Lactobacillus plantarum probiotic induces Nrf2-mediated antioxidant signaling and eNOS expression resulting in improvement of myocardial diastolic function.

Yorkshire swine were fed standard diet (n = 7) or standard diet containing applesauce rich in caffeic acid with Lactobacillus plantarum (n = 7) for 3 wk. An ameroid constrictor was next placed around the left coronary circumflex artery, and the dietary regimens were continued. At 14 wk, cardiac function, myocardial perfusion, vascular density, and molecular signaling in ischemic myocardium were evaluated. The L. plantarum-applesauce augmented NF-E2-related factor 2 (Nrf2) in the ischemic myocardium and induced Nrf2-regulated antioxidant enzymes heme oxygenase-1 (HO-1), NADPH dehydrogenase quinone 1 (NQO-1), and thioredoxin reductase (TRXR-1). Improved left ventricular diastolic function and decreased myocardial collagen expression were seen in animals receiving the L. plantarum-applesauce supplements. The expression of endothelial nitric oxide synthase (eNOS) was increased in ischemic myocardial tissue of the treatment group, whereas levels of asymmetric dimethyl arginine (ADMA), hypoxia inducible factor 1α (HIF-1α), and phosphorylated MAPK (pMAPK) were decreased. Collateral-dependent myocardial perfusion was unaffected, whereas arteriolar and capillary densities were reduced as determined by α-smooth muscle cell actin and CD31 immunofluorescence in ischemic myocardial tissue. Dietary supplementation with L. plantarum-applesauce is a safe and effective method of enhancing Nrf2-mediated antioxidant signaling cascade in ischemic myocardium. Although this experimental diet was associated with a reduction in hypoxic stimuli, decreased vascular density, and without any change in collateral-dependent perfusion, the net effect of an increase in antioxidant activity and eNOS expression resulted in improvement in diastolic function.NEW & NOTEWORTHY Colonization of the gut microbiome with certain strains of L. Plantarum has been shown to convert caffeic acid readily available in applesauce to 4-vinyl-catechol, a potent activator of the Nrf2 antioxidant defense pathway. In this exciting study, we show that simple dietary supplementation with L. Plantarum-applesauce-mediated Nrf2 activation supports vascular function, ameliorates myocardial ischemic diastolic dysfunction, and upregulates expression of eNOS.

Gut microbiota regulates cardiac ischemic tolerance and aortic stiffness in obesity.

The gut microbiota has emerged as an important regulator of host physiology, with recent data suggesting a role in modulating cardiovascular health. The present study determined if gut microbial signatures could transfer cardiovascular risk phenotypes between lean and obese mice using cecal microbiota transplantation (CMT). Pooled cecal contents collected from obese leptin-deficient (Ob) mice or C57Bl/6j control (Con) mice were transplanted by oral gavage into cohorts of recipient Ob and Con mice maintained on identical low-fat diets for 8 wk (n = 9-11/group). Cardiovascular pathology was assessed as the degree of arterial stiffness (aortic pulse wave velocity) and myocardial infarct size following a 45/120 min ex vivo global cardiac ischemia-reperfusion protocol. Gut microbiota was characterized by 16S rDNA sequencing, along with measures of intestinal barrier function and cecal short-chain fatty acid (SCFA) composition. Following CMT, the gut microbiota of recipient mice was altered to resemble that of the donors. Ob CMT to Con mice increased arterial stiffness, left ventricular (LV) mass, and myocardial infarct size, which were associated with greater gut permeability and reduced cecal SCFA concentrations. Conversely, Con CMT to Ob mice increased cecal SCFA, reduced LV mass, and attenuated myocardial infarct size, with no effects on gut permeability or arterial stiffness. Collectively, these data demonstrate that obesity-related changes in the gut microbiota, independent of dietary manipulation, regulate hallmark measures of cardiovascular pathology in mice and highlight the potential of microbiota-targeted therapeutics for reducing cardiovascular pathology and risk in obesity.NEW & NOTEWORTHY These data are the first to demonstrate that cecal microbiota transplantation (CMT) can alter cardiovascular pathology in lean and obese mice independent from alterations in dietary intake. Myocardial infarct size was reduced in obese mice receiving lean CMT and worsened in lean mice receiving obese CMT. Lean mice receiving obese CMT also displayed increased aortic stiffness. These changes were accompanied by alterations in short-chain fatty acids and gut permeability.

The Roles of 27 Genera of Human Gut Microbiota in Ischemic Heart Disease, Type 2 Diabetes Mellitus, and Their Risk Factors: A Mendelian Randomization Study.

Manipulation of the gut microbiota presents a new opportunity to combat chronic diseases. Randomized controlled trials of probiotics suggest some associations with adiposity, lipids, and insulin resistance, but to our knowledge no trials with "hard" outcomes have been conducted. We used separate-sample Mendelian randomization to obtain estimates of the associations of 27 genera of gut microbiota with ischemic heart disease, type 2 diabetes mellitus, adiposity, lipid levels, and insulin resistance, based on summary data from CARDIoGRAAMplusC4D and other consortia. Among the 27 genera, a 1-allele increase in single nucleotide polymorphisms related to greater abundance of Bifidobacterium was associated with lower risk of ischemic heart disease (odds ratio = 0.985, 95% confidence interval (CI): 0.971, 1.000; P = 0.04), a 0.011-standard-deviation lower body mass index (95% CI: -0.017, -0.005), and a 0.026-standard-deviation higher low-density lipoprotein cholesterol level (95% CI: 0.019, 0.033), but the findings were not robust to exclusion of potential pleiotropy. We also identified Acidaminococcus, Aggregatibacter, Anaerostipes, Blautia, Desulfovibrio, Dorea, and Faecalibacterium as being nominally associated with type 2 diabetes mellitus or other risk factors. Results from our study indicate that these 8 genera of gut microbiota should be given priority in future research relating the gut microbiome to ischemic heart disease and its risk factors.

The Intriguing Link between the Intestinal Microbiota and Cardiovascular Disease.

Human microbiota is a term conventionally used to define the normal flora of microbes living in all of us, most of which are resident in the gastrointestinal tract. Despite it having been known for some time that the vast majority of intestinal bacteria exert a strong influence on human life, recent technologic breakthroughs have made it possible to more accurately characterize the host microbial communities and explore their relationship with many human diseases. Notably, the evidence accumulated over the past 10 years suggests that a reasonable relationship can now be established between gut microbiota composition and the risk of cardiovascular disease. The most convincing information comes from data generated by studies involving trimethylamine-N-oxide (TMAO)-producing bacteria. It seems now clear that these bacterial strains may actively contribute to increase the concentration of endogenous TMAO and consequently enhance the risk of ischemic and thrombotic disorders, so opening intriguing scenarios for effective prevention of cardiovascular disease by targeting the intestine by means of diet, probiotics, prebiotics, antibiotics, or even transplantation of gut microbes.

Investigation of bacterial translocation in chronic ischemic heart failure in the rat.

BACKGROUND: Increased markers of systemic inflammation had been found in patients with acute heart failure. These and other findings led to the hypothesis of an increased rate of bacterial translocation in severe or acute heart failure, leading to systemic inflammation. The present study examined if bacterial translocation occurs under physiological conditions in rats and if its rate and spectrum changes in chronic compensated ischemic heart failure. METHODS: Myocardial infarction (MI) was induced by proximal ligation of the left anterior descending coronary artery or a sham operation was performed. Rats were followed up for six months and mesenteric lymph nodes of the surviving animals with large MI were excised and bacterial translocation was quantified by cultivating viable bacteria. RESULTS: Induction of a large MI led to a significant cardiac remodelling, elevated levels of atrial natriuretic peptide, and pulmonary oedema. There was no difference in the spectrum or in the rate of bacterial translocation compared with controls, neither comparing all cultured bacteria nor predefined subgroups (e.g., intestinal bacteria). CONCLUSIONS: Bacterial translocation is a physiological process with no gradual increase in chronic compensated heart failure in rats.

[ROLE OF MICROFLORA OF THE ABDOMINAL CAVITY EXUDATE IN THE ENDOGENIC INTOXICATION OCCURRENCE IN PATIENTS, SUFFERING COMPLICATED ACUTE CHOLECYSTITIS WITH CONCURRENT CARDIAC INSUFFICIENCY OF ISCHEMIC GENESIS].

While complicated acute cholecystitis (ACH) course the focus of infection constitutes one of the main causes of the endogenic intoxication (EI) occurrence, what leads to ischemic and hypoxic myocardial damage. There were presented the treatment results analysis in 213 patients, ageing 60 years old and older, managed for an ACH, complicated by peritonitis, paravesical abscess, with concurrent cardiac insufficiency of ischemic genesis, to whom laparoscopic cholecytectomy (LCHE) was conducted. Microflora of the abdominal cavity exudates in the patients, suffering an ACH of various severity, was studied. More rapid regression of inflammatory process, the EI severity and the ischemic-hypoxic myocardial affection reduction, positive impact on hemodynamics, reduction of myocardial ischemia severity were noted while local affection, when bacteriophages for treatment were applied.

Seroprevalence of Chlamydophila pneumoniae in ischaemic heart disease.

We investigated the presence of Chlamydophila pneumoniae antibodies in 125 patients with cardiovascular disease and in 128 controls. C. pneumoniae antibodies were measured by microimmunofluorescence assay. A significantly high prevalence of IgG C. pneumoniae antibodies at titre > or = 8 was found in patients (84%) in comparison to controls (47.6%). Considering as cut-off the IgG titre > or = 32, 52% of patients with coronaropathies and 18.75% of controls resulted positive (p < 0.0001). IgA C. pneumoniae antibodies were found in patients and controls without statistically significant differences. High C. pneumoniae antibodies (titre > or = 256) were found in 11% of patients with acute myocardial infarction (AMI) and in none of the controls. In patients, the percentage of IgG and IgA seropositivity increased with age and decreased in patients aged > 70 years. Only patients with AMI are at risk of having antibodies against C. pneumoniae (OR = 6.69). None of the known risk factors for cardiovascular disease was significantly associated with C. pneumoniae seropositivity IgG. This is the first report in our area on the possible association of C. pneumoniae IgG seropositivity and acute ischemic events.

Potential link between Helicobacter pylori and ischemic heart disease: does the bacterium elicit thrombosis?

Over the past fifteen years, numerous observations have linked Helicobacter pylori (H. pylori) infection to ischemic heart disease (IHD). Despite the controversial literature data, it has been postulated that if a role is plausible, it will be in the early events of the acute coronary syndrome. According to this model, we focused on the potential pathogenic mechanisms relating H. pylori to IHD like platelet aggregation and thrombosis. To identify all publications in this field, a MEDLINE search of studies published in English from 1965 to 2009 was conducted. Although very few investigations were found, these showed data of paramount importance. In particular, it has been demonstrated that some strains of H. pylori bind von Willebrand factor and interact with glycoprotein Ib to induce platelet aggregation in humans. In experiments from animal models, such infection promoted the formation of platelet aggregates by both a marked increase in the flux of rolling leukocytes and the appearance of platelet and leukocyte-platelet aggregates in gastric venules. This aggregate formation was abrogated by antibodies against specific adhesion molecules (L- and P-selectin). The future challenge is to gain more knowledge in this field and to translate these information into clinical practice.

Helicobacter pylori and cardiovascular disease: update 2019.

Many studies have been performed concerning the potential role of Helicobacter pylori (H. pylori) in different extra-gastric diseases. Ischemic heart disease (IHD) remains the leading cause of mortality in developed countries. The traditional cardiovascular risk factors could not predict all cases of IHD. Hence, the scientists explore other potential etiologic factors, especially infections. H. pylori infection has been suspected to have a role in the pathogenesis of atherosclerosis. However, after 25 years from the first description, the role of the bacterium in the pathogenesis of IHD remains controversial and enigmatic. Since H. pylori infection is persistent and stimulates both a local and a systemic immune response that could cause significant changes in the markers of inflammation like cytokines, C-reactive protein, heat shock protein, fibrinogen, triglycerides, high density lipoprotein, it has been supposed that the outcomes of this process are atherosclerosis and a prothrombotic state which eventually leads to IHD. Alternative pathogenic mechanisms have been hypothesized, including the occurrence of molecular antigenicity. This hypothesis supposed that H. pylori could provoke autoimmunity as a result of molecular mimicry. The eradication of H. pylori infection as cardiovascular prevention strategy has been the object of some studies. However, the results are of difficult interpretation. Further studies, especially with a cohort and interventional design, have to be performed to reveal the potential relationship between H. pylori and IHD.

Scrub Typhus and Abnormal Electrocardiography.

This study compared the frequency of abnormal electrocardiogram (ECG) types between scrub typhus patient group and age- and gender-matched health checkup group and their associations with disease severity in scrub typhus patient. Demographic characteristics and ECG and laboratory findings of patients with scrub typhus admitted to Chosun University Hospital, and normal subjects visiting the hospital for health checkup from January 2008 to December 2012 were retrospectively studied. Electrocardiogram abnormalities at admission were observed in 72 of 165 (43.6%) scrub typhus confirmed patients. The following ECG abnormalities were observed: arrhythmic group (31 cases, 18.8%), ischemic change group (25 cases, 15.1%), prolonged QT group (32 cases, 19.4%).Compared with the age and gender-matched health checkup group, ECG abnormalities were more commonly observed in scrub typhus patient group (13.9% versus 43.6%, P < 0.001). In addition, when compared with the normal ECG group, scrub typhus in the abnormal ECG group showed greater disease severity and this phenomenon was particularly prominent in the prolonged QT group. Based on our study prolonged QT observed in approximately 20% of patients with scrub typhus, clinicians should pay additional attention to drugs that affect QT interval.

High prevalence of Cag-A positive H. pylori strains in ischemic stroke: a primary care multicenter study.

BACKGROUND: Previous studies suggested an association between CagA-positive H. pylori strains and ischemic stroke. The aim of the present study was to assess the prevalence of Helicobacter pylori infection and CagA status in patients with atherosclerotic stroke in the primary care setting. MATERIALS AND METHODS: A total of 106 consecutive patients (age 76.6 +/- 8 years; males 52%) with well-documented history of atherosclerotic stroke and 106 sex-age- (age 76.5 +/- 9 years; males 52%) and social background-matched controls without relevant vascular diseases. Risk factors for ischemic stroke were recorded in all subjects. H. pylori infection was assessed by[13]C-urea breath test. A serologic assay for specific IgG against CagA was performed in infected subjects. RESULTS: A trend toward a higher prevalence of H. pylori was observed in cases (63%) with respect to controls (54%) without reaching a statistical significance. CagA positivity was associated to a higher risk of atherosclerotic stroke (adjusted odds ratio 2.69, 95% confidence interval 1.37-5.30). CONCLUSIONS: Our findings suggest that CagA-positive strains of H. pylori are significantly associated to atherosclerotic stroke. This is not a merely confirmative study since it has been performed for the first time in the primary care setting and included only subjects with an active infection.

Potential relationship between Helicobacter pylori and ischemic heart disease: any pathogenic model?

Helicobacter pylori (H.pylori), causal agent of several gastroduodenal diseases, has been involved in diverse aspects of many extragastric manifestations, including ischemic heart disease (IHD). The present paper focuses on the potential pathogenic mechanisms relating H. pylori to IHD. Since H. pylori DNA has been detected in the coronary arteries only in sporadic occasions, and considering that long-term inflammation might raise cytokine levels in the bloodstream, an indirect pathway is more plausible. Moreover, the evidence that some strains of H. pylori induce platelet aggregation supports a role in the acute phase of IHD. In conclusion, because IHD is a multifactorial disease, it is evident that H. pylori is not the only cause. Thus, the definition of H. pylori or other infectious agents as culprits requires a multidisciplinary approach.

[The role of endothelial dysfunction and Chlamydia pneumoniae infection in patients with ischemic stroke].

The research purposed to investigate the Chlamydia Pneumoniae infection in patients with ischemic stroke and to establish the correlation with elevated C. pneumonia antibody titers and endothelial dysfunction. 72 patients with acute ischemic stroke, aged 45 to 75 (45 male and 32 female) have been researched. Patients were grouped according to etiology of stroke (based on International classification TOAST). The blood was taken in 48 hours from stroke onset. ELISA method was applied to detect the antibodies against C. Pneumoniae. The intima-media thickness of the common carotid artery were assessed by B-mode ultrasonography (Acuson128XP/10) with a 7.5-MHz linear-array transducer. Flow-mediated dilatation (FMD) of the brachial artery were measured from high-resolution, 2-dimensional ultrasound images obtained by an ultrasound machine with a 7.5-MHz linear-array transducer. Free NO were examined by Electron Paramagnetic Resonance (EPR) method in blood. Control consisted with 15 healthy volunteers. Multivariate logistic regression showed a significant positive correlation between blood elevated titers of IgA and IgG of stroke patients and the intima-media thickness of the carotid artery (correlation coefficient by Pearson r = 0,31; p<0,05, r = 0,27; p<0,05). On multiple regression analysis, percent FMD showed a significant negative correlation with the intima-media thickness of the common carotid artery (r= -0,57, p<0,05), positive correlation between NO and the intima-media thickness of the carotid artery (r= 0,72, p<0,05). Association between antibody seropositivity for C. pneumoniae and increase of the IMT in the common carotid artery indicates persistent chronic infection in patients with ischemic stroke. Correlation between NO, an increase of the IMT in the common carotid and artery flow-mediated dilation of brachial artery indicates on the participation of NO in development of endothelial dysfunction and its significant role in pathogenesis of ischemic stroke. These findings support the concept that NO-inducible endothelial dysfunction is related to atherogenesis.

Gut-Derived Serum Lipopolysaccharide is Associated With Enhanced Risk of Major Adverse Cardiovascular Events in Atrial Fibrillation: Effect of Adherence to Mediterranean Diet.

BACKGROUND: Gut microbiota is emerging as a novel risk factor for atherothrombosis, but the predictive role of gut-derived lipopolysaccharide (LPS) is unknown. We analyzed (1) the association between LPS and major adverse cardiovascular events (MACE) in atrial fibrillation (AF) and (2) its relationship with adherence to a Mediterranean diet (Med-diet). METHODS AND RESULTS: This was a prospective single-center study including 912 AF patients treated with vitamin K antagonists (3716 patient-years). The primary end point was a composite of MACE. Baseline serum LPS, adherence to Med-diet (n=704), and urinary excretion of 11-dehydro-thromboxane B2 (TxB2, n=852) were investigated. Mean age was 73.5 years; 42.9% were women. A total of 187 MACE (5.0% per year) occurred: 54, 59, and 74 in the first, second, and third tertile of LPS, respectively (log-rank test P=0.004). Log-LPS (hazard ratio 1.194, P=0.009), age (hazard ratio 1.083, P<0.001), and previous cerebrovascular (hazard ratio 1.634, P=0.004) and cardiac events (hazard ratio 1.822, P<0.001) were predictors of MACE. In the whole cohort, AF (versus sinus rhythm) (ß 0.087, P=0.014) and low-density lipoprotein cholesterol (ß 0.069, P=0.049) were associated with circulating LPS. Furthermore, Med-diet score (ß -0.137, P<0.001) was predictive of log-LPS, with fruits (ß -0.083, P=0.030) and legumes (ß -0.120, P=0.002) negatively associated with log-LPS levels. Log-LPS and log-TxB2 were highly correlated (r=0.598, P<0.001). Log-LPS (ß 0.574, P<0.001) and Med-diet score (ß -0.218, P<0.001) were significantly associated with baseline urinary excretion of TxB2. CONCLUSIONS: In this cohort of AF patients, LPS levels were predictive of MACE and negatively affected by high adherence to Med-diet. LPS may contribute to MACE incidence in AF by increasing platelet activation.

Updated review (2006) on Helicobacter pylori as a potential target for the therapy of ischemic heart disease.

UNLABELLED: Despite knowledge about the classical risk factors for ischemic heart disease (IHD) has increased, all the differences in morbidity as well as mortality from this disease cannot be fully explained. Hence the importance of looking for other causal mechanisms. Numerous infectious agents have been linked to IHD and among these also Helicobacter pylori (H. pylori). However, a number of studies have reported conflicting RESULTS: The present review attempts to highlight on the update pertaining a potential etiologic role of H. pylori infection in the pathogenesis of IHD. Some new evidences have emerged in the last years in literature. While epidemiological approach seems to confirm previous uncertainties (hypothetical role of the bacterium in the acute phase), experiments have demonstrated the presence of bacterial DNA in the plaque. Furthermore, the most encouraging evidence of a possible association emerges from an intervention small trial showing a significant reduction of coronary events after H. pylori eradication. Because IHD is the outcome of a multiciplity of factors, many of which with only a limited individual effect, complete understanding of causation is difficult. It may be possible to identify some factors, such as H. pylori, the effects of which are large enough to be potential target for prevention. This is of major public health importance, since the eradication of the infection is easy and certainly much less expensive than long-term treatment for other risk factors. Prospective population-based studies and interventional trials, focusing on the advantage of the eradication of H. pylori infection on the prevention or the reduction of recurrence in subjects with IHD, should be performed in order to provide support of a causal relationship. This represents a promising direction for future studies.

Extragastric manifestations of Helicobacter pylori infection.

Since the discovery of Helicobacter pylory (H. pylori), several studies have been published concerning a hypothetical role of this bacterium in different extragastric diseases, such as ischemic heart disease, idiopathic thrombocytopenic purpura, iron deficiency anemia or other disorders. The majority of those studies may be classified as epidemiological or eradicating trials but there are also case reports or in vitro studies. Idiopathic thromobocytopenic purpura represents the disease showing a stronger link with H. pylori infection. There are also increasing evidences on the role of H. pylori infection in iron deficiency anemia and ischemic heart disease. On the contrary, the association between H. pylori infection and other diseases is still controversial, as is supported in the majority of the cases by case reports, small pilot studies or just in vitro data.

Helicobacter pylori infection and ischemic heart disease: could experimental data lead to clinical studies?

Despite the remarkable advances made in primary prevention and treatment, ischemic heart disease (IHD) remains the leading cause of death and a significant cause of disability in developed countries. Since traditional cardiovascular risk factors failed to predict all cases of IHD, there is an intensive research to explore other potential etiologic factors. Among these, numerous studies have considered the theoretical link between IHD and chronic infections, including Helicobacter pylori (H. pylori). Considering that epidemiologic studies have produced conflicting results, due to geographical variations of IHD and H. pylori prevalence as well as heterogeneity of study designs, an alternative way to analyze this topic is to assess if consistency for a biological plausibility exists. In this review we critically analyzed the experimental data on this topic, to assess whether their results could lead future clinical studies.

Acute Chlamydia pneumoniae infection with heat-shock-protein-60-related response in patients with acute coronary syndrome.

Recent evidence has suggested an association between Chlamydia pneumoniae infection and coronary atherosclerosis. A significant association has also been detected between heat shock protein (HSP) 60 antibody and the severity of coronary atherosclerosis. The aim of this study was to define the relationship between instability of ischemic heart disease (IHD) and serum levels of HSP60 and C. pneumoniae antibodies. Blood samples for the measurement of serum antibody titers were obtained from 1131 patients with ischemic heart disease (65+/-9 years; male/female, 828/303) and 127 non-IHD controls with normal coronary arteries (64+/-9 years; male/female, 60/67) on the day of cardiac catheterization. The serum levels of anti-human HSP60 IgG antibody and anti-chlamydial IgM, but not IgG or IgA, antibody were significantly higher in ACS patients than in stable IHD patients or controls. These results suggest that acute C. pneumoniae infection with HSP60-related immunological responses may contribute to the pathophysiology of acute coronary syndromes.

Helicobacter pylori infection and ischaemic heart disease: an overview of the general literature.

In the last years, a considerable number of studies have been performed on the correlation between Helicobacter pylori infection and ischaemic heart disease. The reason is the supposed role of some chronic infections in the genesis and development of vessel wall injury and atheromatous plaque, as already reported for Chlamydia pneumoniae and herpes viruses. While this association may be theoretically conceivable, it still remains debated from a practical point of view. Epidemiological and animal studies as well as some eradicating trials gave conflicting results, while studies investigating the specific molecular mimicry mechanisms induced by H. pylori strongly support the association. Moreover, none of the studies performed so far did take into account the effect of the genetic susceptibility to develop ischaemic heart disease or to respond to H. pylori infection. In particular, while the exposure to some known risk factor for atherosclerosis should lead to develop ischaemic heart disease, no condition or exposure, either individual or in combination, completely explains the occurrence and the progression of the disease, as many patients develop ischaemic heart disease in the absence of any risk factor. Based on these concepts, can we state that H. pylori infection may cause the same effect in patients with ischaemic heart disease as in healthy subjects? Further studies are needed in order to clarify this issue.

Periodontitis in cardiology--a clinical perspective.

The association between ischemic cardiovascular disease and infectious disease is very dubious, and evidence points in several directions. Chronic periodontitis has been proposed as a potential risk factor based on many studies. A review of these studies demonstrates that the majority of them are retrospective epidemiological studies and therefore of little value in determining a possible association. New data seems to indicate an association between atherosclerosis and alveolar bone loss, thus indicating that a long-standing burden of infection is related to the slow process of atherosclerosis plaque buildup. Future secondary prevention studies will have to be performed to determine if periodontal therapy intervention results in decreased cardiovascular mortality or morbidity, proving a strong association between the two diseases.