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Low levels of vitamin D among patients with systemic lupus erythematosus (SLE) were associated with greater disease activity and an increased likelihood of cardiovascular risk factors such as high blood pressure and elevated lipids, a large cohort study found.
Those who were in the lowest quartile of 25-hydroxyvitamin D [25(OH)D] had significantly higher scores on the Systemic Lupus Erythematosus Disease Activity Index 2000 (SLEDAI-2K) compared with those in the highest quartile (7 versus 4.7, P<0.001), according to Apinya Lertratanakul, MD, of Northwestern University in Chicago, and colleagues.
In addition, patients in the highest quartile of 25(OH)D were less likely to have hypertension (adjusted OR 0.49, 95% CI 0.31-0.77) or hyperlipidemia (adjusted OR 0.50, 95% CI 0.28-0.87), the researchers reported online in Arthritis Care & Research.
Vitamin D deficiency has been linked with cardiovascular risk factors and established cardiovascular disease (CVD) in large epidemiologic studies, and SLE patients typically have low levels of the vitamin.
"Vitamin D is also thought to have a significant role in several autoimmune diseases including SLE. The vitamin D receptor is expressed in cells involved in the innate and adaptive immune responses and this receptor is thought to have immunomodulatory, antiproliferative, antibacterial, and anti-inflammatory properties," the researchers noted.
Lertratanakul and colleagues previously identified relationships between cardiovascular risk factors and vitamin D levels in women with SLE, although body mass index appeared to at least partly be responsible for this association.
Therefore, to further examine potential links between vitamin D and cardiovascular risk factors and events, they analyzed data from 875 patients enrolled in the Systemic Lupus International Collaborating Clinics registry.
Almost 90% of the patients were women and more than half were white. Mean age was 39, and disease duration averaged 13.5 years. Mean SLEDAI-2K was 5.6.
Levels of 25(OH)D were low, at less than 30 ng/mL, in 72%, and the mean level was 23.8 ng/mL. The lowest quartile included patients whose levels ranged from 4 ng/mL to 13 ng/mL, while the top quartile had levels between 31 ng/mL and 91 ng/mL.
At the time of enrollment, more than two-thirds were taking corticosteroids, at a mean daily dose of 23.3 mg. Two-thirds also were taking hydroxychloroquine, and almost 40% were on immunosuppressants such as azathioprine.
Among those in the lowest quartile of 25(OH)D levels, almost 80% were on corticosteroids and 57% were taking an antimalarial, compared with 58% and 72% of those in the highest quartile, respectively.
In the overall cohort, 35% were hypertensive, 16% had hyperlipidemia, 6.5% were diabetic, and 26% had renal disease.
Unadjusted analysis found significant associations of low vitamin D levels with high blood pressure, elevated lipids, increased C-reactive protein (CRP), and high disease activity scores.
The associations remained significant after adjustment for age, sex, race, location, and body mass index in the highest versus lowest quartile for CRP (beta coefficient -0.44, 95% CI -0.85-minus 0.03) and SLEDAI-2K score (beta coefficient -2.37, 95% CI -3.25-minus 1.31).
Lertratanakul and colleagues then considered 25(OH)D levels and the 32 incident cardiovascular events that occurred during a mean follow-up period of almost 6 years.
They found no statistically significant association between 25(OH)D level and events such as myocardial infarction and angina.
"However, a trend is present that suggests those in higher quartiles are less likely (lower hazard ratios) to develop any CVD event when compared with the lowest quartile," they wrote. Those hazard ratios compared with the lowest quartile were:
- Quartile 2, HR 1.15 (95% CI 0.46-2.84)
- Quartile 3, HR 0.68 (95% CI 0.21-2.13)
- Quartile 4, HR 0.63 (95% CI 0.20-1.97)
Patients who had low 25(OH)D levels had higher SLEDAI-2K scores and more often were using corticosteroids. The relationship with steroids has previously been established, and in a mouse model, was associated with high 24-alpha-hydroxylase activity.
"Data on whether or not corticosteroids contribute to atherosclerosis is controversial, but some studies suggest that treating inflammation may decrease the progression of subclinical atherosclerosis," the researchers noted.
It's been less clear whether antimalarial treatment influences vitamin D levels. One study suggested that hydroxychloroquine interfered with the conversion of 25(OH)D to a more biologically active form in patients with sarcoidosis, but other studies saw no effect.
"Given these findings, the question remains whether supplementation with vitamin D should be more aggressively pursued in the management of SLE," the authors stated.
A limitation of the study was its inability to demonstrate causality. In addition, low levels of vitamin D may be a marker of a lack of exposure to sunshine among SLE patients, who often have photosensitivity, rather than reflecting established or subclinical cardiovascular disease.
Nonetheless, they concluded, "Specific attention to maintaining optimal 25(OH)D levels may be beneficial in the management of SLE."
The researchers reported receiving grants from the National Institutes of Health, Kirkland Scholars Award, the Driskill Foundation, and Pfizer.
- Reviewed by Zalman S. Agus, MD Emeritus Professor, Perelman School of Medicine at the University of Pennsylvania and Dorothy Caputo, MA, BSN, RN, Nurse Planner