A Heart In Danger

Many patients expressed an interest in the outcome of the study and appreciated being able to contribute to increasing knowledge of their disease. In part for this reason, each study subject received reprints of papers describing the results of the studies in which they participated. Similarly, doctors were grateful for additional information obtained at no cost to the patient which, in some cases, prompted changes in therapy. They, too, valued the opportunity to be part of a scientific study.

Correlation between Lupus and Atherosclerosis

Patients underwent carotid ultrasonography and echocardiography. (See Figure 1, page 14.) They were assessed for traditional cardiovascular disease risk factors, SLE disease activity and damage, treatment history, autoantibody profile, and the presence of inflammatory mediators. Each SLE patient was individually matched to a control subject based on age, gender, race, and blood pressure status. Control subjects were drawn from individuals participating in an NIH-funded study at our institution that used a similar imaging protocol to examine the impact of job strain, aging, and hypertension on preclinical cardiovascular disease. Because a large control population had already been evaluated, we were able to complete our study more quickly and leverage NIH funding for both projects.

When we analyzed the entire population (lupus and controls), we found that only the presence of lupus, age, and (equivocally) cholesterol level were independent risk factors for atherosclerosis.¹¹ Atherosclerosis was significantly increased in lupus (carotid plaque in 37.1% of SLE patients versus 15.2% of controls), most strikingly in younger individuals. (See Figure 2, page 14.) This increase was not attributable to traditional cardiovascular risk factors or corticosteroid therapy. In fact, SLE was the strongest independent correlate of carotid atherosclerosis among patients and control subjects comparable with regard to traditional risk factors.

What were the unique characteristics of SLE patients with carotid plaque? Clinical features and autoantibody specificities were different in SLE patients with and without plaque. We saw two distinct disease patterns: one characterized by prolonged, smoldering disease with high damage scores, limited production of autoantibodies, and more prevalent atherosclerosis; the other with a wider spectrum of autoantibody specificities, a history of more aggressive immunosuppressive therapy, and less prevalent plaque.¹¹

We found that atherosclerosis was associated with longer disease duration, higher damage score, and less aggressive immunosuppressive therapy. This finding argues that chronic inflammation is atherogenic in SLE. While circulating markers of inflammation were high in many SLE patients, there were no significant differences in levels of these markers between patients with and without plaque.

Whereas C-reactive protein, sICAM, and sCD40L are associated with increased risk of cardiovascular events in the general population, these markers appear to lose discriminatory power for predicting adverse cardiovascular outcome in conditions like lupus, where inflammatory molecule levels are elevated compared to the general population. Not surprisingly, levels of markers of inflammation were abnormal in many patients with SLE, and longitudinal, rather than cross-sectional, studies are more likely to define their relation to the development and progression of atherosclerosis.

RA and Cardiovascular Disease

Based on our findings in lupus patients and evidence that patients with RA also often die prematurely from cardiovascular disease, we thought it would be worthwhile to apply our protocol to examine the prevalence and clinical and biological features of preclinical atherosclerosis in RA.