CLINICAL RESEARCH STUDY

Vitamin D, Metabolic Dyslipidemia, and Metabolic

Syndrome in Rheumatoid Arthritis
Joshua F. Baker, MD, MSCE,a Nehal N. Mehta, MD, MSCE,b,c Daniel G. Baker, MD,d Gary Toedter, PhD,e
Justine Shults, PhD,b Joan Marie Von Feldt, MD, MSEd,f Mary B. Leonard, MD, MSCEb,g
a

Department of Medicine, Division of Rheumatology, bCenter for Clinical Epidemiology and Biostatistics, and cDepartment of
Medicine, Division of Cardiovascular Medicine, University of Pennsylvania, Philadelphia; dClinical Immunology and eBiomarker,
Centocor Research and Development, Malvern, Pa; fDivision of Rheumatology, Veterans Affairs Medical Center, Philadelphia, Pa;
g
Childrens Hospital of Philadelphia, University of Pennsylvania School of Medicine, Philadelphia.

ABSTRACT
PURPOSE: Vitamin D deficiency is a potential risk factor for cardiometabolic disease. We investigated the
associations between vitamin D and dyslipidemia and the metabolic syndrome in patients with rheumatoid
arthritis, a group at high risk for cardiovascular disease.
METHODS: Serum 25(OH)vitamin D and lipoprotein levels were measured at baseline in a random sample of
499 participants, ages 18-85 years, enrolled in a randomized trial of golimumab (GOlimumab Before Employing methotrexate as the First-line Option in the treatment of Rheumatoid arthritis of Early onset or GO-BEFORE
Trial). Participants had rheumatoid arthritis with active disease, and were nave to methotrexate and biologic
therapies. Multivariable linear regression was performed to assess associations between vitamin D levels and
lipoprotein fractions. Multivariable logistic regression was performed to determine the odds of hyperlipidemia
and the metabolic syndrome in participants with vitamin D deficiency (20 ng/mL).
RESULTS: In multivariable linear regression, vitamin D levels (per 10 ng/mL) were associated inversely
with low-density lipoprotein (: 0.029 [0.049, 0.0091], P .004) and triglyceride (: 0.094
[0.15, 0.039] P .001) levels, adjusted for demographic, cardiovascular, and disease-specific variables. Vitamin D and high-density lipoprotein levels were not associated in univariate or multivariate
analyses. Vitamin D deficiency was associated independently with an increased odds of hyperlipidemia
(odds ratio 1.72; 95% confidence interval, 1.10-2.45; P .014) and metabolic syndrome (odds ratio 3.45;
95% confidence interval, 1.75-6.80; P .001) in adjusted models.
CONCLUSIONS: In conclusion, vitamin D deficiency was associated with the metabolic syndrome and
dyslipidemia in rheumatoid arthritis, suggesting a potential role in cardiovascular disease risk. Large-scale,
prospective studies are needed to determine if vitamin D supplementation improves lipoprotein levels and
reduces cardiovascular risk in rheumatoid arthritis.
2012 Elsevier Inc. All rights reserved. The American Journal of Medicine (2012) 125,
1036.e9-1036.e15
KEYWORDS: Lipoproteins; Metabolic syndrome; Rheumatoid arthritis; Triglycerides; Vitamin D

Funding: None.
Conflict of Interest: None. Gary Toedter and Daniel Baker are employees of Janssen Biotech, Inc.
Authorship: All authors had access to the data and a direct role in
writing the manuscript.
Requests for reprints should be addressed to Joshua F. Baker, MD,
MSCE, Division of Rheumatology, Department of Medicine, Hospital of
the University of Pennsylvania, 8 Penn Tower Building, One Convention
Center Blvd., Philadelphia, PA 19104.
E-mail address: bakerjo@uphs.upenn.edu

0002-9343/$ -see front matter 2012 Elsevier Inc. All rights reserved.
http://dx.doi.org/10.1016/j.amjmed.2012.01.025

Recent studies have reported that vitamin D deficiency is

associated with an increased risk of cardiovascular disease
in the general population.1 Potential mechanisms include
up-regulation of the renin-angiotensin-aldosterone system,
adverse effects on vascular endothelial and smooth muscle
function,2 and impaired glucose tolerance in vitamin D-deficient states.3 Vitamin D deficiency has been linked to
dyslipidemia and metabolic syndrome.4,5
Rheumatoid arthritis is associated with an increased
risk of dyslipidemia,6 metabolic syndrome,7 and cardio-

1036.e10

The American Journal of Medicine, Vol 125, No 10, October 2012

vascular disease.8 Vitamin D deficiency also is common

I125 radioimmunoassay method considered more sensitive and
9
in rheumatoid arthritis. How vitamin D deficiency may
specific than other radioimmunoassays without any significant
relate to the cardiometabolic abnormalities often seen in
positive or negative bias.11,12 The antibody has equal affinity
chronic inflammatory diseases such as rheumatoid arthrifor both vitamin D2 and vitamin D3, and the assay has comtis is not known.
parable measurement characteristics to liquid chromatography,
To our knowledge, the associtandem mass spectrometry, the gold
ations between vitamin D defistandard.11,13 Vitamin D deficiency
ciency, dyslipidemia, and metawas defined as 25(OH) vitamin D
CLINICAL SIGNIFICANCE
bolic syndrome have not been
20 ng/mL based on the recent Inexamined in systemic inflammastitute of Medicine report.14,15
Vitamin D deficiency is associated with
tory diseases such as rheumatoid
Wang et al16 have previously demgreater odds of prevalent hyperlipidemia
arthritis. The objective of this
onstrated that a cutoff of 15-20
independent of demographic, disease sestudy was to examine the associang/mL best defines risk categories
verity, and cardiovascular risk factors
tions among vitamin D levels,
for incident cardiovascular events in
among subjects with rheumatoid arthritis.
low-density lipoprotein (LDL),
Framingham offspring.
triglyceride (TG), and high-denIt is accepted that 25(OH) vi Low vitamin D levels also are indepensity lipoprotein (HDL) levels, and
tamin
D is the most appropriate
dently associated with greater odds of
the metabolic syndrome at basemeasure
of adequate vitamin D
prevalent metabolic syndrome.
line in rheumatoid arthritis particistores,17 because 1,25(OH) vitapants in the randomized controlled
min D levels are often preserved
trial of golimumab (GOlimumab
in the case of deficiency. FurBefore Employing methotrexate as the First-line Option in
thermore, recent literature suggests that 25(OH) vitamin
the treatment of Rheumatoid arthritis of Early onset or
D is substrate for intracellular synthesis of 1,25 vitamin
GO-BEFORE Trial). Assessment of these associations will
D in monocytes, macrophages, and other immune cells
provide greater insight into potentially modifiable risk facthat may be important in the development of
tors for metabolic syndrome and cardiovascular disease in
atherosclerosis.18
these high-risk patients.
Five possible geographic regions were assigned to participants based on the country of measurement (North
America, South America, Europe, Southeast Asia, and AusMETHODS
tralia). Season of vitamin D measurement was determined
Study Setting
using the hemisphere of the country and the month of
measurement.
Golimumab is a fully human monoclonal antibody to tumor
necrosis factor alpha. This study is ancillary to the GOOutcome Measures
BEFORE trial (Clintrials.gov identifier NCT00361335) that
As part of the original trial, fasting whole blood samples
included 637 rheumatoid arthritis patients. The study comwere sent to Quintiles Central Laboratories (Quintiles, Durpared the efficacy of methotrexate or golimumab alone to
ham, NC) for laboratory studies including a standard clinicombination therapy with methotrexate and golimumab in
cal lipid profile (TG, total cholesterol, HDL, and calculated
methotrexate and biologic therapy nave subjects. The trial
10
LDL). This laboratory service is certified for standardizaresults have been previously published.
tion of lipid analyses by the Standardization Program of the
Subjects 18 years or older were recruited multinationally
Center for Disease Control and Prevention and the National
from 90 centers. Inclusion criteria included meeting AmerHeart, Lung and Blood Institute. Hyperlipidemia was deican College of Rheumatology criteria for rheumatoid arfined as: 1) a TG level of 150 mg/dL; 2) an LDL of 160
thritis for at least 3 months and active disease defined by the
mg/dL; or 3) an HDL 50 mg/dL for women or 40 mg/dL
presence of at least 4 swollen and tender joints. Participants
for men, as previously described.19,20 Participants that rewere required to have at least 2 of the following: an elevated
ported lipid-lowering therapy also were considered to have
erythrocyte sedimentation rate or C-reactive protein; erohyperlipidemia.
sions on radiographs; an elevated cyclic citrullinated pepMetabolic syndrome was defined using the International
tide antibody titer or rheumatoid factor; or morning stiffness
Diabetes
Federation definition and the Adult Treatment
for 30 minutes. Using a random-number generator, we
Panel
III
definition.21 Comparable results were obtained
selected 499 participants (80% sample) from the original
using both definitions; therefore, the International Diabetes
trial and determined vitamin D levels at baseline, before the
Federation criteria are presented throughout. Measures of
initiation of therapy.
waist circumference were not available, thus metabolic synVitamin D Measurement
drome was considered present in an obese patient (body
Vitamin D levels were measured on baseline samples stored at
mass index [BMI] 30) with any 2 of the following: an
70C (Heartland Assays, Ames, IA). This laboratory uses a
elevated TG level 150 mg/dL; an HDL level 40 mg/dL
DiaSorin (DiaSorin Inc., Stillwater, Minn) 25(OH)vitamin D
in males and 50 mg/dL in females; a fasting glucose 100

Baker et al

Vitamin D and Dyslipidemia in Rheumatoid Arthritis

mg/dL (or previous diagnosis of diabetes); or a previous

diagnosis of hypertension or treatment with medications for
hypertension. We also evaluated metabolic syndrome as a
categorical outcome in ordinal logistic regression using the
components of the syndrome. Because there were only 3
subjects with all 5 components, the subjects with 4 or 5
components were combined.
Potential confounders included estimated glomerular filtration rate (GFR) generated using the Modification of Diet
in Renal Disease Study Equation.22 Nonlaboratory variables
evaluated included patient-reported regular aerobic exercise
(yes/no), a history of smoking (ever/never), presence of
metabolic syndrome, diabetes, and hypertension, and the
use of steroids at baseline. Disease activity was measured
using the disease activity score 28 (DAS28), which incorporated the erythrocyte sedimentation rate. Results from a
Health Assessment Questionnaire also were available.

Statistical Analysis
Data were analyzed using Stata version 11 software (StataCorp LP, College Station, Tex). The association between
vitamin D levels and continuous variables were assessed
using Spearmans rank (for skewed correlations). Mean and
median lipoprotein levels were tested for equality across
categorical variables using t-tests (or rank-sum tests for
nonparametric data) and analysis of variance.
A primary goal of this study was to evaluate the associations between vitamin D level (as a continuous and categorical variable) and baseline lipoprotein and TG levels
using multivariable linear and logistic regression analysis.
In initial multivariable linear regression analysis, LDL, TG,
HDL, and vitamin D levels were evaluated as continuous
natural log-transformed variables. Possible confounding
cardiovascular and disease-specific covariables were considered in development of the model as described. Confounding was considered present if the strength of association changed by more than 15% when the variable of
interest was included in the model.23 Multivariable logistic
regression models using categorical variables for the association between vitamin D deficiency (20 ng/mL) and the
presence of hyperlipidemia and presence of metabolic syndrome were used to facilitate clinical interpretation of the
study findings. Ordinal logistic regression also was used to
evaluate the association of vitamin D deficiency and the
number of components of the metabolic syndrome (1, 2, 3,
and 4-5). Goodness of fit for regression models was evaluated using Hosmer-Lemeshow goodness-of-fit tests for logistic regression models and by graphing residuals and
using Wilk tests for linear regression models. The Brant test
was used to test the proportional odds assumption in the
ordinal regression models.

RESULTS
Baseline Characteristics of Participants
Subject characteristics at enrollment are summarized in Table 1 in the entire sample and according to vitamin D

1036.e11

deficiency category. Very few participants reported use of

vitamin D supplements at baseline (2.2%). The median
vitamin D level (interquartile range) among study participants was 20.7 (14.5-28.2) ng/mL, with 48% of participants
defined as deficient (20 ng/mL). Patients with vitamin D
deficiency were older, had a higher BMI, and were more
likely to be female. Deficient patients also were significantly
more likely to have diabetes, hypertension, and metabolic
syndrome. Overall, 12.4% of participants met criteria for the
diagnosis of metabolic syndrome and 49.4% were defined as
having hyperlipidemia. Thirty-one patients (6.2%) were on
lipid-lowering therapy.

Association of Vitamin D and Lipoproteins

Median LDL and TG levels varied significantly according
to vitamin D level (P .01) (Figure). Linear regression
analyses demonstrated a significant inverse association between vitamin D levels and LDL and TG levels (Table 2).
These associations were unchanged after adjusting for age,
sex, race, BMI, GFR, DAS28, season of measurement,
geographic region, steroid use at baseline, diabetes, hypertension, and exercise. The associations remained significant
and unchanged in magnitude after excluding patients on
lipid-lowering therapy. In contrast, there were no significant
associations between vitamin D and HDL levels (data not
shown) in any of the models.
The associations between vitamin D deficiency (20
ng/mL) and hyperlipidemia (defined as above) are presented
in Table 3. In multivariable analyses, vitamin D deficiency
was independently associated with greater odds of hyperlipidemia (odds ratio [OR] 1.66; 1.11-2.47; P .013), adjusted for age, sex, race, BMI, GFR, DAS28, season of
measurement, geographic region, steroid use, diabetes, hypertension, and exercise. Similarly, each 10 ng/mL greater
vitamin D level was associated with a lower odds of hyperlipidemia (OR 0.78; 0.63-0.96; P .019). Exclusion of participants reporting lipid-lowering therapy did not change the
results. In multivariable models, vitamin D deficiency was
associated with a greater odds of an LDL level over 160
mg/dL (OR 2.35; 1.25-4.41; P .008) and a greater odds of
a TG level over 150 mg/dL (OR 2.32; 1.46-3.68; P .001).
Vitamin D deficiency was not associated with a higher odds
of low HDL.

Association of Vitamin D and Metabolic

Syndrome
Table 4 demonstrates an independent, dose-dependent increase in odds of the metabolic syndrome for each successive quartile of vitamin D level after controlling for the
above factors (excluding BMI, diabetes, and hypertension).
In separate analyses, a vitamin D level 20 ng/mL (OR
3.45; 1.75-6.80; P .001) and a vitamin D level 30 ng/mL
(OR 6.39; 1.47-27.7; P .013) were both associated with an
increased odds of metabolic syndrome. Vitamin D deficiency also was associated with a greater number of components of the metabolic syndrome in an ordinal regression

1036.e12
Table 1

The American Journal of Medicine, Vol 125, No 10, October 2012

Baseline Participants Characteristics According to Vitamin D Deficiency Status

Baseline Variables

All Participants

Vitamin D 20 ng/mL

Vitamin D 20 ng/mL

P Value

n (%)
Age (years)
Race
Asian, n (%)
White, n (%)
Black, n (%)
Other, n (%)
Sex, male, n (%)
BMI (kg/m2)
GFR (mL/min/1.73m2)
Winter measurement, n (%)
Diabetes, n (%)
Hypertension, n (%)
Metabolic syndrome, n (%)
Smoking, past/current, n (%)
Regular exercise, n (%)
Steroid use, n (%)
Lipid-lowering therapy, n (%)
Laboratory studies
Serum albumin (g/dL)
Low-density lipoprotein
Triglycerides
High-density lipoprotein
Disease-specific measures
DAS28 Score ESR
ESR (mm/h)
CRP (mg/dL)
HAQ score
Evaluator assessment
Pain on VAS
Erosion score
Joint space narrowing
Van der Heidje-Sharp
score
CCP positive, n (%)
Disease duration (years)

499 (100)
49.5 12.4

259 (52)
47.7 11.8

240 (48)
51.5 12.6

N/A
.001
.05

92 (18)
367 (74)
6 (1)
34 (7)
83 (17)
27.2 6.0
89.3 21.5
219 (45)
25 (5)
135 (27)
53 (11)
169 (34)
69 (14)
268 (54)
31 (6)

44 (17)
195 (75)
1 (0.4)
19 (7)
54 (21)
26.5 5.98
88.0 20.7
111 (44)
8 (3)
61 (23)
16 (6)
92 (36)
41 (16)
140 (54)
13 (5)

48 (20)
172 (72)
5 (2)
15 (6)
29 (12)
27.9 5.99
90.8 22.2
108 (46)
17 (7)
74 (31)
37 (15)
77 (32)
28 (12)
128 (53)
18 (8)

.01
.01
.1
.7
.05
.07
.01
.4
.2
.9
.2

4.2 0.4
108 (88-130)
107 (82-151)
57 (48-67)

4.2 0.4
104 (84-126)
103 (79-139)
56 (46-67)

4.2 0.4
111 (94-137)
116 (85-171)
58 (47-67)

.8
.001
.01
.5

6.30
38
1.3
1.56
6.2
6.65
4.5
1
6

6.24
40
1.2
1.49
6.3
6.55
4.5
1
6

6.37
38
1.45
1.62
6.1
6.7
4.5
1
6

.2
.5
.4
.05
.3
.07
.7
.8
.8

(1.15)
(28-60)
(0.5-3.4)
(0.66)
(5.1-7.4)
(5.1-8)
(1.5-12.5)
(0-7)
(2-21.5)

373 (75)
1.2 (0.5-4.2)

(1.24)
(25-62)
(0.5-3.5)
(0.68)
(5.1-7.6)
(4.9-7.8)
(1.5-12.5)
(0-7.8)
(2-21)

200 (77)
1.1 (0.5-4)

(1.04)
(29-60)
(0.5-3.35)
(0.63)
(5.1-7.3)
(5.2-8.2)
(2-12.5)
(0-6.5)
(2-21.75)

172 (72)
1.4 (0.55-4.55)

.2
.2

Continuous variables are presented as mean (SD) or median (interquartile range). Categorical variables are presented as %. The P value represents
the comparison between vitamin D deficiency categories.
BMI body mass index; CCP cyclic citrullinated peptide; CRP C-reactive protein; DAS28 disease activity score 28; ESR erythrocyte sedimentation rate; GFR glomerular filtration rate; HAQ Health Assessment Questionnaire; VAS visual analog scale.

model (OR 1.80; 1.28-2.53; P .001). In multivariable

analysis, vitamin D deficiency was increasingly more likely
in patients with a greater number of components of the
metabolic syndrome (P .03). Predicted mean vitamin D
levels were lower in subjects with a greater number of
components of the metabolic syndrome after adjustment in
multivariable models (P .02). Vitamin D deficiency was
not significantly associated with significantly greater odds
of hyperglycemia or diabetes (OR 1.29; 0.80-2.07), nor with
a history of hypertension (OR 1.23; 0.77-1.96).

DISCUSSION
These data demonstrate that vitamin D deficiency was associated with higher LDL and TG levels and greater odds of

hyperlipidemia and the metabolic syndrome in participants

with rheumatoid arthritis from the golimumab (GO-BEFORE) randomized controlled trial. These results expand on
this potential novel pathway involved in metabolic dyslipidemia.24 These novel findings were independent of traditional cardiovascular risk factors and measures of disease
activity. Taken together, these observations suggest that
vitamin D deficiency might contribute to the increased prevalence of metabolic syndrome and cardiovascular disease
observed in rheumatoid arthritis and possibly other inflammatory diseases.
Vitamin D deficiency is common in the general population and in patients with rheumatoid arthritis.9,25 Vitamin D
deficiency also has been linked with metabolic derange-

Baker et al

Vitamin D and Dyslipidemia in Rheumatoid Arthritis

ments, including abnormal lipoproteins, which also may be

frequently seen in rheumatoid arthritis.6 Therefore, our findings are highly relevant in helping to provide a potential link
between rheumatoid arthritis, dyslipidemia, and an increased risk of cardiovascular disease. Indeed, vitamin D
has been associated with atherosclerosis at each stage of its
development from subclinical plaque to the associated cardiovascular morbidity and mortality.26,27
The mechanism by which vitamin D deficiency is associated with increased prevalence of metabolic syndrome and
dyslipidemia has not been elucidated. Prior studies demonstrated that vitamin D stimulated the expression of insulin
receptor,28 and low vitamin D levels were associated with
beta-cell dysfunction.29 Vitamin D deficiency was independently associated with insulin resistance and beta-cell function in patients at risk for diabetes.30 Vitamin D receptor
polymorphisms also have been associated with insulin resistance.31 One study demonstrated that correction of vitamin D deficiency was associated with improvements in
metabolic syndrome, suggesting that vitamin D deficiency
may contribute to impaired insulin signaling.32 In addition,
the relationship between vitamin D deficiency and dyslipidemia may be due, in part, to vitamin D effects on hepatic
lipid metabolism.33 Vitamin D promotes intestinal calcium

1036.e13

Table 2 Multivariable Linear Regression Analysis Evaluating

the Associations between Natural Log-transformed Vitamin D
Level and Natural Log-transformed LDL and TG Level
Lipoprotein Fraction
Model 1*
LDL
TG
Model 2
LDL
TG
Model 3
LDL
TG
Model 4
LDL
TG

Coefficient

95% CI

0.084
0.31

0.15 to 0.018 .013

0.50 to 0.12 .002

0.080
0.26

0.15 to 0.014 .017

0.44 to 0.073 .006

0.091
0.28

0.16 to 0.023 .008

0.47 to 0.098 .003

0.093
0.28

0.16 to 0.025 .008

0.47 to 0.088 .004

P Value

CI confidence
interval;
LDL low-density
lipoprotein;
TG triglycerides.
*Adjusted for age, sex, race.
Adjusted for age, sex, race, body mass index (BMI), diabetes,
hypertension, and smoking status.
Adjusted for age, sex, race, BMI, diabetes, hypertension, smoking,
glomerular filtration rate (GFR), exercise, and C-reactive protein (CRP).
Adjusted for age, sex, race, BMI, GFR, exercise, smoking, diabetes,
hypertension, CRP, geographic region, disease activity (DAS28), steroid
use, and season of measurement.

absorption, and calcium may bind to fatty acids to form

insoluble complexes that inhibit lipid absorption. Thus, vitamin D deficiency may lead to abnormal processing of
lipids due to alterations in calcium availability.34
Alternatively, vitamin D is sequestered in body fat, and
obesity may be associated with a decreased bioavailability
of the hormone.35 Therefore, vitamin D may instead be a

Table 3 Multivariable Logistic Regression Analysis

Evaluating the Odds of Hyperlipidemia According to Vitamin D
Status
Variable
Model 1*
Vitamin
Model 2
Vitamin
Model 3
Vitamin
Model 4
Vitamin

Figure Box plots of low-density lipoprotein and triglyceride

levels by vitamin D quartile.

Odds Ratio

95% CI

P Value

D 20 ng/mL

1.63

1.14-2.35

.008

D 20 ng/mL

1.51

1.03-2.21

.033

D 20 ng/mL

1.62

1.10-2.39

.015

D 20 ng/mL

1.64

1.10-2.45

.015

CI confidence interval.
*Adjusted for age, sex, race.
Adjusted for age, sex, race, body mass index (BMI), diabetes,
hypertension, and smoking status.
Adjusted for age, sex, race, BMI, glomerular filtration rate (GFR),
exercise, smoking, diabetes, hypertension, and C-reactive protein (CRP).
Adjusted for age, sex, race, BMI, GFR, exercise, smoking, steroid use
at baseline, diabetes, hypertension, CRP, geographic region, disease
activity (DAS28), and season of measurement.

1036.e14

The American Journal of Medicine, Vol 125, No 10, October 2012

Table 4 Multivariable Logistic Regression Analysis for the

Odds of the Presence of Metabolic Syndrome by Quartile of
Vitamin D Level

ings mandate further studies evaluating the effects of vitamin

D supplementation in patients with rheumatoid arthritis, a
high-risk group for cardiovascular disease.

Vitamin D Quartile*

Odds Ratio

95% CI

P Value

References

28.2 ng/mL
20.8-28.2 ng/mL
14.5-20.7 ng/mL
14.5 ng/mL

1
2.66
5.40
7.59

0.77-9.20
1.67-17.45
2.37-24.30

.12
.005
.001

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CI confidence interval.
*Adjusted for age, sex, race, glomerular filtration rate (GFR), region,
disease activity (DAS28), smoking, exercise, steroid use at baseline,
C-reactive protein, and season of measurement.

marker of visceral fat content. Additionally, fatty liver disease is associated with low vitamin D levels, suggesting that
greater hepatic fat content might impair hepatic 25-hydroxylation of vitamin D.33 Furthermore, vitamin D-binding
protein, a member of the albumin gene family that transports vitamin D to target tissues, along with 25(OH) vitamin
D3 itself, has been identified in very low-density lipoprotein
particles.36 Thus, it is not known if measurement of vitamin
D is affected by the presence of lipoprotein particles. Further study is necessary to clarify the nature of this association in rheumatoid arthritis.
Strengths of this study include the large sample size,
standardized measures of disease characteristics, cardiovascular risk factors, confounding variables, and comprehensive assessment of lipoprotein and vitamin D levels. The
primary limitation of this study is the observational and
cross-sectional design, which may be subject to residual
confounding and prevents assessment of temporal associations. Randomized clinical studies are essential to establish
these associations. An additional limitation is the lack of
data on dietary intake. Subjects with poor dietary habits
might be more likely to have both elevated lipoproteins and
low vitamin D levels. However, the association was independent of albumin, a measure of nutritional status. The
findings also were independent of geographic region; therefore, they are not likely explained by regional variation in
dietary habits. A third limitation is that the study population
was predominantly female (congruent with the demographics of the disease), and there were too few men to stratify the
results by sex. Our study did not include measures of waist
circumference, and the use of BMI as a surrogate measure
may have resulted in misclassification of the number of
components of the metabolic syndrome. However, the
strength and consistency of the associations between vitamin D status, the presence of metabolic syndrome, and the
number of components of the metabolic syndrome suggests
that the lack of waist circumference data was not an important limitation.
In conclusion, low 25(OH) vitamin D was associated with
increased odds of elevated LDL and TG as well as metabolic
syndrome at baseline in subjects with rheumatoid arthritis
independent of numerous potential confounders. These find-

Baker et al

Vitamin D and Dyslipidemia in Rheumatoid Arthritis

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