title: Systemic inflammation and arrhythmic risk: lessons from rheumatoid arthritis.
abstract: Rheumatoid arthritis (RA) is a chronic immuno-mediated disease primarily affecting the joints, characterized by persistent high-grade systemic inflammation. Cardiovascular morbidity and mortality are significantly increased in RA, with >50% of premature deaths attributable to cardiovascular disease. In particular, RA patients were twice as likely to experience sudden cardiac death compared with non-RA subjects, pointing to an increased propensity to develop malignant ventricular arrhythmias. Indeed, ventricular repolarization (QT interval) abnormalities and cardiovascular autonomic nervous system dysfunction, representing two well-recognized risk factors for life-threatening ventricular arrhythmias in the general population, are commonly observed in RA. Moreover, large population-based studies seem to indicate that also the prevalence of atrial fibrillation is significantly higher in RA subjects than in the general population, thus suggesting that these patients are characterized by an abnormal diffuse myocardial electrical instability. Although the underlying mechanisms accounting for the pro-arrhythmogenic substrate in RA are probably intricate, the leading role seems to be played by chronic systemic inflammatory activation, able to promote arrhythmias both indirectly, by accelerating the development of ischaemic heart disease and congestive heart failure, and directly, by affecting cardiac electrophysiology. In this integrated mechanistic view, lowering the inflammatory burden through an increasingly tight control of disease activity may represent the most effective intervention to reduce arrhythmic risk in these patients. Intriguingly, these considerations could be more generally applicable to all the diseases characterized by chronic systemic inflammation, and could help elucidate the link between low-grade chronic inflammation and arrhythmic risk in the general population.
authors.forename: Pietro Enea
authors.initials: PE
authors.lastname: Lazzerini
authors.forename: Pier Leopoldo
authors.initials: PL
authors.lastname: Capecchi
authors.forename: Franco
authors.initials: F
authors.lastname: Laghi-Pasini
mesh_terms: D001145:Arrhythmias, Cardiac / Q000209:etiology*; D001172:Arthritis, Rheumatoid / Q000150:complications*; D016207:Cytokines / Q000378:metabolism; D016757:Death, Sudden, Cardiac / Q000209:etiology; D004562:Electrocardiography; D004812:Epidemiologic Methods; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D009203:Myocardial Infarction / Q000209:etiology; D009205:Myocarditis / Q000209:etiology; D032383:Myocytes, Cardiac / Q000502:physiology; D012307:Risk Factors
chemical_list: D016207:Cytokines
keywords: Arrhythmic risk; Atrial fibrillation; Cytokines; Rheumatoid arthritis; Sudden cardiac death; Systemic inflammation; Ventricular arrhythmias