132

ORIGINAL ARTICLE
ABSTRACT
Aim: to understand the proportion of dyslipidemia in
systemic lupus erythematosus (SLE) patients and the
influencing factors of dyslipidemia.
Methods: an observational, cross-sectional study was
conducted on new and longstanding SLE patients who had
been diagnosed based on ARA criteria 1982 with 1997
revision. They had been hospitalized and treated at
Department of Internal Medicine, Cipto Mangunkusumo
National Central General Hospital and the other private
Hospitals in Jakarta, i.e. Kramat Hospital, Agung Hospital
and Cempaka Putih Islamic Hospital in July November
2003. The sample was selected by non probability sampling
method with consecutive sampling technique. Every
participant underwent history taking, physical and
laboratory examination.
Results: there were 77 patients satisfying the inclusion
criteria. The proportion of dyslipidemia in this study was
75.3%. By confidence interval of 95%, the proportion of
dyslipidemia in SLE patient was 65.3% - 84.6%. The
distribution of lipid profile in sample population were 43%
with total cholesterol > 200 mg/dL, 26% with HDL
cholesterol level < 40 mg/dL, 26.4% with LDL cholesterol
level > 130 mg/dL and 44.2% with triglycerides serum level
> 150 mg/dL. The characteristics of influencing factors in
dyslipidemia prevalence for sample population consisted of
24.7% with renal involvement, 53.2% with > 3 years illness
periods, 26% had received > 30 mg/day prednisone, 94.8%
had not received chloroquines, and 58.4% had illness
activity of Mex-SLEDAI > 2. By bivariate analysis, we found
that illness period < 3 years tends to affect dyslipidemia with
OR value of 12.04 (CI 95%, 2.54-57.05, p = 0.001). After
conducting multivariate analysis by backward methods, it
appears that only one significant influencing factor of
dyslipidemia prevalence in SLE patient i.e. Illness period of
< 3 years with OR value of 12.04 (CI 95% 2.54 57.05,
p = 0.001).
Conclusion: illness period of < 3 years is represent a
significant correlative factor for dyslipidemia prevalence.
Prednisone > 30 mg/dL is the correlative factor for total cho-
lesterol > 200 mg/dL and triglycerides > 150 mg/dL. Mex-
SLEDAI > 2 is the correlative factor for HDL
cholesterol < 40 mg/dL.
Key words: dyslipidemia, systemic lupus erythematosus.
INTRODUCTION
Dyslipidemia is a lipid-metabolism disorder, which is
characterized by increased or decreased serum lipid
fraction (lipoprotein). The main defects of lipid fraction
are: increased total cholesterol and low density
lipoprotein (LDL) cholesterol level, increased
triglycerides serum level, and decreased high density
lipoprotein (HDL) cholesterol level.
1-5
Dyslipidemia is a
quite important problem in systemic lupus
erythematosus (SLE) patient, which causes morbidity
and mortality. As known, dyslipidemia is one of
atherosclerosis risk-factor, and main mortality cause of
longstanding SLE patient.
2-5, 7-10
The prevalence of
coronary atherosclerosis increases in SLE patients and
the prevalence age decreases.
10
Manzi reported that
coronary heart disease (CHD) was found in 6.6% of
SLE women, compared to only 1.6% in healthy women.
Myocardial infarct may occur at any age, with a ratio of
52.4 times at 35-44 years of age.
2,11
*Department of Internal Medicine, Faculty of Medicine, University of
Indonesia, Cipto Mangunkusumo National Central General Hospital,
** Division of Rheumatology, *** Division of Clinical Allergy and
Immunology, **** Division of Endocrinology Metabolic, Department
of Internal Medicine, Faculty of Medicine, University of Indonesia,
Cipto Mangunkusumo National Central General Hospital,
***** Faculty of Public Heath, University of Indonesia.
The Proportion of Dyslipidemia in Systemic Lupus
Erythematosus Patient and Distribution
of Correlated Factors
Linda K Wijaya*, Yoga Iwanoff Kasjmir**, Nanang Sukmana***,
Imam Subekti****, Joedo Prihartono*****
133
Vol 37 Number 3 July-September 2005 The Proportion of Dyslipidemia in SLE Patient
There are some conditions which influence dyslipidemia
prevalence in SLE, i.e. auto-antibody in lipoprotein
metabolism; renal involvement, disease activity and
increased lipid level due to prednisone treatment; while
hydroxychloroquines decrease the lipid level.
6
Systemic lupus erythematosus (SLE) is a
multisystem disease in which tissues undergo damage
mediated by tissue-binding auto antibodies and immune
complexes, as well as complement.
12-14
Prevalence of
systemic lupus erythematosus in general population is 1
per 2,000 and this prevalence is associated with race,
ethnic and socio-economic status. Prevalence of SLE in
the United States is 14.6 to 50.8 per 100,000, the
highest prevalence is 15 to 40 years age-group, with
female to male ratio about 6-10 : 1.
14,15
The prevalence
in Indonesia has not been accurately determined. The
incidence in the period of 1971 1975 at Cipto
Mangunkusumo National Central General Hospital was
15.02 per 10,000 hospital care.
13
Based on
hospitalization data at the Department of Internal
Medicine Ward, Cipto Mangunkusumo National Central
General Hospital, there were 38 SLE patients
hospitalized in 2002 and 42 SLE patients in 2003.
16
Leong
et al conducted a lipid-profile study for 100 SLE patients
in Singapore and they found that 73% of SLE patients
had abnormal lipid profile caused by renal disorder and
steroid administration.
17
Wallace also found
hypercholesterolemia and hypertriglyceridemia in SLE
patients.
7,17
Alekberova et al found dyslipidemia in 1/3 of
60 SLE patients.
18
SLE treatment may also cause
dyslipidemia. Prednisone may increase total
cholesterol, VLDL cholesterol, LDL cholesterol and
triglycerides level.
2,6,11,17
Renal involvement frequently
causes dyslipidemia in SLE patients.
6
Leong et al found
increased total cholesterol, LDL, and triglycerides level,
as well as ratio of total cholesterol/HDL.
17
Bruce et al, found a correlation between systemic
lupus erythematosus disease activity index and
total cholesterol, LDL and HDL level. There was lipid
abnormality about 79% of HDL and 31% of
triglycerides for active lupus patients.
6
This study was conducted because there was
increasing dyslipidemia prevalence of systemic lupus
erythematosus patient in Indonesia and moreover,
because the increased mortality rate is caused by
dyslipidemia.
By understanding the proportion and distribution of
influencing factors of dyslipidemia in SLE patients, we
expect that we can be alerted about dyslipidemia
prevalence, which finally will enhance prevention against
its consequences.
METHODS
An observational, cross-sectional study was
conducted in the new and longstanding SLE patients who
had been diagnosed based on ARA criteria 1982 with 1997
revision. They had been hospitalized and treated at
Department of Internal Medicine, Cipto Mangunkusumo
National Central General Hospital and the other private
Hospitals in J akarta, i.e. Kramat Hospital, Agung
Hospital and Cempaka Putih Islamic Hospital in July
November 2003. The inclusion criteria were: patients diag-
nosed of SLE according ARA criteria 1982, with 1997
revision and willing to participate in this study. The
exclusion criteria was on hypothyroid. The sample was
selected by non probability sampling method with
consecutive sampling technique. The dependent variable
was dyslipidemia, which was characterized by one or more
of conditions as follow: increased cholesterol level >200
mg/dL and or increased triglycerides level >150 mg/dL
and or decreased HDL cholesterol level <40 mg/dL and or
increased LDL cholesterol level >130 mg/dL. The
independent variables were: renal involvement, prednisone
treatment by >30 mg / day doses, and no chloroquines
treatment, disease activity based on Mex-SLEDAI, illness
period <3 years. Before any examination was conducted
in this study, every sample had received some
explanations about the examination procedures and
objectives. Informed consent for this study was done by
signing informed consent form. Then, every participant
underwent history taking, physical and laboratory
examination. The characteristic data of participants were
analyzed by computer program, SPSS version 10 by
descriptive-statistic method i.e. by prevalence percentage.
We used chi-square test for statistical analysis, and the
correlation was calculated by odds ratio and multivariate
analysis by using logistic regression method with backward
methods.
RESULTS
There were 77 samples satisfying the inclusion
criteria, 74 females and 3 males.
By these data, we could see that the highest sample
population was female (96.1%), with 31-40 years of age
(33.8%), and had university education level (41.6%).
On figure 1, we could see that the highest frequency of
illness period was newly diagnosed to 1 year-diagnosed in
20 patients. There were 16 patients with illness period of 1
to 3 years, 6 patients with illnessperiod of 3 5 years, 15
patients with illness period of 5-7 years, 8 patients with
illness period of 7-9 years, 3 patients with illness period of
9-11 years, 4 patients with illness period of 13-15 years, and
2 patients with illness period of 15-17 years.
134
Linda K Wijaya, etal Acta Med Indones-Indones J Intern Med
Table 5, shows that cholesterol level >200 mg/dL
was found in 40.3% of SLE patients, triglyceride level
>150 mg/dL was found in 44.2% HDL cholesterol
<40 mg/dL was found in 26% and LDL cholesterol >130
mg/dL was found in 36.4% of SLE patients.
THE DISTRIBUTION OF MEX-SLEDAI DESCRIPTION
IN SAMPLE POPULATION
In this study, the illness activity was measured by
Mex-SLEDAI. (Table 6)
Figure 1. The Graph of Illness Period Frequency of SLE Patients
PREVALENCE OF PATIENTS WITH DYSLIPIDEMIA
Figure 2, shows that the prevalence of sample with
dyslipidemia was 75%. With 95% confidence interval, of
65.3% - 84.6%.
On table 2, we can see that the subject with
dyslipidemia were 100% male (3 samples) and 74.3%
female (55 samples), while based on the age-group, there
was 78.9% with dyslipidemia for <25 years of age, 65.0%
for 25-30 years of age, 73.1% for 31-40 years of age
and 91.7% for more than 41 years of age.
INFLUENCING FACTORS OF DYSLIPIDEMIA
PREVALENCE
By these data, we can see that 24.7% of subjects
had renal involvement, 46.8% had illness period of <3
years, 26% received >30 mg/day prednisone, 94.8% did
not received chloroquines and 58.4% had Mex SLEDAI
illness activity >2. (Table 3)
THE RESULT OF LIPID PROFILE EXAMINATION
Table 4, shows that the mean value of cholesterol
level was 192.6 mg/dL, triglyceride 160.3 mg/dL, HDL
cholesterol 48.6 mg/dL and LDL cholesterol level 118.1
mg/dL.
Figure 2. Prevalence of Sample Who Experienced Dyslipidemia
Table 1. The Characteristic of Subjects
The characteristic of subjects N %
Sex
- Male 3 3.9
- Female 74 96.1
Age Groups
- < 25 years 19 24.7
- 25 - 30 years 20 26.0
- 31 - 40 years 26 33.8
- 41 + years 12 15.6
Education Level
- Elementary 7 9.1
- Junior High School 9 11.7
- Senior High School 29 37.7
- University 32 41.6
20
16
6
15
8
3 3
4
2
0
5
10
15
20
25
Illness Period (year)
F
r
e
q
u
e
n
c
y
0-0,99
1-2,99
3-4,99
5-6,99
7-8,99
9-10,99
11-12,99
13-14,99
15-16,99
75%
25%
dyslipidemia
without dyslipidemia
Table 2. The Characteristic of Subjects with Dyslipidemia
Dyslipidemia
Yes No
N % N %
Sex
- Male 3 100 - -
- Female 55 74.3 19 25.7
Age
- < 25 years 15 78.9 4 21.1
- 25 30 years 13 65.0 7 35.0
- 31 40 years 19 73.1 7 26.9
- 41 + years 11 91.7 1 8.3
Table 3. The Influencing Factors of Dyslipidemia Prevalence
in Sample Population
No The Influencing factors
of dyslipidemia
n %
1. Renal involvement
- Yes 19 24.7
- No 58 75.3
2. Illness period
- < 3 years 36 46.8
- 3 years 41 53.2
3. Prednisone dose
- < 30 mg/day 57 74
- 30 mg/day 20 26
4. Chloroquines
- No Chloroquines 73 94.8
- 250-500 mg/day 4 5.2
5. Mex-SLEDAI
- 2 45 58.4
- < 2 32 41.6
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Vol 37 Number 3 July-September 2005 The Proportion of Dyslipidemia in SLE Patient
Of 77 sample populations, there were greatest
amounts of mucocutaneus and lymphopenia disorder.
Renal disorder was found in 19 samples (24.7%).
Vasculitis in 17 samples (22.1%), fatigue in 16 samples
(20.8%), arthritis in 10 samples (13%), leucopenia in 8
samples (10.4%), fever on 7 samples (9.1%),
thrombocytopenia, serocytis, and neurologic disorder in
3 (3.9%), 2 (2.6%) and 1 sample (1.3%) respectively.
But myocytis and hemolysis were not found, which were
characterized by Hb <12 gr/dL and reticulocyte
correction >3.
BIVARIATE ANALYSIS OF SOME VARIABLES
AGAINST DYSLIPIDEMIA
Based on statistical test, correlations of some
variables against dyslipidemia are presented in table 7.
Renal Involvement
There was renal involvement in 78.9% subjects with
dyslipidemia. By chi-square statistic analysis test, we
found p =0.768, which meant that renal involvement
had no tendency to influence the dyslipidemia prevalence.
The OR value was 1.31 (CI 95% 0.38-4.57).
Illness Period
The dyslipidemia prevalence of 94.4% was found in
SLE patient who had illness period less than 3 years.
Illness period <3 years tends to influence dyslipidemia
prevalence with OR value of 12.04 (CI 95% 2.54-57.05).
Prednisone
There was 90% dyslipidemia of SLE patients who
had received >30 mg/day prednisone. Statistical
analysis shows no significant correlation was observed
(p =0.130), (OR=3.82, CI 95% 0.80-18.33, p=0.130).
Chloroquines
There were 74.0% SLE patients who had
dyslipidemia and had not received any chloroquines.
Statistical analysis shows no correlation. The OR value
was 0.31, CI 95% 0.04-2.18, p =0.507.
Mex -SLEDAI
There were 84.4% dyslipidemia prevalence with the
score >2 based on illness activity measurement of SLE
patients using the Mex-SLEDAI method. There was a
tendency but not significant that Mex-SLEDAI
influence dyslipidemia. The OR value was 3.26, CI 95%
1.11-9.57, p =0.053.
THE RESULT OF MULTIVARIATE ANALYSIS
Based on multivariate analysis, all variables with
p <0.25 were included in the analysis. The variables
included were prednisone and illness period.
The multivariate analysis of logistic regression by
backward methods found that illness period of <3 years
was correlated with dyslipidemia prevalence in SLE, with
p = 0.001 OR 12.04 (CI 95% 2.54-57.05). Then, we
conducted some analysis of independent variables against
cholesterol and triglycerides.
Table 4. Mean Value and Standard Deviation of Lipid Profile
Laboratories min max Mean SD Median
Total Cholesterol 111 318 192.6 45 189
Triglyceride 30 507 160.3 98.3 142
HDL Cholesterol 12 96 48.6 15.5 48
LDL Cholesterol 51 210 118.1 33.2 119
Table 5. The Distribution of Lipid Profile in Sample Population
Amount Percent
Cholesterol
200 mg/dL 31 40.3
< 200 mg/dL 46 59.7
Triglyceride
150 mg/dL 34 44.2
< 150 mg/dL 43 55.8
HDL-C
< 40 mg/dL 20 26.0
40 mg/dL 57 74.0
LDL-C
130 mg/dL 28 36.4
< 130 mg/dL 49 63.6
Table 6. Distribution of Mex-SLEDAI in Sample Population
No. Description n %
1. Neurologic disorder 1 1.3
2. Renal disorder 19 24.7
3. Vasculitis 17 22.1
4. Haematologic disorder
Haemolisis (Hb< 12 gr/gL and
retikulocytes correction > 3%)
- -
Thrombocytopenia
(Platelets < 100.000)
3 3.9
5. Myocytis - -
6. Arthritis 10 13
7. Mucocutaneus disorder 27 35.1
8. Serocitis 2 2.6
9. Fever 7 9.1
Fatigue (Unexplained fatigue) 16 20.8
10. Leucopenia (leucocytes
< 4000/mm
3
)
8 10.4
Lymphopenia (lymphocytes
< 1200 mm
3
)
27 35.1
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Linda K Wijaya, etal Acta Med Indones-Indones J Intern Med
Chloroquines
There was hypercholesterolemia in 41.1% SLE
patients who had not received chloroquines treatment. By
chi-square statistic analysis test, we found p =0.644, which
meant that negative chloroquines treatment had no tendency
to influence the prevalence of cholesterol level 200 mg/
dL. The OR value was 2.09 (CI 95% 0.21-21.10).
Mex -SLEDAI
There was 91.1% hypercholesterolemia prevalence
with the score > 2 based on illness activity
measurement of SLE patients using the Mex-SLEDAI
methods. But, by chi-square statistic analysis test, we
found p =0.261 hence there was no influencing
tendency between Mex-SLEDAI and cholesterol level
200 mg/dL. The OR value was 1.93 (CI 95% 0.75-4.98).
THE RESULT OF MULTIVARIATE ANALYSIS AGAINST
TOTAL CHOLESTEROL
Multivariate analysis was conducted for all variables
with p <0.25. The included variables were prednisone
and illness period.
The multivariate analysis of logistic regression by
backward methods found that the variable which tends
to influence cholesterol level 200 mg/dL in systemic
lupus erythematosus was prednisone dose of 30 mg/
day with p=0.040 OR 3.00 (95% CI 1.05-8.58).Bivari-
ate Analysis of Some Variables Against Triglycerides
BIVARIATE ANALYSIS OF SOME VARIABLES
AGAINST TOTAL CHOLESTEROL
Renal Involvement
Renal involvement was found in 47.4% of subjects
who had cholesterol level >200 mg/dL. By chi-square
statistic analysis test, we found p =0.647, which meant
renal involvement had no tendency to influence the
prevalence of cholesterol level >200 mg/dL. The OR
value was 1.47 (CI 95% 0.52-4.19).
Illness Period
SLE patients with illness period <3 years had
hypercholesterolemia prevalence of 50%. By chi-square
statistic analysis test, we found p =0.161, which meant
there was no tendency of illness period <3 years to in-
fluence cholesterol level >200 mg/dL The OR value was
2.15 (CI 95% 0.85-5.44).
Prednisone
60% of SLE patients who had > 30 mg/day
prednisone experienced hypercholesterolemia. By
chi-square statistic analysis test, we found p =0.068, which
meant 30 mg/day prednisone dose has no tendency to
influence cholesterol level 200 mg/dL in SLE patient. The
OR value was 3.00 (CI 95% 1.05-8.58).
Table 7. The Bivariate Analysis Result of Some Variables Against Dyslipidemia
Dyslipidemia OR p Value
Yes No (CI 95%)
n % n %
Renal involvement
- Yes 15 78.9 4 21,1 1.31 0.768
- No 43 74.1 15 25,9 (0.38-4.57)
Illness period
- < 3 years 34 94.4 2 5,6 12.04 0.001*
- 3 years 24 58.5 17 41,5 (2.54-57.05)
Prednisone dose
- 30 mg/day 18 90 2 10 3,83 0.130
- < 30 mg/day 40 70.2 17 29,8 (0.80-18.33)
Chloroquines
-No Chloroquines 54 74.0 19 26,0 0.31 0.567
- 250-500 mg/day 4 100 - - (0.04-2.18)
Mex SLEDAI
- 2 38 84.4 7 15,6 3.26 0.053
- < 2 20 62.5 12 37.5 (1.11-9,57)
* significant
Table 8. The Multivariate Analysis Against Dyslipidemia
Variable OR Min Max p
Prednisone dose 30
mg/day
3.83 0.80 18.33 0.130
Illness period < 3 years 12.04 2.54 57.05 0.001
Mex-SLEDAI 2 3.26 1.11 9.57 0.053
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Vol 37 Number 3 July-September 2005 The Proportion of Dyslipidemia in SLE Patient
BIVARIATE ANALYSIS OF SOME VARIABLES
AGAINST TRIGLYCERIDES
Renal Involvement
Renal involvement was found in 57.9% subject who
had triglycerides level 150 mg/dL By chi-square
statistic analysis test we found p =0.261, which meant
renal involvement had no tendency to influence the
prevalence of triglycerides level 150 mg/dL. The OR value
was 2.09 (CI 95% 0.73-5.99).
Illness Period
There was 61.1% of SLE patient who had illness
period <3 years and had triglycerides level 150 mg/dL
By chi-square statistic analysis test we found p =0.010
which meant there was influencing tendency between
illness period <3 years and triglycerides level 150 mg/
dL. The OR value was 3.80 (CI 95% 1.47-9.82).
Prednisone
There was 75% triglycerides level >150 mg/dL of SLE
patients who had received >30 mg/day prednisone. By
chi-square statistic analysis test, we found p =0.003, which
meant prednisone dose 30 mg/day tends to influence the
prevalence of triglyceride level 150 mg/dL in SLE pa-
tients. The OR value was 6.00 (CI 95% 1.89-18.99).
Chloroquines
There was triglycerides level >150 mg/dL in 43.8%
SLE patients who had not received chloroquines
treatment. By chi-square statistic analysis test, we found
p =1.000, which meant SLE patients who had not
received chloroquines treatment had no tendency of
triglycerides level 150 mg/dL. The OR value was 0.78
(CI 95% 0.10-5.85).
Mex -SLEDAI
There was 55.6% prevalence of triglyceride level
>150 mg/dL with the score >2 based on illness activity
measurement of SLE patients using the Mex-SLEDAI
methods. By chi-square statistic analysis test, we found
p =0.031, which meant there was influencing tendency
between Mex-SLEDAI and triglyceride level 150 mg/dL.
The OR value was 3.19 (CI 95% 1.21-8.42).
THE RESULT OF MULTIVARIATE ANALYSIS AGAINST
TRIGLYCERIDES
Multivariate analysis was conducted for all variables
with p <0.25. The included variables were prednisone,
illness period and Mex-SLEDAI.
The multivariate analysis of logistic regression by
backward methods found that the variable which tends
to influence triglyceride level 150 mg/dL in systemic lu-
pus erythematosus was prednisone dose of 30 mg/day
with p=0.002 OR 6.00 (95% CI 1.90-18.99 ).
THE BIVARIATE ANALYSIS OF SOME VARIABLES
AGAINST HDL-CHOLESTEROL
Renal Involvement
Renal involvement was found in 47.4% of subjects who
had HDL cholesterol level <40 mg/dL. By chi-square
statistic analysis test, we found p =0.032, which meant
renal involvement had a tendency to influence the HDL
cholesterol level <40 mg/dL. The OR value was 3.85 (CI
95% 1.26-11.72).
Table 9. The Bivariate Analysis Result of Some Variables Against Total Cholesterol
Total cholesterol OR p* Value
200 mg/dL < 200mg/dL (CI 95%)
n % n %
Renal involvement
- Yes 9 47.4 10 52.6 1.47 0.647
- No 22 37.9 36 62.1 (0.52-4.19)
Illness period
- < 3 years 18 50 18 50 2.15 0.161
- 3 years 13 31.7 28 68.3 (0.85-5.44)
Prednisone dose
- 30 mg/day 12 60 8 40 3,00 0.068
- < 30 mg/day 19 33.3 38 66.7 (1.05-8.58)
Chloroquines
-No Chloroquines 30 41.1 43 58.9 2.09 0.644
- 250-500 mg/day 1 25.0 3 75 (0.21-21.10)
Mex SLEDAI
- 2 21 46.7 24 53.3 1.93 0.261
- < 2 10 31.3 22 68.8 (0.75-4.98) 0.261
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Linda K Wijaya, etal Acta Med Indones-Indones J Intern Med
THE BIVARIATE ANALYSIS OF SOME VARIABLES
AGAINST LDL CHOLESTEROL
The bivariate analysis result of some variables
against LDL cholesterol.
Renal Involvement
Renal involvement was found in 36.8% of subjects
who had LDL cholesterol level >130 mg/dL. By
chi-square statistic analysis test, we found p =1.000,
which meant that renal involvement had no tendency to
influence the LDL cholesterol level >130 mg/dL. The
OR value was 1.03 (CI 95% 0.35-3.01).
Illness Period
There was 50.0% of SLE patients with illness
period <3 years had LDL cholesterol level >130 mg/
dL. By chi-square statistic analysis test, we found p =
0.032, which meant there was tendency of illness period
<3 years to influence LDL cholesterol level >130 mg/
dL. The OR value was 3.10 (CI 95% 1.18-8.15).
Prednisone
There was 40% of SLE patients who had >30 mg/
day prednisone accompanied by LDL cholesterol level
>130 mg/dL. By chi-square statistic analysis test, we
found p =0.902, which meant that by 30 mg/day
prednisone dose, there was no tendency to influence LDL
cholesterol level >130 mg/dL in SLE patients. The OR
value was 1.23 (CI 95% 0.43-3.51).
Chloroquines
There was LDL cholesterol >130 mg/dL in 37%
SLE patients who had not received chloroquines. By chi-
square statistic analysis test, we found p =1.000, which
meant that SLE patients who had not received any
chloroquines treatment had no tendency to influence the
prevalence of LDL cholesterol level >130 mg/dL. The
OR value was 1.761 (CI 95% 0.17-17.78).
Mex -SLEDAI
There was 37.8% of LDL cholesterol level >130 mg/
dL prevalence with the score >2 based on illness activity
measurement of SLE patients using the Mex-SLEDAI
methods. By chi-square statistic analysis test, we found
p =0.948, which meant that there was no influencing
tendency between Mex-SLEDAI and LDL cholesterol
level >130 mg/dL. The OR value was 1.16 (CI 95% 0.45-
2.98).
Because there was only one variable with p <0.25 in
bivariate analysis against LDL cholesterol >130 mg/dL,
i.e. illness period, then the multivariate analysis can not be
continued.
Illness Period
There was 33.3% of SLE patients with illness period
<3 years who had HDL cholesterol level <40 mg/dL.
By chi-square statistic analysis test, we found p =0.263,
which meant there was no tendency of illness period
<3 years to influence HDL cholesterol level <40 mg/dL.
The OR value was 2.06 (CI 95% 0.73-5.83).
Prednisone
There was 40% of SLE patients who had >30 mg/day
prednisone with HDL cholesterol level <40 mg/dL. By
chi-square statistic analysis test, we found p =0.172, which
meant that by 30 mg/day prednisone dose, there was no
tendency to influence HDL cholesterol level <40 mg/dL in
SLE patients. The OR value was 2.50 (CI 95% 0.83-7.49).
Chloroquines
There was HDL cholesterol <40 mg/dL in 26% SLE
patients who had not received chloroquines treatment. By
chi-square statistic analysis test, we found p =1.000, which
meant that negative chloroquines treatment had no
tendency to influence the prevalence of HDL
cholesterol level <40 mg/dL. The OR value was 1.06
(CI 95% 0.10-10.77).
Mex -SLEDAI
There was 37.8% of HDL cholesterol level <40 mg/
dL prevalence with the score >2 based on illness activ-
ity measurement of SLE patients using the Mex-SLEDAI
method. By chi-square statistic analysis test, we found p
=0.011, which meant there was influencing tendency
between Mex-SLEDAI and HDL cholesterol level <40
mg/dL. The OR value was 5.87 (CI 95% 1.55-22.25).
THE RESULT OF MULTIVARIATE ANALYSIS AGAINST
HDL CHOLESTEROL
Multivariate analysis was conducted for all variables
with p <0.25. The included variables were prednisone,
renal involvement and Mex-SLEDAI.
The multivariate analysis of logistic regression by
backward methods found that the variable which tends
to influence HDL cholesterol level <40 mg/dL in
systemic lupus erythematosus was Mex-SLEDAI with
p=0.009 OR 5.87 (CI 95% 1.55-22.25 ).
Table 10. The Multivariate Analysis Against Total Cholesterol
Variable OR Min Max p
Prednisone dose 30
mg/day
3.00 1.05 8.58 0.068
Illness period < 3 years 2.15 0.85 5.44 0.161
139
Vol 37 Number 3 July-September 2005 The Proportion of Dyslipidemia in SLE Patient
Department of Internal Medicine, Cipto Mangunkusumo
National Central General Hospital and the other private
Hospital in J akarta, i.e. Kramat Hospital, Agung
Hospitals and Cempaka Putih Islamic Hospital with
75.3%. We found the prevalence of dyslipidemia in SLE
range from 65.3% - 84.6% with confidence interval 95%.
The result of this study is almost similar to the study
conducted by Leong et al (1994) in Singapore which
demonstrated the prevalence of dyslipidemia about 73%.
9,17
This similar prevalence is caused by genetic similarity of
Asian ethnic. We still need further study even in Leong
study, in which most of the sample were Chinese while in
this study were Malayan.
In this study there were total cholesterol level >200
mg/dL in 40.3% subjects, triglycerides level >150 mg/dL in
44.2%, HDL cholesterol level <40 mg/dL in 26% and LDL
cholesterol level >130 mg/dL in 36.4% subjects.
Wallace (1991) found significant hypercholes-
terolemia (>240 mg/dL) in 88 of 434 SLE patients (21%)
and hyper triglycerides (>200 mg/dL) in 17.6%
subjects.
7,8
It is different because Wallace conducted the
study with quite large sample size i.e. 570 subjects with
higher cholesterol and triglyceride limits. Alekberova et
al (1999) studied the characteristic of blood
cholesterol in 60 SLE patients and they found dyslipidemia
in 1/3 SLE patients. There was increased LDL-
cholesterol level of 35% subjects, triglycerides level of
30%, and low HDL level of 32% subjects.
18
Those
different results are apparently influenced by population
characteristic and the methods. Alekberova used case
control methods on healthy subjects.
DISCUSSION
Study Limitation
The sample size of this study has fulfilled minimal
sample size appropriate to statistical calculation.
Nevertheless, we also realize that there are some
disadvantages if we use cross-sectional study method,
so that it is difficult to determine the significance of
dyslipidemia risk factor and there is unequal sample size
of some certain sample calculations. Consequently, there
is unstable statistic value. There are some variations of
patients characteristics, from the newly diagnosed SLE
patients to the patients who had experienced SLE for 16
years; there is another dyslipidemia risk factor which may
influence dyslipidemia in SLE. Finally, it may
influence the risk-factors evaluation.
We assume that there are some influencing
factors of dyslipidemia occurrence theoretically, which
is not readily investigated by this study, because of
method and source limitations. The diet history-taking
was not conducted in this study, so that confounding
effect of diet can not be totally excluded.
The Prevalence of Dyslipidemia
In this study we found the prevalence of dyslipidemia
in SLE patients who had been hospitalized and treated at
Table 11. The Bivariate Analysis Result of Some Variables Against Triglycerides
Triglyceride OR p Value
150 mg/dL < 150mg/dL (CI 95%)
n % n %
Renal involvement
- Yes 11 57.9 8 42.1 2,09 0.261
- No 23 39.7 35 60.3 (0.73-5.99)
Illness period
- < 3 years 22 61.1 14 38.9 3.80 0.010*
- 3 years 12 29.3 29 70.7 (1.47-9.82)
Prednisone dose
- 30 mg/day 15 75 5 25 6.00 0.003*
- < 30 mg/day 19 33.3 38 66.7 (1.89-18.99)
Chloroquine
-No Chloroquine 32 43.8 41 56.2 0.78 1.000
- 250-500 mg/day 2 50.0 2 50.0 (0.10-5.85)
Mex SLEDAI
- 2 25 55.6 20 44.4 3.19 0.031*
- < 2 9 28.1 23 71.9 (1.21-8.42)
* significant
Table 12. The Multivariate Analysis Against Triglycerides
Variable OR Min Max p
Prednisone dose 30
mg/day
6.00 1.89 18.89 0.003
Illness period < 3 years 3.80 1.47 9.82 0.010
Mex-SLEDAI 3.19 1.21 8.42 0.031
140
Linda K Wijaya, etal Acta Med Indones-Indones J Intern Med
Sex
In this study there were 74 females and 3 males,
which is consistent with SLE publication i.e. there is
higher incidence in female. Some studies reported
female domination up to 90% of SLE cases.
15,37
occurs after 55 years of age.
15
The other study also found
that the highest SLE incidence in New-York
Afro-American female are between 15-44 years old, 20-
39 years of age in Pittsburg and 25-34 years of age in Bal-
timore. These SLE incidences are correlated to
hormonal change, which occur in puberty and growth
period.
37
The study result indicates that the distribution of
dyslipidemia based on age is almost evenly distributed,
i.e. 78.9% (15 subjects) of the age <25 years, 65% (13
subjects) between 25-30 years, 73.1% (19 subjects)
between 31-40 years, and 91.7% (11 subjects) over than
41 years of age. These indicate that dyslipidemia may
occur at any age.
The Influence of Renal Involvement Factor Against
Dyslipidemia
SLE is an autoimmune disease, which is
characterized by immune complex in small blood vessel
of some organs, especially the kidney. Renal involvement
frequently influences dyslipidemia prevalence in SLE
patients.
17,29
In this study, there was no influence of renal
involvement against dyslipidemia. But, if we conduct
respective analysis for each lipoprotein, apparently there
is an influencing tendency of HDL cholesterol by
bivariate analysis, with p = 0.032 and OR 3.85 (CI 95%,
1.26-11.72).
The study results which correlate the influence of
renal involvement and dyslipidemia indicate different re-
sult. Leong et al (1994) found SLE patients with renal
involvement in inactive disease activity; and by LACC
criteria (lupus activity criteria count) with the score
Because of higher SLE prevalence in female
compare to male, then in this study we found dyslipidemia
in female of 74.3% (55 subjects) and 100% males
(3 subjects). The high prevalence of dyslipidemia in male
(100%) indicates as if there is quite high dyslipidemia
prevalence in male, but this is caused by less male samples
which were only 3 subjects. We assumed that higher
predilection of female compare to male is caused by
hormonal factors which associated in SLE pathogenesis.
Lahita reported some abnormality of estrogen and
androgen metabolism.
37
Age
In this study, the youngest age was 15 years old and
the oldest was 51 years with the mean age of 30 years.
This study indicates similar result with American study i.e.
SLE may be diagnosed at any age, the peak age includes
second to fourth decades with the mean age of 30 years
old. The prevalence of SLE onset between 15-54 years old
is 80%, while under 16 years of age is 20%, and 15%
Table 13. The Bivariate Analysis Result of Some Variables Against HDL-C
HDL-C OR p Value
< 40mg/dL 40 mg/dL (CI 95%)
n % n %
Renal involvement
- Yes 9 47.4 10 52.6 3.85 0.032*
- No 11 19.0 47 81.0 (1.26-11.72)
Illness period
- < 3 years 12 33.3 24 66.7 2.06 0.263
- 3 years 8 19.5 33 80.5 (0.73-5.82)
Prednisone dose
- 30 mg/day 8 40 12 60 2.50 0.172
- < 30 mg/day 12 21.1 45 78.9 (0.83-7.49)
Chloroquine
-No Chloroquine 19 26.0 54 74.0 1.06 1.000
- 250-500 mg/day 1 25.0 3 75.0 (0.10-10.77)
Mex SLEDAI
- 2 17 37.8 28 62.2 5.87 0.011*
- < 2 3 9.4 29 90.6 (1.55-22.25)
* significant
Table 14. The Multivariate Analysis Against HDL-C
Variable OR Min Max p
Prednisone dose 30
mg/day
2.50 0.83 7.49 0.172
Renal involvement 3.85 1.26 11.72 0.032
Mex-SLEDAI 5.87 1.55 22.25 0.011
141
Vol 37 Number 3 July-September 2005 The Proportion of Dyslipidemia in SLE Patient
<2, they found significant triglycerides, total cholesterol
and TC/HDL level by multivariate method.
17
As known, renal involvement is correlated to
abnormal lipid profile. Proteinuria is a stimulus to increase
lipid synthesis and urinary HDL loss may play an
important role in lipid synthesis. The other study found
that hyperlipidemia in animal study may disturb the renal
function and controlling hyperlipidemia may inhibit the
glomerulosclerosis process which may cause renal
failure. We expect that hyperlipidemia-controlling effort
in SLE patients may reduce the mortality caused by
renal involvement.
17,28,29,42
The Inf l uence of Pr edni sone Fact or Agai nst
Dyslipidemia
SLE treatment may cause dyslipidemia. Prednisone
may increase total cholesterol, VLDL cholesterol, LDL
cholesterol and triglycerides.
6,7
In this study we found that prednisone treatment by
>30 mg/day has not shown any influences against
dyslipidemia prevalence in SLE patients, which by
bivariate analysis we found p =0.130 with OR 3.83 (CI
95% 0.80-18.33). After every analysis has been
conducted for each lipid profile, we found that
prednisone treatment by >30 mg/day has a tendency to
correlate with cholesterol level >200 mg/dL, which in
bivariate analysis we found p =0.068 and OR 3.00 (CI
95% 1.05-8.58). Similar to the multivariate analysis, we
also found significant value i.e. p =0.040 and OR 3.00
(CI 95% 1.05-8.58). Prednisone also has influencing
tendency against triglyceride level >150 mg/dL. By
bivariate analysis we found p =0.003 and OR 6.00 (CI
95% 1.89-18.99), and by multivariate analysis we found
significant value i.e. p =0.002 with OR 6.00 (CI 95%
1.90-18.99).
This study is also consistent with the study
conducted by Ettinger et al (1987) that also found
increased triglycerides and cholesterol level of SLE
patients who had prednisone compared to placebo.
31,43
Corticosteroids which is used in SLE treatment has
important role in the pathogenesis of lipoprotein
abnormality.
31,32
Steroid administration is one of strong
factor in dyslipidemia occurrence. This is consistent with
the study of Leong et al (1994), which found significant
increased total cholesterol, LDL, triglycerides level, low
HDL level in the patients who had received prednisone,
with mean dose of 30 mg/day.
17
Ilowit et al found
increased total cholesterol and triglycerides level in SLE
patients who received steroid treatment.
17
Gregor et al said that prednisone administration more
than 10 mg/day may cause abnormal lipid profile.
34
Petri
et al studied 264 SLE patients and predicted increased
cholesterol level of 7.5 mg/dL for every increment of 10
mg prednisone.
7,23
The mechanism of corticosteroids causing
lipoprotein metabolism alteration is through
hypercothicolism which causes insulin resistance and
hyperinsulinemia, which consequently will stimulate
hepatic VLDL and HDL production.
31,32,33
The in vitro
study indicates that corticosteroids inhibit receptor
uptake and LDL internalization, and corticosteroid
supplement may also disturb VLDL catabolism through
decreased activity of lipoprotein lipase.
32
We assume that
the mechanism of increased HDL is caused by
increased hydrolysis of VLDL. Short-period f corticos-
teroid administration will increase the activity of
Table 15. The Bivariate Analysis Result of Some Variables Against LDL-C
LDL-C OR p Value
130 mg/dL < 130mg/dL (CI 95%)
N % n %
Renal involvement
- Yes 7 36.8 12 63.2 1.03 1.000
- No 21 36.2 37 63.8 (0.35-3.01)
Illness period
- < 3 years 18 50 18 50 3.10 0.036
- 3 years 10 24.4 31 75.6 (1.18-8.15)
Prednisone dose
- 30 mg/day 8 40.0 12 60.0 1.23 0.902
- < 30 mg/day 20 35.1 37 64.9 (0.43-3.51)
Chloroquine
-No Chloroquine 27 37.0 46 63.0 1.76 1.000
- 250-500 mg/day 1 25.0 3 75.0 (0.17-17.78)
Mex SLEDAI
- 2 17 37.8 28 62.2 1.16 0.948
- < 2 11 34.4 21 65.6 (0.45-2.98)
142
Linda K Wijaya, etal Acta Med Indones-Indones J Intern Med
lecithin-cholesterol acyl transferase (LCAT), which
finally will increase HDL
2
. While in contrary, long-
period of corticosteroid administration will suppress the
HDL
2
level.
31
The Inf l uence of Chl oroqui nes Fact ors Agai nst
Dyslipidemia
Chloroquines has protective nature against
dyslipidemia,
35,46
so that SLE patients who had not
received chloroquines tends to have dyslipidemia.
In this study we found that SLE patients who had not
received chloroquines had no influence against dyslipidemia
prevalence after the analysis either by bivariate or
multivariate methods. These may be caused by small sample
size of subjects receiving chloroquines. We expect that if
we conduct a study with more subject samples
receiving chloroquines then it will give better significant
result.
Wallace (1990) conducted study in 155 SLE female
patients who received only chloroquines, chloroquines and
prednisone, only prednisone and none of drugs. They found
that in the patient who has received chloroquines,
cholesterol, triglyceride and LDL level were significantly
reduced. In the patient who had received both drugs, there
were decreased LDL levels of 15% (p <0.05) and
decreased triglycerides level (p <0.05) compared to the
patient who had only received steroids.
35
Petri et al conducted analysis in 264 patients, and they
found that hydroxyl-chloroquines dose of 200-400 mg is
correlated to decreased cholesterol level of 8.9 mg/dL.
2,6,32
The mechanism of how does chloroquines may
decrease lipid level has not been established yet,
eventhough chloroquines have multiple effects on
hepatic-cholesterol metabolism. Experimental animal
study showed that chloroquines decreased acid-bile
serum level and cholesterol level up to 10-20% and
inhibited by the VLDL secretion. In tissue culture,
chloroquines is also known as lisosomotropic agents
which inhibit proteolysis of some LDL receptors and
increase the amount of LDL receptor because
chloroquines mediate decreased cholesterol synthesis,
although internal hydrolysis inhibition of ester-cholesterol
may also increase the amount of LDL receptor.
35,37
The Inf l uence of Mex-SLEDAI Fact or Agai nst
Dyslipidemia
There are some criteria to evaluate illness activity
such as British Isles Lupus Assessment Group (BILAG),
European Consensus Lupus Activity Measurement
(ECLAM), Systemic Lupus Activity Measure (SLAM),
Systemic Lupus Erythematosus Disease Activity Index
(SLEDAI), Mexican Modification of the Systemic
Lupus Erythematosus Disease Activity I ndex
(Mex-SLEDAI ), etc.
40,41
I n this study, we used
Mex-SLEDAI criteria because Mex-SLEDAI has
adequate reliability similar to the original SLEDAI
(r=0.894 vs 0.8670) and it has inexpensive cost.
40,41
The
illness criteria include active illness if the Mex-SLEDAI
score >2 and inactive illness if the score are <2.
In this study, we found that an active SLE patient
has no influence against dyslipidemia prevalence. But if
we conduct some analyses against every lipid profile
either by bivariate or multivariate method, then we will
find influencing tendency between Mex-SLEDAI and
HDL cholesterol <40 mg/dL. By bivariate analysis we
found p = 0.011 with OR 5.87 (CI 95%, 1.55-22.25),
while by multivariate analysis we found p =0.009 with R
5.87 (CI 95% 1.55-22.25).
This study is consistent with the study of Romero et
al that found low HDL cholesterol level in SLE patients.
Romero also used the Mexican modification of the
systemic lupus erythematosus disease activity index.
(Mex-SLEDAI) in order to observe correlation factors
of illness activity. Apparently, illness activity correlated
to HDL and triglycerides level.
25
We thought that low HDL level in active SLE
patients is caused by the activity of lipproteinlipase
mediated by increased tumor necrosis alpha and
interleukin 1 in active SLE and the HDL will return to
normal value if there is SLE remission.
12,17,33
These had
been proven by Ilowite, who found HDL level return to
normal value after SLE remission.
17
Alekberova et al found that in the active SLE
patient, there is increased triglyceride level, low HDL
level and increased cholesterol level. The alteration of
lipid profile is more severe and more atherogenic in
maximal SLE activity, while the quantity, quality, and HDL
composition may cause anti-atherogenic alteration on li-
poprotein of SLE patients.
18
Borba et al (1997) found increased triglyceride and
VLDL level and low HDL level for inactive SLE
patients. While in the active patient, there was greater
increased VLDL and triglyceride level as well as
decreased HDL.
19
In this study, we investigated fasting-lipid profile in
36 SLE patients who had not received treatment
compared to 30 controls. The illness activity was
measured by SLEDAI. From the study result we found
increasing VLDL and TG results as well as decreased
HDL level in the active patient compared to inactive SLE
patients. We found significant correlation between
SLEDAI score and all of lipid fraction.
38
Leong et al (1994) used the criteria of Lupus
Activity Criteria Count (LACC) to evaluate illness
143
Vol 37 Number 3 July-September 2005 The Proportion of Dyslipidemia in SLE Patient
activity and they found low HDL, increased mean value
of total cholesterol, LDL, triglycerides and TC/. HDL in
active illness.
17
Ilowite et al found low HDL and increased
triglycerides in active illness.
17
Bruce reported that Borba et al found a correlation
between systemic lupus erythematosus disease
activity index and total cholesterol, LDL and HDL level.
In an active Lupus patient, there was 79% risk of abnor-
mal HDL and 31% risk of abnormal triglyceride. The
presence of vasculitis was highly correlated to lipid
profile abnormality and decreased activity of lipoprotein
lipase enzymes. Active lupus may decrease HDL level
through suppression of lipoprotein lipase.
2,38
Ilowite et al evaluated 10 SLE children, and they found
that illness activity is correlated to low HDL level.
7
In
that study, they found decreased HDL level and
increased triglyceride level in active disease.
12
The Inf l uence of Il l ness Peri od Fact or Agai nst
Dyslipidemia Prevalence
In this study we found an influencing tendency
between illness period <3 years and dyslipidemia
prevalence in SLE patients because by bivariate
analysis we found p =0.001 with OR 12.04 (CI 95%
2.54-57.05). After the multivariate analysis had been
conducted, we found significant correlation, i.e. p=0.001
with OR 12.04 (CI 95% 2.54 57.05).
Illness period <3 years indicates associated tendency
to dyslipidemia. We thought that this may be caused by
the high illness-activity itself, and the patients are still
using high-dose steroid, so that the illness period acts as
a risk-factor causing dyslipidemia.
Furthermore, we conducted analysis of illness
period <3 years against every lipoprotein. By bivariate
analysis against cholesterol level >200 mg/dL we found
p =0.161 with R 2.15 (CI 95% 0.85-5.44). By bivariate
analysis against triglyceride level >150 mg/dL, we found
p =0.010 with OR 3.80 (CI 95% 1.47-9.82). By
bivariate analysis against HDL cholesterol level <40 mg/
dL, we found p =0.263 with OR 2.06 (CI 95% 0.73-
5.83). By bivariate analysis against LDL cholesterol level
>130 mg/dL, we found p =0.036 with OR 3.10 (CI 95%
1.18-8.15).
From the study result we found that bivariate
analysis for illness period <3 years indicates influencing
tendency against dyslipidemia prevalence. Similarly,
illness period <3 years indicates influencing tendency
against triglyceride level >150 mg/dL
Bruce et al found increased total cholesterol in 75.4%
SLE patients. For the first 3 years, since they had been
diagnosed as SLE, persistent cholesterol occurred in
40.3% (134 patients). Bruce found 79% CHD and some
significant CHD predictors such as onset age >35 years,
high-steroid accumulation and no chloroquines treatment.
Persistent hypercholesterolemia in the first 3 years of
SLE is a mortality risk factor.
22,23
Alekberova et al found high triglycerides, low HDL
level in the patient with more than 5 years illness.
18
CONCLUSION
In SLE patients we found that illness period of <3 years
represents a significant factor for dyslipidemia
prevalence. Prednisone >30 mg/dL is the correlative
factor for total cholesterol >200 mg/dL and triglycerides
>150 mg/dL. Mex-SLEDAI >2 is the correlative factor
for HDL cholesterol <40 mg/dL.
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