1052 Blindern
Oslo, N-0316
Norway


Lise Lund Håheim D.D.S., Dr. Philos
Professor, Institute of Oral Biology and Institute of Basic Medical Sciences
University of Oslo; Institute of Oral Biology
PO Box 1052 Blindern
Oslo, N-0316
Norway


Kimmo Mattila MD, Ph.D
Infectious Diseases Specialist, Helsinki and Uusimaa Hospital District
Stenbäckinkatu 9 A
Helsinki
HUS, 00029
Finland


Ingar Olsen D.D.S., Ph.D
Professor of oral microbiology, Institute of oral bology
University of Oslo
PB 1052 Blindern
Oslo, 0316
Norway


Per Ramberg D.D.S., Odont. Dr.
Associate professor, Specialist in Periodontology, Institute of Odontology, Department of Periodontology
The Sahlgrenska Academy at University of Gothenburg
Medicinaregatan 12, Box 450
Gothenburg
SE, 405 30
Sweden


Paul M. Ridker MD, MPH
Eugene Braunwald Professor of Medicine, Harvard Medical School
Director, Center for Cardiovascular Disease Prevention
Brigham and Women's Hospital, 900 Commonwealth Avenue East
Boston
MA, 02215
USA


Dag Steinar Thelle M.D., MPH
Professor, Institute of Basic Medical Sciences
University of Oslo
PO Box 1122 Blindern, N-0317
Oslo
Norway


Jan L. Wennström D.D.S., Odont. Dr.
Professor and chair, Department of Periodontology, Institute of Odontology
The Sahlgrenska Academy at University of Gothenburg
PO Box 450, SE405 30 Göteborg
Sweden




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