Release Date:  March 25, 1998

PA NUMBER:  PA-98-046


National Institute of Nursing Research
National Heart, Lung, and Blood Institute


The National Institute of Nursing Research (NINR) and the National Heart, Lung,
and Blood Institute (NHLBI) seek research applications for investigator-initiated
research relevant to the development and/or testing of dietary interventions to
improve the cardiovascular disease (CVD) risk profiles in children and
adolescents, especially those at increased risk for CVD or for development of CVD
risk factors because of genetics, family history, socioeconomic status (SES),
race/ethnicity, levels of blood cholesterol or blood pressure, or other factors. 
This program announcement (PA) seeks four different, but related, types of
studies:  (1) observational studies identifying determinants of nutrient intakes
and determinants of dietary effects on levels of CVD risk factors, (2)
intervention studies examining the effects on diet and CVD risk factors of
approaches to improve dietary behavior to meet current dietary recommendations,
(3) intervention studies examining the true magnitude of effects on CVD risk
factors of dietary or nutrient changes under conditions of high adherence, and
(4) studies directed toward advancing measurement methodologies or behavioral
theories which could then be applied to intervention studies.  Of particular
interest is the examination of effects of dietary interventions on individuals
with different genetic profiles.  The overall goal of this PA is to identify
dietary interventions, alone or in combination with other interventions, that can
improve CVD risk factor profiles in children and adolescents.  Studying male and
female children and adolescents of different socioeconomic, racial, ethnic, and
age groups is strongly encouraged.


The Public Health Service (PHS) is committed to achieving the health promotion
and disease prevention objectives of Healthy People 2000, a PHS-led national
activity for setting priority areas.  This Program Announcement (PA), Diet and
Cardiovascular Disease Risk in Children and Adolescents, is related to the
priority area of physical activity, nutrition, educational and community-based
programs, heart disease and stroke, and children and adolescents.  Potential
applicants may obtain a copy of Healthy People 2000 (Full Report:  Stock No. 017-
001-00474-0 or Summary Report: Stock No. 017-001-00473-1) through the
Superintendent of Documents, Government Printing Office, Washington, DC 20402-
9325 (telephone 202-512-1800).


Research applications may be submitted by foreign and domestic, for-profit and
non-profit organizations, public and private, such as universities, colleges,
hospitals, laboratories, units of State and local governments, and eligible
agencies of the Federal government.  Racial/ethnic minority individuals, women,
and persons with disabilities are encouraged to apply as Principal Investigators.


The primary mechanism of support will be the National Institutes of Health (NIH)
research project grant (R01); another possible mechanism is the R18
(Demonstration and Education Research).  Responsibility for the planning,
direction, and execution of the proposed project will be solely that of the
applicant.  Any applicant planning to submit a new investigator-initiated grant
application requesting $500,000 or more in direct costs in any one year must
contact Institute program staff before submitting the application (see INQUIRIES,
below).  Furthermore, the applicant must obtain agreement from Institute staff
that the Institute will accept the application for consideration for award. 
Additional information can be found in the NIH Guide Volume 25, Number 14, May
3, 1996.  Responses to Program Announcements are subject to this policy.



The NIH convened a Special Emphasis Panel (SEP), Intervention Studies in Children
and Adolescents to Prevent Cardiovascular Disease, in September 1997.  The SEP
reviewed the efficacy and effectiveness of interventions to prevent and improve
known cardiovascular disease risk factors in children and adolescents; reviewed
the current knowledge about emerging and new risk factors; and developed
recommendations for future research directions for preventive intervention
studies in children and adolescents.  This PA was developed in response to panel
recommendations.  The minutes of the panel meeting are available at and  This PA covers a wide range of
topics relevant to nutrition and CVD risk factors, with a focus on children and

Dyslipidemia, obesity, smoking, hypertension, and physical inactivity have been
identified as risk factors for CVD.  Elevations of total blood cholesterol, body
weight, and blood pressure, the onset of smoking, and a physically inactive
lifestyle in childhood and adolescence increase the probability that CVD risk
factors will develop in adulthood; therefore, risk reduction interventions at an
early age could have life-long implications for improved health.  Certain sub-
populations (e.g., lower socioeconomic groups, African-Americans, those with a
family history of CVD) are at increased risk for CVD or for development of CVD
risk factors in adulthood.  Genetic epidemiologic studies indicate that there is
a significant heritability component to CVD risk.  Risk reduction in populations
at higher risk could contribute substantially to improving the public's
cardiovascular health.

Diet has been associated with eight of the ten leading causes of death in the
United States. High saturated fat and high cholesterol diets increase total and
LDL-cholesterol, and high levels of dietary sodium increase blood pressure. 
Recommendations have been made for the nation to modify and improve dietary
intake, specifically to decrease dietary saturated fat, cholesterol, and sodium,
and to maintain optimal weight, in order to prevent premature morbidity and
mortality from CVD.  However, diets of youth of the United States are high in
saturated fat and sodium, and unhealthful dietary practices in childhood may
contribute to such practices in adulthood.  Focusing on dietary change in
children and adolescents may provide substantial benefit because some studies
suggest that dietary behaviors are established early.

Observational studies are needed to define behavioral and social determinants of
dietary practices. In addition, environmental factors, including those related
to culture and SES, that influence children's and adolescents' diets in the
United States need to be identified.  The evidence provided by these
observational studies can then be applied to development of relevant

Although both population-wide (including environmental) and individual-level
interventions have shown promise, additional work is necessary to develop highly
effective interventions for long-term adherence to dietary changes.  The
effectiveness of differing approaches at differing ages and with different
population groups, e.g., by SES or race/ethnicity, requires additional research. 
Two areas of opportunity for additional research are the school and the community
because few population-wide and community interventions have been tested that
have focused solely on diet. For both population-wide and individual-level
interventions, nutritional adequacy of the children and adolescents should be
ensured and assessed.  For example, interventions that promote increased
consumption of processed reduced-fat foods, or other shifts in types of foods,
should assess nutritional adequacy (e.g., zinc, calcium, iron, and calories).

Studies indicate that increased levels of homocysteine may play a role in the
development of coronary artery disease and that elevated levels of blood
homocysteine are related to deficient levels of vitamins B6, B12, and folate. 
The effects of vitamin supplementation and the relationship of diet and nutrition
on homocysteine levels in children and adolescents need to be determined.

Elevated blood pressure levels of children and adolescents predispose them to
hypertension as an adult.  Several micronutrients appear to be related to blood
pressure levels, including sodium, potassium, calcium, and magnesium.  Very
little research has been conducted on the effects of macronutrients on blood
pressure in children and adolescents, although macronutrients have been
implicated as having effects on blood pressure in adults.  Additional research
needs to be conducted to determine effects on blood pressure of micronutrients
obtained in foods and by supplements, of macronutrients, and of whole dietary

Insufficient fetal growth and low birth weight have been hypothesized to be
related to a child's later risk factors for CVD.  Additional observational and
intervention research is needed to define further these associations and to
determine if a causal relationship exists.

In order to assess the effects of interventions, self-report approaches to
measuring dietary intake are often used, yet these may be biased if used in a
study where participants are not blinded to their treatment assignment.  Further
development and validation of self-report methods for dietary assessment for use
in intervention studies is needed.  Biomarkers of nutrient intake and dietary
adherence could be used, e.g., blood or urine measurements, yet there is a
paucity of these biomarkers.  More research is needed to define long-term markers
as well as short-term markers of dietary intake.  Short-term markers are
particularly useful for intervention studies.  Currently used markers include
blood cholesterol to assess consumption of saturated fats, and serum carotenoids
and red blood cell folate to assess consumption of fruits and vegetables. 
However, these markers are not precise enough for assessment at the individual

Development of interventions often require modification of existing behavioral
theories or development of new theories.  Additional development and testing of
new behavioral theories, specifically as applicable to children and adolescents,
are needed.

Objectives and Scope

The applying investigator must identify the research question to be addressed,
which must be related to the four types of studies identified under PURPOSE,
above, to be considered a response to this PA.  The investigator must provide a
clear rationale for the importance of the research question and for selection of
the target population to be studied.  (See also REVIEW CONSIDERATIONS, below).

Examples of topics for each type of study that would be responsive to this PA are
provided below.  Applications can address, but are not limited to, these
examples.  Children and/or adolescents must be the targeted population.

1. observational studies identifying determinants of nutrient intakes and
determinants of dietary effects on CVD risk factors; examples include:

o The identification of behavioral, social, economic, cultural, and environmental
determinants of children's dietary fat intake in population groups at high risk
of developing CVD as adults (e.g., minorities, low SES).

o The identification of behavioral, social, economic, cultural, and environmental
determinants of dietary sodium intake in African-American adolescents, who are
at high risk of developing hypertension.

o Identification of genetic factors that may modify the effects of diet on blood
cholesterol levels, blood pressure levels, and body fat.

o Elucidation of the relationships between maternal nutrition and levels of blood
pressure, blood cholesterol, and obesity (or body size and composition) in

2. intervention studies examining the effects on diet and CVD risk factors of
approaches to improve dietary behavior to meet current dietary recommendations;
examples include:

o The development and testing of behavioral interventions to change high-fat and
high-sodium dietary behaviors in high-risk minority populations (for example,
African-Americans, Hispanics) and in low SES groups.

o The development and testing of unique interventions utilizing modern technology
in various settings for reaching children and adolescents (e.g., the Internet,
computer-delivered programs).

o The development and testing of environmental-change interventions (such as
availability of foods in the school setting, modification of fast-food restaurant
offerings in the community) on the consumption of dietary fat and sodium.

o The effects of fat-modified foods on adherence to lower-fat/sodium diets,
including assessment of adequacy of individuals' nutritional status.

o The effectiveness of behavioral interventions in individuals with high risk
versus those with average risk (e.g., by informing participants of their risk
status or genetic predisposition).

3. intervention studies examining the true magnitude of effects on CVD risk
factors of dietary or nutrient changes under conditions of high adherence;
examples include:

o The effect of supplements of vitamins B6, B12, and folate on blood homocysteine

o The effects of micronutrient supplements on blood pressure levels.

o The effects of dietary macronutrients on blood pressure levels.

o The effects of various whole dietary patterns on blood pressure and blood
cholesterol levels.

o The effects of dietary nutrients or patterns on individuals with different
genetic polymorphisms or gene frequencies that are potentially related to blood
pressure, lipid profiles, adiposity, obesity, or other risk factors.

4. Studies directed toward advancing measurement methodologies or behavioral
theories which could then be applied to intervention studies; examples include:

o The refinement of self-report methods for measuring dietary intake and

o The development and testing of biomarkers, e.g., in blood or urine, to provide
more objective assessments of dietary intake.

o The development or refinement of behavioral theory as relates to prediction of
dietary behaviors.


It is the policy of the NIH that women and members of minority groups and their
subpopulations must be included in all NIH supported biomedical and behavioral
research projects involving human subjects, unless a clear and compelling
rationale and justification is provided that inclusion is inappropriate with
respect to the health of the subjects or the purpose of the research.  This
policy results from the NIH Revitalization Act of 1993 (Section 492B of Public
Law 103-43).

All investigators proposing research involving human subjects should read the
"NIH Guidelines For Inclusion of Women and Minorities as Subjects in Clinical
Research," which have been published in the Federal Register of March 28, 1994
(FR 59 14508-14513) and in the NIH Guide for Grants and Contracts, Volume 23,
Number 11, March 18, 1994. Investigators may obtain copies of the policy from the
program staff listed under INQUIRIES.  Program staff may also provide additional
relevant information concerning the policy.


Applications are to be submitted on grant application form PHS 398 (rev. 5/95)
and will be accepted at the standard application deadlines as indicated in the
application kit.  Application kits are available at most institutional offices
of sponsored research and may be obtained from the Division of Extramural
Outreach and Information Resources, National Institutes of Health, 6701 Rockledge
Drive, MSC 7910, Bethesda, MD 20892-7910, telephone 301/710-0267, email: The title and number of the program announcement must be typed
in Section 2 on the face page of the application.

The complete original application and five legible copies must be sent or
delivered to:

6701 ROCKLEDGE DRIVE, ROOM 1040 - MSC 7710
BETHESDA, MD  20892-7710
BETHESDA, MD  20817 (for express/courier service)


Applications will be assigned on the basis of established PHS referral
guidelines.  Applications that are complete will be evaluated for scientific and
technical merit by an appropriate peer review group convened in accordance with
the standard NIH peer review procedures.  As part of the initial merit review,
all applications will receive a written critique.  Applications will also undergo
a process in which only those deemed to have the highest scientific merit,
generally the top half of applications under review, will be discussed, assigned
a priority score, and receive a second level review by the appropriate national
advisory council or board, when applicable.

The goals of NIH-supported research are to advance our understanding of
biological systems, improve the control of disease, and enhance health.  In the
written review, comments on the following aspects of the application will be made
in order to judge the likelihood that the proposed research will have a
substantial impact on the pursuit of these goals.  Each of these criteria will
be addressed and considered in the assignment of the overall score:

1. Significance
Does this study address an important problem?  If the aims of the application are
achieved, how will scientific knowledge be advanced?  What will be the effect of
these studies on the concepts or methods that drive this field?

2. Approach
Is the conceptual framework, design, methods, and analyses adequately developed,
well integrated, and appropriate to the aims of the project?  Does the applicant
acknowledge potential problem areas and consider alternative tactics?

3. Innovation
Does the project employ novel concepts, approaches or methods?  Are the aims
original and innovative?  Does the project challenge existing paradigms or
develop new methodologies or technologies?

4. Investigator
Is the investigator appropriately trained and well suited to carry out this work? 
Is the work proposed appropriate to the experience level of the principal
investigator and other researchers (if any)?

5. Environment
Does the scientific environment in which the work will be done contribute to the
probability of success?  Do the proposed experiments take advantage of unique
features of the scientific environment or employ useful collaborative
arrangements?  Is there evidence of institutional support?

In addition, the adequacy of plans to include both genders and minorities and
their subgroups as appropriate for the scientific goals of the research will be
reviewed.  Plans for the recruitment and retention of subjects will also be

The initial review group will also examine the provisions for the protection of
human and animal subjects, the safety of the research environment, and
conformance with the NIH Guidelines for the Inclusion of Women and Minorities as
Subjects in Clinical Research.


Applications will compete for available funds with all other recommended
applications assigned to that Institute.  The following will be considered in
making funding decisions: quality of the proposed project as determined by peer
review, availability of funds, and program priority.


Inquiries are encouraged.  We welcome the opportunity to clarify any issues or
questions from potential applicants.

Direct inquiries regarding scientific and programmatic issues to:

Hilary D. Sigmon, PhD, RN
Division of Extramural Activities
National Institute of Nursing Research
Building 45, Room 3AN-12
Bethesda, MD 20892-6300
Telephone:  (301) 594-5970
FAX:  (301) 480-8260

Marguerite Evans, M.S., R.D.
Division of Epidemiology and Clinical Applications
National Heart, Lung, and Blood Institute
6701 Rockledge Drive, Room 8126
Bethesda, MD  20892-7936
Telephone:  (301) 435-0380
FAX:  (301) 480-1669/1773

Direct inquiries regarding fiscal matters to:

Jeff Carow
Grants Management Officer
National Institute of Nursing Research
Building 45, Room 3AN-12, MSC 6301
Bethesda, MD  20892-6301
Telephone:  (301) 594-6869
FAX:  (301) 480-8260

Marie Willett
Grants Management Section
National Heart, Lung, and Blood Institute
6701 Rockledge Drive, Room 7156, MSC 7926
Bethesda, MD  20892-7926
Telephone:  (301) 435-0144
FAX:  (301) 480-3310


This program is described in the Catalog of Federal Domestic Assistance No.
93.361.  Awards are made under authorization of the Public Health Service Act,
Title IV, Part A (Public Law 78-410, as amended by Public Law 99-158, 42 USC 241
and 285) and administered under PHS grants policies and Federal Regulations 42
CFR 52 and 45 CFR Part 74.  This program is not subject to the intergovernmental
review requirements of Executive Order 12372 or Health Systems Agency review.

The PHS strongly encourages all grant and contract recipients to provide a smoke-
free workplace and promote the non-use of all tobacco products.  In addition,
Public Law 103-227, the Pro-Children Act of 1994, prohibits smoking in certain
facilities (or in some cases, any portion of a facility) in which regular or
routine education, library, day care, health care or early childhood development
services are provided to children.  This is consistent with the PHS mission to
protect and advance the physical and mental health of the American people.

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