Pragmatic Aspect of C-Reactive Protein Alone and in Combination with Lipid Profile in Patients with Coronary Artery Disease
A. Vijaya Anand,
P. Sampath Kumar,
S. Sheik Abdulla,
B. Hari Krishnan
The present study was designed to evaluate the association of inflammatory
marker C-reactive protein (CRP) alone and in combination with lipid profile
in the prognosis of coronary artery disease (CAD) since the cardio vascular
disease (CVD) is considered to be a multifactorial disease driven by inflammatory
reactions. One hundred and fifty patients were recruited for the study,
of which, 75 belongs to control and 75 were test group. For the entire
study population CRP and lipid profile were measured. Among the patients
with complication (test group), there was a significant elevation in the
levels of CRP and lipid profile than the control. It was also found that
a combination of measurement of CRP with total cholesterol (TC) or low-density
lipoprotein (LDL) cholesterol testing may proven to be even a better marker
of risk response in patients with CAD.
to cite this article:
A. Vijaya Anand, S. Kalavathy, M. Chenniappan, P. Sampath Kumar, N. Manoharan, S. Sheik Abdulla, R. Chandrasekar and B. Hari Krishnan, 2008. Pragmatic Aspect of C-Reactive Protein Alone and in Combination with Lipid Profile in Patients with Coronary Artery Disease. Journal of Medical Sciences, 8: 743-746.
It is awesome to note that the death rates in the cardiovascular diseases
(CVD) are incredibly increasing. This is due to the fact that the markers
that are in existence fail to introspect the facts in detail. The Framingham
study showed that 35% of cases of coronary artery disease (CAD) were in
people with normal total cholesterol (TC) levels (Castelli, 1996). These
findings point out the need for markers that better predict cardiovascular
risk. In the most recent years, special importance is being laid on inflammation
in the pathogenesis of atherosclerosis and its complication. Inflammation
also regulates the production of the acute phase proteins such as C-reactive
protein (CRP), fibrinogen and serum amyloid A (Gabay and Kushner, 1999;
Uhlar and Whitehead, 1999). The serum concentration of CRP can increase
>1000-fold upon inflammation and with a half-life of 19 h, CRP is a
very stable downstream marker of the inflammatory process (Black et
al., 2004). Because CRP is such a sensitive indicator of the inflammatory
process, it has been extensively studied whether plasma concentrations
of CRP and other circulating inflammatory proteins (e.g., fibrinogen,
interleukin-6) have predictive value in the pathogenesis of CVD.
Many clinical and population studies, with cross-sectional and nested
case control designs, proved these inflammatory mediators to be predictors
of CVD (Danesh et al., 1998; Koenig et al., 1999; Ridker
et al., 1998a, 2000). Most clinical studies report that CRP is
an independent predictor of risk of atherosclerosis (Libby and Ridker,
2004), cardiovascular events (Black et al., 2004), atherothrombosis
(Pepys and Hirschfield, 2001), hypertension (Sesso et al., 2003)
and myocardial infarction (Ridker et al., 2002), even after considering
other cardiovascular risk factors such as age, smoking, obesity, diabetes,
hypercholesterolemia and hypertension. However, the prognostic value of
CRP in combined with lipid profile in patients with CVD and its application
in secondary prevention, have been investigated recently. The content
of this study details about the assessment of the prognostic value for
CRP alone, as well as in combination with various blood lipids in patients
MATERIALS AND METHODS
Patients: The study population consisted of 75 patients (test
group) with a mean age of 62.3±8.1 years, admitted to the Ramakrishna
Hospital Cardiac Care Unit. The control group included 75 patients with
mean age of 59.1±6.8 years, who entered the one day hospitalized
health check program, were included in this study. The present study included
the taking of a full medical history, physical examinations, blood chemistry
and an electrocardiogram. The diagnosis of CVD was based on a history
of ischemic chest pain and characteristic ECG changes. All patients gave
written informed consent before the study. This study was carried out
from April 2005 to September 2007.
Biochemical parameters and assay: Samples for the analysis of
CRP and lipid profile were obtained in the fasting state. The venous blood
samples were drawn into pyrogen-free blood collection tubes without additive.
The serum was collected after centrifugation at 3500 rpm for 3 min and
then stored at -70° C until analyzed. CRP was measured by using immunoturbidometry
method. Estimation of TC, serum triglycerides (TG) and high-density lipoprotein
(HDL) cholesterol, were performed colorimetrically by using commercial
kits. The value of low-density lipoprotein (LDL) cholesterol and very
low-density lipoprotein cholesterol (VLDL), were calculated using Friedwald`s
equation. The value of TC/HDL cholesterol ratio and LDL/HDL cholesterol
ratio were calculated by TC/HDL cholesterol and LDL/HDL cholesterol, respectively.
Statistical analysis: Statistical analysis was performed with
SPSS 12 statistical software package. Data were recorded on a pre-designed
proforma and managed on spreadsheet. All the entries were checked for
any error. Descriptive statistics for quantitative variables were computed
by mean and standard deviation. Means in the two groups were compared
by Student`s t-test. In this study, p<0.05 has been considered as statistically
The present study demonstrates that considerable variability is observed
between control and test group. Among the patients with complication the
baseline mean CRP concentration increased significantly (p<0.001) than
the control (Table 1). The mean level of CRP in control
is found to be 0.5±0.3 and in test group 1.3±0.7 (patients
||Baseline clinical characteristics
The mean levels of TC in control is found to be 159.5±28.3 and
in test group 199.5±36.5. The mean levels of TG in control is found
to be 135.6±60.4 and in test group 167.8±78.5. Thus, there
is a significant increase of TC (p<0.001) and TG (p<0.01) levels
in test group than the control. The mean levels of HDL cholesterol in
control is found to be 39.7±7.0, in the test group 41.9±8.1.
The mean levels of LDL cholesterol or bad cholesterol in control is found
to be 92.7±25.3, in the test group 124.9±36.8. Significant
increase (p<0.001) was noted in the mean level of LDL cholesterol in
test group. The mean level of VLDL cholesterol in control is found to
be 27.0±12.1, in the test group 33.1±15.6. The elevated
level of CRP and lipid profile seems to be a strong indicator of CAD risk.
The mean levels of TC/HDL cholesterol ratio in control is 4.0±0.7
and in test group 5.4±1.2. The mean levels of LDL/HDL cholesterol
ratio in control is 2.3±0.7 and in test group 3.4±1.1.
Atherosclerosis is an inflammatory disease and it was thought that circulating
factors associated to inflammation might be predictors of CVD in general
populations. In 2003, despite the lack of consistent epidemiological data,
the Centers for Disease Control and Prevention (CDC) and the American
Heart Association (AHA) concluded that it is reasonable to measure CRP,
a sensitive circulating marker of inflammation, as an adjunct to the measurement
of established risk factors in order to assess the risk of CAD (Pearson
et al., 2003).
The results of the present study indicate that an elevated CRP level
is a strong indicator of cardiovascular events. CRP plasmatic levels might
increase in patients with acute coronary syndrome (ACS). Elevated CRP
plasmatic concentrations carry out a prognostic significance, both in
subjects with ST elevation ACS (Brunetti et al., 2006) and with
unstable angina - non-ST elevation ACS (Sabatine et al., 2002;
Zebrack et al., 2002). Moreover, increased levels of CRP could
be detected also in subjects with risk factors for CVD such as hypertension
(Lakoski et al., 2005) or diabetes (Kahn et al., 2006).
Based in part on these data, high-sensitivity assays for CRP have become
existing in standard clinical laboratories. However, clinical application
of CRP testing will depend not only on demonstration of independent predictive
value, but also on demonstration that addition of CRP testing to traditional
screening methods improves cardiovascular risk prediction. The most important
findings of the present study is that the patients with a combination
of elevated levels of CRP and TC or LDL cholesterol showed the highest
risk compared to the measurement of only one of these marker. Results
of the present study also suggest that the atherogenic metabolic disturbance
may be adequately reflected by the variation in the TC/HDL cholesterol
and LDL/HDL cholesterol ratio.
The concurrent assessment of CRP and blood lipids, representing two different
pathophysiological features of atherosclerosis, may be superior in identifying
patients at high coronary risk. Findings from Multiple Risk Factors Interventional
Trail (MRFIT) demonstrated a direct positive association between CRP and
CAD mortality in men followed over a 17 year period (Kuller et al.,
1996). Similar positive association between CRP and future coronary events
in apparently healthy men was also demonstrated by Physician`s Health
Study (PHS) data set (Ridker et al., 1998b). Blake and Ridker (2001)
indicated that CRP was the single most powerful predicator of cardiovascular
risk in all of the inflammatory and lipid markers. In this multivariate
analysis, matched for age and smoking and adjusted for other cardiovascular
risk factors, found that only CRP and TC/HDL cholesterol ratio were independent
predictors of future cardiovascular risk. Furthermore, available studies
suggest that the concentration of CRP testing with traditional lipid screening
may significantly improve cardiovascular risk prediction, particular when
LDL cholesterol is low (Blake and Ridker, 2001).
CAD is multifactorial in etiology. Among a variety of serum biomarkers
of CAD risk, CRP is one of the most supported by research and clinical
utility. The present findings suggest that the measurement of CRP with
lipid profile might be useful for risk stratification in patients with
CAD. Modifying the risk factors or maintaining a healthy lifestyle, such
as losing excess weight, no smoking and regular exercise, can be recommended
as ways to reduce CRP and lipid profile levels and the risk of CAD.
The authors are thankful to Mr. P.R. Suresh Babu, Micro Labs, Trichy,
for his technical assistance.
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