Abstract
Spurred by the 2016 release of the National Heart, Lung, and Blood Institute’s (NHLBI) Strategic Vision, the Division of Cardiovascular Sciences (DCVS) developed its Strategic Vision Implementation Plan (SVIP) – a blueprint for reigniting the decline in cardiovascular disease (CVD) mortality rates, improving health equity, and accelerating translation of scientific discoveries into better cardiovascular health (CVH). The six scientific focus areas of the SVIP reflect the multifactorial nature of CVD and include 1) addressing social determinants of CVH and health inequities, 2) enhancing resilience, 3) promoting CVH and preventing CVD across the lifespan, 4) eliminating hypertension-related CVD, 5) reducing the burden of heart failure, and 6) preventing vascular dementia. This paper presents an update of strategic vision implementation activities within DCVS. Overarching and cross-cutting themes include training the scientific workforce and engaging the extramural scientific community to stimulate transformative research in cardiovascular sciences. In partnership with other NIH Institutes, Federal agencies, industry, and the extramural research community, DCVS strategic vision implementation has stimulated development of numerous workshops and research funding opportunities. SVIP activities highlight innovative intervention modalities, interdisciplinary systems approaches to CVD reduction, a life course framework for CVH promotion and CVD prevention, and multi-pronged research strategies for combatting COVID-19. As new knowledge, technologies, and areas of scientific research emerge, DCVS will continue its thoughtful approach to strategic vision implementation, remaining poised to seize emerging opportunities and catalyze breakthroughs in cardiovascular sciences.
Keywords: Social Determinants of Health; Health Inequities; Cardiovascular Health Promotion; Resilience; Hypertension; Heart Failure; Vascular Dementia; National Heart, Lung, and Blood Institute; Strategic Vision
INTRODUCTION
Encouraged by more than a half-century of breakthroughs in cardiovascular medicine and research, the Division of Cardiovascular Sciences (DCVS) developed its plan for implementing the 2016 National Heart, Lung, and Blood Institute’s (NHLBI) Strategic Vision against a backdrop of stalled progress toward improved cardiovascular health (CVH).1,2 Successes, such as significant declines in ischemic heart disease mortality, are tempered by challenges, including decelerated improvement of cardiovascular disease (CVD) mortality rates; striking disparities in CVD morbidity and mortality; a disturbingly high proportion of maternal deaths attributable to CVD; the COVID-19 pandemic; and systemic inequities that impede efforts to combat emerging threats to CVH.3,4
The priorities outlined in the DCVS Strategic Vision Implementation Plan (SVIP) reflect NHLBI’s resolve to reignite the decline in CVD mortality rates, improve health equity, and translate scientific discoveries into CVH by capitalizing on advances in omics technologies, data science, health informatics, cardiovascular imaging, and digital health. The DCVS SVIP emphasizes six scientific focus areas that map onto the NHLBI’s eight Strategic Vision objectives1:
Addressing social determinants of CVH and health inequities
Enhancing resilience
Promoting CVH and preventing CVD across the lifespan
Eliminating hypertension-related CVD
Reducing the burden of heart failure
Preventing vascular dementia
The SVIP focus areas reflect the multifactorial nature of CVD and emphasize a synergistic, integrative, and multidisciplinary approach to CVH promotion and CVD prevention. For example, uncontrolled hypertension is a risk factor for both heart failure and vascular dementia. Addressing social determinants of health, promoting CVH early in the life course, and enhancing resilience are avenues to reduce the risks of hypertension, heart failure, vascular dementia, and other CVD conditions. Since the 2016 release of the NHLBI Strategic Vision, DCVS working groups centered on SVIP focus areas have translated these priorities into Institute activities that stimulate research in CVD risk, prevention, diagnosis, and treatment. To identify research gaps and opportunities in SVIP focus areas, stimulate extramural research, and guide investigator-initiated applications, DCVS has convened numerous workshops (Table 1). DCVS has also developed or participated in numerous funding opportunities, including notices of special interest (NOSIs), and Institute-initiated funding opportunity announcements (FOAs) and requests for applications (RFAs; Table 2). Many of these funding opportunities, particularly NOSIs, are directed toward the parent R01 FOAs, which support basic and clinical research.
Table 1.
Workshops
Meeting Title | Topic/Research Type | Links |
---|---|---|
Harnessing Novel Data Sources and Technologies for the Study of Social Determinants of Health in Heart, Lung, Blood, and Sleep Disorders, 9/2020 | SDoH/Population Science | https://datascience.nih.gov/news/harnessing-novel-data-sources-and-technologies-study-social-determinants-health-heart-lung |
Diagnostics and Disease Management Tools for Use in Underserved Populations, 4/2021 | SDoH/Population Science | https://www.nhlbi.nih.gov/events/2021/diagnostics-and-disease-management-tools-use-underserved-populations-nhlbi-research |
Food Insecurity, Neighborhood Food Environment, and Nutrition Health Disparities: State of the Science, 9/2021 | SDoH/Population Science | https://www.nhlbi.nih.gov/events/2021/food-insecurity-neighborhood-food-environment-and-nutrition-health-disparities |
Identifying Research Opportunities for Asian American, Native Hawaiian, and Pacific Islander Health, 3/2021 | SDoH/Population Science | https://www.nhlbi.nih.gov/events/2021/identifying-research-opportunities-asian-american-native-hawaiian-and-pacific-islander |
NHLBI Sleep 101 Symposium: Sleep Health in the Pandemic and Beyond, 9/2021 | SDoH, Resilience, CVH/Population Science | https://www.nhlbi.nih.gov/events/2021/sleep-101-symposium-sleep-health-pandemic-and-beyond |
Enhancing Resilience for Cardiovascular Health and Wellness 7/2018 | Resilience/Basic Research | https://www.nhlbi.nih.gov/events/2018/enhancing-resilience-cardiovascular-health-and-wellness |
Exerkines in Health, Resilience, and Diseases, 8/2020 | Resilience/Basic Research | https://www.nhlbi.nih.gov/events/2020/nhlbi-and-niddk-workshop-exerkines-health-resilience-and-diseases-executive-summary |
Engineering Extracellular Vesicles for HLBS Diseases, 9/2021 | Resilience/Basic Research | https://www.nhlbi.nih.gov/events/2021/engineering-extracellular-vesicles-heart-lung-blood-and-sleep-diseases-workshop |
Methodological Approaches for Whole Person Research, 9/2021 | Resilience/Basic Research | https://www.nccih.nih.gov/news/events/methodological-approaches-for-whole-person-research |
Promoting Cardiovascular Health in Early Childhood (0-5 years) and Transitions in Childhood through Adolescence, 6/2018 | CVH/Basic, Clinical, and Population Research | https://www.nhlbi.nih.gov/events/2018/promoting-cardiovascular-health-early-childhood-0-5-years-and-transitions-childhood |
E-Cigarette Prevention and Cessation in Youth and Young Adults, 4/2020 | CVH/Population Science | https://www.nhlbi.nih.gov/events/2020/workshop-addresses-youth-vaping-epidemic |
Pregnancy and Maternal Conditions that Increase Risk of Morbidity and Mortality, 5/2020 | CVH/Population Science | https://www.nhlbi.nih.gov/events/2020/maternal-mortality-workshop |
Precision Nutrition: Research Gaps and Opportunities, 1/2021 | CHV/Population and Clinical Research | https://www.nhlbi.nih.gov/events/2021/precision-nutrition-research-gaps-and-opportunities-workshop |
Cardiovascular Risk Prediction for Maternal Mortality and Morbidity and Beyond, 2/2021 | CVH/Clinical Research | https://www.nhlbi.nih.gov/events/2021/cardiovascular-risk-prediction-maternal-mortality-and-morbidity-and-beyond-workshop |
Cardiovascular Risk Across the Lifespan for Polycystic Ovary Syndrome, 10/2021 | CVH/Population Science | https://www.nhlbi.nih.gov/events/2021/cardiovascular-risk-across-lifespan-polycystic-ovary-syndrome-workshop |
Hypertension: Barriers to Translation, 12/2018 | Hypertension/Basic and Clinical Research | https://www.nhlbi.nih.gov/events/2018/nhlbi-working-group-hypertension-barriers-translation-executive-summary |
In the U.S., Why has Blood Pressure Control Declined Nationally, and What Solutions Will Improve Blood Pressure Control?, 10/2020 | Hypertension/Population Science | https://www.nhlbi.nih.gov/events/2020/why-has-blood-pressure-control-declined-nationally-and-what-solutions-will-improve |
Toward Precision Medicine: Understanding Circadian Rhythms in Blood Pressure Regulation and Chronotherapy in Hypertension, 10/2021 | Hypertension/Population Science | https://www.nhlbi.nih.gov/events/2021/toward-precision-medicine-circadian-rhythm-blood-pressure-and-chronotherapy |
Webinar Series on Research Priorities in Atrial Fibrillation to Advance Population, Clinical and Basic Research: Ablation, 3/2019 | HF/Basic, Clinical, and Population Research | https://nhlbi.nih.gov/events/2019/webinar-series-research-priorities-atrial-fibrillation-ablation |
Improving heart failure care for older adults: Gaps and strategies to optimize care transitions, 9/2021 | HF, CVH/ Population Science | https://www.nhlbi.nih.gov/events/2021/improving-heart-failure-care-older-adults-gaps-and-strategies-optimize-care-transitions |
Extracorporeal CPR for Out-of-hospital Cardiac Arrest, 8/2021 | HF/Clinical Research | https://www.nhlbi.nih.gov/events/2021/extracorporeal-cpr-ecpr-out-hospital-cardiac-arrest |
Eradication of Rheumatic Heart Disease, 11/2021 | HF/Population Science | https://www.nhlbi.nih.gov/events/2021/eradication-rheumatic-heart-disease-assessing-research-challenges-and-opportunities |
Vascular Contributions to Cognitive Impairment and Dementia, 5/2018 | VCID/Basic and Clinical Research | https://www.nhlbi.nih.gov/events/2018/nhlbi-working-group-vascular-contributions-cognitive-impairment-and-dementia-executive |
Future Clinical Trials to Test Promising Approaches for Reducing Vascular Contributions to Cognitive Impairment and Dementia, 11/2019 | VCID/Clinical Research | https://www.nhlbi.nih.gov/events/2019/future-clinical-trials-test-promising-approaches-reducing-vascular-contributions |
Opportunities and Challenges in Establishing a Comprehensive Assessment of Cognitive and Dementia-like Phenotypes Associated with Existing Models of Vascular Disease, 9/2021 | VCID/Basic Research | https://www.nhlbi.nih.gov/events/2021/opportunities-and-challenges-establishing-comprehensive-assessment-cognitive-and |
SDoH indicates Addressing Social Determinants of Cardiovascular Health (CVH) and Health Inequities; Resilience, Enhancing Resilience; CVH, Promoting CVH and Preventing Cardiovascular Disease (CVD) Across the Lifespan; Hypertension (HTN), Eliminating Hypertension-Related CVD; HF, Reducing the burden of heart failure; and VCID, Preventing Vascular Dementia
Table 2.
Funding Initiatives
Initiative Title | Topic/ Research Type | Links |
---|---|---|
Disparities Elimination through Coordinated Interventions to Prevent and Control Heart and Lung Disease Risk (DECIPHeR) (UG3/UH3 Clinical Trial Optional), 3/2019 | SDoH/Hypertension/Population and Clinical Research | https://grants.nih.gov/grants/guide/rfa-files/rfa-hl-20-003.html |
DECIPHeR - Research Coordinating Center (U24 Clinical Trial Not Allowed), 3/2019 | SDoH/Hypertension/Population and Clinical Research | https://grants.nih.gov/grants/guide/rfa-files/rfa-hl-20-004.html |
Native American Research Centers for Health (S06 Clinical Trials Optional), 3/2020 | SDoH/Population Science | https://grants.nih.gov/grants/guide/pa-files/PAR-20-125.html |
Notice of Special Interest (NOSI): Availability of Administrative Supplements and Urgent Competitive Revisions for Research on the 2019 Novel Coronavirus and the Behavioral and Social Sciences, 4/2020 | SDoH/Population Science | https://grants.nih.gov/grants/guide/notice-files/not-od-20-097.html |
NOSI: Emergency Competitive Revisions for Community-Engaged Research on COVID-19 Testing among Underserved and/or Vulnerable Populations, 6/2020 | SDoH/Population Science | https://grants.nih.gov/grants/guide/notice-files/NOT-OD-20-121.html |
NOSI: Digital Healthcare Interventions to Address the Secondary Health Effects Related to Social, Behavioral, and Economic Impact of COVID-19, 6/2020 | SDoH/Population Science | https://grants.nih.gov/grants/guide/notice-files/not-mh-20-053.html |
Intervention Research to Improve Native American Health (R01 Clinical Trial Optional), 8/2020 | SDoH/Population Science | https://grants.nih.gov/grants/guide/pa-files/PAR-20-238.html |
Transformative Research to Address Health Disparities and Advance Health Equity at Minority Serving Institutions (U01 Clinical Trial Allowed), 3/2021 | SDoH/Population Science | https://grants.nih.gov/grants/guide/rfa-files/RFA-RM-21-022.html |
Understanding and Addressing the Impact of Structural Racism and Discrimination on Minority Health and Health Disparities (R01 Clinical Trial Optional), 3/2021 | SDoH/Population Science | https://grants.nih.gov/grants/guide/rfa-files/RFA-MD-21-004.html |
Transformative Research to Address Health Disparities and Advance Health Equity (U01 Clinical Trial Allowed), 3/2021 | SDoH/Population Science | https://grants.nih.gov/grants/guide/rfa-files/RFA-RM-21-021.html |
NOSI: Research to Address Vaccine Hesitancy, Uptake, and Implementation among Populations that Experience Health Disparities, 12/2021 | SDoH/Population Science | https://grants.nih.gov/grants/guide/notice-files/NOT-MD-22-006.html |
New Epidemiological Cohort Study among Asian Americans, Native Hawaiians, and Pacific Islanders (AsA-NHPI): Clinical/Community Field Centers (UG3/UH3-Clinical Trial Not Allowed), 7/2022 | SDoH/Population Science | https://grants.nih.gov/grants/guide/rfa-files/RFA-HL-23-015.html |
New Epidemiological Cohort Study among AsA-NHPI: Coordinating Center (U24-Clinical Trial Not Allowed), 7/2022 | SDoH/Population Science | https://grants.nih.gov/grants/guide/rfa-files/RFA-HL-23-016.html |
NOSI: The Influence of Host Resilience on Heterogeneity of Acute Respiratory Distress Syndrome/Acute Lung Injury, 9/2020 | Resilience/Basic Research | https://grants.nih.gov/grants/guide/notice-files/NOT-HL-20-814.html |
NOSI: Promoting Research on Interoception and Its Impact on Health and Disease, 1/2021 | Resilience/Basic Research | https://grants.nih.gov/grants/guide/notice-files/NOT-AT-21-002.html |
NOSI: Somatic Cell Gene Editing Therapies To Improve Transplantation Outcomes, 10/2021 | HF/Basic Research | https://grants.nih.gov/grants/guide/notice-files/NOT-AI-21-080.html |
Early Intervention to Promote Cardiovascular Health of Mothers and Children (ENRICH) Multisite Clinical Centers (Collaborative UG3/UH3 Clinical Trial Required), 2/2021 | CVH/Clinical Science | https://grants.nih.gov/grants/guide/rfa-files/RFA-HL-22-007.html |
ENRICH Multisite Resource and Coordinating Center (U24 Clinical Trial Required), 2/2021 | CVH/Clinical Science | https://grants.nih.gov/grants/guide/rfa-files/RFA-HL-22-008.html |
Limited Competition for the Continuation of Epidemiology of Diabetes Interventions and Complications Study Research Center (Collaborative U01 Clinical Trial Not Allowed), 8/2021 | CVH/Basic Research | https://grants.nih.gov/grants/guide/rfa-files/RFA-DK-21-503.html |
NOSI: Promoting Cardiovascular and Cardiometabolic Health in Early Stages of the Lifecourse: Pre-adolescence Through Adolescence to Young Adulthood, 8/2021 | CVH/Population and Clinical Science | https://grants.nih.gov/grants/guide/notice-files/NOT-HL-21-015.html |
NHLBI Big Data Analysis Challenge: Creating New Paradigms for Heart Failure Research, 2/2020 | HF/Basic Research | https://www.nhlbi.nih.gov/grants-and-training/funding-opportunities-and-contacts/NHLBI-heart-failure-data-challenge |
Cardiovascular Biorepository for Type 1 Diabetes (U24 Clinical Trial Not Allowed), 8/2021 | HF/Basic Research | https://grants.nih.gov/grants/guide/rfa-files/rfa-dk-21-010.html |
NOSI: Improving Outcomes in Cancer Treatment-Related Cardiotoxicity, 11/2021 | HF/Basic Research | https://grants.nih.gov/grants/guide/notice-files/NOT-CA-22-001.html |
Development and Validation of Advanced Mammalian Models for Alzheimer's Disease-Related Dementias (R61/R33 Clinical Trial Not Allowed), 1/2019 | VCID/Basic Research | https://grants.nih.gov/grants/guide/pa-files/PAR-19-167.html |
NOSI: Promoting research to understand vascular contributions to cognitive impairment and dementia, 10/2021 | VCID/Basic Research | https://grants.nih.gov/grants/guide/notice-files/NOT-HL-23-002.html |
Catalyze: Enabling Technologies and Transformative Platforms for HLBS Research (R33 - Clinical Trials Not Allowed), 1/2021 | HLBS/Basic Research | https://grants.nih.gov/grants/guide/rfa-files/RFA-HL-23-010.html |
SVIP activities have leveraged the rich resources of our Institute, such as NHLBI cohort studies, which have provided rationale for addressing CVD, identified disparities, and unveiled effective intervention points. DCVS’ pursuit of health equity is reflected in the many SVIP activities centered on addressing health disparities, improving population health, and training the next generation of researchers to address social determinants of CVH. For example, amid disturbing increases in CVD-related maternal morbidity and mortality, and glaring disparities therein,3 multiple SVIP activities have centered on CVH during pregnancy and the postpartum period. Prevention and treatment of CVD across the life course features prominently among workshop topics, and a common theme among working groups is identifying factors of CVD resilience and risk. Notably, SVIP activities highlight our Institute’s rapid and strategic response to COVID-19, as well as NHLBI’s commitment to advancing the promise of precision cardiology.
In collaboration with the extramural research community, other NIH Institutes, Centers, and Offices (NIH ICOs), Federal agencies, non-profit organizations, and industry, DCVS has made considerable progress towards implementing the NHLBI Strategic Vision. SVIP-centered activities conducted since the 2019 DCVS strategic plan publication2 are found in Tables 1 and 2, with key deliverables highlighted in Table 3 and specific activities summarized below. DCVS has identified future research opportunities to engender further progress in SVIP implementation and stimulate transformative research in cardiovascular sciences (Table 4).
Table 3.
Strategic Vision Implementation Deliverables
Peer-reviewed white papers and workshop reports |
Funded projects* | |
---|---|---|
SDoH | Suglia et al., 202042; Paul et al., 202143; Kanaya et al., 202244; Brown et al., 20227 |
7 projects RFA-HL-20-003 1 project RFA-HL-20-004 1 project RFA-MD-21-004 2 projects NOT-OD-20-097 1 project NOT-OD-20-120 1 project PAR-20-238 |
Resilience | Gao and Galis, 202014; Chow et al., 202215 |
1 project NOT-HL-20-814 2 projects NOT-AT-21-002 1 project NOT-AT-21-002 |
CVH | Daniels et al., 201918; Suglia et al., 202042 |
7 projects RFA-HL-22-007 (ENRICH) 1 project RFA-HL-22-008 (ENRICH) 3 projects NOT-OD-20-104 3 projects NOT-OD-21-071 1 project NOT-EB-21-001 |
Hypertension (HTN) | Sigmund et al., 202022; Commodore-Mensah et al., 202245 | 3 projects RFA-HL-20-003 (DECIPHeR) |
HF | Al-Khatib et al., 202046; Delisle et al., 202147; O’Donnell et al., 202148; Mehra et al., 202249 |
6 projects RFA-HL-21-015 (HeartShare) 1 project RFA-HL-21-016 (HeartShare) 5 projects NHLBI HF Big Data Challenge |
VCID | Zlokovic et al., 202050 Muratoglu et al., 202251 |
25 projects NOT-AG-18-008 34 projects NOT-AG-18-039 25 projects NOT-AG-20-008 25 projects NOT-AG-20-034 |
Hyperlinks lead to projects in NIH RePORTER
Table 4.
Future Research Opportunities
Basic | Clinical | Population | |
---|---|---|---|
SDoH | Identify mechanisms of SDoH influence on CVD risk and pathogenesis | Develop multi-level interventions to reduce health disparities | Leverage cohort studies and novel data sources to further evaluate CVD-SDoH associations |
Resilience | Identify the molecular drivers of resilience and factors that influence ARDS/ALI recovery | Develop multi-level interventions that promote resilience in vulnerable populations | In cohort studies, assess longitudinal impacts of adverse environmental conditions on resilience |
CVH | Identify biomarkers in childhood, and trajectories through adolescence, to examine associations of early life environment with CVD risk | Develop interventions to improve dietary and medication adherence for older patients with HF | Elucidate impacts of adverse pregnancy outcomes on CVH trajectories |
HTN | Leverage imaging and single-cell technologies to assess HTN-induced changes at cellular- and tissue-levels | Develop clinical trials for early intervention and new treatments for diverse hypertensive patient populations | Develop deeply-phenotyped cohorts for improved HTN risk and treatment prediction |
HF | Elucidate HF pathophysiology after onset of atrial fibrillation | Develop improved algorithms for clinical decision-making processes for advanced HF | Conduct deep phenotyping studies to define HFpEF subtypes |
VCID | Develop animal models that recapitulate progressive changes in human dementia | Develop clinical trials that test efficacy of CVD interventions for VCID | Elucidate population-level differences in VCID risk and trajectory. |
Addressing social determinants of CVH and health inequities
Social determinants of health (SDoH) are non-medical conditions in which people are born, work, play, and live.5 These conditions are shaped by hierarchical and multilevel federal, state, municipal, and local systems, as well as socio-cultural and family practices. SDoH include socioeconomic status, health care and education access and quality, neighborhood and environmental characteristics, and social and community context. The COVID-19 pandemic and heightened awareness of structural/systemic social injustice have underscored the interplay of SDoH factors in contributing to health inequities. Widening and persistent health disparities highlight the need for continued stimulation of scientific discoveries that address and improve SDoH factors and reduce heart, lung, blood, and sleep (HLBS) inequities. A major DCVS goal is to actively mitigate — not just observe or elucidate — SDoH in promoting CVH and preventing CVD to reduce or eliminate health disparities and promote health equity.
A portfolio analysis using the SDoH Research, Condition, and Disease Categorization (RCDC) term6 indicated that only 4.3% of NHLBI applications funded within Fiscal Years 2008-2020 were in the area of SDoH, though the number of SDoH-funded applications increased 121% over this period.7 Using the Healthy People 2020 SDoH subcategories,8 the most highly funded SDoH areas were identified as Health and Health Care (62%), Economic Stability (61%), and Neighborhood/Built Environment (54%). In addition to funding SDoH-relevant research, DCVS has led multiple SDoH-related scientific workshops and participated in various FOAs. For example, a 2020 NHLBI workshop, “Harnessing Novel Data Sources and Technologies for the Study of Social Determinants of Health in Heart, Lung, Blood, and Sleep Disorders,” discussed how researchers can leverage digital technology and novel data sources to enhance SDoH research. This meeting also examined the influence of the digital divide and unintended consequences of novel technologies in widening health disparities, and implementation strategies to enhance the scientific use of novel data sources for SDoH research.
Additionally, through its Center for Translation Research and Implementation Science (CTRIS), NHLBI initiated the Disparities Elimination through Coordinated Interventions to Prevent and Control Heart and Lung Disease Risk (DECIPHeR) Alliance to test evidence-based multi-level interventions for reducing or eliminating cardiovascular and/or pulmonary disparities and improve health in high-burden communities (Table 2). This effort consists of a Research Coordination Center and Implementation Research Centers that engage diverse multidisciplinary stakeholders to effectively deliver evidence-based interventions to high-burden populations. NHLBI will also participate in Advancing Prevention Research for Health Equity (ADVANCE), a trans-NIH research effort to develop new preventive interventions and strategies to deliver existing interventions in populations experiencing health disparities.9
DCVS has developed or participated in training initiatives specifically focused on SDoH and health disparities, such as a 2021 NHLBI workshop to discuss SDoH training experiences and the need for cross-institutional and interdisciplinary SDoH-training approaches. A portfolio analysis conducted as part of this workshop showed roughly 7% of NHLBI’s total training awards mapped to SDoH. Workshop opportunities for advancing SDoH training included more mechanisms that protected time for mentoring and training, particularly for mid-career and senior mentors; increased networking prospects; and greater support, including infrastructure development, for less research-intensive institutions. Other training-related activities include participation in the NIH Common Fund program Community Partnerships to Advance Science for Society (ComPASS), which includes skill development and training curricula and aims to reduce health disparities by developing community-driven, healthy equity structural interventions.10
Future research directions include continued support of SDoH-related applications to reduce health inequities and advocating for clinical studies to measure SDoH. NHLBI has joined a trans-NIH SDoH Special Interest Group that will address SDoH in research by establishing interdisciplinary research teams, engaging community organizations and members in the full spectrum of research, using innovative and interdisciplinary research methods, and focusing intervention implementation in communities most affected by health inequities. NHLBI will continue to prioritize diversifying the scientific workforce and training of the next generation of scientists in SDoH, taking inspiration from past efforts such as the Diversity Training Workshop, which discussed the strengths, limitations, and gaps of current diversity-focused training mechanisms;11 and a 2021 NHLBI workshop that discussed current challenges in maintaining a sufficient pool of physician-scientists, women, and underrepresented researchers.12
Enhancing Resilience
The DCVS Enhancing Resilience Working Group has been guided by the discussions at the initial 2018 NHLBI workshop on “Enhancing Resilience for Cardiovascular Health and Wellness” (Table 1). To facilitate a shared understanding of “resilience,” attendees adopted a simplified working definition of the term: “Resilience is the ability of living systems to successfully maintain or return to homeostasis in response to physical, molecular, individual, social, societal, or environmental stressors or challenges.” One workshop-identified opportunity was to pursue understanding and integration of the many facets of resilience. To this end, the Resilience Working Group collaborated with other DCVS SVIP working groups. For example, in collaboration with the Heart Failure Working Group and through NHLBI lectures, the working group examined potential contributions of mitochondrial genetics to cardiovascular resilience.13 Invited extramural experts also discussed various aspects of resilience related to COVID-19 complications. Endothelial cell resilience has emerged as a key contributor to avoiding COVID-19-related and overall CVD morbidity, an issue highlighted in a call to action for research into the underpinnings of endothelial resilience.14
The Resilience Working Group has expanded to include representatives from the other NHLBI Divisions and to address topics beyond CVH, such as the role of host resilience as a critical determinant of outcomes in acute respiratory distress syndrome/acute lung injury (ARDS/ALI; Table 2). The Resilience Working Group recognized the need for effective communications and cooperation across NIH ICOs, resulting in other NIH resilience-related initiatives. For example, in collaboration with the National Institute of Diabetes and Digestive and Kidney Disease (NIDDK), NHLBI organized a 2020 workshop focused on the actions of exercise molecular mediators called “Exerkines.” The “Exerkines in Health, Resilience, and Diseases” Workshop was attended by over 300 participants from 10 countries (Table 1). A white paper, including specific considerations about how exercise may contribute to enhancing cardiovascular health and resilience, was published.15
NHLBI was also one of the Trans-NIH Resilience Working Group inaugural members, which includes several ICOs.16 As the first order of business, NHLBI representatives proposed a shared definition of resilience. Trans-ICO collaboration during a 2020 resilience-focused NIH workshop resulted in the following statement: “NIH seeks fundamental knowledge about the nature and behavior of living systems and the application of that knowledge to enhance health, lengthen life, and reduce illness and disability through the study of resilience. Resilience encompasses the capacity to resist, adapt to, recover, or grow from a challenge.”16 NHLBI also contributed to the development of a proposed framework for designing or identifying studies already funded by NIH that could test the contribution and mechanisms underlying resilience in various contexts. The Resilience Research Design Tool is proposed for consideration by potential applicants and NIH staff when planning research interventions to study resilience.16 A webinar series highlighting different resilience topics related to the mission of various NIH ICOs is ongoing.
NHLBI participates in the trans-NIH NOSI “Promoting Research on Interoception [the perception of sensations from inside the body] and Its Impact on Health and Disease” (Table 2). For this NOSI, NHLBI is interested in basic, translational, and clinical research to examine interoceptive processes and mechanisms mediating HLBS normal biological function and disease pathophysiology. Future research directions include increasing cross-collaborations to study resilience and enable training of the next generation of resilience researchers. This could help shift the current cardiovascular research paradigm from reactive to proactive by incorporating concepts of resilience from therapeutics to preventive and implementation science approaches.
Promoting CVH and Preventing CVD Across the Lifespan
Improving CVH across the lifespan, from pregnancy, infancy, early childhood, and adulthood through older adulthood, remains critical for reducing CVD burden. Understanding age-associated physiologic changes and disease progression across the lifespan will inform opportunities to identify risk, address chronic diseases earlier in their development, and initiate prevention efforts to reduce chronic disease burden. It is critical to identify the factors that lead to poorer CVH, beginning in utero and at the earliest stages of life, as well as lifestyle and behavioral interventions to prevent CVD later in life. Accumulation of risk factors, including hypertension, diabetes mellitus, smoking, poor diet, and physical inactivity, contributes to adverse cardiovascular events in later life. Thus, bold new strategies, spanning medicine, public health, and health policy, are needed to combat CVD.
DCVS and the Center for Translation and Implementation Science are collaborating on major efforts to improve maternal CVH, such as the Maternal Health Community Implementation Project17 and the “Early Intervention to Promote Cardiovascular Health of Mothers and Children (ENRICH)” initiative, which will investigate whether an early intervention delivered within the context of a home visiting program can enhance both maternal and early childhood CVH (Table 2). Similarly, limited metrics for ideal CVH during key pediatric developmental periods motivated publication of an initiative to define these metrics and stimulate epidemiological research on CVH trajectory during childhood (Table 2).
A 2018 workshop “Promoting CVH in Early Childhood and Transitions in Childhood through Adolescence” included interdisciplinary experts who discussed the state of the science, identified research gaps, and provided opportunities for promoting CVH in early childhood and transitions through adolescence.18,19 Similarly, NHLBI published a 2021 NOSI, “Promoting Cardiovascular and Cardiometabolic Health in Early Stages of the Lifecourse: Pre-adolescence and Adolescence to Young Adulthood,” to stimulate research on the mechanisms of cardiometabolic health and disease pathogenesis in vulnerable groups and to develop precision prevention interventions to address risk factors during these life stages (Table 2). Finally, in collaboration with the DCVS’ Reducing the Burden of Heart Failure Working Group, a recent workshop “Improving Heart Failure Care for Older Adults: Optimizing Care Transitions” gathered experts to address gaps in treatment and care strategies underlying plateauing improvements in heart failure hospitalizations and the tremendous morbidity burden on older adults who are managing this disorder (Table 1).
Future research and training opportunities include elucidating the impact of early-life environmental exposures on CVD risk trajectories and integrating the life course perspective into clinician training. NHLBI is working with other ICOs including the National Institute of Child Health (NICHD), NIH Office of Research in Women’s Health (ORWH), and the National Institute of Aging (NIA) to stimulate research across the lifespan.
Eliminating Hypertension-Related CVD
Hypertension or high blood pressure (BP) is a major preventable risk factor for CVD and stroke.20 According to the 2017 American College of Cardiology/American Heart Association Hypertension Clinical Practice Guidelines, nearly half of American adults have hypertension, defined as a systolic BP ≥ 130 mmHg or a diastolic BP ≥ 80 mmHg or self-reported antihypertensive medicine use.21 A recent serial cross-sectional analysis of National Health and Nutrition Examination Survey (NHANES) data from 1999 to 2018 reported that hypertension control (defined as systolic BP level <140 mm Hg and diastolic BP level <90 mm Hg) rates were stagnant during 2007-2014 and then worsened after 2013-2014.20
NHLBI and the Centers for Disease Control and Prevention (CDC) convened a 2020 workshop to discuss the reasons for the decline in hypertension control, barriers to regaining previous improvements, possible solutions at multiple levels, research priorities, and policy changes that might facilitate addressing this national problem (Table 1). NHLBI also organized a workshop, involving experts from varied hypertension research backgrounds, to identify barriers for the translation of basic science discoveries and knowledge of pathobiology into better hypertension treatments that can reach diverse patient populations (Table 1). Eight major challenges were identified by the workshop: 1) communication gaps among basic and clinical researchers, 2) incomplete understanding of hypertension antecedents, 3) gene-environment and gene-gene interactions to improve therapeutic decisions, 4) relevance of animal models to humans, 5) detection and reversal of patient nonadherence to hypertension medication, 6) age-related BP changes in children and young adults, 7) insufficient engagement of diverse stakeholders to enhance uptake and feasibility of clinical trials and their findings, and 8) how to bring efficacious community-based interventions up to scale.22
To facilitate the adoption of hypertension research findings into real-world settings, NHLBI currently supports three projects involving hypertension control implementation via the DECIPHeR program described above (Tables 2 and 3). NHLBI convened a workshop “Toward Precision Medicine: Circadian Rhythm of Blood Pressure and Chronotherapy for Hypertension” to identify knowledge gaps related to gene-environment and gene-gene interactions in BP regulation (Table 1). Future research includes collection of BP measurements and related data through NHANES to monitor trends in hypertension prevalence and control and assess the impact of future interventions. BP-related data are collected repeatedly at the clinical examinations of NHLBI-funded cohort studies, revealing longitudinal BP patterns and CVD risk trajectories. Further research into the association between long-term changes in BP levels and hypertension status and CVD outcomes will inform understanding and treatment of hypertension-associated CVD.
Reducing the Burden of Heart Failure
Heart failure (HF) continues to be a major public health burden and is rising in prevalence as the population ages. HF is often categorized by a single measurement, ejection fraction, that is poorly related to its pathophysiology. Heart failure with preserved ejection fraction (HFpEF) accounts for approximately half of the ~6.5 million HF cases in the U.S., involves multiple cardiac and extra-cardiac abnormalities, has a 50% mortality rate 5 years post-diagnosis, and has only recently had its first positive trial showing that empagliflozin reduces cardiovascular death and HF hospitalization.23 Thus, there is an urgent need to improve the identification of HF subtypes through deep phenotyping to advance understanding of disease mechanisms, prevention, diagnosis, and treatment, with the long-term goal of applying personalized approaches to treat specific HF patients.
To better understand HF pathophysiology, NHLBI issued a “Big Data Analysis Challenge: Creating Paradigms for HF Research” competition to solicit innovative, open-source models that can define HF subtypes and generate new research hypotheses (Table 2). The recently awarded NHLBI HeartShare Program will also define HF subtypes based on biological mechanisms through deep phenotyping, imaging, and omics of HFpEF patients (Table 2). HeartShare’s objectives are to: 1) analyze large datasets from diverse HFpEF patients, including those in NHLBI cohorts; 2) relate biological measurements with clinical outcomes; and 3) create and validate HF diagnostic algorithms that can be used by clinicians. The long-term goal is to better understand HFpEF pathophysiology and identify treatment targets with the ultimate aim of precision medicine trials. Efforts are ongoing for HeartShare’s expansion with a public-private partnership between the NIH and industry as a HF Accelerated Medicines Partnership (HF AMP) to improve understanding of HF disease pathways and facilitate better selection of treatment targets.24
Recent relevant NHLBI workshops have examined the circadian mechanisms underlying sudden cardiac death; the molecular, immunological, and pathological pathways underpinning myocarditis; the pathophysiology, prevention, treatment, and role of SDOH in combatting atrial fibrillation; and reducing readmissions and improving transitions of care in older HF patients (Table 1). Future research includes exploring artificial intelligence approaches in cardiovascular imaging toward improved clinical implementation and precision medicine, developing better animal models for HFpEF, and prevention and treatment of chemotherapy-induced HF in cancer patients.
Preventing Vascular Dementia
Dementia is a public health crisis and an umbrella term that describes loss of cognitive function, including thinking, remembering, and behavioral abilities, that is severe enough to interfere with one’s daily life. Alzheimer’s disease (AD) is the most common dementia diagnosis, but AD as a clinical syndrome has mixed pathology and multifactorial etiology. Having biomarker evidence of AD is not the equivalent of AD clinical syndrome. Individuals with AD pathology (amyloid-β deposition and pathologic tau) might not develop dementia without underlying vascular dysfunction or other co-existing conditions.
Human pathology findings suggest that over 50% of clinical AD patients have vascular injuries. The presence of cardiovascular risk factors, such as hypertension, obesity, diabetes, and smoking, particularly earlier in adulthood, has been associated with dementia and faster cognitive decline. The lack of an effective treatment for dementia underscores the urgency to identify and test treatment for modifiable risk factors. Notably, the results of the Systolic Blood Pressure Intervention Trial-MIND substudy (SPRINT-MIND) were published since the 2019 publication of the SVIP and demonstrated that intensive treatment of systolic BP can reduce the incidence of mild cognitive impairment.25
To understand research gaps and opportunities in basic, translational, and clinical research in vascular dementia, NHLBI, in collaboration with the National Institute of Aging (NIA) and the National Institute for Neurological Disorders and Strokes (NINDS), organized three workshops from 2018-2021 (Table 1). The first workshop sought to identify research opportunities in basic and epidemiological research toward understanding vascular contributions to cognitive impairment and dementias (VCID). In 2019, a second workshop examined lessons learned from recently completed VCID trials, the promise of ongoing trials, and opportunities for additional clinical trials that deliver more effective interventions. In 2021, NHLBI convened the third workshop focused on establishment of a comprehensive assessment of neurological phenotypes, including cognitive deficiencies, associated with existing vascular disease animal models that have been used to study cardiovascular disorders (Table 1).
NHLBI joined an NINDS-led FOA to support the Development and Validation of Advanced Mammalian Models for Alzheimer's Disease-Related Dementias in 2019 (Table 2). Although no meritorious applications were funded by NHLBI from this FOA, there was considerable interest from the research community in this topic, and the unmet needs for VCID animal models persist. Researchers interested in developing and/or validating VCID animal models may consider applying through one of the NHLBI “Catalyze: Enabling Technologies and Transformative Platforms for HLBS Research” FOAs (Table 2). Recently, NHLBI, with participation from NINDS and NIA, published a NOSI to encourage collaborative and multidisciplinary research in VCID driven by investigators’ interests that may require studying multiple organs and systems in the same grant (Table 2).
In addition to future VCID research described in the three workshop reports/executive summaries (Tables 1 and 3), there are numerous other research opportunities, including many that synergize with other SVIP focus areas, such as promoting CVH across lifespan and addressing SDoH. For example, further exploration of the association of childhood and early adult adverse CVD risk factors with VCID is required, as is identifying SDoH factors that contribute to VCID. NHLBI cohort study procedures feature cognitive assessments, and ancillary studies (e.g., Multiethnic Study of Atherosclerosis-MIND and Atherosclerosis Risk in Communities-Neurocognitive Study) have also been established. Future work in these and other cohort studies will further unearth links between CVH and cognitive function. Regardless of the scientific areas, collaboration among researchers from various disciplines and across the translational research spectrum will be critical to advance VCID research.
Understanding, Preventing, and Treating Acute and Post-Acute (Long) COVID-19
The serious cardiovascular, pulmonary, and hematologic complications of COVID-19 have placed NHLBI at the forefront of combatting the pandemic. NHLBI’s multi-pronged strategy spans the research spectrum and includes initiating and participating in COVID-19 research funding opportunities that reflect its commitment to addressing COVID-19 etiology, outcomes, and disparities (Table 2).26
A pillar of NHLBI’s pandemic response is leveraging its research infrastructure, including clinical trial networks and cohort studies, to rapidly conduct research on COVID-19. For example, as part of the trans-NIH Accelerating COVID-19 Therapeutic Interventions and Vaccines (ACTIV) Initiative, NHLBI’s Collaborating Network of Networks for Evaluating COVID-19 and Therapeutic Strategies (CONNECTS) leverages NHLBI networks to investigate COVID-19 risk factors and identify potential therapies.27 The Collaborative Cohort of Cohorts for COVID-19 (C4R) study leverages NHLBI’s population-based cohorts to investigate long-term COVID-19 effects and identify factors of risk and resilience.28 In addition, the Long-Term Outcomes After the Multisystem Inflammatory Syndrome In Children (MUSIC) Study leverages the NHLBI Pediatric Heart Network to understand multisystem inflammatory syndrome in children (MIS-C), a COVID-19-related condition that disproportionately affects Black and Latinx children.29 NHLBI is addressing Long COVID through participation in the NIH Researching COVID to Enhance Recovery (RECOVER) initiative, which aims to understand, prevent, and treat Long COVID30
Community engagement is central to NHLBI’s strategy for reducing COVID-19 disparities. With the National Institutes on Minority Health and Health Disparities (NIMHD), NHLBI co-leads the NIH Community Engagement Alliance (CEAL) against COVID-19. disparities.31 This initiative fosters partnerships with communities disproportionately burdened by COVID-19 to address mistrust and misinformation, increase COVID testing and vaccination, and promote inclusion in clinical trials. NHLBI also participates in Rapid Acceleration of Diagnostics-Underserved Populations (RADX-Up), community-based projects that evaluate and expand COVID-19 testing, and implement culturally-tailored testing, in underserved and vulnerable populations.32
Training the Next Generation of Cardiovascular Scientists
Training the next generation of HLBS researchers is critical for advancing DCVS SVIP goals, hence NHLBI leadership in several training and career development opportunities.33 Among these are opportunities to recruit and retain researchers from diverse backgrounds, which is a high NHLBI priority. NHLBI’s commitment to inclusive excellence is reflected in the many diversity-related funding opportunities in which the Institute has initiated or participated,34 including the NHLBI Programs to Increase Diversity Among Individuals Engaged in Health-Related Research (PRIDE); the Helena Mishoe Fellowship for Underrepresented Scientists; and the NHLBI Mentored Research Scientist Career Development Award to Promote Faculty Diversity in Biomedical Research (K01).
NHLBI participates in the Support for Research Excellence (SuRE) Award programs to develop and sustain research excellence at institutions that receive limited NIH support and serve students from groups underrepresented in biomedical research.35,36 NHLBI also participates in the Faculty Institutional Recruitment for Sustainable Transformation (FIRST) program, an NIH Common Fund initiative to recruit and support a diverse cohort of new research faculty.37 In addition, NHLBI participates in the Maximizing Opportunities for Scientific and Academic Independent Careers (MOSAIC) program, which supports the career transitions of postdoctoral researchers from diverse backgrounds.38
NHLBI supports women in science through participation in the Office of Research in Women’s Health (ORWH) Supplements to Promote Research Continuity and Retention, which help sustain research during critical life events, including childbirth. NHLBI will also participate in the ORWH Research Education Program (R25), supporting skills development and curriculum/methods development on topics relevant to sex/gender influences on HLBS diseases/disorders. Future directions include enhancing opportunities for transition of K awardees into independent research positions, stronger integration of data science into our training portfolio, and expanding research opportunities for physician-scientists.
CONCLUSIONS
The activities described herein emphasize a vision of enhanced CVH for all, encompassing concepts, areas of research, and emerging opportunities that can stimulate cutting-edge, transformative research in cardiovascular sciences. DCVS SVIP implementation has resulted in development of nearly 50 workshops/seminars and nearly 30 research funding opportunities (Tables 1 and 2). These activities span the research spectrum, offer avenues through which health equity can be achieved, leverage scientific and technological advances, and present a multi-pronged research strategy for tackling COVID-19. Key deliverables include peer-reviewed white papers, workshop executive reports, and NHLBI-funded projects (Table 3). SVIP implementation has also stimulated partnerships within NHLBI and with other NIH Institutes. Examples include collaboration with the Center for Translation Research and Implementation Science on hypertension and maternal well-being; partnerships with various ICOs, such as ORWH, NIA, NICHD, NIDDK, and NINDS; the Trans-NIH Resilience Working Group; the Trans-NIH SDoH Interest Group; trans-HHS partnerships (ENRICH), and public-private partnerships (HF AMP).
Giving shape to a vision of enhanced CVH for all requires forethought in an ever-evolving landscape in which new knowledge, areas of research, and technologies emerge. Thus, DCVS has identified opportunities for future research in pursuit of this vision (Table 4). Examples include leveraging the NHLBI Trans-omics for Precision Medicine Program (TOPMed)39 and BioData Catalyst40 to facilitate a systems-based understanding of CVD. Importantly, 60% of sequenced TOPMed participants are of non-European ancestry, ensuring health equity in the age of precision medicine. NHLBI will continue to stimulate research and training in data science, bioinformatics, and omics technology that address the complexity and heterogeneity of disorders such as heart failure.
Since the 2019 DCVS SVIP publication, NHLBI has developed two new cohort studies: The Risk Underlying Rural Areas Longitudinal (RURAL) cohort study;41 and an epidemiological cohort study among Asian Americans, Native Hawaiians, and Pacific Islanders (Table 2). Future research in these cohorts will extend NHLBI’s legacy of addressing CVH disparities and identifying factors of CVD risk and resilience in different populations. We will continue to address COVID-19 development, outcomes, and disparities, applying elements of NHLBI’s pandemic response (e.g., platform trial and “network of networks” approaches) to CVD prevention and treatment.
Just as the NHLBI SV, on which the DCVS SVIP is predicated, engaged the extramural community in its development, DCVS has sought input from extramural researchers in achieving SVIP goals. DCVS will continue this engagement through NHLBI-organized workshops, in which extramural researchers participate to help identify gaps and barriers in research and recommend new research opportunities. DCVS will also continue inviting extramural researchers to present at the DCVS Strategic Vision Webinar Series. NHLBI frequently issues Requests for Information (RFI), through which the extramural community can contribute to strategic visioning efforts. Though much remains to be done to turn discovery into CVH, reignite the decline in CVD mortality, and close the equity gap in CVD and CVH, future DCVS endeavors and those discussed herein lay the groundwork for success.
Supplementary Material
Non-standard Abbreviations and Acronyms
- AD
Alzheimer’s Disease
- BP
Blood Pressure
- CVD
Cardiovascular Disease
- CVH
Cardiovascular Health
- DCVS
Division of Cardiovascular Sciences
- FOA
Funding Opportunity Announcement
- HF
Heart Failure
- HFpEF
Heart Failure with Preserved Ejection Fraction
- HLBS
Heart, Lung, Blood, and Sleep
- NHANES
National Health and Nutrition Examination Survey
- NHLBI
National Heart, Lung, and Blood Institute
- NIA
National Institute on Aging
- NIH ICOs
National Institute of Health Institutes, Centers and Offices
- NINDS
National Institute for Neurological Disorders and Stroke
- NOSI
Notice of Special Interest
- RFA
Request for Application
- RCDC
Research, Condition, and Disease Categorization
- SDoH
Social Determinants of Health
- SVIP
Strategic Vision Implementation Plan
- VCID
Vascular Contributions to Cognitive Impairment and Dementias
Footnotes
DISCLAIMER: 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.
Disclosures: None
Supplemental Material
Members of DCVS Strategic Vision Implementation Working Groups
References
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