Clinical Characteristics of Clinical Characteristics of Pre- Symptomatic Vulnerable Pre- 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

Ridker PM, Circulation 2003, 107:363-9

Risk stratificationRisk stratification

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?

Different clinical Different clinical presentation of ACSpresentation of ACS

TYPE 1InfarctionInfarction out of the blue preceded out of the blue preceded and followed by complete and followed by complete stabilitystability

TYPE 2Unstable 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

CRP levels > 3mg/lCRP levels > 3mg/lin: ~ 65% of UA (IIIB)

~ 100% of MIs preceded by UA ~ 45% of MIs not preceded by UA

Biasucci LM et al. Circulation 1999Bogarty P et al. Circulation 2001

Persisting CRP elevation post discharge predics recurrent instability

Liuzzo et al. NEJM 1994 and JACC 1999

CRP Levels> 3 mg/l in UACRP Levels> 3 mg/l in UA

0102030405060708090

100

admissiondischarge 3 months 1 year

Patie

nts (

%)

Biasucci LM, Circulation 1999

Biasucci LM, Circulation 1999CRP<3 mg/LCRP<3 mg/LCRP>3 mg/LCRP>3 mg/L

%

Cum. Survival

P<0.001

Event free survival according to Event free survival according to CRP levels at discharge in UACRP levels at discharge in UA

Months

Multiple unstable Multiple unstable plaques in ACSplaques in ACS

• Multiple unstable coronary plaquesGoldstein et al, NEJM 2000Zairis M et al, Atherosclerosis 2000

• Widespread coronary inflammationBuffon et al, NEJM 2002

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

Mechanisms of inflammation in ACS

• Infectious and non infectious agents: bacteria, viruses, oxydants, toxins

• Immunological stimuliCirculation: Liuzzo 1999, 2000; Caligiuri 2000, Biasucci 2003

• Enhanced inflammatory responsivenessMaseri NEJM 1997; Liuzzo: Circulation 1998, 2001;JACC 1999

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.

Inflammatory mechanisms are correlated Inflammatory mechanisms are correlated with recurrence of instability: they may with recurrence of instability: they may be multiple and not equally important in be 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 triggers Inhibition of key inflammatory final triggers of thrombosis appears an attractive of thrombosis appears an attractive therapeutic target.therapeutic target.

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.