HIGH SENSITIVITY HIGH SENSITIVITY C-REACTIVE PROTEIN IN C-REACTIVE PROTEIN IN

CARDIOVASCULAR CARDIOVASCULAR DISEASE AND MORTALITYDISEASE AND MORTALITY

Gary A. Lopez, M.DGary A. Lopez, M.D..Makati Medical CenterMakati Medical Center

Asian Hospital and Medical CenterAsian Hospital and Medical Center

Cardiovascular disease is the most Cardiovascular disease is the most frequent cause of mortality in the frequent cause of mortality in the Philippines , the U.S., and many parts Philippines , the U.S., and many parts of the world.of the world.

Most events caused by acute Most events caused by acute coronary events from coronary artery coronary events from coronary artery diseasedisease

ATHEROTHROMBOSIS LEADS TO CARDIAC AND VASCULAR EVENTS

COEXISTENCE OF ATHEROSCLEROTIC VASCULAR DISEASE

Pathology of Acute Coronary Syndrome

PlaqueRupture

PlaqueErosion

CalcifiedNodules

LuminalThrombosis

Acute CoronarySyndrome

Type of Type of Vulnerable Vulnerable

PlaquePlaqueFrequencyFrequency Pathological FindingsPathological Findings

Plaque RupturePlaque Rupture 55 – 60%55 – 60%

Numerous neutrophils, Numerous neutrophils, Macrophages and monocyte Macrophages and monocyte infiltration of thrombusinfiltration of thrombus

Plaque ErosionPlaque Erosion 30 – 35%30 – 35%

Few or absent macrophages Few or absent macrophages and lymphocytesand lymphocytes

Calcified NoduleCalcified Nodule 2 – 7%2 – 7%

Fibrin in between bony Fibrin in between bony spicules along with spicules along with osteoclasts and inflammatory osteoclasts and inflammatory cellscells

Virnani et al., JACC vol. 47, no. 8, 2006

FORMATION OF THE FIBROFATTY PLAQUE

FORMATION OF THE YOUNG ATHEROSCLEROTIC LESION

MATURATION OF THE ATHEROSCLEROTIC PLAQUE

AVERAGE COMPOSITION OF ADVANCED CORONARY PLAQUE

High-Risk, Vulnerable and Thrombosis-High-Risk, Vulnerable and Thrombosis-Prone PlaqueProne Plaque

- synonyms to describe a plaque that is at - synonyms to describe a plaque that is at increased risk of thrombosis and rapid stenosis increased risk of thrombosis and rapid stenosis progressionprogression

Inflamed Thin-cap FibroatheromaInflamed Thin-cap Fibroatheroma - an inflamed plaque with a thin cap covering a - an inflamed plaque with a thin cap covering a

lipid-rich, necrotic core. Suspected to be a high lipid-rich, necrotic core. Suspected to be a high risk/vulnerable plaque.risk/vulnerable plaque.

Vulnerable patientVulnerable patient - a patient at high risk (vulnerable/prone) to - a patient at high risk (vulnerable/prone) to

experience a cardiovascular ischemic event due experience a cardiovascular ischemic event due to a high atherosclerotic burden, high to a high atherosclerotic burden, high risk/vulnerable plaques, and/or thrombogenic risk/vulnerable plaques, and/or thrombogenic blood.blood.

NON-INVASIVE TESTS TO IDENTIFY HIGH-NON-INVASIVE TESTS TO IDENTIFY HIGH-RISK CORONARY DISEASE (>10% 1-YEAR RISK CORONARY DISEASE (>10% 1-YEAR

RISK OF CARDIAC EVENTS)RISK OF CARDIAC EVENTS)

1. MRI of the coronary arteries1. MRI of the coronary arteries

2. Multislice (64-slice) CT angiography of the 2. Multislice (64-slice) CT angiography of the coronary arteries with calcium scoringcoronary arteries with calcium scoring

3. Myocardial perfusion imaging using 3. Myocardial perfusion imaging using radionuclide techniques.radionuclide techniques.

4. Positive emission tomography4. Positive emission tomography..

CORONARY ANGIOGRAPHYCORONARY ANGIOGRAPHY

An invasive cardiac diagnostic procedure using An invasive cardiac diagnostic procedure using catheterization techniques and fluoroscopic catheterization techniques and fluoroscopic visualization.visualization.

Should be performed in asymptomatic high-risk Should be performed in asymptomatic high-risk patients.patients.

Provide risk stratification to alter therapy.Provide risk stratification to alter therapy.

C- REACTIVE PROTEINC- REACTIVE PROTEIN

A circulating pentraxinA circulating pentraxin Produced predominantly in the liver as part of the Produced predominantly in the liver as part of the

acute phase responseacute phase response Expressed in smooth muscle cells within diseased Expressed in smooth muscle cells within diseased

atherosclerotic arteriesatherosclerotic arteries Plays a major role in human innate immune Plays a major role in human innate immune

responseresponse Provides a stable plasma biomarker for low-grade Provides a stable plasma biomarker for low-grade

systemic inflammationsystemic inflammation

C-REACTIVE PROTEINC-REACTIVE PROTEIN

Composed of five 23 kD subunitsComposed of five 23 kD subunits

Has a half-life of 19 hoursHas a half-life of 19 hours

Neither consumed nor produced during Neither consumed nor produced during the reaction.the reaction.

Ideally 2 assays, averaged, fasting or Ideally 2 assays, averaged, fasting or nonfasting, and optimally 2 weeks apart, nonfasting, and optimally 2 weeks apart, provide a more stable level of this marker.provide a more stable level of this marker.

C-REACTIVE PROTEINC-REACTIVE PROTEIN

Stable for over long periods of timeStable for over long periods of time

Has no circadian rhythmHas no circadian rhythm

Not affected by food intakeNot affected by food intake

Therefore screening can be done on an outpatient basis at Therefore screening can be done on an outpatient basis at the time of cholesterol evaluation.the time of cholesterol evaluation.

Cost of high-sensitivity C-reactive Cost of high-sensitivity C-reactive protein at Makati Medical Centerprotein at Makati Medical Center

= 925.00 pesos= 925.00 pesos

MECHANISMS OF HSCRP ELEVATION IN MECHANISMS OF HSCRP ELEVATION IN RELATION TO ATHEROTHROMBOTIC RELATION TO ATHEROTHROMBOTIC

EVENTSEVENTS

UnknownUnknown TheoriesTheories

1. Inflammation of atherosclerotic plaques leading to HSCRP 1. Inflammation of atherosclerotic plaques leading to HSCRP elevation elevation

2. HSCRP may contribute to pathogenesis of atherosclerosis 2. HSCRP may contribute to pathogenesis of atherosclerosis due to interaction with lipids, lipoproteins, complement and due to interaction with lipids, lipoproteins, complement and coagulationcoagulation

3. HSCRP is detected in atherosclerotic plaques3. HSCRP is detected in atherosclerotic plaques

C-REACTIVE PROTEINC-REACTIVE PROTEIN

Mechanisms of influencing direct vascular Mechanisms of influencing direct vascular vulnerability:vulnerability:

1. increased expression of endothelial PAI-1.1. increased expression of endothelial PAI-1. 2. enhanced expression of adhesion molecules2. enhanced expression of adhesion molecules 3. reduced endothelial nitric oxide bioactivity.3. reduced endothelial nitric oxide bioactivity. 4. altered LDL uptake by macrophages4. altered LDL uptake by macrophages 4. colocalization with complement within 4. colocalization with complement within

atherosclerotic lesions.atherosclerotic lesions. 5. inhibition of intrinsic fibrinolysis5. inhibition of intrinsic fibrinolysis

THE INFLAMMATORY PATHWAY

USES OF ELEVATED HSCRPUSES OF ELEVATED HSCRP

Neonatal medicine - infectionNeonatal medicine - infection

Atherosclerotic and coronary heart diseaseAtherosclerotic and coronary heart disease

OsteoarthritisOsteoarthritis

CONDITIONS ASSOCIATED WITH MAJOR ELEVATION OF SERUMCONDITIONS ASSOCIATED WITH MAJOR ELEVATION OF SERUM CRP CRP

InfectionsInfections

Allergic complications of infectionAllergic complications of infection

Rheumatic feverRheumatic fever

Erythema nodosum leprosumErythema nodosum leprosum

Inflammatory diseaseInflammatory disease

Rheumatoid arthritisRheumatoid arthritis

Juvenile chronic arthritisJuvenile chronic arthritis

Ankylosing spondylitisAnkylosing spondylitis

Psoriatic arthritisPsoriatic arthritis

Systemic vasculitisSystemic vasculitis

Polymyalgia rheumaticaPolymyalgia rheumatica

Reiter’s diseaseReiter’s disease

Crohn’s diseaseCrohn’s disease

Familial Mediterranean feverFamilial Mediterranean fever

NecrosisNecrosis

Myocardial infarctionMyocardial infarction

Tumour embolizationTumour embolization

Acute pancreatitisAcute pancreatitis

TraumaTrauma

SurgerySurgery

BurnsBurns

FracruresFracrures

Malignant neoplasiaMalignant neoplasia

Lymphoma, Hodgkin’s diseaseLymphoma, Hodgkin’s disease

Carcinoma, sarcomaCarcinoma, sarcoma

ROLE OF INFECTION IN ATHEROTHROMBOSISROLE OF INFECTION IN ATHEROTHROMBOSIS

1. Clamydia , Helicobacter, Herpes simplex virus and 1. Clamydia , Helicobacter, Herpes simplex virus and CytomegalovirusCytomegalovirus

-- lead to systemic inflammation.-- lead to systemic inflammation.

-- lead to increased risk of cardiovascular events.-- lead to increased risk of cardiovascular events.

2. Clamydia and viral species have been identified in 2. Clamydia and viral species have been identified in atheromatous lesions.atheromatous lesions.

Need 2-3 weeks to check HSCRP in Need 2-3 weeks to check HSCRP in patients with injury or infection due to patients with injury or infection due to marked degree of inflammation.marked degree of inflammation.

Hormonal replacement therapyHormonal replacement therapy

may augment levels of HSCRPmay augment levels of HSCRP

Cushman et al, Citculation 100:717-722;1999

NON-PHARMACOLOGIC METHODS TO REDUCE NON-PHARMACOLOGIC METHODS TO REDUCE HSCRPHSCRP

1. WEIGHT REDUCTION1. WEIGHT REDUCTION

2. EXERCISE2. EXERCISE

VALUE OF HSCRP VALUE OF HSCRP MEASUREMENTSMEASUREMENTS

Conventional CRP assays cannot quantify serum proteins Conventional CRP assays cannot quantify serum proteins less than 5 mg/l.less than 5 mg/l.

HSCRP > 2.5 mg/literHSCRP > 2.5 mg/liter

Two to five-fold increased risk of suffering a coronary event Two to five-fold increased risk of suffering a coronary event in the future in patients with angina or in healthy normal in the future in patients with angina or in healthy normal adult population.adult population.

May predict progression of atherothrombotic events in May predict progression of atherothrombotic events in cerebrovascular and peripheral vascular disease.cerebrovascular and peripheral vascular disease.

HSCRP > 3 mg/literHSCRP > 3 mg/liter

Poor outcome in patients with severe unstable angina Poor outcome in patients with severe unstable angina ( increased risk of death, acute myocardial infarction, ( increased risk of death, acute myocardial infarction, or need for urgent revascularization intervention).or need for urgent revascularization intervention).

Predicts early reocclusion in patients undergoing PCI.Predicts early reocclusion in patients undergoing PCI.

“Your blood pressure and cholesterol are fine, but your hsCRP… “

USE OF HSCRP IN PRIMARY AND USE OF HSCRP IN PRIMARY AND SECONDARY PREVENTIONSECONDARY PREVENTION

More than 24 prospective epidemiologic primary prevention More than 24 prospective epidemiologic primary prevention studies evaluated the role of hsCRP as a determinant of studies evaluated the role of hsCRP as a determinant of vascular risk – vascular risk – all reported positive findingsall reported positive findings..

10 of these studies were powered to evaluate the risk 10 of these studies were powered to evaluate the risk prediction role of hsCRP beyond that associated with prediction role of hsCRP beyond that associated with traditional factors included in global assessment algorithms traditional factors included in global assessment algorithms such as the Framingham Risk Score.such as the Framingham Risk Score.

HSCRP HAS STRONG PREDICTIVE VALUE IN:HSCRP HAS STRONG PREDICTIVE VALUE IN:

1. currently healthy men1. currently healthy men

2. currently healthy women2. currently healthy women

3. elderly people3. elderly people

4. high-risk smokers4. high-risk smokers

5. stable and unstable angina5. stable and unstable angina

6. prior myocardial infarction6. prior myocardial infarction

ADDITIVE VALUE OF HSCRP AFTER ADJUSTMENT FOR RISK FACTORS

RELATIVE RISKS OF FUTURE CV EVENTS ACCORDING TO BASELINE LEVELS OF HSCRP

PROSPECTIVE STUDIES RELATING BASELINE HSCRP LEVELS TO THE RISK OF FIRST CV EVENTS

ADDITIVE VALUE OF HSCRP OVER TOTAL CHOLESTEROL, HDL-C AND APO B:APO A RATIO

Ridker et al, Women’s Health Study , NEJM, 2002; 347; 1557-65

Ridker et al,Clinical application of CRP for CV disease detection and prevention,Circulation 107:363,2003

GUSTO IV ACS Trial

PROGNOSTIC UTILITY OF HSCRP, TROPONIN, AND BNP IN ACUTE CORONARY ISCHEMIA

Baseline levels of HSCRP associate with Baseline levels of HSCRP associate with increased risk of developing Type 2 increased risk of developing Type 2 diabetes mellitus.diabetes mellitus.

Prediction of vascular events is beyond the Prediction of vascular events is beyond the components of the metabolic syndrome or components of the metabolic syndrome or presence of frank diabetes.presence of frank diabetes.

NATIONAL HEALTH AND NUTRITION EVALUATION SURVEY (NHANES)

Rotterdam Scan StudyRotterdam Scan Study

Higher HSCRP levels are associated with the Higher HSCRP levels are associated with the presence and progression of cerebral white presence and progression of cerebral white matter lesions in the periventricular and matter lesions in the periventricular and subcortical regions.subcortical regions.

Data implies small vessel disease progression.Data implies small vessel disease progression.

Van Dijk EJ et al, Circulation, 2005;112:900-5

Recent observationsRecent observations

1. Statins lower CRP in a manner largely 1. Statins lower CRP in a manner largely independent of LDL-C reduction.independent of LDL-C reduction.

2. Efficacy of statin therapy may be related to the 2. Efficacy of statin therapy may be related to the underlying level of vascular inflammation as underlying level of vascular inflammation as detected by HS-CRP.detected by HS-CRP.

CHOLESTEROL AND RECURRENT EVENTS CHOLESTEROL AND RECURRENT EVENTS (CARE) TRIAL(CARE) TRIAL

Risk reduction with Pravastatin was greater in Risk reduction with Pravastatin was greater in patients with elevated HSCRPpatients with elevated HSCRP

Pravastatin significantly reduced elevated HSCRP Pravastatin significantly reduced elevated HSCRP levels over a 5-year periodlevels over a 5-year period

PRAVASTATIN OR ATORVASTATIN EVALUATION AND PRAVASTATIN OR ATORVASTATIN EVALUATION AND INFECTION THERAPY-THROMBOLYSIS IN MYOCARDIAL INFECTION THERAPY-THROMBOLYSIS IN MYOCARDIAL

INFARCTION 22 TRIAL (PROVE IT-TIMI 22)INFARCTION 22 TRIAL (PROVE IT-TIMI 22)

1. level of HS-CRP achieved after initiation of statin therapy is 1. level of HS-CRP achieved after initiation of statin therapy is as important as LDL-C for subsequent vascular events.as important as LDL-C for subsequent vascular events.

2. best overall survival was seen not only with patients whose 2. best overall survival was seen not only with patients whose LDL-C was lowered to <70 mg/dl but also whose HS-CRP LDL-C was lowered to <70 mg/dl but also whose HS-CRP lowered < 2 mg/l.lowered < 2 mg/l.

3. this result was present regardless of statin regimen used.3. this result was present regardless of statin regimen used.

4. measuring and monitoring of HS-CRP following initiation of 4. measuring and monitoring of HS-CRP following initiation of statin therapy may be required to maximize benefit similar statin therapy may be required to maximize benefit similar to use of LDL-C.to use of LDL-C.

Ridker et al, NEJM, 2005; 352: 20-8

PROVE IT - TIMI 22 – CUMULATIVE RATE OF RECURRENT M.I. OR DEATH AMONG STATIN-TREATED PATIENTS ACCORDING TO ACHIEVED LEVELS OF LDL-C AND HSCRP

PROVE IT - TIMI 22 – RATE OF RECURRENT M.I OR DEATH AMONG STATIN-TREATEDPATIENTS ACCORDING TO LDL-C AND HSCRP AFTER 30 DAYS

REVERSAL studyREVERSAL study

Patients were randomized to moderate lipid lowering with Patients were randomized to moderate lipid lowering with Pravastatin 40 mg or intensive lipid lowering with Pravastatin 40 mg or intensive lipid lowering with Atorvastatin 80 mg for 18 months.Atorvastatin 80 mg for 18 months.

Measurement of atherosclerotic burden by IVUS was Measurement of atherosclerotic burden by IVUS was carried out during baseline catheterization and at study carried out during baseline catheterization and at study completion. 502 patients completed the trial, 249 on completion. 502 patients completed the trial, 249 on Pravastatin and 253 for Atorvastatin. The 2 treatment Pravastatin and 253 for Atorvastatin. The 2 treatment groups were well matched: ave. age was 56 yrs, about 70% groups were well matched: ave. age was 56 yrs, about 70% were male, and 20% were diabetic. Baseline LDL-were male, and 20% were diabetic. Baseline LDL-cholesterol was 150 mg/dl in both groups, triglycerides 197 cholesterol was 150 mg/dl in both groups, triglycerides 197 mg/dl, and C-reactive protein (CRP) approximately 3 mg/dl.mg/dl, and C-reactive protein (CRP) approximately 3 mg/dl.

By the end of the treatment group, LDL-chol was By the end of the treatment group, LDL-chol was significantly lower among patients who had been significantly lower among patients who had been randomized to the Atorvastatin group.randomized to the Atorvastatin group.

REVERSAL STUDY : Secondary EndpointsREVERSAL STUDY : Secondary Endpoints

EndpointsEndpoints PravastatinPravastatin

( n=249)( n=249)

AtorvastatinAtorvastatin

( n=253)( n=253)P value,P value,

Pravastatin Pravastatin vs.vs.AtorvastatinAtorvastatin

Change in total Change in total AtheromaAtheroma

Volume (mm3)Volume (mm3)

+ 4.4+ 4.4 -0.9-0.9 .02 *.02 *

P value vs baselineP value vs baseline .01 **.01 ** .72 **.72 ** ----

Change in % Change in % obstructiveobstructive

Volume (%)Volume (%)

+1.6+1.6 +0.2+0.2 .0002 *.0002 *

P value vs baselineP value vs baseline .0001 **.0001 ** .18 **.18 ** ----

Change in hsCRP Change in hsCRP (%)(%)

-5.2-5.2 -36.4-36.4

* Wilcoxon signed rank test**Wilcoxon rank sum test

ASSESSMENT OF THE CLINICAL UTILITY OF NOVEL MARKERS OF CV RISKASSESSMENT OF THE CLINICAL UTILITY OF NOVEL MARKERS OF CV RISK

MarkerMarker Assay Assay conditions conditions standardized?standardized?

Prospective Prospective studies studies consistent?consistent?

Additive to total Additive to total cholesterol and cholesterol and HDL-C?HDL-C?

Additive to Additive to Framingham Framingham risk?risk?

Lipoprotein Lipoprotein (a)(a) -- +/-+/- +/-+/- --HomocysteineHomocysteine ++ ++ +/-+/- --Tissue Tissue plasminogen plasminogen activator and activator and PAI-1PAI-1

+/-+/- + + +/-+/- --

Lipoprotein Lipoprotein densitydensity -- +/- +/-

-- --

FibrinogenFibrinogen -- ++ ++ --High-High-sensitivitysensitivity

CRPCRP

++ ++ ++ ++

Ridker et al, Risk Factors for Atherothrombotic Disease, 2005, 939-54

ACC/AHA CLASSIFICATIONSACC/AHA CLASSIFICATIONS

Class 1Class 1

Conditions for which there is evidence and/or general agreement that a Conditions for which there is evidence and/or general agreement that a given procedure or treatment is useful and effective.given procedure or treatment is useful and effective.

Class IIClass II

Conditions for which there is conflicting evidence and/or a divergence of Conditions for which there is conflicting evidence and/or a divergence of opinion about the usefulness/efficacy of a procedure or treatment.opinion about the usefulness/efficacy of a procedure or treatment.

Class IIaClass IIa Weight of evidence/opinion is in favor of usefulness/efficacy Weight of evidence/opinion is in favor of usefulness/efficacy

Class IIbClass IIb Usefulness/efficacy is less well established by evidence/opinion. Usefulness/efficacy is less well established by evidence/opinion.

Class IIIClass III

Conditions for which there is evidence and/or general agreement that a Conditions for which there is evidence and/or general agreement that a procedure /treatment is not useful/effective and in some cases may be procedure /treatment is not useful/effective and in some cases may be harmful.harmful.

ACC/AHA GUIDELINES FOR THE MANAGEMENT OF PATIENTS WITH ACC/AHA GUIDELINES FOR THE MANAGEMENT OF PATIENTS WITH UNSTABLE ANGINA AND NON-ST-SEGMENT ELEVATION MYOCARDIAL UNSTABLE ANGINA AND NON-ST-SEGMENT ELEVATION MYOCARDIAL

INFARCTION Nov, 2002INFARCTION Nov, 2002

II. Initial evaluation and ManagementII. Initial evaluation and Management

B. Early Risk Stratification RecommendationsB. Early Risk Stratification Recommendations

Class IIbClass IIb

1. C-reactive protein (CRP) and other markers of inflammation 1. C-reactive protein (CRP) and other markers of inflammation should be measured.should be measured.

CENTERS FOR DISEASE CONTROL AND PREVENTION / CENTERS FOR DISEASE CONTROL AND PREVENTION / AMERICAN HEART ASSOCIATIONAMERICAN HEART ASSOCIATION

MARKERS OF INFLAMMATION AND CARDIOVASCULAR MARKERS OF INFLAMMATION AND CARDIOVASCULAR DISEASE: A STATEMENT FOR HEALTHCARE DISEASE: A STATEMENT FOR HEALTHCARE PROFESSIONALSPROFESSIONALS

It is reasonable to measure HSCRP as an adjunct to the It is reasonable to measure HSCRP as an adjunct to the major risk factors to further assess absolute risk for major risk factors to further assess absolute risk for coronary disease primary prevention – coronary disease primary prevention – optional.optional.

HSCRP measurement appears to be best employed to HSCRP measurement appears to be best employed to detect enhanced absolute risk in persons in whom multiple detect enhanced absolute risk in persons in whom multiple risk factor scoring projects a 10-year CHD risk in the range risk factor scoring projects a 10-year CHD risk in the range of 10% to 20% - of 10% to 20% - intermediate risk.intermediate risk.

Pearson et al,Pearson et al,Circulation, 2003; 107:449Circulation, 2003; 107:449

CDC/AHA ISSUES ON HSCRPCDC/AHA ISSUES ON HSCRP

1. When and in whom should HSCRP be used?1. When and in whom should HSCRP be used?

2. What is the purpose for its measurement and the likelihood that 2. What is the purpose for its measurement and the likelihood that further diagnostic and therapeutic plans change on the basis of further diagnostic and therapeutic plans change on the basis of tests results?tests results?

3. No clinical trials have been completed in which a population has 3. No clinical trials have been completed in which a population has been randomly allocated to HSCRP screening and both groups been randomly allocated to HSCRP screening and both groups followed up prospectively to determine the benefits and harms of followed up prospectively to determine the benefits and harms of the screening.the screening.

4. Few data on the cost-effectiveness of screening with HSCRP, taking 4. Few data on the cost-effectiveness of screening with HSCRP, taking into account further testing and treatment of persons classified as into account further testing and treatment of persons classified as being at low risk.being at low risk.

CDC/AHA RECOMMENDATIONSCDC/AHA RECOMMENDATIONS

1. HSCRP > 3.0 mg/L (high risk) – may allow intensification of medical 1. HSCRP > 3.0 mg/L (high risk) – may allow intensification of medical therapy to further reduce the risk and to motivate patients to therapy to further reduce the risk and to motivate patients to improve their lifestyle or comply with medications prescribed to improve their lifestyle or comply with medications prescribed to lower their risk.lower their risk.

2. Low risk individuals (<10% in 10 years) will unlikely to have a high 2. Low risk individuals (<10% in 10 years) will unlikely to have a high risk (>20%) identified thru HSCRP testing.risk (>20%) identified thru HSCRP testing.

3. High risk individuals (>20% in 10 years) or with established 3. High risk individuals (>20% in 10 years) or with established atherosclerotic disease generally should be treated intensively atherosclerotic disease generally should be treated intensively regardless of their HSCRP levels. (limited use of HSCRP in regardless of their HSCRP levels. (limited use of HSCRP in secondary prevention).secondary prevention).

CDC/AHA RECOMMENDATIONSCDC/AHA RECOMMENDATIONS

4. In patients with stable coronary disease or acute coronary 4. In patients with stable coronary disease or acute coronary syndromes, HSCRP measurement may be useful as an syndromes, HSCRP measurement may be useful as an independent marker for assessing likelihood of recurrent events, independent marker for assessing likelihood of recurrent events, including death, myocardial infarction, or restenosis after PCI.including death, myocardial infarction, or restenosis after PCI.

5. Secondary preventive interventions with proven efficacy should 5. Secondary preventive interventions with proven efficacy should not be dependent on HSCRP levels.not be dependent on HSCRP levels.

6. Serial testing of HSCRP should not be used to monitor effects of 6. Serial testing of HSCRP should not be used to monitor effects of treatment.treatment.

The CDC/AHA Workshop identified CRP as The CDC/AHA Workshop identified CRP as the current analyte of choice , but do not the current analyte of choice , but do not support its use in risk prediction or patient support its use in risk prediction or patient management at this point in time.management at this point in time.

ISSUES ON HS-CRPISSUES ON HS-CRP

No firm data to date that lowering CRP No firm data to date that lowering CRP levels per se will lower vascular risk.levels per se will lower vascular risk.

It remains controversial whether CRP It remains controversial whether CRP plays a direct causal role in plays a direct causal role in atherogenesis.atherogenesis.

CONCLUSIONCONCLUSION

Data for high-sensitivity C-reactive protein Data for high-sensitivity C-reactive protein provides evidence that biomarkers beyond those provides evidence that biomarkers beyond those taditionally used for vascular risk detection and taditionally used for vascular risk detection and monitoring can play important clinical roles in monitoring can play important clinical roles in prevention and treatment.prevention and treatment.

Thank YouThank You