Study of Correlation between Value of Serum C - reactive protein And Abnormalities of Electrocardiogram in Patients Suspected of
Coronary Artery Disease.
Serum CRP abnormalities and its relationship with LDL/HDL ratio in patients of coronary artery disease.
Authors – Dr.Neha Jaiswal1 , Dr. Arvind Bhake2
1.Post-graduate,Department of Pathology,Jawahar lal Nehru Medical college, Sawangi ,Meghe ,Wardha.
2.Director and Proffesor ,Department of Pathology,Jawahar lal Nehru Medical college, Sawangi ,Meghe ,Wardha.
E- mail address – 1. [email protected] 2. [email protected] Corresponding Author – Dr. Neha Jaiswal
WORD LIMIT –1910
INSTITUTIONAL ETHICAL COMMITTEE NO – - DMIMS(DU)/IEC/2019/7929 DECLARATION – No conflict of interest exists whatsoever with publication of this
study.
KEYWORDS- C reactive protein , LDL/HDL ratio , Coronary artery disease , STEMI , NSTEMI.
Abstract
The C- Reactive protein has been reported as a predictor of coronary events indicating inflammatory process of atherosclerosis .The hyperlipidemia has long been known one of the major risk factors for coronary artery disease.The present study investigate the relationship between CRP and LDL/HDL ratio in the patients of myocardial infarction.Objectives- The study was carried out to determine serum levels of CRP and LDL/HDL ratio in patients of STEMI and NSTEMI. Method – The study was carried out on 50 patients of ECG proven myocardial infarction .The CRP and lipid profile estimation was carried out by standard lab procedure. Results– 37 patients were found to have raised CRP level with determined cut off of 11 ng/ml. 44 patients were observed to carry decreased value of HDL. There were 28 patients who had raised
LDL/HDL ratio .No relationship between raised level of CRP and abnormalities of LDL/HDL ratio. Conclusion – The study deduced that majority of coronary artery disease patients showed increased level of CRP .The CRP was raised in STEMI more than in NSTEMI.The raised level of CRP had no association with LDL/HDL ratio in patients of coronary artery disease.
INTRODUCTION
Coronary heart disease is known as the leading causeof death in developing countries.[1]Despite advances in the diagnosis and treatment of coronary artery disease, it is still among the most common causes of death and disability in the world, which endangers global health.[2]
The term “acute coronary syndrome” (ACS) encompasses a range of thrombotic coronaryarterydiseases,includingunstableangina(UA),andbothST–
segmentelevation(STEMI)andNon-STsegment elevation myocardial infarction (NSTEMI), mostly induced by local coronary thrombosis as an acutecomplicationofatherosclerosis.[3]
Patientswithan acute coronary syndrome have a high risk of suffering subsequent cardiac events.[3]
Coronary plaque disruption, with consequent platelet aggregation and thrombosis, is the most important mechanism by which atherosclerosis leads to the acute ischemic syndromes of unstable angina, acute myocardial infarction, and sudden death.[3
With growing evidence that atherosclerosis is an inflammatory process, several plasma markers of inflammationhavebeenevaluatedaspotentialtoolsfor the prediction of coronary events.[3]These markers of inflammationincludeserumamyloidA,interleukin–6, homocysteines, fibrinogen levels, fibrinolytic capacity, apolipoprotein–A,apolipoproteinB-100,lipoprotein(a) and C-reactive protein(CRP).3
CRP, a marker of systemic inflammation and one of acute phase proteins increases in
cases of inflammation,
infectionandcollagenvasculardiseases.CRPincreasesfasterthanother
acutephasereactants,anditsdeclineoccursmorequickly afterremovingtheirritantand on recession of inflammation.(4).
Various studies has observed the prognostic and predictive role of CRP in mortality of
patients with acute coronary syndrome and
heartfailure.Thereisanecessitytoconductasimpletestsuch as the measurement of high- sensitivity CRP to achieve an acceptable prediction about the extent of coronary artery and ischemic heart involvement(5,6). CRP has been shown to predict risk in a wide variety of clinical settingshas incremental value in addition to standard lipid screening for primary prevention of coronary syndrome..[5,6,7]
Studies conducted showsthatCRPpredictstheriskofdeathormyocardial infarction within 30 days among patients undergoing percutaneous coronary intervention.CRP was found to be
independently associated with the recurrence of
cardiovasculareventsandwithdeathinthemidtolong term.[9,10]
IthasbeensuggestedthatCRPmaynotonly be a marker of generalized inflammation but directly andactivelyparticipatesinbothatherogenesis[11,12]and atheromatous plaquedisruption .Measurement of CRP serum level in the patient can be used as a diagnostic tool to assess the risk of cardiovasculardiseases.
Furthermore, Identifying and evaluating CRP levels with result of electrocardiogram of acute coronary events, provides a substantial contribution to prediction of ischemic heart disease severity even prior expensive actions andsometimesinvasiveimaging(7,8).
Studies show that CRP has statistically stronger correlation than compared to LDL/HDL ratio14.Therefore the present study is carried out to find the correlation between levels of serum C.R.P and LDL /HDL ratio in patients with ECG proven coronary artery disease.
AIM
The purpose of this study is to study the correlation between serum levels of C.R.P and LDL/HDL ratio with abnormalities in electrocardiogram in patients with coronary artery disease.
OBJECTIVES
1)To determine the serum levels of CRP in patients with STEMI and NSTEMI.
2)To determine the LDL/HDL ratio in patients with STEMI and NSTEMI.
MATERIALS AND METHOD
The study was carried out with the following material and methods . The IEC permission was obtained –DMIMS(DU)/IEC/2019/7929 Type Of Study-Prospective .
Duration of study-2 years .
Sample Size-50 patients of coronary artery disease.
Allpatients attending medicine OPD with clinical features suggestive of coronary artery disease wereassessedby adetailedhistoryandphysicalexamination.
Relevant laboratoryinvestigations were carried out todocumentpresenceofcoronary artery disease.
Serum CRP levels was checked in all patients by dry chemistry method with clinical features suggestive of coronary artery disease.
7 ml of patient‟s venous blood was drawn under asceptic conditions in plain bulb. The CRP estimations were carried out in central clinical laboratory y dry chemistry on Vitros 5600, Ortho Clinical Diagnosis.
Inclusion Criteria:
1.Patients who presented with history of typical chest painshowing ECG of ST and NST myocardial infarction.
Exclusion criteria :
1.Patients with inflammatory or neoplastic conditions likely to be associated with an elevatedCRP , 2. Patientswithvalvularheartdisease, hepatic failure and renalfailure , 3.Patients on NSAIDS and steroids.
RESULTS
There were 37 male and 13 female who suffered myocardial infarction and the maximum number of cases were
observed in the age range of 61-70 years as shown in Table 1 .
Table 1 : Age and Gender distribution.
AGE (years) GENDER STEMI NSTEMI
MALE N=36
FEMALE N=14
21-30 01 00 00 01
31-40 00 00 00 00
41-50 09 00 06 03
51-60 10 06 10 06
61-70 11 02 10 03
71-80 06 05 06 05
TOTAL (N=50)
37 13 32 18
Out of 50 patients 32 had STEMI while 18 had NSTEMI.
There were no patient below age of 40 suffering from myocardial infarction except for 1 who suffered NSTEMI.
The LDL level were normal (below 150) in all cases except 2.(Table 2)
Table 2 : LDL level in study subjects.
LDL RANGE mg/dl
TOTAL NO. OF CASES-50
TOTAL NO OF CASES -50
STEMI NSTEMI
1-50 05 03 02
51-100 23 14 09
101-150 20 11 09
151-200 02 01 01
There were 2 cases who had LDL level in range of 151-200 who suffered with single case of each category STEMI and NSTEMI . However low levels of HDL were observed in 44 cases of myocardial infarction.(Table 3)
TABLE 3 : HDL level in study subjects.
HDL RANGE mg/dl
TOTAL CASES=50
TOTAL NO OF CASES -50
STEMI NSTEMI
1-20 05 03 02
21-40 39 23 16
41-60 10 07 03
There were 10 cases who had normal HDL but suffered myocardial infarction. Out of these 10 cases 7 were STEMI and 3 were NSTEMI.
The LDL/HDL ratio within normal range was observed in 2 cases.But 28 cases show more than normal LDL/HDL ratio.(Table 4)
Table 4 : LDL/HDL ratio in study subjects.
LDL/HDL Total NO . TOTAL NO OF
RATIO OF CASES CASES -50
STEMI NSTEMI
NORMAL
=2.5
02 00 02
>NORMAL 28 18 10
<NORMAL 20 12 08
There were 20 cases who had less than normal LDL/HDL ratio which was unusual phenomenon.
The cut-off for CRP for current study was 11.
Out of 50 patients 37 had raised CRP level.(Table 5) Table 5 : CRP levels in study subjects.
CRP
RANGE(ng/ml)
Total no. of cases
TOTAL NO. OF CASES-50
STEMI NSTEMI
5-10 13 00 13
11-20 23 18 05
21-30 14 14 00
There were 13 patients who had CRP level less than the CRP cut-off and still suffered Myocardial infarction.However these cases mostly belonged to NSTEMI.
The correlation between LDL/HDL ratio and CRP in 50 cases of Myocardial infarction is shown in table 6
Table 6 : Correlation between CRP and LDL/HDL ratio LDL/HDL
RATIO
C reactive protein n=50 Total STEMI NSTEMI
5 – 10 11 – 21 – 30 5 – 11 – 21–
ng/ml 20 ng/ml
ng/ml 10 ng/ml
20 ng/ml
30 ng/ml
Normal (2.5) 00 00 00 01 01 00 02
>Normal (2.5) 00 14 05 07 02 00 28
<Normal (2.5) 00 04 09 05 02 00 20
Total 00 18 14 13 05 00 50
There was 1 case with normal LDL/HDL ratio and normal CRP but still suffered NSTEMI.When correlation was performed of the patients with more than normal LDL/HDL ratio for raised CRP ,there were 21 cases of which 19 belonged to STEMI and 2 belonged to NSTEMI.
Thus, sizeable number of patients have both the abnormality for raised HDL/LDL ratio and raised C-reactive protein .The rest of the patients had less than normal LDL/HDL ratio but still had raised CRP;11 cases of STEMI and 2 cases of NSTEMI.
DISCUSSION
The incidence of myocardial infarction beyond the age of 40 years have been reported in most of the studies reviewed for the present study.1,4,7,10
The present observed that age is a risk factor for myocardial infarction where all 50 cases baring 1 were beyond age 40 similar to the observations of foresaid studies.1,4,7,10
The male to female ratio tilted to the former for myocardial infarction as has been quoted by the previous studies.Similar distribution of gender has been made in the foresaid studies.1,2,10,14 Okin et al15 reported LDL level 121 +/- 34 in a large study population who were showing echocardiomyography of ST segment depression.
Srivastava et al14 and Agarwal et al14reported total cholesterol level of 165.5 +/- 31.3 in 43 cases who suffered of myocardial infarction.
The present study has only 2 patients who had more than normal value of LDL.This observation of the present study to the observation of Srivastava et al14 for LDL was either in normal range or mildly elevated in patients of myocardial infarction.
The present study has observed 35 patients who had HDL level less than that of normal that is below 40.Of the total cases 23 were STEMI and 12 were NSTEMI.In another 5 cases the HDL level were less than 20.
The study of Srivastava et al14 and Agarwal et al14observed LDL/HDL ratio 2.5+/-0.93 in their 43 cases of acute myocardial infarction with STEMI.Razvi et al 4 observed the low level of HDL of P value 0.05 in the individuals with myocardial infarction.The present study too had observed that a significant population of 20 cases had an abnormal LDL/HDL ratio as observed in the studies of Srivastava et al 14 and Agarwal et al14.
The following is the table that shows the value of abnormally elevated CRP for STEMI and NSTEMI in various studies reviewed for the present work.
AUTHOR TOTAL NO
OF CASES
CRP VALUES
STEMI NSTEMI Myocardial Infarction Sheikh Aet al3 963 29.4+/- 1.7 27.1+/-1.7 -
Mubark et al17 60 - - >40
Magadale et al16 326 - - 25-40
PRESENT STUDY
50 11-30 11-20 -
The CRP was found to be raised in condition of myocardial infarction in above quoted studies to which the observation of present study agrees5,6,9,12..
The study of Sheikh et al 3 have observed the abnormally raised CRP values more in STEMI than NSTEMI myocardial infarction.The present study has made a parallel observation that the CRP values of higher in STEMI as compared to NSTEMI .
The study of Srivastava et al14 and Agarwal et al14 that LDL/HDL ratio was elevated in 29.9 % cases and CRP level was elevated in 60.5 % casesThe comparision of LDL/HDL ratio with the CRP values showed that the rise of CRP level was independent of alteration of LDL/HDL ratio.
The present study is in agreement to the observations of Srivastava et al14 and Agarwal et al14that the rise of CRP level is more sensitive biochemical alteration in myocardial infarction as compared to alteration of LDL/HDL ratio.
There were 22 cases in the present study without high LDL/HDL ratio but still showed elevated CRP levels.
The study concludes that the majority of patients do show raised CRP levels over a cut off of 11 ng/ml.However there is a proportion of population who suffers of coronary artery disease without significantly disturbed CRP levels . Their exists no relationship between the rising values of CRP with abnormal LDL/hdl ratio.
A significant population of the present study showed low levels of HDL entailing the importance of role of HDL in prevention of coronary artery disease.CRP levels appear to be raised more in STEMI than in NSTEMI as is evident by the results of the present study.
References :
1.Rashidinejad Hamidreza et al.The relationship between HS-CRP serum levels with the results of cardiac perfusion SPECT imaging in patients with suspected coronary artery disease.Asian journal of biomedical and pharmaceutical sciences,2015,5(50),2015,30-33.
2.Mohammad Mehdi Razban et al „The relationship between serum levels of HS-CRP and coronary lesion severity.Chujul medical vol 89,No 3,2016:352-364.
3.Sheikh A et al „C reactive protein as a predictor of adverse outcome in patients with acute coronary syndrome,Heart views jan-march 2012 issue vol 13.
4. Razavi A, Baghshani MR, Rahsepar AA, et al. Association between C - reactive protein, pro - oxidant - antioxidant balance and traditional cardiovascular risk factors in an Iranian population. Ann Clin Biochem 2013Mar;50(Pt2):115-21.
5 Casas JP, Shah T, Hingorani AD, Danesh J, Pepys MB. C-reactive protein and coronary heart disease: a critical review. J Intern Med. 2008 Oct;264(4):295-314. doi:10.1111/j.1365- 2796.2008.02015.x.
6.Folsom AR, Aleksic N, Catellier D, Juneja HS, Wu KK. C-reactive protein and incident
coronary heart disease in the Atherosclerosis Risk
InCommunities(ARIC)study.AmHeartJ.2002Aug;144(2):233-8.
7.Kazemi-BajestaniSM,Ghayour-MobarhanM,EbrahimiM,Moohe- batiM,EsmaeiliHA,FernsGA.C-reactiveproteinassociatedwithcor-
onaryarterydiseaseinIranianpatientswithangiographicallydefinedcoronary artery disease.
Clin Lab. 2007;53(1-2):49-56.
8.BuckleyDI,FuR,FreemanM,RogersK,HelfandM.C-reactivepro- tein as a risk factor for coronary heart disease: a systematic review and meta-analyses for the U.S. Preventive Services Task Force. Ann Intern Med. 2009 Oct6;151(7):483-95.
9.Heeschen C, Hamm CW, Bruemmer J, Simoons ML. Predictive value of C-reactive protein
and troponin T in patients with
unstableangina:Acomparativeanalysis.CAPTUREInvestigators.
Chimericc7E3AntiplateletTherapyinUnstableanginaRefractory tostandardtreatmenttrial.JAmCollCardiol2000;35:1535-42.
10. Lindahl B, Toss H, Siebahn A, Venge P, Wallentin L. Markers of myocardial damage and
inflammation in relation to long-term
mortalityinunstablecoronaryarterydisease.FRISCStudyGroup. Fragmin during Instability in Coronary Artery Disease. N Engl J Med2000;343:1139-47.
11.BiasucciLM,LiuzzoG,GrilloRL,CaligiuriG,RebuzziAG,Buffon
A,etal.ElevatedlevelsofC-reactiveproteinatdischargeinpatients with unstable angina predict recurrent instability. Circulation 1999;99:855-60.
12.de Winter RJ, Bholasingh R, Lijmer JG, Koster RW, Gorgels JP, Schouten Y, et al.
Independent prognostic value of C-reactive protein and troponin I in patients with unstable angina or non- Q-wave myocardial infarction. Cardiovasc Res1999;42:240-5.
13.Kuller LH, Tracy RP, Shaten J, Meilahn EN. Relation of C-reactive protein and coronary heart disease in the MRFIT nested case- control study. Multiple Risk Factor Intervention Trial.
Am J Epidemiol1996;144:537-47.
14.Shrivastava P et al „C reactive protein and Apo B as better predictor of STEMI than lipid profile.International journal of research in medical sciences October 2016/vol 4/issue 6/pg4583.
15.Okin PM, Roman MJ, Best LG, Lee ET, Galloway JM, Howard BV, et al. C-Reactive Protein and Electrocardiographic ST-Segment Depression Additively Predict Mortality. Journal of the American College of Cardiology. 2005 Jun;45(11):1787–93.
16.Krintus M, Kozinski M, Stefanska A, Sawicki M, Obonska K, Fabiszak T, et al. Value of C- Reactive Protein as a Risk Factor for Acute Coronary Syndrome: A Comparison with Apolipoprotein Concentrations and Lipid Profile. Mediators of Inflamation. 2012;2012:1–10.
17.Mach F, Lovis C, Gaspoz J-M, Unger P-F, Bouillie M, Urban P, et al. C-reactive protein as a marker for acute coronary syndromes. European Heart Journal. 1997 Dec 2;18(12):1897–902.
