Lupus is a chronic inflammatory autoimmune disease with heterogeneous clinical manifestations.1 Direct organ-specific inflammation in the heart can lead to pericarditis, myocarditis, and valvular disease. Cardiovascular involvement includes coronary heart disease, which is responsible for significant morbidity and mortality in this population.2 According to a systematic review that included 28 studies, the risk of cardiovascular disease in people with lupus is increased, with the specific risks of myocardial infarction, congestive heart failure, cerebrovascular disease, and overall cardiovascular disease mortality all being at least doubled relative to the general population.3 The increased relative risk is particularly high among premenopausal women with lupus, given the relatively low risk of heart disease among their counterparts in the general population. The University of Pittsburgh found that women aged 35 to 55 years with lupus were more than 50 times more likely to suffer a nonfatal myocardial infarction than women without lupus within a similar age group in the Framingham Offspring Study.4 A prospective cohort from the Nurses’ Health Study found that among women with lupus compared to the general population, the relative risk for coronary heart disease was 2.25 (95% confidence interval [CI] [1.37 – 3.69]) after adjustment for potential confounding factors.5 Though the magnitude of increased risk varies, the finding itself of an increased risk of cardiovascular disease among lupus patients remains robust and persistent across epidemiologic studies.6
The increased risk of cardiovascular disease can be attributed to accelerated atherosclerosis in people with lupus. The etiology of this phenomenon is not completely understood. The pathogenesis of cardiovascular disease in this population is likely multifactorial and involves traditional cardiac risk factors, disease-related factors, and the adverse effects of medical treatments targeting lupus.6 Although the prevalence of traditional cardiac risk factors (e.g., obesity, hyperlipidemia, diabetes, and hypertension) is higher among people with lupus,6 the increased risk conferred by these factors alone is not enough to account for the increased rate of heart disease. This mismatch was demonstrated by the Toronto Risk Factor Study, which found that the Framingham risk factor formula, a widely accepted tool to assess the 10-year risk of a cardiovascular event, did not reflect the increased coronary risk factors among people with lupus compared to age-matched controls.7
Systemic inflammation likely contributes to the accelerated atherosclerosis and increased cardiovascular disease risk seen in people with lupus. Various immunologic pathways have been proposed to explain this relationship, including oxidative stress, antiphospholipid antibodies, dysregulation of the complement system, and cytokines as mediators of atherosclerotic plaque formation.2 These proposed mechanisms are supported by the association of increased disease activity, as evidenced by low complement levels and increased C-reactive protein, with corresponding greater cardiovascular disease risk in lupus patients.8,9 Furthermore, active and severe disease necessitates increased use of glucocorticoid treatment. Glucocorticoids are associated with a higher risk of heart disease among people with lupus as well as an elevated risk of diabetes mellitus and other cardiac risk factors, including high cholesterol, hypertension, and increased weight.10 For this reason, it is recommended that glucocorticoids be used at the lowest possible dose for the shortest length of time.
References
- Kiriakidou M, Ching CL. Systemic lupus erythematosus. Ann Intern Med. 2020;172(11):ITC81-ITC96.
- Lisnevskaia L, Murphy G, Isenberg D. Systemic lupus erythematosus. Lancet. 2014;384(9957):1878-1888.
- Schoenfeld SR, Kasturi S, Costenbader KH. The epidemiology of atherosclerotic cardiovascular disease among patients with SLE: a systematic review. Semin Arthritis Rheum. 2013;43(1):77-95.
- Manzi S, Meilahn EN, Rairie JE, et al. Age-specific incidence rates of myocardial infarction and angina in women with systemic lupus erythematosus: comparison with the Framingham Study. Am J Epidemiol. 1997;145(5):408-415.
- Hak AE, Karlson EW, Feskanich D, Stampfer MJ, Costenbader KH. Systemic lupus erythematosus and the risk of cardiovascular disease: results from the nurses' health study. Arthritis Rheum. 2009;61(10):1396-1402.
- Symmons DP, Gabriel SE. Epidemiology of CVD in rheumatic disease, with a focus on RA and SLE. Nat Rev Rheumatol. 2011;7(7):399-408.
- Bruce IN, Urowitz MB, Gladman DD, Ibañez D, Steiner G. Risk factors for coronary heart disease in women with systemic lupus erythematosus: the Toronto Risk Factor Study. Arthritis Rheum. 2003;48(11):3159-3167.
- Pons-Estel GJ, González LA, Zhang J, et al. Predictors of cardiovascular damage in patients with systemic lupus erythematosus: data from LUMINA (LXVIII), a multiethnic US cohort. Rheumatology (Oxford). 2009;48(7):817-822.
- Nuttall SL, Heaton S, Piper MK, Martin U, Gordon C. Cardiovascular risk in systemic lupus erythematosus--evidence of increased oxidative stress and dyslipidaemia. Rheumatology (Oxford). 2003;42(6):758-762.
- Magder LS, Petri M. Incidence of and risk factors for adverse cardiovascular events among patients with systemic lupus erythematosus. Am J Epidemiol. 2012;176(8):708-719.
