NHLBI Working Group
Integrative Approach to Identifying Patients at High Risk of a Cardiovascular Event in the Near Future

December 5-6, 2005
Executive Summary

The National Heart, Lung, and Blood Institute convened a Working Group (WG) on December 5-6, 2005, in Gaithersburg, Maryland provide basic and clinical research recommendations to the NHLBI for developing an integrated approach, or algorithm, to identify those individuals at high risk for an acute myocardial infarction (AMI) or sudden cardiac death (SCD) in the near-term. The WG was asked to consider near-term risk factors--such as “vulnerable plaque”, “vulnerable blood”, and susceptibility of the myocardium to ischemia and arrhythmias--in developing this approach

Discussion:

Current clinical cardiology practices in risk assessment and their limitations were discussed. A thorough review of the relevant basic and clinical science (including cardiovascular biomarkers, proteomics, genetics, psychosocial factors, imaging, coagulation, and vascular and myocardial susceptibility) took place. The kinds of research needed to facilitate our ability to detect early signs that might trigger acute cardiovascular events were then explored. Integrated approaches to identifying individuals at high risk for AMI or SCD, use of risk scores and their limitations and challenges, and the role of mathematical modeling in developing a risk score algorithm were also discussed. Participants were then divided into two sub-groups and charged with: (i) defining “near-term” for future event prediction, (ii) discussing how to integrate new knowledge and technological advances into a near-term risk assessment, and (iii) recommending the types of basic and clinical research that would be needed to develop a near-term risk assessment tool. The entire group then discussed and combined the recommendations from each sub-group.

Recommendations:

The WG defined “near-term” as within one year. They recommended the following to develop an algorithm to assess near-term risk:

• Develop novel biomarkers using technologies such as proteomics, genomics, metabolomics, and genetics. Develop other assessment techniques by using factors such as circulating endothelial cells, micro-endothelial particles, endothelial progenitor cells, myocardial markers, and mechanism-based markers, as risk reporters. Markers should be developed using time-series studies in asymptomatic patients expected to have higher event rates than occur in the general population. The early kinetics of these markers, their validation in the clinical setting, development of informatics’ platforms, and prediction modeling, must all be considered.
• Develop novel molecular imaging strategies for near-term risk prediction in selected populations that have been determined to be at a higher risk than the general population.
• Conduct studies to explore the underlying mechanisms, to discover reporters for those mechanisms, and to better understand both the environmental and genetic determinants that may account for individual differences for the following areas:
  • Plaque disruption
  • Thrombus formation and propagation (including the contributing factors from blood and plaque)
  • Triggering mechanisms for acute cardiovascular events (i.e., why did the event happen today, not tomorrow?)
• Develop and validate a “Modified Framingham Score” that might include additional event risk indicators, such as already-known factors like hemoglobin A1C, microalbuminuria, hsCRP, calcium score, CT angiography, as well as any novel markers (as noted above), validated family history, gender, and environmental variables. The scoring system should be flexible so as to allow addition of new variables as they are discovered and validated. The endpoints should be broadened to include those associated with peripheral arterial disease, cerebrovascular disease, and aortic aneurysms. The modified scoring system would be used as a broad screening tool to determine who would benefit from the more specific, near-term, risk assessment tools such as molecular imaging. Barriers to clinical implementation of such a risk assessment tool should be considered and addressed in its development.

Publication Plans:

A summary of the workshop proceedings and recommendations will also be published in a peer-reviewed scientific journal.

NHLBI Contact:

• H. Eser Tolunay, Ph.D., NHLBI, NIH
  TolunayE@mail.nih.gov
• Cheryl L. McDonald, M.D., NHLBI, NIH
  McDonalC@mail.nih.gov

Working Group Members

Co-Chairs:

• Kim A. Eagle, M.D., University of Michigan
• Sidney C. Smith, Jr., M.D., University of North Carolina at Chapel Hill

Members:

• William C. Aird, M.D., Beth Israel Deaconess Medical Center
• Robert S. Balaban, Ph.D., National Heart, Lung, and Blood Institute
• Susan K. Bennett, M.D., George Washington University Hospital
• Roger S. Blumenthal, M.D., The Johns Hopkins University School of Medicine
• Michael P. Brenner, Ph.D., Harvard University
• Nancy R. Cook, Sc.D., Brigham and Women’s Hospital
• Shaun R. Coughlin, M.D., Ph.D., University of California at San Francisco
• Karina W. Davidson, Ph.D., Columbia College of Physicians and Surgeons
• Edward D. Frohlich, M.D., Ochsner Clinic Foundation, New Orleans
• Geoffrey Ginsburg, M.D., Ph.D., Duke University
• Philip Greenland, M.D., The Feinberg School of Medicine, Northwestern University
• Gail P. Jarvik, M.D., Ph.D., University of Washington Medical Center
• Peter Libby, M.D., Brigham and Women’s Hospital
• Carl J. Pepine, M.D., University of Florida College of Medicine
• Jeremy N. Ruskin, M.D., Massachusetts General Hospital
• Arthur Stillman, M.D., Ph.D., Emory University
• Mark B. Taubman, M.D., University of Rochester Medical Center
• Jennifer Van Eyk, Ph.D., Johns Hopkins University
• Joel I. Verter, Ph.D., Statistics Collaborative, Inc., Washington, D.C.

Last updated: March 30, 2006