Predictive value of vulnerable plaques in the carotid arteries for risk of coronary heart disease and stroke
06 / 2006 - unknown
A primary aim in cardiovascular prevention is to identify subjects who are vulnerable to acute coronary events. Despite the development of several risk prediction models, traditional cardiovascular risk factors fail to predict the development of cardiovascular disease in a large proportion of cases. In the past decade, it has been recognized that plaque vulnerability is much more important than plaque size for the development of acute events. The recognition of the role of the vulnerable plaque in the development of cardiovascular events provides a novel opportunity for improved risk assessment. Magnetic resonance imaging (MRI) has the potential to measure plaque structure in asympotmatic subjects. MRI of the coronary arteries remains difficult due to their small size and motion but the accuracy of multi-sequence MRI for identifying features of vulnerable plaque in human carotid atherosclerosis has been demonstrated. Plaque vulnerability has been found to be multifocal and therefore, although local factors play an important role, plaque vulnerability is likely to be a generalized phenomenon. In the present proposal, we will examine the structure of atherosclerotic plaques in the carotid arteries, and their development to overt cardiovascular disease. The ultimate aim is to develop a novel risk assessment strategy which includes the assessment of vulnerable plaque. The research questions are: (1) What is the predictive value of vulnerable carotid plaques detected by multi-sequence MRI for risk of coronary heart disease? (2) What is the predictive value of vulnerable carotid plaques detected by multi-sequence MRI for risk of stroke? The study will be embedded in the Rotterdam Study, a population-based study among more than 10,000 subjects aged 45 years and older (2006-2010). All subjects will undergo an ultrasound examination of the carotid arteries. Subjects with one or more carotid plaque of 3 mm or thicker on ultrasound will undergo an MRI scan to measure plaque structure. Based on an expected prevalence of carotid plaques of this thickness of 10%, 1000 subjects will be invited for an MRI scan. The risk of coronary heart disease and stroke of subjects with vulnerable plaques will be compared to that of subjects without carotid plaques and subjects with stable carotid plaques. Objectives In this project, we will evaluate the predictive value of vulnerable plaques in the carotid arteries, as assessed by multi-sequence MRI, for risk of coronary heart disease and stroke. The ultimate aim is to develop a novel risk assessment strategy which includes the assessment of plaque structure. The specific objectives are: (1) To determine the predictive value of vulnerable carotid plaques detected by multi-sequence MRI for risk of coronary heart disease. (2) To determine the predictive value of vulnerable carotid plaques detected by multi-sequence MRI for risk of stroke. Relevance for cardiovascular diseases During the past decade, the understanding of the pathophysiology of cardiovascular disease has undergone a remarkable evolution. These advances - based on the recognition of the impact of plaque vulnerability - have altered the concepts of and clinical approaches to chronic and acute phases of cardiovascular disease. The emergence of new imaging techniques, including those for the assessment of plaque structure, provides new opportunities for risk prediction. Prevention of cardiovascular events can potentially achieve large gains in both life years and quality of life. Fighting the same standard risk factors in all subjects, as is common clinical practice, however, ignores the complexity of atherogenesis and its multifactorial etiology. A strategy that includes the assessment of vulnerable plaque may guide conventional and anti-inflammatory therapy in targeted subjects. Awareness of a high-risk status may improve compliance to diet and medication, as well as influence treatment goals. The final aim is to slow disease progression and to reduce the risk of thrombotic complications, thereby reducing the risk of a first atherosclerotic disease event. The project will also enhance understanding of the pathophysiology of cardiovascular disease and its results may facilitate further study of the mechanisms of plaque vulnerability.