Impaired endothelial function in SLE patients without cardiovascular diseases
Patients with systemic lupus erythematosus (SLE) without cardiovascular conditions have impaired endothelial function, a new case-controlled study has shown. Factors that contribute to endothelial dysfunction include renal diseases and diastolic hypertension.
“In this case-control study of SLE patients free of clinical cardiovascular disease and stringently-matched [healthy controls], both with identical and on average, normal [carotid intima-media thickness (cIMT)], we observed worse endothelial function as assessed by [brachial artery endothelium-dependent flow-mediated dilation (baED-FMD)] in SLE,” said researchers.
BaED-FMD was significantly lower in the 71 adult SLE patients (mean age 39.21±13.4 years; 91.5 percent female; 3.72±2.8 percent) than in the 71 healthy controls (HCs; mean age 40.37±12.9 years; 91.5 percent female; 4.63±3.1 percent; p=0.032). [Sci Rep 2017;7:7320]
Serum concentrations of adipocyte fatty acid binding protein (aFABP) was also significantly higher in SLE patients than in HCs (14.82±3.3 vs 13.69±4.6 ng/mL; p=0.015). In contrast, there was no significant difference in cIMT (0.56±0.1 vs 0.56±0.1; p=0.872).
A meta-analysis of 25 studies that compared the baED-FMD between SLE patients (n=1,313) and HCs (n=1,012) showed that the effect size of aggregated baED-FMD was significantly lower in SLE patients than in HCs (standardized mean difference [SMD], -1.077; 95 percent CI, -1.497 to -0.657; p<0.001).
After removing 12 low-quality studies according to the Newcastle-Ottawa scale scores, SLE patients still had significantly lower baED-FMD than HCs (SMD, -0.926; -1.414 to -0.438; p<0.001).
“Because of the modest sample size with potential lack of statistical power in the current case-control studies and those in the literature, we attempted to increase the statistical power by aggregating our data with those available in the literature using meta-analysis,” explained researchers.
Diabetes mellitus (p=0.04747), higher diastolic blood pressure (p=0.04419), aspirin use (p=0.0119) and renal involvement (p=0.02721) in SLE patients were all associated with higher baED-FMD differences between SLE patients and HCs, according to a mixed-model meta-regression analysis.
“Surprisingly, aspirin use was found to be associated with poorer endothelial function in patients with SLE in our meta-regression analysis. Although counter-intuitive, this may indicate confounding by indication as aspirin may be prescribed for those patients perceived to have higher vascular risk,” according to researchers.
Adult patients who fulfilled the SLE criteria of the American College of Rheumatology were recruited from the Lupus Clinic of the National University Hospital in Singapore. Those with acute illness at recruitment, and who were positive for antiphospholipid antibodies and lupus anticoagulants were excluded.
Peripheral venous blood samples were collected from the participants and were analysed for anti-double stranded DNA, C3, C4, aFABP, high-density lipoprotein cholesterol and total cholesterol levels. Ultrasound was used to determine baED-FMD.
The findings of the meta-regression showed that SLE patients “with [diabetes mellitus], diastolic hypertension and renal lupus who may be at greater risk of developing endothelial dysfunction, a precursor of frank atherosclerosis,” said researchers.
“As such, lupus patients with [these] comorbidities … should deserve more judicious and aggressive monitoring for unfavourable cardiovascular outcomes,” they added.