The inextricable link between atherosclerosis and prototypical inflammatory diseases rheumatoid arthritis and systemic lupus erythematosus

Abstract

The increased burden of cardiovascular disease in patients with rheumatoid arthritis and systemic lupus erythematosus has recently become the focus of intense investigation. Pro-atherogenic risk factors and dysregulated inflammation are the main culprits, leading to enhanced atherosclerosis in subgroups of patients with inflammatory diseases. Common molecular pathways shared by atherosclerosis and inflammatory disease may be involved. In this review we map the key determinants of the increased incidence of cardiovascular disease in patients with inflammatory diseases at each step of the atherogenesis. IntroductionResearch during the past 20 years has driven a major shift in how atherosclerosis is conceptualized. Initially branded as a passive accumulation of lipids in the vessel wall, atherosclerosis is now recognised as an 'inflammatory disease' [1]. Striking similarities can be identified between atherosclerosis and prototypical inflammatory diseases (Figure 1). In parallel, there is growing evidence that cardiovascular disease (CVD) is the leading cause of mortality in patients with chronic inflammatory diseases [2], including rheumatoid arthritis (RA), systemic lupus erythematosus (SLE), Sjögren's disease and systemic sclerosis. This review first summarizes the impact of CVD on the lives of patients with inflammatory diseases. Second, we map the key molecular determinants of the increased prevalence of CVD in patients with inflammatory diseases at each step of the progression of atherosclerosis (initiation, progression and thrombotic complications). We focus on RA and SLE, for which more evidence is currently available. The clinical impact of atherosclerosis in inflammatory diseasesAtherosclerosis and rheumatoid arthritis Cardiovascular manifestations such as pericarditis, myocarditis and atrioventricular block are classic complications of RA and SLE. However, most of the cardiovascular mortality in RA patients is not due to these manifestations but rather to ischaemic heart disease secondary to coronary atherosclerosis [3]. In the Nurses' Health Study [4], patients with RA had more than twofold greater risk for myocardial infarction (MI) compared with patients without RA. Worryingly, RA patients are almost six times more likely to have had an undiagnosed MI and twice as likely to experience sudden death [5]. RA patients are also far less likely to report forewarning symptoms, such as angina [5,6], potentially hampering early detection of atherosclerotic disease.In support of these observations, RA patients have an increased prevalence of subclinical atherosclerosis, with a greater incidence of carotid artery plaque and increased carotid intima/media thickness (IMT) [7,8] as well as multivessel coronary artery disease compared with control individuals [9]. Systemic lupus erythematosus and cardiovascular diseaseThree decades ago, Urowitz and coworkers [10] recognized that CVD and MI were major causes of mortality in patients with SLE. In fact, patients with SLE are five or six times more likely to hav...

Endothelial progenitor cells: Are they displaying a function in autoimmune disorders?

“…Atherosclerotic plaque and sinovia from RA patients share same features, including a typical inflammatory microenvironment composed by infiltrating leucocytes (Full et al, 2009), cytokines, adhesion molecules and an activated endothelial phenotype. The loss of protective antioxidant and anti-inflammatory mechanisms seems to be responsible for the endothelial dysfunction which is the earliest, but yet reversibile, stage of atherosclerotic plaque formation (Deanfieldet et al, 2007).…”

HU-444, a Novel, Potent Anti-Inflammatory, Nonpsychotropic Cannabinoid

“…Increasingly, RA is known to be associated with cardiovascular inflammatory diseases leading to enhanced mortality in patients (Full et al, 2009). Key cellular and molecular components associated with the onset and ongoing inflammatory processes in RA have been identified, although yet the specific antigen/environmental agent triggering the onset of the autoimmune pathways remains uncharacterized (Feldmann et al, 2010).…”

Comparison of Heart Rate Variability Adjusted for Age and Heart Rate in Women With Rheumatoid Arthritis and Women Without Rheumatic Diseases

“…Большинство случаев ССО развивается у больных РА с низким или умеренным кардиоваскулярным рис-ком (согласно существующим стандартным методам его определения) [31], поэтому актуален поиск новых пре-дикторов ССО. Предполагается, что увеличение кар-диоваскулярного риска при РА обусловлено сходными Вариабельность ритма сердца у женщин с ревматоидным артритом иммуновоспалительными механизмами, лежащими в основе патогенезаданного заболевания и атеросклероза [32][33][34]. Системное воспаление приводит к развитию дислипидемии, нарушению углеводного обмена, дис-функции эндотелия, запуску ремоделирования сер-дечно-сосудистой системы, повышению протромбо-генного потенциала [35,36], что, в свою очередь, может способствовать возникновению нарушений вегетатив-ной регуляции сердечной деятельности [37,38].…”