DEPARTMENT OF HEALTH AND HUMAN SERVICES
NATIONAL INSTITUTES OF HEALTH
National Heart, Lung, and Blood Institute
FY 2005 Budget Justification
Authorizing Legislation: Section 301 and title IV of the
Public Health Service Act, as amended.
Budget Authority:
FY 2003
Actual |
FY 2004
Estimate |
FY 2005
Estimate |
Increase or
Decrease |
FTE |
BA |
FTE |
BA |
FTE |
BA |
FTE |
BA |
880 |
$2,791,822,000 |
856 |
$2,878,106,000 |
853 |
$2,963,953,000 |
(3) |
$85,847,000 |
This document provides justification for the FY 2005 activities
of the National Heart, Lung, and Blood Institute (NHLBI), including
HIV/AIDS activities. A more detailed description of NIH-wide Fiscal
Year 2005 HIV/AIDS activities can be found in the NIH section
entitled "Office of AIDS Research (OAR)."
INTRODUCTION
The NHLBI provides leadership for a national program in diseases
of the heart, blood vessels, lungs, and blood; sleep disorders;
and blood resources. It plans and conducts—through work
in its own laboratories and through grant- and contract-supported
activities in extramural scientific institutions—an integrated
and coordinated program of basic research, clinical investigations
and trials, observational studies, and demonstration and education
projects related to the causes, prevention, diagnosis, and treatment
of the diseases under its purview and to the clinical use of blood
and all aspects of the management of blood resources. Since FY
1993, the Institute has been the home of the National Center on
Sleep Disorders Research and, since FY 1998, it has had responsibility
for the NIH Women’s Health Initiative. The NHLBI supports
research training and career development of new and established
investigators in fundamental sciences and clinical disciplines
to enable them to conduct research relative to its mission. In
addition, it conducts educational activities, including development
and dissemination of materials for health professionals, patients,
and the general public, with a strong emphasis on prevention.
The following material summarizes the latest scientific progress
and promising future opportunities.
SCIENCE ADVANCES
Study Finds Possible New Indicator of Heart Disease Risk
A recent study suggests that levels of a type of adult stem cell
in the bloodstream—the endothelial progenitor cell (EPC)—may
indicate a person’s risk of developing cardiovascular disease
(CVD). When vascular endothelial cells (cells that line the blood
vessels) are damaged or destroyed, the EPCs are thought to replace
them. Scientists studying healthy men aged 21 and older found
that the number of EPCs circulating in the blood was inversely
related to CVD risk. In addition, they found that the EPCs of
those at higher risk aged faster than the cells of those at lower
risk, and that blood vessels were much less likely to dilate and
relax properly in persons with low levels of the cells. Although
much more research needs to be done, the findings suggest that
it may some day be possible to test a person’s risk of developing
CVD by taking a blood sample and measuring the level of EPCs.
Gradual Restoration of Blood Flow after Ischemia Benefits Heart
Muscle Tissue
Scientists recently made progress in their search for safer ways
of restoring blood flow to heart tissue damaged by ischemia (a
deficiency of blood flow) caused by blockages in the coronary
arteries. Time is critical in the restoration of blood flow to
the heart muscle because its interruption for several hours leads
to tissue death, and yet sudden restoration of blood flow (e.g.,
via balloon angioplasty) can exacerbate heart tissue injury. NIH-supported
researchers recently reported a new approach to reduce injury
to heart cells deprived of blood flow. Using a canine model, they
found that applying a regimen of brief, nonlethal, ischemic periods
immediately after blood flow was restored reduced the extent of
heart muscle damage by approximately 50 percent. A similar decrease
in lethal arrhythmias was also found. Since about 1.1 million
people in the United States suffer heart attacks each year1
and many of the survivors go on to develop debilitating heart
failure, decreasing the amount of cardiac tissue damage from heart
attacks could significantly reduce mortality and morbidity and
also lower health care costs.
Magnetic Resonance Imagine (MRI) Provides Faster, More Accurate
Way
to Diagnose Heart Attacks
More than 5 million patients with chest pain visit emergency departments
each year.2 Many who are suffering heart attacks must wait up to
12 hours for results of diagnostic blood tests before they can
begin receiving life-saving treatment. Still others, with unstable
angina, are sent home undiagnosed, only to have their angina later
progress to a heart attack. A recent study (part of a collaborative
program including the NHLBI, the NIH Clinical Center, and Suburban
Hospital in Bethesda, Maryland) has shown that advanced MRI technology
can detect heart attack and unstable angina in emergency room
patients with chest pain more accurately and faster than standard
diagnostic tests. Cardiac MRI allows clinicians to view the heart
and arteries in “real time” and determine how well
the heart is pumping, how adequate the supply of blood is to specific
areas of the heart, and whether there is evidence of permanent
heart damage. Since patients can be scanned in under 40 minutes,
use of MRI technology could save many lives and reduce disability
among those who survive by allowing doctors to diagnose cardiac
emergencies and start appropriate treatment substantially faster
than at present. Researchers estimate that diagnostic cardiac
MRIs could be used in hospital emergency departments nationwide
within just a few years.
Insulin-Sensitizing Drugs May Reduce Cardiovascular Disease (CVD)
in Diabetic Patients
With the advent of effective approaches to regulate blood sugar
levels, the greatest health threat for persons with diabetes has
become CVD. New research suggests that thiazolidinediones—a
class of insulin-sensitizing drugs often prescribed for diabetics
to enable their cells to use insulin more efficiently—may
also reduce CVD risk. Much scientific evidence links inflammation
to CVD development, and researchers recently found that diabetics
have higher blood levels of a protein known to trigger inflammation
than non-diabetics. Moreover, when diabetic patients were treated
with thiazolidinediones, levels of the inflammation-inducing protein
fell by almost 30 percent. The results offer hope that treatment
with insulin-sensitizing drugs like thiazolidinediones or other
anti-inflammatory drugs might prevent or delay progression of
CVD in patients with diabetes.
Scientists Find Better Predictor of Impending Aneurysm Rupture
If the aorta, the large artery that carries blood from the heart
to the rest of the body, widens in the abdominal area—a
condition known as abdominal aortic aneurysm (AAA)—it can
rupture and cause fatal bleeding. Physicians do not know how to
limit the growth of AAAs, and since surgery to repair them is
risky it is usually recommended only when aneurysms reach a diameter
of 4.5-5.0 cm. Smaller diameter aneurysms can also rupture, but
heretofore no method was available for predicting whether a given
aneurysm is likely to do so. In a recent study of 103 patients
with AAAs, scientists used a non-invasive technology called computed
tomography to produce 3-dimensional images of the aneurysms and
to measure the amount of stress they impose on the artery wall.
They found that the level of stress was directly related to the
risk of rupture regardless of aneurysm diameter. If results are
confirmed in a clinical trial, this technique could provide doctors
better information concerning the relative risks of surgery and
rupture.
Reducing Copper Levels May Help to Treat Injured Blood Vessels
A recent study in rats tested whether reducing levels of copper
in the body would prevent injured arteries from narrowing and
becoming blocked, a usual response to arterial injury. Copper
was a likely candidate for testing because it has been shown to
promote inflammation, a part of the body’s response to injury
and infection that contributes to the development of CVD. Rats
given tetrathiomolybdate (TTM), a drug that binds tightly to copper
and helps remove it from the body, suffered less narrowing of
the arteries after arterial injury than did rats that were not
given the drug. Moreover, TTM appeared to promote reendothelialization—replacement
of damaged blood vessel cells with new cells. The findings offer
hope that drugs which reduce copper levels may eventually prove
useful for preventing narrowing and blockage of blood vessels
and promoting reendothelialization in humans as well.
Using Nanoparticles to Deliver Drugs Shows Promise for Preventing
Restenosis
Angioplasty is a common procedure used to open up blocked coronary
arteries and restore blood flow. Although it is initially successful
in most patients, restenosis, or renarrowing, of the arteries
often occurs weeks or months later. Restenosis is caused, in part,
by proliferation of vascular smooth muscle cells (VSMCs) in the
artery. Recently, scientists have begun using nanoparticles—tiny
particles small enough to interact with DNA and proteins—to
increase the effectiveness of drugs that stop VSMCs from proliferating.
Scientists found that anti-proliferative drugs were more effective
when inserted into nanoparticles specifically designed to stick
to VSMCs. The improved performance is probably due to the nanoparticles
ability to “target” the drugs directly to the VSMCs.
If this technique can be applied in clinical studies, it holds
promise for slowing restenosis after angioplasty.
Preventing Congenital Heart Disease in the Infants of Diabetic
Mothers
Babies born to mothers who suffer from diabetes are three times
more likely to have congenital heart defects than the newborns
of non-diabetic mothers, and valve malformations are quite common.
In a recent study using mouse embryos, researchers exposed the
endocardial cushions—bulges of the heart lining in embryos
that eventually develop into the heart valves—to varying
levels of glucose. Findings showed that high levels of glucose
during a narrow window of time prevented proper development, perhaps
because glucose decreased the levels of a vascular growth factor
(VEGF-A) needed for the cushions to form. When the growth factor
was added, cushions grew properly despite the presence of high
glucose levels. The study identifies a critical period of time
in mice when the developing heart is sensitive to high glucose
and a possible mechanism by which the resulting heart malformations
could be prevented.
Findings May Help to Eliminate the Side Effects of Glucocorticoids
Glucocorticoids are widely prescribed drugs with highly beneficial
anti-inflammatory and immunosuppressant properties, but their
use can cause high blood pressure, a major risk factor for cardiovascular
disease. Understanding the mechanism by which glucocorticoids
raise blood pressure is an essential first step toward preventing
this side effect. Findings from a recent study in rats suggest
that glucocorticoids increase blood pressure because they decrease
levels of the protein GTP cyclohydrolase 1 (GTPCH1) which is needed
for the production of nitric oxide (NO), a compound known to dilate
blood vessels. Scientists can now concentrate on GTPCH 1 as a
possible target to treat the hypertension caused by glucocorticoid
therapy.
Study Findings Suggest Revised Approach to Therapy for Atrial
Fibrillation
Atrial fibrillation (AF) is a common type of heart arrhythmia affecting
over 2 million people in the United States.3 It is increasingly
prevalent, especially in the elderly, and is an important risk
factor for stroke. The preferred and most frequently used initial
therapy for AF has been a strategy to restore and maintain a normal
heart rhythm. However, a recent clinical trial found that this
strategy prevents deaths no better than the alternative, often
secondary, approach of merely controlling the rate at which the
heart beats. Moreover, the heart-rhythm strategy does not lower
risk of stroke, enhance quality of life, or improve cognitive
function, and may have some disadvantages, including more hospitalizations
and adverse drug effects. These findings are expected to alter
fundamentally the approach to preventing complications of AF in
many patients.
All-in-one Approach to Lifestyle Changes Effectively Lowers Blood
Pressure
Nearly 50 million American adults have high blood pressure4
and as a result they are at increased risk of having a stroke
or heart disease. Lifestyle changes, such as losing excess weight,
eating a heart-healthy diet, increasing physical activity, and
quitting smoking, can lower high blood pressure. To date, most
behavioral interventions encouraged people to make only one or
two lifestyle changes at a time. However, findings from a recent
clinical trial indicate that an all-in-one approach to lifestyle
changes is feasible and effective in lowering blood pressure.
Trial participants who simultaneously implemented healthy lifestyle
changes also significantly reduced their weight and became more
fit. These findings offer encouragement to Americans with above-normal
blood pressure (120 to 139 mm Hg systolic and 80 to 89 mm Hg diastolic)
by showing that multiple lifestyle changes can be made at once
to lower blood pressure and in turn, reduce cardiovascular disease
risk.
High Rates of Blood Pressure Control Are Obtainable
Uncontrolled high blood pressure (=140/90 mm Hg) raises risk of
stroke and heart disease. Unfortunately, only a minority of Americans
with hypertension have their blood pressure under control, despite
the availability of effective antihypertensive medications. However,
results from the Antihypertensive and Lipid-Lowering Treatment
to Prevent Heart Attack Trial (ALLHAT) show what can be achieved.
Blood pressure control rates among ALLHAT participants increased
from 24.7 percent at the beginning of the trial to 66 percent
after five years of followup. Perhaps most notably, the ALLHAT
gains in blood pressure control were achieved in a variety of
clinical practice settings and in subgroups of people known to
have difficulty controlling their blood pressure, such as blacks,
the elderly, and patients with diabetes. These results offer patients
encouragement that blood pressure control is obtainable and challenge
physicians to continue working with their patients until adequate
blood pressure control is achieved.
Hostility and Impatience Increase Long-term Risk of Developing
Hypertension
Young adulthood and early middle age are critical periods for the
development of hypertension and other risk factors for heart disease.
A recent study examined the effects of personality characteristics
and emotional states exhibited by younger people on long-term
risk for hypertension. It found that hostility and impatience
(two features of the so-called Type A personality) increased the
risk. However, the other psychological and social factors examined,
such as competitiveness (another Type A feature), depression,
and anxiety, did not increase risk. These findings help researchers
zero in on behavioral characteristics that require further study.
They also highlight the need for people to be able to recognize,
modify, and manage their harmful psychosocial behaviors so that
they can thrive in the fast-paced U.S. society without compromising
their cardiovascular health.
Quality of Life Improved for Recent Heart Attack Patients Treated
for Depression
Social isolation and depression are risk factors for death and
recurrent heart attack in heart disease patients. Results from
the first major study to evaluate the effects of treating depression
and low social support in patients who recently suffered a heart
attack surprisingly showed no reduction in deaths or second heart
attacks. However, study participants experienced significant improvement
in their social functioning, were less depressed, and enjoyed
a higher quality of life. These findings show that treatment for
depression and low social support can improve the quality of life
of heart attack patients and underscore the importance of evaluating
and treating heart attack patients who show signs of depression.
Sleep Disturbances Underrated by Healthcare Professionals
Insomnia is a common affliction characterized by difficulty falling
asleep, difficulty staying asleep, or short sleep duration. The
extent to which it is associated with medical and psychiatric
disorders is only now being appreciated. Recent findings from
the Women’s Health Initiative suggest a correlation between
insomnia and depression. Other studies suggest that, for men,
insomnia correlates with elevated levels of tumor necrosis factor-alpha,
which at high levels is associated with higher risks for heart
disease, high blood pressure, and insulin resistance. Since poor
sleep is associated with decreased quality of life, increased
physical complaints, and decreased work productivity, early assessment
and treatment of insomnia symptoms, including depression, might
reduce associated risks of psychiatric and cardiovascular disease.
Sleep Loss Is Coupled to Obesity in Children
Inadequate or disturbed sleep disrupts neuroendocrine, metabolic,
and immunologic functions, and impairs motivational drive and
cognitive functions. Of interest to researchers studying body
weight, sleep loss disrupts hormonal regulation of glucose metabolism
and interferes with satiety signals arising from food consumption.
Previous studies found that carbohydrate craving associated with
sleep deprivation is linked to obesity and that excessive daytime
sleepiness due to sleep disorders is likely to decrease participation
in physical activities and exacerbate weight gain. A recent study
of adolescents found a link between poor sleep quality and obesity.
Each hour of sleep disturbance decreased the daily physical activity
level by 3 percent. More promising, however, was the finding that
every hour of increased sleep time decreased the odds of obesity
by 80 percent. These results suggest that developing strategies
to help children overcome sleep disorders could be an important
step in combating the obesity epidemic facing the United States.
Antibiotic Resistance During Cystic Fibrosis Linked to Local Condition
in Airways
The lungs of cystic fibrosis (CF) patients become persistently
colonized with Pseudomonas aeruginosa early in life. Despite a
vigorous inflammatory response and the rapid influx of white blood
cells into the CF airways to combat the bacteria, P. aeruginosa
infections become chronic, airways are destroyed, and lung function
declines, eventually resulting in death. An initiating event in
the pathogenesis of CF is mucus stasis, caused by the inability
of the airways to effectively expel mucus. Recent studies have
revealed that this stagnant mucous environment becomes anaerobic
(i.e., without oxygen) due to high oxygen consumption by bacteria,
neutrophils, and CF airway cells. Although P. aeruginosa normally
requires oxygen, it apparently adapts well to the anaerobic conditions
in the mucus-rich environment of the lungs of CF patients. Furthermore,
a class of antibiotics known as macrolides have shown efficacy
against anaerobic P. aeruginosa, suggesting new possibilities
for fighting infection, not just in patients with CF, but also
in patients with asthma and chronic obstructive pulmonary disease.
Immunosuppressant Drug May Hold Key for Treating Lymphangioleiomyomatosis
Lymphangioleiomyomatosis (LAM) is a rare, progressive, ultimately
fatal lung disease that affects several hundred young women in
the United States. It is characterized by formation of cysts in
the lungs due to excessive overgrowth of atypical smooth muscle
cells. No treatments are available to halt or reverse the progression
of LAM, and lung transplantation is the only established therapy
for those with end-stage lung disease. Recently, investigators
determined that rapamycin, an immunosuppressant drug used to prevent
graft rejection in patients undergoing kidney transplantation,
can effectively inhibit the overgrowth of LAM cells in vitro.
Although clinical trials in humans will be necessary before its
usefulness is established, rapamycin is the first drug to show
potential for slowing or stopping the progression of LAM.
Therapeutic Effects of Immunostimulatory DNA Sequences (ISS)
Overstimulation of a key component of the immune system, called
the Th2 lymphocyte, appears to play a significant role in the
pathogenesis and propagation of allergic inflammation in asthma.
Previous studies using mouse models of acute asthma have demonstrated
that ISS, which are short segments of DNA that are identical to
portions of certain bacterial genomes, can suppress Th2 expression,
thereby reducing the undesirable infiltration of cells called
eosinophils into the airways and reducing airway inflammation
and hyperreactivity. Researchers have recently demonstrated that
ISS are as effective as corticosteroids, the standard therapy
for severe, acute exacerbations of asthma, in reducing airway
inflammation in the mouse model. ISS appear to be well tolerated
in humans, and trials will determine whether they could become
an important immunotherapy for restoring immune balance to treat
asthma.
Genotype Determines Asthma Patients’ Response to Beta Agonists
Beta agonists, the most commonly prescribed drugs for controlling
asthma symptoms, relax airway muscles by binding directly to beta-receptors
located on the muscle surface. However, researchers have demonstrated
that certain patients who have mutations in the beta-receptors
do not respond well to beta agonists; instead, their asthma control
deteriorates. In the recent Beta-Adrenergic Responses by Genotype
(BARGE) trial, investigators examined the genotype of patients
and found that those with the receptor mutation had better peak
flow response (a measure of breathing ability) while taking placebo
than while taking the beta agonist albuterol. Based on BARGE,
investigators suggest that patients with the mutation, who constitute
one-sixth of the U.S. asthmatic population, may improve their
asthma control when completely withdrawn from beta agonists. Identification
of those with the mutation could lead to better management strategies
for asthma.
Adenovirus Enhances Inflammatory Responses of Pulmonary Cells
Adenovirus infections of the respiratory tract are especially common
in people with emphysema. This observation has led to speculation
that adenoviral infection might be a risk factor for development
or progression of emphysema, but cellular and molecular mechanisms
that might explain the link between adenoviral infection and emphysema
are not yet well defined. Researchers recently inserted the gene
for the adenoviral E1A protein, a protein that controls virus
replication, into cultured human bronchial epithelial cells. The
investigators found that cells with E1A, but not controls lacking
E1A, expressed high levels of transforming growth factor beta,
intercellular adhesion molecule 1, and interleukin 8, all immune
factors that play a part in inflammation. The critical role of
the adenoviral E1A protein is especially significant since it
suggests that strategies for inhibiting its expression could lead
to better therapies and outcomes for emphysema patients.
Transmission of Asthma Susceptibility
The prevalence of asthma began increasing in the United States
in the 1960s, and today it is a major health problem that disproportionately
affects children. Increasing evidence supports the hypothesis
that in utero and perinatal exposure of mother and child to allergens
increases the child’s subsequent risk of developing asthma.
Investigators, using mouse models, found that asthma susceptibility
can be transferred in utero from mother to offspring in a process
that seems to be dependent on mediators that prime the immune
system for asthma development. Defining the biologic mechanisms
that drive the development of asthma will provide the basis for
new interventions for treatment and prevention.
Women Benefit Even More than Men from Quitting Smoking
Cigarette smoking is a leading cause of chronic obstructive pulmonary
disease (COPD), and smokers who develop COPD are strongly urged
to quit. A recent study of middle-aged smokers with mild to moderate
COPD found that in the first year after quitting smoking, women’s
lung function improved more than twice as much as men’s.
Among participants who quit smoking, improved lung function remained
greater for women than for men throughout the duration of the
five-year study. While both men and women benefit from quitting
smoking, results of the study should be especially encouraging
to women who are considering kicking the habit.
Fungal Infection Linked to COPD
Although chronic obstructive pulmonary disease (COPD) occurs almost
exclusively among cigarette smokers, only a small proportion of
smokers develop it, which suggests that factors other than smoking
are likely to contribute to its pathogenesis. Mounting evidence
suggests that inflammation due to infection in the lungs may play
a role. Recent studies observed that the immune response in the
lung tissues of persons infected with Pneumocystis carinii, a
fungus that frequently causes pneumonia in AIDS patients and other
immunocompromised individuals, is similar to that found in patients
with COPD. Using sensitive detection techniques, investigators
discovered that P. carinii was present in patients with COPD,
even though they had no clinical signs of pneumonia. This new
link between COPD and P. carinii, which responds to several antibiotics,
opens the way for new prevention options for COPD.
Landmark Federal Cooperative Study Defines Role of Lung Volume
Reduction Surgery
Lung-volume-reduction surgery (LVRS) was first used to treat emphysema
during the 1950s. Although some patients seemed to benefit from
the procedure, high mortality and morbidity discouraged its widespread
use until the early 1990s, when some surgeons began performing
LVRS again. The National Emphysema Treatment Trial (NETT), a collaboration
between the NIH and the Health Care Financing Administration (now
known as the Centers for Medicare and Medicaid Services, CMS),
clarified the short- and long-term risks and benefits of LVRS
and identified the characteristics of patients most likely to
benefit from LVRS as well as those who are at greater risk of
death and complications from LVRS. The NETT reflects a unique
relationship in which the NIH funded and administered the study
and CMS supported participants’ care costs. Additionally,
the Agency for Healthcare Research and Quality contributed support
for analysis of the cost-effectiveness of LVRS. The study results
provide a scientific basis for reassessment of Medicare coverage
for LVRS.
Genetic Variation Affects Severity of Acute Lung Injury
Sepsis, or “blood poisoning,” is the tenth leading
cause of death in the United States5 and is the most common risk
factor for acute lung injury (ALI) and its more severe form, the
acute respiratory distress syndrome (ARDS). Patients with lung
injury resulting from sepsis typically spend nearly 2 weeks in
intensive care units, and only half come out alive. Although overall
mortality rates from sepsis have decreased over the past 22 years,
its incidence has risen. Both the death rate and incidence are
nearly twice as high for black males as for white patients. Investigators
have recently found polymorphisms, or variations, in DNA that
are associated with an increased risk of developing ALI or ARDS
from sepsis. Strikingly, they also determined that these polymorphisms
are more common in black patients. Their findings emphasize the
need for continued study of the association between outcomes and
variations in DNA and may lead to better diagnosis and therapy
for those patients at greatest risk for ALI/ARDS.
Improvements in Platelet Storage May Save Costs and Lives
When people weigh the risks associated with transfusions of blood
or blood products, they usually think about the viruses that cause
hepatitis, AIDS, or West Nile disease. For recipients of platelet
transfusions, however, the major risk is bacterial infection.
Unlike most blood products, platelets cannot be refrigerated.
They must be stored at room temperature, which leads to rapid
bacterial growth and a diminished shelf life. Although researchers
had known for years that platelets stored at cool temperatures
rapidly disappeared from the blood stream once transfused, no
one understood why. Researchers recently noted that certain proteins
on platelet surfaces rearrange when cooled, and that the rearrangement
triggers removal of platelets by the liver. They also demonstrated
that the rearrangement could be prevented upon refrigeration by
storing platelets in a modified solution. Platelets transfused
after being stored in the new medium and then refrigerated functioned
as if they had been stored at room temperature and did not activate
the removal process. This new approach to platelet storage could
significantly improve the shelf life of platelets; reduce the
number of units that must be discarded; limit the substantial
expense of collecting, storing, and ultimately disposing of platelets
that are not used; and protect patients by reducing the risk of
infection.
Low-Intensity Warfarin Therapy Prevents Recurrence of Blood Clots
without Adding Risks
Deep vein thrombosis (DVT) is the formation of a blood clot in
an intramuscular vein. DVT typically arises in a leg vein, and,
left untreated, it can lead to pulmonary embolism, a potentially
fatal condition in which a detached clot travels to the lungs
and enters a pulmonary artery. Risk factors for DVT include long
periods of inactivity that decrease blood flow, such as immobilization
after surgery and travel on long airplane flights. DVT patients
are treated with heparin for 5 to 10 days to prevent clots from
getting larger, then given warfarin, an anticoagulant drug, for
several months to prevent DVT recurrence. However, 6 to 9 percent
of patients develop additional clots after the therapy is completed.
Prolonged use of warfarin is associated with an elevated risk
of dangerous bleeding episodes. In 1998, the NHLBI launched a
multi-center clinical trial to determine whether warfarin given
at a dose that causes a lower intensity of anticoagulation could
prevent the recurrence of DVT and pulmonary embolism following
completion of the standard, higher-intensity warfarin regimen.
The trial, called Prevention of Recurrent Venous Thromboembolism
(PREVENT), showed a 64-percent reduction in episodes of DVT and
pulmonary embolism in study participants taking low-intensity
warfarin compared with those taking a placebo. In addition, researchers
found no evidence of significant risks such as major hemorrhage.
Story of Discovery: Researcher Wins Nobel Prize for Solving the
Mystery of Water Transport
Water constitutes 70 percent of the human body and, as a result,
its organization and distribution in the body must be carefully
controlled. To function properly, some cells must take on water
quickly while others must keep water out. Many serious medical
conditions are related to improper regulation of water. Some,
such as congestive heart failure and pulmonary edema, are associated
with excessive fluid retention. Others, such as diabetes insipidus,
represent a failure (in this case, of the kidneys) to absorb sufficient
amounts of water.
Despite water’s critical role in human health, cellular water
transport remained a mystery of biological science until Dr. Peter
Agre discovered aquaporin-1, a protein that plays a critical role
in water transport. A hematologist supported by the NHLBI, Dr.
Agre was not investigating water transport when he discovered
aquaporins in 1991. Instead, he was studying the Rh antigen, a
protein that is one determinant of blood type. Dr. Agre was trying
to isolate Rh protein from red blood cells when he came upon an
unknown protein in his samples. Rather than discarding the protein
as a contaminant, however, Dr. Agre’s research group examined
it and discovered that the protein closely resembled others found
in abundance on cells from kidney tubules and plant stems. Although
plant cells, kidney cells, and blood cells might not seem to have
much in common, Dr. Agre and colleagues recognized that these
three cell types share a propensity to take on water readily.
Researchers had speculated since the mid-nineteenth century that
cells contain special pores through which water enters and exits.
Believing that the new protein might be the heretofore undiscovered
water channel, Dr. Agre performed a simple yet elegant experiment
in which he modified frog eggs to express the protein on their
surface. When he placed altered and unmodified eggs into a dilute,
aqueous solution, the modified eggs rapidly expanded as they took
on water and, within minutes, exploded; the normal frog eggs did
not. Additional studies by Dr. Agre’s group and others confirmed
that this protein, which was later named aquaporin-1, was the
long-sought-after water pore, demonstrated that water was the
only molecule that could flow through the channel, and identified
members of the aquaporin protein family in a wide range of plant,
animal, and even bacterial cells.
Twelve years after the discovery of aquaporin, researchers believe
that defective aquaporin molecules play a role in a variety of
human diseases and conditions, including diabetes insipidus, Sjogren's
syndrome (a disease characterized by dry eyes and diminished production
of saliva), and cataracts. The importance of aquaporin –
which also has been discussed in the context of developing therapies
to prevent or reduce lung injury, dangerous swelling of the brain
after injury or stroke, and congestive heart failure – was
recognized by the Royal Swedish Academy of Sciences. In 2003,
the Academy presented the Nobel Prize in Chemistry, which Alfred
Nobel designated for “. . . those who, during the preceding
year, shall have conferred the greatest benefit on mankind . .
. [by making] the most important chemical discovery or improvement,”
to Dr. Agre for his role in solving the mystery of how the water
flows into and out of cells.
Researchers Overcome Barrier to Safe, Effective Gene Therapy for
Hemophilia Patients
One of many challenges facing gene therapy researchers is how to
control where therapeutic DNA integrates into the genome. The
risks associated with inserting a gene in the wrong place recently
made headlines when two patients in a French gene transfer study
developed leukemias that may have been caused when the new DNA
disrupted the delicate mechanisms that control cellular growth
and activity. Now, researchers studying hemophilia B appear to
have identified a gene transfer approach, based on a mechanism
that viruses use to infect bacteria, that specifies where the
DNA is inserted. Animal testing indicates that the gene localizes
to the proper site and produces therapeutic amounts of the replacement
protein, Factor IX. Furthermore, protein production occurs only
in the targeted tissue (i.e., the liver) and is maintained over
several months in mouse models of the disease.
A Decade of NHLBI Intramural Research Leads to Safer, More Effective,
Bone Marrow Transplants for a Variety of Diseases
In the early 1990s, even the best candidates for bone marrow transplants
had less than a 60 percent of being cured—and a 30 percent
chance that the procedure itself would kill them. The prognosis
was especially bad for patients over 30, people with advanced
conditions, and those lacking identically matched sibling marrow
donors. Therefore, when the NIH Clinical Center opened its bone
marrow transplantation unit in 1993, researchers sought to minimize
the risks associated with transplant; improve the likelihood that
the procedure would be curative; and make the procedure more successful
for a broad range of patients. Their studies answered questions
about stem cell doses, methods to prevent donor cells from launching
an immune response against a patient’s own tissues, and
pre- and post-transplant regimens to prevent life-threatening
infections. Thanks to these efforts, bone marrow transplants are
more effective and safer for some patients today than ever before.
The best suited bone marrow transplant recipients now face less
than a 20-percent chance of succumbing to transplant-related complications,
and have a 75-percent chance of being disease-free 5 years after
transplant. Furthermore, whereas bone marrow transplant once was
considered only for patients suffering from bone marrow or blood
diseases, researchers have extended the procedure to treat some
patients who have metastatic cancers.
Umbilical Cord Blood Is the Preferred Source of Stem Cells for
Patients with Thalassemia or Sickle Cell Disease
Stem cell transplantation is the only available cure for thalassemia
and for sickle cell disease. Because other therapeutic options
exist for both diseases, the risks associated with bone marrow
transplantation have generally been deemed to be unacceptably
high. Now, researchers have found that pediatric patients who
receive stem cell transplants to cure sickle cell disease or thalassemia
fare better if the donor stem cells come from the umbilical cord
blood of a matched sibling rather than from a sibling’s
matching bone marrow. Whereas sickle cell disease and thalassemia
patients who receive bone marrow transplants from HLA-matched
siblings have a 6- to 15-percent chance of dying from transplant
related complications, each of the 44 umbilical cord blood recipients
studied was alive 47 months after receiving the transplant. Moreover,
79 percent of the children who had thalassemia and 90 percent
of those with sickle cell disease survived without any serious
complications, and an even larger percent survived without developing
chronic graft-versus-host disease.
Hydroxyurea Therapy Improves Survival in Most Severely Affected
Sickle Cell Patients
Sickle cell disease (SCD) is an inherited disease that, in the
United States, primarily affects people of African ancestry. Treatments
for adults suffering from SCD did not exist until 1995, when the
Multicenter Study of Hydroxyurea (MSH) in Sickle Cell Anemia showed
that treatment with the drug hydroxyurea resulted in a 50-percent
reduction in the number of painful crises and episodes of a life-threatening,
pneumonia-like illness called acute chest syndrome. Moreover,
during the 2½ year study, patients receiving hydroxyurea
required 50 percent fewer blood transfusions and hospitalizations.
After the MSH ended, trial participants, in consultation with
their physicians, could choose to continue, stop, or start hydroxyurea
therapy and to participate in a subsequent observational study.
The follow-up study showed that hydroxyurea not only protects
adults who have SCD from painful crises and acute chest syndrome,
but also prolongs their lives. Even the sickest patients—those
who suffered three or more crises a year—benefited. Because
severely ill patients require more emergency room visits and hospitalizations
than those who have less severe disease, the results have important
implications both for improving patient care and for decreasing
health care costs.
NIH ROADMAP
Because the NHLBI is a disease-oriented institute, clinical research
is an essential component of its portfolio. Particularly with
regard to clinical trials, the Institute has worked to develop
efficient, less costly research approaches to evaluating therapeutic
and preventive strategies. The ALLHAT (Antihypertensive and Lipid-Lowering
to Prevent Heart Attack Trial), for example, involved 42,000 patients
and could easily have cost more than $400 million if conducted
in a traditional manner. Instead, it was conducted as a “large
simple trial” with participation of physicians from many
types of medical settings. As a result, the actual cost of the
trial was markedly reduced. The NHLBI has also developed and refined
the “clinical research network” concept and successfully
applied it to study of conditions such as pediatric cardiovascular
disease, asthma, acute respiratory distress syndrome, and Cooley’s
anemia. The networks provide an infrastructure that enables rapid
and efficient testing of new therapies as they come to light.
Thus, the NHLBI is an enthusiastic participant in the initiative
titled Re-Engineering the Clinical Research Enterprise: Feasibility
of Integrating and Expanding Clinical Research Networks, which
was issued on December 2 as part of the NIH Roadmap for Accelerating
Medical Discovery to Improve Health. This new contract solicitation
encourages development of activities that demonstrate how clinical
research networks can collaborate to conduct clinical trials and
other multicenter clinical research studies. Once clinical researchers
understand how networks can overcome challenges such as those
presented by differences in study management, investigator interests,
disease definitions, reporting procedures, data-and specimen-sharing
policies, and informatics tools, they will be able to address
more extensive research questions and to conduct clinical research
more efficiently than the current system allows. By applying lessons
learned from this roadmap initiative, the NHLBI will be better
able to accelerate the pace of heart, lung, blood, and sleep research
and to reduce barriers that prevent research advances from becoming
incorporated into clinical practice and improving patient care.
NHLBI NEW INITIATIVES
Clinical Trials for the Prevention and Treatment of Infections
after Cardiac Surgery
With greater numbers of cardiac surgeries being performed each
year, cardiovascular infections caused by the bacterium Staphylococcus
aureus are becoming a national medical problem. Results of a recent
study of over 16,000 coronary artery bypass graft (CABG) surgery
patients, published in the August 2003 edition of the Journal
of the American Medical Association, found postsurgical infection
to be the most common reason for readmission to the hospital within
30 days of CABG surgery. Statistics from the Centers for Disease
Control and Prevention indicate that the presence of S. aureus
in the blood of hospital patients is becoming much more common.
Perhaps even more alarming is that S. aureus is becoming more
resistant to antibiotics. The NHLBI plans to initiate two parallel
randomized clinical trials to address the prevention and treatment
of S. aureus in cardiac surgery patients. The main objective of
one, the Prevention Trial, is to prevent infection of the sternum
with S. aureus in patients undergoing cardiac surgery. The main
objective of the other, the Treatment Trial, is to decrease mortality
and morbidity for patients with an infection in a major wound
that requires two or more days of antibiotic treatment within
30 days of surgery. Both trials will assess the costs and benefits
of new anti-bacterial strategies compared with standard medical
care and should provide a basis for improved control of such infections.
Reduction of Cardiovascular Risk in American Indians and Alaska
Natives
American Indian/Alaska Native (AI/AN) communities bear a heavy
burden of cardiovascular disease (CVD) and modifiable CVD risk
factors. Despite extensive documentation of these problems in
observational studies, few intervention studies have been launched
to test possible solutions. Tribal leaders have urged that research
in their communities focus on finding solutions for the most serious
health issues they face, including obesity, diabetes, CVD, and
sleep difficulties. To address their concerns, the Institute will
test approaches to reducing CVD risk factors in AI/AN populations.
A central feature of the initiative will be the development of
interventions that can be incorporated into the clinical programs
of community health care systems or delivered through other public-health
avenues in native communities.
Cardiovascular Disease Risk in Jackson, Mississippi
The Jackson Heart Study (JHS) was initiated in 1998 to identify
factors associated with increased prevalence and severity of CVD
in 5,500 African American adults living in the Jackson, Mississippi,
area. The study, which will be extended through FY 2009, is uniquely
positioned to identify factors that influence the development
and worsening of CVD in African Americans, with an emphasis on
manifestations related to hypertension such as coronary artery
disease, heart failure, stroke, peripheral arterial disease, and
renal disease. Expansion of the JHS will enable support for additional
clinical examinations and data collection of CVD risk-associated
measures. It will also sustain and enlarge the Jackson-area community
health education component, which uses data derived directly from
the JHS cohort to develop and disseminate practical, up-to-date
information on reduction of risk factors, practice of healthy
lifestyles, and adherence to proven risk-reducing therapies.
Bioengineering Approaches for Prevention and Treatment of Overweight
and Obesity
Bioengineering offers the promise of new approaches for addressing
the obesity epidemic. For example, recent advances in imaging
of body fat content should prove useful in improving specificity
of diagnosis and treatment. Further progress is needed to allow
cellular-level identification of lipids and application to animal
models as well as humans. Potentially valuable methods are likely
to include development of ultrasound, computed tomography, and
MRI techniques in combination with appropriate spectroscopic approaches.
A particularly difficult technical challenge is obtaining sufficiently
precise measurements of energy intake and expenditure. What is
needed is the equivalent of a “magic wristwatch” from
which the wearer could easily determine whether an energy intake
goal has been exceeded or an energy expenditure goal has been
met. New approaches might provide accurate, convenient, easily
understood, and inexpensive devices that would foster research,
improve clinical management of adults and children, and help the
public eat less and exercise more.
NHLBI Centers for the Application of Nanotechnology to
Heart, Lung, Blood, and Sleep Disorders
The rapidly advancing field of nanotechnology offers a wealth of
opportunities for the diagnosis and treatment of heart, lung,
and blood diseases and sleep (HLBS) disorders. Unfortunately,
investigators with nanotechnology experience rarely focus their
efforts on HLBS research, and investigators focused on HLBS disorders
are generally unskilled in the development and use of nanomaterials
and nanotechnologies. Therefore, a crucial need exists to foster
partnerships between the nanotechnology and HLBS research communities.
A new NHLBI program initiative will facilitate the interaction
of scientists from a wide range of complementary disciplines,
such as biologists, engineers, physicists, mathematicians, and
physicians, with the overriding goal of creating nanotechnology
applications for HLBS medicine. Each center will train young scientists
and physicians and will be expected to make materials, reagents,
and devices available to other researchers and to disseminate
technological advances.
Interstitial Lung Fibrosis Clinical Research Network
The NHLBI will develop an Interstitial Lung Fibrosis Clinical Research
Network to conduct clinical trials of treatments for patients
who have idiopathic pulmonary fibrosis (IPF). IPF, an interstitial
lung disease with an especially severe course, has a high fatality
rate and no predictably effective treatment. A lack of success
from clinical trials of promising compounds is leading clinicians
and researchers to believe that a multi-pronged attack with several
agents may be required to treat IPF. Although combination therapies
have not been tested carefully, they are gaining acceptance by
the medical community and rigorous evaluations of new therapeutic
approaches are urgently needed. This initiative will establish
centers to evaluate the efficacy of several antifibrotic and anti-inflammatory
drugs in stabilizing lung disease.
Pulmonary Complications of Sickle Cell Disease
Implementation of comprehensive clinical care programs for children,
prophylactic penicillin therapy to prevent life-threatening infections,
and transfusion programs to prevent stroke have helped many children
with sickle cell disease to survive to adulthood. As adults, however,
many suffer from chronic organ damage, especially in the lungs,
and are at risk for a life-threatening condition known as acute
chest syndrome. Even if the episodes of acute chest syndrome are
not themselves fatal, adults who frequently experience acute chest
syndrome tend to die at younger ages than those who have fewer
events. A program will be initiated to stimulate basic and clinical
research on the pulmonary complications of sickle cell disease
by funding interactive large grants that integrate basic research
on the relationship between red blood cell sickling and lung injury
with clinical investigations.
An NHLBI/National Hemophilia Foundation Cooperative Research Program
for Improved Hemophilia Therapy
The NHLBI and the National Hemophilia Foundation are planning a
cooperative research program to improve treatments for bleeding
disorders such as hemophilia or von Willebrand disease. Although
desmopressin, a hormone that increases the availability of proteins
essential for blood clotting, can help control bleeding in many
people with von Willebrand disease and some who have a mild form
of hemophilia, not all patients respond to it and most become
progressively less responsive after repeated doses. Most people
who have hemophilia receive regular intravenous injections of
replacement clotting factor to prevent undesirable bleeding, but
this regimen is difficult for small children and unpleasant for
older children and adults. In addition, many individuals with
severe hemophilia develop inhibitors that neutralize the ability
of replacement factors to clot blood. The new program will address
the inadequacies of current therapies by supporting research in
several areas identified in discussions with the Foundation. Examples
include research to control or reduce the immune response against
coagulation factors so that people who have hemophilia can continue
to benefit from prophylactic treatments of replacement clotting
factors; to improve delivery of replacement clotting factor and
improve the effectiveness of clotting factors themselves so that
patients do not have to receive the frequent, unpleasant injections
associated with current hemophilia therapy; and to develop new
molecules that interfere with the uncontrolled bleeding associated
with von Willebrand disease and hemophilia without causing undesirable
clotting so that patients who do not benefit from current treatments
have other options.
Genetic and Cellular Discovery in Myelodysplastic Syndromes (MDS)
The increasing prevalence of MDS in the United States is largely
due to the aging of the American population and the greater consequent
opportunities for exposures to cytotoxic and mutagenic chemicals.
MDS, which increasingly are being found in patients following
successful cancer therapy or transplantation procedures, have
highly variable disease processes. Their heterogeneity makes them
difficult to characterize and has limited the development of new
therapeutic approaches. A new initiative to support the profiling
of biologic and clinical markers of MDS is expected to lead to
a better understanding of the diseases and to the discovery of
molecular therapeutic targets for different stages of disease.
Genetic and Cellular Discovery in Myeloproliferative Disorders
(MPD)
The prevalence of MPD is increasing in the U.S. population, but
no curative therapies other than hematopoietic stem cell transplantation
exist. The heterogeneous nature of MPD has complicated efforts
to characterize and to study the highly variable disease processes
in MPD and has limited the development of new therapeutic approaches.
This new program would support analysis of genes that are expressed
in MPD and identification of gene products that are associated
with or responsible for the development or progression of MPD
to a malignant and fatal outcome. Such discoveries will be critical
to the development of new therapies for MPD patients who are not
suitable candidates for hematopoietic stem cell transplantation.
OTHER AREAS OF INTEREST
New High Blood Pressure Clinical Practice Guidelines Issued
A special committee of the National High Blood Pressure Education
Program, representing professional, voluntary, and Federal organizations,
developed new clinical practice guidelines for the prevention,
detection, and treatment of high blood pressure. Called The Seventh
Report of the Joint National Committee on Prevention, Detection,
Evaluation, and Treatment of High Blood Pressure (JNC 7), the
guidelines feature updated blood pressure categories, including
a new “prehypertension” level. The guidelines also
streamline the steps by which doctors diagnose and treat patients
and recommend the use of inexpensive diuretics as part of the
drug treatment plan for high blood pressure in most patients.
Results from more than 30 clinical studies provided the foundation
for the new recommendations and demonstrated the critical importance
of lowering blood pressure, irrespective of age, gender, race,
or socioeconomic status. Special web pages and educational materials
have been developed for health care professionals, patients, and
the public to inform them of the JNC 7 guidelines and to raise
awareness about the dangers of high blood pressure.
Study Tests Ways to Help Americans Keep Weight Off
The NHLBI launched a major study that could help solve one of the
hardest aspects of weight control – keeping lost pounds
off. In phase I of the Weight Loss Maintenance Trial, participants
will receive counseling to help them make lifestyle changes to
reduce their weight. In phase II, participants who lost 9 or more
pounds in phase I will be randomly assigned to one of three weight-maintenance
strategies: self-directed/usual care, personal contact, or interactive
technology. Phase II participants will try to maintain their weight
loss for 2 ½ years. To be eligible for the study, participants
must be overweight or obese, aged 25 years or older, and taking
medication to control high blood pressure and/or high blood cholesterol.
About 60 percent of the study participants will be women and 40
percent will be African Americans. The study will determine which
weight-maintenance strategies help people achieve long-term success
and what effect these strategies have on heart disease risk factors
and quality of life.
Hearts N’ Parks Program Brings Science and Skills to 50 Communities
The Hearts N’ Parks program, a community-based lifestyle
initiative, transfers research knowledge about the health risks
associated with overweight and obesity to the community level
and empowers people to make better lifestyle choices in order
to improve their overall health. Data collected during the first
year of the program show that it is positively influencing health-related
behaviors. For example, children, adolescents, and adults reported
adopting healthier eating behaviors after participating in a Hearts
N’ Parks program. Additionally, adults reported boosting
their level of regular physical activity after the program. Hearts
N’ Parks, sponsored by the NHLBI and the National Recreation
and Park Association, incorporates science-based information about
lifestyle choices that can reduce the risk of coronary heart disease
and skills for adopting heart-healthy behaviors into regular activities
offered by park and recreation departments and other community-based
agencies. The program encourages Americans of all ages to seek
a healthy weight, follow a heart-healthy eating plan, and engage
in regular physical activity. More than 50 Hearts N’ Parks
sites are now active in 11 states throughout the country.
Trial Seeks to Lower Risk of Heart Disease and Stroke in Adults
with Type 2 Diabetes
The NHLBI is moving forward with a full-scale, landmark, clinical
trial to test the best approaches to lowering the risk of heart
disease and stroke in adults with type 2 diabetes. The Action
to Control Cardiovascular Risk in Diabetes (ACCORD) trial will
enroll 10,000 adults with type 2 diabetes in 70 clinics around
the United States and Canada. The trial will evaluate the effects
of intensively controlling blood sugar along with aggressively
controlling blood pressure and blood lipid levels. Results from
the ACCORD trial will help physicians determine the best ways
to treat diabetic patients to prevent the most common and serious
consequence of diabetes – cardiovascular disease. The NHLBI
is sponsoring the trial in collaboration with the National Institute
of Diabetes and Digestive and Kidney Diseases.
Red Dress Raises Heart Disease Awareness for Women
Employing the power of symbolism, the NHLBI has recruited an influential
ally in its fight against heart disease – the red dress.
As a national symbol for women and heart disease awareness, the
red dress is paired with the message that “heart disease
doesn’t care what you wear, it’s not just a man’s
disease.” Women are getting the message; more than 55,000
red dress pins, created by a noted jewelry designer, were requested
and distributed in the initial six months. Additionally, red dresses
from America’s leading fashion designers are being displayed
across the nation as featured exhibits at community events designed
to alert women to their heart disease risk. The Red Dress Project
is a component of The Heart Truth, a national awareness campaign
to motivate women 40-60 years of age to take their heart health
seriously and take steps to lower their risk of heart disease.
The Heart Truth is being conducted in partnership with the American
Heart Association, the Office on Women’s Health of the U.
S. Department of Health and Human Services, WomenHeart–the
National Coalition for Women with Heart Disease, and other organizations
committed to the health and well-being of women.
Interrelationships Between Sleep, Fatigue, and HIV/AIDS
As new therapies extend the life expectancy of HIV-infected patients,
the long-term adverse effects of HIV infection on quality of life
are becoming increasing apparent. Although relatively unstudied,
sleep disturbances and fatigue are highly prevalent and disabling
symptoms in a majority of HIV-infected individuals. Indeed, sleep
complaints are among the first symptoms of HIV infection and are
correlated with decreasing CD4+ lymphocyte counts in otherwise
asymptomatic HIV seropositive individuals. Studies indicate that
HIV infection disrupts the normal cycle of alternating rapid-eye-movement
(REM) and non-REM periods associated with restorative sleep. The
impairment in sleep quality may diminish immunological and cognitive-motor
function, as well as produce fatigue that interferes with the
ability to perform daily activities. The NHLBI, in collaboration
with the National Institute of Mental Health, has initiated a
new research program to elucidate the etiology of sleep disturbances
and fatigue
associated with HIV/AIDS. Knowledge gained from the program is
likely not only to benefit HIV/AIDS patients, but also to improve
fundamental understanding of the relationship between sleep and
chronic disease in general.
NHLBI-ICRH Collaboration
The National Heart, Lung, and Blood Institute is the first of the
NIH components to develop collaborative research programs with
its counterpart institute, the Institute of Circulatory and Respiratory
Health (ICRH), of the Canadian Institutes of Health Research (CIHR).
To advance research in areas of importance in heart, lung, and
blood diseases, the two institutes are together initiating programs
to address new strategies to resuscitate heart attack and trauma
patients; develop new cellular and molecular imaging of heart,
lung, and blood systems; and improve management of thrombotic
disorders such as heart attack, stroke, deep vein thrombosis,
and pulmonary embolism. Each of the programs will be conducted
at multiple sites in Canada and the United States for several
years, beginning in 2004. The collaboration will accelerate research
progress in these areas by enabling support for more investigators
than either Canada or the United States could support separately.
Budget Policy
The Fiscal Year 2005 budget request for the NHLBI is $2,963,953,000,
an increase of $85,847,000 and 3.0 percent over the FY 2004 Final
Conference Level. Also included in the FY 2005 request, is NHLBIs
support for the trans-NIH Roadmap initiatives, estimated at 0.63%
of the FY 2005 budget request. This Roadmap funding is distributed
through the mechanisms of support, consistent with the anticipated
funding for the Roadmap initiatives. A full description of this
trans-NIH program may be found in the NIH Overview.
A five year history of FTEs and Funding Levels for NHLBI are shown
in the graphs below. Note that the Fiscal Year 2001 FTE figure
is not comparable to the figures in the succeeding years due to
NIH’s consolidation of its Human Resources function in FY
2003.
NIH’s highest priority is the
funding of medical research through research project grants (RPGs).
Support for RPGs allows NIH to sustain the scientific momentum
of investigator-initiated research while providing new research
opportunities. The FY 2005 NIH request provides for an aggregate
1.3 percent increase in average cost for Research Project Grants,
consistent with the Gross Domestic Product deflator. The NHLBI
is providing an average cost increase of 1.9 percent for direct
recurring costs in noncompeting continuation awards. Competing
RPGs are based on an average cost increase of 1 percent.
Advancement in medical research is dependent on maintaining the
supply of new investigators with new ideas. In the Fiscal Year
2005 request, NHLBI will support 2,009 pre- and postdoctoral trainees
in full-time training positions. Stipend levels for pre-doctoral
and post-doctoral recipients supported through the Ruth L. Kirschstein
National Research Service Awards will remain at FY 2004 levels.
The Fiscal Year 2005 request includes funding for 67 research centers,
658 other research grants, including 579 clinical career awards,
and 195 R&D contracts. Intramural Research and Research Management
and Support receive increases to support increased pay and estimated
inflationary increases in FY 2005.
NHLBI plans to support several initiatives on obesity in FY 2005
including; allocating $1,000,000 for an initiative with NICHD
on prevention and treatment of pediatric obesity in primary care
settings and $1,500,000 for bioengineering approaches for prevention
and treatment of overweight and obesity.
The mechanism distribution by dollars and percent change are displayed
below:
National Heart, Lung, and Blood Institute
Budget Mechanism - Total
MECHANISM |
FY 2003
Actual |
FY 2004
Final Conference |
FY 2005
Estimate |
No. |
Amount |
No. |
Amount |
No. |
Amount |
|
|
|
|
|
|
3,123
|
$1,386,101,000
|
3,179
|
$1,456,883,000
|
3,158
|
$1,495,524,000
|
(97) |
4,189,000 |
(100) |
5,015,000 |
(100) |
5,319,000 |
|
|
|
|
|
|
21
|
2,963,000 |
23 |
3,174,000 |
23 |
3,206,000 |
1,043
|
460,697,000
|
1,030 |
467,881,000
|
1,058
|
483,717,000 |
355
|
176,906,000 |
350
|
177,794,000 |
362
|
181,717,000 |
675
|
282,786,000 |
666
|
288,982,000 |
682
|
300,886,000 |
13
|
1,005,000 |
14
|
1,105,000 |
14
|
1,114,000 |
1,064 |
463,660,000 |
1,053 |
471,055,000 |
1,081 |
486,923,000 |
4,187 |
1,853,950,000
|
4,232 |
1,932,953,000
|
4,239 |
1,987,766,000
|
239
|
66,251,000 |
247
|
71,000,000 |
250
|
73,100,000 |
4,426 |
1,920,201,000
|
4,479 |
2,003,953,000
|
4,489 |
2,060,866,000
|
|
|
|
|
|
|
77
|
138,941,000 |
70
|
141,984,000 |
67
|
152,187,000 |
0
|
0 |
0
|
0 |
0
|
0 |
0
|
0 |
2
|
1,235,000 |
2
|
1,880,000 |
0
|
0 |
0
|
0 |
0
|
0 |
0
|
0 |
0
|
0 |
0
|
0 |
77 |
138,941,000
|
72 |
143,219,000
|
69 |
154,067,000
|
|
|
|
|
|
|
552
|
65,817,000 |
567
|
67,880,000 |
579
|
69,812,000 |
0
|
0 |
0
|
0 |
0
|
0 |
24
|
21,772,000 |
28
|
23,300,000 |
29
|
23,750,000 |
0
|
0 |
0
|
0 |
0
|
0 |
0
|
2,718,000 |
0
|
2,806,000 |
0
|
2,869,000 |
53
|
22,865,000 |
49
|
13,017,000 |
50
|
13,250,000 |
629 |
113,172,000
|
644 |
107,003,000
|
658 |
109,681,000
|
5,132 |
2,172,314,000 |
5,195 |
2,254,175,000 |
5,216 |
2,324,614,000 |
MECHANISM |
FY 2003
Actual |
FY 2004
Final Conference |
FY 2005
Estimate |
FTTPs† |
Amount |
FTTPs |
Amount |
FTTPs |
Amount |
185
|
8,543,000 |
185
|
8,675,000 |
185
|
8,725,000 |
1,784
|
77,242,000 |
1,802
|
79,326,000 |
1,824
|
79,952,000 |
1,969 |
85,785,000
|
1,987 |
88,001,000
|
2,009 |
88,677,000
|
|
|
|
|
|
|
|
184
|
290,500,000 |
189
|
281,267,000 |
195
|
291,200,000 |
(1) |
(100,000) |
(2) |
(200,000) |
(2) |
(200,000) |
MECHANISM |
FY 2003
Actual |
FY 2004
Final Conference |
FY 2005
Estimate |
|
FTEs†† |
Amount |
FTEs |
Amount |
FTEs |
Amount |
431
|
156,598,000 |
428
|
165,553,000 |
426
|
169,000,000 |
449
|
86,625,000 |
428
|
89,110,000 |
427
|
90,462,000 |
0
|
0 |
0
|
0 |
0
|
0 |
|
0 |
|
0 |
|
0 |
880 |
2,791,822,000 |
856 |
2,878,106,000 |
853 |
2,963,953,000 |
MECHANISM |
FY 2003
Actual |
FY 2004
Final Conference |
FY 2005
Estimate |
0 |
9,884,000 |
18,664,000 |
214,308,000 |
218,000,000 |
224,000,000 |
†FTTP: Full time Training Positions
‡SBIR: Small Business Innovation Research; STTR: Small Business
Technology Transfer
††FTP: Full Time Equivalents
‡ ‡ Amounts included in above tables
|