Pathogenesis of Atherosclerosis in RA
Many of the underlying mechanisms of pathogenesis of atherosclerosis are shared in patients with and without RA, with inflammation playing a significant role in the development of CAD. In RA, chronic inflammation may accelerate the progression of atherosclerosis through the combined effects of cytokines, abnormal function of T lymphocytes, macrophages, dendritic cells, coagulation abnormalities, and oxidative stressors.
Role of Inflammation in Development of CAD
Inflammation plays an important role in MI among patients with RA, as supported by a study that documented elevated levels of tumor necrosis factor (TNF)-alpha and interleukin (IL)-6 in patients with RA. High levels of TNF-alpha and IL-6 were associated with the severity of subclinical atherosclerosis as measured by coronary artery calcification and were independent of Framingham risk score and diabetes mellitus.
Ongoing and persistent disease activity may be necessary to maintain progression of atherosclerotic burden. A study found no detectable signs of atherosclerosis in patients with newly diagnosed RA as compared to controls when measuring endothelial-dependent flow-mediated dilation and intima media thickness despite elevated serum markers for endothelial activation.
Screening for CAD in RA
Given the increased incidence of CAD in patients with RA, a yearly cardiovascular evaluation that includes a focused history and physical examination is recommended. Electrocardiography should be considered in patients who are ≥50 years of age. There should also be a low threshold for proceeding to exercise or pharmacologic stress testing in those with symptoms or ECG findings suggestive of CAD.
Diagnosis of CAD in RA
Exercise or pharmacologic stress testing is suggested for those with any symptoms suggestive of CAD such as angina, atypical chest pain, or exertional dyspnea. Any electrocardiographic findings suggestive of CAD should be followed up with further testing, which may include angiography.
Differential Diagnosis of CAD in RA
As in the general population, the differential diagnosis of chest pain in a patient with RA is broad. Some disorders that may be of particular interest are chest wall pain, pericarditis, herpes zoster infection, pulmonary hypertension, and thoracic aortic aneurysm or dissection.
Treatment of CAD in RA
Statin therapy reduces cardiovascular risk may have a beneficial effect on markers of inflammation in RA, including C-reactive protein (CRP) and erythrocyte sedimentation rate (ESR). NSAIDs should be used with particular caution in patients with RA, with attention to the presence or absence of CVD, the degree of risk for gastroduodenal damage, and the need for long-term oral anticoagulation or antiplatelet therapy. The risk of atherosclerosis associated with glucocorticoid use should be minimized by using the minimum effective dose of a glucocorticoid for the shortest possible time. Strict control of inflammation due to RA with both nonbiologic DMARDs and/or biologic DMARDs (eg, anti-TNF therapy) may reduce the increased CV risk seen in patients with RA.
Treatment of Acute Coronary Syndrome in RA
The medical management of patients with RA and acute coronary syndrome (ACS) is the same as in patients without RA. However, patients with RA who present with ACS may have poorer outcomes than other patients. In a retrospective study of 40 patients with RA and 40 age- and sex-matched controls, all with ACS, subsequent CV deaths were significantly more likely in those with RA (40% vs 15%), as was all-cause mortality (47% vs 25%).
Epidemiology of Concomitant CAD and RA
A meta-analysis of 24 observational studies comprising 111,758 patients found that the risk of CAD mortality was 59% higher in patients with RA as compared to the general population.
Risk Factors for CAD in Setting of RA
Traditional risk factors for CAD in the general population include hypertension, cigarette smoking, diabetes, older age, and dyslipidemia. In the Nurses’ Health Study, risk factors for cardiovascular disease were compared in women with and without RA. Use of anti-inflammatory drugs such as glucocorticoids, NSAIDs, and COX-2-selective inhibitors may contribute to increased risk for coronary thrombosis. Inflammation may worsen insulin resistance and impair pancreatic beta-cell function. These metabolic changes may contribute to accelerated atherosclerosis and to the higher incidence of ischemic heart disease characteristic of patients with diabetes mellitus.
Further Estimation of Patient-Specific Risk for CAD in RA
Another method developed for CV risk stratification in RA is the coronary artery expanded CV risk prediction score for RA (ERS-RA). The score includes 4 RA-related variables that when combined with traditional risk factors more accurately estimate risk for CAD as compared to traditional risk factor estimations. The variables include disease activity (Clinical Disease Activity Index >10 vs ≤10), disability (modified Health Assessment Questionnaire disability index >0.5 vs ≤0.5), daily prednisone use, and disease duration (≥10 vs <10 years).
Estimation of Patient-Specific Risk for CAD in RA
A method for risk adjustment in patients with RA has been proposed by the European League Against Rheumatism (EULAR) expert panel, which suggested multiplying commonly used risk calculators, such as the Systematic Coronary Risk Evaluation (SCORE) method or the Framingham risk model, by a factor of 1.5 in patients with RA who fulfill at least 2 of following 3 criteria: RA for longer than 10 years, positive testing for anti-cyclic citrullinated peptide antibodies or rheumatoid factor, or presence of extra-articular manifestations of RA
Prevention of CAD in RA
The key elements in the prevention of CAD in patients with RA are aggressive management of traditional risk factors and optimization of anti-inflammatory and immunomodulatory therapy to achieve effective disease control. This approach is consistent with EULAR recommendations. The following lifestyle modifications can reduce the risk factors for CHD: smoking cessation, healthy diet, moderate exercise, weight control, and blood pressure control.
Patients with rheumatoid arthritis (RA) and other chronic inflammatory diseases are at increased risk of developing coronary artery disease (CAD). Chronic inflammation is thought to enhance the development of atherosclerosis as a net result of effects mediated by cytokines, immune complexes, elevated levels of C-reactive protein (CRP), and endothelial dysfunction.
Abnormal function of T cells, dendritic cells, and macrophages has been shown to mediate inflammation and cause acceleration of atherosclerotic plaque formation. The increased risk of CAD-related events does not appear to be mediated entirely through traditional risk factors for atherosclerosis. Use of anti-inflammatory drugs such as glucocorticoids, nonsteroidal anti-inflammatory drugs (NSAIDs), and cyclo-oxygenase (COX)-2-selective inhibitors may contribute to increased risk for coronary thrombosis.
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Correct Answer: C
ST-segment elevation and T-wave inversions do not generally occur simultaneously in pericarditis, although they commonly coexist in acute ST-segment elevation myocardial infarction (STEMI).