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European Journal of Heart Failure 2003 5(4):427-434; doi:10.1016/S1388-9842(03)00011-4
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© 2003 European Society of Cardiology

Cardiovascular aging and heart failure

Helen Oxenham* and Norman Sharpe

Department of Cardiology, Royal Infirmary of Edinburgh, Lauriston Place Edinburgh, Scotland, EH3 9QW, UK

* Corresponding author. Tel.: +44-131-536-1000; fax: +44-131-536-2021 E-mail address: helen.oxenham{at}btopenworld.com


   Abstract
Top
 Abstract
1. Introduction
 2. Arterial wall
 3. Myocardium
 4. Changes in cardiovascular...
 5. Consequences of age-related...
 6. Conclusions
 References
 
The aging process is a major factor that contributes to changes seen in the cardiovascular system in older people. Stiffening of the arterial tree alters afterload and left ventricular geometry and although resting left ventricular systolic function is maintained, left ventricular diastolic function changes substantially. Cardiovascular function in older people during exercise is also significantly altered but can be modified by exercise training in older adults or genetic modification in animals. Age-related changes in cardiovascular structure and function also lower the threshold at which cardiac diseases become apparent. This review describes the changes in cardiovascular structure and function at rest and during exercise in older people and highlights their consequences.

Key Words: Aging • Cardiovascular function • Exercise • Heart failure

Received September 16, 2002; Revised December 16, 2002; Accepted January 15, 2003


   1. Introduction
Top
 Abstract
 1. Introduction
2. Arterial wall
 3. Myocardium
 4. Changes in cardiovascular...
 5. Consequences of age-related...
 6. Conclusions
 References
 
Significant changes have been noted in the structure and function of the cardiovascular system in older people that are considered to be the result of aging. These changes can be regarded as either adaptive or early preclinical disease, but they occur in the absence of clinically manifest dysfunction. Age-related changes are influenced by the presence of cardiovascular disease; therefore in order to study the effects of age on the cardiovascular system, individuals without subclinical or overt disease need to be identified [1]. Given the high prevalence of coronary artery disease in this population, careful screening is required and invasive tests such as coronary angiography may be necessary [2].

Evidence regarding aging and human cardiovascular function is generally limited by imaging techniques that can be applied serially to measure anatomy and function and are non-invasive. The effects of age in isolation can be examined using animal models, although translation of animal data to the human model cannot always be assumed. This article reviews the evidence, both in the human and selected animal models, for the changes in cardiovascular structure and function that are associated with the aging process (Table 1).


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  		Table 1 Cardiovascular changes associated with aging and their clinical consequences

 

   2. Arterial wall
Top
 Abstract
 1. Introduction
 2. Arterial wall
3. Myocardium
 4. Changes in cardiovascular...
 5. Consequences of age-related...
 6. Conclusions
 References
 
Increasing age is associated with increased intimal thickness, vascular smooth muscle hypertrophy, fragmentation of the internal elastic membrane and an increase in the amount of collagen and collagen cross-linking in arterial walls [3,4]. A progressive dilatation and elongation of major arteries as well as increased arterial thickening and stiffness accompany these microscopic changes [5]. Arterial stiffening is associated with aging in Western societies even in the absence of demonstrable cardiovascular disease [6,7]. It manifests itself as increased systolic blood pressure [3], widening of the pulse pressure and increased pulse wave velocity [6,8]. These changes create early reflected pressure waves that alter the pressure waveform, lead to an increase in the late systolic pressure peak and contribute to the increased central vascular systolic blood pressure identified in older people [8]. Increased arterial stiffness also causes increases in afterload and end systolic wall stress, which may lead to the development of left ventricular hypertrophy.


   3. Myocardium
Top
 Abstract
 1. Introduction
 2. Arterial wall
 3. Myocardium
4. Changes in cardiovascular...
 5. Consequences of age-related...
 6. Conclusions
 References
 
3.1. Left ventricular mass and dimensions
Although age is a major demographic variable that could affect left ventricular structure, contrasting findings have been reported regarding the relationship between left ventricular mass and age. In the Framingham study, left ventricular mass increased significantly with age in the whole population, but not in a subgroup of normal individuals [9]. Other studies have also concluded that, after excluding subjects with coexisting disease, advancing age is not associated with an increase in left ventricular mass [7,10]. In healthy aging individuals, left ventricular structure has been observed to remodel primarily with an increase in relative wall thickness (ratio of wall thickness to chamber radius) but with little or no increase in overall left ventricular mass [11]. This concentric remodeling parallels the age-related stiffening of the arterial tree whilst hypertension commonly results in concentric hypertrophy of the myocardium with an increase in left ventricular mass. Thus, the increase in left ventricular mass that is often reported to accompany increasing age is likely to be predominantly a function of extra-myocardial influences rather than an intrinsic myocardial aging process.

The relationships between age, left ventricular wall thickness and left ventricular volumes are also controversial. Some studies report small reductions [11] and others small increases [12] in left ventricular volumes or left ventricular wall thickness [7,11] with advancing age. Errors in wall thickness measurements and derived calculations of left ventricular mass [13] may explain this disparity. Significant changes in left ventricular outflow tract geometry occur in older people [13] resulting in a narrowing of the angle between the aorta and the interventricular septum. This changes the position of the interventricular septum relative to the chest wall and leads to systematic errors in echocardiographic M-mode measurements across the left ventricle. In addition, up to 10% of people over the age of 65 years [13] are noted to have a ‘septal bulge’, or widening of the proximal interventricular septum on echocardiography, which may also be a result of the anatomical alterations described above.

3.2. Cellular changes
Histopathological data tend to support the finding that increasing age does not result in an increase in left ventricular mass. Approximately 35% of the total number of myocytes in the ventricles is lost between the age of 30 and 70 years [14]. The cause of this cell death is unknown, but a reduction in capillary density has been noted to occur with increasing age and may lead to ischaemic injury [10]. Perhaps as a compensatory mechanism to account for the cell loss, the volume of the remaining myocytes increases [7,14]. Whether aging in humans is associated with significant changes in myocardial collagen content remains controversial [12]. However, the expansion of the myocyte and non-myocyte compartments of the myocardium occurs in such a way that the proportions of these two structural constituents remain unchanged [14] and no overall increase in myocardial volume with advancing age is observed.

3.3. Molecular changes
Important cellular and molecular alterations underlie the functional abnormalities of the aging myocardium and may represent adaptive compensatory phenomena that result in energy preservation. The alterations include a defect in sarcoplasmic reticulum Ca2+ ATPase pump activity, which controls the rate of Ca2+ reuptake into the sarcoplasmic reticulum during relaxation [15]. There is also a significant reduction in cardiac sarcoplasmic reticulum Ca2+ ATPase protein concentration [16]. Experimental evidence suggests that these changes cause significant prolongation of isovolumetric relaxation [17]. A switch in myosin iso-enzyme type from one with high (V1) to one with low (V3) ATPase activity [12,14] has also been documented in senescent rats. Prolonged contraction and slower myocardial fiber relengthening accompanies this change [14], which has not been observed in the human myocardium.

3.4. Left ventricular function
3.4.1. Systolic function
Left ventricular systolic function remains relatively well preserved and there are no significant alterations in left ventricular ejection fraction, cardiac output or stroke volume at rest [18] with increasing age in men or women [5,12,19]. Recently, we used cardiac magnetic resonance imaging with tagging to assess myocardial function in healthy older adults and were also able to confirm these findings [20]. Our study did, however, show changes in the material motion of the myocardium which were consistent with the 20% reduction in longitudinal shortening and 18% increase in short axis shortening between the ages of 18 and 70 years identified previously in echocardiographic studies [21]. Although their significance is uncertain, alterations in the material motion of the left ventricle accompanying increasing age may be due to the larger mass to end diastolic volume ratio that has been identified in older people.

3.4.2. Left ventricular diastolic function
In contrast to left ventricular systolic function, advancing age is associated with marked alterations in left ventricular diastolic function [22,23]. In humans, cardiac catheterization is the standard technique for direct measurement of diastolic function by using left ventricular filling pressure to assess the rate of left ventricular relaxation. Unfortunately, this technique is invasive and therefore has limited applications. Doppler echocardiography is now accepted as an excellent non-invasive method with which to assess left ventricular diastolic function by measuring blood flow from the left atrium to the left ventricle. Despite significant limitations with this technique such as heart rate [24] and load dependence [25], the parameters obtained provide useful information regarding changes in diastolic function with aging.

3.4.2.1. Transmitral flow
Several large studies have confirmed a significant association between early, E, and late, A, transmitral flow velocities and age [23,26]. Changes in these indices occur gradually and progressively [26,27] and consist of a reduction in early left ventricular filling of approximately 50% [28,29] together with a 40% increase in late left ventricular filling between 30 and 70 years of age [30]. These findings have been shown to be independent of cardiovascular disease [29] or central haemodynamic parameters [22], are accompanied by a prolongation of the deceleration time of the E wave [12,31] an increase in left atrial size [23] and are present in more than 85% of healthy people over the age of 70 years [27]. Doppler indices are reflective of flow patterns and are not synonymous with function; therefore, it is questionable whether age-associated changes in diastolic function signify pathology in an individual subject [26] but it is generally accepted that mitral inflow pattern change with age is likely to be an effect of aging alone.

3.4.2.2. Myocardial diastolic velocities
Tissue Doppler imaging measures low amplitude myocardial velocities and can provide a measurement of the rate of longitudinal dimension or volume change during diastole [32]. This technique has been shown to be less load and heart rate dependent than transmitral flow velocities and it can therefore provide additional information regarding the diastolic properties of the left ventricle with advancing age. Myocardial velocities measured using tissue Doppler imaging of the mitral annulus during diastole also fall progressively with increasing age [32]. A significant fall in the ratio of early to late myocardial velocities, E'/A' with increasing age is also seen [33–35] and although reversal of the transmitral E/A ratio occurs in the seventh decade, reversal of the E' to A' ratio occurs in the fifth decade [32].

3.4.2.3. Left ventricular compliance
It has long been suggested that aging is accompanied by a stiffening of the left ventricle in normal people, yet there is little direct evidence to support this theory. Reduced left ventricular compliance associated with increasing age was identified in an animal study using invasive, simultaneous monitoring of pressure and volume [12]. Passive compliance has been measured in rats and in the absence of hypertension or other cardiovascular disease, does not appear to change with age [36]. Direct evidence that age-related increases in left ventricular stiffness occur in humans came from a study that measured left ventricular pressure–volume relationships in elderly people with chest pain who were being assessed by coronary angiography [19]. An increase in left ventricular diastolic stiffness that correlated and increased with advancing age was observed and these findings were confirmed in a similar study [37].

3.4.2.4. Myocardial relaxation
Myocardial relaxation is a complex process that depends upon early diastolic release of elastic energy that has accumulated during systole [38]. It can be measured indirectly by assessing the time constant of left ventricular pressure decay during isovolumetric relaxation, {tau} [39–41], or non-invasively, by measuring isovolumetric relaxation time and transmitral flow velocities using Doppler echocardiography [29]. Unfortunately, the techniques used to measure myocardial relaxation yield conflicting results regarding the relationship between myocardial relaxation and aging [12,40,42]. In addition, they are unable to directly assess the complex and non-uniform [43], three-dimensional untwisting motion that occurs during myocardial relaxation and diastole. However, animal studies and research using tagged magnetic resonance imaging [20] have been able to identify a significant prolongation of myocardial relaxation in mammalian hearts with advancing age.


   4. Changes in cardiovascular function with exercise
Top
 Abstract
 1. Introduction
 2. Arterial wall
 3. Myocardium
 4. Changes in cardiovascular...
5. Consequences of age-related...
 6. Conclusions
 References
 
Significant changes in cardiovascular function during exercise are noted in aging healthy adults [44]. These changes in some way parallel the adaptations that can occur with deconditioning and result in an altered response to exercise [45].

4.1. VO2max
Oxygen uptake, VO2, is a common measurement for evaluating the capacity of the cardiovascular system and is used as a reflection of maximum cardiac output [46]. VO2max is the greatest amount of oxygen a person can use while performing dynamic exercise and is significantly related to age, gender, exercise habits, heredity and cardiovascular clinical status [47]. A progressive decline in VO2max generally occurs with advancing age, starting between the ages of 20 and 30 years and falling by approximately 10% per decade [18,44,48,49], (Fig. 1). The decline is present in sedentary populations [12] but is less marked [49] when normalized to an index of muscle mass [12] and is seen in longitudinal [50] as well as cross sectional aging studies [5]. Central cardiovascular factors that may influence VO2max through failure to divert enough blood to the muscles, include a reduced cardiac output, reduced maximum heart rate and reduced stroke volume during exercise in older people [12] (Fig. 2).


Figure 1
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  		Fig. 1 Maximum exercise capacity declines with advancing age.

 


Figure 2
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  		Fig. 2 Causes of reduced exercise capacity in older adults.

 
4.2. Maximum heart rate, cardiac output, stroke volume, ejection fraction
Although resting heart rate shows little alteration with age [51], maximum heart rate during exercise decreases progressively from the age of 10, by approximately one beat per minute per advancing year [5,18,44,52]. The mechanism for the reduction in maximum heart rate is unknown [52], but it is not attributable to disease and is not affected by physical conditioning of any duration or intensity [12,51,53,54]. There is an increase in elastic and collagenous tissue in the conducting system of the heart with advancing age as well as a pronounced reduction in the number of pacemaker cells in the sino-atrial node. This results in a significantly diminished intrinsic sinus node rate at rest but also impairment of the chronotropic response to sympathetic nervous system stimulation during exercise.

There have been few large studies measuring cardiac output during exercise in older populations. However, most studies conclude that cardiac output tends to decrease with advancing age during exercise [45,55] by approximately 1.2 l/min per decade and is most noticeable in the eighth decade [12,52]. Stroke volume index at peak exercise is reduced in older individuals [5,45,56] and is thought to be the consequence of age-related reductions in inotropic and chronotropic β adrenergic stimulation, increases in vascular stiffness and aortic impedance and impaired left ventricular diastolic function [57]. Ejection fraction at peak exercise is also reduced in older individuals [45,56,58] because increased afterload, reduced aortic compliance [45] and increased left ventricular wall stress may separately or in combination compromise the ejection of blood during exercise [56]. Administration of a vasodilating agent in older people significantly decreases arterial stiffness, systemic vascular resistance, end diastolic and end systolic volumes and leads to an increase in ejection fraction at rest and during exercise [59].

4.3. β adrenergic responsiveness
Whilst both β adrenergic receptor density and the ratio of β1 to β2 receptors do not change with aging [61], senescent myocytes show a decreased responsiveness to β adrenergic stimulation [57]. Evidence in humans and animals suggests that the effectiveness of β adrenergic modulation on myocardial contractility [12], heart rate and vascular tone declines with advancing age [56,57] and is likely to account for some of the altered responses of the cardiovascular system to exercise in older people [60]. In older, healthy men, compensation for the age-related cardiovascular changes is accomplished by attempting to maintain stroke volume through substantially increasing left ventricular end diastolic volume [18,51]. Exercise induced increases in stroke volume and cardiac output therefore depend on augmented cardiac filling with greater reliance on the Frank Starling mechanism in older people. The Frank Starling mechanism is however, less effective in the elderly due to reduced maximal contraction, reduced augmentation of contractility [5] and increased afterload. Thus, whilst increases in end diastolic volume partially offset the age-related decrease in maximal heart rate, end systolic volume fails to decrease adequately and stroke volume remains significantly reduced compared to younger men [62].

4.4. Changes in diastolic function during exercise
Aging is associated with marked alterations of diastolic filling parameters during both isometric [63] and aerobic exercise [64]. During exercise, the duration of diastole is shortened dramatically secondary to tachycardia. The consequence of a reduced left ventricular filling period coupled with age-associated diastolic impairment may result in filling rates on exertion that are too low to achieve an adequate increase in cardiac output during exercise [65]. Exercise is associated with a progressive acceleration of isovolumetric relaxation [66] secondary to increased elastic recoil. This occurs as a result of increased calcium reuptake secondary to β adrenergic stimulation during exercise [67]. β blockade dampens this effect and has been shown to eliminate age-related differences in diastolic filling between young and old men. Thus some of the reduced left ventricular filling identified in older men on exercise is due to a reduced suction effect and this in turn is due to reduced β-adrenergic responsiveness [57].


   5. Consequences of age-related changes in cardiovascular structure and function
Top
 Abstract
 1. Introduction
 2. Arterial wall
 3. Myocardium
 4. Changes in cardiovascular...
 5. Consequences of age-related...
6. Conclusions
 References
 
Age-related changes may represent physiological impairment or one end of a spectrum of clinical disease. Such changes are likely to lower the threshold for the clinical manifestation of cardiac disease and although they are very common, their significance with respect to the subsequent development of cardiac diseases such as diastolic heart failure is uncertain. A steep increase in the prevalence of heart failure has been noted in older adults [68] in whom a substantial proportion are found to have normal or near normal left ventricular systolic function. The cause of heart failure in these people may be the age-related changes described above. For example, a significant reduction in early left ventricular filling may leave the left ventricle less distended and result in a failure of the Frank Starling mechanism. This, together with an age-associated reduction in left ventricular compliance means that during episodes of myocardial ischaemia or uncontrolled hypertension, left atrial and left ventricular end diastolic pressures increase, leading to pulmonary congestion and oedema. Thus, age-related changes in cardiovascular function, together with the high prevalence of hypertension and coronary artery disease in an older population combine to greatly reduce cardiovascular reserve and significantly increase the risk of heart failure in older adults [69]. Changes in diastolic function are also thought to account for an increase in left atrial size and pressure with advancing age. Hypertension may accentuate these changes and lead to the development of atrial fibrillation, which has a prevalence of approximately 5% in people over 65 years of age [18]. The development of atrial fibrillation in an older person further impairs left ventricular diastolic filling by removing the substantial component that atrial contraction provides. Thus, whilst young adults rely little on atrial contraction to achieve rapid and complete left ventricular filling, older people may lose up to 30% of their cardiac output secondary to loss of atrial contraction. This, combined with a shortened diastolic filling time secondary to rapid ventricular responses further impairs left ventricular diastolic filling, causing an increase in left atrial pressure that may lead to heart failure.

Reduced β adrenergic responsiveness limits heart rate and the contractile response to stress in older people. As a result, the non-compliant left ventricle is unable to accommodate increases in intravascular volume. Pulmonary oedema therefore occurs more readily when older adults receive intravascular fluid, particularly if they require large volumes or where left ventricular function is further impaired by cardiac disease. Decreases in intravascular volume are also poorly tolerated and significant reductions in stroke volume and cardiac output may follow diuretic or vasodilator therapy in older people.


   6. Conclusions
Top
 Abstract
 1. Introduction
 2. Arterial wall
 3. Myocardium
 4. Changes in cardiovascular...
 5. Consequences of age-related...
 6. Conclusions
References
 
The aging process is a major factor that contributes to changes seen in the cardiovascular system in older people. Stiffening of the arterial tree is responsible for alterations in afterload and left ventricular geometry and although resting left ventricular systolic function is unchanged, left ventricular diastolic function alters substantially. Significant alterations in cardiovascular function are also noted during exercise in older people. These are less marked in master athletes and show partial reversibility following exercise training. Animal studies provide further evidence that the ‘aging’ of the cardiovascular system may be modified by physical activity or genetic modification, however, further research is required to evaluate the permanence and significance of these common physiological and structural age-related phenomena. Age-related changes in cardiovascular structure and function significantly lower the threshold at which cardiac diseases become apparent and should be understood by all health care professionals involved in the care of older people.


   References
Top
 Abstract
 1. Introduction
 2. Arterial wall
 3. Myocardium
 4. Changes in cardiovascular...
 5. Consequences of age-related...
 6. Conclusions
 References
 

  1. Kuller L., Borhani N., Furberg C., et al. Prevalence of subclinical atherosclerosis and cardiovascular disease and association with risk factors in the Cardiovascular Health Study. Am J Epidemiol (1994) 139:1164–1179.[Abstract/Free Full Text]
  2. Psaty B.M., Kuller L.H., Bild D., et al. Methods of assessing prevalent cardiovascular disease in the Cardiovascular Health Study. Ann Epidemiol (1995) 5:270–277.[CrossRef][Medline]
  3. Lakatta E. Do hypertension and aging have a similar effect on the myocardium? Circulation (1987) 75(Suppl_I):I-69.
  4. Joyner M.J. Effect of exercise on arterial compliance. Circulation (2000) 102:1214–1215.[Free Full Text]
  5. Lakatta E.G. Cardiovascular aging in health. Clin Geriatr Med (2000) 16:419–444.[CrossRef][Web of Science][Medline]
  6. Vaitevicius P., Fleg J., Engel J., et al. Effects of age and aerobic capacity on arterial stiffness in healthy adults. Circulation (1993) 88:1456–1462.[Abstract/Free Full Text]
  7. Kitzman D., Scholz D., Hagen P., Ilstrup D., Edwards W. Age-related changes in normal human hearts during the first ten decades of life. Part II (Maturity): A quantitative anatomic study of 765 specimens from subjects 20 to 99 years old. Mayo Clin Proc (1988) 63:137–146.[Web of Science][Medline]
  8. Nichols W., O'Rourke M., Avolio A., et al. Effects of age on ventricular–vascular coupling. Am J Cardiol (1985) 55:1179–1184.[CrossRef][Web of Science][Medline]
  9. Dannenberg A.L., Levy D., Garrison R.J. Impact of age on echocardiographic left ventricular mass in a healthy population (the Framingham Study). Am J Cardiol (1989) 64:1066–1068.[CrossRef][Web of Science][Medline]
  10. Olivetti G., Melissari M., Capasso J., Anversa P. Cardiomyopathy of the aging human heart. Myocyte loss and reactive cellular hypertrophy. Circ Res (1991) 68:1560–1568.[Abstract/Free Full Text]
  11. Ganau A., Saba P.S., Roman M.J., de Simone G., Realdi G., Devereux R.B. Ageing induces left ventricular concentric remodelling in normotensive subjects. J Hypertens (1995) 13:1818–1822.[Web of Science][Medline]
  12. Lakatta E. Cardiovascular regulatory mechanisms in advanced age. Physiol Rev (1993) 73:413–467.[Free Full Text]
  13. Swinne C.J., Shapiro E.P., Jamart J., Fleg J.L. Age-associated changes in left ventricular outflow tract geometry in normal subjects. Am J Cardiol (1996) 78:1070–1073.[CrossRef][Web of Science][Medline]
  14. Anversa P., Palackal T., Sonnenblick E.H., Olivetti G., Meggs L.G., Capasso J.M. Myocyte cell loss and myocyte cellular hyperplasia in the hypertrophied aging rat heart. Circ Res (1990) 67:871–885.[Abstract/Free Full Text]
  15. Tate C.A., Taffet G.E., Hudson E.K., Blaylock S.L., McBride R.P., Michael L.H. Enhanced calcium uptake of cardiac sarcoplasmic reticulum in exercise-trained old rats. Am J Physiol (1990) 258:H431–H435.[Web of Science][Medline]
  16. Cain B.S., Meldrum D.R., Joo K.S., et al. Human SERCA2a levels correlate inversely with age in senescent human myocardium. J Am Coll Cardiol (1998) 32:458–467.[Abstract/Free Full Text]
  17. Schmidt U., del Monte F., Miyamoto M.I., et al. Restoration of diastolic function in senescent rat hearts through adenoviral gene transfer of sarcoplasmic reticulum Ca(2+)-ATPase. Circulation (2000) 101:790–796.[Abstract/Free Full Text]
  18. Morley J.E., Reese S.S. Clinical implications of the aging heart. Am J Med (1989) 86:77–86.[Web of Science][Medline]
  19. Chen C.H., Nakayama M., Nevo E., Fetics B.J., Maughan W.L., Kass D.A. Coupled systolic-ventricular and vascular stiffening with age: implications for pressure regulation and cardiac reserve in the elderly. J Am Coll Cardiol (1998) 32:1221–1227.[Abstract/Free Full Text]
  20. Oxenham H., Young A., Cowan B., Doughty R., Sharpe N. Age-related changes in myocardial relaxation using tagged MRI. J Am Coll Cardiol (2001) (Suppl A):37.
  21. Wandt B., Bojo L., Hatle L., Wranne B. Left ventricular contraction pattern changes with age in normal adults. J Am Soc Echo (1998) 11:857–863.[CrossRef][Web of Science][Medline]
  22. Kitzman D., Sheikh K., Beere P., Philips J., Higginbotham M. Age-related changes of Doppler left ventricular filling indexes in normal subjects are independent of left ventricular mass, heart rate, contractility and loading conditions. J Am Coll Cardiol (1991) 18:1243–1250.[Abstract]
  23. Gardin J.M., Arnold A.M., Bild D.E., et al. Left ventricular diastolic filling in the elderly: the cardiovascular health study. Am J Cardiol (1998) 82:345–351.[CrossRef][Web of Science][Medline]
  24. Harrison M., Clifton G., Pennell A., DeMaria A., Cater A. Effect of heart rate on left ventricular diastolic transmitral flow velocity patterns assessed by Doppler echocardiography in normal subjects. Am J Cardiol (1991) 67:622–627.[CrossRef][Web of Science][Medline]
  25. Farias C.A., Rodriguez L., Garcia M.J., Sun J.P., Klein A.L., Thomas J.D. Assessment of diastolic function by tissue Doppler echocardiography: comparison with standard transmitral and pulmonary venous flow. J Am Soc Echo (1999) 12:609–617.[CrossRef][Web of Science][Medline]
  26. Schirmer H., Lunde P., Rasmussen K. Mitral flow derived Doppler indices of left ventricular diastolic function in a general population; the Tromso study. Eur Heart J (2000) 21:1376–1386.[Abstract/Free Full Text]
  27. Sagie A., Benjamin E.J., Galderisi M., et al. Reference values for Doppler indexes of left ventricular diastolic filling in the elderly. J Am Soc Echo (1993) 6:570–576.[Medline]
  28. Wei J. Age and the cardiovascular system. N Engl J Med (1992) 327:1735–1739.[Web of Science][Medline]
  29. Benjamin E.J., Levy D., Anderson K.M., et al. Determinants of Doppler indexes of left ventricular diastolic function in normal subjects (the Framingham Heart Study). Am J Cardiol (1992) 70:508–515.[CrossRef][Web of Science][Medline]
  30. Kuo L.C., Quinones M.A., Rokey R., Sartori M., Abinader E.G., Zoghbi W.A. Quantification of atrial contribution to left ventricular filling by pulsed Doppler echocardiography and the effect of age in normal and diseased hearts. Am J Cardiol (1987) 59:1174–1178.[CrossRef][Web of Science][Medline]
  31. Pearson A., Gudipati C., Nagelhout D., Sear J., Cohen J., Labovitz A. Echocardiographic evaluation of cardiac structure and function in elderly subjects with isolated systolic hypertension. J Am Coll Cardiol (1991) 17:422–430.[Abstract]
  32. Sohn D., Chai I., Dong-jun L., et al. Assessment of mitral annulus velocity by Doppler tissue imaging in the evaluation of left ventricular diastolic function. J Am Coll Cardiol (1997) 30:474–480.[Abstract]
  33. Rodriguez L., Garcia M., Ares M., Griffin B.P., Nakatani S., Thomas J.D. Assessment of mitral annular dynamics during diastole by Doppler tissue imaging: comparison with mitral Doppler inflow in subjects without heart disease and in patients with left ventricular hypertrophy. Am Heart J (1996) 131:982–987.[CrossRef][Web of Science][Medline]
  34. Garcia M., Thomas J., Klein A. New Doppler echocardiographic applications for the study of diastolic function. J Am Coll Cardiol (1998) 32:865–875.[Abstract/Free Full Text]
  35. Lee S, Park S, Choe S, et al. Age-associated changes in parameters of mitral annular dynamics assessed by pulsed Doppler myocardial imaging. J Am Coll Cardiol 2000;Suppl 40.
  36. Brenner D., Apstein C., Saupe K. Exercise training attenuates age-associated diastolic dysfunction in rats. Circulation (2001) 104:221–226.[Abstract/Free Full Text]
  37. Downes T.R., Nomeir A.M., Smith K.M., Stewart K.P., Little W.C. Mechanism of altered pattern of left ventricular filling with aging in subjects without cardiac disease. Am J Cardiol (1989) 64:523–527.[CrossRef][Web of Science][Medline]
  38. Ohte N., Narita H., Hashimoto T., Akita S., Kurokawa K., Fujinami T. Evaluation of left ventricular early diastolic performance by color tissue Doppler imaging of the mitral annulus. Am J Cardiol (1998) 82:1414–1417.[CrossRef][Web of Science][Medline]
  39. Nishimura R., Tajik J. Evaluation of diastolic filling of the left ventricle in health and disease: Doppler echocardiography is the clinicians’ Rosetta stone. J Am Coll Cardiol (1997) 30:8–18.[Abstract]
  40. Yamakado T., Takagi E., Okubo S., et al. Effects of aging on left ventricular relaxation in humans. Analysis of left ventricular isovolumic pressure decay. Circulation (1997) 95:917–923.[Abstract/Free Full Text]
  41. Oki T., Tabata T., Yamada H., et al. Clinical application of pulsed Doppler tissue imaging for assessing abnormal left ventricular relaxation. Am J Cardiol (1997) 79:921–928.[CrossRef][Web of Science][Medline]
  42. Little W.C., Warner J.G., Rankin K.M., Kitzman D.W., Cheng C.P. Evaluation of left ventricular diastolic function from the pattern of left ventricular filling. Clin Cardiol (1998) 21:5–9.[Web of Science][Medline]
  43. Brutsaert D.L. Nonuniformity: a physiologic modulator of contraction and relaxation of the normal heart. J Am Coll Cardiol (1987) 9:341–348.[Abstract]
  44. Malbut-Shennan K., Young A. The physiology of physical performance and training in old age. Cor Art Disease (1999) 10:37–42.
  45. Stratton J.R., Levy W.C., Cerqueira M.D., Schwartz R.S., Abrass I.B. Cardiovascular responses to exercise. Effects of aging and exercise training in healthy men. Circulation (1994) 89:1648–1655.[Abstract/Free Full Text]
  46. Jones N.L., Killian K.J. Exercise limitation in health and disease. N Engl J Med (2000) 343:632–641.[Free Full Text]
  47. Fletcher G.F., Balady G., Froelicher V.F., Hartley L.H., Haskell W.L., Pollock M.L. Exercise standards. A statement for healthcare professionals from the American Heart Association. Writing Group. Circulation (1995) 91:580–615.[Free Full Text]
  48. Fleg J.L., Lakatta E.G. Role of muscle loss in the age-associated reduction in VO2max. J Appl Physiol (1988) 65:1147–1151.[Abstract/Free Full Text]
  49. Ogawa T., Spina R.J., Martin W.H., et al. Effects of aging, sex, and physical training on cardiovascular responses to exercise. Circulation (1992) 86:494–503.[Abstract/Free Full Text]
  50. McGuire D., Levine B., Williamson J., et al. A 30-year follow-up of the Dallas Bed Rest and Training study. II Effect of age on cardiovascular adaptation to exercise training. Circulation (2001) 104:1358–1366.[Abstract/Free Full Text]
  51. Green J.S., Crouse S.F. Endurance training, cardiovascular function and the aged. Sports Med (1993) 16:331–341.[Web of Science][Medline]
  52. Tate C.A., Hyek M.F., Taffet G.E. Mechanisms for the responses of cardiac muscle to physical activity in old age. Med Sci Sports Exercise (1994) 26:561–567.[Web of Science][Medline]
  53. Spina R.J., Ogawa T., Kohrt W.M., Martin W.H.d, Holloszy J.O., Ehsani A.A. Differences in cardiovascular adaptations to endurance exercise training between older men and women. J Appl Physiol (1993) 75:849–855.[Abstract/Free Full Text]
  54. Pollock M.L., Mengelkoch L.J., Graves J.E., et al. Twenty-year follow-up of aerobic power and body composition of older track athletes. J Appl Physiol (1997) 82:1508–1516.[Abstract/Free Full Text]
  55. Spina R.J., Turner M.J., Ehsani A.A. Exercise training enhances cardiac function in response to an afterload stress in older men. Am J Physiol (1997) 272:H995–H1000.[Web of Science][Medline]
  56. Rodeheffer R.J., Gerstenblith G., Becker L.C., Fleg J.L., Weisfeldt M.L., Lakatta E.G. 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 (1984) 69:203–213.[Abstract/Free Full Text]
  57. Spina R.J., Turner M.J., Ehsani A.A. Beta-adrenergic-mediated improvement in left ventricular function by exercise training in older men. Am J Physiol (1998) 274:H397–H404.[Web of Science][Medline]
  58. Port S., Cobb F.R., Coleman R.E., Jones R.H. Effect of age on the response of the left ventricular ejection fraction to exercise. N Engl J Med (1980) 303:1133–1137.[Abstract]
  59. Nussbacher A., Gerstenblith G., O'Connor F.C., et al. Hemodynamic effects of unloading the old heart. Am J Physiol (1999) 277:H1863–H1871.[Web of Science][Medline]
  60. Stratton J.R., Levy W.C., Schwartz R.S., Abrass I.B., Cerqueira M.D. Beta-adrenergic effects on left ventricular filling: influence of aging and exercise training. J Appl Physiol (1994) 77:2522–2529.[Abstract/Free Full Text]
  61. Taffet G.E., Michael L.A., Tate C.A. Exercise training improves lusitropy by isoproterenol in papillary muscles from aged rats. J Appl Physiol (1996) 81:1488–1494.[Abstract/Free Full Text]
  62. Upton M.T., Rerych S.K., Roeback J.R. Jr., et al. Effect of brief and prolonged exercise on left ventricular function. Am J Cardiol (1980) 45:1154–1160.[CrossRef][Web of Science][Medline]
  63. Swinne C.J., Shapiro E.P., Lima S.D., Fleg J.L. Age-associated changes in left ventricular diastolic performance during isometric exercise in normal subjects. Am J Cardiol (1992) 69:823–826.[CrossRef][Web of Science][Medline]
  64. Levy W.C., Cerqueira M.D., Abrass I.B., Schwartz R.S., Stratton J.R. Endurance exercise training augments diastolic filling at rest and during exercise in healthy young and older men. Circulation (1993) 88:116–126.[Abstract/Free Full Text]
  65. Vanoverschelde J.J., Essamri B., Vanbutsele R., et al. Contribution of left ventricular diastolic function to exercise capacity in normal subjects. J Appl Physiol (1993) 74:2225–2233.[Abstract/Free Full Text]
  66. Miyashita T., Okano Y., Takaki H., Satoh T., Kobayashi Y., Goto Y. Relation between exercise capacity and left ventricular systolic versus diastolic function during exercise in patients after myocardial infarction. Cor Art Disease (2001) 12:217–225.[CrossRef]
  67. Libonati J.R. Myocardial diastolic function and exercise. Med Sci Sports Exercise (1999) 31:1741–1747.[Web of Science][Medline]
  68. Vasan R., Larson M., Benjamin E., Evans J., Reiss C., Levy D. Congestive heart failure in patients with normal versus reduced left ventricular ejection fraction. Prevalence and mortality in a population-based cohort. J Am Coll Cardiol (1999) 33:1948–1955.[Abstract/Free Full Text]
  69. Rich M. Epidemiology, pathophysiology and etiology of congestive heart failure in older adults. J Am Ger Soc (1997) 45:968–974.[Web of Science][Medline]

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