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Abstract
Background Endothelium-dependent flow-mediated dilation (ED-FMD), a biophysical marker of endothelial dysfunction, is apparently impaired in patients with systemic lupus erythematosus (SLE). However, such observation is inconsistent because of the lack of standardization of the methodology of ED-FMD measurement and inclusion of patients with different comorbidities amongst different studies.
Objectives Firstly, we evaluated if ED-FMD is indeed impaired in SLE patients naïve of cardiovascular disease and its traditional risk factors. Secondly, we aimed to determine if the putative contribution of SLE to endothelial dysfunction is in fact confounded by demographic-, disease- and treatment-related factors.
Methods We assessed and compared the brachial artery ED-FMD (baED-FMD) using the Prosound Alpha-10 ultrasound system® between SLE patients without cardiovascular disease and cardiovascular risk factors and healthy controls (HC) matched for age, gender and body mass index (BMI). Exclusions were pregnancy, a history hypertension, diabetes mellitus, chronic kidney disease, cardiovascular and cerebrovascular diseases, and statin therapy. SLE-related disease activity and organ damage in the SLE patients were assessed using SELENA-SLEDAI and SLICC/ACR DI, respectively. With inclusion of our own data from this case-control study, we performed a comprehensive meta-analysis of case-control studies which compared baED-FMD between SLE patients and HC by determining the effect size of baED-FMD as standard mean difference (SMD). Demographic and clinical factors associated with the effect size were explored by mixed-model meta-regression.
Results Seventy one SLE patients and 71 HC were studied, and there were 6 men in each group. The mean±SD age and BMI of SLE patients and HC were 39.21±13.4 and 40.37±12.9 years, and 22.54±5.1 and 22.86±4.2 kg/m2, respectively. In SLE patients, the mean±SD daily prednisolone dose, SELENA-SLEDAI and SLICC/ACR DI were 13.43±14.4mg, 6.52±5.4 and 0.17±0.4, respectively. SLE patients had significantly lower baED-FMD than HC (3.72±2.8% vs 4.63±3.1%, p=0.032). In the SLE group, no association between baED-FMD and age, gender, BMI, blood pressure, duration of SLE, serum C3, C4 and anti-dsDNA levels, SELENA-SLEDAI, SLICC/ACR DI and daily prednisolone dose was found. Similarly, no association was noted between baED-FMD and age, gender and BMI in the HC group. Meta-analysis of 25 case-control studies involving 1,313 SLE patients and 1,012 HC with the random effects model revealed significantly lower baED-FMD in SLE patients compared to HC (SMD -1.077, p<0.001) (see Fig for forest plot). The presence of diabetes mellitus (p=0.04747), higher diastolic blood pressure (p=0.04419) and renal involvement (p=0.02721) were associated with more discrepant baED-FMD between both groups.
Conclusions SLE patients naïve of cardiovascular disease and its traditional risk factors have impaired endothelial function. While SLE-related disease activity and organ damage are not apparently related to endothelial dysfunction, the presence of diabetes mellitus, renal disease and diastolic hypertension are potential contributors to endothelial dysfunction in SLE patients.
Disclosure of Interest None declared