Full Text PA-97-018
NIH GUIDE, Volume 25, Number 44, December 20, 1996
PA NUMBER:  PA-97-018
P.T. 34

  Cardiovascular Diseases 

National Institute on Aging
National Heart, Lung, and Blood Institute
National Institute of Nursing Research
The goal of this program announcement (PA) is to foster research that
will enhance our understanding of age-associated changes in the
cardiovascular system and, moreover, how these normal changes
increase susceptibility to cardiovascular disease.  The PA documents
eight areas of research opportunities highlighted by the National
Institute on Aging (NIA) Cardiovascular Aging Advisory Panel.
Another goal of this PA is to promote cardiovascular health during
the aging process.  The National Institute on Aging (NIA), National
Heart, Lung, and Blood Institute (NHLBI), and the National Institute
of Nursing Research (NINR) encourage submission of
investigator-initiated research project grant (R01) and First
Independent Research Support and Transition (FIRST) (R29) award
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 PA,
Cardiovascular Aging Research, is related to the priority area of
heart disease and stroke.  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).
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.
Awards under this program to foreign institutions will be made only
for studies of very unusual scientific merit, need, and opportunity.
Foreign institutions are not eligible for First Independent Research
Support and Transition (FIRST) (R29) awards.
Applicants from institutions that have a General Clinical Research
Center (GCRC) funded by the NIH National Center for Research
Resources may wish to identify the GCRC as a resource for conducting
the proposed research.  If so, a letter of agreement from either the
GCRC Program Director or Principal Investigator should be included
with the application.
This program will use the traditional NIH investigator-initiated
research project grant (R01) and FIRST (R29) award mechanisms.
Investigators interested in career development (K-series) in the
cardiovascular aging field are encouraged to respond to NIA's
Mentored Research Scientist Development Award in Aging program.  This
program was announced in the NIH Guide for Grants and Contracts, Vol.
25, No. 12, April 19, 1996.  The Nursing Mentored Research Scientist
Development Award (K01) was published in the NIH Guide for Grants and
Contracts, Vol. 24, No. 2, June 16, 1995.  Investigators seeking
career development in the area of nursing and cardiovascular aging
research are encouraged to respond to this mechanism.
The total project period for an application submitted in response to
this solicitation may not exceed five years.  Because the nature and
scope of the research proposed may vary, it is anticipated that the
size of awards will vary as well.  An investigator planning to submit
an application requesting $500,000 or more in direct costs for any
year is advised that he or she must contact the Institute program
staff listed under INQUIRIES before submitting the application, i.e.,
as plans for the research are being developed, to obtain agreement
from program staff that the Institute or Center will accept the
application for consideration of award.  An application of such a
size received without indication of prior staff concurrence and
identification of that contact will be returned to the applicant
without review.  Investigators planning to request $500,000 or more
in direct costs are referred to the policy update notice in the NIH
Guide for Grants and Contracts, Volume 25, Number 14, May 3, 1996.
Applicants proposing human intervention studies are referred to the
NIA policy notice in the NIH Guide for Grants and Contracts, Volume
25, Number 33, October 4, 1996.  This program will not support large,
multi-center, clinical trials.  Awards will be administered under PHS
grants policy as stated in the Public Health Service Grants Policy
Statement, DHHS Publication No. (OASH) 94-50,000 (rev. 4/1/94).
Age is a major risk factor for cardiovascular disease.  Deaths from
cardiovascular disease rise significantly with advancing age as does
the number of older individuals suffering from this disease.
Cardiovascular disease remains a main cause of disability and the
leading cause of death of older Americans, killing approximately 50
percent of individuals 65 years of age or older.  Disability due to
cardiovascular disease limits the activity and significantly erodes
the quality of life of millions of older Americans each year.
It is estimated that there are 33 million people in the United States
(about 13 percent of the total population) 65 years of age or older.
Individuals aged 85 and older, known as the "oldest old," are the
fastest growing segment of the older population.  According to the
Bureau of the Census, by the year 2030, there will be approximately
70 million people in the United States over 65 years of age (about 20
percent of the total population).  The increasing number of older
persons may lead to increased susceptibility to age-associated
cardiovascular disease (e.g., atrial fibrillation and congestive
heart failure) and its related morbidity, infirmity, and dependency.
New research may hold promise in addressing this upcoming burden.
Although age is a major risk factor for cardiovascular disease, the
reasons remain to be determined.  To better appreciate the link
between aging and development of disease, we need to better
understand normal aging, i.e., aging in the absence of disease, and
also how aging increases cardiovascular morbidity.  Age-associated
changes in cardiac function, circulatory hemodynamics, blood pressure
regulation, and lipid metabolism all contribute to the development of
cardiovascular disease in older persons.  Ongoing research supported
by the NIA is defining important age-related changes in the
cardiovascular system.  Yet, to ensure continued success and
productivity in this important area, new research is needed to
expand, and to integrate, the wealth of knowledge already accumulated
at the basic and systems physiology levels.
To address this issue, a scientific panel composed of non-federal
scientists was recently convened by the Geriatrics Program, NIA. The
panel's charge was to identify promising new areas for research
opportunities in the cardiovascular aging field.  The following eight
research areas highlighted by the NIA Cardiovascular Aging Advisory
Panel are neither prioritized nor meant to be restrictive. They
represent a synthesis of ideas generated by the panel and later
augmented by NIA staff.  A more detailed description of the research
recommendations has been published in the September 1996 issue (Vol.
44, No. 9, pp.1114-1117) of the Journal of the American Geriatrics
Society.  Potential applicants are encouraged to read the article:
"Report from the NIA.  Research Recommendations for Cardiovascular
Aging Research."
Recommendation 1.  Foster clinically related research, focused on an
integrative approach, in continuing to define important
age-associated changes in the cardiovascular system and how these
normal changes may contribute to cardiovascular morbidity.  The goal
is to stimulate new research that incorporates the advances made in
cellular, structural, and molecular biology in the study of function
in whole animals and humans.  Fostering integrative biomedical
research, by using the tools of molecular biology for the study of
function, will lead to a better understanding of human health, aging
processes, and susceptibility to cardiovascular disease.
Recommendation 2.  Expand research on cardiovascular-renal
interactions in aging including the importance of gender and racial
differences; changes in arterial blood pressure control and fluid and
electrolyte balance; neurohumoral influences (e.g., changes in renal
responsiveness to aldosterone and vasopressin); autonomic function
and reflex mechanisms; and drug metabolism and clearance.  An
additional area includes the role of the aging kidney in
age-associated cardiovascular diseases including hypertension,
coronary heart disease, and congestive heart failure.  This systems
physiology approach to aging research is not restricted to
cardiovascular-renal interactions and may include other relevant
Recommendation 3.  Develop new methodologies to measure blood vessel
wall stiffening and support new studies which will enhance our
understanding of vascular stiffening in aging and its link (if any)
in promoting atherosclerosis.  Once thought to be a part of normal
aging without consequence, stiffening of the large elastic arteries,
such as the aorta, may lead to increased susceptibility to
cardiovascular disease.  The NIA has released a program announcement
on "Aging, Vascular Stiffness, and Cardiovascular Function" in the
NIH Guide for Grants and Contracts, Vol. 24, No. 24, June 30, 1995.
Applicants interested in this area of research should respond to the
June 1995 NIH Guide announcement.
Recommendation 4.  Examine the effects of aging on cardiac diastolic
function including the relationship between systolic and diastolic
function; e.g., adaptation, remodeling, and/or dysfunction during
aging.  Studies are needed to better understand diastolic performance
in aging, including defining an easily measured and reproducible
marker for diastolic dysfunction.  This area of research is important
because about 40 percent of older heart failure patients have
diastolic dysfunction (with normal systolic function) as the etiology
of their condition.  Research on the importance of age-associated
changes in the atria (e.g., development of fibrosis) in increasing
susceptibility to atrial fibrillation, and stroke, is also needed.
Recommendation 5.  Studies are needed to examine the importance of
gender differences in the aging cardiovascular system.  Examples
include the effects of sex steroids on the structure and function of
the aging heart and blood vessels, regulation of lipoprotein
metabolism, and body composition.  Research on gender differences in
renin-angiotensin-aldosterone reactivity and drug
metabolism/clearance are needed.  Research is also needed on
ascertaining the mechanisms of action for estrogen-mediated
cardioprotection in older, postmenopausal, women.  This area is
important because one in five women over 65 years of age has some
form of heart disease.
Recommendation 6.  Examine the role of social and behavioral factors
in promoting cardiovascular health.  This includes the development of
new approaches to enhance participation of older persons in exercise
programs, or other forms of physical activity, as a means to foster
health promotion and disease prevention.  The importance of physical
activity was the topic of discussion at the recent NIH Consensus
Development Conference on "Physical Activity and Cardiovascular
Health."  Potential applicants are encouraged to read the NIH
Consensus Statement in The Journal of the American Medical
Association 276(3): 241-246, 1996. Investigators interested in this
area of research are referred to NIA's program announcement on
"Psychosocial Geriatrics Research: Health Behaviors and Aging," NIH
Guide for Grants and Contracts, Volume 22, Number 11, March 19, 1993.
Recommendation 7.  Support research on the clinical pharmacology of
cardiovascular drugs in older individuals, including pharmacodynamic
and pharmacokinetic studies.  Cardiovascular drugs comprise one of
the most widely prescribed classes of medications in older persons.
Yet, few studies focus on the special needs of older individuals
(including gender and racial differences in drug action) and also may
not take into account important age-associated physiologic changes
that may alter drug absorption, distribution, metabolism, and
clearance.  Development of new drugs to treat age-associated
cardiovascular disorders would benefit from more basic clinical
Recommendation 8.  Develop appropriate large animal models for
clinically related cardiovascular aging research (in vivo) which
mimic human age-related changes and conditions. Well defined large
animal models are needed which both mimic the human condition and
clearly separate the study of normal aging from disease development
in old age.  Model development for the study of diastolic dysfunction
is a continuing need.  Development of transgenic large animal models
for the study of cardiovascular function in old age is an attractive
Expanding research in the cardiovascular aging field will
significantly augment our understanding of human health, aging
processes, and susceptibility to cardiovascular disease.  This new
understanding will lead to the development of interventions to
prevent and/or treat age-associated cardiovascular disease.  The
potential public health benefit, in terms of both health care cost
savings and improving the quality of life of older persons, i.e.,
adding "life" to years, may be considerable.
NIA, NHLBI, and NINR encourage submission of investigator-initiated
research on the topics listed and also on any other relevant
cardiovascular aging issues that are responsive to the general
research objectives of this program.
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 new policy results
from the NIH Revitalization Act of 1993 (Section 492B of Public Law
103-43) and supersedes and strengthens the previous policies
(Concerning the Inclusion of Women in Study Populations, and
Concerning the Inclusion of Minorities in Study Populations), which
have been in effect since 1990.  The new policy contains some
provisions that are substantially different from the 1990 policies.
All investigators proposing research involving human subjects should
read the "NIH Guidelines for Inclusion of Women and Minorities as
Subjects in Clinical Research," which has been published in the
Federal Register of March 28, 1994 (FR 59 14508-14513) and reprinted
in the NIH Guide for Grants and Contracts, Volume 23, Number 11,
March 18, 1994.
Investigators also may obtain copies of the policy from the program
staff listed under INQUIRIES.  Program staff may also provide
additional relevant information concerning the policy.
The research grant application form PHS 398 (rev. 5/95) is to be used
in applying for these grants.  These forms are available at most
institutional offices of sponsored research and from the Office of
Extramural Outreach and Information Resources, National Institutes of
Health, 6701 Rockledge Drive, MSC 7910, Bethesda, MD 20892-7910,
telephone (301) 435-0714, FAX (301) 480-0525, Email:
Applications for the FIRST (R29) award must include at least three
sealed letters of reference attached to the face page of the original
application.  FIRST (R29) award applications submitted without the
required number reference letters will be considered incomplete and
will be returned without review.  FIRST (R29) award applications must
also be prepared according to the requirements of Just-In-Time
procedures, as announced in the NIH Guide for Grants and Contracts,
Vol. 25, No. 10, March 29, 1996.  There may be a significant delay in
the processing and review of a FIRST (R29) award application that has
not been prepared according to the instructions in the NIH Guide
notice.  In addition, for all applications, the title and number of
the PA must be typed on line 2 of the face page of the application
form and the YES box must be marked.
The completed 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  20817-7710 (for express/courier service)
Applications will be assigned on the basis of established Public
Health Service 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 and undergo
a process in which only those applications 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.
Review Criteria
o  Scientific, technical, or medical significance and originality of
the proposed research;
o  Appropriateness and adequacy of the experimental approach and
methodology proposed to carry out the research;
o  Qualifications and research experience of the Principal
Investigator and staff, particularly, but not exclusively, in the
area of the proposed research;
o  Availability of the resources necessary to perform the research;
o  Appropriateness of the proposed budget and duration in relation to
the proposed research;
o  Adequacy of the provisions for the protection of human and animal
subjects and safety of the research environment; and
o  Adequacy of plans to include both genders and minorities and their
subgroups as appropriate for the scientific goals of the research.
Plans for the recruitment and retention of subjects will also be
Scored applications will compete for available funds with all other
scored applications assigned to an Institute or Center.  The
following will be considered in making funding decisions: Quality of
the proposed project as determined by peer review; Availability of
funds; and Program balance among research areas of the program
Written and telephone inquiries are encouraged.  The opportunity to
clarify any issues or questions from potential applicants is welcome.
Direct inquiries regarding programmatic issues to:
Dr. Andre J. Premen
Geriatrics Program
National Institute on Aging
7201 Wisconsin Avenue, Suite 3E327, MSC 9205
Bethesda, MD  20892-9205
Telephone:  (301) 496-6761
FAX:  (301) 402-1784
Dr. David Robinson
Division of Heart and Vascular Diseases
National Heart, Lung, and Blood Institute
6701 Rockledge Drive, Suite 10193, MSC 7956
Bethesda, MD  20892-7956
Telephone:  (301) 435-0545
FAX:  (301) 480-2849
Dr. Hilary D. Sigmon
Program Science Administrator
National Institute of Nursing Research
Building 45, Room 3AN-12
Bethesda, MD  20892-6300
Telephone:  (301) 594-5970
FAX:  (301) 480-8260
Direct inquires regarding fiscal matters to:
Mr. Joseph Ellis
Grants and Contracts Management Office
National Institute on Aging
7201 Wisconsin Avenue, Suite 2N212, MSC 9205
Bethesda, MD  20892-9205
Telephone:  (301) 496-1472
FAX:  (301) 402-3672
Mr. William W. Darby
Grants Management Office
National Heart, Lung, and Blood Institute
6701 Rockledge Drive, Room 7128, MSC 7926
Bethesda, MD  20892-7926
Telephone:  (301) 435-0177
FAX:  (301) 480-3310
Mr. Jeff Carow
Grants Management Office
National Institute of Nursing Research
Building 45, Room 3AN-18
Bethesda, MD  20892-6300
Telephone:  (301) 594-6869
FAX:  (301) 480-8256
This program is described in the Catalog of Federal Domestic
Assistance Nos. 93.866, 93.837, and 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, 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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