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ARRA Investments in Coronary Artery Disease


Public Health Burden
Coronary artery disease (CAD) is the leading cause of death in the United States and is rapidly becoming the most common cause of death and disability throughout the world.  It can cause chest discomfort and activity limitation and, in its more severe forms, heart attacks, heart failure, and sudden death.  Over the past 50 years, death rates from CAD have steadily declined, but the aging of the population and the increased prevalence of obesity and diabetes threaten to reverse that trend.

Molecular Biology and Causes
High cholesterol levels, hypertension, smoking, and diabetes are risk factors for CAD.  Recent research has focused on underlying disease influences, including genetics and inflammation.  ARRA grants are supporting research to:
  • Investigate the genes and blood proteins that are typically involved in allergic diseases as possible direct or indirect causes of CAD.1
  • Understand how genes regulate high-density lipoprotein (HDL) cholesterol, the kind of cholesterol that is thought to protect against the development of CAD.2
  • Study the actions of cellular adhesion molecules, which are thought to regulate the behavior of white blood cells that damage the walls of the coronary arteries early in CAD.3
  • Assess how the severity of the disease may be related to the activity of certain types of early-stage blood cells and circulating microparticles.4
Diagnostic Technology Development
Currently available imaging technologies are not able to identify coronary artery plaque that is likely to become problematic in the absence of intervention.  ARRA-supported research projects focused on developing new methods to image potentially life-threatening disease include studies to:
  • Develop new ultrasound methods to image coronary arteries from the inside of blood vessels in order to differentiate stable from unstable blockages.5
  • Develop a technique to assess the severity of coronary blockages and using it to evaluate patients undergoing standard assessment of blockages.6
  • Use advanced nuclear technology to detect inflammation in the walls of coronary arteries of patients with HIV infection.7
  • Test a new ultrasound imaging agent to detect microscopic changes in the small vessels of the heart.8
  • Develop high-resolution CT (computed tomography) to image microscopic changes in the cap that overlies blockages in the coronary arteries and minute calcium deposits.9
Comparative Effectiveness
Careful evaluation of different imaging technologies as they are used in standard clinical settings is being supported by ARRA funding to:
  • Compare several diagnostic methods to evaluate risk in people with at least one close relative who experienced a heart attack at an early age.10
  • Compare the ability of different diagnostic methods to predict response to common treatments of CAD such as bypass surgery and stenting (insertion of a tube to keep a blocked artery open).11
  • Compare CT imaging of coronary blockages with standard stress testing in 10,000 patients having symptoms suggestive of CAD for prevention of subsequent coronary events.12
Clinical Management
Clinical management of CAD can be complex, involving lifestyle, drug, device, and surgical therapies.  ARRA funds are supporting projects to:
  • Develop a novel bio-active and bio-degradable arterial stent that can be molded to the specific size and shape of a patient’s arteries.13
  • Use electronic health records to develop mathematical models that compare the outcomes of coronary artery stenting with coronary artery bypass surgery.14
  • Plan a large-scale clinical trial to assess the value of hybrid revascularization, in which both surgical and stenting approaches are coordinated to achieve optimal blood flow to heart muscle.15
  • Use data and blood specimens from over 40,000 participants in completed clinical trials to identify patients who may benefit from statin therapy.16
  • Develop easy-to-calculate, user-friendly “risk scores” that would enable clinicians to estimate long-term survival following coronary artery bypass surgery or coronary artery stenting.17



  1. 3R01HL079353-04S1 -- Role of the 5-lipoxygenase Pathway in Atherosclerosis -- Allayee, Hooman (CA)
  2. 1RC2HL102419-01 -- Building on GWAS for NHLBI-Disease, the CHARGE Consortium -- Boerwinkle, Eric (TX)
  3. 1R01HL093077-01A1 -- Cellular Adhesion Molecules: Genes, Phenotypes, and Coronary Atherosclerosis -- Gross, Myron (MN)
  4. 1RC1HL099528-01 -- Validation of a Vascular Health Profile for Cardiovascular Disease -- Mohler, Emile (PA)
  5. 1R01HL088523-01A1 -- IVUS Detection of Rupture Prone Plaques -- Doyley, Marvin (NY)
  6. 1R01HL089941-01A1 -- Fractional Flow Reserve Measurement Based on Coronary Angiographic Images -- Molloi, Sabee (CA)
  7. 1R01HL095123-01 -- Inflammatory Mechanisms and Treatment Strategies for Atherosclerosis in HIV -- Grinspoon, Steven (MA)
  8. 1RC1HL100659-01 -- Molecular Imaging of Ischemic Memory with Ultrasound: Transition to Humans -- Lindner, Jonathan (OR)
  9. 1RC1HL101157-01 -- Predicting Cardiovascular Risk in Vulnerable Plaque Rupture -- Weinbaum, Sheldon (NY)
  10. 1RC1HL099747-01 -- Novel Technologies to Identify Preclinical Coronary Disease Risk in High Risk Families -- Becker, Lewis (MD)
  11. 1RC1HL101060-01 -- Comparative Effectiveness of Noninvasive Cardiac Imaging -- Di Carli, Marcelo (MA)
  12. 1R01HL098237-01, -- PROMISE Trial: Clinical Coordinating Center -- Douglas, Pamela (NC); 1 R01 HL098236-01 -- PROMISE Trial: SDCC -- Lee, Kerry (NC)
  13. 1RC1HL100491-01 -- A Revolutionary Therapy for Atherosclerosis: Liquid Cast Arterial Stents -- Ameer, Guillermo (IL)
  14. 1RC1HL099872-01 -- Improved Estimates of the Comparative Treatment Effects of CABG and PCI -- Hlatky, Mark (CA)
  15. 1RC1HL100951-01 -- Hybrid Revascularization vs Percutaneous Coronary Intervention: A Planning Grant -- Vassiliades, Thomas (GA)
  16. 1RC1HL099634-01 -- Genetic Risk Stratification to Identify Individuals for Early Statin Therapy -- Sabatine, Marc (MA)
  17. 1RC1HL099122-01 -- Long-term survival following coronary revascularizations -- Hannan, Edward (NY)


 
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