myocardial infarction and CRP

CRP AND MYOCARDIAL INFARCTION

Myocardial Infarction

Ischemic necrosis of myocardium due to sudden occlusion of coronary artery due to atheromatous plaque.

Signs and symptoms

prolong cardiac pain radiating to chest, arms, throat and back.

Signs and symptoms……

Increased Erythrocyte Sedimentation Rate.

Chest x rays shows pulmonary edema.

Atherosclerosis A form of arteriosclerosis where the

tunica intima of large and medium sized arteries is affected due to formation of fibrofatty plaques or atheromas.

RISK FACTORS

ATHEROSCLEROSIS

Oral contraceptiv

e pills

Diabetes mellitus

smoking

Hypertension

Myocardial

Infarction

Inflammation

Infections

obesity

RISK ACCORDING TO AGE AND SEX

Ages

Myocard

ial in

farc

tion

p

er

1000

pers

on

s y

ears

INFLAMMATION

A complex reaction in tissues that consist mainly of responses of blood vessels and leucocytes.

-Robbins and Cotrans

A protective response triggered by inflammatory mediators (interleukins, tumor necrosis factor).

Inflammation …..

One of the main cause of atherosclerosis.

Inflammation as a main cause of myocardial infarction has been a subject of studies for years as conformed by various studies .

-Ross 1999, Semeri etal 1992, Thompson etal 1995

Some predisposing factors like Diabetes,Hypertension,Hyperlipidemia can intensify inflammation of coronary arteries.

Indicators of inflammation (ICAM-1, VCAM-1, IL-1, IL-6, TNF, CRP).

C- reactive protein (CRP)- an important inflammatory marker.

Measuring inflammatory indicators other than screening plasma lipid is a useful prediction of myocardial infarction.

In case inflammation is cause,CRP may reveal the etiology and can be guide for management strategy.

C-Reactive Protein An acute phase protein , the level

rises in response to inflammation. It is a pentraxin , each subunit

having MW -33kDa. Synthesized by hepatocytes in

response to factors released by fat cells (adipocytes).

Structure of CRP

Binds to phosphocholine and activate complement system and also enhance phagocytosis by macrophages.

Increased level of CRP may be induced by metabolic, infective, immunologic or other processes.

Normal concentration - >10 mg/L, slightly increases with aging.

Higher levels are found in late pregnancy, bacterial infections , viral infections, mild inflammations and burns.

Increased CRP level indicate tissue damage and inflammation.

CRP levels: - Decreased by : Statins, aspirin, α-tocopherol (vitamin E) and loss of weight - Increased by : hormonal therapy will increase CRP

levels.

CRP is more sensitive and accurate reflection of acute phase response than ESR (Erythrocytes Sedimentation Rate)

CRP relationship with Myocardial infarction

CRP is a prognostic marker of cardiovascular events.

Predict myocardial infarction, stroke, peripheral arterial disease and sudden cardiac death.

CRP is an indirect marker of increased cytokine response to inflammation.

Person with high CRP level had relative risk of myocardial infarction 3 to 4 times higher than those with low level.

CRP levels and the risk group

S.No.

CRP level (mg/L)

Risk group

1. < 1 Low

2. 1 – 3 Moderate

3. > 3 High

CRP is stronger predictor of myocardial infarction than LDL cholesterol.

In clinical practice; even LDL cholesterol level below 130mg/dl and with c-RP level >3mg/L represent high risk group.

Because of less specificity of CRP, highly sensitive CRP(hsCRP) has been used these days.

Advantage of CRP over other inflammatory indicators like Interleukins, Tumor Necrosis Factor:

Easy Effective Inexpensive to measure.

Should not be measured within 3 weeks of acute inflammation

CRP measured within 12 hours of onset of symptom is not related to long term prognosis.

CRP and hsCRP Measurement and

Clinical Recommendation

Clinical laboratory methods to measure

serum CRP level :

1.Latex Agglutination method - Qualitative latex agglutination

method - Semiquantitative latex agglutination

method

2.Quantitative Method -ELISA -Immunoflourescence Quantitative test

Qualitative Latex Agglutination Method

1st laboratory method to measure CRP level.

Agglutination and precipitation indicates the presence of CRP in the serum sample.

A positive result indicate a CRP level greater than 10mg/L.

Can be performed within 10 to 20 minutes.

Semi quantitative Latex Agglutination Method

Dilution of serum

Mixed with latex reagent

Agglutination was observed

Highest dilution in which agglutination is observed

corresponds to approximate concentration of CRP-ligand complex

This method detects CRP level in between 6-10 mg/L.

Quantitative Method

Most rapid, sophisticated and sensitive method.

2 types: - ELISA - Immunoflourescence Quantitative

Test

Processing of ELISA:

Monoclonal Anti-CRP Antibodies conjugated with an

Enzyme

Diluted human serum is added

Formation of CRP-ligand complexes

Removal of unbound Antibodies

Florescent marked CRP-ligand complex is measured under Radio Immune Assay(RIA)

Clinical Application It is a strong predictor of CVS

events than cholesterol.

It adds prognostic information at all level of metabolic syndrome.

Prediction of risk group of CVS problem:

CRP level< 1mg/L: low risk group CRP level 1-3mg/L:moderate risk

group CRP level>3mg/L:High risk group

Interpretation Biochemical and pathological components are responsible for

formation of Atherosclerotic plaque

Manifests as myocardial infarction

hsCRP and CRP are useful diagnostic and prognostic marker of myocardial infarction.

Various methods are still on the way for the prognostic and diagnostic purpose of MI.

Latex agglutination method , ELISA and

immunofluorescence test commonly used for measurement of CRP.

ACKNOWLEDGEMENT

Thank you