Hearts & Arteries

Bert Coleman swims three days a week, 88 laps at a time or about 1.25 miles - not so unusual these days if it weren't for his age: He is 65. Coleman fits anyone's picture of physical fitness: He looks healthy; his muscles are strong; he has no excess fat. And for those who need hard evidence, such as cardiovascular scientists, he scores high on the best tests available of physical fitness. On one level it's no surprise that someone who exercises is also physically fit; we take it for granted. But below the surface of that assumption lie intriguing questions. "We know that older people who exercise regularly can do more aerobic work, meaning they are more physically fit," says Edward Lakatta, who is chief of the Laboratory of Cardiovascular Science at the NIA. "But we want to know what changes in the aging heart and blood vessels allow this to happen. What is the link?" Coleman is a volunteer in a study that is looking for answers to this question. But already Lakatta and his colleagues know that the aging heart is not synonymous with a weakening or declining heart. They have learned this through studies over the last two decades that have put together a picture of what happens during "normal" aging - aging in the absence of disease. And now that they understand the aging process, they can turn to the study of lifestyles - such as Coleman's three-times-a-week swimming schedule - to see whether such habits make a difference to the aging heart.

The Effects of Normal Aging

The NIA's studies of normal aging have revealed a series of fine-tuned adjustments that allow the heart to meet the needs of the aging body. This picture is radically different from the one that prevailed several decades ago, when marked declines in overall heart function were thought to be the norm. The revolution in perspective began in the 1970s when researchers came upon their first surprise: The walls of the heart, as it ages, grow thicker. Thickening of the Heart Walls Up until then, the people who study aging - gerontologists - thought that the heart shrank with age. One reason was that early researchers knew about the older heart mainly through chest x-rays and autopsy studies of people who were institutionalized, often with chronic illnesses. These people's hearts, which were affected by disease or extremely sedentary lives, often were smaller than those of younger, healthier people. Then, in the late 1950s, gerontologists began to study healthy volunteers, such as those who take part in the Baltimore Longitudinal Study of Aging. Soon after this came new technologies like echocardiography and radionuclide imaging, exciting because they gave information on wall thickness and cavity size and how they change with time during a given heart beat. Where x-rays provide a static, shadowy silhouette, the newer technologies give thickness, diameter, volume, and in some cases, shape before and during the beat.One of the first soundings of the heart's inner compartments was reported in Finland, where A.J. Sjogren's echocardiograms revealed the thickening of the walls of the left ventricle, the heart's main pumping chamber. Of the heart's four compartments, this one holds the most fascination for cardiovascular scientists; it pumps far harder than the other chambers, starting the blood on its round-about and many-branched journey through the blood vessels. Even a small alteration in this chamber - like wall thickness - makes a significant difference in heart function. Physical Fitness and Aging Many studies have found that physical fitness (measured as maximum oxygen consumption) declines between 5 and 10 percent a decade, but this figure varies widely. Intrigued by the differences, researchers have studied physical fitness in middle-age and older people who remain competitive in sports. The results: These "master athletes" have twice the physical fitness as sedentary people of the same age. Other studies have also shown a connection between regular exercise and physical fitness. For instance, sedentary middle-age men who undertook a 6 - to 8- month training program had significant increases in fitness, and people who exercise regularly have higher fitness levels as they get older.   The thicker walls supplied the first clue that the heart might be adjusting, rather than simply declining, with age. Scientists think that the increased thickness allows the walls to compensate for the extra stress they bear with age (stress imposed by pumping blood into stiffer blood vessels, for instance). When walls thicken, stress is spread out over a larger area. Other findings about the left side of the heart soon followed. In Baltimore, Gary Gerstenblith and his NIA colleagues studied both the left ventricle and the left atrium, the receiving chamber into which the blood flows before passing into the ventricle. Their echocardiograms with BLSA volunteers showed that in addition to the left ventricular wall growing thicker, the cavities of the left atrium and ventricle increased. This study also yielded one other finding - a curious one: The mitral valve appeared to close more slowly in older people. The mitralvalve is at the gateway between the left atrium and ventricle. As the ventricle fills, its two flaps, like a trap door with two separate panels, float up on the rising pool of blood and come almost together to close the passage. If this valve were closing more slowly in older people, as the echocardiograms indicated, then the ventricle must be filling more slowly. Between Beats Why should this be so? And did it make any difference? Researchers turned their attention to a time period, the fraction of a second between heart beats called diastole. During diastole, the heart relaxes, fills with blood, and readies for the next contraction or systole. Heart researchers divide the moments of diastole into even shorter periods. There is the early filling phase when blood from the atrium pushes the mitral valve open, flows rapidly into the ventricle, and floats the valves shut. This early diastolic filling is the phase that takes longer as people grow older, according to the Gerstenblith study. Then comes a late filling phase, when the atrium contracts, forces open the valves a second time, and delivers a last surge of blood to the ventricle, just before it too contracts. Why should early diastolic filling slow down as people age? Could it be because the ventricle wall was not relaxing between heart beats as quickly as it once had? This possibility intrigued the Baltimore scientists because it fit neatly with another stray piece to the puzzle. In animal studies severalyears earlier, Lakatta had learned that rat hearts studied in the laboratory took longer to relax after a contraction when they were from older rats. Later imaging studies in humans confirmed the animal studies: Between beats, the aging ventricle fills with blood more slowly because it is relaxing more slowly than it had when young. Just Before the Beat But now another piece of the diastolic puzzle needed to be filled in. If the left ventricle fills more slowly with blood, does this mean it has less blood pooled at the end of diastole and thus less to send out to the body? The answer is no, and the reason was found in another of the adjustments that the heart makes to age. At the National Heart, Lung, and Blood Institute, scientists showed that the heart compensates for the slower early filling rate by filling more quickly in the late diastolic period. It happens like this: As the mitral valve slowly closes, incoming blood from the lungs pools in the left atrium, which is now larger andholds more blood than when young. In the last moments of diastole, the heart's pacemaker triggers the first electrical impulse (the action potential), which will lead to contraction. The impulse spreads across the cells of the two atriums. The left atrium, stretched with a greater volume of blood in older hearts, contracts harder, pushing open the valves and propelling the blood to the left ventricle. The late surge from the atrium's contraction occurs at all ages but is stronger in older hearts and delivers a greater volume of blood to the left ventricle. As a result, at the end of diastole, the volume of blood in older hearts is about the same (in women) or slightly greater (in men) than in younger hearts. Pumping The next step in this chain of events is contraction or systole, and here the puzzle becomes more complex. Picture the ventricle at the end of diastole filled with a volume of blood that is equal to or slightly greater than the volume inyounger hearts; this is called its end diastolic volume. When the contraction comes, it forces out a certain amount of blood - the stroke volume. But not all is pumped out at once. A portion remains in the ventricle, and this is the end systolic volume. These measurements are important because the links between end diastolic volume, stroke volume, and end systolic volume make up a complex set of dynamics that researchers had to sort out as they attempted to understand what difference aging makes in the heart's pumping ability. The various volumes differ according to age, they may differ according to gender - an area that is just beginning to be explored - and they differ depending on degree of physical activity (see Measuring the Heart) Pumping at Rest The heart rate slows down with age in both men and women when they are sitting at rest. In men, the heart compensates partly for this decline in two ways. First, the increase in end diastolic volume that comes with age means that there ismore blood to pump; and second, the greater volume stretches the ventricular walls and brings into play a peculiar property of muscle cells - the more they are stretched, the more they contract. This phenomenon is called the Frank-Starling mechanism and together with the greater volume to be pumped, it helps to make up for the lower heart rate. In women, end diastolic volume while sitting does not increase with age, so stroke volume does not increase. The difference between the genders probably reflects their different needs rather than a difference in their hearts' pumping abilities. Women tend to have less lean muscle mass than men, and it's lean muscle that needs the most oxygen. When studies compare oxygen consumption based on amount of lean muscle rather than overall body size, the gender differences disappear. Women, in other words, use the same amount of oxygen per unit of lean muscle as do men. Pumping During Exercise During any kind of activity - even moving from a sitting to a standingposition - the heart must pump more blood to the working muscles. In younger people it does this by increasing the heart rate and squeezing harder during contractions, sending more blood with each beat. But age brings changes. Heart rate still rises during exercise, but it can no longer rise as high. Contractions increase in force, but not by as much; one of the most characteristic changes in the aging heart is the loss of the ability to contract as much as it did when young. If it cannot beat as fast or squeeze down as hard, then how does the heart respond to the demands of vigorous exercise? This is the scenario: During exercise, the walls of the older ventricle are stretched by the increased load of blood at end diastole. They cannot pump as efficiently as they once could, but because there is a greater end diastolic volume, they put out about the same amount of blood with each beat. In addition, the increased stretch triggers a series of events that adds calcium ions to the heart muscle cells and increases the calcium's ability to interact with the contractile machinery of the cell - the Frank-Starling mechanism at the molecular level. (More on the cellular mechanisms of aging is found in "Cellular Clues.") The result of these adaptations and adjustments is that the heart is able to meet the needs of the exercising older body. Cardiovascular scientists have several ways to measure heart function. Age, physical activity, and gender all make a difference. The figures given here are in milliliters (ml) per square meter of body surface. They are based on studies with healthy adults, age 20-80, in the Baltimore Longitudinal Study of Aging. End diastolic volume: The volume of blood in the left ventricle at the end of diastole, just before the next beat. At rest, about 65-75 ml per square meter, increasing with age. During exercise, increases in older people, especially in men after age 40. End systolic volume: The amount of blood left in the heart at the end of the beat or systole. At rest, about 25 ml per square meter, increasing with age until about age 70. During exercise, decreases, but not as much in older as in younger people. Ejection fraction: The fraction of end diastolic volume pumped out with each heartbeat. At rest, about 65%, decreasing slightly until about age 60, then rising slightly. During exercise, increases up to about 90% at peak exercise capacity in younger people. The increase is less in older people, reaching about 75% at peak exercise capacity. Stroke volume: The amount of blood pumped with each beat. At rest, about 45-55 ml per square meter; resting stroke volume increases with age in men, not in women. During exercise, increases by about the same amount in both older and younger people, in association with the higher end diastolic volume (Frank-Starling phenomenon). Heart rate: The number of beats per minute. At rest, between 50 and 80. During exercise, increases dramatically, but less in older than in younger people. Maximum heart rate: The number of beats per minute during rigorous exercise; declines 25-30% between ages 20 and 80. Cardiac output: The amount of blood pumped each minute (heart rate x stroke volume). At rest, about 3-4 ml per minute per square meter; decreases in women with age. During exercise, about 10 ml per minute per square meter in young people; decreases by about 30% between ages 20 and 80 due to the decline in maximum heart rate.

The Effect of Lifestyle: Regular Exercise

With this understanding of how the heart adjusts with age, researchers are now turning to people like Coleman who have a regular exercise program. How do their hearts work in comparison with those of 60- and 70-year-olds who do not exercise?Scientists know that regular exercise causes certain changes in the hearts of younger people: Resting heart rate is lower, heart mass is higher, and stroke volume is higher than in their sedentary counterparts. Now there is evidence that these changes occur even when exercise training begins later in life, at age 60 or 70 for instance. In other words, points out Lakatta, "you don't lose the ability to be conditioned." The evidence continues to mount. For example, as activity levels increase, older male athletes have the same increase as younger menin cardiac output, according to studies at NIA and by Ali Ehsani, John Holloszy and colleagues at Washington University in St. Louis, Missouri. At maximum exercise capacity, both stroke volume and cardiac output increase in older men. In many ways, at maximum capacity, older athletes' heart function seems to be closer to that of younger men than to that of older men who do not exercise regularly. Other studies are honing in on some of the molecular changes that take place during exercise (See Exercise and the Aging Myocyte). Questions remain about the precise relationships between age and lifestyle, but cardiovascular scientists can begin to make some educated guesses. It looks more and more as though regular physical activity keeps the aging heart working like a younger heart. Regular exercise, moreover, may influence how or when disease develops and with what severity. Going by what is known so far, it seems a good bet that Coleman's exercise program is keeping his heart healthy and his risk of heart disease down. Selected Readings Ehsani AA, Ogawa T, Miller TR, Spina RJ, and Jilka SM. Exercise training improves left ventricular systolic function in older men. Circulation 83:96-103, 1991. Fleg JL and Lakatta EG. Role of muscle loss in the age-associated reduction in VO2max. Journal of Applied Physiology 65:1147-1151, 1988. Fleg JL, Schulman SP, O'Connor FC, Gerstenblith G, Becker LC, Fortney S, Goldberg AP, and Lakatta EG. Central and peripheral cardiovascular adaptations in highly trained older men. Journal of Applied Physiology, 1994 (in press). Fleg JL, Schulman SP, O'Connor FC, Gerstenblith G, Clulow JF, Renlund DC, and Lakatta EG. Effects of acute beta adrenergic blockade on age-associated changes in cardiovascular performance during dynamic exercise. Circulation, 1994 (in press). Gerstenblith G, Frederiksen J, Yin FCP, Fortuin NJ, Lakatta EG, and Weisfeldt ML. Echocardiographic assessment of a normal adult aging population. Circulation 56:273-278, 1977. Holloszy JO. Exercise, health, and aging: A need for more information. Medicine and Science in Sports and Exercise 15:1-5, 1983. Lakatta EG. Cardiovascular regulatory mechanisms in advanced age. Physiological Reviews 73:413-467, 1993. Rodeheffer RJ, Gerstenblith G, Becker LC, Fleg JL, Weisfeldt ML, and Lakatta EG. Exercise cardiac output is maintained with advancing age in healthy human subjects: Cardiac dilatation and increased stroke volume compensate for a diminished heart rate. Circulation 69:203-213, 1984. Sjogren AL. Left ventricular wall thickness determined by ultrasound in 100 subjects without heart disease. Chest 60:341-346, 1971. Spirito P and Maron BJ. Influence of aging on Doppler echocardiographic indices on left ventricular diastolic function. British Heart Journal 59:672-679, 1988.

The term, physical fitness, evokes a general picture of health and vitality but in cardiovascular science it is a measurable entity. The element measured is oxygen (O2) consumption. O2 consumption is the amount of oxygen used by the body. Scientists calculate oxygen consumption by 1) determining how much oxygen is in the arteries, 2) subtracting from this the oxygen in the veins after the blood passes through the cells, and 3) multiplying the result by the amount of blood the heart pumps each minute (cardiac output). O2 consumption= (O2 in arteries - O2 in veins) x cardiac output As oxygen-rich blood leaves the heart, it flows through smaller and smaller arteries, then arterioles, then capillaries, until it reaches individual cells. The blood diffuses into cells where its oxygen is extracted, then passes back out and into the veins - first the tiny vein capillaries, then larger and larger veins, until it reaches the heart again. The amount of O2 consumed at peak exercise (VO2 max) is considered the best measure of physical fitness. Both heart and peripheral factors improve with exercise training, boosting physical fitness. Stroke volume is higher in conditioned older men, and oxygen extraction also improves.