Background

Despite extensive research and the existence of several effective therapeutic interventions, hypertension remains an important public health challenge in the United States. Over the past 3 decades, NHLBI has made significant investments in hypertension research; however, translation of knowledge of pathophysiology and basic science discoveries into better treatments that can reach diverse patient population groups remains inefficient.

The goals of this working group were: (1) to provide an overview of recent discoveries that may be ready for translation in pre-clinical and clinical studies; (2) to identify barriers to moving basic science discoveries into translation and clinical studies and trials; and (3) to identify barriers to effective dissemination and implementation in real-world settings.

Working Group Discussion

The working group brought together 16 extramural experts in hypertension research from broad backgrounds in basic, translational, clinical, population, and implementation sciences. The members were selected from diverse areas in hypertension research in order to facilitate cross-cutting discussion to spark innovative ideas for future research pathways and to identify major areas of barriers in hypertension research and clinical application. NHLBI staff organized and participated in the meeting.

The working group focused on key challenges and barriers that hinder the progress of basic science translation through clinical trials and implementation. Five sessions were followed by a general group discussion. Session topics included: barriers to basic science discovery that could lead to new drugs or treatments; barriers to moving forward from animal studies to human studies; barriers to moving from translation to patients; barriers to advancing from clinical studies to clinical practice; and barriers to moving from clinical findings and guidelines to real-world settings and implementation.

Barriers and Recommendations

The working group identified the following barriers:

• Communication gaps among basic science researchers, clinical researchers, and clinicians in the field of hypertension that are preventing translation of fundamental discoveries to better blood pressure control
• Limited understanding of the antecedents of hypertension (e.g., fetal programming, epigenetics)
• Potential limited relevance of various animal models to humans
• Patient nonadherence to antihypertensive medication
• Poor understanding and validation of methods for detection and reversal of nonadherence
• Limited understanding of age-related changes in blood pressure in children and young adults and determinants of blood pressure for early prevention
• Limited understanding of gene-environment and gene-gene interactions to improve guidance of hypertension treatment choices
• Insufficient engagement of diverse stakeholders (e.g., payers, insurers) through all study phases to enhance uptake and feasibility
• Knowledge gap for how efficacious community-based interventions can be brought to scale

The working group’s recommendations are to:

• Encourage innovative translational research that requires collaboration among basic and clinical scientists and includes patient-oriented research
• Facilitate training that encourages collaboration and cross-training in basic science and clinical application
• Develop new drugs and treatments (e.g., potassium-rich diets) to target diverse hypertensive patient populations (e.g., patients with resistant hypertension)
• Capitalize on resources currently or previously supported by NHLBI (e.g., databases, clinical populations, clinical trials) that will facilitate discovery
• Develop new technologies for better phenotyping of humans and animals through
  • Imaging in vivo
  • Single cell analysis (central repository and analysis)
  • Analysis of large datasets
  • Validation of surrogate endpoints and biomarkers
  • Robust long-term follow-up
  • Assessment of tissue and organ-based sympathetic activity
• Support studies related to the roles of sex and gender differences in vascular complications of hypertension
• Develop and use animal models better suited to the scientific question posed
• Develop approaches for optimal methods of detection and reversal of antihypertensive medication nonadherence
• Strengthen evidence base for genetic screening tools for both risk of hypertension and optimal treatment options, with collection of genetic data in clinical trials and population-based studies across the lifespan
• Support clinical trials for early intervention of hypertension, particularly in stage 1 hypertension and younger populations, and tracking of long-term outcomes
• Develop strategies to engage health care practitioners with strong patient relationship bonds and trust to promote lifestyle modification in high-risk populations
• Support studies that focus on multi-level, collaborative system approaches including patients, providers, and health systems (at a minimum of 2 levels)
• Encourage researchers to incorporate implementation science methodologies that can look broadly to bridge health care and community settings
• Support clinical trials designed to use quasi-experimental or mixed methodologies and those that specifically address the questions, such as “who does it work for?” and “when does it work?”
• Convene representatives and leaders from NHLBI, health care systems, payers, industry, insurers, and other government agencies to address implementation science in hypertension
• Support training for the next generation of health disparities and implementation science researchers, which includes lay persons, community health workers, etc.

Publication Plans

The working group plans to prepare a manuscript for publication in a peer-reviewed journal.

NHLBI Contacts

Young S. Oh, PhD
Division of Cardiovascular Sciences (DCVS), NHLBI
Email: yoh@nhlbi.nih.gov
Phone: 301-435-0560

Working Group Members

Co-Chairs

• Curt Sigmund, PhD, Medical College of Wisconsin
• Robert M. Carey, MD, University of Virginia

Working Group Participants

• Lawrence Appel, MD, Johns Hopkins University
• Donna Arnett, PhD, University of Kentucky
• Hayden Bosworth, PhD, Duke University
• William Cushman, MD, Veterans Affairs Medical Center, Memphis
• Cheryl Dennison-Himmelfarb, PhD, Johns Hopkins University
• John Hall, PhD, University of Mississippi
• David Harrison, MD, Vanderbilt University
• Jay Horton, MD, UT Southwestern Medical Center
• Alicia McDonough, PhD, University of Southern California
• Suzanne Oparil, MD, University of Alabama at Birmingham
• John Osborn, PhD, University of Minnesota
• Joseph Ravenell, MD, New York University
• Mohan Raizada, PhD, University of Florida
• Ricardo Rocha, MD, Novartis Pharmaceuticals Corporation
• Marc Charette, PhD, Vascular Biology and Hypertension Branch, DCVS, NHLBI
• Paula Einhorn, MD, Clinical Applications and Prevention, DCVS, NHLBI
• Larry Fine, MD, Clinical Applications and Prevention, DCVS, NHLBI
• Zorina Galis, PhD, Vascular Biology and Hypertension Branch, DCVS, NHLBI
• David Goff, MD, Director, DCVS, NHLBI
• Lucy Hsu, MPH, Epidemiology Branch, DCVS, NHLBI
• Michael Wolz, MA, Epidemiology Branch, DCVS, NHLBI

NIH Organizers

• Melissa Green Parker, PhD, Health Inequities and Global Health Branch, Center for Translation Research and Implementation Science, NHLBI
• Christine Maric-Bilkan, PhD, Division of Kidney, Urologic, and Hematologic Diseases, National Institute of Diabetes and Digestive and Kidney Diseases
• Holly Nicastro, PhD, Clinical Applications and Prevention Branch, DCVS, NHLBI
• Young Oh, PhD, Vascular Biology and Hypertension Branch, DCVS, NHLBI
• Jacqueline Wright, DrPH, Epidemiology Branch, DCVS, NHLBI