Objective. To determine the relationship between serum vitamin D and markers of subclinical cardiovascular disease (CVD) in patients with SLE.Methods. We recruited SLE patients (≥4 ACR 1997 criteria) from outpatient clinics between January 2007 and January 2009. Vitamin D deficiency was defined as serum 25(OH)D <20 ng/ml measured by ELISA. Disease activity was measured using the SLEDAI-2K score. Aortic pulse wave velocity (aPWV) was measured using PulseTrace 3600 (Micromedical) and carotid plaque (CP) and intima–media thickness (IMT) assessed using B-mode Doppler US.Results. Seventy-five women with SLE were recruited with a median (interquartile range) disease duration of 16 (8–27) years. Patients with vitamin D deficiency had higher BMI (P = 0.014) and insulin resistance (P = 0.023) than those with 25(OH)D >20 ng/ml. Subjects with SLEDAI-2K ≥4 had lower 25(OH)D than those with SLEDAI-2K <4 (median 12.9 vs 20.3 ng/ml, P = 0.031). Aortic stiffness was significantly associated with serum 25(OH)D [log(aPWV) β (95% CI) −0.0217 (−0.038, −0.005), P = 0.010] independently of BMI, CVD risk factors and serum insulin. Adjustment for disease activity reduced the strength of the association. There was no association between 25(OH)D and CP or IMT.Conclusions. Vitamin D deficiency is associated with increased aortic stiffness in SLE, independent of CVD risk factors and insulin. Increased inflammatory disease activity may be the mechanism by which vitamin D deficiency mediates vascular stiffness in this patient group.

Our study highlights the need for clinical vigilance to identify modifiable risk factors in the clinical setting and in particular with male patients. The pattern of organ involvement did not differ in SLE patients with CHD events. However, the higher pre-event SDI, azathioprine exposure, and pattern of damage items (disease-related rather than therapy-related) in cases suggests that a persistent active lupus phenotype contributes to CHD risk. In this regard, corticosteroids and azathioprine may not control disease well enough to prevent CHD. Clinical trials are needed to determine whether classic risk factor modification will have a role in primary prevention of CHD in SLE patients and whether new therapies that control disease activity can better reduce CHD risk.

There is an urgent need for clinical trials to examine both the lipid-lowering and inflammatory hypotheses of atherosclerosis in rheumatoid arthritis and systemic lupus erythematosus. Novel targeted therapies in development may also have a major impact on future coronary heart disease risk in these conditions.

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Systemic lupus erythematosus (SLE) is a multisystem autoimmune disease with a strong female predilection. Cardiovascular morbidity and mortality is a frequent complication, particularly in females aged 35-44 years, in whom the risk of myocardial infarction is raised 50-fold. The mechanisms underlying this increased risk are not fully understood. Certain traditional risk factors, such as hypertension and diabetes mellitus, are more common in SLE patients than in the general population. These factors do not, however, completely account for the increased cardiovascular risk; factors such as renal impairment, increased homocysteine levels and early menopause probably have a role. In addition, several factors more specifically related to lupus are proposed to be of importance, including chronic inflammation, antiphospholipid antibodies and therapy, especially corticosteroid use. Thus, we need to be proactive in our approach to risk-factor management in SLE patients. Here, we propose that, like diabetes mellitus, SLE should be considered a coronary heart disease equivalent condition for baseline risk and that assessment of cardiovascular risk should be done routinely. In addition to lifestyle modifications, blood pressure and cholesterol levels should be stringently controlled, and administration of aspirin should be considered in selected patients. The increased use of certain interventions, such as statins, also needs to be more widely investigated in this population.

Patients with systemic lupus erythematosus (SLE) have accelerated cardiovascular disease and dysfunctional endothelial repair mechanisms. Myeloid angiogenic cells (MACs), derived from circulating monocytes, augment vascular repair by paracrine secretion of pro-angiogenic factors. We observed that SLE MACs are dysfunctional and secrete pro-inflammatory cytokines. We also found that the vitamin D receptor was transiently expressed during MAC differentiation and that in vitro, calcitriol increased differentiation of monocytes into MACs in both SLE and in a model using the prototypic SLE cytokine, interferon-alpha. The active form of vitamin D (calcitriol) restored the SLE MAC phenotype towards that of healthy subjects with reduced IL-6 secretion, and normalised surface marker expression. Calcitriol also augmented the angiogenic capacity of MACs via the down-regulation of CXCL-10. In SLE patients treated with cholecalciferol for 12 weeks, the improvement in endothelial function correlated with increase in serum 25(OH)D concentrations independently of disease activity. We also show that MACs were able to positively modulate eNOS expression in human endothelial cells in vitro, an effect further enhanced by calcitriol treatment of SLE MACs. The results demonstrate that vitamin D can positively modify endothelial repair mechanisms and thus endothelial function in a population with significant cardiovascular risk.

Objective. Patients with systemic lupus erythematosus (SLE) have a higher rate of premature death compared to the general population, suggesting a phenotype of premature senescence in SLE. Telomere length can be used to assess overall biologic aging. This study was undertaken to address the hypothesis that patients with SLE have reduced telomere length.Methods. Telomere length was measured crosssectionally in whole blood from SLE patients and agematched healthy female controls, using real-time quantitative polymerase chain reaction. SLE-related and cardiovascular risk factors were assessed.Results. We compared telomere length in 63 SLE patients and 63 matched controls with a median age of 50.8 years (interquartile range [IQR] 37-59 years) and 49.9 years (IQR 32-60 years), respectively. The median relative telomere length in SLE patients was 0.97 (IQR 0.47-1.57), compared to 1.53 (IQR 0.82-2.29) in controls (P ‫؍‬ 0.0008). We then extended our cohort to measure telomere length in 164 SLE patients. Shorter telomere length was associated with Ro antibodies (␤ ؎ SE ؊0.36 ؎ 0.16; P ‫؍‬ 0.023), and longer telomere length was associated with steroid therapy (0.29 ؎ 0.14; P ‫؍‬ 0.046). We also noted an association of longer telomere length with increasing body mass index (␤ ؎ SE 0.07 ؎ 0.01; P < 0.0001) and tobacco smoking (0.64 ؎ 0.26; P ‫؍‬ 0.016), as well as with the presence of carotid plaque (0.203 ؎ 0.177; P ‫؍‬ 0.032).Conclusion. Telomere length is shortened in SLE patients compared to controls and does not appear to be a reflection of disease activity or immune cell turnover. Subsets of patients such as those positive for Ro antibodies may be particularly susceptible to premature biologic aging. The predictive value of telomere length as a biomarker of future risk of damage/mortality in SLE requires longitudinal evaluation.Systemic lupus erythematosus (SLE) is associated with premature coronary heart disease and endothelial dysfunction (1). We have also noted a higher prevalence of subclinical atherosclerosis in SLE as assessed using high-resolution B-mode ultrasonography of the carotid wall (2). To date, the precise mechanisms underlying the early onset of atherosclerosis in SLE are unclear. However, the observation that atherosclerosis, a condition usually associated with aging, occurs at an earlier age in SLE patients leads to the hypothesis that premature biologic aging may occur in this population.Telomeres are unique structures that form the physical ends of chromosomes and are believed to play a protective role. Telomeres consist of tandem repeats of 6 basepairs ending with a 150-200-nucleotide G-rich 3Ј single-stranded overhang and associated proteins. Importantly, DNA polymerases are unable to replicate the lagging single strand of chromosomal ends, which results in telomere shortening with cell division; therefore, the The views expressed herein are those of the authors and not necessarily those of the NHS.

ObjectivesWe aimed to describe the rate and determinants of carotid plaque progression and the onset of clinical cardiovascular disease (CVD) in a UK SLE cohort.MethodsFemale patients with SLE of white British ancestry were recruited from clinics in the North-West of England and had a baseline clinical and CVD risk assessment including measurement of carotid intima–media thickness (CIMT) and plaque using B-mode Doppler ultrasound. Patients were followed up (>3.5 years after baseline visit) and had a repeat carotid Doppler to assess progression of plaque and CIMT. Clinical CVD events between visits were also noted.ResultsOf 200 patients with a baseline scan, 124 (62%) patients had a second assessment at a median (IQR) of 5.8 (5.2–6.3) years follow-up. New plaque developed in 32 (26%) (4.5% per annum) patients and plaque progression was observed in 52 (41%) patients. Factors associated with plaque progression were older age (OR 1.13; 95%  CI 1.06 to 1.20), anticardiolipin (OR 3.36; 1.27 to 10.40) and anti-Ro (OR 0.31; 0.11 to 0.86) antibodies. CVD events occurred in 7.2% over 5.8 years compared with 1.0% predicted using the Framingham risk score (p<0.001). Higher triglycerides (OR 3.6; 1.23 to 10.56), cyclophosphamide exposure ‘ever’ (OR 16.7; 1.46 to 63.5) and baseline Systemic Lupus International Collaborating Clinics damage index score (OR 9.62; 1.46 to 123) independently predicted future CVD events.ConclusionAccelerated atherosclerosis remains a major challenge in SLE disease management. A more comprehensive approach to CVD risk management taking into account disease factors such as severity and anticardiolipin antibody status may be necessary to improve CVD outcomes in this high-risk population.