By: Jennifer Galvet, PharmD Candidate c/o 2024

             Ankylosing spondylitis (AS) is a systemic inflammatory condition that primarily affects a person’s back.¹ It is a form of arthritis that affects the spine and causes inflammation of the spinal joints, leading to severe, chronic pain and discomfort.² Ankylosing spondylitis can also impact other areas of the body, including the shoulders, ribs, heels, and the small joints of the hands and feet.² Most importantly, the condition is linked to cardiovascular disease.¹

The connection between ankylosing spondylitis and heart disease

The Spondylitis Association of America (SAA) has concluded that AS places patients at increased risk for numerous cardiovascular diseases. Ischemic heart disease, for example, is defined by inadequate blood supply to a local area due to blockage of the blood vessels supplying the area. Blood flow, and therefore oxygen, is restricted to the heart and can ultimately lead to heart attack.³ The risk of conduction disturbances; the heart beating either too slow or too fast, is increased in those with AS. In a healthy heart, electrical impulses travel down the left and right branches of the ventricles at the same speed, allowing both ventricles to contract simultaneously. When these conduction disturbances occur, electrical signals take an alternative path through the ventricles, resulting in arrhythmia. ⁴Cardiomyopathy, classified by the enlargement and weakening of the heart, and aortitis, inflammation of the aorta, are both linked to AS as well. ¹

Chronic inflammation associated with AS can strain the heart over time, according to the Arthritis Foundation, and this inflammation can increase the risk of heart attack, stroke, atrial fibrillation (irregular heartbeat), atherosclerosis (buildup of plaque in arteries), high blood pressure, and heart failure.¹ Inflammation can potentially promote the growth of plaques, loosen plaque in the arteries, and trigger blood clots, the primary cause of heart attacks and strokes.⁵ A 2015 meta-analysis determined that those living with AS had a substantial increased risk of coronary heart disease in comparison with the general population. ⁹A 2018 study looking at medical and pharmacy claims determined that genetic factors could also play a role in the connection between AS and cardiovascular disease.¹⁰ An additional study researched the prevalence of comorbidities associated with AS in 6,679 people aged 18 and older. In comparison with a control group, those with AS had higher rates of angina, myocardial heart attack, atherosclerosis, cerebrovascular disease or stroke, venous thromboembolism, coronary artery disease, and hypertension.¹ However, researchers did not specifically look at potential causes. They determined that genetic factors are potentially responsible for the higher rates of cardiovascular disease in people with AS and that these commonalities between both diseases might make AS a marker for cardiovascular disease. ¹ A 2006 meta-analysis of published scans confirmed sites on chromosomes 3q, 6p (the major histocompatibility complex), 10q, 16q and 19q in AS susceptibility. Non-major histocompatibility complex candidate gene analyses have confirmed that the IL-1 gene complex is also responsible for nearly half of the susceptibility to AS and comorbidities such as heart disease. ¹¹ The use of genotyping chips, derived from the International Hapmap resource, which provides an extensive genomic coverage of large disease cohorts, made it possible to conduct these successful genome-wide association studies. This led to the identification and validation of the IL-1 gene complex.

Treating Ankylosing spondylitis while maintaining heart health

Nonsteroidal anti-inflammatory drugs (NSAIDs) such as ibuprofen (Advil® and Motrin®) and naproxen (Aleve®) are the primary treatment for AS. The mechanism of action of NSAIDs involves the inhibition of the enzyme cyclooxygenase (COX). Cyclooxygenase is required to convert arachidonic acid into thromboxanes, prostaglandins, and prostacyclins. The therapeutic effect of NSAIDs is the result of the lack of these eicosasnoids. Through the inhibition of this enzyme, thromboxanes are inhibited from their role in platelet adhesion, and prostaglandins are unable to cause vasodilation, increase temperature set point in the hypothalamus, or play a role in anti-nociception.⁶

Nonsteroidal anti-inflammatory drugs are associated with an increased risk of cardiovascular incidents, diclofenac (Voltaren®) appearing to have the highest.¹,⁶ However, a 2015 study involving more than 400 participants living with AS determined that infrequent use of NSAIDs actually presented a higher risk of a cardiac event compared to long term use.¹ Prednisone, a steroid used to treat many diseases associated with inflammation, is another medication used for the treatment of AS1. Prednisone decreases inflammation by suppressing the migration of polymorphonuclear leukocytes and reversing increased capillary permeability. ⁷ However, prednisone can complicate heart health because of its associated risk of hypertension, hyperlipidemia, and atherosclerosis. To combat this, many disease-modifying medications and biological drugs for AS are used to help reduce inflammation in the body while protecting the heart.¹ Such agents include TNF alpha inhibitors such as etanercept (Enbrel®), Infliximab (Remicade®) , Adalimumab (Humira®), Golimumab (Simponi®), and Certolizumab pegol (Cimzia®) or IL-17 inhibitors such as secukinumab (Cosentyx®) and ixekizumab (Taltz®) when the response to TNF alpha inhibitors is inadequate. ⁸

Lifestyle changes that prevent cardiovascular disease

Although there is an increased risk of heart disease associated with AS, lifestyle changes may decrease this risk. Quitting or avoiding smoking, eating a healthy diet, maintaining a moderate weight, engaging in regular exercise, and adhering to AS treatment(s) help protect heart health. Controlling blood pressure, limiting alcohol consumption, managing stress and any other chronic illnesses, such as diabetes, will lower the risk of heart disease substantially. Regular doctor visits are imperative to the management of AS as well. ¹

An individual living with Ankylosing spondylitis is already at increased risk of heart disease due to chronic inflammation and potential genetic factors. Continuing to maintain a healthy lifestyle and adhering to all medical advice from your health care providers, while being aware of the associated risks, is essential in taking control of one’s health and preventing heart disease.

References:

1. Fletcher J. Ankylosing spondylitis and the heart: what is the link?. MedicalNewsToday. https://www.medicalnewstoday.com/articles/ankylosing-spondylitis-heart-health. Published 02/18/2021.Accessed 3/02/2021
2. Spondylitis Association of America. Overview of ankylosing spondylitis. Spondylitis Association of America. https://spondylitis.org/about-spondylitis/types-of-spondylitis/ankylosing-spondylitis/ Accessed 3/02/2021
3. American Heart Association. Silent ischemia and ischemic heart disease. American Heart Association. https://www.heart.org/en/health-topics/heart-attack/about-heart-attacks/silent-ischemia-and-ischemic-heart-disease. Accessed 3/02/2021
4. American Heart Association. Conduction disorders. American Heart Association. https://www.heart.org/en/health-topics/arrhythmia/about-arrhythmia/conduction-disorders. Accessed 3/02/2021
5. John Hopkins Medicine. Fight inflammation to help prevent heart disease. John Hopkins Medicine. https://www.hopkinsmedicine.org/health/wellness-and-prevention/fight-inflammation-to-help-prevent-heart-disease. Accessed 3/02/2021
6. California Northstate University California Northstate University College of Medicine Ghlichloo I(1), Gerriets V(2). In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2021-. 2020 May 18. Nonsteroidal Anti-inflammatory Drugs (NSAIDs). Accessed 3/02/2021
7. West Virginia University School of Medicine Henry Ford Hospital McLaren Oakland Hosp – Michigan State Un Puckett Y(1), Gabbar A(2), Bokhari AA(3). In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2021-. 2020 Apr 22. Prednisone. Accessed 3/02/2021
8. UpToDate. Treatment of axial spondyloarthritis (ankylosing spondylitis and nonradiographic axial spondyloarthritis) in adults. UpToDate. https://www-uptodate-com.jerome.stjohns.edu/contents/treatment-of-axial-spondyloarthritis-ankylosing-spondylitis-and-nonradiographic-axial-spondyloarthritis-in-adults. Accessed 06/17/2021.
9. Ungprasert P, Srivali N, Kittanamongkolchai W. Risk of coronary artery disease in patients with ankylosing spondylitis: a systematic review and meta-analysis. Ann Transl Med. 2015;3(4):51. doi: 10.3978/j.issn.2305-5839.2015.02.05. Accessed 3/02/2021
10. Walsh JA, Song X, Kim G, Park Y. Evaluation of the comorbidity burden in patients with ankylosing spondylitis using a large US administrative claims data set. Clin Rheumatol. 2018;37(7):1869-1878. doi: 10.1007/s10067-018-4086-2 Accessed 3/02/2021
11. Reveille JD. The genetic basis of ankylosing spondylitis. Curr Opin Rheumatol. 2006;18(4):332-41. Accessed 3/02/2021

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