Vitamin D Linked With Worse Lupus
Published: Jan 30, 2014
Jan 30, 2014
Walsh, Staff Writer, MedPage Today
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
Patients with systemic lupus erythematosus who have
higher 25(OH)D levels are more likely to have lower disease
Patients with lupus who have higher 25(OH)D levels are
also less likely to have hypertension and hyperlipidemia.
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.
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
Lertratanakul, MD, of Northwestern University in Chicago,
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),
reported online in Arthritis Care & Research.
D deficiency has been linked with
risk factors and
cardiovascular disease (CVD) in large epidemiologic
studies, and SLE patients typically have low levels of the 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
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
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
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.
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.
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.
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.
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
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.
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)
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
whether or not corticosteroids contribute to atherosclerosis is
controversial, but some studies suggest that treating inflammation
may decrease the progression of subclinical atherosclerosis," the
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
saw no effect.
these findings, the question remains whether supplementation with
vitamin D should be more aggressively pursued in the management of
SLE," the authors stated.
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
Nonetheless, they concluded, "Specific attention to maintaining
optimal 25(OH)D levels may be beneficial in the management of SLE."
researchers reported receiving grants from the National Institutes
of Health, Kirkland Scholars Award, the Driskill Foundation, and