Rheumatology Patients at Increased Risk for Cardiac Disease

During a session at the 2017 American College of Rheumatology Annual Meeting in San Diego, California, a cardiologist joined rheumatologists to give a detailed look at the relationship between rheumatic conditions and cardiovascular disease. Rekha Mankad MD, FACC, director of the women’s heart clinic at Mayo Clinic in Rochester, Minnesota, presented “Getting to the Heart of the Matter: The Heart in Autoimmune Diseases.”

Mankad began with the sobering statement that increased morbidity and mortality from heart disease is present in all autoimmune diseases. She pointed to recent data demonstrating that patients with connective tissue diseases had a higher rate of coronary artery disease compared with the total population. “All of these diseases should alert you that this patient population needs to be looked at a little differently,” she said.

Mankad addressed several areas of concern for the rheumatologist:

Pericardial disease. According to Mankad, approximately 50% to 60% of patients who have systemic lupus erythematosus (SLE) will experience pericardial effusions, most of which are asymptomatic. She recounted the case of a 50-year-old male patient with SLE who was referred to her clinic after his rheumatologist suspected cardiac irregularities. Testing demonstrated pericardial effusion. “His heart [was] kind of swimming inside of this large pericardial effusion,” she said. “Obviously this had happened very slowly.” Four liters of fluid had to be extracted from the patient’s pericardial space.

Pericardial disease also affects patients with rheumatoid arthritis (RA), Mankad said, though pericarditis is typically observed post-mortem in this patient population.

Treatment for pericardial diseases in patients with rheumatic diseases is typically geared toward the treatment of a disease flare itself, including the use of high-dose steroids to aggressively treat inflammation. “I tell patients it’s a yin-yang,” Mankad said on the use of steroids, noting that chronic steroid use is associated with increased cardiovascular risk, but that high-dose steroids drive down inflammation.

With respect to other treatments for rheumatologic autoimmune inflammation, such as anti—tumor necrosis factor biologics, Mankad noted that while these therapies improve arterial function, there is some concern about whether they increase the risk of heart failure. “The jury is out on whether they cause it,” she said.

Valvular heart disease. Antiphospholipid syndrome, an autoimmune disease that primarily affects young women and that is often associated with SLE, can cause cardiac lesions. These lesions are accumulations of immune complexes, fibrin, and platelet thrombi. The lesions often involve the mitral valve, and range from small nodules to large, verrucous lesions that may necessitate valve replacement. The risk factor for patients with SLE developing such lesions “might be somewhere between 10 and 20%,” said Mankad, who highlighted the fact that disease activity is not correlated with the risk of developing lesions. In order to identify these problems early, she said, “we should be doing echoes at baseline” in patients with SLE.

In patients with RA, echocardiographic abnormalities may be present in any valve, and those patients who have the highest erythrocyte sedimentation rates (ESR) tend to have more aortic stenosis. Mankad encouraged rheumatologists who hear a heart murmur to follow these patients more closely.

Heart failure in RA. Mankad presented data from Mantel et al, published in the Journal of the American College of Cardiology, showing that the rate of heart failure overall, per 1000 person years, was 4.1 (range, 3.0 to 5.1) in patients with RA versus 3.2 (range, 2.9 to 3.6), for the general population (hazard ratio, 1.22; 95% confidence interval). She said that, in looking at these data, “It wasn’t just about coronary heart disease. It had to be this other entity [RA] as well.”

She added that inflammatory markers for RA typically peak 6 months prior to a diagnosis of heart failure, the rate of hospitalization for heart failure is approximately 20% higher in patients with RA than in patients without RA (7.4 versus 5.5 hospitalization days per patient per year), and that mortality from heart failure is “substantially higher” in patients with RA.

Ischemic heart disease. “So much happens with inflammation,” said Mankad, explaining that systemic inflammation in autoimmune conditions leads to endothelial dysfunction, which in turn produces arterial stiffness (associated with ischemic heart disease). “Basically, things are stiff. They don’t relax well.”

She discussed the case of a 40-year-old female patient with Raynaud’s phenomenon, SLE, and a connective tissue disease who had ongoing atypical chest pain that could not be explained until a computed tomography scan showed coronary calcification. “We know that that this is a real phenomenon,” said Mankad. “There is something wrong with their coronary arteries. They were called crazy, and their stress tests were said to be false positives…[but] “they’re real.”

Like those with Raynaud’s or SLE, patients with RA also have elevated risks for ischemic heart disease. Somewhat surprisingly, a body mass index (BMI) under 20 is associated with a higher risk of heart disease, as well as with lower survival. Mankad suggests that the “high inflammatory milieu is actually driving the BMI down” in these patients, and that low BMI should not be taken as an indication of low risk in a patient with RA.

Recommendations for Rheumatologists

Mankad said “I don’t expect you guys to do a full cardiovascular assessment with a patient,” but urged rheumatologists to “use a high index of suspicion to perform [cardiovascular testing],” which might include tonometry and pulse wave velocity testing to assess arterial stiffness, brachial artery testing to check endothelial function, and a carotid ultrasound to detect plaque and assess carotid intima-media thickness.

Finally, Mankad suggested that statins might be initiated as adjunctive RA therapy, pointing to results of the TARA trial, in which atorvastatin was associated with significant improvements in disease activity score, C-reactive protein, ESR, and cholesterol levels in patients with RA.