I read with great interest the article by Hirata et al, showing altered coronary vasomotor function in young patients with systemic lupus erythematosus (SLE) (1). A few points warrant further explanation by the authors.
Hirata and colleagues excluded some possible confounding factors that might influence endothelial function, such as diabetes mellitus, hypertension, and hypercholesterolemia. Although the authors regarded the menstrual cycle to be a confounding factor in vascular reactivity, they did not consider cyclosporin A as a confounding factor that may affect vascular response to adenosine triphosphate. Considering the fact that 26% of the 19 patients with SLE were given cyclosporin A, it is tempting to speculate that the study results might have been affected by cyclosporin A therapy. Although the authors emphasized the deleterious effect of cyclosporin A on endothelial function, they did not discuss this as a limitation factor.
As is well known, calcineurin inhibitors such as cyclosporin A have been shown to interact with vasoactive metabolites, causing arterial hypertension and arteriosclerosis (2, 3). Cyclosporin A is known to impair vascular vasodilatation and may induce vasoconstriction (4, 5). Cyclosporin A therapy may alter nitric oxide regulation, leading to an impaired vasodilatory response (6). Moreover, the deleterious effect of cyclosporin A on endothelial cells may increase over time (7). Therefore, the authors should have mentioned the duration of cyclosporin A therapy.
Another point regarding this study that must be emphasized is the lack of a disease control group. The presence of a disease control group might have helped us to determine whether or not altered coronary vasomotor function is specific for young patients with SLE or is secondary to nonspecific inflammatory stimuli.
Recent studies have shown that as SLE progresses, the type of coronary involvement may change from nonocclusive coronary events or coronary thrombosis to vascular wall inflammation and finally coronary atherosclerosis (8, 9). My colleagues and I conducted a comprehensive review of the English literature from 1975 to 2006, to analyze data on acute myocardial infarction (MI) in patients with SLE in whom acute MI had developed at age 35 years or earlier (9). The lag time between the onset of the SLE manifestations and the occurrence of acute MI was shorter in patients with normal coronary arteries or coronary thrombosis than in those with coronary arteritis/aneurysm and coronary atherosclerosis. Thus, it can be speculated that altered coronary vasomotor function in a subgroup of young patients with SLE may result in coronary events, including acute MI, without atherosclerosis and coronary vasculitis or aneurysm.
Finally, traditional risk factors as well as other risk factors for coronary heart disease could be managed through adoption of some preventive measures.