On March 29, 2007, the National Heart, Lung, and Blood Institute released its
to provide a guide for its research and training programs over the next decade. The plan consists of a set of goals that reflect the successive
movement of scientific discovery from “form to function” (Goal 1), “function to causes” (Goal 2),
and “causes to cures” (Goal 3). Within each goal, specific-research Challenges are provided
that address the overarching Goal. The Division of Prevention and Population Sciences (DPPS)
supports research in all three goal areas, though most efforts are concentrated in Goal 3, which
includes studies in populations.
The DPPS Strategic Plan uses the NHLBI Strategic Plan as its framework. Specific programs –
either ongoing or planned – and possible future research areas are provided within each Goal
and under specific Challenges. In addition, the Division works in close collaboration with other
Divisions at the NHLBI, most notably the Division of Cardiovascular Diseases,
which directly shares research objectives in prevention, diagnosis, and
treatment of cardiovascular diseases, and with other Federal agencies, such as the
National Center for Health Statistics, the Agency for Healthcare Research and Quality, the Food
and Drug Administration, and the Centers for Disease Control and Prevention.
The Division of Prevention and Population Sciences
The Division of Prevention and Population Sciences supports and provides leadership for
population- and clinic-based research on the causes, prevention, and clinical care of
cardiovascular, lung, and blood diseases . Research includes a broad array of epidemiological
studies to describe disease and risk factor patterns in populations and to identify risk factors for
disease; clinical trials of interventions to prevent disease; studies of genetic, behavioral,
sociocultural, and environmental influences on disease risk and outcomes; and studies of the
application of prevention and treatment strategies to determine how to improve clinical care and
public health. The Division also supports training and career development for these areas of
research. The Division is organized into four major components: the Epidemiology Branch, the
Clinical Applications and Prevention Branch, the Women's Health Initiative Branch, and the
Office of Biostatistics Research.
NHLBI Strategic Plan Goals and Strategies and DPPS Programs and Plans
Goal 1: To Improve Understanding of the Molecular and Physiological Basis of Health
and Disease, and To Use That Understanding To Develop Improved Approaches to
Disease Diagnosis, Treatment, and Prevention.
Challenge 1.1: To delineate mechanisms that relate molecular events to health and
1.1.b. Identify intracellular targets of key signaling and transcriptional pathways in normal and
The Division supports observational interventional studies, such as the PROGENI studies that
expose individuals to either putatively efficacious or proven therapies to change risk factor levels
and that include collection of DNA for genome-wide association studies (GWAS). Investigators
are able to determine how environmental perturbations and genetic variants interact to affect risk
factor responses. These studies may be used to investigate the efficacy of therapeutic and life
style interventions to promote the advancement of personalized medicine.
The Division recognizes the value of adding provocative tests of known effective interventions
and additional “omics” measures to existing and new studies to better understand gene by
environment interactions on risk factors and disease, constituting a “to bench and back”
1.1.c. Determine key genetic variants that are associated with specific diseases and delineate
the molecular mechanism that account for susceptibility or resistance to disease.
The Division supports family studies, candidate gene studies, and GWA studies on multiple
cohorts and case-control studies through the SHARe and STAMPEED programs. It also
supports one of the largest GWA studies of African American cohorts through the CARe
program. Fine-mapping and sequencing studies occur through the NHLBI-sponsored
Resequencing and Genotyping Centers. All of these programs include worldwide data sharing to
maximize interrogation of huge data sets. Additional population-based research and basic
science may elucidate novel molecular mechanisms that account for disease susceptibility.
Proteomic and metabolomic (as well as other “-omics” measures) overlaying these initial GWAS
cohorts allow systems approaches to explore biological pathways.
The Division is embarking upon expansion of the GWAS to other cohorts including additional
minority populations from the Women’s Health Initiative. Minority populations reflect different
gene pools, different clinical profiles and different environmental conditions.
1.1.d. Define molecular, cellular, and organ-specific responses to environmental challenges and
the mechanisms by which heritable and non-genetic factors interact in disease initiation and
progression and in therapeutic response.
The Division supports a number of well-known large-scale longitudinal cohort studies such as
ARIC, MESA, CHS, WHI, CARDIA, and the Framingham Study that include clinical and imaging
measures of manifest and subclinical disease, and that include environmental measures such as
diet, physical activity, sleep, and psychological factors. The recent introduction of extensive
genotyping in these cohorts will allow assessment of gene by environment interactions on
disease initiation and progression.
In conjunction with other Institute initiatives, the Division recognizes the value in adding more
refined environmental measures and measures of gene expression and proteomics to evaluate
the effect of exposures on gene products and disease development. Other projects might
include epigenetics, e.g. genome-wide methylation patterns, and their association with risk
factors and disease.
1.1.e. Determine the role of systemic pathological processes, such as inflammation, immunity,
and infection, in the development and evolution of disease.
The Division oversees a number of well-known cohort studies, including the Framingham Heart
Study, ARIC, MESA, WHI, CARDIA, the Jackson Heart Study, the Strong Heart Study, and the
GOCADAN Study that include systemic measures of inflammation, immunity and infection.
These studies also include genotyping and environmental and lifestyle measures to better
understand how multiple inflammatory factors contribute to disease initiation and progression.
Biomarkers are constantly being added and refined to provide more objective and integrated
measures of environmental exposures in existing and new cohorts.
Challenge 1.2. To discover biomarkers that differentiate clinically relevant disease
subtypes and that identify new molecular targets for application to prevention and
diagnosis – including imaging and therapy
1.2.a. Identify molecular signatures that allow complex disease phenotypes to be stratified into
clinically relevant categories.
The Division supports research initiatives to identify the value of putative biomarkers for disease
diagnosis, progression, and treatment effectiveness. New biomarkers will be evaluated for
predictive value and refined disease phenotyping taking advantage of accessible stored samples
along with cumulative risk factor, environmental, genetic and clinical data.
The Division recognizes the value of assessing gene expression, proteomics, and metabolomics
in existing cohorts to provide further opportunities for biomarker discovery for identification of
subtypes of disease and for prediction of response to perturbations or interventions.
Goal 2: To Improve Understanding of the Clinical Mechanisms of Disease and Thereby
Enable Better Prevention, Diagnosis, and Treatment.
Challenge 2.1: To accelerate translation of basic research findings into clinical studies
and trials and promote translation of clinical research findings back to the laboratory.
2.1.c. Integrate, analyze, and share extant and emerging genotypic and phenotypic data.
The Division supports multiple well-known large-scale cohort studies (e.g., Framingham Heart
Study, MESA, ARIC, CARDIA, Jackson Heart Study, Hispanic Community Health Study, the
Strong Heart Study, WHI observational component, and CHS) and clinical trials (e.g., Women’s
Health Initiative and ACCORD) that include detailed data on multiple clinical and subclinical
phenotypes. Extensive genotypic data have been obtained for some cohorts (e.g., Framingham,
ARIC, and Strong Heart Study), while progress is being made towards obtaining similar data for
others (WHI and MESA). Working with the National Center for Bioinformatics (NCBI) at the
National Library of Medicine, the Division has already made available for the general scientific
community combined genotype-phenotype data on the Framingham Heart Study (Framingham
SHARe). Additional data sets from PROGENI and STAMPEED will provide genotype-
phenotype data for response to known efficacious interventions, and for case-control studies of
heart, lung and blood clinical outcomes. BioLINCC, jointly managed with the Division of Blood
Diseases and Resources will facilitate the scientific community’s access to biospecimens and
data from a wide variety of observational and clinical trial studies. The Division also supports a
program to translate basic behavioral science into clinical and public health interventions aimed
at preventing obesity.
The Division recognizes that the optimal value of these cohort and trial databases will depend on
maximal integration of data across levels of function (e.g., genetic, molecular, organ-based,
whole individual, community) and across cohorts (i.e., pooling data as much as possible), on
developing robust analytical approaches to complex data structures, and on enabling widespread
sharing of data with the scientific community while assuring protection of confidentiality for
Challenge 2.2: To enable early and accurate risk stratification and diagnosis of
cardiovascular, lung, and blood disorders.
2.2.a. Exploit noninvasive imaging methods to detect and quantify subclinical disease.
The Division supports a number of observational and intervention studies that focus on
noninvasive imaging tests, such as carotid ultrasonography, echocardiography, magnetic
resonance imaging (MRI), and computerized tomography (CT), to identify subclinical disease
and study their associations with cardiovascular events and risk factors. These imaging
measures may be used to improve risk stratification, provide insights into pathophysiology and
disease development, and identify viable targets for disease prevention.
The Division acknowledges the value of advances in noninvasive imaging to further understand
mechanisms of initiation, progression, and reversal of disease and enable measurement of the
clinical outcomes of interventions. The Division recognizes the need to advance research on
noninvasive measures from a sole focus on diagnosis and prognosis to additional focus on
outcomes and comparative value.
2.2.b. Apply new discoveries in biomarkers to improve risk assessment, diagnosis, prognosis,
and prediction of response to therapy.
The Division supports multiple observational studies and clinical trials that systematically
measure multiple novel biomarkers for possible risk stratification, diagnostic, and predictive tools.
Biological samples are obtained during clinical examinations and stored for longitudinal analyses
while also measuring initiation and progression of subclinical and clinical disease.
The Division supports improved risk prediction by supporting large population studies that include
all population groups, including adequate numbers of women and minorities. The Division
recognizes that improved ability to detect subclinical disease and monitor disease progression
could potentially transform clinical decision-making and motivate lifestyle choices and behaviors
that affect clinical outcomes. The Division is considering programs using -omics technologies to
uncover new biomarkers that may become useful tools for evaluating risk and individual
responsiveness to interventions in populations and, ultimately, for identifying new therapeutic
Challenge 2.3: To develop personalized preventive and therapeutic regimens for
cardiovascular, lung, and blood diseases.
2.3.a. Improve the understanding of interactions between genetic and environmental factors that
influence disease development and progression and response to therapy.
The Division conducts observational studies that evaluate genetic associations with phenotypic
response to known efficacious environmental effects (e.g., PROGENI), and genetic studies in
conjunction with clinical trials to evaluate genetic determinants of drug effects on major
cardiovascular clinical outcomes (e.g., ALLHAT and GenHAT). Efforts are underway (e.g.,
through CARe, SHARe and STAMPEED) to make combined phenotype and genotype data
from the large observational studies (e.g., Jackson Heart Study, ARIC, CHS, CARDIA) available
for scientific communities to better understand how genetic and environmental factors interact to
contribute to disease initiation and progression. These studies identify subgroups based on
genotype that may be most likely to benefit from targeted environmental changes designed to
reduce the development or progression of cardiovascular diseases.
The Division recognizes that identification and evaluation of such associations may enhance
understanding of complex traits and permit investigators to explore the relationship between
genetic variants, gene expression, and gene-environmental interactions, and move clinical
medicine and public health practice towards genetically-guided preventative and therapeutic
approaches. The Division is considering programs that develop more precise measures of
environmental exposures through integrated biomarkers, “-omics” measures, and more robust
definitions of clinical phenotypes. There is considerable interest in validation and calibration of
dietary and physical activity data from questionnaires and novel technologies. The Division is
planning to develop shared databases with information from multiple studies to facilitate
integration and analysis of results.
2.3.b. Identify and evaluate interventions to promote health and treat disease in genetically
defined patient sub-groups by altering developmental or environmental exposures including
drugs, diet and exercise, sleep duration and quality, and infectious agents and allergens.
The Division supports intervention studies and clinical trials that evaluate health promotion and
disease treatment strategies in selected patients and populations by altering environmental
exposures including drugs, diet and exercise. For example, the Division supports programs,
such as PROGENI, that aim to identify novel genes that interact with specific environmental
exposures to modify risk factors for cardiovascular disease.
The Division encourages novel approaches for modeling complex interactions between gene
and environmental exposures. Large cohort studies often include measures of exposure to
drugs, allergens, and infectious agents in addition to information about diet, exercise, and
psychosocial factors. The generated results may provide a wealth of information for generating
hypotheses and identifying potential interventions.
Challenge 2.4: To enhance the evidence available to guide the practice of medicine, and
improve public health.
The Division has a long and distinguished tradition of excellence in the conduct of observational
cohorts that characterize disease risk and provide insights for viable treatment targets. It further
supports randomized clinical trials (e.g. hypertension treatment trials: HDFP, SHEP, ALLHAT;
dietary and other lifestyle interventions: DASH, PREMIER, ACT, WMT); multiple risk factors:
MRFIT; hormone replacement therapy: WHI) that provide the highest level of evidence to guide
the practice of medicine and public health. Many of the current rigorous standards of evidence
upon which practice guidelines, especially JNC-7 and obesity, are based on the Division-
supported studies. Division-sponsored community- and clinic-based studies provide guidance on
the best ways to prevent risk factors and to help clinicians effectively treat diseases and risk
The Division remains committed to ongoing generation of evidence that will inform disease
prevention, diagnosis, and treatment. The ongoing ACCORD trial has reported its first results on
target glucose levels while the hypertension and lipid components continue. Trials such as
ALLHAT and TOHP continue to yield new information about practice. Other trials, such as
SPRINT, a trial that could have a major impact on hypertension management, are in planning.
Goal 3: To Generate an Improved Understanding of the Processes Involved in Translating
Research into Practice and Use That Understanding To Enable Improvements in Public
Health and To Stimulate Further Scientific Discovery.
Challenge 3.1: Complement bench discoveries and clinical trial results with focused
behavioral and social science research
The Division supports behavioral and social science research to investigate the relationship
among psychosocial risk factors (e.g., depression, social support, hostility, stress), health-
damaging and health-promoting behaviors, and cardiovascular risk factors and outcomes and
delineate the physiologic, neural, and behavioral mechanisms that mediate these associations.
Other work seeks to identify psychological, social and behavioral factors (e.g. motivational,
emotional and cognitive processes) that are involved in the formation, change, or maintenance
of cardiac risk factor behaviors and develop and test innovative interventions to ameliorate
psychosocial and behavioral risk factors (e.g., nutrition, physical activity and tobacco smoking)
and improve cardiovascular health.
Ongoing projects aim to identify high-risk subgroups of depressed patients and develop better
treatments for depressed CHD patients. Other projects are evaluating the effects of stress
management interventions, using innovative strategies, based on basic behavioral and social
sciences research, to promote healthy behaviors. The Division is particularly interested in
elucidating the psychosocial, behavioral and sociocultural factors responsible for health
disparities with the aim to develop and test cost-effective interventions that may both reduce
disparities while improving overall public health. Special projects are focusing on American
Indians and Alaska Natives, as well as other groups at high CVD risk such as Hispanic/Latino
populations, African Americans, rural and low-income groups and immigrants. Studies of
gene/environment interactions supported by DPPS include the influence of genes on behavior as
well as the neurohormonal pathways through which psychosocial factors influence gene
Future research directions include investigating the use of new technologies and novel
intervention methods (such as adaptive designs and systems science approaches) to develop
and test interventions; studies investigating the influence of genes and neurohormonal pathways
on behavior; studies that address the importance of psychological, cognitive and social sequellae
of heart disease; and the need for user-friendly and reliable tools to measure quality of life and
outcomes of heart diseases and treatments.
3.1.a. Develop and evaluate new approaches to implement proven preventive and lifestyle
The Division supports research on behavioral, clinical, community and healthcare approaches to
reduce cardiovascular diseases. Projects range from observational analyses to clinical and
community trials. The Division supports research in nontraditional families, low SES, rural and
immigrant populations, as well as research to prevent health disparities (such as a program
testing implementation of programs to control high blood pressure in African Americans);
interventions at individual and group levels including those in schools, worksites, neighborhood
and community, health care settings, family and community-based approaches; and studies that
examine the extent to which risk stratification and application of personalized medicine can
improve effectiveness in cardiovascular disease prevention and treatment. The Division
supports studies to prevent and treat obesity in childhood and in young and older adults; studies
on weight loss maintenance in adults; novel dietary strategies; complementary or alternative
medicine for cardiovascular disease prevention; trials in physical activity; hypertension
prevention and treatment interventions in diverse population; and health disparities research.
The Division will continue to pursue and implement research approaches that are novel including
those that integrate genetic, basic and social sciences, lifestyle behavioral changes and
personalized medicine for cardiovascular disease prevention and treatment.
3.1.b. Develop and evaluate policy, environmental, and other approaches for use in community
settings to encourage and support lifestyle changes
The Division supports and conducts research on policy and environmental approaches including
those in worksites, schools, health-care and other community settings (e.g., churches) to
improve health and prevent cardiovascular diseases. The Division also supports studies that use
novel methods to assess environmental and policy changes. Intervention approaches to prevent
cardiovascular diseases are conceptualized on a population basis. Studies include those that
focus on obesity prevention, physical activity or community cardiovascular disease prevention.
Environmental strategies include, for example, those that influence the social environment (e.g.,
social network, family), physical environment (e.g., providing sidewalks, safe neighborhoods,
access to fitness clubs), and community environments (e.g., smaller portion sizes at restaurants
or fresh fruits in supermarkets). Policy strategies include those that focus on health outcomes as
a result of implementation of clinical guidelines (e.g., dietary, physical activity, and blood
pressure guidelines), and enactment of laws and regulations (e.g., smoking bans, tax
modifications, point-of-purchase nutrition labeling, and “smart growth” strategies, such as
The Division recognizes the value of research that uses multi-level intervention approaches
focusing not only on the individual but on social environment-, physical environment-,
community-, and systems-level influences.
3.1.c: Develop and evaluate interventions to improve patient, provider, and health care system
behavior and performance in order to enhance quality of care and health outcomes.
The Division supports research that evaluates patient-, clinician-, system-, and multi-level
interventions to improve clinical care delivery for prevention and treatment of cardiovascular
diseases and to eliminate health disparities. A substantial proportion of these projects are
individual- or cluster-randomized clinical trials. Programs include initiatives on improving heart
failure disease management, a cardiovascular research network in community-based care,
studies on weight loss in obese adults with cardiovascular risk factors, trials assessing innovative
strategies to improve clinical practice through guidelines in heart, lung, and blood diseases, and
studies to improve hypertensive care for inner city minorities.
The Division seeks to enhance quality of life and cardiovascular outcomes by supporting and
conducting research that generates new knowledge, as well as knowledge that facilitates
implementation of effective patient, clinician and/or health system interventions.
Challenge 3.2. To identify cost-effective approaches for prevention, diagnosis, and treatment
3.2.a. Evaluate the risks, benefits, and costs of diagnostic tests and treatments in representative
populations and settings
The Division supports health services and outcomes research that evaluates the most effective
and efficient ways to deliver health care in real-world settings, translating scientific discovery into
communities. One such example is the evaluation of implantable cardioverter defibrillators for
primary prevention in the HMO-based Cardiovascular Research Network, evaluating both
clinical and cost outcomes. The Division also supports large-scale trials that rigorously evaluate
the comparative clinical effectiveness of treatment options on health outcomes as well as the
relative cost-effectiveness of these options. Such studies include ALLHAT, ACCORD, and
The Division acknowledges the importance of research on health services, cost-effectiveness,
and outcomes that evaluates clinically feasible diagnostic tests and interventions in real-world
settings, investigates interventions to eliminate disparities in health care delivery, and pursues the
development and evaluation of improved metrics of health care quality and outcomes focusing
on value-based diagnostics and treatments. It has funded linking cohort study data to CMS data,
which provides information on medical care utilization, costs, and outcomes.
3.2.b. Develop research designs, outcome measures, and analytical methods to assess
prevention and treatment programs in community and health care settings across populations
The Division supports various research designs including individual and group randomized
designs, quasi-experimental designs, “natural experiments” (or opportunist evaluations), and
traditional longitudinal (including long-term) cohort studies. The Division supports the analysis of
data systems that characterize various population groups, access to health care, patterns of
health care use, family structure, work roles, quality of life, clinical health status, and data
analyses from clinical trials to examine, for example, cost-effectiveness, return on investment
and other economic and health outcomes. Through the improved measures of diet and physical
activity for genes and environment initiative (GEI), research is being conducted to develop novel,
reliable and valid technologies that have low subject burden, and are economically feasible for
use in studies of free-living and diverse populations to improve assessment of diet and physical
The Division, through the Office of Biostatistics Research (OBR), supports the application of
traditional statistical methods and the development of novel statistical methodologies for
analyses of clinical trials and epidemiological studies. OBR statisticians collaborate widely with all
divisions of NHLBI, including the Division of Intramural Research, as well as with other NIH
Institutes and other national and international research organizations and universities. OBR’s
methodological interests include survival analysis, longitudinal data analysis, mid-trial corrections
(trial extension and early stopping), and efficient study designs, including the monitoring of
clinical studies for efficacy and safety while they are ongoing.
The Division will continue to identify and pursue statistical challenges within traditional clinical
study frameworks and in the emerging areas of genetic and genomic research. Further areas of
research include study design and analytic strategies for genetic-guided clinical trials and for
clinical trials randomizing on genotypes. It is also anticipated that the areas of personalized
medicine and personalized genomics will be the focus of further statistical developments.
Challenge 3.3: To promote the development and implementation of evidence-based
guidelines in partnership with individuals, professional and patient communities, and
health care systems and to communicate research advances effectively to the public.
3.3.a. Establish evidence-based guidelines for prevention, diagnosis, and treatment and identify
gaps in knowledge.
The Division supports many well-known large-scale cohort studies and clinical trials that yield
data critical for evidence-based clinical practice guidelines. The Framingham Risk Score has
been integrated in cardiovascular guidelines such as the National Cholesterol Education Program.
Recent findings from the ACCORD study will certainly impact the clinical guidelines on the
management of diabetes in high-risk patients. In collaboration with the DPPS, the Division for
the Application of Research Discoveries (DARD) leads the NHLBI effort in establishing
integrated guidelines that holistically address the full range of cardiovascular risk factors.
The Division acknowledges the importance of pooled multiple cohorts and or clinical trial
databases to help stratify risks for disorders other than coronary heart disease events, such as
clinical heart failure. There is increasing interest in implementation research that seeks to identify
optimal methods for incorporating guidelines in routine practice. Findings from these studies may
impact the process of developing clinical guidelines.
3.3.b. Develop personalized and community- and health care system-oriented approaches to
increase the use of evidence-based guidelines by individuals, communities, health care providers,
public institutions, and, especially, by populations that experience a disproportionate disease
The Division supports programs that speed the implementation of research findings into health
care and community settings. The Division encourages research that enhances the
understanding of contributions of individual health behaviors, community-based organizational
and environmental polices, and health systems innovations to reduce health disparities.
The Division is supporting new, innovative evaluation projects on the outcomes of community
programs that target the control of childhood obesity. Findings from these observations would
help inform other communities on the usefulness of applying similar policies for the control of
childhood obesity in their own communities. These programs may also provide novel ideas for
generating personalized approaches to increase the use of evidence-based guidelines by
populations that experience a disproportionate disease burden.
3.3.c. Communicate research advances effectively to the public.
The Division energetically works to communicate research advances to the public. It
collaborates with the NHLBI press staff in the Division for the Application of Research
Discoveries (DARD) to publicize major NHLBI funded prevention- and population-based
research advances. The Division actively identifies potential newsworthy research results prior
to the publication of articles or presentation of findings at major scientific conferences; the
Division further works with the NHLBI press staff to prepare the news releases and respond to
outside press inquiries. Aside from the general public, the Division supports communicating
research advances to participants and communities of its longitudinal cohort studies.
The Division is committed to continuing support DARD as they lead NHLBI in speeding the
application of scientific advances in the prevention, detection, and treatment of cardiovascular,
long, and blood diseases and narrow the discovery-delivery gap. In addition, the Division will
continue to highlight and communicate research findings to communities and participants of its
large-scale longitudinal cohort studies.
List of NHLBI study abbreviations, names, and web sites:
||Genome-Wide Association (Studies)
||Joint National Committee on the Detection, Evaluation, and
Treatment of High Blood Pressure