Clinical Characteristics of Pre- Symptomatic Vulnerable Patients; are There Different Types? Clinical Characteristics of Pre- Symptomatic Vulnerable 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 stratification

Triggers 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 presentation of ACS TYPE 1 Infarction out of the blue preceded and followed by complete stability TYPE 2 infarction  followed by Unstable angina  followed by infarction  followed by recurrent ACS Maseri A, Italian Heart J 2003, 4:345-6

CRP 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

CRP Levels> 3 mg/l in UA admissiondischarge3 months1 year Patients (%) Biasucci LM, Circulation 1999

CRP<3 mg/L CRP>3 mg/L % Cum. Survival P<0.001 Event free survival according to CRP levels at discharge in UA Months

Multiple unstable plaques 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

CRP <2.5 mg/L CRP mg/L CRP >7.2 mg/L % pts no plaques simple plaques complex plaques P=0.013 Carotid plaques in UA Lombardo A, submitted

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

Conclusions 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 with recurrence of instability: they may be multiple and not equally important in all patients. Conclusions 2 Conclusions 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 of thrombosis appears an attractive 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.