SAN DIEGO—It’s no secret: Autoimmune, inflammatory rheumatic disease raises a patient’s risk of cardiovascular disease (CVD).
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Explore This IssueJanuary 2018
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“Inflammation may affect all aspects of the cardiac structure and function,” said Rekha Mankad, MD, FACC, director of the Women’s Heart Clinic at the Mayo Clinic in Rochester, Minn. Dr. Mankad also oversees a cardio-rheumatology clinic to assess and treat these complex patients. On Nov. 6 at the ACR/ARHP Annual Meeting, she discussed heart disease risk assessment and complications in rheumatic diseases. Rheumatoid arthritis patients have the highest CVD risk, followed by those with inflammatory bowel diseases.1 Survival rates are lower in RA patients due to heart disease.2
“We see this risk in lupus as well. Rheumatologists have become incredibly good at treating lupus, so very active, early disease doesn’t take the lives of these patients, but as they live longer, heart disease is the reason for late deaths,” said Dr. Mankad.3 Ankylosing spondylitis patients may have higher rates of vascular death because AS often causes aortitis and aortic regurgitation.4 Lupus elevates a patient’s risk for pericardial effusion, which is often asymptomatic. Pericarditis usually happens during active lupus flares.
Valve Choice Matters
Antiphospholipid antibody syndrome, frequently seen in lupus, may cause valvular complications like Libman-Sacks endocarditis or nonbacterial thrombotic endocarditis (NBTE). Its bland lesions are filled with immune complexes, fibrin and platelet thrombi.
“Why are these lesions important to recognize? Because you must figure out the right valve replacement choice. We are talking about a young patient population in lupus, women who are potentially in their childbearing years,” she said. Mechanical valves are preferable to bioprosthetic valves in this population, although it is important to carefully manage anticoagulation, especially if patients become pregnant.
Valve disease occurs in up to 20% of lupus patients and can worsen over time, she said. “This may be a population where we should be doing echocardiograms at baseline, although that’s not part of the guidelines.” Even healed lesions may lead to fibrosis later, she said.
Heart failure risk is also higher in RA.5 “As we age, everyone’s heart failure risk goes up, but if you have RA, that risk goes up dramatically,” she said. One study showed that RA patients’ inflammatory markers peaked six few months before their diagnoses.6 “This tells us that inflammation, which we know affects the joints and all parts of the body, certainly affects the myocardium and makes these patients more prone to heart failure.”
When disease activity is high, even early RA patients have a higher risk of non-ischemic heart failure, and male sex in RA raises the risk of both ischemic and non-ischemic heart failure, said Dr. Mankad.7
“Heart failure seen in the RA population is what we call ‘hef-hef,’ or heart failure with a preserved ejection fraction,” she said. “This is a much more complicated entity, and we don’t really know what causes it.”8 RA patients with heart failure are more likely to be hospitalized and have higher mortality rates than the general population.
High inflammation causes arteries to act abnormally, even if they are not obstructed. “They don’t relax or dilate appropriately with the level of activity you are doing. They remain stiff,” she said. Patients may present with chest pain, but their coronary arteries look normal. In the past, cardiologists assumed the test results were off, but now recognize inflammation’s effect on these patients, who have higher rates of silent myocardial infarction and sudden cardiac deaths.9 High inflammatory markers cause an almost equal risk of CVD as smoking or hypertension in RA patients, so consider all of these factors to assess risk, said Dr. Mankad.
Inflammation & Plaque
Paradoxically, a low body mass index is a risk factor for heart disease in RA patients. “It may not be because they are healthier and exercise, but that the inflammatory disease is actually making them too thin. The high inflammatory milieu drives BMI down in these patients,” she said.10
Look for signs of heart disease even in premenopausal women who have lupus. “No matter what your age, having lupus increases your risk of plaque,” she said.11 Hydroxychloroquine and steroid treatment may reduce plaque in lupus patients. “Lupus patients have a lot of CVD risk factors, like all of us do. Hyperlipidemia, hypertension, smoking and sedentary lifestyle are common in the lupus population and this does lead to plaque. If you have lupus and these traditional risk factors, your likelihood of having plaque is higher.”
RA and lupus flares may spike lipid levels, so “if I get a patient’s cholesterol profile, and realize they had a flare at the time, I check it again later, because I just don’t know where they are when they’re at their best.”
Coronary angiograms are invasive and costly, but another option to assess risk is a brachial artery reactivity test, said Dr. Mankad. It uses a blood pressure cuff to test the artery’s dimension before and after pressure. RA and SLE patients often show poorer dilation.
“But if we find this, can we do something different for the patient? I certainly talk to these patients about the risks, and we talk about nonpharmacological ways to improve their endothelial function: diet, exercise and weight loss,” she said. Statins can improve both inflammation and cholesterol levels in these patients, “but should they be used routinely in RA patients? Obviously, the guidelines don’t say so.”12
Treat Inflammation Aggressively
Long-term corticosteroids have a negative effect on carotid artery thickness, said Dr. Mankad.13 “If you’re using bursts of steroids here and there, maybe it’s OK because you’re driving down the inflammation. But if you’re using them chronically, lots of bad things can happen.” TNF inhibitors appear to have a slightly better effect on CVD risk than non-biologic DMARDs, she said.14
Rheumatologists should watch for clues that suggest a patient needs more extensive cardiovascular screening, she said. “Always have a high index of suspicion and, depending on the patient, watch for the symptoms and signs of heart disease.”
Susan Bernstein is a freelance journalist based in Atlanta.
- Baena-Diez JM, Garcia-Gil M, Comas-Cufi M, et al. Association between chronic immune-mediated inflammatory diseases and cardiovascular risk. Heart. 2017 Aug 28;0:1.
- Gabriel SE, Crowson CS, Kremers HM, et al. Survival in rheumatoid arthritis: A population-based analysis of trends over 40 years. Arthritis Rheum. 2003;48(1):54–58.
- Abu-Shakra M, Urowitz MB, Gladman DD, et al. Mortality studies in systemic lupus erythematosus: Results from a single center, II, predictor variables for mortality. J Rheum. 1995 Jul;22(7):1265–1270.
- Haroon NN, Paterson JM, Li P, et al. Patients with ankylosing spondylitis have increased cardiovascular and cerebrovascular mortality: A population-based study. Ann Int Med. 2015 Sep;163:409–416.
- Nicola PJ, Maradit-Kremers H, Roger VL, et al. The risk of congestive heart failure in rheumatoid arthritis: A population-based study over 46 years. Arthritis Rheum. 2005 Feb;52(2):412–420.
- Maradit-Kremers H, Nicola PJ, Crowson CS, et al. Raised erythrocyte sedimentation rate signals heart failure in patients with rheumatoid arthritis. Ann Rheum Dis. 2007;66:77–80.
- Mantel A, Holmqvist M, Andersson DC, et al. Association between rheumatoid arthritis and risk of ischemic and non-ischemic heart failure. J Am Coll Cardiol. 2017 Mar;69(10):1275–1285.
- Davis JM 3rd, Roger VL, Crowson CS, et al. The presentation and outcome of heart failure in patients with rheumatoid arthritis differs from that of the general population. Arthritis Rheum. 2008 Sep;58(9):2603–2611.
- Maradit-Kremers H, Crowson CS, Nicola PJ, et al. Increased unrecognized coronary heart disease and sudden deaths in rheumatoid arthritis: A population-based cohort study. Arthritis Rheum. 2005 Feb;52(2):402–411.
- Escalante A, Haas RW, del Rincon I. Paradoxical effect of body-mass index on survival in rheumatoid arthritis: Role of comorbidity and systemic inflammation. Arch Intern Med. 2005 Jul;165(14):1624–1629.
- Roman MJ, Shanker BA, Davis A, et al. Prevalence and correlates of accelerated atherosclerosis in systemic lupus erythematosus. New Engl J Med. 2003;349:2399–2406.
- McCarey DW, MacInnes IB, Madhok R, et al. Trial of atorvastatin in rheumatoid arthritis (TARA): double-blind, randomised, placebo-controlled trial. Lancet. 2004;363(9426):2015–2021.
- Giles JT, Post WS, Blumenthal RS, et al. Longitudinal predictors of progression of carotid atherosclerosis in rheumatoid arthritis. Arthritis Rheum. 2011 Nov;63(11):3216–3225.
- Solomon DH, Curtis JR, Saag KG, et al. Cardiovascular risk in rheumatoid arthritis: Comparing TNF-α blockage with non-biologic DMARDs. Am J Med. 2013 Aug;126(8):730e9–730e17.