Discovering ways to reduce cardiovascular disease morbidity and mortality is a major focus of study in SLE research. The results reported herein underscore the potential importance of exercise and physical activity in modifying subclinical markers of atherosclerosis in patients with SLE. In bivariate analysis, decreased physical activity as assessed by the SF-36 was associated with increased carotid plaque and IMT. Moreover, decreased physical activity as assessed by self-reported total METs per week was associated with presence of piHDL in SLE patients.
After accounting for potentially confounding variables, decreased physical activity (<225 METs per week) remained significantly associated with piHDL in patients with SLE. We have previously reported that in patients with SLE, piHDL is significantly associated with carotid plaque and IMT in multivariate analyses (18
). Taken together, these results suggest that exercise may moderate the relationship between SLE and cardiovascular disease development, possibly by decreasing inflammatory mediators, such as piHDL. Indeed, several studies have demonstrated that regular exercise exerts anti-inflammatory effects (31
), and a diet and exercise intervention has also been shown to improve anti-inflammatory HDL function (19
). Because inflammation has been implicated at several points in the carotid atherosclerotic process (33
), exercise may slow carotid atherogenesis. Although limited clinical data exists to support this hypothesis, experimental studies have found that exercise not only regresses atherosclerotic plaque, but also improves plaque stability (34
In contrast to piHDL, the associations between physical activity as assessed by the SF-36 and IMT and plaque were no longer significant after controlling for potentially confounding variables. These results are consistent with recent findings from the MESA group (9
). A plausible explanation for these results is that physical activity may have a greater impact on IMT progression versus absolute IMT levels. In support of this notion, Sato and colleagues (35
) found that walking distance was inversely associated with IMT progression over six months in patients with coronary heart disease. Similarly, The Women’s Healthy Lifestyle Project (WHLP) trial demonstrated that a diet and exercise intervention slowed IMT progression among peri- and post-menopausal women over four years (36
). Given the cross-sectional nature of the current study, the effects of physical activity on IMT and plaque progression could not be determined.
The present study has important strengths and limitations. The major strengths include using of a specific patient cohort and controlling for confounding variables, such as markers of SLE disease activity and damage and traditional cardiac risk factors. Moreover, the physical activity measurements not only assessed the frequency and duration of exercise, but also considered the type and intensity of each activity, which together may more reliably capture actual metabolic output. However, the assessment of physical activity is based on participant recall. Self-report surveys are subject to both recall and social desirability bias (37
). A second shortcoming is that causality cannot be determined. It is possible that advanced subclinical atherosclerosis decreases the ability to perform exercise.
Another strength of the present study is the use of an ethnically diverse patient cohort. While the present study was not powered to evaluate differences between specific racial groups, , we found no significant race/ethnicity differences in the associations between physical activity and subclinical atherosclerosis.. However, we did find that African American patients had significantly higher IMT (0.66 (0.13)) compared with non-African American patients (0.53 (0.13)), t = 5.1, p <0.0001).
To address the possibility that clinical activity of SLE is also associated with decreased physical activity, we investigated the relationship between exercise and disease activity and damage assessment measures and found no significant correlations. This negative finding could signify either that the instrument is flawed or that there is not a clinically significant association between exercise and the activity of SLE. There are no validated measures of SLE severity, to our knowledge; thus, this particular association could not be evaluated.
An additional limitation of this study is selection bias. Because the study population consists predominantly of patients receiving outpatient care for their SLE, the findings may not be generalizable to inpatient populations. A final limitation is the use of surrogate markers of cardiovascular disease. Although IMT and plaque are accepted, validated surrogate markers of carotid atherosclerosis (38
), piHDL is a novel biomarker linked to cardiovascular disease and is still under study. To adequately assess the impact of physical activity on cardiovascular disease and to implement effective strategies for reducing disease burden, future prospective studies are needed to examine the impact of exercise on cardiac events in SLE patients.
These limitations notwithstanding, to our knowledge the present study is the first to evaluate the relationship between physical activity and subclinical atherosclerosis in patients with SLE. While multiple factors affect atherogenesis in patients with SLE, physical activity appears to play a role in reducing inflammation associated with cardiovascular disease. Through encouraging patients with SLE to engage in physical activity, physicians may improve health outcomes in this vulnerable patient population.