The link between inflammation, oxidative stress and systemic disease is an important area of interest in vascular medicine. Both the New England Journal of Medicine and the Journal of the American College of Cardiology have published papers affirming that inflammation plays a key role in the development and progression of not only coronary artery disease but also of systemic atherosclerosis. Also, several inflammatory markers have been identified as risk factors in the development of heart and vascular disease. Because oral infection and periodontal disease lead to inflammation and oxidative stress, the link between oral health and cardiovascular disease is becoming increasingly clear. Several other studies have been published affirming the link between periodontal disease and vascular disease, including heart attack and stroke.

Arterial plaque development and dangers

Atherosclerosis and plaque development result from LDLs (or low-density lipoproteins, the bad cholesterol) and inflammatory cells entering the endothelial space within an artery. As plaques develop within the walls of an artery, they cause blockage. Even worse, plaque rupture leads to development of a thrombus (or blood clot) and ultimately to heart attack or, in the brain, stroke. Arterial disease risk factors including inflammation

Physicians have known for a long time that certain risk factors are associated with arterial disease. These include high circulating levels of glucose (e.g., from diabetes), nicotine use, high cholesterol, high blood pressure, stress, chronic infections, and other factors. It appears that these factors cause damage to the endothelium, i.e., the lining of an artery, allowing the progress of plaque development.

Studies linking inflammation and vascular disease

These studies point to a link between systemic inflammation and vascular disease. In fact, several recent studies have affirmed the link.

  • Inflammation plays a key role in the development and progression of not only coronary artery disease, but in systemic atherosclerosis.
    (New England Journal of Medicine, April 2005)
  • Several inflammatory markers have been indentified as risk factors in the development of heart and vascular disease.
    (Journal of the American College of Cardiology, May 2008)
  • Inflammation is now recognized as being pivotal in the pathogenesis of atherosclerosis.
    (American Heart Journal, July 2005; 150 (1) 11-18)
  • A landmark study known as the Jupiter Trial, followed more than 17,000 men and women who had normal cholesterol levels and no history of heart disease, but who did have high levels of C-reactive protein (CRP), a marker for systemic inflammation. Half the group were given a statin, the potent anti-inflammatory rosuvastatin (trade-named Crestor®). The other half received a placebo. The statin group reduced their LDL level by 50 percent. They also reduced their level of CRP by 37 percent. When the study looked at the occurrence of heart attack and stroke in the two groups, they found that those taking the statin had a 54 percent lower risk of heart attack and a 48 percent lower risk of stroke.

Studies linking periodontal disease, inflammation, and vascular disease
Additional studies have focused specifically on periodontal disease as a key factor in the inflammation leading to vascular disease.

  • [There is a] statistically significant correlation between the number of periodontal pathogens present in subgingival biofilm samples and the presence of coronary heart disease.
    (CORODONT study, Archives of Internal Medicine, 2006; 166:554-559)
  • Periodontal disease with elevated bacterial exposure is associated with CHD events and early atherogenesis (CIMT), suggesting that the level of systemic bacterial exposure from periodontitis is the biologically pertinent exposure with regard to atherosclerotic risk.
    (Journal of Periodontology, Dec. 2007; 78(12)2289-302)
  • Subjects with advanced periodontal disease exhibit endothelial dysfunction and evidence of systemic inflammation (elevated CRP levels) possibly placing them at increased risk for cardiovascular disease.
    (Arteriosclerosis, Thrombosis, and Vascular Biology, 2003; 23:1245)
  • CRP levels are elevated three times higher in patients with combination of periodontal disease and coronary artery disease, versus subjects with either disease alone.
    (Clinical and Diagnostic Laboratory Immunology, March 2002, p. 425-432, Vol. 9, No. 2)
  • Periodontitis results in higher systemic levels of CRP, IL-6 and neutrophils. These elevated inflammatory factors may increase inflammatory activity in atheroscelortic lesions potentially increasing the risk for cardiac or cerebrovascular events.
    (Periodontology, 2000; 71:1528-1534)
  • A significant association was observed between tooth loss levels and carotid artery plaque prevalence.
    (INVEST study, Stroke, 2003; 34:2120-2125)
  • Overall periodontal bacterial burden was related to carotid IMT, a marker of carotid plaque development. This relationship was specific to causative bacterial burden and the dominance of etiologic bacteria in the observed microbiological niche. This provides evidence of a direct relationship between periodontal microbiology and subclinical atherosclerosis in the carotid artery.
    (Circulation, 2005; 111:576-582)
  • A consensus paper on the relationship between heart disease and gum disease was published concurrently in the American Journal of Cardiology and the Journal of Periodontology. The study confirmed that inflammation is a major risk factor for heart disease, and periodontal disease may increase the inflammation level throughout the body. A number of studies show that patients with periodontal disease have an increased risk for cardiovascular disease. Current evidence indicates that management of one disease may reduce the risk for the other.

The data and published studies are accumulating to substantiate that infection and periodontitis and inflammation are closely associated with coronary heart disease. Further, infection, periodontitis and inflammation are associated with atherosclerosis in the carotid artery.

Relationship Between Periodontal Disease, Tooth Loss, and Carotid Artery Plaque: The Oral Infections and Vascular Disease Epidemiology Study (INVEST )
A significant association was observed between tooth loss levels and carotid artery plaque prevalence.
Association Between Respiratory Disease in Hospitalized Patients and Periodontal Disease: A Cross-Sectional Study
Recent research indicated that periodontal infection may worsen systemic diseases, including pulmonary disease. Respiratory infections, such as pneumonia and the exacerbation of chronic obstructive pulmonary disease, involve the aspiration of bacteria from the oropharynx into the lower respiratory tract. Results: The comparison of study-population demographics on the basis of age, sex, education, and income showed no significant differences between groups. Patients with respiratory…
Moderate to Severe Adult Periodontitis Increases Risk of Rheumatoid Arthritis in Non-Smokers and Is Associated with Elevated ACPA Titers: The ARIC Study
Moderate to severe periodontitis may be a risk factor for the development of Rheumatoid Arthritis (RA) in non-smokers. Individuals with moderate to severe periodontitis have higher anti-citrullinated peptide antibodies (ACPA) titers than those with no or mild periodontitis. There is evidence of an interaction between smoking and periodontitis increasing the likelihood of high-titer ACPA…
The impact of hospitalization on oral health: a systematic review
Poor oral health of hospitalized patients–an increase in dental plaque accumulation and gingival inflammation and a deterioration in mucosal health–is associated with an increased risk of hospital-acquired infections and reduced life quality.
Relationship between Oxidative Stress and Inflammatory Cytokines in Diabetic Nephropathy
The prevalence of diabetes has dramatically increased worldwide due to the vast increase in the obesity rate. Diabetic nephropathy is one of the major complications of type 1 and type 2 diabetes and it is currently the leading cause of end-stage renal disease. Hyperglycemia is the driving force for the development of diabetic nephropathy. It is well known that hyperglycemia increases the…
Association Between Chronic Periodontal Disease and Obesity: A Systematic Review and Meta-Analysis
Study found a positive association of an obesity-periodontal disease relationship that was consistent and coherent with a biologically plausible role for obesity in the development of periodontal disease. However, with few qualify longitudinal studies, there is an inability to distinguish the temporal ordering of events, thus limiting the evidence that obesity is a risk factor for periodontal disease or that periodontitis might…
Free Radicals and Cardiovascular Diseases: An Update
Increased production of reactive oxygen species (ROS) are involved in the development and progression of cardiovascular diseases. In a number of cardiovascular disease conditions, the delicate equilibrium between free-radical generation and antioxidant defense is altered in favor of the former, thus leading to redox imbalance i.e. escalating oxidative stress and increased tissue injury. This review focuses on the updated evidences concerning involvement…
Effect of periodontal treatment on metabolic control, systemic inflammation and cytokines in patients with type 2 diabetes
The clinically successful non-surgical periodontal therapy tended to reduce systemic inflammation and the concentration of some circulating cytokines for patients with type 2 diabetes mellitus (T2DM.)
Inflammation and Factors That May Regulate Inflammatory Response
The concept of inflammation is long established. Immune responses to injury and infection are necessary; however, they cause problems when inflammatory processes are maladaptive, leading to chronic diseases. Innovative research is needed to elucidate the intricate pathways involved in chronic inflammation. Ultimately, the question is how these can be used to better diagnose or treat the late-stage sequelae that many lines of…
Inflammation and Periodontal Diseases: A Reappraisal – Introduction to Perio Journal Supplement
Recognition of the research advances and importance of inflammatory mechanisms in essentially all of the chronic diseases of aging, including periodontal diseases, led the American Academy of Periodontology to convene a conference on January 29 and 30, 2008 in Boston titled, “Inflammation and Periodontal Diseases: A Reappraisal.” This conference brought together opinion leaders in several major diseases and in the inflammatory mechanisms…
Gum disease can increase the time it takes to become pregnant
Women who are trying to become pregnant should make sure they visit their dentist and brush their teeth regularly, after preliminary research revealed that gum disease potentially can lengthen the time it takes for a woman to become pregnant by an average of an extra two months. For the first time, fertility experts have shown that, from the time that a woman…
The new periodontal disease: navigate the emerging solutions
Periodontitis is an oral disease that is not limited to local tissue destruction. Escalating evidence over 20 years of research suggests there are various inflammatory pathways that link periodontitis to systemic damage. These etiological mechanisms are all metastatic in nature, and include the following:• Metastatic spread of gram negative bacteria that gain access to the vasculature as a result of breach of…
The Collagen-Binding Protein Cnm Is Required for Streptococcus mutans Adherence to and Intracellular Invasion of Human Coronary Artery Endothelial Cells
Blocking the collagen-binding protein Cnm in Streptococcus mutans may prevent patients from developing infective endocarditis or coronary atherosclerosis. Streptococcus mutans, a predominantly hard tissue (tooth) colonizer, is considered the primary etiologic agent of dental caries, an infectious disease that affects 60 to 90% of the population worldwide. Streptococcus mutans was the most frequently detected bacteria in diseased heart valve tissues and atheromatous…
The Effect of Dental Care on Cardiovascular Disease Outcomes: an Application of Instrumental Variables in the Presence of Heterogeneity and Self-Selection
This is an extensive epidemiologic study based on the Health and Retirement Study (HRS), a biennial longitudinal survey of individuals over 50 years old (and spouses). The data from 1996, 1998, 2000, 2002 and 2004 was included. Although there are limitations to the study, most notably lack of information on detailed dental treatment procedures, they found that women who receive dental care may…
Impacts of Periodontitis on Nonfatal Ischemic Stroke: Comparison with Hypertension and Diabetes Mellitus
Periodontitis is a strong independent risk factor for nonfatal ischemic stroke and its impact is almost the same as that of Hypertension (HPT) and higher than that of Diabetes Mellitus (DM) in adults in their 40s and 50s. This poster was presented at the 2011 IADR meeting as a poster.
Association of Oral Inflammation and Symptoms of Active Rheumatoid Arthritis
This case report presents dental treatment of oral inflammation and subsequent reduction of symptoms of active rheumatoid Arthritis (RA).
The American Journal of Cardiology and Journal of Periodontology Editors’ Consensus: Peiodontitis and Atheroscloerotic Cardiovascular Disease
Aim of this document is to provide health professionals, especially cardiologists and periodontists, a better understanding of the link between atherosclerotic cardiovascular disease and periodontitis. In recent years, the immune system, once believed to be only a vital defense against infection and a promoter of healing–except in the instances of a few uncommon connective tissue disorders–is now recognized as a significant active…
Periodontal Therapy Reduces the Severity of Active Rheumatoid Arthritis in Patients Treated With or Without Tumor Necrosis Factor Inhibitors
Rheumatoid arthritis (RA) and periodontitis are common chronic inflammatory conditions. Recent studies showed a beneficial effect of periodontal treatment on the severity of active RA. Conclusions: Non-surgical periodontal therapy had a beneficial effect on the signs and symptoms of RA, regardless of the medications used to treat this condition.
Rheumatoid arthritis and periodontal disease
The prevalence of periodontal disease has increased two-fold among patients with rheumatoid arthritis (RA) compared to the general population. This increased prevalence reflects shared pathogenic mechanisms, including an increased prevalences of the shared epitope HLA-DRB1-04; exacerbated T-cell responsiveness with high tissue levels of IL-17; exaggerated B-cell responses, with plasma cells being the predominant cell type found within gingival tissue affected with periodontitis and…
A randomized, controlled trial on the effect of non-surgical periodontal therapy in patients with type 2 diabetes. Part 1: effect on periodontal status and glycaemic control
This study provides evidence that non-surgical periodontal treatment contributes to improved glycaemic control in type 2 diabetes mellitus patients.
The association between rheumatoid arthritis and periodontal disease
The existence of a rheumatic or other inflammatory systemic disease may promote Periodontitis (PD) in both its emergence and progress. However, there is evidence that PD maintains systemic diseases. In this review, we also discuss in detail the fact that oral bacterial infections and inflammation seem to be linked directly to the etiopathogenesis of rheumatoid arthritis (RA). There are findings that…
Inflammation as a potential mediator for the association between periodontal disease and Alzheimer’s disease
Periodontal disease (PDD) is associated with increased risk of cardiovascular disease, cerebrovascular disease, and mortality in many studies, while other studies have begun to suggest an association of PDD with Alzheimer’s disease (AD). This paper discusses how infectious pathogens and systemic infection may play a role in AD. The roles of infection and inflammation are addressed specifically with regard to known AD…
Inflammation and Alzheimer’s disease: Possible role of periodontal diseases
Recently, chronic periodontitis has been associated with several systemic diseases including Alzheimer’s disease (AD.) In this article we review the pathogenesis of chronic periodontitis and the role of inflammation in AD. In addition, we propose several potential mechanisms through which chronic periodontitis can possibly contributes to the clinical onset and progression of AD. Because chronic periodontitis is a treatable infection, it might…
Erectile dysfunction might be associated with chronic periodontal disease: two ends of the cardiovascular spectrum
Men in their 30s to mid-40s with chronic periodontal disease (CPD) exhibited an increase in mild and moderate to severe erectile dysfunction (ED) in this study. These preliminary findings are consistent with theories that associate these conditions with systemic inflammation, endothelial dysfunction, and atherosclerosis. The study population consisted of 305 men who filled the Sexual Health Inventory for Men (SHIM) questionnaire in…
The effect of subantimicrobial-dose–doxycycline periodontal therapy on serum biomarkers of systemic inflammation
Doxycycline treatment decreased CRP and MMP9. 128 eligible postmenopausal women with chronic periodontitis assigned to a twice-daily regimen of subantimicrobial-dose–doxycycline (SDD) or placebo tablets for two years as an adjunct to periodontal maintenance therapy. In the intent-to-treat analysis across two years, SDD treatment reduced median high-sensitivity C-reactive protein (hs-CRP) by 18 percent (primary outcome; P = .02) and reduced serum matrix metalloproteinase…
Invasive Dental Treatment and Risk for Vascular Events
When performing dental treatments for patients with vascular disease, providers may wish to warn patients that vascular events increase in the first 4 weeks after invasive dental treatment. Treatment of periodontal disease may reduce cardiovascular risk in the longer term, but studies have suggested a link among dental procedures, acute inflammation, and endothelial dysfunction. However, whether such acute inflammatory effects translate into…
Periodontal Disease and Overall Health: A Clinician’s Guide
Colgate sponsored a group of respected and scholarly clinicians and scientists who, in eighteen chapters, provide a current and thoughtful perspective on the relationship of periodontal disease to systemic conditions…
Reducing stillbirths: prevention and management of medical disorders and infections during pregnancy.
Periodontal disease emerged as a clear risk factor for stillbirth but no interventions have reduced stillbirth rates.
Periodontal bacteria and hypertension: the oral infections and vascular disease epidemiology study
Chronic infections, including periodontal infections, may predispose to cardiovascular disease. We investigated the relationship between periodontal microbiota and hypertension…
Systemic inflammation in cardiovascular and periodontal disease: comparative study.
Epidemiological studies have implicated periodontal disease (PD) as a risk factor for the development of cardiovascular disease (CVD).
Periodontal Disease is Associated with Brachial Artery Endothelial Dysfunction and Systemic Inflammation
Epidemiological studies suggest that severe periodontal disease is associated with increased cardiovascular disease risk, but the mechanisms remain unknown.
Markers of systemic bacterial exposure in periodontal disease and cardiovascular disease risk: a systematic review and meta-analysis.
Recent meta-analyses reported a weak association between periodontal disease (PD) on clinical examination and cardiovascular disease (CVD). Systemic bacterial exposure from periodontitis, which correlates poorly with the clinical examination, has been proposed as the more biologically pertinent risk factor.
Periodontal infections and coronary heart disease: role of periodontal bacteria and importance of total pathogen burden in the Coronary Event and Periodontal Disease (CORODONT) study.
Chronic inflammation from any source is associated with increased cardiovascular risk. Periodontitis is a possible trigger of chronic inflammation. We investigated the possible association between periodontitis and coronary heart disease (CHD), focusing on microbiological aspects.
Inflammation and coronary artery disease
Inflammation is now recognized as being pivotal in the pathogenesis of atherosclerosis. This review highlights key concepts in our current understanding of the role of inflammation in the initiation, progression, and complication of atherosclerosis…
Periodontal diseases
Periodontitis results in loss of connective tissue and bone support and is a major cause of tooth loss in adults. In addition to pathogenic microorganisms in the biofilm, genetic and environmental factors, especially tobacco use, contribute to the cause of these diseases. Common forms of periodontal disease have been associated with adverse pregnancy outcomes, cardiovascular disease, stroke, pulmonary disease, and diabetes.
Toothbrushing, inflammation, and risk of cardiovascular disease: results from Scottish Health Survey
Poor oral hygiene is associated with higher levels of risk of cardiovascular disease and low grade inflammation, though the causal nature of the association is yet to be determined…
Inflammation: Connecting the Mouth and Body?
The American Academy of Periodontology seeks to educate the public about research findings which support what dental professionals have long suspected: Infections in the mouth can play havoc elsewhere in the body. For a long time it was thought that bacteria was the factor that linked periodontal disease to other infections in the body; however, more recent research demonstrates that inflammation may…
Ongoing Study – linking treatment of Periodontal infections to heart disease – Phase II
Epidemiological studies indicate that individuals with severe periodontal disease have significantly increased risk for cardiovascular disease. Periodontal disease, a chronic bacterial infection of the gums, is associated with recurrent bacteremia and a state of systemic inflammation that may convert endothelial cells to a pro-atherogenic phenotype with increased expression of inflammatory factors and loss of the anti-thrombotic, growth inhibitory, and vasodilator properties of…

Other Publications

Gum Disease Raises Arthritis Risk
We’ve known for a while that there is an association between gum disease and rheumatoid arthritis. But our new work suggests periodontal disease is causal,” says study head Jerry A. Molitor, MD, PhD, associate professor in the division of rheumatology and autoimmune disease at the University of Minnesota, Minneapolis. Compared to people with mild or no periodontitis surrounding two or three teeth, people…
Gum Disease Linked to Rheumatoid Arthritis
Periodontitis is far more common among people with rheumatoid arthritis than in the general population, researchers said during the European League Against Rheumatism (EULAR) annual meeting in June 2009. The findings suggest that the two conditions share common mechanisms, so that patients with one disease may also benefit from screening for the other. It may even be that biologic drugs given for rheumatoid arthritis…
Gum disease affects fertility
Gum disease affects fertility, and may add two-plus months to getting pregnant. Fertility drugs may contribute towards gingivitis. Gum disease affects men’s sperm modality…
Gum disease and diabetes
Ninety-three percent of people who have gum disease, but who indicated that they had never been told by a medical provider that they had diabetes, were in fact at risk for diabetes,” said Dr. Sheila Strauss, a psychologist at the NYU Dental School, who has analyzed statistics of people with gum disease. The American Diabetes Association recommends testing every three years for people…

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