From Vulnerable Plaque to Vulnerable Patient

Abstract

Atherosclerotic cardiovascular disease results in >19 million deaths annually, and coronary heart disease accounts for the majority of this toll. Despite major advances in treatment of coronary heart disease patients, a large number of victims of the disease who are apparently healthy die suddenly without prior symptoms. Available screening and diagnostic methods are insufficient to identify the victims before the event occurs. The recognition of the role of the vulnerable plaque has opened new avenues of opportunity in the field of cardiovascular medicine. This consensus document concludes the following. (1) Rupture-prone plaques are not the only vulnerable plaques. All types of atherosclerotic plaques with high likelihood of thrombotic complications and rapid progression should be considered as vulnerable plaques. We propose a classification for clinical as well as pathological evaluation of vulnerable plaques. (2) Vulnerable plaques are not the only culprit factors for the development of acute coronary syndromes, myocardial infarction, and sudden cardiac death. Vulnerable blood (prone to thrombosis) and vulnerable myocardium (prone to fatal arrhythmia) play an important role in the outcome. Therefore, the term "vulnerable patient" may be more appropriate and is proposed now for the identification of subjects with high likelihood of developing cardiac events in the near future. (3) A quantitative method for cumulative risk assessment of vulnerable patients needs to be developed that may include variables based on plaque, blood, and myocardial vulnerability. In Part I of this consensus document, we cover the new definition of vulnerable plaque and its relationship with vulnerable patients. Part II of this consensus document will focus on vulnerable blood and vulnerable myocardium and provide an outline of overall risk assessment of vulnerable patients. Parts I and II are meant to provide a general consensus and overviews the new field of vulnerable patient. Recently developed assays (eg, C-reactive protein), imaging techniques (eg, CT and MRI), noninvasive electrophysiological tests (for vulnerable myocardium), and emerging catheters (to localize and characterize vulnerable plaque) in combination with future genomic and proteomic techniques will guide us in the search for vulnerable patients. It will also lead to the development and deployment of new therapies and ultimately to reduce the incidence of acute coronary syndromes and sudden cardiac death. We encourage healthcare policy makers to promote translational research for screening and treatment of vulnerable patients.

Joint Effect of Carotid Plaque and C‐Reactive Protein on First‐Ever Ischemic Stroke and Myocardial Infarction?

“…TRFs have well‐known limitations for accurate assessment of individual cardiovascular risk 1, 31. It is crucial to identify biomarkers that may improve the identification of subjects at risk and guide preventive treatment.…”

“…For plaque area, the risk estimates in our study were stronger in women than in men, suggesting that assessment of carotid plaque may be a more important tool in risk classification of women than in men. It is suggested that <10% of the population who test positive for atherosclerosis will experience a near‐term event 1. Identification of reliable imaging and serological markers of disease activity is therefore essential to improve the selection of vulnerable patients and cost‐effectiveness of screening with carotid ultrasound in the primary prevention setting.…”

“…Elevated CRP may be related to mechanisms involved in plaque rupture in acute CVD syndromes, such as production of proteolytic metalloproteinases (matrix metalloproteinases 2 and 9) 9. In addition, CRP is closely correlated to obesity, diabetes mellitus, hypercholesterolemia, and cigarette smoking 1, 3, 8. These are all conditions that lead to a prothrombotic state 1.…”

“…In addition, CRP is closely correlated to obesity, diabetes mellitus, hypercholesterolemia, and cigarette smoking 1, 3, 8. These are all conditions that lead to a prothrombotic state 1. CRP has been shown to induce tissue factor expression by vascular endothelial cells and smooth muscle cells and increase plasminogen activator inhibitor‐1 activity with concomitant reduction in tissue type plasminogen activator activity, resulting in overall impaired fibrinolysis 10.…”

“…Approximately one third of individuals who experience a first‐time cardiovascular event are misclassified as being at low risk on the basis of traditional risk factors (TRFs) 1. Novel biomarkers that can improve cardiovascular disease (CVD) risk prediction are long awaited.…”