Subclinical Atherosclerosis In Systemic Sclerosis

BackgroundSystemic sclerosis (SSc) is a chronic disease of unknown etiology, characterized by enhanced fibrosis, and microvascular abnormalities. During the past several decades, the death rates due to cardiovascular disease or cerebrovascular disease in SSc patients substantially increased and are currently responsible for20-30%of mortality. Various autoimmune rheumatic diseases such as rheumatoid arthritis and systemic lupus erythematosus accelerate atherosclerosis. Although microvascular disease is a hallmark of SSc, increasing evidence shows that atherosclerosis is also present in SSc, and the rate of atherosclerosis may be increased in SSc patients compared to healthy individuals. Intima-media thickness (IMT) of the carotid artery, coronary flow reserve (CFR), flow mediated dilation (FMD), pulse wave velocity (PWV), and ankle brachial pressure index (ABI) can be used as a marker of early atherosclerosis.ObjectivesTo investigate the prevalence of clinical and subclinical atherosclerosis in systemic sclerosis (SSc) patients and its associated features and mechanisms.Methods1. SSc patients who met the American College of Rheumatology criteria for the disease and healthy controls, were investigated for previous cardiovascular events, cardiovascular risk factors, and features of subclinical atherosclerosis, that is PWV, ABI, and IMT for some patients. Their blood samples and clinical information were collected.2. Measure lipoprotein-associated phospholipase A2(Lp-PLA2), Interleukin-6(IL-6), oxidized low-density lipoprotein antibody(oxLDL-Ab) by method of ELISA, and investigate the relationship between them and subclinical atherosclerosis.3. Measure Asymmetric Dimethylarginine (ADMA) level by HPLC-MS/MS, and investigate the relationship between ADMA and subclinical atherosclerosis.Results1.110SSc patients, including51dcSSc and59lcSSc patients, and99healthy controls matched for sex, age, and traditional cardiovascular risk factors were investigated. PWV was significantly higher in SSc patients than healthy controls (P<0.001). 2. Compared with healthy controls, ADMA (P<0.001), oxLDL-Ab (P<0.001), Lp-PLA2(P=0.005) and IL-6(P<0.001) level in SSc patients were significantly higher.3. Age (P<0.001), BMI (P=0.014), obesity (P=0.021), hypertension (P=0.003) and PAH (P=0.037) in elevated PWV group were significantly higher than those in normal PWV group.4. Lp-PLA2(P=0.003) and Arg (P<0.001) level in elevated PWV group were significantly higher than those in normal PWV group.5. Age and Lp-PLA2were independent risk factor of elevated PWV in SSc patients.6. In all subjects, age, SBP and SSc were independent factors associated with PWV level.Conclusion1. Our study confirms an increased prevalence of subclinical atherosclerosis in SSc patients compared with sex-, age-, and traditional cardiovascular risk factor-matched healthy controls.2. In SSc patients Lp-PLA2associates with subclinical atherosclerosis, and can be used as a predictor of elevated PWV.