Earlier treatment in adults with high lifetime risk of cardiovascular diseases: What prevention trials are feasible and could change clinical practice? Report of a National Heart, Lung, and Blood Institute (NHLBI) Workshop

Ann Marie Navar; Lawrence J Fine; Walter T Ambrosius; Arleen Brown; Pamela S Douglas; Karen Johnson; Amit V Khera; Donald Lloyd-Jones; Erin D Michos; Mahasin Mujahid; Daniel Muñoz; Khurram Nasir; Nicole Redmond; Paul M Ridker; Jennifer Robinson; David Schopfer; Deborah F Tate; Cora E Lewis

doi:10.1016/j.ajpc.2022.100430

Earlier treatment in adults with high lifetime risk of cardiovascular diseases: What prevention trials are feasible and could change clinical practice? Report of a National Heart, Lung, and Blood Institute (NHLBI) Workshop

Am J Prev Cardiol. 2022 Nov 13:12:100430. doi: 10.1016/j.ajpc.2022.100430. eCollection 2022 Dec.

Authors

Ann Marie Navar¹, Lawrence J Fine², Walter T Ambrosius³, Arleen Brown⁴, Pamela S Douglas⁵, Karen Johnson⁶, Amit V Khera^{7

8}, Donald Lloyd-Jones⁹, Erin D Michos¹⁰, Mahasin Mujahid¹¹, Daniel Muñoz¹², Khurram Nasir¹³, Nicole Redmond², Paul M Ridker¹⁴, Jennifer Robinson¹⁵, David Schopfer², Deborah F Tate¹⁶, Cora E Lewis¹⁷

Affiliations

¹ University of Texas Southwestern Medical Center, USA.
² National Heart, Lung and Blood Institute, USA.
³ Wake Forest University School of Medicine, USA.
⁴ University of California at Los Angeles, USA.
⁵ Duke University, USA.
⁶ University of Tennessee, USA.
⁷ Center for Genomic Medicine, Massachusetts General Hospital, USA.
⁸ Verve Therapeutics, USA.
⁹ Northwestern University, USA.
¹⁰ Johns Hopkins University, School of Medicine, USA.
¹¹ University of California at Berkeley, USA.
¹² Vanderbilt University Medical Center, USA.
¹³ Houston Methodist, USA.
¹⁴ Center for Cardiovascular Disease Prevention, Brigham and Women's Hospital, USA.
¹⁵ University of Iowa, USA.
¹⁶ The University of North Carolina at Chapel Hill, USA.
¹⁷ University of Alabama at Birmingham, USA.

Abstract

More than half of U.S. young adults have low ten-year but high lifetime risk of cardiovascular disease (CVD). Improving primary prevention in young adulthood may help reduce persistent CVD disparities and overall CVD morbidity and mortality. The National Heart, Lung, and Blood Institute (NHLBI) convened a workshop in 2021 to identify potential trial opportunities in CVD prevention in young adults. The workshop identified promising interventions that could be tested, including interventions that focus on a single cardiovascular risk factor (e.g., lipids or inflammation) to multiple risk factor interventions (e.g., multicomponent lifestyle interventions or fixed-low dose combination of medications). Given the sample size and duration for a trial with hard endpoints, more research is needed on the utility of intermediate endpoints identified noninvasively such as subclinical coronary atherosclerosis as a surrogate endpoint. For now, clinical outcomes trials with hard endpoints will more likely change clinical practice. Trial efficiency depends on accurate identification of high-risk young adults, which can potentially be done using traditional risk equations, coronary artery calcium screening, computerized tomography coronary angiography, and polygenic risk scores. Trials in young adults should include enhanced recruitment strategies with intense community engagement to enroll a trial population that is racially, ethnically, geographically, and socially diverse. Despite the challenges in conducting large prevention trials in young adults, recent advances including innovation in clinical trial conduct, new therapies and successful interventions in older populations, and an increasing recognition of a lifespan approach to risk assessment have made such trials more feasible than ever.

Disclosures: The views expressed in this manuscript are those of the authors and do not necessarily represent the views of the National Heart, Lung, and Blood Institute; the National Institutes of Health; or the U.S. Department of Health and Human Services.

Keywords: Atherosclerotic cardiovascular disease; Cardiovascular Disease; Risk assessment; Young adults.

Publication types

Review