Establishing Funding Priorities for Hypertension Research
A Modest Proposal
For more than a half century, the National Institutes of Health (NIH) has funded both basic and clinical/translational research that has contributed to an improved understanding of the pathophysiology of hypertension and to the development and implementation of approaches for hypertension prevention and treatment. Milestones in hypertension research over the past century, many of which were based on NIH support, have recently been reviewed.1 These initiatives have undoubtedly been a factor in the improved hypertension control rates and the reduction of hypertension-related cardiovascular disease and stroke mortality since the 1960s. Between 1999 and 2015, in the United States, age-adjusted cardiovascular disease mortality decreased by 43% (287.0 per 100 000 in 1999 and 162.7 in 2015).2 Stroke mortality also decreased by 43% (50.7 in 1999 and 28.6 in 2015).
Nevertheless, hypertension remains a formidable public health problem. Worldwide, the prevalence of hypertension is estimated to be 32%, totaling ≈1 billion people, and hypertension is the leading cause of death.3 In the United States between 1999 and 2014, the age-adjusted prevalence of hypertension has increased from ≈29% to 34% (from >75 to >85 million people), although hypertension control rates have increased from 32% to 54% during that time period.3–5 To achieve blood pressure control, most patients require ≥2 antihypertensive drugs.6 Cardiovascular diseases, including heart disease, hypertension, heart failure, and stroke, continue to be leading causes of death in the United States.3 In the United States, hypertension affects 46% of patients with cardiovascular disease and 72% of those who have had a stroke.7 Overall, hypertension contributes to 19% of total US mortality, and in 2014, >400 000 deaths included high blood pressure as a primary or contributing cause.3 Cardiac failure, including diastolic dysfunction with normal systolic function, is among the most common causes of hospitalization of elderly patients in the United States and other industrialized societies.8 Hypertension costs the nation ≈$51 billion per year in direct and indirect medical expenses.3 The continued high prevalence of hypertension, partly because of aging of the population and obesity and the persistence of health disparities, documents the need for more effective hypertension prevention and control strategies.
In the 1970s, the National Heart, Lung, and Blood Institute (NHLBI) established a Hypertension Task Force with the following objectives: (1) evaluate current state of knowledge; (2) assess the state of hypertension research; and (3) recommend future research emphasis, manpower and training needs, animal models, resources, and new technologies. The Task Force, chaired by Drs Harriet Dustan and Edward Frohlich, had broad representation. It consisted of 20 members, most of whom served as chairmen of 12 subgroups. The Task Force report covered a wide range of topics and was published in 9 volumes in 19799 (Table S1 in the online-only Data Supplement).
Building on this legacy, the purpose of this report is to suggest initiation of a renewed process leading to the development of a long range, comprehensive hypertension roadmap to guide future research funding priorities.
Overview of Previous NIH Funding Priorities
Approximately 100 years ago, the Actuarial Society of America demonstrated an association between higher levels of blood pressure and mortality.10 The Framingham Heart Study, launched in 1948, confirmed and expanded evidence for the cardiovascular risks of elevated blood pressure, especially in concert with other risk factors.11 In 1972, NIH established the National High Blood Pressure Education Program designed to educate patients and physicians about the risks of hypertensions and the necessity of controlling blood pressure and their underlying factors of risk. In 1976, the first of periodic reports of the Joint National Committee on Detection, Evaluation, and Treatment of High Blood Pressure was published.12 These reports provided physicians with recommendations for hypertension prevention and treatment, based on up-to-date information.
Results of clinical trials have had a profound impact on the treatment of hypertension. The first cardiovascular, multicenter, double-blinded, and placebo-controlled study was the Veterans Administration Hypertension Research Series of reports.13,14 Examples of subsequent NIH projects and program initiatives are cited in the Table. Molecular genetics continues to be a priority. Several requests for applications have addressed high-risk, underserved populations, both in the United States and abroad. In addition, in 2014, NIH partnered with the Patient-Centered Outcomes Research Institute to study how to improve blood pressure control in high-risk individuals. On the basis of grants, contracts, and other funding mechanisms, between 2012 and 2017 (estimated), annual NIH expenditure for hypertension-related research ranged from $214 to $222 million per year.15
Establishing Future Hypertension Research Funding Priorities
Since publication of the 1979 Hypertension Task Force Report, the human genome has been sequenced, and high-throughput technologies have been developed that allow for the development of molecular networks in health and disease. Application of these technologies may permit patient-specific approaches for hypertension prevention and treatment.16 In addition, the electronic medical record provides increased opportunities for data sharing. As previously stated by Elias Zerhouni, the former Director of NIH,
In this genomic age, the rapid development of genome-related technologies and the massive increase in research data have begun to enable multidimensional studies of complex but common diseases and are forcing scientists to re-evaluate current strategies for staging biomedical research.17
In view of the persistent problem of uncontrolled hypertension and recent advances in scientific technology, this may be an opportune time to develop and prioritize recommendations for future research funding. Periodically, NIH has convened ad hoc groups to develop recommendations for targeted areas of hypertension-related research (eg, clinical trials, epigenetics, obesity, role of microbiota in blood pressure regulation, epidemiology, and prevention of cardiovascular disease). As recently reported, NHLBI is committed to maintaining a balanced portfolio of basic, translational, clinical, and population science researches.18 In its strategic vision, the institute “…looks to its investigator community to identify mission-oriented strategic priorities and help chart the future together.” Currently, there are bidirectional translation gaps between the basic, clinical, and community domains. Bridging these gaps will require an integrated transdisciplinary, collaborative team approach that involves the creation of fundamentally new conceptual frameworks, hypotheses, and research strategies that synthesize diverse approaches that transcend traditional boundaries. This requires translationalists who can engage community members with clinical and basic scientists. However, the continuing paucity of physician-scientists is a major challenge to conducting translational research.19
The crucial role of the physician-scientist in the clinical research enterprise has been repeatedly emphasized.19 It is imperative that a new planning initiative simultaneously include pragmatic recommendations about the magnitude, composition, and training requirements for developing and sustaining a robust workforce engaged in hypertension research. Although not unique to hypertension research, for almost 4 decades, many preeminent clinician scientists have been sounding the alarm of the vanishing clinical investigator.19–21 Historically, grant applications to NIH for clinical research have not fared as well in study section reviews as applications for basic research.22 Expansion of the workforce with well-trained, committed clinical investigators will be particularly challenging in what has been termed an erroneous assumption of never-ending rapid growth in biomedical science that has created an unsustainable, hypercompetitive system that is discouraging even the most outstanding prospective students.23
Recommendations of task forces convened by NIH, the Institute of Medicine, and the Association of American Medical Colleges have previously addressed these concerns.9,24–26 In response, several structural changes favoring clinical research were made within NIH. Reengineering the clinical research enterprise was 1 of 3 fundamental themes of NIH 2003 roadmap for medical research. Despite NIH establishment of a program in 2005 to fund Clinical and Translational Science awards, expansion of clinical research training programs, and a trainee loan repayment program, in contrast to the over production of PhD scientists, the number of physician-scientists in the clinical research community continues to dwindle. Although barriers to recruitment and retention have frequently been articulated, pragmatic strategies for overcoming these barriers and financial constraints remain to be developed. Recommendations about composition and training might be influenced by concepts of requisite competencies for translating science into applications to improve health, team science, multidisciplinary integration, and incorporation of clinical research into clinical practice.
A Modest Proposal
The results of hypertension-related research and their translation into the clinical arena over the past half century have an impressive legacy. Nevertheless, both globally and in the United States, hypertension remains a leading cause of mortality. Charting the future, NIH might convene a multidisciplinary planning group to develop a transdisciplinary roadmap for hypertension research. NHLBI has recently completed a comprehensive planning process for the institute that includes 4 goals, 8 objectives, and 132 research priorities.27 A broad range of “partners” participated in the development of the report. In a separate report, an NIH Physician-Scientist Working Group made several recommendations to strengthen the workforce, including suggesting changes to grant funding and training approaches.28 The workforce is currently planning to introduce pilot programs to recruit and retain clinical investigators.29 Although not specifically focused on hypertension, these reports and initiatives could serve as excellent backgrounds for a roadmap for hypertension research and related clinical investigator training. A comprehensive, but hypertension-focused, research planning process would serve to prioritize and integrate topical areas. Approaches to clinical investigator training should assure that trainees acquire the necessary competencies to be successful.
In addition to including basic and clinical scientists from academia, the planning group might include representatives of potential funders from NIH and other government agencies, professional societies committed to hypertension research, industry, and foundations. Inclusion of colleagues from outside the United States would provide additional expertise and potentially unique opportunities for collaboration. Each of these stakeholders has a distinctive perspective. Government funding agencies must be mindful of the public good, whereas industry is more market driven. Foundations have more flexibility to take on new initiatives. Insurers are another potential funding source. As previously suggested,30,31 developing collaborative partnerships among these stakeholders and leveraging resources may provide a more robust funding resource for research and training. Through funding mechanisms such as Funding Opportunity Announcements, programmatic priorities should not preclude investigator-initiated research, which has been the bedrock of NHLBI support. However, some percent of resources might be allocated for program-defined projects.
In conclusion, despite sustained research support and successes, hypertension remains a formidable problem, both in the United States and worldwide. Consequently, it seems reasonable to ask the question: “What more can be done?” The ultimate goal is to develop new strategies to more effectively prevent and treat hypertension and its related cardiovascular/renal consequences.
T.A. Kotchen receives support from the National Center for Advancing Translational Sciences, National Institutes of Health (award no. KL2TR001438) and a grant from the American Heart Association (ID No. 15SFRN24370000). The content is solely the responsibility of the author and does not necessarily reflect the official views of the National Institutes of Health or the American Heart Association.
The opinions expressed in this article are not necessarily those of the editors or of the American Heart Association.
The online-only Data Supplement is available with this article at http://hyper.ahajournals.org/lookup/suppl/doi:10.1161/HYPERTENSIONAHA.117.10100/-/DC1.
- © 2017 American Heart Association, Inc.
- Kotchen TA
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