Rheumatoid pericarditis was first described by Charcot in 1881 (14) and is thought to be a common CVD manifestation of RA (Fig. 35E.1). Autopsy studies have reported pericardial disease in up to 50% of RA patients (15) and more recently echocardiographic studies have reported that pericardial disease occurs in up to 30% of RA cases (16). However, clinically significant pericarditis is observed infrequently in RA, affecting fewer than 2% of patients (17,18). It is possible that the prevalence of pericarditis in RA is declining because of more effective disease-modifying antirheumatic drugs (DMARD) or because RA is becoming a less severe disease (19). Pericarditis is associated with increased disease severity and is more common in male RA patients. Patients are usually rheumatoid factor positive and they frequently have rheumatoid nodules and erosive joint disease. Systemic symptoms are common and include fatigue, weight loss, and other extraarticular system involvement (18).

The pericardial fluid is classically exudative containing leukocytes, elevated levels of lactate dehydrogenase, and a low concentration of glucose, but these findings are not universal (18). Chronic inflammation can cause thickening of the pericardium that can lead to constrictive pericarditis, which is a rare sequela of severe or recurrent pericarditis in RA (20). Calcification of the pericardium is rarely seen in RA pericarditis (21). Pericardial effusions that develop owing to infection are rarely seen in RA. However, if there is any suspicion that the pericarditis may be infectious, cultures for tuberculosis and fungi as well as standard culture of pericardial fluid should be obtained; many RA patients are immunosuppressed by their DMARDs.

The vast majority of patients respond to treatment with non-steroidal anti-inflammatory drugs (NSAIDs). After infection has been ruled out, short courses of oral steroids may be used, and DMARD therapy should be increased to control active rheumatoid disease. Colchicine has been used to treat recurrent non-RA pericarditis; however, it is not clear whether this is beneficial in RA pericarditis (22).

There are rare case reports of rheumatoid nodules affecting the endocardium or heart valves causing valve dysfunction. In particular, there have been several reports of aortic valve nodulosis causing regurgitation requiring aortic valve replacement (23,24) and mitral valve nodules causing embolic disease (25). There has also been one report in the literature of an endocardial nodule mimicking an atrial myxoma (26).

Based on autopsy studies, diffuse endocardial involvement in RA appears to be a relatively common manifestation of RA (27). Valvular abnormalities are frequently seen on echocardiographic studies and it has been hypothesized that heart valve involvement may be an additional extraarticular manifestation of RA (28). Hospital-based studies report a prevalence of nonspecific aortic and/or minimal mitral regurgitation in 5% to 30% of RA patients (29,30,31). Mitral valve insufficiency seems to be associated with nodular RA, which suggests that heart valve involvement reflects more severe RA disease (32). It appears
that the valve lesion is due to infiltration of inflammatory cells that leads to thickening and calcification at the base of the valve and valve ring (27,33). However, symptomatic valve disease is a very rare manifestation of RA.

Myocarditis occurs in RA either as the result of focal granulomatous disease affecting the myocardium or more diffuse fibrosing lesions, and is a common finding at autopsy (33). It is commonly asymptomatic, but may lead to the development of cardiac failure or disruption of the conducting system of the heart.

It seems that ECG evidence of conduction abnormalities and arrhythmias are common in patients with RA. One study reported that 50% of RA patients had evidence of cardiac arrhythmias on 24-hour ECG monitoring, although this arrhythmia prevalence was similar to that seen in a hospital-based non-RA control group (34). Another study reported a higher prevalence of abnormal ventricular repolarization in RA patients compared to control patients (35). Complete heart block (CHB) has been described in association with RA, possibly due to disruption of the atrioventricular (AV) node by rheumatoid granulomata (36,37). Autonomic nervous system disturbance has been observed in RA cohorts (38,39), which may be a risk factor for silent CVD events (40,41).

There is increasing evidence that RA patients have an increased prevalence of CHD due to atherosclerosis. This appears to be responsible for much of the excess CVD mortality observed in RA. Several studies have shown that RA patients have a two- to threefold increase in rates of myocardial infarction (MI) when compared to the general population (42,43). In addition, Maradit-Kremers et al. (41) have highlighted that RA patients are more likely to experience silent ischemia and sudden cardiac death. In one UK RA cohort cardiovascular admissions were not increased despite increased cardiovascular mortality (8). Therefore, it is possible that the true prevalence of CHD events in RA is underestimated by these hospital-based studies. Also patients who fail to present with typical CHD symptoms are unlikely to benefit from interventions to improve CHD outcomes. There is a need to educate both physicians and patients to be more aware that CHD events may not present typically in association with RA.

Several CVD risk factors, including cigarette smoking and obesity, have also been identified as risk factors for the development of RA (44). Some of these, including age, smoking, hypertension, and lipid levels have been associated with subclinical atherosclerosis in RA (45). Cigarette smoking is associated with more severe RA and it may be this disease severity and inflammation that promotes atherosclerosis in RA. However, studies of RA populations have not found that traditional CVD risk factors explain the increased CVD events seen in these patients (42,43). One study revealed that a low body mass index (BMI) was associated with increased CVD mortality and it has been hypothesized that a low BMI reflects increased inflammatory disease burden in RA (46). This demonstrates how difficult it is to separate the effects of the RA disease activity from the effects of CVD risk factors when investigating CVD in RA.

CVD epidemiology in the general population has revealed the importance of several novel CHD risk factors including homocysteine, thrombotic markers, insulin resistance, and markers of inflammation (47). There is a high prevalence of these “novel” risk factors in patients with inflammatory joint disease. Patients with RA have been found to have abnormal homocysteine metabolism (48), which may be exacerbated further by the use of methotrexate or sulphasalazine (49). However, it is not known whether elevated homocysteine levels predict future CHD events in RA patients. Thrombotic markers may be increased in RA due to systemic inflammation and have been associated with CHD events in RA (50). Insulin resistance has been recognized to complicate RA. It is also associated with inflammation, obesity, steroid use, and CVD (51). Of particular interest in RA is the association between inflammation and CVD. Atherosclerosis is now thought to be an inflammatory condition (52) and prospective study has recognized markers of inflammation, including C-reactive protein (CRP), are predictors of future CHD events in both the general (53) and in inflammatory polyarthritis populations (54). Other studies have found that erythrocyte sedimentation rate (ESR) measurements predict CHD events in RA (55). It seems that in RA an elevated CRP is associated with endothelial dysfunction (56), which may promote atherosclerosis in RA patients.

Understanding the pathogenesis of CHD in RA is complicated; several factors, including inflammation, RA disease severity, and cardiovascular risk factors, all interact with each other. It may be that with a combined approach, allowing for modification of CHD risk factors and reduction of inflammation using immunosuppressive agents, the cardiovascular mortality in RA can be reduced. Although coronary arteritis is observed at autopsy in 10% of RA cases (27), this rarely leads to MI or damage.

Clinically significant aortic regurgitation occurs in approximately 2% to 10% of patients with AS. The prevalence of valve disease increases with longer disease duration and AS severity. Stenotic aortic valve lesions have not been described in association with AS. Inflammation of the ascending aorta
at the level of the sinuses of Valsalva causes distortion and dilatation of the aortic ring. Fibrotic thickening and downward retraction of the valve cusp bases with inward rolling of the edges of the valve cusps occur, and these factors contribute to the development of aortic incompetence (60). These “characteristic” pathologic findings have also been described in association with other seronegative spondarthropathies. Fibrosis may extend down from the nonseptal portion of the aorta to involve the mitral leaflet. This can occasionally give rise to mitral valve insufficiency. Mitral insufficiency may also develop secondary to left ventricular dilatation caused by aortic regurgitation. Asymptomatic mitral prolapse is observed in approximately 10% of patients with AS.

AV conduction blocks have been reported in association with AS and other spondarthropathies and are thought to represent the most common cardiac complication of AS. However, the prevalence of these conduction defects varies markedly between studies. One early study of 190 patients described first-degree AV block in 15% of AS patients whereas another study found ECG evidence of AV block in only 6% (61). It seems that HLA B27 related disease processes are more prevalent in cardiology patients requiring permanent pacemakers (62) and there is some evidence that AV block may occur intermittently in AS patients. This suggests that the conduction disturbance may be initially due to a reversible inflammatory process rather than disruption owing to fibrosis (60). Other arrhythmias include increased frequencies of both atrial and ventricular arrhythmias with evidence of prolonged QT dispersion being noted in nearly 60% of AS patients in one study (61). This suggests that the whole conducting system may be affected in AS and damage is not limited to AV nodal tissue.

Disturbance of the autonomic nervous system has been described in AS, with evidence of decreased parasympathetic activity (63). These findings were more marked in AS patients with active inflammatory disease and as similar findings have been observed in other systemic inflammatory conditions this disturbance of the autonomic nervous system may be related to systemic inflammation rather than specifically due to AS.

Although patients with known aortic valve insufficiency may develop ventricular failure as a secondary phenomenon, myocardial involvement in AS may also occur in the absence of aortic valve disease. Left ventricular dilatation and impaired diastolic function of the left ventricle have been described in association with AS (64) and diastolic ventricular dysfunction is observed even in patients with less severe AS disease.

AS is not typically associated with accelerated atherosclerosis. One small study revealed ECG evidence of ischemic heart disease in 18% of AS patients (65). However, a study utilizing data from the UK General Practice Research Database did reveal that men with AS had a 40% increase in rates of first MI compared to men without AS (66). Rates of traditional CVD risk factors appear to be similar in AS patients (64), so it is possible that chronic inflammation associated with AS may promote accelerated atherosclerosis in this condition. NSAIDs are the main treatment for AS symptom control and many patients will have long-term exposure to these drugs. Therefore, these patients may be at increased risk of NSAID-associated cardiovascular side effects, including hypertension (67), and congestive cardiac failure given the association between AS and left ventricular dysfunction (68).