The high incidence of premature or early onset atherosclerotic cardiovascular disease (ASCVD) is one of the most compelling and, as yet, incompletely appreciated clinical challenges facing rheumatologists caring for patients with systemic lupus erythematosus (SLE).
Improved therapies have reduced the likelihood that patients with systemic autoimmunity will succumb to their primary disease, and as a result, the awareness of an increased cardiac risk in these patients has slowly grown. At Hospital for Special Surgery in New York City, recognition that young women followed for lupus were suffering heart attacks led us to design a study to formally examine the prevalence and associated clinical features of ASCVD in this population.
The presence of ASCVD in lupus patients was initially identified in two reports from the 1970s: an autopsy study showing atherosclerotic narrowing of coronary arteries in relatively young SLE patients and a clinical study demonstrating a bimodal pattern of mortality from SLE with late deaths due to myocardial infarction.1,2
During the next 25 years, evidence accumulated to confirm that ASCVD is an important cause of death and hospitalization in the SLE population. In series reported after 1975, 6% to 45% of deaths in SLE patients were due to coronary artery disease—many in premenopausal women—and the prevalence of clinically manifest ischemic disease (myocardial infarction [MI] or angina) ranged from 6% to 20%.3 In the Pittsburgh SLE Registry, women age 35 to 44 were more than 50 times likelier to have an MI than historical controls from the Framingham population.4
While classical risk factors for cardiovascular disease (age, hypertension, smoking, family history, diabetes mellitus, and hypercholesterolemia) are operative in SLE patients, the risk for MI conferred by SLE increased 10.1-fold in one study after controlling for these factors, suggesting that SLE itself, and/or its treatment, were primarily responsible for ASCVD.5 Although there was consensus that clinical events due to ASCVD appeared prematurely and more frequently in SLE, their absolute number was small and the prevalence of underlying preclinical atherosclerosis was not known and its causes not understood.
Rheumatology-Cardiology Collaboration
At the same time rheumatologists were recognizing that ASCVD was more common in patients with systemic autoimmunity, cardiologists and vascular biologists began to appreciate that immunological processes participate in atherogenesis. By the 1990s, evidence emerged for immune triggers of cardiovascular disease—classical risk factors were not the full story—and basic and clinical science journals were replete with studies describing the relationship between inflammation and atherosclerosis.6-8
