Grant: Project Grant

Research in the area of hypertension had initially focused in 2 areas: 1) the small vessels (arterioles), which provide the bulk of resistance, and 2) cardiac output. This led to the development of drugs that focused on these two concepts. The limited efficacy of these drug in elderly, diabetics and patients with kidney disease were evident as the major determinant of their type of hypertension was mostly related to stiffness of large arteries. Indeed, vascular stiffness has become synonymous with vascular aging. Stiffness of blood vessels is a major cause of arterial high blood pressure and increased incidence of heart failure and stroke. However, the way that arterial stiffness is measured, it is blood pressure dependent, and this makes it difficult to distinguish the cause and effect relationship between blood pressure and vascular stiffness. While stiffness of large arteries has been studied over the past two decades, our progress has shown that we are better with a model that integrates large, medium and small sized vessels. The integrated and novel vision may be a paradigm shifting concept that is need to approach the problem of hypertension in the elderly subjects, with diabetes or kidney disease. Supported by Heart and Stroke foundation, we have discovered that stiffness of the arteries behave differently in response to accelerated aging. Therefore, we proposed a new index of vascular aging that is shown to be better and it has the added advantage of being blood pressure independent. This new index is based on the theory of arterial stiffness gradient. In this study, our objectives are to determine how we can modulate arterial stiffness gradient, and how this modulation can affect blood circulation in the smaller blood vessels. In this proposal we will conduct studies in two groups of patients with or without kidney disease. This novel index of vascular aging is key concept in risk stratification and development of novel therapeutic strategies.