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Aging Hearts and Arteries: A Scientific Quest by National Institute of Aging - HTML preview

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INTRODUCTION

Age is the major risk factor for cardiovascular disease. Heart disease and stroke incidence rises steeply after age 65, accounting for more than 40 percent of all deaths among people age 65 to 74 and almost 60 percent at age 85 and above. People age 65

and older are much more likely than younger people to suffer a heart attack, to have a stroke, or to develop coronary heart disease and high blood pressure leading to heart failure. Cardiovascular disease is also a major cause of disability, limiting the activity and eroding the quality of life of millions of older people each year. The cost of these diseases to the Nation is in the billions of dollars.

To understand why aging is so closely linked to cardiovascular disease, and ultimately to understand the causes and develop cures for this group of diseases, it is essential to understand what is happening in the heart and arteries during normal aging—aging in the absence of disease. This understanding has moved forward dramatically in the past 30 years. The purpose of this booklet is to tell the story of this progress, describe some of the most important findings, and give a sense of what may lie ahead.

While we know a great deal about cardiovascular disease and its risk factors, new areas of research are beginning to shed further light on the link between aging and the development and course of the disease. For instance, scientists at the National Institute on Aging (NIA) are paying special attention to certain age-related changes that occur in the arteries and their influence on cardiac function. Many of these changes, once considered a normal part of aging, may put people at increased risk for cardiovascular disease.

This and other compelling research on the aging heart and blood vessels takes place at many different research centers. A great deal of the work is being done by researchers in the Laboratory of Cardiovascular Science at the NIA or by NIA-funded scientists at other institutions. Others have worked at or been funded by the National Heart, Lung, and Blood Institute (NHLBI). NIA and NHLBI are two of 27 research institutes and centers at the National Institutes of Health, and their work is complementary. NIA research focuses on the effects of aging on the heart, blood vessels, and other parts of the body, while NHLBI works to understand the diseases and risk factors that affect the heart and blood vessels.

Both perspectives are bringing us closer to the possibility that heart disease and stroke will someday be defeated. Research on the basic biology of the aging cardiovascular system nurtures hope that we as a Nation need not accept the high rates of death and disability and the enormous health care costs imposed by cardiovascular disease among older people in our society.

RICHARD J. HODES, MD, DIRECTOR, NATIONAL INSTITUTE ON AGING

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A Host O F I N T E R C O N N E C T I O N S

The heart is purest theater…throbbing in its cage palpably as any nightingale.

RICHARD SELZER, MD, AMERICAN SURGEON AND AUTHOR

It is scarcely as big as the palm of your hand yet it Scientists called gerontologists, who study aging,

sustains life, pumping up to 5 quarts or more of

are seeking to answer these and other questions.

blood per minute to the body’s organs, tissues,

As a result of this probing, some old ideas about

and cells. In a typical day, it beats 100,000 times.

the aging cardiovascular system are giving way to

And in a lifetime, it beats more than 2.5 billion

new theories. In other cases, gerontologists are just times. Even as you rest, your heart is working

beginning to explore some questions, and the heart

twice as hard as your leg muscles would if you

and arteries are yielding their secrets grudgingly.

were running at full speed.

But to truly understand what is emerging and what

Little wonder then that from earliest mythology to

remains mysterious, we’ll need to start where these

modern medicine, the heart has fascinated and

gerontologists began: in the normal, healthy heart.

perplexed us. Fortunately, today we know far

more about the heart and the blood vessels than

The Intricate Pump

was known even a decade ago. Yet for all scientists

The heart is a marvel of coordination and timing.

have learned, there is still much more to unravel.

Almost completely composed of muscle called

Investigators, for instance, now know that the car-

myocardium, it is well-equipped for its life-long

diovascular system undergoes significant changes

marathon of ceaseless beating. It is essentially two

as we age, and the heart and arteries that we are

pumps in one. The right side pumps blood to the

born with are surprisingly different in later life.

lungs to load up on oxygen and dispose of carbon

But how and why do these changes occur? What

dioxide. The left side pumps oxygen-rich blood to

influence do these changes have on our risk of

the body.

developing heart disease and other cardiovascular

To accomplish these tasks, the heart depends on a

disorders as we get older? Are there any underlying

precise sequence of contractions involving its two

signs—even in people who appear to have healthy

upper chambers—the right and left atria—and its

hearts—that precede and predict who will develop

two lower ones, the right and left ventricles.

severe cardiovascular disease and who won’t?

Between these chambers are two valves, each with

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two or three flaps, also known as cusps. The tricus-

quarter of a second. As they travel, the impulses

pid valve separates the right atrium and the right

are relayed through switching stations at precise

ventricle. Its counterpart, separating the left atrium intervals, eventually causing millions of interlocked and the left ventricle, is called the mitral valve. The cells to contract in near unison.

pulmonic valve controls blood flow out of the right

ventricle to the lungs where it picks up oxygen. The

Age, Change, and Adaptation

aortic valve controls the flow of oxygenated blood

The major sequences in this ever-moving picture

out of the left ventricle into the body. Normally

of the heart beat have been known for nearly 400

these valves let blood flow in just one direction.

years. But gerontologists are uncovering another

The heart beats in two synchronized stages. First,

influence on this chain of events—age—and the

the right and left atria contract at the same time

picture appears to be even more complex. Aging,

pumping blood into the right and left ventricles.

it turns out, brings not a simple slowing down of

Then the mitral and tricuspid valves close. A

heart function, as one might expect, but a set of

intricate alterations: a slowing here, an enhance-

split second later, the ventricles contract (beat)

ment there, a minor adjustment elsewhere. The

simultaneously to pump blood out of the heart.

result of these numerous small alterations is adap-

Together, these coordinated contractions produce

tation. In various ingenious, important ways, the

the familiar “lub-dub” sound of a heart beat—

heart at age 65 has adapted to meet the needs of

slightly faster than once a second. After contracting, the 65-year-old body.

the heart muscles momentarily relax, allowing

blood to refill the heart.

However, these refinements have a downside. In

recent years, gerontologists have learned that

To picture how this all works, imagine that as the

some changes in the structure and function of the

heart relaxes dark red blood returning from the

aging cardiovascular system, even in a healthy

body flows into the right atrium. This blood carries

older person without any diagnosed medical con-

little oxygen and is laden with carbon dioxide,

dition, can actually greatly increase the risk of

which is produced by body tissues. When the right

developing cardiovascular diseases, including high

atrium contracts, it propels oxygen-poor blood

blood pressure, atherosclerosis, and heart failure.

through the tricuspid valve into the right ventricle.

In fact, these changes can create the nearly perfect

In turn, the right ventricle pumps blood into the

setting for the onset of severe cardiovascular dis-

pulmonary artery. From there, it flows into the

ease in some healthy older people.

lungs where it picks up oxygen and returns to the

left atrium. When it contracts, the left atrium

Gerontologists seeking to reconcile these two

pumps the now bright red oxygenated blood

conflicting pictures of cardiovascular aging are

through the mitral valve into the left ventricle,

intensely studying the fundamental underpin-

which pumps it into the aorta, from which it is

nings of the age-associated changes in the heart

distributed to other arteries to nourish your cells,

and arteries in hopes of discovering new ways to

tissues, and organs. Then the cycle begins again.

effectively prevent and treat cardiovascular disease

in older people. This quest—from the impact of

This cardiac cycle is regulated by nerve impulses,

the smallest molecule to the influence of diet and

generated by the heart’s internal pacemaker called

exercise—is radically changing how scientists

the sinoatrial node (SA node), a small bundle of

think about the cardiovascular system.

specialized cells located in the right atrium. These

impulses cause the heart to beat. Once generated by

The notion, for instance, that heart cells can’t

the SA node, the impulses spread in a coordinated

replicate themselves is being reconsidered.

fashion across the heart muscle in less than a

Gerontologists now know far more about how

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aging affects blood vessels and how this process

The modern era of heart research has also

influences the development of atherosclerosis.

depended heavily on the development of powerful,

They are learning much more about how

non-invasive technologies, such as echocardiogra-

physical activity, diet, and other lifestyle factors

phy, magnetic resonance imaging, and radionuclide

influence the “rate of aging” in the healthy older

imaging, which have allowed investigators to easily

heart and arteries.

see valves, walls, and chambers of the heart and

the flow of blood through these chambers. Two

In the Beginning

techniques, thallium scintigraphy, a highly sensitive radionuclide stress test that can detect hidden

Untangling the effects of age from those of disease

coronary artery disease, and stress electrocardio-

and lifestyle is a theme that appears again and

gram (ECG), a measurement of the electrical

again in modern studies of aging. It wasn’t always

activity of the heart, are particularly useful. In

so. In the 1940s and 50s, clinical gerontologists

combination, these two tests allow researchers to

had to conduct most of their studies in chronic

differentiate between the effects of age and the

care hospitals or nursing homes. The people they

effects of coronary disease that is so prevalent

studied lived sedentary lives, and many may have

among older people—effects that were once

had undetected heart disease or other illnesses.

entangled and indistinguishable.

From this perspective, it appeared as if virtually

all bodily functions, including the cardiovascular

The Next Steps

system, deteriorated markedly with age.

As you explore this booklet, you will find that sci-

Then, in 1958, the National Institutes of Health

entists have learned a tremendous amount about

(NIH) launched the Baltimore Longitudinal Study

aging. Today, more than ever, they understand

of Aging (BLSA). This ongoing investigation, now

what causes your blood vessels and heart to age

part of the National Institute on Aging (NIA), has

and know a lot about how this process interacts

tracked the lives of more than 3,000 people from

with cardiovascular disease-related changes. In

age 20 to 90 and older in an effort to document

addition, they have even pinpointed risk factors

the normal or usual physiological changes that

that increase the odds a person will develop car-

occur in a stable population of people who live in

diovascular disease as well as other illnesses. And

the community rather than institutions. BLSA

while many mysteries of the aging heart and arter-

data have been valuable to scientists searching for

ies remain unsolved, gerontologists have discov-

different ways in which aging, lifestyle, and disease ered much about how to prevent or postpone

affect the heart and blood vessels.

heart disease in later life.

Scientists have been fascinated with the heart for centuries. Left: This 1523 woodcut by Jacopo Berengario da Carpi was sophisticated for its time. Right: Today, researchers use magnetic resonance imaging (MRI) 7

and other high-tech tools to study the living heart.

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T H E Ag ing H E A RT

The heart is a tough organ: a marvelous mechanism that, mostly without repairs, will give valiant pumping service up to a hundred years.

WILLIS JOHN POTTS, MD, AMERICAN SURGEON, 1895-1968

For 92-year-old John Bicknell, this is the best of

assumption lie intriguing questions that scientists

times. A long-retired English professor, he remains

are just beginning to answer. “We know that older

mentally and physically active. In addition to

people who exercise regularly can do more aerobic

singing in community choirs and performing in

work, meaning they are more physically fit,” says

local musical theater productions, he continues to

Edward Lakatta, MD, who is chief of the

mow his own large yard and often walks up to a

Laboratory of Cardiovascular Science at the NIA.

mile or two a day around his island home in Maine.

“But for decades gerontologists have wanted to

know what changes in the

As he walks around his property, Bicknell some-

aging heart and arteries

times gathers small twigs and branches for kin-

allow this to happen.

dling, and makes a mental note of larger deadfall

Fortunately, in the past few

so he and his son-in-law can return later to cut it

years, we have uncovered

up and haul it back to the house in a truck. An

some remarkable new clues

avid boater, he frequently motors between the

that have clarified how and

island and the mainland. In the summer, he enjoys

why these changes occur.

swimming with his grandchildren in the brisk, but

At the same time, however,

invigorating waters of a nearby cove.

we have detected some

After a recent trip to England and France, he

intriguing evidence that

returned home to a brewing winter storm. The

transforms much of what

next morning, he shoveled 9-inches of snow off

we once thought of as nor-

his deck and front porch.

mal cardiovascular aging.”

John Bicknell

He looks healthy; his muscles are strong; he has no

Many of these adjustments are remarkably effi-

excess fat. And while gerontologists now know

cient, helping the older heart work as well as pos-

that John Bicknell’s 92-year-old heart is not quite

sible. But some ultimately may be detrimental. In

the same as it was when he was 22, it continues to

particular, some gerontologists suspect several of

serve him extraordinarily well.

these age-related changes may lower the heart’s

resistance to disease and compromise its ability

On one level, it’s not surprising that an older

to respond to increased demands for blood and

person who exercises regularly is more physically

oxygen during stress.

fit and better able to care for himself than most

other people his age. But below the surface of that

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“Fortunately, in the past few years, we have uncovered some remarkable new clues that have clarified how and why these changes occur. At the same time, however, we have detected some intriguing evidence that transforms much of what we once thought of as normal cardiovascular aging.”

EDWARD LAKATTA, MD, CHIEF OF THE LABORATORY OF CARDIOVASCULAR SCIENCE, NIA The Effects of Normal Aging

researchers knew about the older heart mainly

through chest x-rays and autopsy studies of people

The emerging methods of studying the heart have

who were institutionalized, often with chronic

led to the growing realization that the many factors

illnesses. These people’s hearts, which were affected influencing the aging heart and blood vessels are

by disease or extremely sedentary lives, often were

interdependent. At least six major factors affect

smaller than those of younger, healthier people.

how the heart fills with blood and pumps it out.

When scientists first discovered these factors, they

Then, in the late 1950s, gerontologists began to

thought they operated independently. But as

study healthy volunteers, such as those who par-

investigators more closely examined these factors,

ticipate in the BLSA. Soon afterward, scientists

they discovered that these six factors influence

devised new technologies like echocardiography

each other in various direct and indirect ways.

and radionuclide imaging. While x-rays provide a

static, shadowy silhouette, echocardiography and

The diagram on the facing page illustrating their

other imaging techniques clearly show thickness,

interdependence is deceptively simple. It shows only

diameter, volume, and in some cases, shape of the

the six broad categories, but each of these terms

heart and how these change with time during a

encompasses a host of related factors. Many of these

given heart beat. Recently, gerontologists have

factors are the focus of rigorous research, including begun using magnetic resonance imaging (MRI)

structural changes in the normal aging heart.

to get a better look at the aging heart. MRI is a

type of body scan that uses magnets and comput-

Structural Changes

ers to provide high-quality images based on vary-

The NIA’s studies of normal aging have revealed a

ing characteristics of the body’s tissues. The tech-

nology allows physicians to noninvasively study

series of fine-tuned adjustments that allow the

the beating heart’s overall structure and function

heart to meet the needs of the aging body. This

continuously in three dimensions.

picture is radically different from the one that

prevailed several decades ago when marked

The thicker left ventricular walls supplied the first declines in overall heart function were thought to

clue that the heart might be adjusting rather than

be the norm. The revolution in perspective began

simply declining with age. Scientists think that the

in the 1970s when researchers came upon their

increased thickness allows the walls to compen-

first surprise: The walls of the left ventricle, as it sate for the extra stress they bear with age (stress

ages, grow thicker.

imposed by pumping blood into stiffer blood ves-

sels, for instance). When walls thicken, stress is

Up until then, gerontologists thought that the

spread out over a larger area of heart muscle.

heart shrank with age. One reason was that early

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CONTRACTILITY

HEART RATE

PRELOAD

CORONARY

AFTERLOAD

FLOW

Heart Dynamics:

Autonomic Nervous System

Six broad factors determine how much blood the heart pumps per minute (cardiac output).

All six are highly interdependent. The following definitions include just a few examples of their interconnections.

HEART RATE — the number of beats per minute;

AFTERLOAD — the forces that resist contrac-

it affects the amount of blood getting to every

tion once it begins; these forces include resist-

organ in the body. It is regulated by the auto-

ance by the arteries to pulsing and steady blood

nomic nervous system.

flow, which depends partly on the “tightness” or

stiffness of arteries. This tightness depends, in

part, on the contractility of vascular smooth

CONTRACTILITY — the ability of the heart

cells with the arteries.

muscle cells to contract in response to an

increase in calcium in their cytosol.

CORONARY FLOW — the flow of blood through

the coronary arteries to the heart muscle itself.

PRELOAD — stretch on the heart cells prior to

Since the coronary flow determines how much

excitation; it is affected by the amount of blood

oxygen reaches the heart muscle cells, it helps

in the left pumping chamber, or ventricle, before

determine their contractility, which affects all

contraction.

other factors.

AUTONOMIC NERVOUS SYSTEM DISCHARGES NEUROTRANSMITTERS — part of the nervous system that controls involuntary muscles such as the heart; it modulates the other five factors in many ways.

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In a Heart Beat

1

2

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Heart muscle relaxes and

Valves float nearly shut and

Electrical impulse begins in sinoatrial

valves open (early diastole)

ventricles fill with blood

node (the heart’s pacemaker); Atria

contract, adding more blood to

ventricles (late diastole)

Heart Filling

pool of blood and come together to close the pas-

sage. If this valve were closing more slowly in older Other findings about the left side of the heart soon

people, as the echocardiograms indicated, then

followed. While at the NIA, Gary Gerstenblith, MD,

perhaps the ventricle was filling more slowly.

and his colleagues studied the left ventricle and

the left atrium, the receiving chamber into which