Early Treatment in High Lifetime Risk of Cardiovascular Diseases: What Prevention Trials are Feasible and Could Change Clinical Practice?

February 19 - 26, 2021
Virtual Workshop


The National Heart, Lung, and Blood Institute (NHLBI) convened a multidisciplinary workshop on possible prevention trials to reduce cardiovascular disease (CVD) risk in adults with a relative low ten-year risk of CVD yet high lifetime CVD risk. Experts reviewed relevant guidelines, summarized the state of the evidence, and explored the design of feasible clinical trials with the potential to change practice—particularly, ways to identify the appropriate cohort, possible interventions, incorporation of treatment strategies to address health disparities, and outcome assessment.


Many young adults and middle-aged adults have short-term (≤10-year) risks for CVD of less than 10 percent but a much higher lifetime risk. For many CVD risk factors, such as LDL cholesterol and systolic blood pressure, an important question is: Are there demonstrated large benefits associated with earlier, more rigorous, and effective treatment of CVD risk factors in the prevention of CVD events?

Workshop Purpose and Objectives

The objectives of the workshop were to:

  • Review the American Heart Association/American College of Cardiology recent guidelines on hypertension (2017), blood cholesterol (2018), and primary prevention of cardiovascular disease (2019) to identify the research gaps for subpopulations with low 10-year CVD risks but high lifetime risk.
  • Evaluate key considerations for designing feasible and potentially practice-changing trials of interventions that might substantially improve CVD prevention in young and middle-aged adults with high lifetime risk.

Concise Summary of Discussions

Presentations and discussions were centered around the following areas.

  • State of the evidence on risk factor interventions among individuals with low 10-year but high lifetime risk.
  • Identifying the ‘right” cohort – risk assessment and its impact on the size of the trial eligible population.
  • Possible lifestyle, behavioral, and pharmacological interventions to be evaluated in trials.
  • Considerations for sucessful implementation of prevention trials and/or treatment strategies for health disparity populations and/or in safety net health care systems.
  • Possible trial endpoints, ranging from major adverse cardiovascular events (MACE) to possible surrogate outcomes.
  • Feasibility of practice-changing prevention trials in young or middle-aged adults with low ten-year risk.

Summary of the potential approaches and research opportunities discussed:

  • More than 50% of the adult population has low short-term risk but high lifetime risk for CVD based on contemporary risk equations.
  • Use of coronary calcium scores, polygenetic risk scores, and other measures of subclinical disease may be useful in identifying the population with higher short-term and lifetime risk.
  • Enhanced recruitment strategies involving more intense community engagement is a key factor to obtaining a trial population that is racially, ethnically, geographically, and socially diverse.
  • Several interventions appear to be promising, ranging from focusing on large reductions in a single cardiovascular risk factor to multiple risk factor interventions.
  • A wide variety of pharmacological interventions were discussed as possible candidates for testing in future trials.
  • Preliminary discussions suggested that some of the discussed trial designs were feasible.
  • In addition to evaluating interventions, trials might make broader contributions to the science of prevention of CVD.

Publication Plans

The meeting participants will develop a workshop report for publication in a peer-reviewed journal. The report will highlight discussions that occurred at the workshop and the research and other opportunities explored.

NHLBI Contact

Lawrence Fine, MD, DrPH
Division of Cardiovascular Sciences, NHLBI


Cora E. (Beth) Lewis MD MSPH, Chair, Department of Epidemiology, School of Public Health, University of Alabama at Birmingham

Ann Marie Navar, MD PhD, Associate Professor, Departments of Internal Medicine and Population and Data Sciences, University of Texas Southwestern Medical Center