Division of Cardiovascular Diseases Strategic Plan

Goals in Cardiovascular Clinical Problems or Disease States

2.2f. Improve diagnostic and therapeutic strategies for lower extremity peripheral arterial disease (PAD)

Table of Contents

• Overview
• Strategies to Accomplish This Goal May Entail
  • Basic Research
  • Translational Research
  • Clinical Research
• Contributing Sources

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Overview

Reduction of blood flow to the limbs in individuals with atherosclerotic PAD may cause pain (claudication) and limit mobility and, when severe, may threaten limb viability (critical limb ischemia). PAD is estimated to affect 8 to 12 million Americans, yet many are unaware of this disease and merely ascribe the signs and symptoms of PAD to "getting older" This misunderstanding can lead to a delay in the diagnosis that may result in more advanced and complicated disease. Even when symptoms are promptly reported, few noninvasive diagnostic measures, such as ankle-brachial index, are routinely employed and no consensus has been reached on optimal therapies for all levels of PAD. Our goal is to facilitate a comprehensive research plan spanning basic, translational, and clinical science approaches that may lead to improved diagnosis, treatment and outcomes of lower extremity PAD.

Strategies to Accomplish this Goal May Entail:

Basic Research:

• Investigate why revascularization may fail to fully reverse damage to “end organs” (skeletal muscle and skin) after chronic under-perfusion.
• Investigate the effects of the chronic reduction of large vessel blood flow on microvasculature.
• Systematically compare vascular biology in diabetics and non-diabetics at molecular, cellular, and tissue levels.
• Study the biology of vascular progenitor cells (endothelial and smooth muscle progenitor cells) and investigate their potential for use in cell-based therapy.
• Identify biomarkers of PAD for detecting sub-clinical disease and monitoring disease progression.

Translational Research:

• Investigate whether there are specific genetic markers that offer protection from, or susceptibility to, PAD.
• Explore the possibility of epigenetic factors on development of PAD.
• Continue the development and validation of noninvasive imaging techniques to assess muscle and skin perfusion.
• Facilitate the development of novel vascular imaging techniques to assess the nature of plaque, including the role of plaque rupture in the pathophysiology of PAD.
• Test and validate biomarkers of PAD in pilot studies.
• Apply basic research findings to improve ischemic wound healing.
• Using drug targets identified in basic research studies, initiate screening of compounds for potential pharmacologic value for PAD.

Clinical Research:

• Initiate studies to develop a scoring system based on clinical and laboratory variables that will aid prediction of those at risk of progression of PAD to critical limb ischemia.
• Determine optimal treatment for PAD from the following currently available therapies: pharmacotherapy, revascularization, supervised exercise and other lifestyle modification, or some combination of these.
• Determine whether, and in what circumstances, endovascular intervention offers benefit over medical therapy for PAD.
• Initiate large clinical trials to validate biomarkers of PAD.

Contributing Sources:

• NHLBI Strategic Plan Goals 1 and 2
• Recommendations from the NHLBI Strategic Plan Level One Final Reports:
  • Vascular Diseases and Hypertension
  • Emerging and Evolving Technologies
  • From Discovery to Clinical Application
  • Personalized Medicine Planning
  • The Critical Role of Inflammation in Ischemic Disorders
• NHLBI Workshops and Working Groups:
  • Workshop on Peripheral Arterial Disease (PAD): Developing A Public Awareness Campaign, 2003

September 2008