Recovery Act 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. Recovery Act 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. Recovery Act-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 Recovery Act 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. Recovery Act 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. 3 R01 HL079353-04S1 – Role of the 5-lipoxygenase Pathway in Atherosclerosis – Allayee, Hooman (CA)
2. 1 RC2 HL102419-01 – Building on GWAS for NHLBI-Disease, the CHARGE Consortium – Boerwinkle, Eric (TX)
3. 1 R01 HL093077-01A1 – Cellular Adhesion Molecules: Genes, Phenotypes, and Coronary Atherosclerosis – Gross, Myron (MN)
4. 1 RC1 HL099528-01 – Validation of a Vascular Health Profile for Cardiovascular Disease – Mohler, Emile (PA)
5. 1 R01 HL088523-01A1 – IVUS Detection of Rupture Prone Plaques – Doyley, Marvin (NY)
6. 1 R01 HL089941-01A1 – Fractional Flow Reserve Measurement Based on Coronary Angiographic Images – Molloi, Sabee (CA)
7. 1 R01 HL095123-01 – Inflammatory Mechanisms and Treatment Strategies for Atherosclerosis in HIV – Grinspoon, Steven (MA)
8. 1 RC1 HL100659-01 – Molecular Imaging of Ischemic Memory with Ultrasound: Transition to Humans – Lindner, Jonathan (OR)
9. 1 RC1 HL101157-01 – Predicting Cardiovascular Risk in Vulnerable Plaque Rupture – Weinbaum, Sheldon (NY)
10. 1 RC1 HL099747-01 – Novel Technologies to Identify Preclinical Coronary Disease Risk in High Risk Families – Becker, Lewis (MD)
11. 1 RC1 HL101060-01 – Comparative Effectiveness of Noninvasive Cardiac Imaging – Di Carli, Marcelo (MA)
12. 1 R01 HL098237-01 – PROMISE Trial: Clinical Coordinating Center – Douglas, Pamela (NC)
13. 1 R01 HL098236-01 – PROMISE Trial: SDCC – Lee, Kerry (NC)
14. 1 RC1 HL100491-01 – A Revolutionary Therapy for Atherosclerosis: Liquid Cast Arterial Stents – Ameer, Guillermo (IL)
15. 1 RC1 HL099872-01 – Improved Estimates of the Comparative Treatment Effects of CABG and PCI – Hlatky, Mark (CA)
16. 1 RC1 HL100951-01 – Hybrid Revascularization vs Percutaneous Coronary Intervention: A Planning Grant – Vassiliades, Thomas (GA)
17. 1 RC1 HL099634-01 – Genetic Risk Stratification to Identify Individuals for Early Statin Therapy – Sabatine, Marc (MA)
18. 1 RC1 HL099122-01 – Long-term survival following coronary revascularizations – Hannan, Edward (NY)

Last Updated April 26, 2010