SUPPLEMENTUM 7, 2005, Journal of Sports Science and Medicine

JOURNAL OF SPORTS SCIENCE & MEDICINE

Supplementum 7

CARDIOVASCULAR BENEFITS AND POTENTIAL HAZARDS OF PHYSICAL EXERCISE
IN ELDERLY PEOPLE^*

^*Doctoral dissertation presented on the 11^stof December 2004 at the Agora Center, Jyväskylä, Finland by permission of Faculty of Medicine of the University of Kuopio.

Mauri Kallinen

The Finnish Centre for Interdisciplinary Gerontology, Department of Health Sciences, University of Jyväskylä, Jyväskylä, Finland;
LIKES-Research Center for Sport and Health Sciences, Jyväskylä, Finland;
Department of Physical and Rehabilitation Medicine, Central Finland Central Hospital, Jyväskylä, Finland;
Kuopio Research Institute of Exercise Medicine, Department of Physiology, Faculty of Medicine, University of Kuopio, Kuopio, Finland

Published (Online)

01 April 2005

This review is based on the following original publications, which will be referred to in the text as Studies 1-4:

1. Kallinen, M., Suominen, H., Vuolteenaho, O. and Alen, M. (1998) Effort tolerance in elderly women with different physical activity backgrounds. Medicine and Science in Sports and Exercise 30, 170-176.

2. Kallinen, M., Kauppinen, M., Era, P. and Heikkinen, E. The predictive value of exercise testing for survival among 75-year-old men and women. Submitted for publication.

3. Kallinen M, Sipilä S, Alen M, Suominen H. (2002) Improving cardiovascular fitness by strength or endurance training in elderly women. A population-based randomized controlled trial. Age and Ageing 31, 247-254.

4.Kallinen M, Era P, Heikkinen E. (2000) Cardiac adverse effects and acute exercise in elderly subjects. Aging 12, 287-294.

ABSTRACT

Large and consistent beneficial effects with few adverse effects have been found in relation to physical exercise in selected samples of elderly subjects. However, thus far, it has not been confirmed to what extent the effects of physical exercise among elderly people are beneficial or even harmful in population-based studies. Additionally, the role of exercise testing among elderly people remains unclear. Firstly, the effects of prolonged physical training on cardiovascular fitness in 66-85-year-old women were examined in a cross-sectional study. Secondly, the predictive value of exercise-test status and results, including exercise capacity for survival, were studied in 75-year-old men and women. Thirdly, the effects of an endurance and strength training programme were examined in women aged 76 to 78 years in a population-based randomized controlled trial. Finally, the cardiac-adverse effects of acute exercise in the form of a cycle ergometer test were clarified in 75-year-old men and women. In the maximal exercise tests the mean peak oxygen uptake was respectively 26.2 and 18.7 ml·kg^-1·min^-1 among the physically active and less active control women. High cycling power (Watts per kg body weight) in the completed ergometer test was associated with decreased risk for death (multivariate HR 0.20; CI 0.08 - 0.50). The 18-week strength training resulted in a 9.4% increase in peak oxygen uptake while the endurance training improved peak oxygen uptake by 6.8%. A significant increase in cycling power in W/kg was found in the strength and endurance training groups compared to controls. Five cases of cardio- or cerebrovascular health problems emerged in the exercise training groups. These health problems were not directly related to physical exertion. In the final study 23 and 7% of the exercise tests in men and women, respectively, were prematurely terminated because of cardiac arrhythmia or ST segment depressions. Using various study designs and methods the effects of physical training on cardiovascular fitness were found to be beneficial among the four different samples of elderly people. High exercise capacity was found to be strongly and independently associated with decreased mortality among elderly men and women. Exercise testing provides information on the risk of death that is incremental to clinical data and traditional risk factors for death. Cardiovascular monitoring during exercise testing is recommended as a safety precaution. Cardio- or cerebrovascular health problems can occur during exercise training programmes involving elderly people, although they may not be directly related to physical exertion. The dose-response relationships in relation to physical exercise among elderly people remain in need of further clarification in population-based trials.

KEY WORDS: Benefits and hazards of exercise, cardiovascular fitness, older people, exercise testing, predictive value, arrhythmia, ST segment depressions.

INTRODUCTION

"Ageing is the process that converts fit adults into frailer adults with increased risk of illness, injury, and death" (Miller, 1999). Ageing is neither a developmental process nor a disease, although a great proportion of older people have some overt or subclinical disease. It is useful but difficult to distinguish whether the age-related changes observed in the human beings are due to ageing itself or consequences of life- style factors, disease processes or genetic factors. These statements offer a basic definition of ageing. However, ageing is a process which individuals encounter in various ways and at different speeds. Ageing also influences different organ systems in varying ways and magnitudes. It is apparent that age-related changes in various physiological characteristics, for example, in cardiovascular fitness vary between the time periods (age cohorts). Studies on these age-related changes encounter problems of cohort and time-of measurement effects, and selection bias due to health (Ingram, 1999).

Physical exercise has effects counter those of age on many body structures and functions (Shephard, 1997a). Cardiovascular fitness, for example, has been found to be markedly higher among older endurance- trained men and women than among older less active subjects (Fitzgerald et al., 1997; Wilson and Tanaka, 2000). Cross-sectional comparisons in aerobic capacity between age groups usually tend to find minimal age- related changes in aerobic capacity because of enhanced selection by health and level of fitness in surviving older age groups. Older people who are fitter and healthier are more likely to survive than their frailer counterparts. Katzel et al. (2001) reported that longitudinal reductions in the absolute VO_2max (in ml·kg^-1·min^-1) among older endurance athletes were two to three times as large as those predicted by cross-sectional analyses or those found longitudinally in their sedentary counterparts. However, Saltin (1986) have suggested that the decline in VO_2max in endurance athletes is comparable regardless of the athletes are studied cross-sectionally or longitudinally.

Since the publication of the origin of the species by Charles Darwin in 1859 it has been claimed that the fittest individuals of different species survive the longest (Balady, 2002; Darwin, 1859). This survival advantage among physically active and fit individuals has been thought to be true in older people (Goraya et al., 2000). Considerable beneficial effects of physical exercise on physical performance have been found in numerous longitudinal surveys and training studies. Recent training studies suggest that adaptation to endurance training is also preserved among the oldest old people (Binder et al., 2002; Malbut et al., 2002; Vaitkevicius et al., 2002). It has been suggested that the magnitude of the gain in aerobic capacity by endurance training is related to age of subject, duration of exercise bouts, length of training programme, and pretraining VO_2max (Green and Crouse, 1995). Most of these cross-sectional and longitudinal studies on cardiovascular fitness have, however, been performed among selected physically active and healthy older people. More data are needed to confirm the beneficial effects of training among the oldest old people aged 75 and over, especially among women, and among those having disabilities.

Strenuous exercise can also have deleterious effects. Few researchers have reported any adverse effects among elderly people both either during acute exhaustive exercise or prolonged physical training. Most of the adverse effects reported have been minor musculoskeletal problems. A large proportion of these studies, again, have been conducted among healthy people below age 75. Subjects with health problems have usually been excluded.

The standard guidelines issued by American College of Sports Medicine (ACSM, 2000) in exercise testing and prescription differ in a few details between elderly and younger people. Exercise testing under the supervision of a physician is recommended for most elderly people during maximal tests and prior to participation in vigorous exercise (ACSM,2000; Fletcher et al., 1995). However, the value of exercise testing both for health screening and predictive purposes among elderly people has been questioned (Gill et al., 2000). It has been suggested that the safety margin in the case of physical exercise is narrower among older than younger people (Kallinen and Alen, 1995). Among older individuals the adverse effects of physical exercise may occur with a lower dose of exercise than among younger individuals. It may also be that older people benefit proportionally more from lower doses of exercise. A relatively few randomised controlled trials have been performed that address the issue of dose-response relationships among elderly people.

REVIEW OF THE LITERATURE

The factors behind age-related decline in physical performance

Muscular strength
Muscular strength is dependant on the amount of the contracting proteins actin and myosin present in the muscles. Loss of these proteins and muscle mass (sarcopenia) starts at the age of 25 and is mainly due to loss and reduction in size of type II muscle fibres. The fibres can change during ageing to types which are neither strictly type I nor type II (Andersen et al., 1999). The mean reduction in the area of the vastus lateralis muscle is 40% between the ages of 20 and 80 (Lexell, 1995). The most apparent decrease in isometric muscle strength is seen after the age of 50 (Larsson and Karlsson, 1978). A similar decline has been reported in isokinetic muscle force (Stanley and Taylor, 1993). The loss of strength seems to proceed more rapidly in women than in men, and is greatest around the menopause. Female sex steroids may play an important role in muscle strength in post-menopausal women (Sipilä et al., 2001; Skelton et al., 1999). Additionally, local growth factors (GH/IGF-I) influence muscle repair, adaptation and other age- related changes in muscles and their function (Harridge, 2003). Muscle satellite cells can form new muscle fibres in cases of muscular trauma and also in response to mechanical stimuli (Seale and Rudnicki, 2000). The age-related changes in skeletal muscle are listed in Table 1.

Older persons who engage in resistance exercise have higher muscle mass and strength than their sedentary counterparts (Sipilä and Suominen, 1993; 1994). Gains in muscular strength greater than 100% have been reported in elderly people after only a few months' strength training (Charette et al., 1991; Fiatarone et al., 1990; 1994; Frontera, 1988). Strength training has also increased muscle cross-sectional area in elderly people (Fiatarone, 1990; Frontera et al., 1988). However, other studies have reported considerably lower changes in muscular strength in elderly people after comparable training intensities and durations (Rice et al., 1993; Sipilä et al., 1996; Skelton et al., 1995). The differences in the gain in muscular strength between these studies may be due to differences in the measure of muscular strength used (1 RM versus isometric muscular strength measurements). Increase in the cross-sectional areas of all fibre types (I, IIA, and IIB) together with a decrease in percentage body fat have been detected after 16 weeks high-intensity resistance training (Hagerman et al., 2000). It has been suggested that age, sex, specific chronic conditions, depression, dementia, nutritional status and functional impairment do not influence adaptation to strength training (ACSM, 1998).

Cardiovascular fitness
The supply of oxygen to the contracting muscles is the most important limiting factor in endurance exercise lasting longer than minute or two. Oxygen uptake is a product of cardiac output and peripheral arteriovenous oxygen difference. Therefore maximal oxygen uptake (VO_2max) is the principal measure of aerobic capacity and cardiovascular fitness. Sustained muscular work leads to hydrogen ion accumulation inside the muscle and a decrease in intramuscular pH. Larger concentrations of inorganic phosphate and a reduced potassium concentration inside muscle cells cause decreased cross-bridge formation, decreased muscle membrane excitation and finally weakness of the muscles.

The ability to perform sustained muscular work is also dependant on the available energy resources, primarily on the muscular stores of glycogen. Although stored fat is substantially used for production of high energy phosphates, glycogen depletion leads eventually to muscle fatigue in prolonged muscular work. The supply of oxygen for oxidation of fat and glycogen and the removal of carbon dioxide are dependant on the cardiovascular (blood flow) and respiratory functions (ventilation).

Several changes occur in the human cardiovascular system during ageing. It is difficult to distinguish whether these changes are related to ageing per se or to the effects of pathological processes in the cardiovascular system, reduced total metabolic tissue mass or physical inactivity. The age-related changes in the human cardiovascular system are listed in Table 2. The most apparent effects of ageing on the human heart are elevated cardiac diastolic volumes and decreased myocardial contractility and maximal heart rates during heavy exercise (Fleg et al., 1995). These alterations are thought to be due to changes in the sympathetic nervous system. An increase in the plasma levels of norepinephrine and epinephrine together with reduced responses to beta-adrenergic stimulation are seen in older subjects (Lakatta, 1993). The increased expression of atrial natriuretic peptides, a marker of increased atrial load and dilatation, is reported to increase in the senescent rodent heart (Younes et al., 1995). Maximal oxygen uptake decreases inevitably with age. This decline in VO_2max is of the order of 5-22% per decade and 0.28 to 1.32 ml·kg^-1·min^-1 per year (Kasch et al., 1999; Posner et al., 1995). A similar decline in aerobic capacity has been reported for both sexes (Fleg and Lakatta, 1988). It has been suggested that the rate of decline in maximal oxygen uptake by age is 50% less in endurance-trained than sedentary adults (Heath et al., 1981).

Declined physical activity and reduced muscle mass account for a large proportion of the reduced maximal oxygen uptake observed during ageing (Ogawa et al., 1992). A smaller stroke volume, decreased maximal heart rate and arteriovenous oxygen difference are also involved in this decline (Fleg, 1994). A twenty-percent lower citrate synthase activity, a marker of aerobic metabolism, has been reported in the muscle of older untrained men aged 58-68 years men compared to corresponding groups of men aged 21 to 33 years (Coggan et al., 1993). In some studies older subjects have reversed a marked proportion of their reduced muscle respiratory capacity by endurance exercise training (Coggan et al., 1993; Meredith et al., 1989). Adaptation in both cardiac function and the peripheral circulation has been detected during exercise training among elderly persons (Beere et al., 1999; Stratton et al., 1994), but peripheral factors may play a major role in adaptation to endurance training in older people (Meredith et al., 1989). Regular intensive endurance exercise has been found to be associated with higher growth hormone and testosterone levels among older runners than their sedentary peers (Hurel et al., 1999). Both hormones are important in preserving fat-free mass during ageing.

Respiratory capacity
It is generally believed that respiratory function does not limit the individual's performance in endurance exercise except in top level athletes (Harms and Stager, 1995). This may not be the case among elderly people.

Detrimental changes are seen during ageing in the chest wall, the bronchial tree, and the lungs (Table 3). These are followed by changes in pulmonary functions e.g. compliance, static lung volumes, pulmonary dynamics, gas exchange, and the oxygen cost of breathing. In some of the oldest persons the ventilatory equivalent, which describes the volume of air ventilated and needed for one litre of oxygen consumed, may exceed 30 l·l^-1. During physical exertion an elderly person may soon approach the dyspnoea threshold in peak tidal volume, which is about 50% of vital capacity (Shephard, 1997a).

Diseases
Ageing is associated with disabling chronic diseases, co-morbidity being quite common. According a recent survey carried out among the Finnish population, 81% of people aged 65 or older have almost one chronic disease (Aromaa and Koskinen, 2002). Thirty percent and 21% of the older men and women have clinically evident myocardial infarction or angina pectoris. In addition to overt coronary heart disease, a large proportion of elderly people may have a symptomless coronary heart disease which it may be possible to detect by exercise ECG and/or thallium scan (Gerstenblith et al., 1980).The prevalence of chronic obstructive pulmonary disease in Finnish older people, according to spirometry, was 27% among older men and 14% among women, respectively. Hip or knee osteoarthritis is evident among 16 to 32% of older men and women (Aromaa and Koskinen, 2002). Psychological factors and cognitive impairment may influence further the management of daily tasks among elderly people (Laukkanen et al., 1993). Poor health was among the commonest obstacles to physical exercise reported in interviews with Finnish elderly men and women (Hirvensalo et al., 1998).

Arteriosclerosis of the coronary arteries decreases coronary blood flow and cause ischaemia in cardiac muscle and deterioration of the pumping power of the ventricles. Under extreme conditions necrosis of the cardiac muscle (myocardial infarction) and a markedly decreased ejection fraction (cardiac failure) follow. The symptoms limiting exercise tolerance in ischaemic heart disease are chest pain and/or dyspnoea. Low creatine phosphate concentrations, high phosphate, high lactate, and low pH values are seen in the skeletal muscles of heart-failure patients during exercise (Wilson et al., 1988). Patients with heart failure have increased sympathetic drive, skeletal and respiratory muscle atrophy and/or weakness, and hyperkinetic cardiovascular responses to physical exercise together with hyperventilation (Chua et al., 1995; Jondeau et al., 1992; Linderholm et al., 1969; Lindsay et al., 1996; Meyer et al., 2001).

The limiting physiological factors during exercise are similar in patients with pulmonary diseases and cardiovascular diseases. An altered ventilation perfusion ratio causes a decrease in PaO₂. Pulmonary hypertension and overload of the myocardium of the right ventricle are usually seen in severe pulmonary emphysema. Also, found among these patients there is reduced skeletal and inspiratory muscle strength together with impaired aerobic capacity of the muscles (Jones and Killian, 2000). In mild chronic bronchitis and bronchial asthma there is no decrease in PaO₂, and the ventilation perfusion ratio could even improve during physical exertion. In many cases the response to exercise is variable among patients with respiratory disorders and these responses are difficult to predict by measuring pulmonary capacity at rest (Jones and Killian, 2000).

Patients with musculoskeletal disorders may be obese, and have decreased muscular strength, endurance and cardiovascular fitness (Ries et al., 1995). A higher prevalence of coronary heart disease has been found among patients assessed before total knee arthroplasty (Philbin, 1995).

Medication
Age and morbidity increase drug use. Elderly women use medication more than elderly men. Diuretics, cardiac glycosides, nitroglycerides and beta-blocking agents as well as analgesics and sedatives are the types of medication most commonly used among the Finnish elderly (Laukkanen et al., 1992). Polypharmacia is also common among elderly people (Laukkanen et al., 1992). Medication may either increase or decrease physical effort tolerance.

Beta-adrenoceptor antagonists (beta-blocking agents) block the β- receptors through which the actions of the sympathetic nervous system are mediated. Two distinct receptors have been found: beta-1- and beta-2 -receptors. Non-selective - blockers attenuate both beta-1- and beta-2-receptor stimulation leading to decreased heart rate, myocardial contractility, glycogenolysis, brochodilatation, vasodilatation and possibly fatty acid mobilisation during exercise. These alterations are advantageous for the patients with coronary heart disease as they decrease the myocardial oxygen demand and increase the myocardial ischaemia threshold. Non-selective beta-blocking agents may lead to central and peripheral limitations of effort tolerance and increased ratings of perceived exertion to external load (Head, 1999). Selective beta-1-blockers have minor negative effects on bronchial dilatation, vasodilatation and fatty acid mobilisation during exercise. Their effects, however, are dose-related, higher doses also having beta-2-blocking effects.

Digitalis increases myocardial contractility by increasing intracellular sodium and calcium (Peel and Mossberg, 1995). This drug is used to treat patients with heart failure and atrial fibrillation to improve left ventricular performance. Digitalis has a narrow therapeutic margin, higher doses causing bradycardia, arrhythmia and fatigue. Digitalis provokes ST segment depression in the ECG, misleadingly indicating myocardial ischaemia. Diuretics increase the excretion of the electrolytes sodium and potassium, and water by the kidneys. A decrease in blood volume results and therefore these drugs are beneficial in hypertension and heart failure. Hypokalemia related to diuretic medication can cause cardiac arrhythmia and muscle fatigue during physical exercise (Peel and Mossberg, 1995).

Calcium antagonists, ACE inhibitors, alpha-1 antagonists and centrally acting alpha-agonists decrease both systolic and diastolic blood pressure and are thus used in hypertension. No significant effects of calcium antagonist and ACE inhibitor medications on maximal oxygen uptake and work rate have been found with among relatively asymptomatic persons. Among patients with marked coronary heart disease or with heart failure these drugs improve hemodynamics and physical effort tolerance. ACE inhibitor use has been found to be associated with a lower decline in muscular strength among elderly hypertensive subjects (Onder et al., 2002).

Nitrates dilate both the system and coronary veins and arteries, reducing the preload of the heart and increasing coronary circulation. These effects are advantageous in patients with coronary heart disease as they increase their endurance work performance (Peel and Mossberg, 1995).

Physical activity
Heredity (Bouchard and Rankinen, 2001), physical activity, body composition and other factors such as life-style and personality contribute to health and health-related fitness (Bouchard and Shephard, 1994). Among physically active individuals the reserve capacity will remain high enough for the performance of the activities of daily living. It has been argued that the decline in the absolute values in cardiovascular fitness is more gentle among physically active than among sedentary persons (Heath et al., 1981; Kasch et al., 1993;1999; Ogawa et al., 1992; Rogers et al., 1990). A large body of evidence exists to show that physical activity is associated with a reduction in all-cause mortality, cardiovascular disease, incidence of type 2 diabetes mellitus, and incidence of colon cancer and osteoporosis (Kesäniemi et al., 2001). A high level of physical activity has been shown to be associated with decreased risk of death in older people in several studies (Bijnen et al., 1999; Glass et al., 1999; Kaplan et al., 1987; Paffenbarger et al., 1986). It also seems evident that regular physical exercise protects against the triggering of cardiac events during vigorous exercise (Mittleman et al., 1993; Willich et al., 1993). On the other hand social and productive activities, such as church attendance, participation in social groups, shopping and gardening have been found to lower the risk of death as much as fitness activities among people aged 65 and older (Glass et al., 1999). Numerous other factors including genetic and socioeconomic factors are also involved in survival (Kujala et al., 2002; Lantz et al., 1998).

A polarisation phenomenon has been found in physical activity habits among elderly people with ageing (Marin, 1988). The proportion of physically very active older people tends to remain almost the same or to increase slightly during the later years of life. The remainder of the older population tend to reduce the amount of their physical activity. The proportion of 75- 84-old Finnish men exercising several times per week to the point of perspiring and heavy breathing was found to be about 17 percent (Hirvensalo et al., 1998). This proportion fell to about 7% over an 8-year follow-up. This declining trend in physical activity has also been seen among women. In a recent extensive survey on the health of Finns aged 30 years and older the most physically active individuals were men aged 65 to 74 years (Aromaa and Koskinen, 2002). Forty-three per cent of the men in this age group exercised at least 4 times per week to the point of light breathing and perspiring. The least physically active were women aged 75 to 84 years of whom fewer than 15% exercised so as to induce light breathing and perspiring at least four times per week. A declining proportion of people were physically active after the age of 74 in both sexes.

Cardiovascular benefits of physical exercise

Effects of physical training on cardiovascular fitness
A marked higher aerobic capacity has been found in several studies comparing older endurance-trained persons with their sedentary counterparts. Inconsistency in the results continues to characterize the results of cross-sectional studies concerning the rate of decline in aerobic capacity between physically active persons and sedentary persons. Fitzgerald et al. (1997) found a steeper decline in absolute maximal oxygen uptake among endurance-trained compared to sedentary women. Jackson et al. (1996) found no difference in the rate of this decline between two corresponding groups of women. In a large meta-analysis this was also true among men (Wilson and Tanaka, 2000). No difference in the relative decline of aerobic capacity has been detected between differently physically active groups of women or men (Fitzgerald et al., 1997; Wilson and Tanaka, 2000). Pollock et al. (1987), however, in a 10-year longitudinal study of runners aged 50 to 82 years reported a 13 percent reduction in maximal oxygen uptake among runners with reduced training intensity compared to a 2 percent loss in maximal oxygen uptake in a group of runners maintaining their habitual training intensity. Similar results have been found in other longitudinal studies among highly physically active subjects (Kasch et al., 1993; 1999; Trappe et al., 1996; Katzel et al., 2001). In the studies by Kasch et al., a lower decline in maximal oxygen uptake expressed in ml·min^-1·kg^-1 body weight was caused by a marked reduction in body weight during the intervention.

Katzel et al. (2001) reported that the longitudinal reductions in absolute VO_2max (in ml·min^-1·kg^-1) were two to three times as large as those predicted by cross-sectional analyses or those found longitudinally in their sedentary counterparts. The relative reduction in aerobic capacity was 22% in older endurance male athletes compared to 14% in sedentary men. The inconsistency of the results in studies comparing the decline in aerobic capacity between physically active and sedentary subjects may be due to differences in the training levels with ageing. It is also obvious that different conclusions can be drawn according to whether the absolute reductions in aerobic capacity are expressed in absolute values (ml·min^-1·kg^-1 or l·min^-1), or as relative decline in aerobic capacity expressed as percentages of the baseline values.

It has been suggested that almost 100% of the age-related decline in aerobic capacity accumulated during 30 years among middle-aged men could be reversed by 6 months' endurance training (McGuire et al., 2001). Up to what age such a kind of reversal in aerobic capacity is possible remains unclear. Considerable increases (up to 38%) in cardiovascular fitness and other positive effects have been reported during endurance exercise programmes among older individuals. Only a few studies, where the exercise dose has been insufficient, have reported no change or even a decrease in cardiovascular fitness with endurance exercise training (Green and Crouse, 1995). The magnitude of the gain in aerobic capacity is dependant on the initial aerobic capacity and age of the subject, and on the duration of the exercise bouts/training programme. The youngest older subjects with the lowest baseline aerobic capacity increased their aerobic capacity most after training with exercise bouts and programme of sufficient duration (Green and Crouse, 1995). However, most studies have been performed among men and subjects younger than 75 years of age excluding subjects with disabilities.

Recent endurance training studies have also been performed among the oldest old and among frail subjects (Binder et al., 2002; Malbut et al., 2002; Vaitkevicius et al., 2002). Binder et al.(2002) found a 13% increase in VO_2peak (95% CI for the improvement 0.9 to 3.6 ml·min^-1·kg^-1) in 9 months' intensive exercise training compared to no increase in VO_2peak after a 9-month low-intensity home exercise program among 115 sedentary men and women aged 83 years (SD, ±4 years) with mild to moderate physical frailty. In this study 15% percent of the target group was excluded from the training programmes because they were considered too frail or ill for vigorous exercise. Furthermore, 27% of the randomized participants dropped out of the study because of medical problems unrelated to the training. Malbut et al. (2002) found a 15% increase in VO_2max after 24 weeks' endurance training in 12 elderly women aged 79 to 91 years, but no change in 9 men. The men in the study by Malbut et al. had a marked higher pretraining VO_2max than women (21.8 vs. 13.8 ml·min^-1·kg^-1) and therefore were not expected to show a large gain in aerobic capacity with endurance exercise training. A six-month community-based moderate endurance training programme resulted in a 6.5% increase in VO_2peak among 22 men and women aged 80 to 92 years in the study by Vaitkevicius et al. (2002). In the latter study the gain in aerobic capacity might have been even more limited had the subjects with submaximal exercise test results after training not been excluded.

Age, sex, specific chronic conditions, depressions, dementia, nutritional status and functional impairment have not been shown to influence adaptation to strength training (ACSM 1998). Some researchers (Hepple et al., 1997; Hagerman et al., 2000) have found beneficial effects of strength training on cardiovascular fitness among elderly people while others have not found any statistically significant differences in cardiovascular fitness with resistance training (Hagberg et al., 1989; Pollock et al., 1991).

Value of exercise-test result including exercise capacity in predicting mortality among elderly people
Exercise testing is widely used to diagnose cardiovascular disease or to evaluate its seriousness. Exercise testing is also recommended for screening purposes for older people starting a vigorous exercise training program (ACSM, 2000) to avoid exercise-triggered cardiovascular complications. Exercise test- results may further have prognostic value with respect to cardiovascular morbidity and mortality as well as all-cause mortality. Exercise capacity, exercise duration, positive exercise electrocardiogram, change in systolic blood pressure during exercise, marked cardiac arrhythmia, and heart-rate recovery have been found to be associated with the risk of death and cardiovascular morbidity even among apparently healthy and asymptomatic populations (Blair et al., 1995; Curfman and Hillis, 2003; Cole et al., 1999; Era et al., 2001; Glover, 1984; Goraya et al., 2000; Gulati et al., 2003; Jouven, 2000; Lakka et al., 1994; McHenry et al., 1984; Messinger-Rapport et al., 2003; Myers et al., 2002; Rywik et al., 1998; Sandvik. et al., 1993). However, relatively few studies have been examined this question among older people and among both sexes (Era et al., 2001; Goraya et al., 2000; Messinger-Rapport et al., 2003).

In the study by Goraya et al. (2000) after adjusting for clinical factors high workload in the treadmill test was the only factor associated with a decreased risk for death and cardiac events among the elderly subjects. One MET (metabolic unit) increase in workload resulted in an 18% reduction in risk for death in elderly persons and a 20% reduction in risk in younger persons. It was concluded that the treadmill exercise testing provided prognostic information that was incremental to the clinical data. The results also showed that the prognostic effect of workload in elderly subjects was of the same magnitude as in younger subjects. However, 72% of the exercise tests among the older participants were done for either the evaluation of documented coronary artery disease or its diagnosis. The participants were selected because of their high likelihood of having coronary heart disease. It is thus difficult to generalise the results of this study across the "normal" elderly population.

It has been suggested that the association of cardiac arrhythmia with subsequent coronary events among apparently healthy older people is weak (Fleg et al., 1993). However, in asymptomatic middle-aged men frequent premature ventricular depolarisations were associated with increased risk of death from cardiovascular causes in a mean follow-up of 23 years (Jouven et al., 2000). It is widely accepted that severe cardiac arrhythmia in relation to coronary heart disease and ischemia increase the risk of subsequent cardiac morbidity and mortality. An ischemic ST segment depression is a predictor of cardiovascular morbidity and mortality (Bruce et al., 1980). Changes in the ST segment are also usually seen in older people's exercise ECGs. The occurrence of ST segment changes is highly predictive of coronary artery disease in subjects with typical symptoms of the disease (angina pectoris). The predictive value, on the other hand, is low when the symptoms are not typical. It is also obvious that the possibility of having both a coronary heart disease and a positive exercise ECG is higher among population with high prevalence of disease i.e. among older people. In a population study Hedbad et al. (1989) found increased mortality among elderly men with ST segment depressions in their 24 hour ambulatory ECG recording. The risk of death was increased also among elderly men with non-symptomatic ST depressions. A high level of physical activity is associated with reduced risk for symptomatic ischemic heart disease. However, in the study of Katzel et al. (1998) the prevalence of exercise- induced silent myocardial ischemia in a maximal exercise test and in tomographic thallium scintigraphy was comparable among master male athletes and among healthy untrained men with no history of ischemic heart disease.

The role and use of exercise testing among elderly people has been questioned by some authors (Gill et al., 2000; Fiatarone Singh, 2002). These authors criticize the routine use of exercise testing among elderly people, starting with a vigorous exercise training programme, as recommended by ACSM and AHA. The difference between vigorous and moderate exercise may be difficult to determine. Furthermore, the interpretation of exercise test results is problematic among elderly people because of non-specific signs and symptoms during testing. Intensive screening by exercise testing and other methods usually excludes a marked proportion elderly people from participating an exercise training programmes. In this way the oldest and frailest people who may obtain the largest benefit from physical exercise may be excluded from exercise training programmes (Fiatarone Singh, 2002).

Possible harmful effects of physical exercise

Effects of acute physical exercise on cardiac function
During heavy exercise plasma ionic concentration of potassium can double compared to the concentration at rest, the decrease in pH could be 0.4 units and increase in plasma catecholamines 15-fold (Paterson, 1996). Pulse rate and systolic blood pressure increase, while diastolic blood pressure tends to decrease slightly. In elderly person the capacity of the heart to increase the heart rate is limited. An aged heart compensates for the decreased left ventricular filling rate in the early diastole by enhanced atrial contraction (Swinne et al., 1992). The left ventricular diastolic volume normalized for body surface area does not differ much between younger and older healthy persons in the resting supine position (Fleg et al., 1995). However, during heavy exercise the diastolic volume of an elderly persons' heart increases suit to the cardiac minute volume to the demands of the working muscles. In younger persons diastolic volume drops to the seated rest level during exhaustive exercise (Fleg et al., 1995). The maximal ejection fraction during exhaustive upright exercise decreases with age due to difficulties in the ability to reduce end-systolic volume (Fleg et al., 1995).

Under the extreme biochemical conditions described above cardiac arrhythmia can be provoked. The heart is, however, protected against this chemical stress during exercise by mechanisms which are unclear. The heart seems to be at greatest risk in the post-exercise period when plasma potassium is low and plasma catecholamines are still at a high level (Paterson, 1996). It has been noticed that cardiac arrhythmia in physical exercise increase with age (Mayuga et al., 1996; Fleg, 1994). Most (about 80%) fatal cardiac arrhythmias are due to coronary atherosclerosis among adult population. Other causes of fatal arrhythmias include cardiomyopathy (10-15%) and among others (< 5%) are primary electrical and genetic ion-channel abnormalities, valvular or congenital heart disease (Huikuri et al., 2001).

General aspects of safety in physical exercise
Acute physical exercise increases the risk of cardiovascular events during the physical effort. The increase in risk is compensated for by a decrease in cardiovascular risk at other times. It is evident that regular physical exercise has beneficial effects on morbidity, mortality, functional decline, mobility, disability, coronary heart disease, and contributes to increase in active life expectancy (Gill et al., 2000). However, an important question is whether the immediate increase in risk during physical effort is age-related. In the epidemiological study by Vuori et al. (1995) both the absolute number of deaths during participation in various physical activities and the risk relative to activity were lower among persons aged 50 to 69 years than in middle-aged people. In contrast Mittleman et al. (1993) found that among people aged 70 years and over the relative risk of onset of myocardial infarction was over double that of younger age groups (< 50 years, 50 to 69 years), although this result did not reach statistical significance in the chi-square test. The researchers also found that the induction time for the onset of myocardial infarction was less than one hour. Furthermore, the corresponding relative risk of persons who were habitually sedentary was 100 compared to 2 among persons engaging in strenuous physical exertion 5 times or more per week (Mittleman, 1993). Similar results were reported by Willich et al. (1993).

Deposition of cholesterol, macrophage infiltration, enlargement of the necrotic core of the plaque, and the accumulation of erythrocyte membranes in an atherosclerotic plaque increase the risk of plaque rupture (Kolodgie et al., 2003). Acute risk factors for exercise-induced cardiac adverse effects are hemodynamic reactivity, hemostatic reactivity and vasoreactivity (Muller et al., 1994). The physical and mental stress quite often serves as an initial triggering mechanism producing hemodynamic changes which leads finally to plaque rupture in the coronary arteries (Muller et al., 1989). The end-point of this complex cascade would be myocardial infarction, cardiac arrhythmia or sudden cardiac death.

Surprisingly few adverse effects during exercise interventions among elderly people have been reported (Belman and Gaesser, 1991; Binder et al., 2002; Buccola and Stone, 1975; Carroll et al., 1992; Cunningham et al., 1987; Ehsani et al., 1991; Hamdorf et al., 1992; Kohrt et al., 1991; Malbut et al., 2002; Puggaard, 2000; Seals et al., 1984; Spina et al., 1993; Suominen et al., 1977a; 1977b; Tzankoff et al., 1972; Vaitkevicius et al., 2002). Most of these effects have been related to musculoskeletal problems. In strength testing Shaw et al. (1995) and Pollock et al. (1991) found some musculoskeletal injuries related to 1RM strength testing. In the study by Pollock et al. (1991) 19% of the elderly subjects sustained a joint injury during 1RM strength testing while 57% of the subjects who began to jog incurred an injury. Strength training resulted in only 2 injuries in 23 subjects (8.7%) and walking in only one injury in 21 subjects (4.8%). A few authors have reported harmful cardiac effects following exercise training among elderly people (DeVries, 1970; Ehsani et al., 1991).

The best way to avoid cardiovascular complications and musculoskeletal problems is prevention. Pre-exercise screening by medical examination is important in this respect. The content of a clinical examination prior to exercise testing and physical training programmes is presented in Table 4. ECG and some blood tests may also be of value in such a pre-exercise evaluation (ACSM, 2000). Plasma N-ANP can be used as a marker of left ventricular dysfunction (Lerman, 1993). The role of plasma C-ANP in the assessment of cardiac function needs to be clarified. The ACSM recommends exercise testing under supervision of the physician in the case of older or sick people starting a heavy exercise training program (ACSM, 2000).

Exercise testing and its safety
The great individual variation in physical capacity and health among elderly people calls for an individual assessment of test modalities (ACSM, 1995; Spirduso, 1995). Methods of assessing endurance capacity can include self-reports, interviews or observations. Measuring cardiovascular fitness can include submaximal or maximal physical capacity tests. During maximal tests the measurement of direct oxygen uptake, carbon dioxide production, ventilation and respiratory exchange ratio (RER) produces accurate measures for aerobic capacity. The value of submaximal tests is limited due to wide individual variation in the maximal heart rates (ACSM, 1995). The most common methods used to asses cardiovascular function during exercise are 12-lead ECG and blood pressure monitoring. Supervision by a physician is recommended when maximal testing is performed with people at high risk (older or sick people) (ACSM, 2000). Exercise testing is used both for diagnostic purposes and to assess physical performance. The diagnostic and prognostic variables generally used during or after exercise testing are listed Table 5. A > 1mm horizontal or downsloping ST segment depression in the early phases of exercise, angina pectoris, marked ventricular arrhythmia, inadequate blood-pressure or heart rate responses during exercise are obvious markers of cardiovascular disease and mean a poor prognosis (Curfman and Hillis, 2003).

Most of the studies related to exercise testing in elderly people have been performed among selected groups of healthy and physically fit elderly subjects. The adverse effects of heavy physical exercise in the form of exercise testing have been found to be minimal in these studies. Morbidity rates of 0 to 232 and mortality rates of 0 to 2.5 per 10 000 exercise tests have been reported (ACSM, 2000). These complication rates depend much on the age and health of the subjects tested. The safety of exercise testing has been studied specifically in the study by Gibbons et al. (1989). It can be calculated from the data given in this study that the complication rate among subjects older than 60 years was 10 times higher than that among the younger subjects. Gibbons et al. (1989) found that the complication rate decreased with time after a cooling-down period phase was added to the exercise protocol. They also found that most of the complications emerged in the immediate or late recovery period (Gibbons et al., 1989).

The American College of Sports Medicine has laid down widely used guidelines for exercise testing and prescription (ACSM, 1995; 2000). According to these recommendations medical clearance is advised prior to maximal exercise testing or participation in vigorous exercise. However, no specific indications for exercise test termination are given for the elderly population. The test modalities need to be modified for elderly populations because of the physiological effects of ageing and concomitant medical problems. It is recommended that exercise testing is started at low intensity, with small increments in work rate and longer stages. Among elderly individuals it is deemed best to keep the total exercise test time between 8 and 12 minutes. The cycle ergometer test is the preferred exercise test loading type (ACSM, 1995). The basic questions related to the safety of exercise testing are: When should the test not be performed? When should a test be stopped? Most of the contraindications for testing and indications for stopping a test are related to cardiovascular disease and cardiovascular disturbances. The contra-indications for exercise testing and indications for test termination are presented in Tables 6 and 7.

Physical training and its safety
The responses to physical exercise are either beneficial or harmful. Improvement in cardio-
vascular fitness and cardiovascular health are among the beneficial effects of an appropriate dose of exercise. High intensity endurance exercise is associated with cardiovascular complications such as cardiac arrhythmia, cardiac arrest and sudden cardiac death. Exercise of high frequency and long duration can provoke musculoskeletal problems.

Exercise type is also important with respect to responses. Aerobic exercise causes changes in the cardiovascular and metabolic body systems whereas anaerobic strength training imposes stress mainly on skeletal muscle. On the other hand the magnitude of stress should be sufficient to induce a process of adaptation in the body's systems, i.e. improvement in cardiovascular fitness or muscular strength.

The intensity of exercise can be defined in absolute terms or relative to the individual's maximal initial level. Usually the level of intensity in endurance exercise is expressed relative to maximal oxygen uptake (i.e. 50-85% VO_2max). The corresponding training heart rates are used by plotting them against the oxygen uptake level during an exercise test (direct method). The direct method is considered to be the best choice when setting an appropriate training intensity for persons with low fitness levels, for those with cardiovascular or pulmonary disease, and for those on some types of medication (e.g., beta-blockers). During exercise testing a safe level of exercise intensity can be established before the adverse effects of exercise arise (ACSM, 2000). Training heart rates expressed as a percentage of the heart rate reserve (i.e. 50-85% of heart rate reserve, HRR) plus resting heart rate (Karvonen et al., 1957) can also be used. The heart rate reserve is calculated by subtracting the maximal heart rate by the resting heart rate. Another way to calculate the training heart rate is to express it as a percentage of the maximal heart rate (i.e. 60-90% of the maximal heart rate, HR_max). The ACSM 2000 recommends the HRR method, which is comparable to the relative values of maximal oxygen uptake. However, among elderly people some authors favour using the percentage of maximal heart rate as it has been found to be accurately related to oxygen uptake in older women and men (Kohrt et al., 1993; Panton et al., 1996). Subjective ratings (rating of perceived exertion, RPE; Borg-scaling 6-20, Borg, 1970) of the intensity of exercise are also used alone or in the combination with other methods.

Muscular strength is best trained using near maximal weights with few repetitions while muscular endurance can be improved by light weights with a greater number of repetitions. Recent guidelines for resistance training among elderly people recommend 8-10 exercises of all the major muscle groups repeated 10-15 repetitions with RPE' s of 12 to 13 (somewhat hard) and a training frequency of two times per week. The resistance training should be at low level during the first 8 weeks to allow adaptation of connective tissues. To maintain adherence to the training program resistance training exercise sessions should not last over 60 minutes. Normal breathing pattern should be maintained while exercising to avoid an excessive rise in systolic and diastolic blood pressure (ACSM, 2000). In addition, to appropriate modes, intensity, duration, frequency and progression of exercise, every exercise session should include warm-up and cooling down exercises to avoid harmful cardiac or musculoskeletal adverse effects (ACSM, 2000).

It has been suggested that the gain in aerobic capacity among elderly people achieved by endurance training is dependant on their initial aerobic capacity. Those with the lowest aerobic capacity have the largest relative potential augmentation of maximal oxygen uptake (ml·min^-1·kg^-1) (Shephard, 1997b). The gain in aerobic capacity is also dependant on the training intensity, frequency and duration. Figure 1 presents the hypothetical dose-response curves for middle-aged and elderly people. It has been suggested that among older individuals both the beneficial and adverse effects of physical exercise may occur with a lower dose of exercise than among younger individuals (Kallinen and Alen, 1995; Shephard, 1997b).

General rules for exercise prescription for elderly people are complicated to obtain because of great individual variation in fitness levels and health. Most of the training studies have been performed among elderly people less than 75 years old. Furthermore, most of these studies have been done among men and healthy people. The general exercise prescription differs in some aspects from that intended for younger age groups. The exercise type should be chosen to cause minimal orthopaedic stress among elderly people. If the effort tolerance of the elderly individual is very limited, one longer exercise session should be divided into several shorter bouts. Exercise duration in aerobic training and repetitions in strength training are the first factors to be increased before increasing training intensity among elderly people (ACSM, 2000). Acute infection, recent myocardial damage, unstable coronary heart disease or significant locomotor disturbances are standard absolute contraindications to progressive exercise training programmes. Other contraindications to progressive endurance or strength training are presented in Table 8. Some warning signs or symptoms, including angina or increased frequency of cardiac arrhythmias (Table 9) in relation to physical exertion, indicate that the exercise programme should be stopped or that the exercise dose, usually intensity, should be reduced.