بسم اهللا الرحمن الرحيم

RISK STRATIFICATION IN PATINETS WITH NSTE -ACS.

BY:DR. AYMAN ABDEL SAMAD.

M.D CARDIOLOGY.

1. NATURAL HISTORY:

-The short-term mortality of patients with unstable angina has been shown to be lower(1.7% at 30 days) than that of patients with NSTEMI or STEMI.

-long term outcomes-for both mortality &nonfatal events- are actually worse for patients with either unstable angina or NSTEMI compared with STEMI.

• SHORT TERM OUTCOME is depenent onthe hemodynamic stateا

• MEDIUM TERM OUTCOME ; transient ST segment shift

• LONG TERM OUTCOME Tn T&I longer term above and beyond conventional risk factors

Prognosis in Unstable Angina / Prognosis in Unstable Angina / NSTEMINSTEMI

PURSUIT trial dataPURSUIT trial data

Mortality in NonMortality in Non--ST ST ↑↑ ACS ACS Patients WithPatients WithMyocardial Infarction During HospitalizationMyocardial Infarction During Hospitalization

FintelFintel D, ACC, 2000D, ACC, 2000

18.318.3%%

5.5%5.5%

12.8% 12.8% ↓↓

(P(P = 0.0001)= 0.0001)

Patients with MI within Patients with MI within 72 hours (n=593)72 hours (n=593)

Patients without MI within Patients without MI within 72 hours (n=8,868)72 hours (n=8,868)

Days following randomizationDays following randomization

% M

orta

lity

% M

orta

lity

3030 6060 9090 120120 150150 180180

202020

151515

101010

555

2-METHODS OF RISK STATIFICATIN.

patients with UA/NSTEMI are a heterogeneousgroup, with a prognosis that ranges from • An excellent outcome with modest adjustments intherapeutic regimen,• high risk of death or MI : in which intensive

treatment is needed.

• High risk subgoups of patients, identified by:-clinical features.-electrocardiographic findings, or-cardiac(or vascular) markers.

• This group appear to derive greater benefit from more aggressive -antithrombotic or

- interventional therapy or- both.

3-CLINICAL VARIABLES:-classification of unstable angina has been

shown in several studies to be useful clinically in identifying high risk patients.

-High risk groups of patients with unstable angina are those with :

-Acute rest pain.-Post-MI unstable angina.-Secondary unstable angina.

4-RISK ASSESSMENT BY ECG :

-The admission ECG is very useful in predicting long-term adverse outcomes.

-Independent predictors of 1-year death or MI included: - LBBB

-ST segment deviation > 0.05mv.

-The presence of T wave changes > 0.1mV, was associated with a modest or no increase in subsequent death or MI.

GUSTO IIb: Correlation of 6-Month Mortality With Baseline ECG Findings in Patients With ACS

Cum

ulat

ive

Mor

talit

y (%

)

0

2

4

6

8

10

0 30 60 90 120 150 180

Days From Randomization

T-wave inversion

ST ↓ ACS

STEMI with fibrinolytics

26. EKG: ST Depression

New LBBB

Non-ST-Segment Elevation MI

5-RISK ASSESSMENT BY CARDIAC MARKERS.

1-Creatine kinase-MBNSTMI= elevated biomarkers of myocardial

necrosis-NSTMI with elevated CK-MB or troponins,

have a worse long-term prognosis than those with unstable angina.

.

CK/MB• Rises 4-6 hours after injury and peaks at 24

hours• Remains elevated 36-48 hours• Positive if CK/MB > 5% of total CK and 2 times

normal• Elevation can be predictive of mortality• False positives with exercise, trauma, muscle

dz, DM, PE

2-Myoglobin• Rises 2-4 hours after injury and peaks at 6-12 hours• Remains elevated 24-36 hours• Not cardiac specific• Rise of 25-40% over 2 hours strongly predictive of MI

ROPONINS :Very specific and more sensitive than CKRises 4-8 hours after injuryRemains elevated for 7-10 daysProvide very useful prognostic information

Linear relationship between the level of troponin T or I & subsequent risk of death The higher the troponin, the higher the mortality risk

rognostic Value of Troponin T or I in ACS: A Meta-Analysis

1.9

6.76.4

20.8

0

5

0

5

0

5

Death Death/MI

RR 3.9(2.9-5.3)

RR 3.8(2.6-5.5)

NegPos (Trop I + T)

-A higher risk of MI was observed with lower vels of troponin in several studies, & thus the erall rate of death or MI is equally high among tients with low or higher troponin values.

-Troponin T & I are useful not only in agnosing MI but also in risk assessment & in rgeting therapies to high risk patients.

1.01.7

3.4 3.7

6.0

7.5

012345678

0 to <0.4 0.4 to <1.0 1.0 to <2.0 2.0 to <5.0 5.0 to <9.0 9.0

Cardiac troponin I (ng/ml)

831 174 148 134 50 67

≥

%%

%%

%

%

nin I Levels and Mortality in Patients with NSTE-ACS

-REACTIVE PROTEIN:-CRP is very promising. Elevated CRP has

related to -increased risk of death-MI-need for urgent revascularization.

-levels of CRP in patients with ACS areoximately five times higher than those of stablents.

-CRP was able to discriminate a high- & a w-risk group: mortality for patients with an evated CRP was 5.8% versus 0.4% for patients thout elevated CRP.

-Mortality can be stratified from0.4% for patients with both markers negative 4.7% if either CRP or troponin was positive 9.1% if both were positive.

Predictive Value of hs-CRP r Mortality from ACS in FRISC Substudy

Cum

ulat

ive

Pro

babi

lity

of D

eath

(%)

Months

CRP 2-10mg/l (n=294)

20

10

00 6 12 18 24 30 36 42 48

CRP >10mg/l (n=309)

CRP <2mg/l (n=314)

-CRP measured at the time of hospitalscharge has been found to be a strong predictor

f outcome over 3 to 12 month.

Other inflammatory markershave offered consistent evidence of an association between systemic inflammation & recurrent adverse events , including serum amyloid Amonocyte chemoattractant protein-1(MCP-1).

WHITE BLOOD CELL COUNT:

mpler marker of inflammationevated WBC counts were ass. with igher risk of mortality & recurrent acute

MI his association was independent of CRP.

CD40 LIGAND :D40L is a member of tumor necrosis factor-pha family of proteins.pressed on the platelet surface when platelets e activated subsequently cleaved, generating a solubledrolytic fragment termed sCD40L.

-it has been found to be both prothromboticproinflammatory & to have a role inerosclerotic process.

-CD40L has been correlated with theree of platelet activation, as measured bytelet monocyte aggregates, & thus is a novelrker of platelet activation.

B-TYPE NATRIURETIC PEPTIDE:-BNP is a neurohormone that is

thesized in ventricular myocardium & releasedesponse to increased wall stress.

-its actions include :natriuresis,odilation, inhibition of sympathetic nervevity, & inhibition of the renin-angiotensin-steron system.

type Natriuretic Peptide (BNP) and Mortality in ACS Patients

0

2

4

6

8

10

0 50 100 150 200 250 300

Days After Randomization

P<.001 Quartile 4(n=630)

Quartile 3(n=632)

Quartile 2(n=632)

Quartile 1(n=631)

-BNP has prognostic value across the full spectrum of patients with ACS, including those with UA/NSTEMI.

-Measurement of BNP in patients withA/NSTEMI is very important to our currentols for risk stratification.

MYELOPEROXIDASE(MPO):MPO is a hemoprotein expressed by utrophils that possesses potent oinflammatory properties & that promotes idation of lipoproteins in vascular atheroma.Marker of .inflammation

.role of neutrophil in vascular lammation and ACS

- MPO serum levels in patients with STE-ACS were associated with increased risk r bsequent deathI . independent of other risk factors & otherdiac markers.

-Elevations of MPO have been seenoughout the coronary vasculature in patientsh UA/NSTEMI.

-Serum Creatinine :

levated creatinine was found to besociated with an adverse prognosis,

ndependent of other standard risk actors.

GLUCOSE : -Adverse outcomes have been seen among abetic patients with acute MI with elevated

dmission glucose values compared with patients ithout hyperglycemia.

-This association was found even among atients without a prior diagnosis of diabetes.

-Adverse oucome also with poor glycemic ontrol, as measured by hemoglobin A1c has een seen in other studies.

raunwald Classification of Risk for Patients with NSTE-ACS

INCAL INDICATORS OF INCREASED RISK IN PATIENTS WITH NSTE-ACS;

History ;age more than 70 yDMpost MI angina PVDCerebrovascular disease

CLINICAL PRESENTATION;Braunwald class II or III (acute ,subacuterest pain)Braunwald class B (secondary UA)HFHypotensionVentricular arrhythmias

ECG ;ST deviation 0.05 MvLBBBT wave inversion 0.03 Mv

Cardiac markersTn T or Tn IBNPCK-MBCD40 LIGANDGLUCOSECREATININEHBA1c

ANGIOGRAM ;Thrombus3 VDREDUCED EF

COMBINED RISK ASSESSMENT -SCORES.

- Comprehensive risk scores that use clinical riables, findings from ECG, & findings from serum rdiac markers.

- the most important baseline determinants of higher ortality were: -increasing age.

-increasing heart rate.-lower systolic BP.-ST segment depression.-signs of heart failure.

TIMI Risk Score

>65 yearsCAD Risk Factorsr Coronary Stenosis >50 % deviationAnginal events <24 hoursA in last 7 days

ated Cardiac Markers (CK-MB or troponin)

redicts risk of death, new/recurrent MI, need for urgentrevascularization within 14 days

is scoring system was used to ratify the risk for patients across a 10 ds gradient of risk om 4.7 % to 40.9 % (p<0.001)

The TIMI Risk Score and Incidence of Adverse Ischemic Events in Patients with

NSTE-ACS

4.78.3

13.219.9

26.2

40.9

0

10

20

30

40

50

0/1 2 3 4 5 6/7Number of Risk Factors

Dea

th, M

I, or

Urg

ent

Rev

ascu

lariz

atio

n (%

)

Risk Stratification

he strongest prognostic markers CRP ; marker of inflammation initiator of atherosclerosisBNP; reflect impaired LV functionTn ;the most sensitive and specific marker of myocyte necrosis

tients with higher TIMI risk scores ;d significant reductions in events when eated with ;

Enoxaparine compared with ufh (heparin)With a GPII B/III A inhibitor compared with lacebo .with an invasive vs conservative strategy.