Background/Purpose

SLE patients have an increased risk of cardiovascular disease (CVD).  Vitamin D deficiency has been associated with both CVD risk factors and subclinical CVD in lupus patients. There is currently no evidence that vitamin D therapy can reduce cardiovascular risk in SLE.  Patients with SLE have endothelial dysfunction and restoration of vascular function may reduce CVD risk.  We conducted an experimental study to determine the effect of vitamin D on endothelial function. 

Methods

Clinically stable female SLE patients were recruited from a single site (Central Manchester).  Serum 25(OH)D was measured by LC-MS and patients were classed as deficient (<20ng/ml) or replete (>30ng/ml).  Patients were treated by their general practitioner according to local protocols (typically 400,000IU cholecalciferol over 10 days then 20,000IU weekly).  Replete patients were not treated and acted as controls.  Patients were assessed at baseline and after 3 months.  Endothelial function was measured using flow-mediated dilatation (FMD) and expressed as endothelium dependent/endothelium independent (ED/EI) dilatation.  Arterial stiffness (pulse-wave velocity, aPWV) was measured using Arteriograph.  Cytokines were measured by ELISA.  Disease activity was measured using the SLEDAI-2K and BILAG-2004 indices.

Results

We recruited n=22 vitamin D deficient patients and n=18 replete patients (median 25(OH)D 13.1 and 34.5ng/ml respectively).  All patients were female and 36/40 (90%) had ≥4 ACR criteria.  Deficient patients were younger (47.0 vs 57.9 years, p=0.007) and more likely to have a history of lupus nephritis (31.8% vs 5.6%, p=0.039) or require steroid (45.4% vs 5.6%, p=0.005) or immunosuppressant therapy (54.5% vs 11.1%, p=0.004).

FMD was strongly influenced by age and the baseline brachial arterial diameter.  ED/EI in contrast was not related to either age or arterial diameter.

Serum 25(OH)D significantly increased in the deficient/treated group compared to the replete/untreated (median change 28.6 vs -0.62ng/ml, p<0.0001) and PTH significantly decreased (-8.6 vs 2.5pg/ml, p=0.039).  There was no change in aPWV, disease activity, serum complement or cytokines (IL-6, TNFα, IP-10 or BAFF).

Change in 25(OH)D was strongly correlated with the change in ED/EI (r=0.650, p=0.006) in the treated group but not the replete group (r=-0.462, p=0.115) (figure).  No association was seen between change in ED/EI and calcium, PTH or blood pressure.  In an ordered logistic regression model the change in ED/EI remained associated with change in 25(OH)D after adjustment for age (OR 1.12 [1.02,1.24], p=0.017). 

Conclusion

Increase in serum 25(OH)D significantly improved endothelial function over a short time period.  This improvement was not due to changes in blood pressure or lupus disease activity.  Vitamin D may be a novelvasculoprotective agent for SLE patients even in the absence of active disease.