Correlation between LDL-cholesterol and C-reactive protein among an apparently healthy population in the city of Athens

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Vol.3, No.6, 338-342 (2011)

doi:10.4236/health.2011.36058

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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: [email protected]

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

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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

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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

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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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