SHAPE Society

1. Clinical Characteristics ofClinical Characteristics of
Pre- Symptomatic VulnerablePre- Symptomatic Vulnerable
Patients; are There Different Types?Patients; are There Different Types?
Attilio Maseri, MD FACC FESC
University Vita-Salute San Raffaele, Milan Italy
No conflict of interest to disclose

2. Ridker PM, Circulation 2003, 107:363-9
Risk stratificationRisk stratification

3. Triggers of ACSTriggers of ACS
Subtle differences in clinical presentation
and phenotypic features may provide
clues suggestive of specific causes of
clinical syndromes.
In anemic patients, clinical history and red cell
features can provide useful information on
specific causes of anemia.
 Could this also be the case for
patients presenting with Acute Coronary
Syndromes?

4. Different clinicalDifferent clinical
presentation of ACSpresentation of ACS
TYPE 1
InfarctionInfarction out of the blue precededout of the blue preceded
and followed by completeand followed by complete stabilitystability
TYPE 2
Unstable angina  followed by
infarctioninfarction  followed byfollowed by recurrent ACS
Maseri A, Italian Heart J 2003, 4:345-6Maseri A, Italian Heart J 2003, 4:345-6

5. CRP levels > 3mg/lCRP levels > 3mg/l
in: ~ 65% of UA (IIIB)
~ 100% of MIs preceded by UA
~ 45% of MIs not preceded by UA
Biasucci LM et al. Circulation 1999
Bogarty P et al. Circulation 2001
Persisting CRP elevation post discharge
predics recurrent instability
Liuzzo et al. NEJM 1994 and JACC 1999

6. CRP Levels> 3 mg/l in UACRP Levels> 3 mg/l in UA
0
10
20
30
40
50
60
70
80
90
100
admission discharge 3 months 1 year
Patients(%)
Biasucci LM, Circulation 1999

7. Biasucci LM, Circulation 1999
CRP<3 mg/LCRP<3 mg/L
CRP>3 mg/LCRP>3 mg/L
%
Cum. Survival
P<0.001
Event free survival according toEvent free survival according to
CRP levels at discharge in UACRP levels at discharge in UA
Months

8. Multiple unstableMultiple unstable
plaques in ACSplaques in ACS
• Multiple unstable coronary plaques
Goldstein et al, NEJM 2000
Zairis M et al, Atherosclerosis 2000
• Widespread coronary inflammation
Buffon et al, NEJM 2002

9. 0
10
20
30
40
50
60
70
CRP <2.5 mg/L CRP 2.5-7.2 mg/L CRP >7.2 mg/L
%
pts
no plaques simple plaques complex plaques
P=0.013
Carotid plaques in UACarotid plaques in UA
Lombardo A, submitted

10. Mechanisms of
inflammation in ACS
• Infectious and non infectious agents:
bacteria, viruses, oxydants, toxins
• Immunological stimuli
Circulation: Liuzzo 1999, 2000; Caligiuri 2000, Biasucci 2003
• Enhanced inflammatory responsiveness
Maseri NEJM 1997;
Liuzzo: Circulation 1998, 2001;JACC 1999

11. Conclusions 1Conclusions 1
 In ACS inflammatory response is
largely independent from global
atherothrombotic burden.
 In some patients, but not in all,
plaque instability may be prolonged in
time and involve multiple vascular
sites.

12. Inflammatory mechanisms are correlatedInflammatory mechanisms are correlated
with recurrence of instability: they maywith recurrence of instability: they may
be multiple and not equally important inbe multiple and not equally important in
all patientsall patients..
Conclusions 2Conclusions 2
Their precise identification is required for a targetted
prevention of inflammation
Patients with recurrent instability and elevated
inflammatory markers are ideal candidates for pilot studies
Inhibition of key inflammatory final triggersInhibition of key inflammatory final triggers
of thrombosis appears an attractiveof thrombosis appears an attractive
therapeutic target.therapeutic target.

13. Exploring the triggers of ACS
Clinical investigators should stop being
“lumpers” and become "splitters”, looking
for distinctive, rather than for common
features, among patients presenting with
coronary atherosclerosis and ACS.