Elevations of Cardiac Troponin not due to Ischemic Heart ... · Elevations of Cardiac Troponin not due to Ischemic Heart Disease Allan S. Jaffe, MD.* Consultant and Professor of Cardiology

CP887679- 0

Elevations of Cardiac Troponin not due to Ischemic Heart Disease

Allan S. Jaffe, MD.*

Consultant and Professor of Cardiology &

Laboratory Medicine and Pathology

Chair, CCLS Division, Department of Laboratory

Medicine and Pathology

Mayo Clinic and Medical School

Rochester, Minnesota

*Dr. Jaffe is or has been a consultant to most of the major diagnostic companies

as well as Novartis.

CP887679- 1

Cut Off Values for Use and Abuse

CP1054921-1

Apple, Wu, Jaffe: AHJ 144:981, 2002

Most STE MIs and NSTE MIs diagnosed by troponin and/or CKMB

•ROC cut off (Mayo value = 0.1 ng/ml)

Value most likely to equate troponin with CKMB .

Mostly NSTE MIs diagnosed with troponin

• 10% CV cut off (Mayo value = 0.03 ng/ml)

Value where confounding due to analytic issues is minimized.

Area where diagnostic information may be limited due to assay variability

• 99th percentile (Mayo value = <0.01 ng/ml)

ESC/ACC recommended cut off value with total precision of <10% as eventual goal.

CP887679- 2

Dea

th o

r m

yoca

rd

ial

infa

rcti

on

at

30 d

ay

s (%

)

77

128

231

601550 447

128

2257 5932 2891 5298 3866 4323

Sens=88% Sens=81% Sens=65%

99th perc. 10% CV ROC

53%65%73%

James S, et al. Am J Med.

2003;115:178 –184

77

0

2

4

6

8

10

12

0.01 microg/L 0.03 microg/L 0.1 microg/L

Below Cutoff

Above Cutoff

601

128

555

231

447

Troponin T Levels and Outcomes in GUSTO IV ACS

CP887679- 3

0369

12

0369

12

0369

12

OR 4.55; 2.66-7.78

Rapid Troponin I Assay

Outcomes in Relation to Troponin Values: The Issue of Assay Sensitivity

CP1148152-9

Int J Cardiol 93:113, 2004

%

Neg

Death MI Death or MI

56 98 92 130 132 205

Troponin T (0.1 g/L)

Troponin T (0.01 g/L)

OR 1.80; 1.30-2.54

1.82; 1.38-2.40

1.64; 1.31-2.06

OR 3.20; 2.22-4.59 2.26; 1.79-2.85

1.47; 1.12-1.93

3.42; 2.57-5.98 4.29; 3.02-6.09

Pos

%

%

41

15

113

139

86

25

136

197

116

36

221

301

CP887679- 4

cTnT Determinants of Elevation in the Community*

% with

elevated

cTnT

P<0.0001

CP1219620-13

Risk determinants present (no.)

No. 2,087 478 120 22

*Circulation, 113: 1958 – 1965, 2006

0

10

20

30

40

0 1 2 >3

CP887679- 5

Prevalence of Detectable cTnT & levels > 99th

percentile URL

Overall population 3546 957 (27.0) 25.0

(22.7 – 27.4)

122 (3.4)

2.0

(1.5 – 2.6)

Restricted population

Without CHD

3428 891 (26.0) 24.2

(21.8 – 26.5)

103 (3.0)

1.8

(1.2 – 2.4)

Without cardiovascular disease 3277 813 (24.8) 23.7

(21.3 – 26.1)

82 (2.5) 1.9

(1.0 – 2.0)

Without cardiovascular disease

or CKDa

3222 773 (24.0) 23.1

(20.7 – 25.5)

65 (2.3) 1.2

(0.8 – 1.7)

Without cardiovascular disease,

CKD, subclinical heart disease,

diabetes, or hypertensionb

2554 510 (20.0) 19.3

(16.8 – 21.8)

43 (1.7) 1.1

(0.6 – 1.7)

. cTnT Level, ng/mL .

. ≥ 0.003 . . ≥ 0.014 .

Sample Sample

Sample Weight-Adjusted Weight-Adjusted

Size, Prevalence, % Prevalence,

Group No. No. (%) (95% Cl) No. (%) 95% Cl)

CP887679- 6

Elevations of Troponins without Overt Ischemic Heart Disease

• Trauma (including contusion, ablation, pacing, ICD firings including atrial defibrillators, cardioversion, endomyocardial biopsy, cardiac surgery, after interventional closure of ASDs)

• Congestive heart failure–acute and chronic

• Aortic valve disease and HOCM with significant LVH

• Hyper and hypotension, especially with arrhythmias

• Postoperative noncardiac surgery patients who seem to do well

• Renal failure

• Critically ill patients, with respiratory failure, gastrointestinal bleeding, sepsis, heat stroke

• Drug toxicity, eg adriamycin, 5 FU, herceptin, snake venoms, carbon monoxide poisoning

• Hypothyroidism

• Abnormalities in coronary vasomotion, including coronary vasospasm

• Apical ballooning syndrome

• Inflammatory diseases eg. myocarditis, eg. Parvovirus B19, Kawasaki disease, sarcoid, smallpox vaccination, or myocardial extension of BE

• Post PCI patients who appear to be uncomplicated

• Pulmonary embolism, severe pulmonary hypertension

• Sepsis

• Burns, esp if TBSA > 30%

• Cardiomyopathies including Infiltrative diseases such as amyloidosis, hemachromatosis, sarcoidosis and scleroderma, non compaction syndrome

• Acute neurological disease, including CVA, subarchnoid bleeds

• Rhabdomyolysis with cardiac injury

• Transplant vasculopathy

• Vital Exhaustion

CP887679- 7

Singulex hsTnlARCHITECT hsTnl

Siemens hsTnlBeckman Access hsTnl

Roche hsTnTBeckman Tnl

Siemens Tnl Ultra (Centaur)Siemens Tnl (Immulite)

AxSYM TnlARCHITECT Tnl

OCD TnlSiemens Tnl (Dimension)

Roche TnlSiemens Tnl (Vista)

IL cTnlAbbott ISTAT

Siemens StratusAlere

BioMerleux

Hig

h

Sen

sit

ive

Assa

ys

Co

nte

mp

ora

ry

Assa

ys

Po

int

of

Ca

re

Assa

ys

Comparison of Normals Detected With Various Assays

Apple et al: Clin Chem 58(11):56, 2012

Detected (%)

CP887679- 8

hsTnI Values at ED Presentation Among Subjects With Non-Elevated Standard cTnI in Initial Sample

hsc

Tn

l valu

es

in

ng

/L

ACSn=17

ADHFn=47

Voloverload(other)

n=6

PEn=7

Cardiac(non-ACS)n=35

Othern=605

99%

LOD

80

60

40

20

0

Korley, Jaffe, AEMJ 2014

CP887679- 9

Relationship of hsc-TnT and Mortality by Diagnosis in Swedeheart

Melki et al: J Am Coll Cardiol 65:1655, 2015

hs-cTnT ng/L

Perc

en

tag

e

hs-cTnT ng/L

HR

ref

ACS

Other cardiac disease

Other non-cardiac

Heart failure

CP887679- 10

All-Cause Mortality by Cardiac Troponin T (n=733)

CP1090800-14Circulation 106:2944, 2002

Time since blood draw (years)

Cumulative survival

(%)

Patients at risk (no.) Baseline 1 yr 2 yr 2.5 yr

cTnT <0.01 g/L 132 106 25 12

cTnT 0.01 to <0.04 g/L 214 166 41 15

cTnT 0.04 to <0.10 g/L 239 180 63 18

cTnT 0.10 g/L 148 93 20 8

0

20

40

60

80

100

0.0 0.5 1.0 1.5 2.0 2.5 3.0

cTnT <0.01 g/L

cTnT 0.04 g/L

cTnT 0.10 g/L

cTnT 0.04

to 0.10 g/L

CP887679- 11

Relationship of Elevated Marker Proteins and Pathology in Patients

Ooi: Clin Chem 46(3):338, 2000

Other Cardiac Pathology

CK MB cTnI cTnT

Old MI or Patchy Fibrosis

CHF

No.

CK MB cTnI cTnT

20

10

0

No.

Recent MI

30

20

10

0

No.

No Myocardial Pathology20

10

0

Healing MI

20% 0%0% 0%

29% 0% 14% 22%

43%50%17%33%

67%48%19%19%

40% 10% 20% 42%13% 25% 25% 63%

CP887679- 12

0.00

0.10

0.20

0.30

0.40

0.50

1 2 3 4 5 6 7 8 9 1011121314151617181920212223242526272829303132

cTnT Values in Patients with ESRD Over Time

Jacobs et al: Ann Clin Biochem 46:283, 2009

cT

nT

(

g/L

)

cTnT t0

cTnT t2

cTnT t4

cTnT t6

99th percentile

10% CV

cTnT

CP887679- 13

Recognized vs Unrecognized

Myocardial Injury

Recognized

Unrecognized

10%

5%

Guest, Jaffe, JAMA 1995

CP887679- 14

Mortality

18.714.7

41.7 40.0

0

10

20

30

40

50

Total Normal cTnI Recog

cardiac

injury

Unrecog

cardiac

injury

%

Guest, Jaffe, JAMA 1995

CP887679- 15

Mortality in Patients with Detectable

Levels of cTnI (Critically Ill Group)

Pt

(%)

21.0

6.2

0

5

10

15

20

25

1

Detectable cTnI

Undetectable cTnI

8/38 11/175

P=0.0085

Wright, Jaffe, AJC 2002

CP887679- 16

0.00

0.20

0.40

0.60

0.80

1.00

0 5 10 15 20 25 30

Short-Term Prognosis of Critically Ill Patientsin the MICU

CP1224061-3

Survivaldistribution

function

Follow-up (days)

Normal troponin <0.01 ng/mL

cTnT <0.01

Elevated troponin >0.01 ng/mL

cTnT ≥0.01

P<0.001

P<0.001

Babuin, Jaffe, CCM 2008

CP887679- 17

0

5

10

15

20

25

30

35

40

45

Mortality at 30 Days By cTnT Level

Mortality

at 30 days(% of

patient)

<0.01

CP1224061-1

≥0.01-0.03 >0.03-0.1 >0.1

1 2.10 2.66 3.58Risk ratio

-- 1.40-3.15 1.82-3.88 2.48-5.1695% CI

cTnT (µg/L)

P<0.005

359 178 206 186

12.8%

26.4%

31.1%

41.4%


CP887679- 18

0.00

0.20

0.40

0.60

0.80

1.00

0 5 10 15 20 25 30

Long-Term Prognosis of Critically Ill Patientsin the MICU

CP1224061-4

Survivaldistribution

function

Follow-up (days)

Normal troponin <0.01 ng/mL

cTnT <0.01

Elevated troponin >0.01 ng/mL

cTnT ≥0.01

P<0.001

P<0.0001


CP887679- 19

*Critical Care Medicine 37:140, 2009

30-Day

Patients at risk 0 day 15 days 30 days 31 days 2.5 years 5 years

cTnT negative 425 371 361 361 143 16

cTnT positive 329 282 254 252 57 8

Pro

po

rtio

n o

f S

urv

ivin

g

Days

30-Day Survivors

Years

Log-rank test:

Chi-square = 11.2

P-value = 0.001

Log-rank test:

Chi-square = 64.0

P-value <0.001

Accelerated Failure Time

Kaplan-Meier

Probability of Death Based on cTnT Values on Admission in Patients With GI Bleeding*

cTnT negative

cTnT negative

cTnT positive

cTnT positive

CP887679- 20

Hs-cTnl and hs-cTnT Concentrations Before and After Exercise Dobutamine

Clinical Chemistry 58:11, 2012

Tro

po

nin

I (

ng

/L)

Tro

po

nin

T (

ng

/L)

Baseline

(n=112/

30/19)

Immedi-

ately

after test

(n=121/

31/18)

1.5 h

after test

(n=154/

32/17)

4.5 h

after test

(n=154/

32/19)

Baseline

(n=106/

24/15)

Immedi-

ately

after test

(n=112/

26/16)

1.5 h

after test

(n=113/

27/17)

4.5 h

after test

(n=123/

31/17)

No ischemia, no prev MI (n=146) No ischemia, but prev MI (n=33) Reversible ischemia (n=19)

CP887679- 21

*The American Journal of Medicine: 123(11):1049, 2010

30-Day


cTnT negative 96 496 492 492 475 244

cTnT positive 36 323 273 269 113 69

Pro

po

rtio

n o

f S

urv

ivin

g

Days

30-Day Survivors

Years

Log-rank test:

Chi-square = 94.3

P-value <0.001

Log-rank test:

Chi-square = 365.6

P-value <0.001

Probability of Death Based on cTnT Values on Admission in Patients With Acute Respiratory

Failure*


Kaplan-Meier

cTnT undetectablecTnT undetectable

cTnT undetectable

cTnT undetectable

CP887679- 22

30-Day


cTnT negative 281 262 221 221 112 38

cTnT positive 643 567 423 421 185 44

Pro

po

rtio

n o

f S

urv

ivin

g

Days

30-Day Survivors

Years

Log-rank test:

Chi-square = 19.2

P-value <0.001

Log-rank test:

Chi-square = 18.6

P-value <0.001


Kaplan-Meier

Probability of Death Based on cTnT Values on Admission in Patients With Sepsis*

cTnT negative

cTnT negative

cTnT positive

cTnT positive

*The American Journal of Medicine: 126(12):1114, 2013

CP887679- 23

Relationship Between hscTnT and Diastolic and RV Echo Measures*

Crit Care Med 42:790, 2014

Log (hs-troponin-T)

Lo

ng

itu

din

al

str

ain

-ra

te e

’-w

ave

Log (hs-troponin-T)

Rig

ht

ven

tric

ula

r en

d-s

ysto

lic

vo

lum

e i

nd

ex

r=-0.356

P<0.0001

r=0.383

P<0.0001

CP887679- 24

Outcomes in Patients With AF Stratified by CHA2DS2-VASc Score and hs-TnT

12,892 Patients ARISTOTLE Trial

0,0

0,5

1,0

1,5

2,0

2,5

3,0

≥5 4 3 2 ≤1

Hijazi: JACC

Stroke and

Systemic Embolism

Str

oke o

r syste

mic

em

bo

lism

(%

)

CHA2DS2VASc score

hs-Troponin-T (ng/L)

≤1.5

>1.5-6.8

>6.8-13

>13

0

1

2

3

4

5

6

7

≥5 4 3 2 ≤1

Cardiac Death

Card

iac d

eath

(%

)

CHA2DS2VASc score


≤1.5

>1.5-6.8

>6.8-13

>13

3314313-16

CP887679- 25

0

1

2

3

4

5

6

≥5 4 3 2 ≤1

Hijazi JACC 2013

3279896-9

Outcomes in Patients With AF Stratified by CHA2DS2-VASc Score and hs-TnT12,892 Patients ARISTOTLE Trial

Major Bleeding

CHA2DS2VASc score

Majo

r b

leed

ing

(%

)


≤1.5

>1.5-6.8

>6.8-13

>13

CP887679- 26

Event Rates in Relation to Levels of hs-Troponin I and CHA2DS2-VASc Risk Score

Hijazi et al: Circulation 129:625, 2014

Stroke and Systemic Embolism

Str

ok

e o

r

sys

tem

ic

em

bo

lis

m (

%)

CHA2DS2-VASc score

Cardiac Death

Ca

rdia

c d

ea

th (

%)

CHA2DS2-VASc score

Major Bleeding

Majo

r b

leed

ing

(%)

CHA2DS2-VASc score

hs-troponin I ng/L

≥3.3

>3.3-5.4

>5.4-10.1

>10.1

CP887679- 27

BMI and Elevated hscTnT

Ndumele et al: JACC: Heart Failure 2:600, 2014

20 25 30 35 40 45

BMI (kg/m2)

5

4

3

2

1

Ad

juste

d O

dd

s R

ati

o (

95%

CI)

CP887679- 28

Incidence of HF by hscTnT and BMI

Ndumele et al: JACC: Heart Failure 2:600, 2014

HR

of

inc

ide

nc

e H

F

Undetectable hs-cTnT

Measureable hs-cTnT

High hs-cTnT

P value for interaction term = .010

CP887679- 29

Relationship of OSA to hs-cTnT

Roca et al: Am J Respir Crit Care Med188:1460, 2013

Hs

-tro

po

nin

T (

g/L

)

0.004(<0.003, 0.006)

None(904)

0.005(<0.003, 0.008)

Mild(475)

0.005(0.003, 0.009)

Moderate(166)

0.006(0.004, 0.01)

Severe(100)

OSA categories

0.003

0.002

0.005

0.01

0.020.030.04

CP887679- 30

Changing hscTnl (Nanosphere) and Mortality

in Acute Heart Failure

Euro J Hrt Failure, Jan 2011

0.75

0.80

0.85

0.90

0.95

1.00

0 20 40 60 80 100

Days

Increasing troponin(41 subjects)Su

rviv

al

Stable or decreasing troponin(65 subjects)

CP887679- 31

Prognosis with hscTnl (Nanosphere) and BNP

in Acute Heart Failure

Euro J Hrt Failure, Jan 2011

0.6

0.7

0.8

0.9

1.0

0 20 40 60 80 100

Days

High BNP & high Tnl(56 subjects)

Ev

en

t fr

ee

(dea

th o

r re

ad

mis

sio

n) Low BNP & low Tnl

(34 subjects)

High BNP & low Tnl(26 subjects)

Low BNP & high Tnl(28 subjects)

CP887679- 32

Death and Hospitalization and hsTnT at Baseline

Latini et al: Circ 116, 2007

0 1 2 3 4 5 6 7 8 9 10

Mortality

Hospitalization for HF

Deciles

Hazardratio

(95% CI)

10

1

CP887679- 33

Mason et al: AHA, 2011

Mortality Based on Change in hscTnT Values

0.0

0.1

0.2

0 1 2

Val-HeFT

Year

All cause

mortality

No. at risk I 1,009 929 491

S 1,409 1,349 738

D 1,056 1,006 589

Log-rank test: P=0.002

0.0

0.2

0.4

0 2 4

GISSI-HF

Year


271 219 122

445 391 260

350 319 170

ISD

I

SD

0.00

0.05

0.10

0 1 2

Year

HF

mortality

No. at risk I 1,009 929 466

S 1,409 1,347 738

D 1,056 1,006 590


0.0

0.1

0.2

0 2 4

Year


271 217 103

445 391 224

350 322 216

ISD

I

S

D

I = >15% increase, S = stable, D = > 15% decrease

CP887679- 34

hscTnT and Markers of Fibrosis

*P<0.01 compared to each of the control groups

Kop et al: Circ Heart Fail 5:406, 2012

g

/L

CITP

cTnT tertiles

g

/L

PIIINP

ng

/mL

PIPI (<3.00-4.75 pg/mL) II (4.75-11.10 pg/mL) III (>11.10 pg/mL)

* *

CITP = carboxyterminal telopeptide of type I collagen

PIIINP = amnioterminal propeptide of procollagen III

PIP = procollagen type I

CP887679- 35

hscTnT Values and Fibrosis by MRI in Patients with HOCM

00.000

0.010

0.020

0.030

0.040

0.050

0.060

HCM fibrosis HCM no fibrosis Control

hsTnT

Journal of Cardiac Failure Vol. 16 No. 12, 2010

CP887679- 36

All Cardiovascular Events in Patients With HOCM by hs-cTnT Values

Kubo et al: JACC, 2013

Follow-up (years)

Even

t fr

ee r

ate

(%

)

Normal hs-cTnT(≤0.014 ng/mL)

n=84

Whole cohort (n=183)P <0.001

Abnormal hs-cTnT group (n=99)P = 0.020

Abnormal hs-cTnT (>0.014 ng/mL)

Lower (n=32)

Middle (n=32)

Upper (n=35)

CP887679- 37

Total Mortality by cTnT Values

P<0.001 for all between-group comparisons by the log-rank test; detectable cardiac troponin T (cTnT) levels are 0.003 ng/mL or greater by the highly sensitive assay; Y-axes shown in blue indicate the range from 0% to 20%

JAMA 304(22):2503, 2010

0

10

20

30

40

0 12 24 36 48 60 72

All-Cause Mortality

Cu

mu

lati

ve

in

cid

en

ce

o

f o

ve

rall

de

ath

(%

)

No. at risk

cTnT

Detectable 957 945 933 914 903 887 651

Undetectable 2,589 2,584 2,576 2,570 2,554 2,552 1,995

Months

0

10

20

30

40

0 12 24 36 48 60 72

No. at risk

0.0014 122 117 115 109 101 94 64

0.0066-<0.0014 278 273 267 261 258 254 182

0.00441-0.00657 279 278 276 271 271 268 209

0.003-0.00440 278 277 275 273 273 271 196

<0.003 2,589 2,584 2,576 2,570 2,554 2,552 1,995

Months

cTnT

Detectable

Undetectable

cTnT category, ng/mL

0.0014

0.0066-<0.0014

0.0041-0.00657

0.003-0.00440

<0.003 (undetectable)

CP887679- 38

0.0

0.2

0.4

0.6

0.8

1.0

0 3 6 9 12 15 18

0.0

0.2

0.4

0.6

0.8

1.0

0 3 6 9 12 15 18

Prognostic Value of hscTnT in Cardiovascular Health Study by hscTnT

Pro

po

rtio

n f

ree o

f h

eart

failu

re

Follow-up (yr)No. at risk

Category 1 1,427 1,380 1,281 1,131 956 763 461

Category 2 697 658 586 508 401 291 169

Category 3 700 642 550 435 333 231 131

Category 4 697 628 505 377 272 176 99

Category 5 700 532 357 213 119 77 36

Heart Failure

Pro

po

rtio

n w

ith

ou

t card

iovascu

lar

death

Follow-up (yr)No. at risk

Category 1 1,427 1,399 1,335 1,209 1,064 889 607

Category 2 697 675 619 554 460 343 229

Category 3 700 664 602 507 400 297 186

Category 4 697 655 565 461 344 231 137

Category 5 700 603 454 291 173 102 48

Cardiovascular Death

Cardiac troponin TCategory 1Category 2Category 3Category 4Category 5 P<0.001P<0.001

Cardiac troponin TCategory 1Category 2Category 3Category 4Category 5

deFilippi: JAMA 304(22), 2010

CP887679- 39

Prognostic Value of Changes in hscTnT

Incid

en

ce r

ate

/100 p

ers

on

-years

Baseline cTnT (pg/mL)

Heart Failure14

<3.00 3.00-5.44

5.45-8.16

8.17-12.94

>12.94

12

0

2

4

6

8

10

Baseline cTnT (pg/mL)

Cardiovascular Death

<3.00 3.00-5.44

5.45-8.16

8.17-12.94

>12.94

(18.1)

>50% decrease

Change 50%

>50% increase

deFilippi: JAMA 304(22), 2010

CP887679- 40

Association of Moderate Physical Activity, Rise in Hs cTnT Level and Risk of New Onset Heart Failure

deFilippi C: J Am Coll Cardiol 60:2539, 2012

Composite score is a sum of walking pace and duration of moderate to intense leisure

activities. A higher score is a faster pace and longer duration of activity

Pro

po

rtio

n w

ith

inc

rea

se

in

hs

cT

nT

Composite activity score

Ra

te o

f in

cid

en

t H

F

pe

r 1

00

pe

rso

n-

ye

ars

Composite activity score

P<0.001Significant increase

No significant increase

CP887679- 41Circulation 2006

Patie

nts(

%)

ACEI group

0

20

40

0%

43%

p<0.001

Controls

50

30

10

(n=0) (n=25)

Primary end-point:

LVEF decrease >10 percent units + <50%

CP887679- 42

TnI Values in Both Groups

45

40 0 0

100

43 41

21

103

100

0

20

40

60

80

100

Early M1 M2 M3 M6 M12

%

CP1252755-8Circ 114:2474, 2006

ACEI group

Control subjects

No. 56 56 56 56 56 55

TnI (ng/mL) 0.18±0.38 0.15±0.34 0.02±0.02 0.01±0.01 0.01±0.01 0.00±0.01

No. 58 58 58 58 57 55

TnI (ng/mL) 0.23±0.44 0.14±0.31 0.10±0.17 0.09±0.29 0.03±0.06 0.01±0.02

CP887679- 43

LVEF with and Without ACEI

80

60

40

20

LV

EF

(%

)

Months

CP1252755-7

Pre-

HDC

1 3 6 12

Months

Pre-

HDC

1 3 6 12

Controls ACEI Group

Circ 114:2474, 2006

TnI increase

No TnI increase

TnI increase

No TnI increase

CP887679- 44

Secondary end-pointsfollow-up 12 months

Sudden death 0 (0%) 0 (0%) 0 (0%) NSCardiac death 2 (2%) 0 (0%) 2 (3%) NSAcute pulmonary edema 4 (2%) 0 (0%) 4 (3%) NS

Heart failure 14 (12%) 0 (0%) 14 (22%) <0.001Life-threatening arrhythmias 11 (10%) 1 (2%) 10 (16%) 0.01

CUMULATIVE EVENTS 31 (28%) 1 (2%) 30 (52%) 0.001

Totaln=112

PACEI n=54

Controlsn=58

Cardinale et al. Circulation 2006

CP887679- 45

Mortality of Patients With and Without Myocardial Injury

Mortality

(%)

JAMA 295(4):398, 2006

0

10

20

30

40

50

0 1 2 3 4 5 6 7 8 9

Time since hospitalization (yr)

P<0.001

Myocardial injury

CP1288005-1

85 67 61 45 31

145 131 156 102 71

No. at risk

No myocardial injury

CP887679- 46

Change in Troponin Concentration at One Year and Risk Reduction

• Change in troponin concentration predicted MI and CHD death at 5 yyindependent of baseline LDL and change in LDL cholesterol (P<0.001)

• Participants with largest reduction in troponin (>40%) on pravastatin had a 4-fold greater reduction in primary endpoint (HR 0.21) than in those participants where troponin was unchanged (HR 0.82); P=0.001 for trend

* Adjusted for age, BMI, heart rate, SBP, DBP, HDL and LDL cholesterol, symptoms of angina, diabetes,

Htn, FHx of premature CHD, minor ECG abnormalities, nitrate use and smoking status

%

No

n-f

ata

l M

I o

r

CH

D d

ea

th (

%)

Reduction in Troponin I by Quarters

HR (95%CI)

1.0 0.82(0.51-1.32)

0.38(0.19-0.76)

0.31(0.14-0.67)

0.21(0.08-0.52)

Placebo Pravastatin

P=0.001

%

Reduction in LDL by Quarters

1.0 0.39(0.20-0.76)

0.39(0.20-0.78)

0.47(0.25-0.87)

0.53(0.29-0.97)

Placebo Pravastatin

P=0.823

Documents

Elevations of Cardiac Troponin not due to Ischemic Heart ... · Elevations of Cardiac Troponin not due to Ischemic Heart Disease Allan S. Jaffe, MD.* Consultant and Professor of Cardiology