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%
Babuin, Jaffe, CCM 2008
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
Babuin, Jaffe, CCM 2008
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
Patients at risk 0 day 15 days 30 days 31 days 2.5 years 5 years
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*
Accelerated Failure Time
Kaplan-Meier
cTnT undetectablecTnT undetectable
cTnT undetectable
cTnT undetectable
CP887679- 22
30-Day
Patients at risk 0 day 15 days 30 days 31 days 2.5 years 5 years
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
Accelerated Failure Time
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
hs-Troponin-T (ng/L)
≤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
(%
)
hs-Troponin-T (ng/L)
≤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
Log-rank test: P=0.0005
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
Log-rank test: P=0.0007
0.0
0.1
0.2
0 2 4
Year
Log-rank test: P=0.001
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
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