Division of Cardiovascular Diseases Strategic Plan

Goals in Cardiovascular Clinical Problems or Disease States

2.2g. Develop new preventive and therapeutic approaches for cerebrovascular disease

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Overview

Stroke is the third leading cause of death in the U.S.  There are approximately 780,000 new cases of stroke and 160,000 stroke deaths per year in this country.  Stroke is also the leading cause of long-term disability.  In addition, 13.9 percent of individuals 71 years or older have some form of dementia in the U.S.  The combined economic burden for both stroke and dementia exceeds $150 billion annually and will increase as the average age of the population increases.  Safe and effective therapies are urgently needed to improve the management of patients with cerebrovascular disease.

We need to better understand the hemodynamic, cellular, and molecular mechanisms that result in cerebral occlusive and hemorrhagic events and regulate cerebral microvascular blood flow.  Pathophysiological alterations in cerebral blood flow underlie the initiation and progression of the cerebrovascular diseases--stroke, vascular dementia, and Alzheimer’s disease.  Improved understanding of these mechanisms will provide new and improved strategies for preventing and treating cerebrovascular disease.  This goal contemplates manipulation of the physical, cellular, humoral, and chemical environment of the brain microvasculature and the neurovascular unit.  Much of the progress relative to this goal is likely to take place through joint efforts with the National Institute of Neurological Disorders and Stroke (NINDS) and/or the National Institute on Aging (NIA).

Strategies to Accomplish this Goal May Entail:

Basic Research:

  • Identify and exploit new biological pathways, networks, and their interconnectivity leading to cerebrovascular diseases.
  • Identify important aspects of neurovascular metabolism and hemostasis.
  • Delineate the role of the pathophysiological changes of the brain microvasculature associated with traditional CV risk factors, such as hypertension, dyslipidemia, hyperinsulinemia, insulin resistance, hyperglycemia and overt type 1 and type 2 diabetes, in the initiation and progression of cerebrovascular diseases.
  • Explore genomic and proteomic approaches to identify new biomarkers for the prediction of individual risk and drug discovery for stroke and vascular dementia.
  • Study the interactions between the vasculature and neurons in the neurovascular unit and how they relate to dementia.

Translational Research:

  • Study brain microcirculatory changes over the life span.
  • Develop new noninvasive techniques to rapidly assess the integrity of brain microcirculation and macrocirculation within the critical therapeutic window.
  • Implement preclinical, phase I and II studies of thrombolytic, antithrombotic, and vasculoprotective and neuroprotective drugs.

Clinical Research:

  • Implement phase III clinical trials of drugs offering promise in basic and phase I and II studies for treating cerebrovascular diseases.
  • Study brain circulatory changes over time and in response to therapeutic interventions.

Contributing Sources:

September 2008

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