CRP- A good predictor of complications early after MI - study of 50 cases

FAZLUL HAQUE 1 NAM MOMENUZZAMAN 2, FATEMA BEGUM, KAISER NASRULLAH KHAN,

K.M.SOHAIL , DIPAL KRISNO ADHIKARY, AM SHAFIQUE, MAHBUB-UL AMIN, ZAHIRUDDIN
M ILIUS, RAZUR RAHMAN ASHIS DEY , ZIAUL HAQUE, FARUK UDDIN

ABSTRACT

Aims

To evaluate the predictive value of C Reactive Protein (CRP) in the events of

early complications after Myocardial Infarction.

Methods & results

A prospective analysis of 50 Myocardial Infarction (MI) patients on admission
and CRP was measured on 3rd /4th day after admission. Patients were classified
into 3 groups according to serum CRP level -

I . crp value < 6 mg/L 16 (32%)

2. crp 6-40 mg/L 24 (48%)
3. crp > 40 mg/L 10 (20%)

Out of 50 patients 44% were in Anterior MI, 36% in Inferior MI, 20% as
NSTEMI. Patients had Canadian Cardiac Society (CCS) II/III angina in 50% and
shortness of breath (NYHA III/IV ) in 44 % cases. Among them with AMI showed
clinical signs of HF (Killip class >1) during the week of study. 8 cases (16%)
presented with cardiogenic shock. Patients with HF were older (mean age), more
frequently were female (%) and had diabetes (%), and had a higher heart
rate(mean) and a smaller LVEF (%) than patients without HF. It was observed tht
in 3rd group of CRP value had more in-hospital mortalities (%) &
complications(%).
CONCLUSION:

High C-reactive protein (CRP) levels have been associated with higher mortality
rate in patients with acute myocardial infarction (AMI)

Introduction

Coronary angiogram fails to show the active dynamic changes that occurred
within vary short period of ischaemic pain. CRP is the marker of that events
and could be used for targeting high risk group for urgent coronary interventions .

Accumulated data suggest that markers of acute inflammation such as C-reactive

[1-3]
protein (CRP) may be reliable predictors of outcome in patients with MI
Although the prognostic value of CRP in patients with myocardial infarction has
not been tested in large studies, several data indicate that CRP is an important
marker of risk also in this clinical setting.[4-6] In a 2-year follow-up of 188 patients
with AMI, Pietila et al[13] observed that the subjects who died of congestive HF
had elevated CRP levels..

The aim of this study was to test the hypothesis that there is a relationship
between high CRP levels and complications progression during the first week of
hospitalization for AMI, and that high CRP level is associated with death and ln-
hospital mortality after AMI.

Methods

50 patients with AMI were prospectively studied.

The patients were followed daily for MACE. CRP serum were obtained during
the 3rd/4th day of hospitalization. The criteria for AMI diagnosis were based on
fulfillment of at least 2 of the following: central chest pain lasting >30 minutes,
typical changes in serum enzymes (total creatine kinase [CK], CK-MB, Troponin
I), typical electrocardiogram changes with occurrence of pathological Q waves
and/or localized ST-T changes in at least 2 contiguous leads.[16]
CRP Measurement

In all patients, venous blood was drawn on the , third/4th day, for measurement
of CRP. . Venous blood samples were put in ice and centrifuged within 20
minutes at 4°C, and the plasma was stored at -20°C until assayed (storage time
<1 month). CRP was measured at the University of Padova by means of the
nephelometric method with particle-bound goat antihuman CRP (Beckman
Instruments, Inc, Fullerton, Calif) and expressed as mg/L. The lower limit of the
measurements range of the assay was 1 mg/L.[17]

Literature Review

Auer J; Berent R; et al 2002 concldes CRP as a marker of inflammation is

significantly increased in patients with AMI and unstable angina shortly after the
onset of symptoms (after a period of 12 hours), supporting the hypothesis of an
activation of inflammatory mechanisms .

Elevated levels of C-reactive protein at discharge in patients with unstable

angina/ NSTEMI predict recurrent instability. This is proved by Biasucci LM;
Liuzzo G; Grillo RL, et al ( 1999 ). In unstable angina, CRP may remain elevated
for at >/=3 months after the waning of symptoms and is associated with recurrent
instability. Elevation of acute-phase reactants in ACS could represent a hallmark
of subclinical persistent instability or of susceptibility to recurrent instability.

Recent data demonstrate that CRP is a strong independent predictor of adverse

cardiac events and death in patients with ACS, but also in patients with stable
ischemic heart disease and in apparently healthy men and women. Furthermore,
CRP is an important prognostic index, for early and late outcome, in patients
undergoing percutaneous coronary interventions, and may be useful in choosing
the therapeutic management of the patient Biasucci LM; Santamaria M; Liuzzo G
et al (2002).
CRP & post procedural increased CRP are independent predictors of a worse
prognosis & future cardiac events. Among hospitalized patients who develop
adverse outcome, fibrinogen, D-Dimer, C Tn I, & CRP plasma level were higher
in those than patients with good outcome (Fiotte, -N, Dichiara, et-al 2002).

An abnormal CRP on admission in patients with unstable angina or NQMI is

associated with increased incidence of major cardiac events within 6 months,
both in patients with normal and abnormal TnI. CRP and TnI have independent
and additive prognostic value in this patient group, and the combination may be
useful for early risk stratification. Bhagat S; Gaiha M; et al ( 2003 ) Lanza GA; De
Filippis M, et al (2002) also proved Independent role of C reactive protein to
predict major events.

Statistical Analysis

Statistical analysis was made using Systat 7.0 for Windows package (SPSS Inc,
Evanston, Ill) and JMP 4.0 for Windows (SAS Institute Inc, Cary, NC).

Data are presented as mean ± SD for continuous measures unless otherwise

specified and as proportion of patients with a characteristic for categorical
variables. All P values are 2-tailed and statistical significance was established as
P < .05.

Results

Of the 50 patients included in the study, all had evidence of AMI on the basis of
the aforementioned criteria. The other 30 subjects of MI were used as a control .
The 2 groups were balanced for age and sex. Nitrates, antiplatelets, and
anticoagulants were more frequently used in the patients with AMI

CRP in Patients With AMI and Controls

CRP was significantly higher in the patients with AMI than the control group. In
the AMI group, 9 (%) patients were taking statins before admission and
41patients (%) started statin treatment during the first day of hospitalization. CRP
levels were similar in the patients with or without statin treatment

CRP value

CRP Value

CRP Value N (%)

<6 ng/m 16(32%)
6-40 ng/m 24(48%)
>46 ng/m 10(20%)

Sex
Age

Highest age - 68 years

Lowest age - 25 years

Types of MI

Types of MI %
Ant (MI) 22(44%)
Inf ( MI) 18(36%)
NSTEMI 10(20%)
Clinical Presentations

CCS II/II 25(50%)

NYHA II/II 12(24%)
NYHA IV 10(20%)

30%

25%

20%

15%
Series1
10%

5%

0%
1 2 3

25%

20% CCF II/II

25%
15%

10% NYHA II/II NYHA IV

12% 10 %
5%

0%
1

Major Risk factors

R/F:
Name of Disease N (%)
DM 22(80 %)
HTN 11( 40%)
 Dyslipidaemia 12 (50%)
F/H 8(30%)
smoking 10 (38 %)

MACE

Name N (%)
Death 1(%)
LVF 20(%)
Cardiogenic shock 8 (%)
Arrhythmia(Brady/ Tachy ) 7(%)
Angina 8 (%)
Others 1 (%)

CRP and HF

Among the patients with AMI, 26 (%) showed clinical signs of HF (Killip class >1)
during the week of study, patients with HF were older, more frequently were
female and had diabetes, and had a higher heart rate and a smaller LVEF than
patients without HF. Time to presentation from onset of symptoms to coronary
care unit, and peak CK-MB did not differ between the 2 groups. Third-day CRP
data were considered for the analyses.

Discussion

This prospective observational study was carried out in the Department of

Cardiology, United Hospital, Dhaka, North – East Medical College , Sylhet during
the period of April 2010 to December 2010. This study was undertaken to To
evaluate the predictive value c reactive protein in the events of complications
early after MI

A total of 50 patients diagnosed as a case of Myocardial infarction was included

in this study. The patients were followed daily for MACE. CRP serum were
obtained during the 3rd/4th day of hospitalization. The criteria for AMI diagnosis
were based on fulfillment of at least 2 of the following: central chest pain lasting
>30 minutes, typical changes in serum enzymes (total creatine kinase [CK], CK-
MB, Troponin I ), typical electrocardiogram changes with occurrence of
pathological Q waves and/or localized ST-T changes in at least 2 contiguous
leads.[16]

The patients were divided into 3 l groups- Group I, Group II, Group-III on the
basis of CRP value . Among 50 patients, 16 patients were in Group I , 24 patients
were in Group II, 10 patients in Group III . Out of 50 patients 36 (%) were males
& 14 (%) were females having a male: female Ratio of. Avanzas et al (2004)
studied on similar sample size (55 patients). The mean age of the study
population was , 48.0 ± 9.8 years respectively ,which is quite similar to the
mean age group of the study by Ben-Hamda et al (2004). Symptoms severity
were noted in the form of CCS and NYHA . 25 (%) were in CCS II/III, and 32
out of 50 (%) presented with HF symptoms NYHA II-IV .

Among the important risk factors of CAD, 39% patients were smoker, 40%
patients were hypertensive, 80% patients were diabetic, 50% patients were
dyslipidaemic and 30% had family history of IHD . There was no difference
observed among four groups of patients in terms of risk factor profile. This is also
shown by Siddique et al (2003).

With incresing anginal pain ,ECG changes were more frequent in class III and IV
in which 62 % showed < 1 mm deprssion , and 24 % with > 1 mm . GUSTO IIb
study and TIMI III Registry of ACS patients showed presence of ST segment
deviation > 0.5 mm confers a worse prognosis .

Echocardiographic findings in three group showed patients with higher CRP

tertile had definitive regional wall motion abnormalities (RWMA) with moderate
to severe LV dysfuction. Weber et al (1999) demonstrated that in patients with
reduced systolic fuction the percentage of multi vessel disease is significantly
higher .

In another study by me ( fazlul et al 2005 ) compared the level of CRP with

the extent of disease , It was found that when CRP value 2.6- 8.6 , Double
vessel disease is prevalent ( 45 % ) followed by single vessel disease (30% )
but with increasing CRP value above 8.7 mg/dll Tripple vessel disease is most
frequent (56 % ) , followed by Double vessel disease (32 % ) , Single vessel
disease (12 % )

CRP and Congestive Heart Failure

To our knowledge, the present study is one of the first to highlight the
relationship between baseline CRP and occurrence of heart failure in the first few
days after AMI. Our data showed that CRP soon after admission was higher in
patients with AMI with clinical signs of HF compared to those in Killip class 1.

These data suggest that CRP may predict the risk of HF or may play a direct role
in augmenting microvascular inflammatory response after ischemic insult.[22] In
other words, the marked CRP rise in patients with AMI with HF at entry or in
those who developed HF in the subsequent days may not only be an
epiphenomenon but may represent a pathogenic process that leads to
myocardial damage and left ventricular dysfunction.[22, 23] Previous data indicate
that CRP may induce complement activation, and a pathogenetic role of
complement activation that may lead to maladaptive cardiac remodeling has
been described in acute ischemic left ventricular damage.[24, 25]
CRP and In hospital MACE :

Previous studies examining the relationship between CRP and cardiovascular

mortality in patients after AMI have found that peak CRP level predicts both in-
hospital mortality and the long-term outcome.[5, 13] The present analysis confirms
the prognostic significance of elevated CRP beyond that defined by traditional
risk predictors after AMI. The peak CRP cut-off value that best discriminated
between the patients prone to death and those who survived was 85 mg/L. In
agreement with the results of others, CRP level proved to be a strong predictor
chiefly of mortality from HF. In fact, the incidence of death from HF was only 1%
among the patients with peak CRP <85 mg/L at baseline, while it was 20%
among those with peak CRP above that value. In our series 20 patients were in
LVF and 4 were in carcinogenic shock , 8 patients were having post MI
angina .

Thus, CRP can be used as a new and even simpler tool for risk stratification and
CRP can be used as a marker to identify those subsets of patients with MI who
may need to undergo invasive strategies on priority basis .

Conclusions

Elevation of baseline CRP in patients with MI are associated with severe

coronary artery disease and higher values are associated with haemodynamic
unstabilities. Although the precise role of CRP requires further elucidation, a
focus on CRP within the first 3 days after AMI may prove useful for identification
of patients who are at greater risk of heart failure and mortality.

CRP are simple, affordable and widely available test which can be easily done in
each and every patient admitted to hospital and CRP can be used as a new and
even simpler tool for risk stratification in MI . More over, coronary angiogram
fails to show the active dynamic changes that occurred within vary short
ischaemic pain periods . CRP is the marker of that events and could be used for
targeting high risk group for urgent coronary interventions .
Limitations of the Study

Several limitations of our study should be mentioned. We are aware that the cut-
off values for CRP prediction of events were based on a statistical test and not
on prospective data. Only longitudinal studies in larger groups will confirm the
validity of our cut-offs.

We have no data to establish whether thrombolysis was successful or not, and

this could affect the incidence of HF and the rate of cardiovascular events, as
well as the levels of CK.

• Number of study population was limited.

• Angiography could not be done very early after admission or every case.

Address of Correspondence:

1. Office : A K Fazlul Haque, MD (Card)-Associate Professor, Dept of

Cardiology , North East Medical College, Sylhet, Bangladesh,Tel : +
88-0821-815632,
Mob+8801815474443,email:drfazlulhaque71@gmail.com

2. Office: NAM Momenuzzaman, D-Card, MD(Card)- Consultant

Cardiologist, United Hospital. Plot no 15, Road no-71, Gulshan 2,
Dhaka-1212,Tel-8836000, 8836444
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