Background: C-reactive protein (CRP) is an acute-phase reactant protein synthesized by the liver in response to acute\ud
stress in a wide range of acute and chronic inflammatory conditions. In healthy subjects and patients presenting with\ud
coronary artery disease (CAD), elevated levels of CRP has repeatedly been demonstrated to predict future cardiovascular\ud
events.\ud
Methods: We measured high sensitivity C-reactive protein (hs-CRP) levels in 382 consecutive patients with CAD and 60 healthy controls by immunoturbidimetry method. Risk factors like hypertension, diabetes mellitus, dyslipidaemia,smoking, obesity and family history of premature CAD were assessed.\ud
Results: The mean age of patients with CAD was 53.5±11.8 years (303 males) and that of control group was 50.83±8.07(28 males). The patient group had significant higher concentration of mean hs-CRP levels when compared\ud
with the healthy control group (1.8±1.9 mg/L vs 0.35±1.1 mg/L, p<0.001). The mean hs-CRP levels of unstable angina\ud
(USA) and myocardial infarction (MI) patients was higher than chronic stable angina (CSA) patients (p<0.05). Based\ud
on the disease severity, we found a significantly higher hs-CRP levels in patients of triple vessel disease when compared\ud
to patients with single vessel disease (p=0.01).\ud
Conclusions: Elevated serum hs-CRP levels provide a useful marker for cardiovascular risk which, when combined\ud
with traditional risk factors, may help improve global risk prediction. Our study showed a significant contribution of\ud
hs-CRP to coronary risk prediction with better discrimination

D. Rajasekhar

G. Subramanyam

K. Latheef

P.V.L.N. Srinivasa Rao

S. Guruprasad

V. Vanajakshamma

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126
Original Article:
High sensitivity C-reactive protein levels across spectrum and severity of
coronary artery disease
S. Guruprasad,1 D. Rajasekhar,1 G. Subramanyam,1 P.V.L.N. Srinivasa Rao,2
V. Vanajakshamma,1 K. Latheef1
Departments of  1Cardiology, 2Biochemistry, Sri Venkateswara Institute of Medical Sciences, Tirupati
ABSTRACT
Background: C-reactive protein (CRP) is an acute-phase reactant protein synthesized by the liver in response to acute
stress in a wide range of acute and chronic inflammatory conditions. In healthy subjects and patients presenting with
coronary artery disease (CAD), elevated levels of CRP has repeatedly been demonstrated to predict future cardiovas-
cular events.
Methods: We measured high sensitivity C-reactive protein (hs-CRP) levels in 382 consecutive patients with CAD and
60 healthy controls by immunoturbidimetry method. Risk factors like hypertension, diabetes mellitus, dyslipidaemia,
smoking, obesity and family history of premature CAD were assessed.
Results: The mean age of patients with CAD was 53.5±11.8 years (303 males) and that of  control group was
50.83±8.07(28 males). The patient group had significant higher concentration of mean hs-CRP levels when compared
with the healthy control group (1.8±1.9 mg/L vs 0.35±1.1 mg/L, p<0.001). The mean hs-CRP levels of unstable angina
(USA) and myocardial infarction (MI) patients was higher than chronic stable angina (CSA) patients (p<0.05). Based
on the disease severity, we found a significantly higher  hs-CRP levels in patients of triple vessel disease when com-
pared to patients with single vessel disease (p=0.01).
Conclusions: Elevated serum hs-CRP levels provide a useful marker for cardiovascular risk which, when combined
with traditional risk factors, may help improve global risk prediction. Our study showed a significant contribution of
hs-CRP to coronary risk prediction with better discrimination.
Key words: High sensitivity C-reactive protein, Chronic stable angina, Atherosclerosis, Dyslipidaemia.
Guruprasad S, Rajasekhar D, Subramanyam G, Srinivasa Rao PVLN, Vanajakshamma V, Latheef K. High sensitivity C-reac-
tive protein levels across spectrum and severity of coronary artery disease. J Clin Sci Res 2012;3:126-30.
Corresponding author: Dr D. Rajasekhar, Professor & Head, Department of Cardiology, S.V. Institute of Medical
Sciences, Tirupati.  e-mail: drdrsekhar@yahoo.co.in
Received: 11 February, 2012.
INTRODUCTION
C-reactive protein (CRP), named for its capac-
ity to precipitate the somatic C-polysaccharide
of Streptococcus pneumonia, was the first
acute-phase protein to be described and is con-
sidered to be an exquisitely sensitive systemic
marker of inflammation and tissue damage.1 In-
flammation plays a major role in all stages of
atherosclerosis, from lesion initiation to plaque
rupture and ultimately the clinical thrombotic
complications.2 Elevated levels of high sensi-
tivity C-reactive protein (hs-CRP) in healthy
patients have been found to be predictive of a
first cardiac event and is useful in identifying
patients at increased risk for a cardiac event.3,4
Being a sensitive marker of inflammation, CRP
responds rapidly to various pro-inflammatory
stimuli, is elevated during atherogenesis and
may serve as a marker of ongoing atheroscle-
rosis. Furthermore, CRP activates complement
after binding to oxidized low-density lipopro-
tein (LDL), and mediates the uptake of LDL-
cholesterol (LDL-C) by macrophages.5 Role of
inflammation in the pathogenesis of atheroscle-
rosis especially the associations between CRP
with cardiovascular risk factors and disease risk
have gained much attention in the recent past.6
Some studies have shown that serum hs-CRP
measurements are predictive of cardiovascular
ischaemia and death in patient populations with
angina or acute coronary syndromes (ACS).7
There is evidence that hs-CRP, a leading in-
flammatory biomarker for clinical application,
is independently associated with the risk of in-
hs-CRP levels in CAD Guruprasad et al127
cidence or recurring cardiovascular events re-
gardless of the lipid levels.8
MATERIAL AND METHODS
Study population
We recruited 382 consecutive patients with
CAD, admitted under care of the Department
of Cardiology, Sri Venkateswara Institute of
Medical Sciences, Tirupati, India, from August
2004 to August 2005. The study included pa-
tients attending out-patient service as well as
admissions into intensive coronary care unit
(ICCU). The patient group included  the entire
spectrum of CAD, ie., chronic stable angina
(CSA), unstable angina (USA) and myocardial
infarction (MI), ST elevation myocardial
infarction(STEMI) and  non-ST elevation myo-
cardial infarction  (NSTEMI). The diagnosis
of CAD was evidenced by electrocardiogram
(ECG) abnormalities, positive exercise testing
[treadmill test (TMT), perfusion scan (Tc-
MIBI)], elevated creatine phosphokinase
(CPK), and its isoenzyme CPK-MB and coro-
nary angiography (CAG). Patients with other
systemic illnesses where CRP is elevated (in-
fections, chronic inflammatory diseases like
rheumatoid arthritis etc.), patients with malig-
nancies, who had recent surgery or trauma, who
were on anti-inflammatory drugs, anti-
hyperlipidaemic agents and glitazones and
women on oral contraceptive pills were ex-
cluded from this study. Sixty healthy individu-
als were recruited into the control group. This
study was approved by the Institutional Ethi-
cal Committee.
Baseline assessment
Baseline assessment in all patients included a
detailed history, physical examination and car-
diovascular examination. Risk factors like dia-
betes mellitus, hypertension, smoking, obesity
and family history of premature CAD were as-
sessed. Earlier history of dyslipidaemia and
history of receiving statin therapy were also
enquired. Obesity was defined as body mass
index (BMI) greater than 25 Kg/m2 in patients
who underwent diagnostic CAG.9
Laboratory and other investigative measure-
ments
All patients underwent routine investigations
like haemoglobin, total white blood cell count,
erythrocyte sedimentation rate, ECG and chest
radiograph. Fasting serum lipid profile [total
cholesterol, high density lipoprotein (HDL)
cholesterol and triglycerides] was done in all
patients by using commercially available kits
on autoanalyzer (Synchron CX9 from Beckman
USA). Low density lipoprotein (LDL) choles-
terol values were calculated using the
Friedewald formula.10 Echocardiography was
done in all patients and controls using Sonos-
7500 (Philips, Netherlands) machine. A subset
of patients (n=221) underwent diagnostic CAG.
Serum samples for hs-CRP estimation were
assayed by Immunoturbidimetry method (Tu-
lip diagnostics, India).
Statistical analysis
All continuous variables were expressed as
mean and standard deviation; whereas categori-
cal variables were expressed as numbers with
percentages. Continuous variables were com-
pared using Students t-test and one-way analy-
sis of variance (one-way ANOVA). Relation-
ship between dependent variable CAD and in-
dependent variables was studied using regres-
sion analysis. All computation and statistical
analysis were done using SPSS version 13.0,
SPSS Inc. Chicago, USA.
RESULTS
The mean age of patients with CAD was
53.5±11.8 years (303 males). The mean age of
control group was 50.8±8.1 years (28 males).
Table 1 shows the clinical characteristics of the
study population and control subjects. The pa-
tients with CAD  had significantly higher hs-
CRP levels when compared with the healthy
control  group  (1.8±1.9  mg/L  vs 0.35±1.1
mg/L; p<0.001). The mean hs-CRP levels in
patients with  CSA, USA and MI are shown in
Table 2. The hs-CRP levels were significantly
higher in USA and MI subgroups when com-
hs-CRP levels in CAD Guruprasad et al128
hs-CRP levels in CAD Guruprasad et al
pared to CSA subgroup (p<0.05). We found a
significantly higher  hs-CRP levels in patients
with triple vessel disease when compared to
patients having single vessel disease (1.9±2.4
mg/L vs 1.4±1.5 mg/L; p=0.01) (Table 3). In
the present study also higher levels of hs-CRP
were in the middle aged asymptomatic healthy
controls (0.7±0.9 in mg/L control group;1.8±1.7
mg/L in patient group; age 31-40 years) than
young subjects (0.2±0.2 mg/L in control
group;1.5±1.1 mg/L in patient group; age 20-
30 years). Regression analysis showed no as-
sociation between mean hs-CRP levels and se-
rum lipid levels.
When the patients were stratified according to
cardiovascular risk  based on the hs-CRP lev-
els, there were 40% patients in lowest risk group
(hs-CRP range 0.1-0.7 mg/L), 15% patients in
moderate risk group (hs-CRP range: 1.2-1.9
mg/L) and 13% persons in highest risk group
(hs-CRP range 3.9-15 mg/L) (Table 4).
Table 1: Clinical characteristics of the study population and control group
Risk factor Patients (n=382) Controls (n=60)  p-value
Age (Years) 53.5±11.8 50.83±8.07 NS
Males [No. (%)] 303 (79%) 28 (47%) NS
Females [No. (%)] 79 (21%) 32 (53%) NS
Hypertension [No. (%)] 192 (50%) 16 (26%) NS
Diabetes mellitus [No. (%)] 155 (41%) 11 (18%) NS
Smoking [No. (%)] 100 (26%) 09 (15%) NS
Haemoglobin (g/dL) 12.67±7.34 – NS
Total cell count (mm3) 11634.68±9055.12 – NS
Total cholesterol (mg/dL) 188.62±47.73 150.28±30.13 NS
LDL cholesterol (mg/dL) 115.94±83.97 103.19±28.60 NS
HDL cholesterol (mg/dL) 38.36±5.85 41.33±6.02 NS
Triglycerides (mg/dL) 156.78±80.08 120.74±39.86 NS
VLDLC (mg/dL) 28.75±17.55 – NS
LVEF (%) 48.30±13.69 – NS
hs-CRP (mg/L) 1.8±1.9 0.35±1.1* 0.001
Data are expressed as mean and standard deviation for continuous variables
*p<0.001
LDL = low density lipoprotein; HDL = high density lipoprotein; VLDLC = very low density lipoprotein cholesterol;
LVEF = left ventricular ejection fraction; hs-CRP = high sensitivity C-reactive protein
Table 2: Mean hs-CRP levels based on type of  disease in patients with CAD (n = 382)
Disease severity No. (%) Mean hs-CRP (mg/L)* p-value
CSA 102 (27) 1.4±1.3
USA 74 (19) 2.0±2.0
MI 206 (54) 2.0±2.0 †
*Data are expressed as mean and standard deviation
†mean hs-CRP levels were significantly lower in CSA group when compared with USA and MI groups (p<0.05)
CAD = coronary artery disease;  CSA = chronic  stable  angina;   USA = unstable  angina;    MI = myocardial
infarction;    hs-CRP = high  sensitivity C-reactive protein129
DISCUSSION
Available evidence in the literature shows that
higher levels of hs-CRP are observed in CAD
patients than normal subjects.11-13 In the present
study also higher levels of hs-CRP were ob-
served in patients when compared to controls
(p<0.001). When comparing the values in three
groups of  CAD patients, significantly higher
levels were observed in  patients with USA and
MI when compared to patients of CSA
(p<0.05). Our findings are in agreement with
the findings of the Chennai study.12 The hs-CRP
levels in the present study are lower than the
observations reported in other studies.14,15 In
this study we observed significantly higher hs-
CRP levels in triple vessel disease than in single
vessel disease (1.9±2.4 Vs 1.4±1.5; p=0.01).
In this study hs-CRP levels were not influenced
by the lipid profile (total cholesterol, HDLC,
LDLC and triglycerides) which showed no as-
sociation in regression analysis. Earlier study
by Achari et al16 showed higher levels of TC
and decreased HDLC in patients than controls.
Present study showed no statistically signifi-
cant difference in mean hs-CRP levels in pa-
tients with normal and elevated TC, LDLC and
triglycerides. However, patients with low
hs-CRP levels in CAD Guruprasad et al
Table 3: Mean hs-CRP levels based on vessel disease severity in 221 patients who underwent CAG
Vessel severity     No. (%) Mean hs-CRP (mg/L)*
Normal coronaries 35 (16) 1.5±1.9
SVD 92 (42) 1.4±1.5
2VD 34 (15) 1.5±1.5
TVD 60 (27) 1.9±2.4†
* data are expressed as mean ± standard deviation
† significantly higher when compared with SVD (p=0.01)
CAG = coronary angiography; SVD = single vessel disease; 2VD = two vessel disease; TVD = triple vessel disease
Table  4: hs-CRP levels and risk distribution in patients with CAD
hs-CRP (mg/L) Risk group Distribution(%)
0.1-0.7 Lowest 40
0.8-1.1 Low 10
1.2-1.9 Moderate 15
2.0-3.8 High 22
3.9-15 Highest 13
CAD = coronary artery disease
HDLC have higher mean hs-CRP levels when
compared to patients with higher HDLC
(p=0.01).
Serum hs-CRP levels have been shown to pre-
dict MI, stroke, peripheral arterial disease and
sudden cardiac death.17,18 In the present study
hs-CRP levels showed positive association with
CAD in univariate logistic regression analysis
(OR: 2.4; 95% CI: 2.4-2.74; p<0.01). In a Japa-
nese study19 lower levels of hs-CRP were ob-
served in young adults (19-27 years) than
middle age group (40-60 years). Our observa-
tions are also similar to this study.
Elevated levels of hs-CRP in patients when
compared to controls, significant difference in
the levels of hs-CRP in acute coronary syn-
dromes, positive association with CAD and
absence of association of hs-CRP with lipid
parameters in our study, suggest that hs-CRP
may act as a risk factor independent of lipid
levels in predicting the risk of CAD.  Our find-
ings also support the observations of Ridker et
al20 who showed that reduced levels of hs-CRP
results in decreased incidence of cardiovascu-
lar events. Thus our findings suggest that higher
levels of hs-CRP are independently associated130
with an increased risk of CAD.
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hs-CRP levels in CAD Guruprasad et al

High sensitivity C-reactive protein levels across spectrum and severity of coronary artery disease

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