|Year : 2019 | Volume
| Issue : 2 | Page : 112-118
|Critical appraisal of bidirectional relationship between periodontitis and hyperlipidemia
Seba Abraham, Arya Premnath, PR Arunima, Reejamol Mohammed Kassim
Department of Periodontology, PMS College of Dental Science and Research, Thiruvananthapuram, Kerala, India
|Date of Submission||02-Sep-2018|
|Date of Acceptance||06-Dec-2018|
|Date of Web Publication||12-Apr-2019|
Dr. Seba Abraham
PMS College of Dental Science and Research, Thiruvananthapuram, Kerala
Source of Support: None, Conflict of Interest: None
| Abstract|| |
Periodontal disease and hyperlipidemia are both multifactorial disease with a high prevalence Worldwide. Cross-sectional and longitudinal prospective clinical studies show some evidence for a bidirectional relationship. Periodontitis and hyperlipidemia share some common risk factors and there exist a mechanistic link between both. Studies have found a positive response to periodontal therapy among hyperlipidemic patients, and statin use by hyperlipidemic patients has shown to influence the periodontal health. However, in spite of the rising prevalence of both diseases, many people remain unaware of their association with each other. Hence, this article summarizes the cyclic relationship between periodontal disease and hyperlipidemia.
Keywords: Hyperlipidemia, lipopolysaccharide, periodontitis, statin
|How to cite this article:|
Abraham S, Premnath A, Arunima P R, Kassim RM. Critical appraisal of bidirectional relationship between periodontitis and hyperlipidemia. J Int Soc Prevent Communit Dent 2019;9:112-8
|How to cite this URL:|
Abraham S, Premnath A, Arunima P R, Kassim RM. Critical appraisal of bidirectional relationship between periodontitis and hyperlipidemia. J Int Soc Prevent Communit Dent [serial online] 2019 [cited 2020 May 27];9:112-8. Available from: http://www.jispcd.org/text.asp?2019/9/2/112/256000
| Introduction|| |
Periodontitis is a chronic inflammatory disease primarily caused by pathogenic microbiota of dental plaque and affects the supporting structures of the tooth. Although 700 different bacterial species are identified in the oral cavity, red complex bacteria comprising of Porphyromonas gingivalis, Treponema denticola, and Tannerella forsythia are recognized as the most important pathogens associated with advanced periodontal disease. There is ample evidence for P. gingivalis as the keystone species in the development of chronic periodontitis Besides microorganisms several contributing factors (cardiovascular disease [CVD], diabetes, smoking, stress, and hyperlipidemia) also play an important role in the development of periodontal disease.
Hyperlipidemia is a state of abnormal lipid profile, which is characterized by elevated blood concentrations of triglycerides (TGs), elevated levels of total cholesterol and low-density lipoprotein (LDL), and decreased levels of high-density lipoprotein cholesterol (HDL). The incidence of dyslipidemia is defined as having at least one of the following criteria: fasting plasma HDL cholesterol <40 mg/dL, LDL cholesterol ≥140 mg/dL, fasting TG ≥150 mg/dL, or self-reported physician-diagnosed dyslipidemia. Modern lifestyle including the food habits and lack of regular exercise has increased the prevalence of hyperlipidemia, which is one of the major concerns of the modern society. It has been observed that infections may hasten the development of atherosclerosis. Hyperlipidemia is considered as an evident risk factor for cardiovascular disease.
Recent literatures have demonstrated an association between periodontal disease and hyperlipidemia. A statistically significant association between borderline to high level of serum total cholesterol and periodontitis have been reported. Periodontitis and hyperlipidemia are chronic inflammatory diseases with complex etiologies. They share some common risk factors such as lipopolysaccharide (LPS)-related responses, hyper-responsive monocytes, genetic and gender predispositions, smoking, and stress and they also share common underlying pathologic mechanisms.
Periodontal microorganisms present in the subgingival plaque particularly P. gingivalis produce endotoxins. These endotoxins and other products produced by the microorganisms can appear in the bloodstream and can impact distinct site and promote local and systemic inflammatory reactions in the host by inducing changes in the plasmatic concentration of cytokines and hormones. These microorganisms can also stimulate foam cell production which is the characteristic features of atherosclerosis. Moreover, periodontal pathogens have been identified and isolated from atheromatous plaques emphasizing the role of periodontal bacteria in atherosclerosis.
Studies have found that periodontal treatment has a beneficial effect on hyperlipidemia and statins a group of medications used to lower lipid level has a protective effect against periodontal attachment loss.
With the rising prevalence of both these diseases, many studies have stated a relationship between hypercholesterolemia and chronic periodontitis [Figure 1]. This article evaluates the association between hyperlipidemia and periodontal disease.
|Figure 1: Describe an outline of bidirectional relationship between periodontitis and hyperlipidemia|
Click here to view
After a thorough literature search in the PubMed, Embase, Scopus, EBSCO, and Google Scholar, we present this article to provide a brief overview of the bidirectional relationship between periodontitis and hyperlipidemia.
| Evidence Based Overview Linking Periodontal Infection and Hyperlipidemia|| |
Infection and hyperlipidemia
Periodontal disease and hyperlipidemia are both chronic inflammatory diseases with an increased number of inflammatory mediators. Chronic local and acute systemic inflammation can alter the lipid metabolism and increase plasma concentration of unregulated cytokines and hormones. Inflammatory chemical mediators released in response to bacterial invasion can spill over into the circulation and can influence the initiation or propagation of atherosclerotic plaque. Fentoǧlu et al. concluded that increased concentration of tumor necrosis factor alpha (TNF α), interleukin-1β (IL-1β), and IL-6 in gingival crevicular fluid (GCF) and serum could be linking factors between periodontitis and hyperlipidemia. Periodontal disease is significantly associated with a reduction in HDL and elevation of LDL and TG which supports the rationale that periodontal disease is associated with lipid metabolic control.
1. Tumor necrosis factor-alpha and interleukin-beta
A wide array of cytokines is produced in periodontal tissues as a response to Gram-negative LPS exposure. These cytokines particularly TNF-α and IL-1β which are significant in periodontal inflammation can influence lipid metabolism by inducing the production of other cytokines, altering the hypothalamic–pituitary–adrenal axis, increasing plasma concentrations of adrenocorticotropic hormone, cortisol, adrenaline, noradrenaline, and glucagon, or altering hemodynamics/amino acid utilization of various tissues involved in lipid metabolism., Thus elevated number of cytokines in chronic inflammatory diseases such as periodontitis can elevate the level of free fatty acids, LDL and TGs and these alterations in serum lipid levels are due to enhanced hepatic lipogenesis,, increased synthesis of TGs, and reduced clearance of both TGs and LDL (due to reductions in lipoprotein lipase activity),, increased adipose tissue lipolysis/blood flow. Thus, any condition elevating TNF α and IL-1β can also be associated with hyperlipidemia and atherosclerosis. Significant association was found between periodontitis and low HDL and high LDL cholesterol levels in women.
Cutler et al. reported that plasma concentrations of lipids are significantly high in individuals with periodontitis than healthy individuals. An association between periodontal disease and TG/HDL ratio was observed in Korean adults. Lipids can alter the gene expression of macrophage to produce activated macrophage which in turn elevate the level of proinflammatory cytokines such as TNFα and IL1β and essential polypeptide growth factors such as platelet-derived growth factor and TGF1β., Furthermore, serum lipids irrespective of mode of induction can increase polymorphonuclear neutrophils (PMN) production and impair wound healing by inhibiting macrophage production of essential polypeptides growth factors.
Role of bacteria
Periodontopathogenic bacteria and their components may have direct access to the circulation through inflamed periodontal tissue, lymphatic vessels or saliva and cause asymptomatic bacteremia or endotoxemia. P. gingivalis and Aggregatibacter actinomycetemcomitans were detected in endothelial cells derived from homogenized atheromatous tissue cultures through specific antibody detection.
Lipopolysaccharide stimulates cytokine release
LPS can stimulate the release of inflammatory mediators and pro-inflammatory cytokines such as IL-1β and TNF-α which are related to hyperlipidemia. IL-1β and TNF-α can stimulate the production of other cytokines and can in turn affect lipid metabolism.
Endotoxemia, lipoprotein level and lipid metabolism
Endotoxemia/bacteremia can elevate levels of free fatty acids, LDL, and total serum triglycerides (TRG) by enhancing hepatic lipogenesis, increasing hydrolysis of fat/blood flow, increasing the production or reducing the elimination of TRG and reducing lipoprotein lipase activity.,
About 80%–97% of LPS is found bound to lipoproteins in the circulation. In healthy individuals, LPS binds to HDL which promotes LPS neutralization. However, in inflammatory conditions instead of HDL, LPS binds to VLDL which can increase hepatic uptake of LPS 3-fold to protect against LPS toxicity.
LPS can also contribute to atherosclerosis by oxidative modification of LDL.
- Oxidized-LDL (Ox-LDL) taken up by macrophage scavenger receptors, can transform macrophage to foam cells (characteristic feature of atherosclerosis) where further degradation does not take place
- Ox-LDL is toxic to endothelial cells and is a strong chemotactic agent for human monocytes.
2. Intact periodontopathogens
Pathogens can travel with platelets resulting in platelet aggregation, thrombus formation and can also invade the endothelial cells. Intact periodontopathogens circulating in the bloodstream within the phagocytic cells (intracellularly/extracellularly) can deposit in atherosclerotic plaque.
Heat shock proteins
An association between periodontal disease and atherosclerosis can be linked to microbial heat shock protein (HSP) and immune response to these HSP. Stressed human tissues such as in chronic inflammatory conditions express HSP which is regulated by the immune system. Most bacteria express HSP which can cross-react with each other and with human HSP. For example, HSP60 (GroEL) expressed by P. gingivalis can cross-react with HSP in endothelial cells, promoting atherosclerosis.
Cardiolipin (CL) which is an anionic lipid, bind to serum protein beta-2 glycoprotein 1 (β2GP1) to form a complex. Physiologic function of this protein is to protect damaged endothelial cell surface. Pathogenic anti-CL antibodies which are similar to peptide sequence in β2GP1 are upregulated in systemic lupus erythematosus, antiphospholipid syndrome, and periodontitis. Anti-CL when complex with β2GP1 can disrupt the protective mechanism of β2GP1 protein and induce vascular thrombosis and early atherosclerosis. In subjects with severe periodontal infection, periodontal therapy may significantly reduce serum anti-β2GP1 concentration, indicating the role of anaerobic bacterial infection in the production of anti-β2GP1 in periodontitis.
Common Risk Factors
Periodontitis and hyperlipidemia share some common risk factors such as LPS-related responses, hyper-responsive monocytes, genetic and gender predispositions, stress, and underlying pathologic mechanisms out of which the most important is smoking.
Smoking can increase fibrinogen levels which further enhance blood viscosity, hemostasis, and ultimately to CVD. Nicotine and other toxic substances present in the cigarette can cause inflammation of vascular endothelial cells either directly or indirectly, which in turn increase von Willebrands factors and tissue plasminogen activator-related hemostatic activity. Smoking can also upregulate vascular adhesion molecules which are related to atherosclerosis plaque formation. Cigarette smoking can stimulate endothelial cells and leads to an activation of key parameters (endothelial nitric oxide synthase 3 and adhesion molecules), known to be involved in the development of endothelial dysfunction and atherogenesis.
Smoking has been considered as a major independent risk factor for periodontitis. A-positive relation was observed between periodontal disease and increasing severity and number of pack-years smoked. Studies have reported that smokers generally have poor oral hygiene. Smoking adversely affects the fibroblast function neutrophils function (impaired chemotaxis and defective phagocytosis), immunoglobulin production and induction of peripheral vasoconstriction. It can also impair the healing response.
2. Common genetic predisposition
Genetically determined hyperinflammatory monocyte phenotypes are seen in periodontitis and hyperlipidemic patients. Hyperactive monocytes associated with periodontitis can create atheromas at distant sites.
Polymorphonuclear neutrophils dysfunction and hyperactivity of white blood cell
Serum lipids, increase PMN/Impair its function and can cause hyperreactivity of white blood cells cells. Hyperreactive white cells were also found to be associated positively with progressive periodontitis in adults. PMN dysfunction provides a biologic explanation for the observed association between periodontal disease and hyperlipidemia.
The long noncoding RNA, ANRIL is the best-replicated risk locus of coronary heart disease (CHD). ANRIL has been consistently associated with CVD by epigenetic modification and gene expression. Since periodontitis and CVD are both inflammatory diseases, the similar link may also exist in periodontal disease suggesting an association between both diseases. Moreover, it was shown that single nucleotide polymorphism in ANRIL is also associated with hsCRP levels in periodontitis patients. However, limited evidence have been provided regarding the frequencies of ANRIL variants in chronic periodontitis patients who often tend to be aged when CVD s occur. Further studies have to be conducted to explore the role of ANRIL and other genetic loci as a contributing genetic risk factor in periodontitis and CVD.
Effect of therapy
1. Effect of periodontal therapy on hyperlipidemia
Studies have suggested that periodontal therapy may be beneficial for individuals with hyperlipidemia. Evidence support that periodontal therapy can decrease the levels of CRP, TNF-α, and IL-6. An association between macrophage activation stimulated by serum LPS and periodontal inflammation have been observed in periodontitis patients with noncontributory medical history. An increase in the ratio of HDL/LDL following periodontal therapy was also noted. It was observed that periodontal infection may weaken the anti-atherogenic effect of HDL thereby enhancing the risk of CHD. Several studies have shown an improvement in serum lipid levels and a decrease in serum proinflammatory cytokine levels in patients with periodontitis and hyperlipidemia following periodontal therapy, while some studies failed to show beneficial effects of periodontal treatment on lipid metabolism. It was reported that nonsurgical periodontal therapy is unlikely to alter serum levels of inflammatory markers such as CRP, fibrinogen, or inflammatory cytokines, 6 weeks after treatment. Yamazaki et al. reported that specific populations responded differently to treatment suggesting an ununiformed relationship between periodontitis and CVD which indicate a need for further studies regarding the impact of periodontal therapy on CVD.
2. Effect of lipid lowering drugs on periodontal disease
Statins are a group of medicines that lower the level of LDL in the blood. Apart from lipid-lowering action, studies provide evidence for anti-inflammatory and potential pleiotropic effects of statins (immunomodulatory, antioxidant, antithrombotic and endothelium stabilization actions, angiogenesis promotion and increase of osteoblastic differentiation, including bone formation) which can elicit a positive impact on periodontal diseases. As evidenced in a recent systematic review, statins could be an adjunctive in promoting periodontal health following nonsurgical therapy and simvastatin was the only drug that showed additional benefits in all evaluated parameters (probing pocket depth, clinical attachment level, and intrabony defect) when compared to groups without statin. Simvastatin treatment inhibits LPS-induced gingival inflammation, osteoclastogenesis, and reduce alveolar bone loss Statins interact with immune response of host by inhibiting adhesion and extravasation of leukocytes in inflammatory sites which in turn diminishes the co-stimulation of T-cells and decrease inflammatory cytokines such as IL-1β, IL-6, and TNF-α., Fentoǧlu et al. evaluated the effect of statins on the level of inflammatory cytokines in GCF and found that the level of TNF-α was reduced in GCF of periodontitis patients after 3 months of systemic administration of statins.
Subgingivally delivered simvastatin gel in chronic periodontitis could enhance the beneficial effect of scaling and root planing (SRP) in pocket reduction, gain in CAL, and bone loss. The effect of different concentrations of local Rosuvastatin (0.1 and 1 mg) in calvarial bone defects was studied, and it was observed that local administration of 1 mg of Rosuvastatin enhanced bone regeneration in calvarial rat defect. Systematic review and meta-analysis find that adjunctive use of locally delivered statins to mechanical SRP is beneficial to increasing bone fill percentage. Improved inflammatory and bleeding control as well as probing depth reduction and CAL gain are possible advantages of these drugs in treating patients with periodontal intrabony defects.
However, some studies failed to prove the beneficial effects of statins on periodontium. In a systematic review done it was concluded that statins have a beneficial effect on bone formation, reducing inflammation, and immunomodulatory effect, however, it was emphasized that statins could not be used as an alternative for standard periodontal treatment. Hence, further studies have to be conducted on the impact of statins on periodontium.
Role of dietary lipids
Dietary lipids play a role in modulating the immune system. Lymphocyte proliferation and cytokine synthesis are established to be reduced by dietary lipids high in saturated fat and an increase of phagocyte activity, and modification of natural killer cell-cell activity are also observed. Fatty acids obtained from dietary lipids gets incorporated to the plasma membrane which alter the phospholipid profiles of lymphocytes, monocytes/macrophages, or polymorphonuclear cells. Diet rich in polyunsaturated fatty acids can suppress the mitogenic response. Immunomodulation induced by IL-1β and TNF-α can be suppressed by dietary lipids. Fatty acids cause a reduction in cell proliferation by inducing apoptosis. Dietary fatty acids can also decrease antioxidant enzyme mRNA levels and enhance radicle induced tissue damage. Enzymatic degradation of these fatty acids can depress the immunocompetence of prostaglandin, leukotrienes, or lipoxins. Circulating lipids above the threshold level have a negative impact on gingival mucosa and elsewhere.
| Conclusion|| |
Recent literatures and studies have demonstrated a cyclic link between periodontal disease and hyperlipidemia. Both are chronic inflammatory diseases with common risk factors. Periodontopathogenic bacteria-induced inflammatory mechanisms and it is influence on atherosclerosis strengthen the premise that periodontitis and hyperlipidemia are bi-directionally linked. Up-regulated cytokines such as IL-1β and TNF-α are common to both diseases. Periodontal therapy has a positive effect on lipid metabolism, and statins are shown to reduce periodontitis.
Although there is evidence to support the concept of association between periodontitis and hyperlipidemia more studies with case–control or cohort designs need to be conducted to fully understand the actual relationship that exists between high lipid profile and periodontitis.
Financial support and sponsorship
Conflicts of interest
There are no conflicts of interest.
| References|| |
Aas JA, Paster BJ, Stokes LN, Olsen I, Dewhirst FE. Defining the normal bacterial flora of the oral cavity. J Clin Microbiol 2005;43:5721-32.
Bodet C, Chandad F, Grenier D. Pathogenic potential of Porphyromonas gingivalis, Treponema denticola
and Tannerella forsythia
, the red bacterial complex associated with periodontitis. Pathol Biol (Paris) 2007;55:154-62.
Hajishengallis G, Darveau RP, Curtis MA. The keystone-pathogen hypothesis. Nat Rev Microbiol 2012;10:717-25.
Saxlin T, Suominen-Taipale L, Kattainen A, Marniemi J, Knuuttila M, Ylöstalo P, et al.
Association between serum lipid levels and periodontal infection. J Clin Periodontol 2008;35:1040-7.
Hansson GK. Inflammation, atherosclerosis, and coronary artery disease. N Engl J Med 2005;352:1685-95.
Nelson RH. Hyperlipidemia as a risk factor for cardiovascular disease. Prim Care 2013;40:195-211.
Thapa S, Wei F. Association between high serum total cholesterol and periodontitis: National Health and Nutrition Examination Survey 2011 to 2012 study of American adults. J Periodontol 2016;87:1286-94.
Kinane DF. Periodontal diseases' contributions to cardiovascular disease: An overview of potential mechanisms. Ann Periodontol 1998;3:142-50.
Scannapieco FA. Position paper of the American academy of periodontology: Periodontal disease as a potential risk factor for systemic diseases. J Periodontol 1998;69:841-50.
Prabhu A, Michalowicz BS, Mathur A. Detection of local and systemic cytokines in adult periodontitis. J Periodontol 1996;67:515-22.
Kebschull M, Demmer RT, Papapanou PN. “Gum bug, leave my heart alone!” – Epidemiologic and mechanistic evidence linking periodontal infections and atherosclerosis. J Dent Res 2010;89:879-902.
Paquette DW, Brodala N, Nichols TC. Cardiovascular disease, inflammation, and periodontal infection. Periodontol 2000 2007;44:113-26.
Fu YW, Li XX, Xu HZ, Gong YQ, Yang Y. Effects of periodontal therapy on serum lipid profile and proinflammatory cytokines in patients with hyperlipidemia: A randomized controlled trial. Clin Oral Investig 2016;20:1263-9.
Fajardo ME, Rocha ML, Sánchez-Marin FJ, Espinosa-Chávez EJ. Effect of atorvastatin on chronic periodontitis: A randomized pilot study. J Clin Periodontol 2010;37:1016-22.
Katz J, Flugelman MY, Goldberg A, Heft M. Association between periodontal pockets and elevated cholesterol and low density lipoprotein cholesterol levels. J Periodontol 2002;73:494-500.
Hayashi C, Gudino CV, Gibson FC 3rd
, Genco CA. Review: Pathogen-induced inflammation at sites distant from oral infection: Bacterial persistence and induction of cell-specific innate immune inflammatory pathways. Mol Oral Microbiol 2010;25:305-16.
Fentoǧlu O, Kirzioǧlu FY, Ozdem M, Koçak H, Sütçü R, Sert T. Proinflammatory cytokine levels in hyperlipidemic patients with periodontitis after periodontal treatment. Oral Dis 2012;18:299-306.
Nepomuceno R, Pigossi SC, Finoti LS, Orrico SR, Cirelli JA, Barros SP, et al.
Serum lipid levels in patients with periodontal disease: A meta-analysis and meta-regression. J Clin Periodontol 2017;44:1192-207.
Gwosdow AR, Kumar MS, Bode HH. Interleukin 1 stimulation of the hypothalamic-pituitary-adrenal axis. Am J Physiol 1990;258:E65-70.
Imura H, Fukata J, Mori T. Cytokines and endocrine function: An interaction between the immune and neuroendocrine systems. Clin Endocrinol (Oxf) 1991;35:107-15.
Chrousos GP. The hypothalamic-pituitary-adrenal axis and immune-mediated inflammation. N Engl J Med 1995;332:1351-62.
Fukushima R, Saito H, Taniwaka K, Hiramatsu T, Morioka Y, Muto T, et al.
Different roles of IL-1 and TNF on hemodynamics and interorgan amino acid metabolism in awake dogs. Am J Physiol 1992;262:E275-81.
Van der Poll T, Romijn JA, Endert E, Borm JJ, Büller HR, Sauerwein HP. Tumor necrosis factor mimics the metabolic response to acute infection in healthy humans. Am J Physiol 1991;261:E457-65.
Feingold KR, Grunfeld C. Tumor necrosis factor-alpha stimulates hepatic lipogenesis in the rat in vivo
. J Clin Invest 1987;80:184-90.
Kurpad A, Khan K, Calder AG, Coppack S, Frayn K, Macdonald I, et al.
Effect of noradrenaline on glycerol turnover and lipolysis in the whole body and subcutaneous adipose tissue in humans in vivo
. Clin Sci (Lond) 1994;86:177-84.
Lanza-Jacoby S, Tabares A. Triglyceride kinetics, tissue lipoprotein lipase, and liver lipogenesis in septic rats. Am J Physiol 1990;258:E678-85.
Fried SK, Zechner R. Cachectin/tumor necrosis factor decreases human adipose tissue lipoprotein lipase mRNA levels, synthesis, and activity. J Lipid Res 1989;30:1917-23.
Lee S, Im A, Burm E, Ha M. Association between periodontitis with blood lipid levels in Korean population. J Periodontol 2017:1-0.
Cutler CW, Shinedling EA, Nunn M, Jotwani R, Kim BO, Nares S, et al.
Association between periodontitis and hyperlipidemia: Cause or effect? J Periodontol 1999;70:1429-34.
Kwon YJ, Park JW, Lim HJ, Lee YJ, Lee HS, Shim JY, et al.
Triglyceride to high density lipoprotein cholesterol ratio and its association with periodontal disease in Korean adults: Findings based on the 2012-2014 Korean national health and nutrition examination survey. Clin Oral Investig 2018;22:515-22.
Doxey DL, Ng MC, Dill RE, Iacopino AM. Platelet-derived growth factor levels in wounds of diabetic rats. Life Sci 1995;57:1111-23.
Pussinen PJ, Vilkuna-Rautiainen T, Alfthan G, Palosuo T, Jauhiainen M, Sundvall J, et al.
Severe periodontitis enhances macrophage activation via increased serum lipopolysaccharide. Arterioscler Thromb Vasc Biol 2004;24:2174-80.
Simonsen L, Bülow J, Madsen J, Christensen NJ. Thermogenic response to epinephrine in the forearm and abdominal subcutaneous adipose tissue. Am J Physiol 1992;263:E850-5.
Samra JS, Summers LK, Frayn KN. Sepsis and fat metabolism. Br J Surg 1996;83:1186-96.
Harris HW, Johnson JA, Wigmore SJ. Endogenous lipoproteins impact the response to endotoxin in humans. Crit Care Med 2002;30:23-31.
Levels JH, Lemaire LC, van den Ende AE, van Deventer SJ, van Lanschot JJ. Lipid composition and lipopolysaccharide binding capacity of lipoproteins in plasma and lymph of patients with systemic inflammatory response syndrome and multiple organ failure. Crit Care Med 2003;31:1647-53.
Barcia AM, Harris HW. Triglyceride-rich lipoproteins as agents of innate immunity. Clin Infect Dis 2005;41 Suppl 7:S498-503.
Ylä-Herttuala S. Macrophages and oxidized low density lipoproteins in the pathogenesis of atherosclerosis. Ann Med 1991;23:561-7.
Witztum JL, Steinberg D. Role of oxidized low density lipoprotein in atherogenesis. J Clin Invest 1991;88:1785-92.
Cathcart MK, McNally AK, Morel DW, Chisolm GM 3rd
. Superoxide anion participation in human monocyte-mediated oxidation of low-density lipoprotein and conversion of low-density lipoprotein to a cytotoxin. J Immunol 1989;142:1963-9.
Iwai T. Periodontal bacteremia and various vascular diseases. J Periodontal Res 2009;44:689-94.
Deshpande RG, Khan MB, Genco CA. Invasion of aortic and heart endothelial cells by Porphyromonas gingivalis
. Infect Immun 1998;66:5337-43.
Hinode D, Nakamura R, Grenier D, Mayrand D. Cross-reactivity of specific antibodies directed to heat shock proteins from periodontopathogenic bacteria and of human origin [corrected]. Oral Microbiol Immunol 1998;13:55-8.
Schenkein HA, Berry CR, Burmeister JA, Brooks CN, Barbour SE, Best AM, et al.
Anti-cardiolipin antibodies in sera from patients with periodontitis. J Dent Res 2003;82:919-22.
Tonetti MS. Cigarette smoking and periodontal diseases: Etiology and management of disease. Ann Periodontol 1998;3:88-101.
Giebe S, Cockcroft N, Hewitt K, Brux M, Hofmann A, Morawietz H, et al.
Cigarette smoke extract counteracts atheroprotective effects of high laminar flow on endothelial function. Redox Biol 2017;12:776-86.
Raulin LA, McPherson JC 3rd
, McQuade MJ, Hanson BS. The effect of nicotine on the attachment of human fibroblasts to glass and human root surfaces in vitro
. J Periodontol 1988;59:318-25.
Kenney EB, Kraal JH, Saxe SR, Jones J. The effect of cigarette smoke on human oral polymorphonuclear leukocytes. J Periodontal Res 1977;12:227-34.
Holt PG. Immune and inflammatory function in cigarette smokers. Thorax 1987;42:241-9.
Clarke NG, Shephard BC, Hirsch RS. The effects of intra-arterial epinephrine and nicotine on gingival circulation. Oral Surg Oral Med Oral Pathol 1981;52:577-82.
Beck J, Garcia R, Heiss G, Vokonas PS, Offenbacher S. Periodontal disease and cardiovascular disease. J Periodontol 1996;67:1123-37.
Van Dyke TE, Horoszewicz HU, Cianciola LJ, Genco RJ. Neutrophil chemotaxis dysfunction in human periodontitis. Infect Immun 1980;27:124-32.
Croft KD, Beilin LJ, Vandongen R, Rouse I, Masarei J. Leukocyte and platelet function and eicosanoid production in subjects with hypercholesterolaemia. Atherosclerosis 1990;83:101-9.
Krause S, Brachmann P, Brandes C, Lösche W, Hoffmann T, Gängler P. Aggregation behaviour of blood granulocytes in patients with periodontal disease. Arch Oral Biol 1990;35:75-7.
Noack B, Jachmann I, Roscher S, Sieber L, Kopprasch S, Lück C, et al.
Metabolic diseases and their possible link to risk indicators of periodontitis. J Periodontol 2000;71:898-903.
McPherson R. Chromosome 9p21 and coronary artery disease. N Engl J Med 2010;362:1736-7.
Holdt LM, Teupser D. Recent studies of the human chromosome 9p21 locus, which is associated with atherosclerosis in human populations. Arterioscler Thromb Vasc Biol 2012;32:196-206.
Teeuw WJ, Laine ML, Bizzarro S, Loos BG. A lead ANRIL polymorphism is associated with elevated CRP levels in periodontitis: A pilot case-control study. PLoS One 2015;10:e0137335.
D'Aiuto F, Ready D, Tonetti MS. Periodontal disease and C-reactive protein-associated cardiovascular risk. J Periodontal Res 2004;39:236-41.
Subramanian S, Emami H, Vucic E, Singh P, Vijayakumar J, Fifer KM, et al.
High-dose atorvastatin reduces periodontal inflammation: A novel pleiotropic effect of statins. J Am Coll Cardiol 2013;62:2382-91.
Ide M, McPartlin D, Coward PY, Crook M, Lumb P, Wilson RF, et al.
Effect of treatment of chronic periodontitis on levels of serum markers of acute-phase inflammatory and vascular responses. J Clin Periodontol 2003;30:334-40.
Yamazaki K, Honda T, Oda T, Ueki-Maruyama K, Nakajima T, Yoshie H, et al.
Effect of periodontal treatment on the C-reactive protein and proinflammatory cytokine levels in japanese periodontitis patients. J Periodontal Res 2005;40:53-8.
Jain MK, Ridker PM. Anti-inflammatory effects of statins: Clinical evidence and basic mechanisms. Nat Rev Drug Discov 2005;4:977-87.
Maeda T, Matsunuma A, Kurahashi I, Yanagawa T, Yoshida H, Horiuchi N, et al.
Induction of osteoblast differentiation indices by statins in MC3T3-E1 cells. J Cell Biochem 2004;92:458-71.
Muniz FW, Taminski K, Cavagni J, Celeste RK, Weidlich P, Rösing CK, et al.
The effect of statins on periodontal treatment – A systematic review with meta-analyses and meta-regression. Clin Oral Investig 2018;22:671-87.
Jin J, Machado ER, Yu H, Zhang X, Lu Z, Li Y, et al.
Simvastatin inhibits LPS-induced alveolar bone loss during metabolic syndrome. J Dent Res 2014;93:294-9.
Sakoda K, Yamamoto M, Negishi Y, Liao JK, Node K, Izumi Y. Simvastatin decreases IL-6 and IL-8 production in epithelial cells. J Dent Res 2006;85:520-3.
Estanislau IM, Terceiro IR, Lisboa MR, Teles Pde B, Carvalho Rde S, Martins RS, et al.
Pleiotropic effects of statins on the treatment of chronic periodontitis – A systematic review. Br J Clin Pharmacol 2015;79:877-85.
Agarwal S, Chaubey KK, Chaubey A, Agarwal V, Madan E, Agarwal MC, et al.
Clinical efficacy of subgingivally delivered simvastatin gel in chronic periodontitis patients. J Indian Soc Periodontol 2016;20:409-16.
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Türer A, Coşkun Türer Ç, Durmuşlar MC, Balli U, Önger ME. The influence of oral administration of rosuvastatin on calvarial bone healing in rats. J Craniomaxillofac Surg 2016;44:1327-32.
Sinjab K, Zimmo N, Lin GH, Chung MP, Shaikh L, Wang HL, et al.
The effect of locally delivered statins on treating periodontal intrabony defects: A systematic review and meta-analysis. J Periodontol 2017;88:357-67.
Chapkin RS, Carmichael SL. Effects of dietary n-3 and n-6 polyunsaturated fatty acids on macrophage phospholipid classes and subclasses. Lipids 1990;25:827-34.
Calder PC. Fatty acids, dietary lipids and lymphocyte functions. Biochem Soc Trans 1995;23:302-9.
de Pablo MA, Ortega E, Gallego AM, Alvarez C, Pancorbo PL, Alvarez de Cienfuegos G. The effect of dietary fatty acid manipulation on phagocytic activity and cytokine production by peritoneal cells from Balb/C mice. J Nutr Sci Vitaminol (Tokyo) 1998;44:57-67.
de Pablo MA, Alvarez de Cienfuegos G. Modulatory effects of dietary lipids on immune system functions. Immunol Cell Biol 2000;78:31-9.
Iacopino AM, Cutler CW. Pathophysiological relationships between periodontitis and systemic disease: Recent concepts involving serum lipids. J Periodontol 2000;71:1375-84.
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