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OUR MISSION: TO REDUCE THE BURDEN OF CARDIOVASCULAR DISEASE
Dr. Raimund Erbel,
Nearly 60% of all deaths from myocardial infarction occur outside the hospital and the events are sudden, often without any sign of warning. The understanding of high-risk atherosclerosis was therefore chosen by the program committee and presented under the chairmen A Maseri, Milan, It and R Erbel, Essen, DE by E Falk, Aarhus, DK, F Crea, Rome, IT, V Fuster, New York, US, and PW Serruys, Rotterdam, NL.
The pathologist E Falk started by pointing out that the disease process starts as early as childhood and the young adult age, but manifests itself decades later, mainly after the age of 50. High-risk assessment should be related to three features 1) plaque burden, 2) activity, and 3) vulnerability. Plaque burden is found in nearly all individuals with sudden death due to myocardial infarction and is not only present in the heart, but also in other vascular territories. Plaque activity does not mean that inflammation has to be present, and inflammation is not equal to instability, he pointed out. In plaques, only few cells are found, necrotic core with no cells and fibrotic tissue with only few cells. Except for the fibrous cap, presenting some macrophages at the rupture tear, it seems not be be a typical picture of inflammation. With regard to the fibrous cap, he found that the AHA recommendations from 1995 published by Stary et al in Circulation, have to be improved, because the thinning of the fibrous cap in atheroma and fibroatheroma has not been described as a special feature of plaques prone to rupture. Plaque vulnerability is typically found as plaque rupture in 75 % of acute coronary syndromes and erosion in the remaining cases with few exceptions. Recently the role of plaque hemorrhage came into the focus of research starting with the description by M Davies, and has recently found to be essential in the pathogenesis of this syndrome by the group of Virmani, starting with neo-vasculariation and ending with intramural bleeding.
The clinical perspectives of high-risk atherosclerosis were presented by F Crea pointing to the important remark that in unstable angina, signs of inflammation are not always found, underlining the weakness of testing for the high sensitive C-reactive protein (CRP) to detect those at risk. But elevated CRP, determined at onset or weeks later, after an event, as well as persistent elevated CRP levels during follow-up mean a worse prognosis. Inflammation points to a local but indicates a general inflammatory state illustrated also by a rise in NF-kappa B levels in mononuclear cells and MMP. So it is not surprising that in unstable angina, similar lesions are found in the carotid tissue when it is removed during surgery. A new finding is the identification of the very aggressive CD 4 + CD28 null cells, which are particularly found in recurrent UA patients. F Crea finished his lecture with an outlook to the role of T-cells: Th 1 and Th2, as well as Th3 cells. The identification of their role has led research to use immunmodulating drugs like Infliximab in order to change the outcome. As statins do not fully reduce cardiovascular risk, such treatments may open the field for additional risk reduction in the future.
The identification of those at risk was the topic of V Fuster, which was a request put forward to research already 30 years ago by M Sones on a symposium in Frankfurt, DE. At that meeting the role of fluoroscopy for detection of coronary calcification was discussed. In his presentation, V Fuster announced the start of a new study in 6000 subjects which will use computed tomography (CT), ultrasound of the carotid and abdominal aorta, as well as the ankle-brachial – index (ABI). Based on the results, additional testings are performed including magnetic resonance imaging and CT angiography. A group of those who are not undergoing imaging have the role of a control group. This study will add information to the ongoing population based studies: the multi-ethnic study on atherosclerosis (MESA) and the Heinz Nixdorf Recall (HNR) study, as well including socio-economic aspects.
While tests for risk assessment reveal a person at risk, modern imaging methods allow detection of vulnerable lesions, as PW Serruys pointed out. He presented the newest technology which is currently used, will be available, or is under development. In an editorial which can be found in the current issue of the JACC, he demonstrates the bridge from new pathological findings to the most advanced study in humans using intravascular ultrasound, angioscopy, and optical coherence tomography (OCT) in patients with acute coronary syndrome. The group of Virmani and Muller demonstrated that > 1 thin fibrous caps are found in 44% of patients and that on average, they have 0.46 thin fibrous caps/patient. Using OCT and angioscopy in all patients, thrombus formation existed, but was detected by intravascular ultrasound in only 33%. Most stimulating was the finding that by OCT, the measured mean fibrous cap thicknes was 49 um+/- 21 um which fits with what the pathologists in the group of Virmani found – thickness < 60 um means plaques at risk.
The understanding of high-risk atherosclerosis is of utmost importance when we want to reduce the number of patients who die outside the hospital and who are mostly found in the general population at low and intermediate risk. At the end, A Maseri put the additional question forward: Once we have tested, when do we have to repeat and at what intervals. Improved risk prediction will influence our attempts for prevention and current guidelines will be different when we will look at them again in 5 years.
Current understanding of high-risk atherosclerosis Basic Science Track
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