Vol.3, No.6, 338-342 (2011)
doi:10.4236/health.2011.36058
C
opyright © 2011 SciRes. Openly accessible at http://www.scirp.org/journal/HEALTH/
Health
Correlation between LDL-cholesterol and C-reactive
protein among an apparently healthy population in
the city of Athens
Anastasios Milionis1, Charalampos Milionis2*
1Social Insurance Institute—Regional Branch of N. Kosmos, (Department of Endocrinology), Athens, Greece;
2General Hospital of Karpenisi—Health Centre of D. Fragista, Karpenisi, Greece; *Corresponding Author:
Received 23 March 2011; revised 5 May 2011; accepted 10 May 2011.
ABSTRACT
Background: The atherogenic LDL is an impor-
tant generative cause for the endothelial dys-
function and the configuration of the athero-
sclerotic lesions. CRP is a sensitive marker of
inflammation on the vascular wall, but also
seems to participate in the ath eromatic process.
The correlation between LDL and CRP could
form valuable guidelines for the initiation of a
treatment with statins for individuals with an
increased risk of ischemic incidents. Objectives:
The aim of the study was to investigate a pos-
sible correlation between LDL and CRP in an
important number of apparently healthy indi-
viduals. Methods: The study material consisted
of the test results of 260 male and 484 female
adults with normal LDL levels who were clini-
cally healthy. The correlation between the LDL
and the CRP values of this group was investi-
gated in this group and CRP was compared with
the respective values of a group of 60 male and
204 female adults with elevated LDL levels. Re-
sults: It was ascertained that there is not a sta-
tistically important correlation between LDL and
CRP values in all groups (men, women, total) of
the population with normal LDL levels. Addi-
tionally, the CRP mean values were not statisti-
cally different between the individuals with
normal and raised LDL. Conclusion: A number
of causes are incriminated for the results. More
studies are definitely needed for the confirma-
tion of the results, particularly if the findings
could lead to the formation of guidelines for the
application of a treatment in people with normal
LDL levels but increased CRP levels.
Keywords: LDL-Cholesterol; C-Reactive Protein;
Atherosclerosis; Cardiovascular Rise
1. INTRODUCTION
Almost half of the vascular events appear in individu-
als with normal lipidemic profile. However, the classic
preventive anti-lipidemic treatment is indicated only for
individuals with hyperlipidemia. There are studies which
have demonstrated that a preventive treatment could be
administered to people with normal cholesterol levels
but increased levels of C-reactive protein (CRP) [1].
Elevated levels of low density lipoprotein (LDL) are
considered to participate in the atherogenic process.
Once deposited in the intima, LDL is subjected to
chemical modifications, such as oxidatation. The oxi-
dated form of LDL up-regulates a number of molecules
which trigger the adherence of monocytes and T-lym-
phocytes to the endothelial cells of the arterial wall. Af-
ter the monocytes and T-lymphocytes bind to the arterial
surface, they migrate into the subendothelial space,
where they differentiate and are transformed into
macrophages and foam cells. The oxidated LDL acts as a
chemoattractant for monocytes and lymphocytes and it
can also inhibit the macrophage mobility. Moreover, the
oxidated LDL can stimulate the production of many in-
flammatory mediators from other vascular cells, result-
ing in the promotion of the inflammation process. The
above actions, among other atherogenic effects, contrib-
ute to the formation of the atherosclerotic plaque [2].
Statins act by inhibiting the activity of the 3-hydroxy-
3-methylglutaryl-coenzyme A (HMG-CoA) reductase.
The latter is an enzyme which participates in the regula-
tion of the hepatic synthesis of cholesterol. Statins are
more effective in reducing LDL-cholesterol but less
drastic in lowering triglycerides and raising HDL-cho-
lesterol. They reduce the incidence of the atherosclerotic
events and are used for primary and secondary preven-
tion against cardiovascular episodes. It is believed that
statins may also have an anti-thrombotic and anti-in-
flammatory effect [3,4].
CRP is a sensitive marker of inflammation. In humans,

A. Milionis et al. / Health 3 (2011) 338-342
Copyright © 2011 SciRes. Openly accessible at http://www.scirp.org/journal/HEALTH/
339339
the plasma levels of CRP may rise rapidly and extend-
edly, as much as 10,000-fold or more, after an acute in-
flammatory stimulus [5]. CRP is mostly synthesized in
the hepatocytes but there is recent evidence which dem-
onstrates the extrahepatic production of CRP in different
cells including atherosclerotic lesions [6]. It is one of the
at least 40 plasma proteins which are defined as acute
phase proteins. Their plasma concentration increases or
decreases by at least 25% during an inflammatory proc-
ess [7]. In recent years, there is plenty of published data
which demonstrates a clinical significance of the raised
plasma levels of CRP for the evaluation of the cardio-
vascular risk in apparently healthy individuals. It is
recommended [8] that cut-off levels of high-sensitivity
CRP < 1.0, 1.0 to 3.0 and > 3.0 mg/L express low, aver-
age and high risk respectively for the development of
cardiovascular disease, even among apparently healthy
individuals with low-to-normal lipid levels. These raised
levels may reflect an underlying chronic inflammation of
the endothelium. In addition, CRP itself may participate
actively in the pathogenesis of atherosclerosis through
biological effects on the endothelial cells, the mono-
cytes-macrophages and the smooth muscle cells [9,10].
Therefore, CRP can constitute a biomarker for the clini-
cal estimation of the cardiovascular disease risk [11].
However, CRP cannot be considered as a specific prog-
nostic marker of ischemic incidents, since it is produced
in almost all the forms of inflammation, infection and
tissue damage.
According to the National Cholesterol Education Pro-
gram Guidelines, the desirable LDL levels in people of
high risk must be under 70 mg/dL [12]. The indication
for treatment with statins concerns all the individuals of
high cardiovascular risk, the individuals of moderate risk
with LDL > 135 mg/dL and the individuals of low risk
with LDL ≥ 190 mg/dL [13]. Although the statin therapy
is firmly established [14-17] and generally acceptable
for secondary prevention, the use of statins for primary
prevention remains a controversial subject [18,19].
The JUPITER trial [20] demonstrated that the admini-
stration of rosuvastatin in apparently healthy individuals
with LDL < 130 mg/dL and CRP > 2 mg/L reduced the
LDL levels by 50% as well as the ischemic vascular in-
cidents approximately by the same percentage. The CRP
levels were also reduced by 37% [21]. This trial tried to
answer the question whether individuals of this category
(normal LDL, increased CRP) would be benefited by
statins. There are also other studies which have demon-
trated that statins lower the CRP levels [22-24]. The as-
sumption that atherosclerosis is partly an inflammatory
process affected also by LDL could justify the use of
statins to individuals non-hyperlipidemic and without
any indications of vascular disease for primary preven-
tion, using the raised CRP levels as a criterion for the
initiation of the treatment. Therefore, the benefits from
statins may extend beyond the LDL reduction alone. At
this point, a critical question emerges. Are the LDL lev-
els independent of CRP levels? The present study aims
at the demonstration of the existence or not of a possible
correlation between LDL and CRP among apparently
healthy individuals with normal LDL and the compari-
son of the mean CRP values between individuals with
normal CRP and individuals with increased CRP.
2. MATERIAL—METHODS
The material of the study includes a series of LDL and
CRP test results from the records of the laboratorial ex-
aminations of the Microbiological Laboratory of the
Regional Department of N. Kosmos of the Social Insur-
ance Institute in the city of Athens from 2008 through
2010. The study population was divided in two groups.
The first group included 260 adult men (mean age 48
years old, mean weight 85 kg, and mean height 1.72 m)
and 484 adult women (mean values 48 years old, 85 kg,
and 1.62 m respectively) whose LDL values were lower
than 130 mg/dL or equal to 130 mg/dL. All the subjects
of the first group were clinically healthy without any
kind of inflammatory disease. The second group in-
cluded 60 men and 204 women with LDL higher than
130 mg/dL and it was used for comparison purposes.
The study was approved by the Administration of the
Institution and conducted after the issuing of the relative
authorization.
The correlation between LDL and CRP was investi-
gated among the individuals with a range of LDL values
≤ 130 mg/dl, separately in men, women and total. The
determination of the LDL limit was based on the JUPI-
TER study, according to which the coexistence of a CRP
value > 2 mg/dl is considered by certain clinical physi-
cians as a situation with increased cardiovascular risk
and imposes the initiation of a treatment with statins. In
addition, the mean values of CRP in the two study
groups were assessed and compared.
The appropriate statistical values of LDL and CRP
(mean, minimum, maximum, median, mode and stan-
dard deviation) among the study population as well as
the statistical comparisons were calculated with the use
of the statistical package SPSS 14.0 (Copyright © SPSS
Inc.).
The total cholesterol values were measured with the
CHO-POD Timber reaction method, the triglycerides
values with a photometrical (GPO-PAP) determination,
the HDL values with the immunoinhibition technique
and the CRP values with the method of turbidimetry.
The LDL values were calculated automatically accord-
ing to the formula “LDL = (total cholesterol—triglyc-

A. Milionis et al. / Health 3 (2011) 338-342
Copyright © 2011 SciRes. Openly accessible at http://www.scirp.org/journal/HEALTH/
340
erides)/5—HDL”. Tests with triglyceride values over
400 mg/dl were excluded. The form of the distributions
of the LDL and CRP values in the first group was exam-
ined and the Pearson’s correlation coefficient was calcu-
lated. The statistical comparisons were performed with a
χ2-test.
3. RESULTS
Table 1 presents the various statistical variables of the
of the LDL and CRP values of in the first group (indi-
viduals with LDL ≤ 130 mg/dL) of the study population.
The average LDL value in the specific group was 95
mg/dL (89 mg/dL in men and 98 mg/dL in women),
whereas the average CRP value in the same group was
0.93 mg/L (0.83 mg/L in men and 0.99 mg/L in women).
The mean CRP value in the entire second group (indi-
viduals with LDL > 130 mg/dL) was 0.90 mg/L (SD ±
0.75). Table 2 shows the Pearson’s correlation coeffi-
cients in the three subcategories (men, women, total) of
the first study group. It was found that the Pearson’s
Table 1. Statistical data of the LDL and CRP values in the first
group (individuals with LDL ≤ 130 mg/dL) of the study popu-
lation (264 men and 484 women).
Statistical variables Sex LDL (mg/dL) CRP (mg/L)
Mean
Men
Women
Total
89
98
95
0.83
0.99
0.93
Median
Men
Women
Total
91
103
101
0.60
0.70
0.70
Mode
Men
Women
Total
55
118
118
0.50
0.60
0.60
Standard deviation
Men
Women
Total
25
23
24
0.82
1,22
1,02
Minimum
Men
Women
Total
41
39
39
0.10
0.01
0.01
Maximum
Men
Women
Total
127
130
130
5.90
10.20
10.20
Table 2. Pearson’s coefficient in the first group (264 men and
484 women, LDL ≤ 130 mg/dL).
LDL CRP
LDL
Pearson
p-Value*
N
1
−
264
0.120
0.339
264
Male
CRP
Pearson
p-Value*
N
0.120
0.339
284
1
−
284
LDL
Pearson
p-Value*
Αριθμός
1
−
484
−0.073
0.425
484
Female
CRP
Pearson
p-Value*
N
−0.0,73
0.425
484
1
−
484
LDL
Pearson
p-Value*
N
1
−
748
−0.008
0.917
748
Total
CRP
Pearson
p-Value*
N
−0.008
0.917
748
1
−
748
* Significance
correlation coefficient was 0.120 in males (p-Value
0.339), −0.073 in females (p-Value 0.425) and −0.008 in
total (p-Value 0.917).
4. DISCUSSION
4.1. Main Discussion
The generative effect of LDL in atherosclerosis and
the pathogenic role of CRP either as an inflammation
marker or as a contributor to the atherogenic process are
acceptable to a great extend by the scientific community.
The initiation of a treatment with statins in people with
normal LDL levels (≤ 130 mg/dL) but increased CRP
levels (> 2.0 mg/L) is currently a research subject with
controversial opinions. The results of the present study
showed there is not a correlation between the LDL and
CRP values among the study groups’ populations. It is
being discussed whether certain factors interfere in this
conclusion.
The process of inflammation can be considered as a
body reaction to the destruction of architectural structure
of the vascular endothelium. In turn, inflammation

A. Milionis et al. / Health 3 (2011) 338-342
Copyright © 2011 SciRes. Openly accessible at http://www.scirp.org/journal/HEALTH/
341341
represents a significant factor which leads to the forma-
tion of atherosclerotic lesions and favors both the desta-
bilization of the atheromatic plaque and the formation of
thrombi [25]. It is assumed that various factors could
differentiate selectively the sensitivity of the vascular
endothelium or affect in various ways the organism’s
reaction to the “toxic” influence of LDL.
According to the Pearson’s correlation coefficient
(0.120 in males, −0.073 in females and −0.008 in total),
the LDL variations were not being followed by respec-
tive variations in the CRP values among the normal LDL
group in the present study. That is to say that an LDL
increase was not accompanied by a statistically respec-
tive CRP increase. Moreover, the comparison of the
mean values of CRP in the two study groups (individuals
with LDL ≤ 130 mg/dL and individuals with LDL > 130
mg/dL) showed that there is no statistically significant
difference (P > 0.05).
4.2. Conclusions
Nowadays, there is a clinical trend which supports the
study and use of certain biochemical markers, such as
oxidized phospholipids on apolipoprotein B-100 parti-
cles (OxPL/apoB), for the prediction of the development
of the atheromatic disease [26]. The findings of the pre-
sent study could also implicate a clinical significance.
They do not reject the initiation of a treatment with stat-
ins in individuals with a normal lipidemic profile but
increased CRP values (>2 mg/L), no matter what discus-
sion is being conducted on this field. However, the spe-
cific treatment should not be based exclusively on the
correlation of the LDL and CRP values, as certain re-
searchers believe, but it should include other criteria too.
Definitely, the coexisting increased levels of LDL and
CRP constitute a dangerous compound, even if the CRP
measurement has not been established as an important
marker for the prevention of cardiovascular incidents
and it is not included in the ordinary tests, unlike the
LDL evaluation. Further studies on this field are cer-
tainly necessary for the formation of well established
guidelines and the broad application of CRP screening
and the initiation of statin therapy or even treatment with
ezetimibe [27] in individuals with normal lipidemic pro-
file.
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