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.

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.

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.

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.

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.

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.

[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.

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.

Intestinal microbiota: a regulator of intestinal inflammation and cardiac ischemia?

Inflammatory bowel diseases (IBD) are chronic, relapsing and remitting gastrointestinal (GI) disorders of unknown etiology. IBD patients commonly exhibit extra-intestinal manifestations and complications of an inflammatory nature, presenting with disorders such as ankylosing spondylitis, uveitis and vasculitis. Although the metabolic syndrome is less prevalent in patients with IBD, they are at an increased risk for atherosclerosis and cardiovascular events. Considerable evidence supports the role of GI microbiota in the development of IBD. Recent studies have also shown a significant interaction between the metabolites of gut microbiota and the development of cardiovascular disease. Here we hypothesize that dysbiosis and/or abnormalities in the function of the intestinal microbiota promote cardiovascular disease in IBD patients, explaining the increased risk of cardiovascular events in these patients.

[A possible correlation between periodontitis and ischaemic heart disease].

Periodontitis is a prevalent chronic inflammatory disease induced by bacterial biofilm in the dental pocket resulting in destruction of the periodontal tissues. Periodontitis is associated with ischaemic heart disease and we here provide a summary of the current evidence linking these two disorders.

Helicobacter pylori and ischemic heart disease.

In the last years, a considerable number of studies have been performed on the relationship between infection from Helicobacter Pylori and atherosclerotic diseases, like stroke and ischemic heart disease. In particular, some infections could have a role on the genesis and development of damage to the vascular wall and of atheromatous plaque. It has been suggested that HP could influence the development of IHD through different pathways, such as endothelial cells colonization, changes in the lipid profiles, increased coagulation and platelet aggregation levels, induction of molecular mimicry mechanisms and the promotion of a low-grade systemic inflammation. Based on this hypothesis, it has been performed a considerable number of studies in order to investigate the role of HP in the development and pathogenesis of CAD. Most of this trials gave conflicting results, some denying the presence of a possible relationship between HP infection and increased risk of CAD. Despite of that, results from these studies have raised new interesting perspectives on coronary heart disease, especially regarding the possibility of modifying the clinical history of the disease through eradication of these microorganisms. The results are contradictory and require further investigation.

Elevated antibody titers to Porphyromonas gingivalis as a possible predictor of ischemic vascular disease - results from the Tokamachi-Nakasato cohort study.

AIM: Limited epidemiological studies have investigated the relationship between ischemic vascular disease and periodontitis in non-Western populations. We investigated this relationship in a Japanese cohort by measuring serum titers of antibodies to periodontopathic bacteria. METHODS: As part of the Tokamachi-Nakasato cohort study, we followed up 7021 participants regarding cardiovascular events over 5 years, and observed 99 ischemic vascular events: 66 cerebral infarctions and 33 cases of ischemic heart disease (IHD). For a nested case-control study, we selected 495 sex- and age-matched control subjects. Conditional logistic regression analysis was used to estimate the odds ratios (OR) and 95% confidence intervals (CI) of ischemic vascular events associated with antibody titers to Porphyromonas gingivalis FDC381 and SU63. Multivariable models were adjusted for traditional cardiovascular risk factors using propensity scores. RESULTS: The highest tertile category of antibody titers to P. gingivalis FDC381 in men was significantly associated with an increased risk of cerebral infarction in only the crude model. The 2nd and 3rd tertile categories of antibody titers to P. gingivalis SU63 were significantly associated with an increased risk of cerebral infarction in men (multivariable ORs (95% CIs) were 7.12 (1.51-33.5) and 9.03 (1.97-41.5), respectively). The association was not appreciably modified when we further adjusted for serum high-sensitivity C-reactive protein levels. Antibody titers to P. gingivalis were not dose-dependently associated with the risk of IHD. CONCLUSION: High serum antibody titers to P. gingivalis SU63 could be a predictor of cerebral infarction in Japanese men independent of traditional risk factors and inflammation.

Systemic inflammation caused by chronic periodontite in patients victims of acute ischemic heart attack.

OBJECTIVE: Infectious and inflammatory processes mediated by bacteria in distant sites have been described as a risk factor for acute ischemic heart disease (AIHD). METHODS: One hundred one patients with AIHD with and without chronic periodontitis (CP) were included in this study. Patients were admitted to the HC UNICAMP and stratified into three groups: in group 1, we selected patients with severe chronic periodontitis (31 men and 19 women, mean age 55.1 +/- 11.29 years old); the group 2 with mild chronic periodontitis (40 men and 28 women, mean age 54.8 +/- 10.37 years old) and group 3 represented by the toothless (43 men and 20 women, mean age 67.5 +/- 8.55 years old). Blood samples were collected to measure the lipid profiles, hematological and blood glucose levels. In addition, biopsies of seventeen coronary arteries with atherosclerosis and an equal number of internal mammary arteries without atherosclerotic degeneration in group 1 were investigated. Statistical analysis by analysis of variance (ANOVA) and Scheffé test for multiple comparisons was performed. RESULTS: Triglyceride and LDL levels were elevated in group 1 than in group 2. HDL were reduced by 20% in group 1 and remained reduced by 8% in toothless. Blood glucose was higher in group 1. DNA of periodontal bacteria was detected in 58.8% of the coronary arteries. CONCLUSIONS: Patients with (AIHD) and severe chronic periodontitis may have altered lipid profile, as well as microorganisms associated with CP can permeate into coronary vessels.

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.

Inflamação sistêmica causada pela periodontite crônica em pacientes vítimas de ataque cardíaco isquêmico agudo / Systemic inflammation caused by chronic periodontite in patients victims of acute ischemic heart attack

OBJETIVO: Processos inflamatórios e infecciosos mediados por bactérias em sítios distantes têm sido descritos como fator de risco à doença coronariana isquêmica aguda (DCIA). MÉTODOS: Cento e oitenta e um pacientes com DCIA, com e sem periodontites crônicas, foram incluídos neste estudo. Os pacientes foram admitidos no HC da UNICAMP e estratificados em três grupos: grupo 1 - pacientes com periodontite crônica grave (31 homens e 19 mulheres; média de idade 55,1 ± 11,29 anos); grupo 2 - pacientes com periodontite crônica leve (40 homens e 28 mulheres; média de idade 54,8 ± 10,37 anos); grupo 3 - pacientes desdentados (43 homens e 20 mulheres; média de idade 67,5 ± 8,55 anos). Amostras sanguíneas foram coletadas para mensurar os perfis lipídico, hematológico e glicêmico. Além disso, biópsias de 17 artérias coronárias com aterosclerose e igual número de artérias mamárias internas sem degeneração aterosclerótica no grupo 1 foram investigadas. Para análise estatística utilizou-se a análise de variância (ANOVA) e o teste de Scheffé para comparações múltiplas. RESULTADOS: Triglicérides e LDL estavam elevados no grupo 1 em relação ao grupo 2. O HDL apresentou-se reduzido em 20 por cento dos pacientes do grupo 1, e em 8 por cento nos desdentados. A glicemia estava elevada no grupo 1. DNA de bactérias periodontais foram detectados em 58,8 por cento das artérias coronárias. CONCLUSÕES: Pacientes com DCIA e periodontite crônica grave podem apresentar perfil lipídico alterado, como também microorganismos associados com as periodontites crônicas graves podem permear dentro de vasos coronarianos.

OBJECTIVE: Infectious and inflammatory processes mediated by bacteria in distant sites have been described as a risk factor for acute ischemic heart disease (AIHD). METHODS: One hundred one patients with AIHD with and without chronic periodontitis (CP) were included in this study. Patients were admitted to the HC UNICAMP and stratified into three groups: in group 1, we selected patients with severe chronic periodontitis (31 men and 19 women, mean age 55.1 ± 11.29 years old); the group 2 with mild chronic periodontitis (40 men and 28 women, mean age 54.8 ± 10.37 years old) and group 3 represented by the toothless (43 men and 20 women, mean age 67.5 ± 8.55 years old). Blood samples were collected to measure the lipid profiles, hematological and blood glucose levels. In addition, biopsies of seventeen coronary arteries with atherosclerosis and an equal number of internal mammary arteries without atherosclerotic degeneration in group 1 were investigated. Statistical analysis by analysis of variance (ANOVA) and Scheffé test for multiple comparisons was performed. RESULTS: Triglyceride and LDL levels were elevated in group 1 than in group 2. HDL were reduced by 20 percent in group 1 and remained reduced by 8 percent in toothless. Blood glucose was higher in group 1. DNA of periodontal bacteria was detected in 58.8 percent of the coronary arteries. CONCLUSIONS: Patients with (AIHD) and severe chronic periodontitis may have altered lipid profile, as well as microorganisms associated with CP can permeate into coronary vessels.

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.