Cardiovascular Involvment in Ankylosing Spondylitis
Chronic inflammatory conditions are established risk factors for the development of cardiovascular disease (CVD). Like most patients with rheumatic disease, patients with ankylosing spondylitis (AS) are at greater risk than the general population for CVD, risk factors for CVD, and cardiovascular mortality. Although studies have attempted to quantify the degree of excess risk of CVD and cardiovascular mortality, it is difficult to determine how AS treatments and AS-related lifestyle changes affect the patient’s cardiovascular risk. None of the studies that analyzed the relationship between cardiovascular risk and AS were randomized, controlled clinical trials; available data derive mainly from observational studies. Nevertheless, an accumulation of data from the 1930s to the present conclusively shows that AS contributes to harmful cardiovascular changes. Clinicians need to be familiar with common cardiovascular complications of AS so they can help patients minimize their risk.
Pharmacologic Agents for Peripheral Disease
Treatments for JSpA are based on agents evaluated in adult SpA.[7,11] The 2011 ACR guidelines are for JIA and are not specific to JSpA. The algorithms for peripheral disease consider the number of active joints and prognosis. First-line treatment is essentially a brief trial of NSAID monotherapy. For persistent activity, the ACR suggests adding or switching to a disease-modifying anti-rheumatic drug (DMARD), such as methotrexate, sulfasalazine, or leflunomide. Glucocorticoid intraarticular injections are advised for all children with active arthritis. DMARDs are effective for peripheral JIA but have not been proven effective for axial disease or enthesitis in JSpA. However, open-label studies indicate sulfasalazine improves symptoms in juvenile AS, ERA, and PsA. For JIA refractory to NSAIDs and DMARDs, ACR guidelines recommend a tumor necrosis factor (TNF) inhibitor. The rate and type of treatment escalation depends on disease activity.
Which Patients Should Be Monitored?
Cardiovascular changes associated with AS may begin early in the disease process. Thus, assessment of cardiovascular risk should be routine for all patients affected with this disease. Preventing CVD or cardiovascular death depends on early identification and effective management of traditional cardiovascular risk factors such as hypertension or hypercholesterolemia. Despite their importance, screening and treatment of CVD risk factors in patients with rheumatic diseases are often suboptimal. One reason for suboptimal management may be confusion over who is responsible for monitoring cardiovascular risk in patients with AS. The lack of disease-specific guidelines for risk assessment is another concern. Ensuring patients with AS are screened and managed appropriately for CVD will require collaboration between the rheumatologist or specialist nurse, the general practitioner, and the patient.
How Should I Evaluate Patients With AS for CVD?
If routine testing and the patient’s history suggest a high risk of CVD, a 24-hour Holter monitor and echocardiography can be useful for detecting signs of cardiac change. Alternatively, calculation of QT dispersion on standard electrocardiogram is a less inexpensive and faster method of assessing whether a patient has an increased risk of arrhythmia and should undergo more extensive testing.
What Should I tell My Patients?
Patients with AS need to understand their increased risk for CVD. It is important to talk with patients about modifiable risk factors for CVD, such as smoking cessation, weight loss, or appropriate exercise. They should be told to report chest pain, which could be the first sign of aortic dissection, a rare but potentially fatal cardiac event. Controlling inflammation may have a beneficial effect on CVD risk, and patients—especially those with high levels of inflammation—should be reminded of the importance of taking their medications for AS as prescribed.
What Are the Cardiovascular Manifestations of AS?
The most frequent cardiovascular manifestations of AS are aortic insufficiency and conduction disorders. Up to 20% of patients with AS have conduction disorders, of which atrioventricular block is the most common.[5,6] Compared with the general population, patients with AS have a 30% to 50% increase in the risk of acute coronary syndromes, deep venous thromboembolism, pulmonary embolism, or stroke. They also have a 25% to 60% greater risk of ischemic heart disease, congestive heart failure, and valvular heart disease. Heart failure may occur secondary to mitral insufficiency. Aortic dissection, which is a rare but frequently fatal complication of aortic insufficiency, has also been observed in patients with AS. Other potential cardiovascular complications include left ventricular diastolic dysfunction, pericarditis, myocardial disease, peripheral vascular disease, and hypertension.[2,3,5]
What Causes Cardiovascular Dysfunction in AS?
Inflammation is the primary contributor to cardiovascular pathologies in AS. Aortitis was the earliest cardiac complication linked to AS. Approximately 60% of patients with AS have aortic root involvement on echocardiography, which presents as thickening, stiffness, and dilation of the aortic root.[2,5] Root dilation results from fibrous scarring of the intima secondary to chronic inflammation and can lead to aortic or mitral regurgitation. Inflammation also damages the interventricular septum wall, which leads to atrioventricular node dysfunction and conduction disorders. Other proposed mechanisms of cardiovascular risk include chronic elevations in inflammatory markers that affect lipid metabolism and insulin activity, autonomic nervous system (ANS) dysfunction, and the presence of human leukocyte antigen (HLA)-B27.[2,7] Human leukocyte antigen (HLA)-B27, an immunogenic marker found in 90% of AS patients, is believed to play a role in the development of conduction disorders.
Which Patients With AS Are at Greatest Risk for CVD?
AS is usually diagnosed when patients are in their early to mid-twenties. Although symptom severity corresponds with the extent of cardiac change, patients have manifested AS-related cardiovascular changes prior to experiencing musculoskeletal symptoms.[2,11] Cardiovascular complications have also been detected in AS patients without cardiac symptoms. Studies show men with AS have a higher prevalence of CVD than women with AS. The relative risk of CVD is greater for AS patients of all ages. One study found men and women with AS in the 20- to 39-year-old cohort had the highest relative risk of CVD. Even juveniles with AS have a higher risk of CVD than juveniles in the general population. The concordance between HLA-B27 positivity and CVD is also stronger in patients with juvenile-onset AS.
What Is the Relationship Between CVD and Mortality in AS?
Cardiovascular disease is the primary cause of mortality in patients with AS. Patients with AS have a 35% greater risk of death from cardiovascular causes than the general population. The risk of overall vascular mortality is 43% greater for patients with AS than for the general population. Factors that independently increase the risk of vascular mortality in patients with AS include advanced age, male sex, lower income, dementia, and peripheral vascular disease.
Do TNF Inhibitors Affect Cardiovascular Risk?
Few studies have evaluated the effects of TNF-inhibitors (TNFis) on cardiovascular risk specifically in patients with AS. The available data are inconclusive as to whether TNFis improve subclinical markers of CVD or reduce CVD risk in patients with AS. A recent longitudinal study found TNFis may slow progression of atherosclerosis, a condition associated with greater carotid intima-media thickness (cIMT) and aortic stiffness in patients with AS. Patients who used a TNFi continuously for 4.9 years had no significant change in cIMT. In contrast, cIMT thickness increased in patients who discontinued TNFi use. Vascular elasticity was unchanged in both groups. The study did not assess whether TNFi use affected the rate of cardiovascular morbidity or mortality. More studies are needed to determine primary or secondary effects of TNFis on cardiovascular risk in patients with AS.
Ankylosing spondylitis (AS) is a chronic inflammatory autoimmune disorder characterized by progressive damage of the axial skeleton and sacroiliac joints due to enthesitis. Patients with AS may also experience inflammation of the peripheral joints and tendons, uveitis, and extra-articular manifestations. An estimated 10% to 30% of patients with AS have cardiovascular involvement, and having AS significantly increases the risk of cardiovascular mortality.
More research is needed to determine the mechanisms of cardiovascular risk in patients with AS and to identify ways to predict which patients with AS are at increased risk of cardiovascular mortality. Data suggest common AS treatments, such as nonsteroidal anti-inflammatory drugs (NSAIDs) and possibly tumor necrosis factor (TNF) inhibitors, may reduce cardiovascular risk, possibly through mediation of inflammation.[3,4] The increased rates of cardiovascular disease (CVD) and cardiovascular mortality associated with AS highlight the need for clinicians to monitor patients and manage their cardiovascular risk.