Low physical activity is associated with proinflammatory high-density lipoprotein and increased subclinical atherosclerosis in women with systemic lupus erythematosus

Accumulating evidence has demonstrated that exercise and physical activity decreases cardiovascular morbidity and mortality in the general population (1, 2). Data from the Framingham Heart Study indicate that in the population aged 50 years or older, high physical activity is associated with an increased life expectancy of 3.7 years in men and 3.5 years in women (3). Moreover, low physical activity appears to be an independent predictor of coronary heart disease (4). Suggested mechanisms for the cardiac benefits of increased physical activity include enhanced glucose regulation and insulin sensitivity, fat redistribution/loss, improved endothelial function, decreased blood pressure and lipid levels, anti-thrombotic effects, and modification of novel cardiovascular risk factors (e.g. inflammatory cytokines) (5). While the cardiovascular benefits of exercise are well recognized, few studies have examined the relationship between physical activity and subclinical markers of atherosclerosis, such as carotid intima-media thickness (IMT) and plaque. A systematic review of cross-sectional, interventional, retrospective or prospective clinical studies demonstrated that physical inactivity is associated with increased IMT (5). However, the same study reported inconsistent associations between structured lifestyle interventions and progression of IMT. Other studies have found no relationship between physical activity and IMT (6, 7), while some have demonstrated an inverse association between physical activity in men, but not in women (8). A recent report from the Multi-Ethnic Study of Atherosclerosis found that walking pace was favorably associated with common carotid IMT; however, this association was no longer significant after controlling for traditional cardiac risk factors (9). Differences in physical activity assessment techniques may contribute to the disparities in these findings. In addition, the majority of studies have evaluated these relationships within the general population. The use of heterogeneous study cohorts may also contribute to result discrepancies. To address this issue, the present study examined the relationships between physical activity and subclinical atherosclerosis in patients with systemic lupus erythematosus (SLE), a patient population with a predilection for premature cardiovascular disease (10). Patients with SLE have an increased risk of coronary artery disease (10) and stroke (11) compared with the general population. Myocardial infarction (MI), the leading cause of death in SLE patients, occurs on average at 49 years of age, 20 years earlier than the general population (12). SLE patients also have significantly increased subclinical atherosclerosis compared with healthy controls, measured as carotid artery plaque or coronary artery calcification (13, 14). Furthermore, the rate of plaque progression over a short period (mean of 4.19 years) is significantly higher than in healthy controls (15). Research suggests that the pathogenesis of SLE-related enhanced atherosclerosis is multi-factorial, involving abnormalities of lipids, inflammation, and autoimmune reactions (16). With regard to lipids, recent studies have demonstrated that dysfunction of high-density lipoproteins (HDL) contributes to atherosclerotic plaque formation in SLE patients (17). Specifically, dysfunctional, proinflammatory HDL (piHDL) is associated with increased IMT and plaque on carotid ultrasound (18). To our knowledge, no studies have assessed whether factors such as diet and lifestyle interventions may improve HDL function in SLE patients. However, a study of obese men exposed to a three-week intensive diet and exercise intervention found a substantial decrease in piHDL levels after the intervention (19). The purpose of the present study was to investigate the relationship between physical activity and subclinical atherosclerosis in patients with SLE. A secondary goal was to examine the relationship between physical activity and piHDL in patients with SLE.