NIH GUIDE, Volume 21, Number 36, October 9, 1992

RFA:  HL-92-11-P

P.T. 34




  Clinical Trial 

National Heart, Lung, and Blood Institute

Letter of Intent Receipt Date:  December 1, 1992

Application Receipt Date:  January 15, 1993

This is to announce a change in the Letter of Intent Receipt Date and

the Application Receipt Date that published in the NIH Guide for

Grants and Contracts, Vol. 21, No. 34, September 25, 1992.

The new Letter of Intent Receipt Date is December 1, 1992 (changed

from November 1, 1992).

The new Application Receipt Date is January 15, 1993 (changed from

December 1, 1992).


Full Text HL-92-11-P


NIH GUIDE, Volume 21, Number 34, September 25, 1992

RFA:  HL-92-11-P

P.T. 34

  Clinical Trial 

National Heart, Lung, and Blood Institute

Letter of Intent Receipt Date:  November 1, 1992
Application Receipt Date:  December 1, 1992


The Division of Epidemiology and Clinical Applications (DECA) invites
cooperative agreement applications for an estimated four Field Centers
and one Coordinating Center to participate, with the assistance of the
National Heart, Lung, and Blood Institute (NHLBI), in a collaborative
multicenter study on dietary patterns and blood pressure.  The overall
objective is to test the effect on blood pressure of dietary patterns
in comparison to a usual American diet.  Because a large number of
investigations have shown that diet is related to blood pressure,
constructing dietary patterns that would ensure (1) high consumption of
nutrients associated with lower blood pressure and (2) low consumption
of nutrients associated with higher blood pressure would provide a
feasible health-promoting intervention for the general public,
including minorities.  Toward this end, the study population will
include approximately two-thirds minorities.  The request for
applications is for an efficacy study of dietary patterns by means of
a randomized, controlled human feeding trial.  The duration of the
grant period would be three years six months for the Field Centers and
four years for the Coordinating Center.  The planning phase prior to
implementation will include collaboratively establishing the
cooperative organizational structure, and collaboratively agreeing upon
the study design and protocol.


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 RFA,
Dietary Patterns and Blood Pressure, is related to the priority areas
of heart disease and stroke, and nutrition.  Potential applicants may
obtain a copy of "Healthy People 2000" (Full Report:  Stock No.
017-001-00474-0) or "Healthy People 2000" (Summary Report:  Stock No.
017-001-00473-1) through the Superintendent of Documents, Government
Printing Office, Washington, DC 20402-9325 (telephone 202-783-3238).


Applications may be submitted by 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.  Foreign organizations are
not eligible to apply and domestic applications may not include
international components.  Applications from minority individuals and
women are encouraged.

Awards for Field Centers and a Coordinating Center under this RFA will
not be made to the same Principal Investigator (PI) to ensure that data
analysis is done independently of data acquisition.  The same
institution may apply for both a Field Center and a Coordinating Center
award, but the applications for each must be separate.

Disciplines and Expertise

For Field Centers this RFA may be of interest to researchers with
expertise in the areas of hypertension, nutrition, dietetics, food
chemistry, cardiovascular epidemiology, preventive medicine, and
internal medicine.  Experience with multicenter collaborative studies
is desirable.  Experience with well-controlled human feeding studies
and access to a metabolic kitchen is essential.

For the Coordinating Center, this RFA may be of interest to researchers
with expertise in the area of biostatistics, nutrition, food chemistry,
and hypertension.  Investigators should have experience in clinical
trial study design, study coordination, data transfer and management,
quality control procedures, and data analysis.  Experience with
multicenter collaborative studies is essential.


The administrative and funding mechanism to be used to undertake this
program will be a cooperative agreement (U01), an assistance mechanism.
Under the cooperative agreement, the NIH assists, supports, and/or
stimulates and is substantially involved with recipients in conducting
a study by facilitating performance of the effort in a "partner" role.
Details of the responsibilities, relationships, and governance of a
study funded under a cooperative agreement are discussed later in this
document under the section entitled TERMS AND CONDITIONS OF AWARD.


An estimated four awards for Field Centers and one award for a
Coordinating Center will be made under this RFA.  A maximum of $6.9
million (including direct and indirect costs) over a four-year period
will be awarded for Field Centers and the Coordinating Center with at
least two-thirds apportioned to the Field Centers.  Approximately $1.65
million will be available for the first year, $2.55 million for the
second year, $1.90 million for the third year, and $0.8 million for the
last year.  This will be allocated among the four Field Centers and the
Coordinating Center.

Awards and level of support are dependent on the receipt of a
sufficient number of applications of high scientific merit. Although
this program is provided for in the financial plans of the NHLBI,
awards pursuant to this RFA are contingent upon the availability of
funds for this purpose.

At this time the NHLBI has no plans for re-issuing this RFA. However,
at the end of the project period of up to three years, six months for
Field Centers and up to four years for the Coordinating Center, the
awardees may submit grant applications through the usual
investigator-initiated grants program.



The strong relationship between diet and blood pressure and the risk of
hypertension was described in detail in Diet and Health (National
Research Council, 1989), a comprehensive review of epidemiologic,
clinical, and laboratory research prepared by the Committee on Diet and
Health of the National Research Council.  Currently only three specific
diet-related factors have been recommended by the Joint National
Committee on High Blood Pressure as a first-line approach in treating
mild hypertension:  caloric restriction for weight reduction, reduced
consumption of alcohol, and lower sodium intake.  Many studies,
primarily observational, have shown significant associations between
blood pressure and diet-related factors other than weight, alcohol, and
sodium.  These include micronutrients such as potassium, calcium, and
magnesium; macronutrients such as type and amount of dietary fats,
particularly polyunsaturated, and protein; and dietary fiber. However,
the results from randomized controlled clinical trials testing these
effects have been inconsistent and equivocal.  On the other hand, the
effect on blood pressure of the vegetarian dietary pattern has been
consistent, based on results from both observation studies and
randomized intervention studies.  This is part of the basis for further
testing the role of dietary patterns in reducing blood pressure.

Vegetarian Diet:  Observational and cross-cultural studies of
vegetarian diets have consistently shown a significant inverse
relationship with blood pressure, even when the effects of weight and
alcohol have been taken into account (Sacks et al., 1974; Sacks and
Kass, 1988; Armstrong et al., 1977; Rouse et al., 1983; Rouse and
Beilin, 1984; Beilin and Margetts, 1987). The results of randomized
controlled clinical trials in normotensives (Rouse et al., 1983) and
mild hypertensives (Margetts et al., 1986) testing the effect of a
vegetarian diet in meat eaters showed decreases in systolic blood
pressure (significant in both studies) and diastolic blood pressure
(significant in only the normotensive study).  The results of these
studies provided support for the blood pressure-lowering effect of a
vegetarian diet and suggest that the vegetarian diet, and not other
unidentified non- dietary factors common to vegetarians, accounts for
the observed decrease in blood pressure.

To determine which specific dietary component may account for the blood
pressure-lowering effect produced by vegetarian diets, numerous studies
have examined individual nutrients and diet-related factors.

Micro-nutrients and Fiber:  The large majority of cross- cultural and
observational studies (National Research Council, 1989) have shown a
significant inverse association between blood pressure and potassium or
sodium/potassium ratio, including the INTERSALT study, the largest
cross-cultural epidemiologic study performed to date (INTERSALT
Cooperative Research Group, 1988).  On the other hand, only a few,
primarily small, short-term clinical trials found potassium supplements
to lower blood pressure.  From a pooled estimate based on a
meta-analysis of 19 trials, potassium was found to significantly lower
SBP by 6.2 mm Hg and DBP by 3.7 mm Hg (Cappuccio and MacGregor, 1991).
However, evidence was least convincing in the larger trials and in
trials that have employed random assignment and blinding of blood
pressure observers (Whelton et al., 1989).  For example, Phase 1 of the
Trials of Hypertension Prevention (TOHP 1) was the largest randomized
trial to date testing a variety of nonpharmacologic interventions, and
data collectors were blinded.  The potassium supplement arm of TOHP 1,
which was of 6 months' duration, failed to detect a significant
lowering of systolic blood pressure (TOHP Collaborative Research Group,

Similarly, calcium intake has been reported to be significantly and
inversely related to blood pressure by a majority of observational
studies (Ackley et al., 1983; McCarron et al., 1984; Garcia-Palmieri et
al., 1984; Kok et al., 1986).  However, a meta-analysis of 19
randomized controlled trials of calcium supplementation yielded
estimates of a small (1.8 mm Hg) significant reduction in systolic, but
no effect on diastolic, blood pressure (Cutler and Brittain, 1990).
The results from TOHP 1 failed to show that calcium supplements lowered
blood pressure (TOHP Collaborative Research Group, 1992).

Dietary intake of magnesium has been inversely related to the incidence
of hypertension (Witteman et al., 1989) and to blood pressure (Joffres
et al., 1987) in some studies, but not others (Harlan et al., 1984).
Results from four small randomized intervention trials reviewed by
Whelton and Klag (1989) as well as results from a recently reported
study (Lind et al., 1991) have not shown a significant reduction in
blood pressure, although the 95 percent confidence intervals were wide
in these studies.  Results from TOHP 1 also did not demonstrate a
reduction in blood pressure by magnesium supplements (TOHP
Collaborative Research Group, 1992).

The epidemiologic evidence linking fiber to blood pressure comes
primarily from studies on vegetarian and other high fiber diets (Sacks
et al., 1974; Sacks and Kass, 1988; Armstrong, 1977; Rouse et al.,
1982).  In general, intervention studies have not demonstrated that
fiber supplementation significantly lowers blood pressure compared to
controls (Brussard et al., 1981; Fehily et al., 1986; Margetts et al,
1987; Schlamowitz et al., 1987; Rossner et al., 1988; Swain et al.,

Mechanisms have been proposed for the role of micronutrients that would
show plausible reasons why they should influence blood pressure.  As an
electrolyte, potassium has an effect on regulation of body fluid
volumes.  It may lower blood pressure through decreasing renin
secretion and increasing urinary sodium excretion.  Potassium also
appears to have a protective effect against endothelial cell damage.
The mechanism by which dietary calcium may act to inversely affect
blood pressure is unclear.  Calcium ions are known to have a prominent
role in the contraction of vascular smooth muscle cells and at higher
concentrations are involved in the relaxation of vascular smooth muscle
cells.  Magnesium has been linked to blood pressure through its
inhibitory effect on smooth muscle cell contractility and therefore as
a vasodilator.  Low levels of magnesium may enhance calcium influx
resulting in increased contractility of smooth muscle. The mechanistic
role for fiber in relation to blood pressure has been mostly
speculative.  The effects of fiber on gastric emptying time, on
absorption rate of nutrients, and on insulin and glucagon (Anderson,
1983) have been proposed as possible mechanisms as to how fiber may
lower blood pressure.

Macronutrients--Dietary Fats and Protein:  A recent review on the
relationship between dietary fats and blood pressure reported that
although cross-cultural comparisons have shown a significant
relationship with saturated fat, in general most observational studies
have not demonstrated a relationship between dietary fat and blood
pressure (Sacks, 1989).  A few small intervention studies have reported
significant reductions in BP from changes in fat intake, but it was not
always clear whether the decrease was significantly different from that
of controls (Rao et al., 1981; Puska et al., 1983; Puska et al., 1985;
Heagerty et al., 1986).  In general, randomized intervention trials
have failed to show a significant effect of dietary fat, whether total
fat, or mainly saturated, monounsaturated, or polyunsaturated (Brussard
et al., 1981; Medical Research Council Research Committee, 1968;
Margetts et al., 1985; Sacks et al., 1987a; Sacks et al., 1987b;
Mensink et al., 1988).  Phase 1 of TOHP also did not find a significant
reduction in blood pressure from fish oil supplements (TOHP
Collaborative Research Group, 1992).  However, more recent data
analyses performed on the MRFIT data set have shown significant
associations with saturated fat, cholesterol, and the Keys score, a
measure that incorporates polyunsaturated and saturated fat and dietary
cholesterol (Stamler et al., 1992).  In these analyses the
polyunsaturated/saturated (P/S) ratio was also found to be inversely
associated with blood pressure.  The Diet and Health (1989) report
concluded that overall, a diet low in total fat with a high P/S ratio
may produce modest reductions in blood pressure (National Research
Council, 1989).

The relationship between protein and blood pressure has been
insufficiently studied. In animals, recent studies have intriguingly
shown that low protein diets increase blood pressure and stroke in
renal impaired or stroke-prone rats, while high protein diets are
protective (Wang et al., 1984; Hostetter et al., 1986).  In humans,
there has been little epidemiologic research assessing the relationship
between protein and blood pressure.  Sacks and Kass (1988) reported
that neither the low protein intake of vegetarians nor the high ratio
of vegetable to animal protein influences blood pressure.  However,
Kimura (1977) reported a higher stroke rate in farmers who had lower
protein intake and lower serum albumin levels than fishermen who had
higher protein intake and higher albumin levels.  Similarly, Kihara et
al. (1984) reported an inverse relationship between blood pressure and
urinary nitrogen to creatinine ratio.  Recently presented data analyses
on diet and blood pressure from MRFIT data (Stamler et al., 1992), and
pooled analyses from the INTERSALT study (Elliott et al., 1991) have
demonstrated statistically significant associations between dietary
protein (MRFIT) and urinary nitrogen (INTERSALT), a measure of protein
intake, with both systolic and diastolic blood pressure.  Thus, the
epidemiologic and animal evidence is suggestive of a favorably
influential role of protein on blood pressure.

Polyunsaturated fat may influence blood pressure by means of
prostaglandin synthesis.  Prostaglandins in the kidney and in vessel
walls play a role in regulating blood pressure, as they can increase
sodium excretion and induce peripheral vasodilation (Weinsier and
Norris, 1985).  Dietary protein, through its constituent amino acids,
may have a protective effect on blood pressure by serving as precursors
for neurotransmitters that are important for central nervous system
functioning, by impacting on small vessel wall structure and thus
influencing resistance, or by having a diuretic or natriuretic effect
through protein metabolites (Lovenberg and Yamori, 1985).

An overall summary of the literature suggests that there is still
strong potential for a number of macronutrients and micronutrients to
play an important role in reducing blood pressure.  Observational and
intervention studies with vegetarian diets, observational studies on
potassium, calcium, and magnesium, and recently reported analyses on
protein from the INTERSALT and MRFIT studies, have demonstrated
significant inverse associations with blood pressure.  Finally, recent
multiple regression analyses from MRFIT have shown that in addition to
lower body mass, alcohol, and sodium intakes, higher intakes of other
nutrients such as potassium, polyunsaturated fat, and protein, and
lower cholesterol intake and Keys score, were significantly associated
with lower blood pressure.

There are a number of reasons for specifying dietary patterns to be
tested rather than specific nutrients.

o  The long-term goal of any dietary study would be to provide
information on an overall healthful dietary pattern that would include
multiple nutrients that have been shown to be effective in lowering
blood pressure.

o  We do not yet know which nutrients might be most effective in
lowering blood pressure.  Specifying a dietary pattern would naturally
include several nutrients that cumulatively are likely to lower blood

o  As more agencies are recommending preventive diets for various
health reasons (heart disease, cancer, osteoporosis), it would be an
important contribution if dietary patterns that are consistent with
other health goals are also shown to reduce blood pressure.  Because of
the high prevalence of hypertension relative to other chronic diseases,
a dietary pattern that lowers blood pressure as well as improves
coronary heart disease risk could have the greatest impact on public

o  For reasons not yet entirely apparent, supplements may not affect
blood pressure to the same extent as do nutrients naturally occurring
in foods.  For example, the physiological effect of fiber can change
substantially depending on the degree of processing it has undergone.
The possibility that supplements are less effective than diet may
explain why observational studies of potassium and calcium, for
example, show an inverse association with blood pressure, whereas
intervention studies, where supplements are most commonly used,
generally do not show a decrease in blood pressure.  Thus, it may be
important to test nutrients as natural components of foods and not as
isolated or processed nutrients.

o  If there is interest in understanding which aspect of the dietary
pattern accounts for the blood pressure-lowering effect, future studies
can be designed to test those hypotheses and investigate the possible
mechanisms involved.

Objectives and Scope

This study will test the effect of dietary patterns on blood pressure
by means of a randomized controlled human feeding trial.  Several
features of this study are specified so that applicants have common
understanding of factors necessary for the collaborative effort, e.g.,
its magnitude, phases, and the handling of certain central functions.
Although some of the characteristics of the subjects and the
experimental interventions are specified, the specific design of the
study testing the effect of dietary patterns on blood pressure remains
in the hands of the investigators.  A number of possible components are
listed purely for illustrative purposes.

In order to accumulate sufficient sample size to test the effect of
dietary patterns on blood pressure, a collaborative effort will be
required by approximately four Field Centers and one Coordinating
Center.  In this collaborative effort participating institutions will
follow a uniform study protocol with standardized data collection

The collaborative protocol will be developed by the Steering Committee,
composed of the awardees and the NHLBI Project Scientist.  The protocol
will be subject to peer review by an uninvolved expert group.  The
study will proceed into its second (or implementation) phase only with
the concurrence of both the awardees and the NHLBI.

Study Design and Population

The study design will be a randomized, controlled clinical trial
testing the effect of dietary patterns on blood pressure.  The effects
on blood pressure of alcohol, sodium, and weight, or a vegetarian
dietary pattern per se are outside the scope of this RFA.

Within the resources allocated for this RFA, the number of treatment
arms in the study design will of necessity be limited.  It is
anticipated that at most four arms (three experimental arms and one
no-treatment control arm) can be supported in the common protocol.

To ensure good compliance with the experimental diets, food comprising
the dietary patterns will be provided to the participants.  Food may be
provided on an out-patient basis that participants remain free-living.

The study population is envisioned to be adults with high normal blood
pressure or with mild hypertension, in order to be more likely to
detect an effect, if present, than in those with completely normal
blood pressure.  Blood pressure inclusion criteria could be, for
example, 80-99 mm Hg for diastolic blood pressure, or 130-159 mm Hg for
systolic blood pressure.

The overall population to be studied should provide data that are
broadly applicable to diverse minority groups as well as whites; thus,
the composition of the study population in this RFA program should
reflect this diversity.  Because of the enormity of the problem of
hypertension in the African American population, at least one center
that will recruit predominantly (90 percent or more) African Americans
will be selected.  It is expected that the other three centers will
recruit over 50 percent minorities.

Applicants should discuss in their proposal the effect size that can
reasonably be expected from the dietary patterns they propose in a
population with high normal blood pressure or mild hypertension and the
sample size required to detect this effect size.  An example of
reasonable reductions in blood pressure that dietary patterns
(summarized below) might be expected to produce is approximately 3 mm
Hg for diastolic blood pressure, and 5 mm Hg for systolic blood
pressure.  In this example, for a four-arm trial, a total study sample
size of approximately 480 participants, with 120 per arm, is
anticipated to be sufficient to detect the existence of these decreases
at 90 percent power in a two-tailed test at an alpha level of .05.
These guidelines are for illustrative purposes only.

In selecting the length of the feeding period, applicants should
balance efficacy considerations with logistical and ethical issues.
The length should be sufficiently long to allow time for the
experimental diets to produce an effect, but not overly long for
reasons of cost, participant compliance, and the necessity of having a
no-treatment control group in participants with borderline high blood
pressure.  An example of a medium term feeding study is twelve weeks.

Because the number of subjects required to test the hypothesis is
likely to be larger than a typical Field Center can manage to feed at
one time, it is likely that several cohorts will be recruited to
accumulate sufficient sample size.  For example, in order to recruit a
total of 480 participants, each of four Field Centers would need to
recruit approximately 120 participants.  To accomplish this, each Field
Center could recruit a total of four cohorts (with randomization of
each among four treatment arms) during a two-year period by recruiting
two cohorts per year of approximately 30 each.

Applicants should include in their applications recruitment criteria
and variables to be measured, including variables that may affect
interpretation of the results because of their relation to blood
pressure and to diet.

Dietary Patterns

The specific dietary patterns to be tested must be proposed and
justified by the applicants.  For example, an overview of the
literature suggests that the macro- and micronutrients associated with
blood pressure can be broadly divided into two types of dietary
patterns according to their natural occurrence in foods:  (1) favorable
macronutrient profile, and (2) higher levels of micronutrients such as
that produced by a high fruit and vegetable dietary pattern.  A third
dietary pattern could, for example, combine elements of both (1) and

A dietary pattern modified in fat and protein that could be expected to
decrease blood pressure could include a diet lower in total fat and
saturated fat, higher in polyunsaturated fat, including omega-3 fatty
acids, and higher in protein, compared to the usual American diet.  The
aim could be, for example, a dietary pattern with the following
distribution of calories:  20 percent protein, 28 percent total fat, 8
percent saturated fat, 8 percent polyunsaturated (for a P/S ratio of
1:1 or higher) and 12 percent monounsaturated.  This dietary pattern is
similar to the National Cholesterol Education Program Step Two diet.
This distribution of macronutrients is presented for illustrative
purposes only and is not intended to imply that this is the dietary
pattern that must be tested.

A dietary pattern high in fruits and vegetables could be the logical
basis for a diet high in the micronutrients, including potassium,
magnesium, and calcium, that have been associated with lower blood
pressure.  This dietary pattern would also naturally be a diet high in

In constructing dietary patterns, special attention needs be paid to
ensure that the nutrient content of each dietary pattern is
sufficiently different from each other.  As an illustration, in the
examples given above, special attention would need to be paid to
calcium, as fruits and vegetables are not particularly rich sources of
calcium, to ensure that a high fruit and vegetable dietary pattern will
contain a higher content of calcium compared to a dietary pattern
modified in fat and protein, and compared to the usual American diet.

Applicants should include in their applications the nutrient
composition of the dietary patterns to be tested, the nutrient database
used to calculate such diets, and plans for verifying the nutrient
content of the dietary pattern through food composition chemical


The timetable for the study may be loosely subdivided into three phases
covering about a three and one-half to four-year period.  There may be
some overlap of functions within each of the phases, and the time
estimates are only approximations.  The purpose of the phases is to
provide broad guidelines of the total scope of work to be accomplished
for this RFA.

Phase I:    Planning and protocol development   6-9 months

Phase II:   Recruitment and implementation       24 months

Phase III:  Study closeout                      6-9 months
                                              (Field Centers)
                                                 12 months
                                         (Coordinating Center)

The first six to nine months of the study may be devoted to planning
and protocol development.  Possible objectives for the planning stage
are to establish eligibility criteria, develop recruitment strategies,
with particular attention paid to minorities, formulate and test
dietary patterns, develop a common protocol, select measurements, help
create data forms, print a manual of operations, and develop procedures
for quality control.  The Principal Investigators, through the Steering
Committee, will lead the planning effort, with the assistance of the
Project Scientist at NHLBI.  Key Field Center staff may also be
involved in the planning. Subcommittees of the Steering Committee may
be formed to help in this effort.

The Coordinating Center will play a key role in the planning stage as
well.  Possible objectives for the planning stage for the Coordinating
Center, in addition to assisting Field Centers in their planning the
study, are to develop the study design, randomization and analytic
plan, select a data acquisition, transfer, and management system, plan
for subcontracts for chemical analysis of dietary aliquots, develop
procedures for quality control, training, and certification, print the
protocol and data forms, develop and produce a Manual of Operations,
and take the lead for the orderly accumulation and transmission of

In Phase II, Field Centers will proceed with subject recruitment and
protocol implementation.  Possible objectives for Phase II for the
Coordinating Center are to provide support to Field Centers with
respect to recruitment and data acquisition, and ongoing quality

In Phase III, after the last participants have completed their
follow-up measurements, Field Centers will review their data and assist
the Coordinating Center in study closeout.  The Coordinating Center
will continue with its activities in data management, cleaning, and
data analysis.  It will also support paper writing efforts through data
analysis, statistical consultation, editorial tasks, and coordination
of meetings. It is anticipated that a main results paper will be
collaboratively prepared by the investigators and submitted for

Applications for Field Centers should present three budget periods of
12 months each, and a fourth budget period of six months; applications
for Coordinating Centers should present four budget periods of 12
months each.


Additional Material to Include in the Application

To promote the development of a collaborative program among the award
recipients, a number of minimum issues need to be addressed in their
application, as discussed below. Field Center applicants should discuss
the rationale of their proposed dietary patterns and describe the
nutrition component of the intervention in detail, including the
nutrient composition of the dietary patterns, the nutrient database to
be used for designing dietary patterns and why that database is
appropriate, and quality assurance to be used during food preparation
and delivery.  Field Center applicants should also discuss the study
design, including statistical aspects of design, eligibility criteria,
methods of randomization, the use of blinded data collectors, baseline
and outcome measures, other relevant measures including objective
measures of dietary compliance, and methods of data collection, their
frequency, and quality control procedures.  Field Center applicants
should document their ability to recruit a sufficient number of
participants and provide them with food, including their experience in
human feeding studies.  Field Center applicants must be able to
interact effectively with the Coordinating Center to transmit and edit
data and should discuss their capability to participate in a
distributed data entry system if this approach is selected.  Field
Center applicants should also state their willingness to follow the
common protocol that will be agreed upon during Phase I.

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.  In such a case, a letter of agreement from either the GCRC
Program Director or Principal Investigator should be included with the

Coordinating Center applicants should discuss the study design,
including their familiarity with issues of dietary patterns and blood
pressure, eligibility criteria, methods of randomization, sample size
and power calculation, baseline and outcome measures, other relevant
measures including objective measures of dietary compliance, methods
and frequency of data collection, methods of data acquisition and
transfer, quality control procedures including training and
certification, nutrient database, chemical analysis of dietary
aliquots, and plans for statistical analysis of results.

Study Organization

Steering Committee

The Steering Committee will be the main governing body of the study
and, at a minimum, will be composed of the PI of the Field Centers, the
Principal Investigator of the Coordinating Center, and the NHLBI
Project Scientist (Nutritionist, Prevention and Demonstration Research
Branch, DECA).   Each center and the NHLBI will have one vote.  The
Committee may meet as often as eight to ten times in the first 12
months of the study and two to three times per year thereafter.  All
major scientific decisions will be determined by majority vote of the
Steering Committee.  The Chairperson, who will be other than an NHLBI
staff member, should be selected by the end of the second meeting of
the Steering Committee.  The first two meetings of the Steering
Committee will be convened by the NHLBI Project Scientist.  The
Steering Committee will have primary responsibility for the development
of the study protocol, facilitating the conduct of the study, and
reporting the study results.  Subcommittees of the Steering Committee
will be established as necessary.  The NHLBI may have one
representative on each subcommittee.

The collaborative protocol will be developed by the Steering Committee.
With data submitted centrally, the protocol will define rules regarding
access to data and publications.  A Data and Safety Monitoring Board,
to be appointed by NHLBI, will review progress at least annually and
report to NHLBI.

Terms and Conditions of Award

The administrative and funding mechanism to be used to undertake this
project will be cooperative agreements (U01), an assistance mechanism.
Under the cooperative agreement, the NIH assists, supports and/or
stimulates, and is involved substantially with recipients in conducting
a study by facilitating performance of the effort in a "partner" role.
Consistent with this concept, the tasks and activities in carrying out
the studies will be shared among the awardees and the NHLBI Project
Scientist.  The tasks or activities in which awardees have substantial
responsibilities include protocol development, participant recruitment
and follow-up, data collection, quality control, interim data and
safety monitoring, final data analysis and interpretation, preparation
of publications, collaboration with other awardees, and collaboration
with the NHLBI Project Scientist.  The NHLBI Project Scientist will
have substantial responsibilities in protocol development, quality
control, interim data and safety monitoring, final data analysis and
interpretation, preparation of publications, collaboration with
awardees, and coordination and performance monitoring.

It is anticipated that awardees will have lead responsibilities in
study design, protocol development, final data analysis and
interpretation, and in the preparation of most publications.  It is
anticipated that the NHLBI Project Scientist will have lead role
responsibilities in quality control and interim data and safety
monitoring, and in the preparation of some publications.  The NHLBI
Project Scientist will have membership on the Steering Committee and,
as appropriate, its subcommittees.

Awards resulting in response to this RFA are for 3-1/2 years for Field
Centers, and 4 years for the Coordinating Center.

Awardees will retain custody of and have primary rights to their data
developed under these awards, subject to Government, e.g., NHLBI, NIH,
or PHS, rights of access consistent with current HHS, PHS, and NIH

The NHLBI reserves the right to terminate or curtail the study (or an
individual award) in the event of (a) substantial shortfall in
participant recruitment, follow-up, data reporting, quality control, or
other major breech of the protocol, or (b) substantive changes in the
agreed-upon protocol to which the NHLBI does not agree, or (c) reaching
a major study endpoint substantially before schedule with persuasive
statistical significance, or (d) human subject ethical issues that may
dictate a premature termination.

Any disagreement that may arise in scientific matters between award
recipients and the NHLBI may be brought to arbitration. An arbitration
panel will be composed of three members--one selected by the Steering
Committee (with the NHLBI member not voting) or by the individual
awardee in the event of an individual disagreement, a second member
selected by NHLBI, and the third member selected by the two prior
members.  This special arbitration procedure in no way affects the
awardee's right to appeal an adverse action that is otherwise
appealable in accordance with the PHS regulations at 42 CFR part 50,
subpart D and HHS regulation at 45 CFR part 16.

These special Terms of Award are in addition to and not in lieu of
otherwise applicable OMB administrative guidelines, HHS Grant
Administration Regulations at 45 CFR part 74, and other HHS, PHS, and
NIH Grant Administration policy statements.



NIH and ADAMHA policy is that applicants for NIH/ADAMHA clinical
research grants and cooperative agreements are required to include
minorities and women in study populations so that research findings can
be of benefit to all persons at risk of disease, disorder, or condition
under study; special emphasis must be placed on the need for inclusion
of minorities and women in studies of diseases, disorders, and
conditions which disproportionately affect them.  This policy is
intended to apply to males and females of all ages.  If women or
minorities are excluded or inadequately represented in clinical
research, particularly in proposed population-based studies, a clear
compelling rationale must be provided.  [Note that in this study, an
over-representation of African Americans and other minorities is called

The composition of the proposed study population must be described in
terms of gender and racial/ethnic group.  In addition, gender and
racial/ethnic issues must be addressed in developing a research design
and sample size appropriate for the scientific objectives of the study.
This information must be included in the form PHS 398 (rev. 9/91) in
Sections 1-4 of the Research Plan, and summarized in Section 5, Human
Subjects.  Applicants are urged to assess carefully the feasibility of
including the broadest possible representation of minority groups.
However, NIH recognizes that it may not be feasible or appropriate in
all research projects to include representation of the full array of
United States racial/ethnic minority populations (i.e., Native
Americans [including American Indians or Alaskan Natives],
Asian/Pacific Islanders, Blacks, Hispanics).

The rationale for studies on single minority population groups should
be provided.

For the purpose of this policy, clinical research includes human
biomedical and behavioral studies of etiology, epidemiology, prevention
(and preventive strategies), diagnosis, or treatment of diseases,
disorders or conditions, including but not limited to clinical trials.

The usual NIH policies concerning research on human subjects also
apply.  Basic research or clinical studies in which human tissues
cannot be identified or linked to individuals are not subject to these
policies.  However, every effort should be made to include human
tissues from women and racial/ethnic minorities when it is important to
apply the results of the study broadly, and this should be addressed by

If the required information is not contained within the application,
the application will be returned.

Peer reviewers will address specifically whether the research plan in
the application conforms to these policies.  If the representation of
women in a study design is inadequate to answer the scientific
question(s) addressed AND the justification for the selected study
population is inadequate, it will be considered a scientific weakness
or deficiency in the study design and will be reflected in assigning
the priority score to the application.

All applications for clinical research submitted to NIH are required to
address these policies.  NIH funding components will not award grants
or cooperative agreements that do not comply with these policies.


Prospective applicants are asked to submit, by November 1, 1992, a
letter of intent that includes a descriptive title of the proposed
research, the name, address, and telephone number of the Principal
Investigator, the identities of other key personnel and participating
institutions, and the number and title of the RFA in response to which
the application may be submitted.

Although a letter of intent is not required, is not binding, and does
not enter into the review of subsequent applications, the information
that it contains is helpful in planning for the review of applications.
It allows NHLBI staff to estimate the potential review workload and to
avoid conflict of interest in the review.

The letter of intent is to be sent to:

C. James Scheirer, Ph.D.
Review Branch, Division of Extramural Affairs
National Heart, Lung, and Blood Institute
Westwood Building, Room 648
5333 Westbard Avenue
Bethesda, MD  20892
Telephone:  (301) 496-7363
FAX:  (301) 402-1660


The research grant application form PHS 398 (rev. 9/91) is to be used
in applying for these grants.  These forms are available at most
institutional business offices; from the Office of Grants Inquiries,
Division of Research Grants, National Institutes of Health, 5333
Westbard Avenue, Room 449, Bethesda, MD 20892, telephone (301)
496-7441; and from the NIH Project Scientist named below.

The RFA label available in the PHS 398 application form must be affixed
to the bottom of the face page of the application.  Failure to use this
label could result in delayed processing of the application such that
it may not reach the review committee in time for review.  In addition,
the RFA title and number must be typed in line 2a of the face page of
the application form and the YES box must be marked.  Send or deliver
the original, signed application and three legible complete photocopies

Division of Research Grants
National Institutes of Health
Westwood Building, Room 240
Bethesda, MD  20892**

Send two additional copies of the application to:

C. James Scheirer, Ph.D.
Review Branch, Division of Extramural Affairs
National Heart, Lung, and Blood Institute
Westwood Building, Room 648
5333 Westbard Avenue
Bethesda, MD  20892
Telephone:  (301) 496-7363


Applications must be received by December 1, 1992.  An application not
received by this date will be considered ineligible.


General Considerations

All applicants will be judged on the basis of the scientific merit of
their proposed study and their documented ability to conduct the
essential study components as broadly outlined in the RESEARCH

Review Method

Upon receipt, applications will be reviewed by the DRG for completeness
and by NHLBI staff for responsiveness to this RFA.  Incomplete
applications will be returned to the applicant without further
consideration.  If the application is judged unresponsive, the
applicant will be contacted and given an opportunity to withdraw the
application or to have it considered for the regular, investigator-
initiated grant program of the NIH.  If the application submitted in
response to this RFA is substantially similar to a grant application
already submitted to the NIH for review, but has not yet been reviewed,
the applicant will be asked to withdraw either the pending application
or the new one.  Simultaneous submission of identical applications will
not be allowed, nor will essentially identical applications be reviewed
by different review committees.  Therefore, an application cannot be
submitted in response to this RFA that is essentially identical to one
that has already been reviewed.  This does not preclude the submission
of substantial revisions of applications already reviewed, but such
applications must include an introduction addressing the previous

Applications judged to be responsive by NHLBI staff will be reviewed
for scientific and technical merit by an initial peer review group,
which will be convened by the Division of Extramural Affairs, NHLBI,
solely to review these applications.  The initial review will include
a preliminary evaluation to determine scientific merit relative to the
other applications received in response to this RFA (triage); the NIH
will remove from further consideration applications judged to be
noncompetitive and promptly notify the Principal Investigator and the
official signing for the applicant organization.  Those applications
judged to be competitive will be further evaluated for
scientific/technical merit by the usual peer review procedures,
including, if deemed appropriate, an applicant interview in or near
Bethesda at the applicant's expense.  Subsequently, they will be
reviewed by the National Heart, Lung, and Blood Advisory Council.

Review Criteria

Applicants are encouraged to submit and describe their own ideas on how
best to meet the goals of the study, but they are expected to address
issues identified under SPECIAL REQUIREMENTS of this Request for
Applications.  Applications will be judged primarily on the scientific
quality of the application, the availability of a study sample with
adequate numbers of participants, evidence of ability to prepare and
deliver food to participants, the discussion of considerations relevant
to this RFA, expertise of the investigators, their capability to
perform the work proposed, and a demonstrated willingness to work
together with other Centers and the NHLBI Project Scientist.

The review group will assess the scientific merit of the study and
related factors, including:

Field Centers

o  Rationale for studying the dietary patterns proposed, including
rationale for the population proposed to be included.

o  Proposed study design, including eligibility criteria, measurements,
nutrition methodology, and measures taken to assure high quality data

o  Feasibility of the proposed project, including plans to recruit
participants and plans delineating the feasibility and logistics of
providing food to participants.

o  Expertise, training, and experience of the investigators and staff,
including the scientific and administrative abilities of the PI and
co-investigators; their potential to accomplish the proposed research
goals; the time they plan to devote to the program for the effective
conduct of the study; their previous experience conducting research on
blood pressure and in providing food to human subjects; and willingness
to work collaboratively with other Field Centers, the Coordinating
Center, and the NHLBI.

o  Facilities, equipment, and organizational structure to effectively
implement the proposed research.

o  Appropriateness of the budget for the work proposed.

Coordinating Center

o  Understanding of the scientific, statistical, logistical, and
technical issues underlying the planned multicenter study, including
issues of blood pressure measurements and feeding studies in humans,
and taking a leadership role in the area of study design, statistics,
logistics, data acquisition and management, quality control, and data

o  Adequacy of the proposed plans for acquisition, transfer,
management, and analysis of data, quality control of data collection
and of the experimental diets, and overall coordination of study

o  The expertise, training, and experience of the investigators and
staff, including the administrative abilities of the Principal
Investigator and co-investigators, and the time they plan to devote to
the program for the effective coordination of the multicenter study.

o  The administrative, supervisory, and collaborative arrangements for
achieving the goals of the program, including willingness to cooperate
with the participating Field Centers and the NHLBI.

o  Facilities, equipment, and organizational structure to effectively
assist Field Centers in implementing the study and in data collection
procedures and in overall coordination of study activities.

o  Appropriateness of the budget for the work proposed.


Applications recommended by the National Heart, Lung, and Blood
Advisory Council will be considered for award based upon (a) scientific
and technical merit and the requirements explicitly stated in this RFA,
(b) program balance, including in this instance, sufficient
compatibility of features to make a successful collaborative program a
reasonable likelihood, and (c) availability of funds.

Letter of Intent                                  November 1, 1992
Application Receipt Date                          December 1, 1992
Review by National Heart, Lung, and Blood
Advisory Council:                                 May 1993
Anticipated Award Date                            July 1, 1993


Written and telephone inquiries are encouraged.  The opportunity to
clarify any issues or questions from potential applicants is welcome.
Inquiries regarding this announcement may be directed to the Project

Eva Obarzanek, Ph.D., R.D.
Prevention and Demonstration Research Branch
Division of Epidemiology and Clinical Applications
National Heart, Lung, and Blood Institute
Federal Building, Room 604
7550 Wisconsin Avenue
Bethesda, MD  20892
Telephone:  (301) 496-2465

Inquiries regarding review and application procedures may be directed

C. James Scheirer, Ph.D.
Review Branch, Division of Extramural Affairs
National Heart, Lung, and Blood Institute
Westwood Building, Room 648
5333 Westbard Avenue
Bethesda, MD  20892
Telephone:  (301) 496-7363
FAX:  (301) 402-1660

Inquiries regarding fiscal and administrative matters may be directed

Mr. William W. Darby
Section Chief, Grants Management Officer
Grants Operations Branch
Division of Extramural Affairs
National Heart, Lung, and Blood Institute
Westwood Building, Room 4A11C
5333 Westbard Avenue
Bethesda, MD  20892
Telephone:  (301) 496-7536
FAX:  (301) 402-1200


This project is described in the Catalog of Federal Domestic Assistance
No. 93.837.  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 74.  This project
is not subject to the intergovernmental review requirements of
Executive Order 12372 or Health Systems Agency review.


Ackley S, Barrett-Connor E, Suarez L.  Dairy products, calcium and
blood pressure.  Am J Clin Nutr 1983;38:457-461.

Anderson JW.  Plant fiber and blood pressure.  Ann Intern Med

Armstrong B, Van Merwyk AJ, Coates H.  Blood pressure in Seventh-Day
Adventist vegetarians.  Am J Epidemiol 1977;105:444-449.

Beilin LJ, Margetts BM. Vegetarian diet and blood pressure. In:
Bibliotheca Cardiologica - Non-Pharmacologic Therapy of Hypertension,
Vol 41; S. Karger AG, 1987, pp 85-105.

Brussard JH, van Raaij JMA, Stasse-Wolthuis M, Katan MB, Hautvast JGAT.
Blood pressure and diet in normotensive volunteers:  absence of an
effect of dietary fiber, protein, or fat.  Am J Clin Nutr

Cappuccio FP, MacGregor GA.  Does potassium supplementation lower blood
pressure?  A meta-analysis of published trials.  J Hypertens

Cutler JA, Brittain E.  Calcium and blood pressure.  An epidemiologic
perspective.  Am J Hypertens 1990;3:1375-1465.

Elliott P, Kesteloot H, Dyer A, Freeman J, Shipley M, Stamler J, Rose
G, Marmot M, Stamler R.  24-hour urinary nitrogen excretion and blood
pressure:  INTERSALT findings. Circulation 1991;84(Suppl 2):II-698.

Fehily AM, Burr ML, Butland BK, Eastham RD.  A randomized controlled
trial to investigate the effect of a high fibre diet on blood pressure
and plasma fibrinogen.  J Epidemiol Commun Hlth 1986:40;334-337.

Garcia-Palmieri MR, Costas R, Cruz-Vidal M, Sorlie PD, Tillotson J,
Havlik RJ. Milk consumption, calcium intake, and decreased hypertension
in Puerto Rico.  Puerto Rico Heart Health Program Study.  Hypertension

Harlan WR, Hull AL, Schmouder RL, Landis JR, Thompson FE, Larkin FA.
Blood pressure and nutrition in adults.  The National Health and
Nutrition Examination Survey.  Am J Epidemiol 1984;120:17-28.

Heagerty AM, Ollerenshaw JD, Robertson DI, Bing RF, Swales JD.
Influence of dietary linoleic acid on leucocyte sodium transport and
blood pressure.  Br Med J 1986;293:295-297.

Hostetter TH, Meyer TW, Rennke HG, Brenner BM, Noddin JA, Sandstrom DJ.
Chronic effects of dietary protein in the rat with intact and reduced
renal mass.  Kidney Int 1986;30:509- 517.

INTERSALT Cooperative Research Group.  INTERSALT: An international
study of electrolyte excretion and blood pressure.  Results for a
24-hour urinary sodium and potassium excretion.  Br Med J

Joffres MR, Reed DM, Yano K.  Relationship of magnesium intake and
other dietary factors to blood pressure:  The Honolulu Heart Study.  Am
J Clin Nutr 1987;45:469-475.

Kihara M, Fujikawa J, Ohtaka M, Mano M, Nara Y, Horie R, Tsunematsu T,
Note S, Fukase M, Yamori Y.  Interrelationships between blood pressure,
sodium, potassium, serum cholesterol, and protein intake in Japanese.
Hypertension 1984;6:736-742.

Kimura N.  Atherosclerosis in Japan:  Epidemiology. Atherosclerosis Rev

Kok FJ, Vandenbroucke JP, van der Heide-Wessel C, van-der Heide RM.
Dietary sodium, calcium, and potassium, and blood pressure.  Am J
Epidemiol 1986;123:1043-1048.

Lind L, Lithell H, Pollare T, Ljunghall S.  Blood pressure response
during long-term treatment with magnesium is dependent on magnesium
status:  a double-blind, placebo- controlled study in essential
hypertension and in subjects with high-normal blood pressure.  Am J
Hypertension 1991;4:674-679.

Lovenberg W, Yamori Y.  Dietary protein, the central nervous system,
and hypertension. In: NIH Workshop on Nutrition and Hypertension
Proceedings.  Horan MJ, Blaustein M, Dunbar JB, Kachadorian W, Kaplan
NM, Simopoulos AP, eds.  Biomedical Information Corp, New York, 1985,
pp. 241-253.

Margetts BM, Beilin LJ, Vandogen R, Armstrong BK.  Vegetarian diet in
mild hypertension: a randomized controlled trial.  Br Med J

Margetts BM, Beilin LJ, Armstrong BK, Rouse IL, Vandongen R, Croft KD,
McMurchie EJ.  Blood pressure and dietary polyunsaturated and saturated
fats:  a controlled trial.  Clin Sci 1985;69:165-175.

Margetts BM, Beilin LJ, Vandongen R, Armstrong BK.  A randomized
controlled trial of the effect of dietary fibre on blood pressure.
Clin Sci 1987;72:343-350.

McCarron DA, Morris CD, Henry HJ, Stanton JL.  Blood pressure and
nutrient intake in the United States.  Science 1984;224:1392-1398.

Medical Research Council Research Committee.  Controlled trial of
soya-bean oil in myocardial infarction.  Lancet 1968;2:693- 700.

Mensink RP, Janssen M-C, Katan MB.  Effect on blood pressure of two
diets differing in total fat but not in saturated and polyunsaturated
fatty acids in healthy volunteers.  Am J Clin Nutr 1988;47:976-980.

National Research Council.  Diet and Health.  Implications for reducing
chronic disease risk. Washington, DC: National Academy Press; 1989.

Puska P, Iacono JM, Nissinen A, Vartianinen E, Dougherty R, Pietinen P,
Leino U, Uusitalo U, Kuusi T, Kostianinen E, Nikkari T, Seppala E,
Vapaatalo H, Huttunen JK.  Dietary fat and blood pressure:  an
intervention study on the effects of a low fat diet with two levels of
polyunsaturated fat.  Prev Med 1985;14:573-584.

Puska P, Iacono JM, Nissinen A, Korhonen HJ, Vartianinen E, Pietinen P,
Dougherty R, Leino U, Mutanen M, Moisio S, Huttunen J.  Controlled,
randomised trial of the effect of dietary fat on blood pressure.
Lancet 1983;1:1-5.

Rao RH, Rao UB, Srikantia SG.  Effect of polyunsaturated-rich vegetable
oils on blood pressure in essential hypertension. Clin Exp Hypertens

Rossner S, Anderson IL, Ryttig K.  Effects of a dietary fibre
supplement to a weight reduction programme on blood pressure. Acta Med
Scand 1988;223:353-357.

Rouse IL, Beilin LJ, Armstrong BK, Vandongen R.  Blood pressure
lowering effect of a vegetarian diet: a controlled trial in
normotensive subjects.  Lancet 1983;i:5-10.

Rouse IL, Armstrong BK, Beilin.  Vegetarian diet, lifestyle and blood
pressure in two religious populations.  Clin Exp Pharmacol Physiol

Rouse IL, Armstrong BK, Beilin LJ.  The relationship of blood pressure
to diet and lifestyle in two religious populations. J Hypertension

Rouse IL, Beilin LJ.  Vegetarian diet and blood pressure.  J
Hypertension 1984;2:231-240.

Sacks FM, Kass EH.  Low blood pressure in vegetarians:effects of
specific foods and nutrients.  Am J Clin Nutr 1988;48:795- 800.

Sacks FM, Rouse IL, Stampfer MJ, Bishop LM, Lenherr CF, Walther RJ.
Effect of dietary fat and carbohydrate on blood pressure of mildly
hypertensive patients.  Hypertension 1987;10:452-460.

Sacks FM, Stampfer MJ, Munoz A, McManus K, Canessa M, Kass EH. Effect
of linoleic and oleic acids on blood pressure, blood viscosity, and
erythrocyte cation transport.  J Am College Nutr 1987;6:179-185.

Sacks FM, Rosner B, Kass EH.  Blood pressure in vegetarians. Am J
Epidemiol 1974;100:390-8.

Sacks FM.  Dietary fats and blood pressure:  A critical review of the
evidence.  Nutr Rev 1989;47:291-300.

Schlamowitz P, Halberg T, Warnoe O, Wilstrop F, Ryttig K. Treatment of
mild to moderate hypertension with dietary fibre. Lancet

Stamler J, Caggiula A, Grandits GA.  Relationships of dietary variables
to blood pressure:  Findings of the Multiple Risk Factor Intervention
Trial.  Circulation 1992;85:6.

Swain JF, Rouse IL, Curley CB, Sacks FM.  Comparison of the effects of
oat bran and low-fiber wheat in serum lipoprotein levels and blood
pressure.  N Engl J Med 1990;322:147-152.

The Trials of Hypertension Prevention Collaborative Research Group.
The effects of nonpharmacologic interventions on blood pressure of
persons with high normal levels:  Results of the Trials of Hypertension
Prevention (Phase 1).  JAMA 1992;267:1213-1220.

Wang H, Ikeda K, Kihara M, Nara Y, Horie R, Yamori Y.  Effect of
dietary urea on blood pressure in spontaneously hypertensive rats.
Clin Exp Pharmacol Physiol 1984;11:555- 561.

Weinsier RL, Norris D.  Recent developments in the etiology and
treatment of hypertension: dietary calcium, fat, and magnesium.  Am J
Clin Nutr 1985;42:1331-1338.

Whelton PK, Klag MJ.  Magnesium and blood pressure:  Review of the
epidemiologic and clinical trial experience.  Am J Cardiol

Whelton PK, Thaker GK, Klag MJ, Seidler AJ.  Blood pressure effects of
potassium supplementation.  Circulation 1989;80:II- 301.

Witteman JCM, Willett WC, Stampfer MJ, Colditz GA, Sacks FM, Speizer
FE, Rosner B, Hennekens CH.  A prospective study of nutritional factors
and hypertension among U.S. women. Circulation 1989;80:1320-1327.


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