ecent research has shown that inflammation plays a key role in coronary artery disease (CAD) and other manifestations of atherosclerosis. Immune cells dominate early atherosclerotic lesions, their effector molecules accelerate progression of the lesions, and activation of inflammation can elicit acute coronary syndromes. This review highlights the role of inflammation in the pathogenesis of atherosclerotic CAD. It will recount the evidence that atherosclerosis, the main cause of CAD, is an inflammatory disease in which immune mechanisms interact with metabolic risk factors to initiate, propagate, and activate lesions in the arterial tree. A decade ago, the treatment of hypercholesterolemia and hypertension was expected to eliminate CAD by the end of the 20th century. Lately, however, that optimistic prediction has needed revision. Cardiovascular diseases are expected to be the main cause of death globally within the next 15 years owing to a rapidly increasing prevalence in developing countries and eastern Europe and the rising incidence of obesity and diabetes in the Western world. 1 Cardiovascular diseases cause 38 percent of all deaths in North America and are the most common cause of death in European men under 65 years of age and the second most common cause in women. These facts force us to revisit cardiovascular disease and consider new strategies for prediction, prevention, and treatment.

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Inflammation, Atherosclerosis, and Coronary Artery Disease

Metabolomics studies hold promise for the discovery of pathways linked to disease processes. Cardiovascular disease (CVD) represents the leading cause of death and morbidity worldwide. Here we used a metabolomics approach to generate unbiased small-molecule metabolic profiles in plasma that predict risk for CVD. Three metabolites of the dietary lipid phosphatidylcholine—choline, trimethylamine N-oxide (TMAO) and betaine—were identified and then shown to predict risk for CVD in an independent large clinical cohort. Dietary supplementation of mice with choline, TMAO or betaine promoted upregulation of multiple macrophage scavenger receptors linked to atherosclerosis, and supplementation with choline or TMAO promoted atherosclerosis. Studies using germ-free mice confirmed a critical role for dietary choline and gut flora in TMAO production, augmented macrophage cholesterol accumulation and foam cell formation. Suppression of intestinal microflora in atherosclerosis-prone mice inhibited dietary-choline-enhanced atherosclerosis. Genetic variations controlling expression of flavin monooxygenases, an enzymatic source of TMAO, segregated with atherosclerosis in hyperlipidaemic mice. Discovery of a relationship between gut-flora-dependent metabolism of dietary phosphatidylcholine and CVD pathogenesis provides opportunities for the development of new diagnostic tests and therapeutic approaches for atherosclerotic heart disease.

/pdf/gut-flora-metabolism-of-phosphatidylcholine-promotes-437q5mia6l.pdf

Gut flora metabolism of phosphatidylcholine promotes cardiovascular disease

Chronic obstructive pulmonary disease (COPD) is a common problem in the elderly. The disease is characterised by intermittent worsening of symptoms and these episodes are called acute exacerbations. The best estimate, based on several lines of evidence, is that approximately half of all exacerbations are caused by bacteria. These lines of evidence include studies of lower respiratory tract bacteriology during exacerbations, correlation of airways’ inflammation with results of sputum cultures during exacerbations, analysis of immune responses to bacterial pathogens, and the observation in randomised, prospective, placebo-controlled trials that antibacterial therapy is of benefit. The most important bacterial causes of exacerbations of COPD are nontypeable Haemophilus influenzae, Moraxella catarrhalis, Streptococcus pneumoniae and Chlamydia pneumoniae.

/pdf/chronic-obstructive-pulmonary-disease-4ipss13czj.pdf

Chronic obstructive pulmonary disease

Endoscopic sphincterotomy complications and their management: an attempt at consensus

Background The pathogenesis of unstable angina is poorly understood, and predicting the prognosis is problematic. Evidence suggests that there may be active inflammation, possibly in the coronary arteries, in this syndrome. We therefore studied the prognostic value of measurements of the circulating acute-phase reactants C-reactive protein and serum amyloid A protein, which are sensitive indicators of inflammation. Methods We measured C-reactive protein, serum amyloid A protein, creatine kinase, and cardiac troponin T in 32 patients with chronic stable angina, 31 with severe unstable angina, and 29 with acute myocardial infarction. Results At the time of hospital admission, creatine kinase and cardiac troponin T levels were normal in all the patients, but the levels of C-reactive protein and serum amyloid A protein were ≥ 0.3 mg per deciliter (exceeding the 90th percentile of the normal distribution) in 4 of the patients with stable angina (13 percent), 20 of the patients with unstable angina (65 percent)...

https://www.nejm.org/doi/pdf/10.1056/NEJM199408183310701

The Prognostic Value of C-Reactive Protein and Serum Amyloid A Protein in Severe Unstable Angina

Serological evidence of an association of a novel Chlamydia, TWAR, with chronic coronary heart disease and acute myocardial infarction.

ANTIGENIC SIMILARITIES BETWEEN BRAIN COMPONENTS AND BACTERIA CAUSING MENINGITIS: Implications for Vaccine Development and Pathogenesis

The oropharyngeal carriage of Haemophilus influenzae type b (Hib) was studied among 725 healthy 3-year-old children who had or had not been immunized with an Hib conjugate vaccine. Oropharyngeal swabs were collected during the childrens' well-child visit to their local child health center. Fourteen (3.5%) of the 398 unvaccinated children were oropharyngeal carriers of Hib, whereas none of the 327 children who had received Hib conjugate vaccine carried Hib (P less than .001). Carriage rates of non-type b H. influenzae (19%) or Streptococcus pneumoniae (18%) were the same irrespective of the Hib vaccination status of the children. Thus Hib conjugate vaccine, unlike Hib polysaccharide vaccine, seems to be able to prevent oropharyngeal colonization by Hib.

Reduction of Oropharyngeal Carriage of Haemophilus influenzae Type b (Rib) in Children Immunized with an Rib Conjugate Vaccine

BACKGROUND An association of chronic Chlamydia pneumoniae infection to coronary heart disease has been suggested recently. In a recent study, we demonstrated circulating immune complexes containing chlamydial genus-specific lipopolysaccharide in patients with coronary heart disease. The objective of the present study was to investigate whether C. pneumoniae species-specific immune complexes are present in chronic coronary heart disease. METHODS AND RESULTS The presence of Chlamydia-specific circulating immune complexes was studied in 46 patients with chronic coronary heart disease and in control subjects. Chlamydial lipopolysaccharide-containing immune complexes were detected with the antigen-specific capture method, and they were present in 41% of patients and 15% of control subjects (p CONCLUSIONS The results suggest that the majority of the patients with chronic coronary heart disease have a chronic C. pneumoniae infection in which chlamydial components have an easy access to circulation to form immune complexes with preexisting antibodies. These findings give further evidence for the association of chronic C. pneumoniae infection with coronary heart disease.

Chlamydia pneumoniae-specific circulating immune complexes in patients with chronic coronary heart disease.

A strong immunological cross-reaction between a major glycolipid antigen of Chlamydia and the innermost (Re) core of the lipopolysaccharide of enteric bacteria was demonstrated with the aid of mutants in which the Re structure is exposed. The chlamydial glycolipid resembled the Re lipopolysaccharide in molecular size, solubility, and endotoxic properties and may thus be functionally equivalent to lipopolysaccharide, an essential and characteristic component of the outer membrane of Gram-negative bacteria.

Maija Leinonen

Papers

Serological evidence of an association of a novel Chlamydia, TWAR, with chronic coronary heart disease and acute myocardial infarction.

ANTIGENIC SIMILARITIES BETWEEN BRAIN COMPONENTS AND BACTERIA CAUSING MENINGITIS: Implications for Vaccine Development and Pathogenesis

Reduction of Oropharyngeal Carriage of Haemophilus influenzae Type b (Rib) in Children Immunized with an Rib Conjugate Vaccine

Chlamydia pneumoniae-specific circulating immune complexes in patients with chronic coronary heart disease.

The genus-specific antigen of Chlamydia: resemblance to the lipopolysaccharide of enteric bacteria