European Perspectives
Journal: Circulation (2006)

A ccording to Dr Luigi Biasucci, "Inflammation is one component in a complex pathological process.Its role in the progression and development of atherosclerosis is probably different from its role in acute coronary syndromes, and it is probably more important in some patients than others."The inflammatory marker C-reactive protein has been shown to be a good predictor of future coronary events.People with the highest overall risk tend to be those with the higher levels of C-reactive protein."However, the relative risk attached to high C-reactive protein levels is reduced when risk factors such as obesity, diabetes, and hypertension are taken into account, suggesting that inflammation is probably a reflection of the patient's overall cardiovascular risk," explained Dr Biasucci."Adipose tissue produces a large number of proinflammatory cytokines, and there is a strong correlation between obesity, metabolic syndrome, diabetes, and inflammation."Even people with relatively low levels of C-reactive protein seem to be at greater risk of coronary events.Dr Biasucci believes that these people may have something hyperreactive that can be triggered to induce plaque rupture or thrombus formation.There could be thousands of possible triggers, including viral or bacterial infection, high lipid levels, and stress.Dr Biasucci said that the process triggered is probably not only inflammatory, but also involves activation of the coagulation system with production of prothrombotic and antithrombotic products.Research efforts need to concentrate on unravelling this activation process so that targeted treatments can be developed."Statins, angiotensin-converting enzyme inhibitors, or angiotensin-2 inhibitors are the best therapies we have so far.These have strong anti-inflammatory effects, but we don't know whether the reduction in events is really due to their antiinflammatory role, or a reduction in cholesterol, or improvement in blood pressure and endothelial function," he said.Dr Biasucci's group has recently shown that tumour necrosis factor-alpha blockers reduce activation of monocytes from patients with acute coronary syndromes in vitro. 1 Other researchers have shown that an antibody for C-reactive protein reduces experimental infarcts in animals. 2 Dr Biasucci pointed out, "We know that C-reactive protein is an important effector of complement and inflammatory cascade after damage.But what I would like to understand is how inflammation causes that damage.This antibody could be useful in infarction if it blocks C-reactive protein," he continued."But I do not think it will block the event as it is a cascade, and a large number of other factors such as interleukin-1 beta, interleukin-6, interferongamma, and lymphocytes would still be active."Pathological studies have shown that the bacterium Chlamydia pneumoniae is found in high concentrations in atherosclerotic plaques and the myocardium of patients who died from myocardial infarction (MI)."It is probably not an innocent bystander, as it can produce a number of products, such as heat shock proteins," Dr Biasucci said."A number of studies have shown that heat shock proteins are associated with the development of heart disease.There are high levels in almost all patients with MI or unstable angina, and they can cross-react very easily with the human ones, as these proteins are well conserved throughout evolution."In ischaemia, human endothelial cells, monocytes (see figure),The idea that inflammation was implicated in cardiovascular disease was initially not taken seriously, but its role is now recognised.