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Vol. 19, No. 2, October 2010 91
Introduction:
Coronary artery disease (CAD) is the end result
of the accumulation of atheromatous plaques
within the walls of the coronary arteries that
supply the myocardium.1
CAD is the largest single cause of death in the
UK and many parts of the world. Each year
there are approximately 60 deaths per 100,000.
Sudden cardiac death is a prominent feature
of CAD. One in every six coronary attacks was
found to present with sudden death as the first,
last, and only symptom.2
In USA, among adults age 20 and older, the total
number of coronary heart disease (CHD) in
2006 was 16,800,000 (about 8,700,000 men and
8,100,000 women). CHD caused about one of
every five deaths in the United States in 2005.
It is the largest single killer of American males
and females.3
National data on incidence and mortality of
coronary heart disease are few in Bangladesh.
The prevalence of coronary heart disease was
estimated as 3.3/1000 in 1976 and 17.2/1000
in 1986 indicating 5 folds in the disease in 10
years.4,5
HIGH SENSITIVE C-REACTIVE PROTEIN (hs-CRP)
AND ITS CORRELATION WITH ANGIOGRAPHIC
SEVERITY OF PATIENT WITH CORONARY ARTERY
DISEASE (CAD)
HASNAT MA1, ISLAM AEMM2, CHOWDHURY AW3, KHAN HILR4, HOSSAIN MZ5
Abstract:
Background: Association between the plasma hs-CRP levels and the severity of coronary
stenosis in subjects remains controversial. This cross sectional study was performed in the
Department of Cardiology, Dhaka Medical College during July 2008 to December 2009, to
determine whether the concentrations of hs-CRP correlate with the coronary atherosclerotic
disease assessed by coronary angiography.
Methods: For this purpose, a total number of 90 consecutive patients having IHD admitted in
the Dhaka Medical College Hospitals were enrolled in this study. Patients were divided into
three groups according to their level of hs-CRP. Out of 90 cases, 22(24.4%) patients were in
group I, in group II 33(36.7%) patients and rest 35(38.9%) were in group III according to their
hs-CRP level.
Severity of CAD was assessed by vessel score, stenosis score and extent score.
Result: Significant positive correlation (r=0.7409; p<0.001 r=0.6648; p<0.001 and r=0.6386;
p<0.001) was found between hs-CRP and vessel score, stenosis score and hs-CRP and extent
score suggesting increasing level of hs-CRP strongly suggestive of extensive coronary artery
disease.
Conclusion: High level of hs-CRP strongly suggestive of extensive coronary artery disease
Key words: hs-CRP, angiogram, coronary artery disease, vessel score, stenosis score and
extent score.
J Dhaka Med Coll. 2010; 19(2) : 91-97.
1. Dr. Mohammad Abul Hasnat, MD-Final Part Student, Dept. of Cardiology, DMCH.
2. Dr. AEM Mazharul Islam, Assistant Professor, Dept. of Cardiology, DMCH.
3. Dr. Abdul Wadud Chowdhury, Associate Professor, Dept. of Cardiology, DMCH.
4. Dr. HI Lutfur Rahman Khan, Professor and Head, Dept. of Cardiology, DMCH.
5. Dr. Mohammad Zaid Hossain, Assistant Professor, Dept. of Medicine, DMCH.
Correspondence: Dr. Mohammad Abul Hasnat, Department of Cardiology, Dhaka Medical College & Hospital
Cell Phone: +8801711229128, Email: drhasnat@hotmail.com
Vol. 19, No. 2, October 2010 92
Traditionally there are some conventional risk
factors like age, male sex, positive family
history, hypertension, smoking,
hyperlipidaemia, metabolic syndrome,
diabetes, lack of exercise, obesity, and some
emerging risk factors, like C-Reactive Protein,
Homocysteine, Fibrinogen.6
Less than 50% of the CAD can be ascribed to
traditional risk factors and rests are
unexplained.7 CRP has emerged as the most
exquisitely sensitive systemic marker of
inflammation and a powerful predictive marker
of future cardiovascular risk. Role for
inflammation has become well established over
the past decade or more in theories describing
the atherosclerotic disease process.8
A body of evidence now suggests that
atherosclerosis represents a chronic
inflammatory response to vascular injury
caused by a variety of agents that activate or
injure endothelium and promote lipoprotein
infiltration, retention, and modification,
combined with inflammatory cell entry,
retention and activation.9
So, from a pathological viewpoint, all stages,
i.e., initiation, growth, and complication of the
atherosclerotic plaque might be considered to
be an inflammatory response to injury.10,11 C-
reactive protein (CRP) is one of the acute phase
proteins that increase during systemic
inflammation.12 Several prospective studies
recently showed that plasma high sensitive C-
reactive protein (hs-CRP) levels, a more
sensitive CRP test, are a powerful predictor of
future myocardial infarction and cardiac death
among apparently healthy individuals.13
However, the association between the plasma
hs-CRP levels and the severity of coronary
stenosis in subjects remains controversial.
Some studies previously demonstrated such
associations whereas other could not found
it.14,15
This study was performed to determine
whether the concentrations of hs-CRP
correlate with the coronary atherosclerotic
disease assessed by coronary angiography.
Objectives:
General Objective:
1. To correlate the levels of hs-CRP with
angiographic severity of coronary artery
stenosis in patients with IHD admitted for
CAG in DMCH.
Specific objectives:
1. To correlate the levels of hs-CRP with vessel
score.
2. To correlate the levels of hs-CRP with
stenosis score.
3. To correlate the levels of hs-CRP with extent
score.
Materials and Methods:
This cross sectional study was done in the
department of cardiology, Dhaka Medical
College during July 2008 to, December 2009.
hs-CRP test was done in immunology
department of BSMMU.
CAG was done in the cath-lab of the
Department of Cardiology, Dhaka Medical
College Hospital.
Inclusion criteria
All patients of IHD admitted for CAG in
department of cardiology DMCH.
Exclusion criteria
1. Patient with past CABG
2. Patient with PTCA
3. Patient with valvular heart disease.
4. Patient with hepatic dysfunction.
5. Patient with a major non-cardiovascular
disease.
6. Patient with collagen vascular disease.
7. Any systemic infection.
8. Unwilling to give consent.
Statistical analysis:
For all statistical analyses, SPSS version 16.0
was used. For all statistical tests, p<0.05 was
considered as statistically significant.
Continuous variables were presented as mean
± SD and numerical variables were presented
as proportions. Continuous variables were
compared through the ANOVA test, categorical
variable by chi-square test, and correlation co-
efficient was done where applicable.
High Sensitive C-Reactive Protein (hs-CRP) and its Correlation Hasnat MA et al.
92
Vol. 19, No. 2, October 2010 93
Observation and Results:
Table I
hs-CRP distribution of the study patients (n=90).
hs CRP Number of Percentage
patients
Group I: <1.0 mg/L 22 24.4
Group II: 1.0 – 3.0 mg/L 33 36.7
Group III: >3.0 mg/L 35 38.9
Total 90 100.0
Table-I shows distribution of hs- CRP levels
among the study patients. A total of 90 cases
were included in the study the age ranged from
20 to 72 years. Among them 73 patients were
male and rest are female.
Patients were divided into three groups according
to their level of hs-CRP. The level of hs-CRP <1.0
mg/L was consider as group I, 1.0 mg/L to 3.0
mg/L group II and >3.0 mg/L group III. Out of 90
cases 22(24.4%) belong to group I, 33(36.7%) was
group II and rest 35(38.9%) was group III.
Table-II
Major risk factors status of the study patients (n=90)
Smoking Group I (n=22) Group II(n=33) Group III (n=35) Pvalue
n % n % N %
Present 9 40.9 22 66.7 21 60.0 0.157NS
Absent 13 59.1 11 33.3 14 40.0
Hypertension
Present 13 59.1 19 57.6 23 65.7 0.769NS
Absent 9 40.9 14 42.4 12 34.3
DM
Present 3 13.6 13 39.4 12 34.3 0.113NS
Absent 19 86.4 20 60.6 23 65.7
Dyslipidemia
Present 13 59.1 21 63.6 21 60.0 0.930NS
Absent 9 40.9 12 36.4 14 40.0
F/H IHD
Present 6 27.3 7 21.2 11 31.4 0.634NS
Absent 16 72.7 26 78.8 24 68.6
Group I= <1.0 mg/L; Group II= 1.0 – 3.0 mg/L; Group III= >3.0 mg/L; NS= not significant
Table III
Distribution of patients by vessel score (n=90)
Vessel score Group I(n=22) Group II(n=33) Group III (n=35) Pvalue
n % n % n %
0 18 81.8 4 12.1 2 5.7
1 2 9.1 16 48.5 4 11.4
2 1 4.5 10 30.3 6 17.1
3 1 4.5 3 9.1 23 65.7
Mean±SD 0.3 ±0.8 1.4 ±0.8 2.4 ±0.9 0.001S
Range (min-max) (0 -3) (0 -3) (0 -3)
J Dhaka Med Coll. Vol. 19, No. 2 October 2010
93
Vol. 19, No. 2, October 2010 94
Table-II shows distribution of major risk factors
among study patients. Regarding the smoking
status it was found that 9(40.9%) in group I,
22(66.7%) in group II and 21(60.0%) in group
III were smoker. No significant (p>0.05)
difference was found among three groups in
chi square test.
Hypertension was found in 13(59.1%) in group
I, 19(57.6%) in group II and 23(65.7%) in group
III. No significant (p<0.05) difference was found
among three groups in chi square test. The
results are shown in the table II.
Diabetes mellitus was found 3(13.6%) in group
I, 13(39.4%) in group II and 12(34.3%) in group
III. No significant (p>0.05) difference was found
among three in chi square test. The results
are shown in the table II.
Family history of IHD was found 6(27.3%),
7(21.2%) and 11(31.4%) in group I, group II and
group II respectively. No significant (p>0.05)
difference was found among three groups in
chi square test. The results are shown in the
table II.
Dyslipidemia was found in 13(59.1%) in group
I, 21(63.6%) in group II and 21(60.0%) in group
III. No significant (p>0.05) difference was found
among three groups in chi square test. The
results are shown in the table II.
Table –III shows distribution of patients by
vessel score. More than eighty (81.8%) had
vessel score ‘0’ in group I, in group II majority
(48.5%) had vessel score 1 and in group III most
(65.7%) had vessel score 3. The mean (±SD)
vessel score was 0.3±0.8, 1.4±0.8 and 2.4±0.9
in group I, group II and group III respectively.
The vessel score difference was statistically
significant (p<0.05) among three groups in
ANOVA test.
Table-IV shows Distribution of patients by
stenosis and extent score. The mean (±SD)
Stenosis score was 3.2±7.4, 23.5±18.9 and
38.3±26.5 in group I, group II and group III
respectively. The mean (±SD) extent score was
8.9±18.0 in group I, 36.1±16.9 in group II and
51.2±16.6 in group III. The Stenosis and extent
score difference were statistically significant
(p<0.05) among three groups in ANOVA test.
Correlation between hs CRP with vessel score
(n=90).
Hs CRP was expressed in mg/L and vessel score
ranges from 0 to 3 depending on the number of
vessel involve. Significant positive correlations
were found between hs-CRP and vessel score.
The values of Pearson’s correlation coefficient
was 0.7409 which is highly significant
(p<0.001). Therefore, there was linear positive
correlation between hs-CRP and vessel score
(Fig. 1).
Table IV
Distribution of patients by stenosis and extent score (n=90)
Group I(n=22) Group II(n=33) Group III (n=35) P value
Mean ±SD Mean ±SD Mean ±SD
Stenosis score 3.2 ±7.4 23.5 ±18.9 38.3 ±26.5 0.001S
Range (min-max) (0 -24) (0 -72) (0 -112)
Extent score 8.9 ±18.0 36.1 ±16.9 51.2 ±16.6 0.001S
Range (min-max) (0 -60) (0 -80) (0 -80)
Group I= <1.0 mg/L, Group II= 1.0 – 3.0 mg/L, Group III= >3.0 mg/L, NS= not significant
Fig.-1: The scatter diagram shows significant
relationship (r=0.7409) between hs-CRP and
vessel score.
High Sensitive C-Reactive Protein (hs-CRP) and its Correlation Hasnat MA et al.
94
Vol. 19, No. 2, October 2010 95
Correlation between hs CRP with stenosis score
(n=90).
Hs CRP was expressed in mg/L and stenosis
score ranges from 0 to 112. Significant positive
correlations were found between hs-CRP and
stenosis score.
The values of Pearson’s correlation coefficient
was 0.6648 which is highly significant
(p<0.001). Therefore, there was linear positive
correlation between hs-CRP and stenosis score
(Fig. 2).
(p<0.001). Therefore, there was linear positive
correlation between hs-CRP and extent score
(Fig.-3).
Discussion
This cross sectional study was carried out with
an aim to correlate the levels of hs-CRP with
angiographic severity of coronary artery
stenosis in patients with IHD admitted for CAG
in DMCH and to correlate the levels of hs-CRP
with vessel score, stenosis score and extent
score.
A total of 90 patients with IHD age ranging from
20 to 70 years were included in the study, who
were admitted for CAG in the department of
Cardiology, Dhaka Medical College during July
2008 to December 2009.
The patients were divided into three groups
according to their level of hs-CRP, which were
<1.0 mg/L was considered as group I, hs-CRP
range from 1.0 to 3.0 mg/L considered as group
II and >3.0 mg/L considered as group III.
According to hs-CRP level 22(24.4%) cases were
in group I, 33(36.7%) cases group II and rest
35(38.9%) cases group III.
Danesh et al.15 reported that in general, CRP
concentrations increase among smokers with
increased cigarette consumption.16 Regarding
the smoking status it was found in this current
study that 40.9%, 66.7% and 60.0% was smoker
in group I, group II and group III respectively.
Koenig et al.16 have shown in their series 50.0
percent of the patients were hypertensive
which is a little inferior to the present study,
where the current study observed that
hypertensive was 59.1% in group I, 57.6% in
group II and 65.7% in group III. Hypertensive
patients was comparatively higher in group III
but no significant (p>0.05) difference was found
among three group.
In the present study, diabetes mellitus was
higher in group II and group III with compared
to group I, but no significant (p>0.05) difference
was found among three groups. Diabetes
mellitus observed in the present study are in
higher with Koenig et al.
The family history of IHD and dyslipidemia were
almost parallel among three groups, which
were not statistically significant (p>0.05)
Fig.-2: The scatter diagram shows significant
relationship (r=0.6648) between hs-CRP and
stenosis score.
Correlation between hs CRP with extent score
(n=90).
Hs CRP was expressed in mg/L and extent score
ranges from 0 to 80. Significant positive
correlations were found between hs-CRP and
extent score.
The values of Pearson’s correlation coefficient
was 0.6386 which is highly significant
Fig.-3: The scatter diagram shows significant
relationship (r=0.6386) between hs-CRP and
extent score.
J Dhaka Med Coll. Vol. 19, No. 2 October 2010
95
Vol. 19, No. 2, October 2010 96
difference among three groups. Nearly one
third of the patient had family history of IHD
and two third had dyslipidemia of the study
patients in the current study.
In this current series it was observed that the
mean (±SD) vessel score was 0.3±0.8 in group
I, 1.4±0.8 in group II and 2.4±0.9 in group III.
More than a eighty (81.8%) had no vessel score
in group I, majority (48.5%) of the patients in
group II patients had vessel score 1 and most
(65.7%) of the patients in group III had vessel
score 3. The mean vessel score difference was
significantly (p<0.05) higher in group III with
compared to others two groups. Similarly, the
mean stenosis score and extent score were
significantly (p<0.05) higher in group III with
compared to others two groups. Where the mean
(±SD) stenosis score was observed in this
current study was 3.2±7.4 in group I patients,
23.5±18.9 in group II patients and 38.3±26.5 in
group III patients. The mean (±SD) extent score
was 8.9±18.0 in group I, 36.1±16.9 in group II
and 51.2±16.6 in group III.
In this present study a significant (p<0.001)
positive correlation coefficient (r=0.7409) was
found between hs-CRP and vessel score, which
indicates that there was linear positive
correlation between hs-CRP and vessel score.
Similarly, significant (p<0.001) positive
correlation coefficient (r=0.6648 and r=0.6386)
were found between hs-CRP with stenosis
score and hs-CRP and extent score. Nyandak
et al.17 who have observed in their studies,
Spearman’s correlation coefficient between
hs-CRP and angiographic stenosis score was
r = 0.316 (p<0.004) and hs-CRP with
angiographic extent score was r= 0.338
(p<0.005).18 Higher hs-CRP levels were
associated with higher stenosis and extent
score in CAD patients, which are consistent
with the present study results.
So, hs-CRP is a single cardiovascular risk factor
and increases CRP concentration within
reference limit are associated with future
cardiovascular events. Elevated level of CRP
can predict the coronary atherosclerotic
disease burden.
Conclusion:
Significant positive correlation was observed
between the extent of coronary artery disease
and hs-CRP levels. Similarly hs-CRP levels were
found to be higher in patients with higher
degree of angiographic stenosis. This shows
that hs-CRP levels have a positive correlation
with the disease burden in CAD patients. hs-
CRP is a single cardiovascular risk factor and
are associated with severity of disease.
Increases CRP concentration within reference
limit are associated with future cardiovascular
events. Elevated level of CRP can predict the
coronary atherosclerotic disease burden.
References:
1. Julian DG, Cowan JC, Mclenachan JM, editors.
Cardiology 8th ed, New York: Elsevier Saunders,
2005; 78-89.
2. Camm AJ, Bunce NH Cardiovascular Disease. In:
Kumar P, Clark M, editors. Clinical Medicine
6th ed London: Elsevier, 2007; 725-832.
3. Heart Disease & Stroke Statistics 2009 Update
At-A-Glance. AHA, 2009.
4. Malik A. Congenital and acquired heart disease:
A survey of 7062 person, Bangladesh Med Res
Coun Bull, 1976; 2:115-9.
5. Latif MA, Saha AC. Cardiovascular disease in
hospital population, J Bangladesh Coll phys surg,
1988; 5: 30-34.
6. Maron DJ, Rider PM, Grundy SM. Prevention
Strategies for Coronary Heart Disease. In: Fuster
V, Walsh RA, O’rourke RA, Wilson PP, editors,
Hurst’s, the heart, 12th edn, New York: Mc Graw
Hill, 2008. 1235-44.
7. Braunwald ES. Lecture–cardiovascular medicine at
the turn of the millennium:triumphs, concerns and
opportunities, N Engl J Med, 1997; 337: 360-9.
8. Tracy RP. Inflammation in cardiovascular disease,
Circulation 1998; 97: 2000-2.
9. Shah PK, Falk E, Fuster V. Atherothrombosis:
Role of Inflammation, In: Fuster V, Walsh RA,
O’rourke RA, Wilson PP, editors, Hurst’s The
Heart, 12th edn, New York: McGraw Hill, 2008.
1203-34.
10. Libby P and Ridker PM. Novel inflammatory
markers of coronary risk, Circulation1999;100:
1148-50.
High Sensitive C-Reactive Protein (hs-CRP) and its Correlation Hasnat MA et al.
96
Vol. 19, No. 2, October 2010 97
11. Plutzky J. Inflammatory pathways in
atherosclerosis and acute coronary syndromes, Am
J Cardiol 2001; 88:10k-15k
12. Geluk CA, Post WJ, Hillege HL, Tio RA, Jan GP
et al. C-reactive protein and angiographic
characteristics of stable and unstable coronary
artery disease: Data from the prospective
PREVEND cohort, Atherosclerosis 2008; 196:
372–82.
13. Zebrack JS, Muhlestein JB, Home BD, Anderson
JL. Intermountain Heart Collaboration Study
Group, C-reactive protein and angiographic
coronary artery disease: independent and additive
predictors of risk in subjects with angina, J Am
Coll Cardiol 2002; 39: 632-7.
14. Hoffmeister A, Rothenbacher D, Bazner U,
Frohlich M, Brenner H, Hombach V et al. Role of
novel markers of inflammation in patients with
stable coronary heart disease, Am J Cardiol 2001;
87: 262-6.
15. Danesh J, Muir J, Wong YK, Ward M, Gallimore
JR, Pepys MB. Risk factors for coronary heart
disease and acute-phase proteins, A population-
based study, Eur Heart J 1999; 20: 954–9.
16. Koenig W, Khuseyinova N, Baumert J, Meisinger
C. Prospective Study of High-Sensitivity C-
Reactive Protein as a Determinant of Mortality:
Results from the MONICA/KORA Augsburg
Cohort Study 1984–1998, Clinical Chemistry
2008; 54(2): 335–42.
17. Nyandak T, Gogna A, Bansal S, Deb M. High
sensitive C-reactive protein (hs-CRP) and its
correlation with angiographic severity of coronary
artery disease (CAD), JIACM 2007; 8(3): 217-21.
J Dhaka Med Coll. Vol. 19, No. 2 October 2010
97

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HIGH SENSITIVE C-REACTIVE PROTEIN (hs-CRP) AND ITS CORRELATION WITH ANGIOGRAPHIC SEVERITY OF PATIENT WITH CORONARY ARTERY DISEASE (CAD)

  • 1. Vol. 19, No. 2, October 2010 91 Introduction: Coronary artery disease (CAD) is the end result of the accumulation of atheromatous plaques within the walls of the coronary arteries that supply the myocardium.1 CAD is the largest single cause of death in the UK and many parts of the world. Each year there are approximately 60 deaths per 100,000. Sudden cardiac death is a prominent feature of CAD. One in every six coronary attacks was found to present with sudden death as the first, last, and only symptom.2 In USA, among adults age 20 and older, the total number of coronary heart disease (CHD) in 2006 was 16,800,000 (about 8,700,000 men and 8,100,000 women). CHD caused about one of every five deaths in the United States in 2005. It is the largest single killer of American males and females.3 National data on incidence and mortality of coronary heart disease are few in Bangladesh. The prevalence of coronary heart disease was estimated as 3.3/1000 in 1976 and 17.2/1000 in 1986 indicating 5 folds in the disease in 10 years.4,5 HIGH SENSITIVE C-REACTIVE PROTEIN (hs-CRP) AND ITS CORRELATION WITH ANGIOGRAPHIC SEVERITY OF PATIENT WITH CORONARY ARTERY DISEASE (CAD) HASNAT MA1, ISLAM AEMM2, CHOWDHURY AW3, KHAN HILR4, HOSSAIN MZ5 Abstract: Background: Association between the plasma hs-CRP levels and the severity of coronary stenosis in subjects remains controversial. This cross sectional study was performed in the Department of Cardiology, Dhaka Medical College during July 2008 to December 2009, to determine whether the concentrations of hs-CRP correlate with the coronary atherosclerotic disease assessed by coronary angiography. Methods: For this purpose, a total number of 90 consecutive patients having IHD admitted in the Dhaka Medical College Hospitals were enrolled in this study. Patients were divided into three groups according to their level of hs-CRP. Out of 90 cases, 22(24.4%) patients were in group I, in group II 33(36.7%) patients and rest 35(38.9%) were in group III according to their hs-CRP level. Severity of CAD was assessed by vessel score, stenosis score and extent score. Result: Significant positive correlation (r=0.7409; p<0.001 r=0.6648; p<0.001 and r=0.6386; p<0.001) was found between hs-CRP and vessel score, stenosis score and hs-CRP and extent score suggesting increasing level of hs-CRP strongly suggestive of extensive coronary artery disease. Conclusion: High level of hs-CRP strongly suggestive of extensive coronary artery disease Key words: hs-CRP, angiogram, coronary artery disease, vessel score, stenosis score and extent score. J Dhaka Med Coll. 2010; 19(2) : 91-97. 1. Dr. Mohammad Abul Hasnat, MD-Final Part Student, Dept. of Cardiology, DMCH. 2. Dr. AEM Mazharul Islam, Assistant Professor, Dept. of Cardiology, DMCH. 3. Dr. Abdul Wadud Chowdhury, Associate Professor, Dept. of Cardiology, DMCH. 4. Dr. HI Lutfur Rahman Khan, Professor and Head, Dept. of Cardiology, DMCH. 5. Dr. Mohammad Zaid Hossain, Assistant Professor, Dept. of Medicine, DMCH. Correspondence: Dr. Mohammad Abul Hasnat, Department of Cardiology, Dhaka Medical College & Hospital Cell Phone: +8801711229128, Email: drhasnat@hotmail.com
  • 2. Vol. 19, No. 2, October 2010 92 Traditionally there are some conventional risk factors like age, male sex, positive family history, hypertension, smoking, hyperlipidaemia, metabolic syndrome, diabetes, lack of exercise, obesity, and some emerging risk factors, like C-Reactive Protein, Homocysteine, Fibrinogen.6 Less than 50% of the CAD can be ascribed to traditional risk factors and rests are unexplained.7 CRP has emerged as the most exquisitely sensitive systemic marker of inflammation and a powerful predictive marker of future cardiovascular risk. Role for inflammation has become well established over the past decade or more in theories describing the atherosclerotic disease process.8 A body of evidence now suggests that atherosclerosis represents a chronic inflammatory response to vascular injury caused by a variety of agents that activate or injure endothelium and promote lipoprotein infiltration, retention, and modification, combined with inflammatory cell entry, retention and activation.9 So, from a pathological viewpoint, all stages, i.e., initiation, growth, and complication of the atherosclerotic plaque might be considered to be an inflammatory response to injury.10,11 C- reactive protein (CRP) is one of the acute phase proteins that increase during systemic inflammation.12 Several prospective studies recently showed that plasma high sensitive C- reactive protein (hs-CRP) levels, a more sensitive CRP test, are a powerful predictor of future myocardial infarction and cardiac death among apparently healthy individuals.13 However, the association between the plasma hs-CRP levels and the severity of coronary stenosis in subjects remains controversial. Some studies previously demonstrated such associations whereas other could not found it.14,15 This study was performed to determine whether the concentrations of hs-CRP correlate with the coronary atherosclerotic disease assessed by coronary angiography. Objectives: General Objective: 1. To correlate the levels of hs-CRP with angiographic severity of coronary artery stenosis in patients with IHD admitted for CAG in DMCH. Specific objectives: 1. To correlate the levels of hs-CRP with vessel score. 2. To correlate the levels of hs-CRP with stenosis score. 3. To correlate the levels of hs-CRP with extent score. Materials and Methods: This cross sectional study was done in the department of cardiology, Dhaka Medical College during July 2008 to, December 2009. hs-CRP test was done in immunology department of BSMMU. CAG was done in the cath-lab of the Department of Cardiology, Dhaka Medical College Hospital. Inclusion criteria All patients of IHD admitted for CAG in department of cardiology DMCH. Exclusion criteria 1. Patient with past CABG 2. Patient with PTCA 3. Patient with valvular heart disease. 4. Patient with hepatic dysfunction. 5. Patient with a major non-cardiovascular disease. 6. Patient with collagen vascular disease. 7. Any systemic infection. 8. Unwilling to give consent. Statistical analysis: For all statistical analyses, SPSS version 16.0 was used. For all statistical tests, p<0.05 was considered as statistically significant. Continuous variables were presented as mean ± SD and numerical variables were presented as proportions. Continuous variables were compared through the ANOVA test, categorical variable by chi-square test, and correlation co- efficient was done where applicable. High Sensitive C-Reactive Protein (hs-CRP) and its Correlation Hasnat MA et al. 92
  • 3. Vol. 19, No. 2, October 2010 93 Observation and Results: Table I hs-CRP distribution of the study patients (n=90). hs CRP Number of Percentage patients Group I: <1.0 mg/L 22 24.4 Group II: 1.0 – 3.0 mg/L 33 36.7 Group III: >3.0 mg/L 35 38.9 Total 90 100.0 Table-I shows distribution of hs- CRP levels among the study patients. A total of 90 cases were included in the study the age ranged from 20 to 72 years. Among them 73 patients were male and rest are female. Patients were divided into three groups according to their level of hs-CRP. The level of hs-CRP <1.0 mg/L was consider as group I, 1.0 mg/L to 3.0 mg/L group II and >3.0 mg/L group III. Out of 90 cases 22(24.4%) belong to group I, 33(36.7%) was group II and rest 35(38.9%) was group III. Table-II Major risk factors status of the study patients (n=90) Smoking Group I (n=22) Group II(n=33) Group III (n=35) Pvalue n % n % N % Present 9 40.9 22 66.7 21 60.0 0.157NS Absent 13 59.1 11 33.3 14 40.0 Hypertension Present 13 59.1 19 57.6 23 65.7 0.769NS Absent 9 40.9 14 42.4 12 34.3 DM Present 3 13.6 13 39.4 12 34.3 0.113NS Absent 19 86.4 20 60.6 23 65.7 Dyslipidemia Present 13 59.1 21 63.6 21 60.0 0.930NS Absent 9 40.9 12 36.4 14 40.0 F/H IHD Present 6 27.3 7 21.2 11 31.4 0.634NS Absent 16 72.7 26 78.8 24 68.6 Group I= <1.0 mg/L; Group II= 1.0 – 3.0 mg/L; Group III= >3.0 mg/L; NS= not significant Table III Distribution of patients by vessel score (n=90) Vessel score Group I(n=22) Group II(n=33) Group III (n=35) Pvalue n % n % n % 0 18 81.8 4 12.1 2 5.7 1 2 9.1 16 48.5 4 11.4 2 1 4.5 10 30.3 6 17.1 3 1 4.5 3 9.1 23 65.7 Mean±SD 0.3 ±0.8 1.4 ±0.8 2.4 ±0.9 0.001S Range (min-max) (0 -3) (0 -3) (0 -3) J Dhaka Med Coll. Vol. 19, No. 2 October 2010 93
  • 4. Vol. 19, No. 2, October 2010 94 Table-II shows distribution of major risk factors among study patients. Regarding the smoking status it was found that 9(40.9%) in group I, 22(66.7%) in group II and 21(60.0%) in group III were smoker. No significant (p>0.05) difference was found among three groups in chi square test. Hypertension was found in 13(59.1%) in group I, 19(57.6%) in group II and 23(65.7%) in group III. No significant (p<0.05) difference was found among three groups in chi square test. The results are shown in the table II. Diabetes mellitus was found 3(13.6%) in group I, 13(39.4%) in group II and 12(34.3%) in group III. No significant (p>0.05) difference was found among three in chi square test. The results are shown in the table II. Family history of IHD was found 6(27.3%), 7(21.2%) and 11(31.4%) in group I, group II and group II respectively. No significant (p>0.05) difference was found among three groups in chi square test. The results are shown in the table II. Dyslipidemia was found in 13(59.1%) in group I, 21(63.6%) in group II and 21(60.0%) in group III. No significant (p>0.05) difference was found among three groups in chi square test. The results are shown in the table II. Table –III shows distribution of patients by vessel score. More than eighty (81.8%) had vessel score ‘0’ in group I, in group II majority (48.5%) had vessel score 1 and in group III most (65.7%) had vessel score 3. The mean (±SD) vessel score was 0.3±0.8, 1.4±0.8 and 2.4±0.9 in group I, group II and group III respectively. The vessel score difference was statistically significant (p<0.05) among three groups in ANOVA test. Table-IV shows Distribution of patients by stenosis and extent score. The mean (±SD) Stenosis score was 3.2±7.4, 23.5±18.9 and 38.3±26.5 in group I, group II and group III respectively. The mean (±SD) extent score was 8.9±18.0 in group I, 36.1±16.9 in group II and 51.2±16.6 in group III. The Stenosis and extent score difference were statistically significant (p<0.05) among three groups in ANOVA test. Correlation between hs CRP with vessel score (n=90). Hs CRP was expressed in mg/L and vessel score ranges from 0 to 3 depending on the number of vessel involve. Significant positive correlations were found between hs-CRP and vessel score. The values of Pearson’s correlation coefficient was 0.7409 which is highly significant (p<0.001). Therefore, there was linear positive correlation between hs-CRP and vessel score (Fig. 1). Table IV Distribution of patients by stenosis and extent score (n=90) Group I(n=22) Group II(n=33) Group III (n=35) P value Mean ±SD Mean ±SD Mean ±SD Stenosis score 3.2 ±7.4 23.5 ±18.9 38.3 ±26.5 0.001S Range (min-max) (0 -24) (0 -72) (0 -112) Extent score 8.9 ±18.0 36.1 ±16.9 51.2 ±16.6 0.001S Range (min-max) (0 -60) (0 -80) (0 -80) Group I= <1.0 mg/L, Group II= 1.0 – 3.0 mg/L, Group III= >3.0 mg/L, NS= not significant Fig.-1: The scatter diagram shows significant relationship (r=0.7409) between hs-CRP and vessel score. High Sensitive C-Reactive Protein (hs-CRP) and its Correlation Hasnat MA et al. 94
  • 5. Vol. 19, No. 2, October 2010 95 Correlation between hs CRP with stenosis score (n=90). Hs CRP was expressed in mg/L and stenosis score ranges from 0 to 112. Significant positive correlations were found between hs-CRP and stenosis score. The values of Pearson’s correlation coefficient was 0.6648 which is highly significant (p<0.001). Therefore, there was linear positive correlation between hs-CRP and stenosis score (Fig. 2). (p<0.001). Therefore, there was linear positive correlation between hs-CRP and extent score (Fig.-3). Discussion This cross sectional study was carried out with an aim to correlate the levels of hs-CRP with angiographic severity of coronary artery stenosis in patients with IHD admitted for CAG in DMCH and to correlate the levels of hs-CRP with vessel score, stenosis score and extent score. A total of 90 patients with IHD age ranging from 20 to 70 years were included in the study, who were admitted for CAG in the department of Cardiology, Dhaka Medical College during July 2008 to December 2009. The patients were divided into three groups according to their level of hs-CRP, which were <1.0 mg/L was considered as group I, hs-CRP range from 1.0 to 3.0 mg/L considered as group II and >3.0 mg/L considered as group III. According to hs-CRP level 22(24.4%) cases were in group I, 33(36.7%) cases group II and rest 35(38.9%) cases group III. Danesh et al.15 reported that in general, CRP concentrations increase among smokers with increased cigarette consumption.16 Regarding the smoking status it was found in this current study that 40.9%, 66.7% and 60.0% was smoker in group I, group II and group III respectively. Koenig et al.16 have shown in their series 50.0 percent of the patients were hypertensive which is a little inferior to the present study, where the current study observed that hypertensive was 59.1% in group I, 57.6% in group II and 65.7% in group III. Hypertensive patients was comparatively higher in group III but no significant (p>0.05) difference was found among three group. In the present study, diabetes mellitus was higher in group II and group III with compared to group I, but no significant (p>0.05) difference was found among three groups. Diabetes mellitus observed in the present study are in higher with Koenig et al. The family history of IHD and dyslipidemia were almost parallel among three groups, which were not statistically significant (p>0.05) Fig.-2: The scatter diagram shows significant relationship (r=0.6648) between hs-CRP and stenosis score. Correlation between hs CRP with extent score (n=90). Hs CRP was expressed in mg/L and extent score ranges from 0 to 80. Significant positive correlations were found between hs-CRP and extent score. The values of Pearson’s correlation coefficient was 0.6386 which is highly significant Fig.-3: The scatter diagram shows significant relationship (r=0.6386) between hs-CRP and extent score. J Dhaka Med Coll. Vol. 19, No. 2 October 2010 95
  • 6. Vol. 19, No. 2, October 2010 96 difference among three groups. Nearly one third of the patient had family history of IHD and two third had dyslipidemia of the study patients in the current study. In this current series it was observed that the mean (±SD) vessel score was 0.3±0.8 in group I, 1.4±0.8 in group II and 2.4±0.9 in group III. More than a eighty (81.8%) had no vessel score in group I, majority (48.5%) of the patients in group II patients had vessel score 1 and most (65.7%) of the patients in group III had vessel score 3. The mean vessel score difference was significantly (p<0.05) higher in group III with compared to others two groups. Similarly, the mean stenosis score and extent score were significantly (p<0.05) higher in group III with compared to others two groups. Where the mean (±SD) stenosis score was observed in this current study was 3.2±7.4 in group I patients, 23.5±18.9 in group II patients and 38.3±26.5 in group III patients. The mean (±SD) extent score was 8.9±18.0 in group I, 36.1±16.9 in group II and 51.2±16.6 in group III. In this present study a significant (p<0.001) positive correlation coefficient (r=0.7409) was found between hs-CRP and vessel score, which indicates that there was linear positive correlation between hs-CRP and vessel score. Similarly, significant (p<0.001) positive correlation coefficient (r=0.6648 and r=0.6386) were found between hs-CRP with stenosis score and hs-CRP and extent score. Nyandak et al.17 who have observed in their studies, Spearman’s correlation coefficient between hs-CRP and angiographic stenosis score was r = 0.316 (p<0.004) and hs-CRP with angiographic extent score was r= 0.338 (p<0.005).18 Higher hs-CRP levels were associated with higher stenosis and extent score in CAD patients, which are consistent with the present study results. So, hs-CRP is a single cardiovascular risk factor and increases CRP concentration within reference limit are associated with future cardiovascular events. Elevated level of CRP can predict the coronary atherosclerotic disease burden. Conclusion: Significant positive correlation was observed between the extent of coronary artery disease and hs-CRP levels. Similarly hs-CRP levels were found to be higher in patients with higher degree of angiographic stenosis. This shows that hs-CRP levels have a positive correlation with the disease burden in CAD patients. hs- CRP is a single cardiovascular risk factor and are associated with severity of disease. Increases CRP concentration within reference limit are associated with future cardiovascular events. Elevated level of CRP can predict the coronary atherosclerotic disease burden. References: 1. Julian DG, Cowan JC, Mclenachan JM, editors. Cardiology 8th ed, New York: Elsevier Saunders, 2005; 78-89. 2. Camm AJ, Bunce NH Cardiovascular Disease. In: Kumar P, Clark M, editors. Clinical Medicine 6th ed London: Elsevier, 2007; 725-832. 3. Heart Disease & Stroke Statistics 2009 Update At-A-Glance. AHA, 2009. 4. Malik A. Congenital and acquired heart disease: A survey of 7062 person, Bangladesh Med Res Coun Bull, 1976; 2:115-9. 5. Latif MA, Saha AC. Cardiovascular disease in hospital population, J Bangladesh Coll phys surg, 1988; 5: 30-34. 6. Maron DJ, Rider PM, Grundy SM. Prevention Strategies for Coronary Heart Disease. In: Fuster V, Walsh RA, O’rourke RA, Wilson PP, editors, Hurst’s, the heart, 12th edn, New York: Mc Graw Hill, 2008. 1235-44. 7. Braunwald ES. Lecture–cardiovascular medicine at the turn of the millennium:triumphs, concerns and opportunities, N Engl J Med, 1997; 337: 360-9. 8. Tracy RP. Inflammation in cardiovascular disease, Circulation 1998; 97: 2000-2. 9. Shah PK, Falk E, Fuster V. Atherothrombosis: Role of Inflammation, In: Fuster V, Walsh RA, O’rourke RA, Wilson PP, editors, Hurst’s The Heart, 12th edn, New York: McGraw Hill, 2008. 1203-34. 10. Libby P and Ridker PM. Novel inflammatory markers of coronary risk, Circulation1999;100: 1148-50. High Sensitive C-Reactive Protein (hs-CRP) and its Correlation Hasnat MA et al. 96
  • 7. Vol. 19, No. 2, October 2010 97 11. Plutzky J. Inflammatory pathways in atherosclerosis and acute coronary syndromes, Am J Cardiol 2001; 88:10k-15k 12. Geluk CA, Post WJ, Hillege HL, Tio RA, Jan GP et al. C-reactive protein and angiographic characteristics of stable and unstable coronary artery disease: Data from the prospective PREVEND cohort, Atherosclerosis 2008; 196: 372–82. 13. Zebrack JS, Muhlestein JB, Home BD, Anderson JL. Intermountain Heart Collaboration Study Group, C-reactive protein and angiographic coronary artery disease: independent and additive predictors of risk in subjects with angina, J Am Coll Cardiol 2002; 39: 632-7. 14. Hoffmeister A, Rothenbacher D, Bazner U, Frohlich M, Brenner H, Hombach V et al. Role of novel markers of inflammation in patients with stable coronary heart disease, Am J Cardiol 2001; 87: 262-6. 15. Danesh J, Muir J, Wong YK, Ward M, Gallimore JR, Pepys MB. Risk factors for coronary heart disease and acute-phase proteins, A population- based study, Eur Heart J 1999; 20: 954–9. 16. Koenig W, Khuseyinova N, Baumert J, Meisinger C. Prospective Study of High-Sensitivity C- Reactive Protein as a Determinant of Mortality: Results from the MONICA/KORA Augsburg Cohort Study 1984–1998, Clinical Chemistry 2008; 54(2): 335–42. 17. Nyandak T, Gogna A, Bansal S, Deb M. High sensitive C-reactive protein (hs-CRP) and its correlation with angiographic severity of coronary artery disease (CAD), JIACM 2007; 8(3): 217-21. J Dhaka Med Coll. Vol. 19, No. 2 October 2010 97