LEADING ARTICLE

Sports Med. 1996 Oct; 22 (4): 213-218 01 12-1642/96/001 O-D21 3/S03.DO/O © Adis International limited. All rights reserved.

Coronary Heart Disease Risk Factors in the Physically Active Impact of Exercise Lars Bo Andersen and Merete Hippe The Copenhagen Center for Prospective Population Studies, Copenhagen Hospital Corporation, Copenhagen, Denmark During the last 3 decades, a great amount of evidence has been collected concerning the benefit of physical activity as protection against coronary heart disease (CHD),D] This paper provides a brief overview of the topic. The benefit of physical activity is achieved by different mechanisms. There is the benefit of exercise, independent of the effect on risk factors, and there are effects of exercise on risk factors such as blood lipids, blood pressure, insulin sensitivity, haemostatic factors, and obesity. Recommendations for physical activity have been given to the public in order to reduce disease, including CHDP,3] Even if some consensus has been reached, the mechanisms by which physical activity affects health, and the type, intensity and frequency for maximal benefit, are still matters of debate. Most agree that some physical activity is better than nothing, independent of modality. There are several reasons why it is difficult to be specific about the exercise that provides maximal protection against CHD. In prospective studies, the patients change their physical activity habits during the follow-up; not only the amount, but also the type and intensity. Baseline intensity is a predictor of future CHD, but conclusions are not uniform)4,5] Different types of physical activity are rarely separated into aerobic exercise, resistive exercise, etc. The study by Paffenbarger and Hale[6] is probably the only study where a resistive type of physical activity was measured primarily. Most other studies have used an index of total energy

expenditure, aerobic exercise or an estimation of aerobic fitness.[7-9] In studies using fitness, the relative risk of CHD between groups is greater than in studies comparing sedentary and active groups. However, a high fitness level can be inherited along with other biological risk factors. We do not know whether the benefit of exercise works through fitness, but a high fitness level is probably not protective in sedentary persons,DO] In some studies, a beneficial effect of an increase in physical activity or fitness level in middle-age has been found, which could suggest a causal relationship.[lO-12] Training studies, where the effect of training on CHD risk factors is measured, or cross-sectional studies analysing the associations between these variables, may not have endpoints like CHD or death. However, many of the limitations in prospective studies can be overcome. Also, physiological mechanisms responsible for the benefit of physical activity can be elucidated and important new information may be gathered from such studies. Training studies usually suffer from lack of statistical power, but the training can be very specific and maintained throughout the observation period. It is not possible to show causal relationships from cross-sectional studies, but as the number of study participants can be large, it is possible to show precise graded associations between physical parameters and CHD risk factors. Also, the beneficial effect of exercise can only be shown on the risk

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factors for CHD in groups where disease has not yet developed (e.g. children). The importance of the effects of exercise on risk factors is based on the fact that lower rates of CHD have been found with lower levels of the risk factors. Atherosclerosis starts in childhood and progresses throughout life, and as a high degree of stability over time has been shown for most risk factors, it may be concluded that a low risk factor level is beneficial not only in adults, but also in children,l13- 15 1 In the following sections, the effects of physical activity and training on the main CHD risk factors will be reviewed. Information from cross-sectional and training studies that add to the understanding of the type, amount and intensity of exercise for maximal benefit will be emphasised.

1. Changes in Risk Factors with Exercise 1.1 Blood Pressure

Aerobic exercise lowers blood pressure in all age groupS.[16,17] The effect is greater for systolic than for diastolic blood pressure, and is greater in hypertensive individuals compared with normotensive individuals.[l8-21] Also, exercise reduces the risk of becoming hypertensive.l 22 - 24 ] In crosssectional studies, blood pressure is inversely related to fitness level, but in studies where both physical activity and fitness are measured, physical

activity is not related to blood pressure after adjustment for fitness level. [25,26] This may be interpreted as the effect of physical activity on blood pressure being mediated through fitness. 1.2 Blood Lipids and Haemostatic Factors

There is increasing evidence that physical activity favourably influences blood lipids by an increase in high density lipoprotein level and a decrease in low density lipoprotein and triglyceride levels (table I),l271 However, there is variation between studies which may be caused by the influence of simultaneous changes in diet and bodyweight, on blood lipids and by a mixture of acute and chronic changes in blood lipids. Changes may also be different in men and women. Most studies in men, report no change in total cholesterol and an increase in high density lipoprotein level with exercise trainingJ28] However, in women, exercise training seems to reduce total cholesteroiJ29] It is uncertain whether changes in blood lipids are positively related to intensity and quantity of physical activity, and to initial level of blood lipids, as is the case for blood pressure. Only a few training studies have separated individuals into those with high and low levels of blood lipids (table I). The effect of training is probably partly mediated through changes in receptors and partly through hormonal changes. Many hyperlipidaemic individ-

Table I. Magnitude of changes in cardiovascular risk factors caused by training Risk factor

Individuals with normal risk factor level

p-Values

High risk individuals

p-Values

Triglycerides (mmol/L)

J,31181 J,3 1181 J,0.1S127]

<0.01 <0.01 <0.01

<0.001 <0.001 <0.05

HDL cholesterol (mmol/L)

iO.03127]

NS

LDL cholesterol (mmol/L)

J,0.13[27]

<0.05

Total cholesterol (mmol/L)

J,0.26[27]

<0.01

J, 10111 J,S111 J,0.41 128] J,0.13 129] iO.03128] iO.04[29] J,0.13[28] J,0.17[29] J,0.04[28] J,0.17[29] i61-65[31]a

SystOlic blood pressure (mmHg) Diastolic blood pressure (mmHg)

Insulin sensitivity (% change) a

i27[30]

<0.05

NS NS NS NS NS NS NS

<0.05

Both exercise and diet.

Abbreviations and symbols: HDL = high density lipoprotein; LDL = low density lipoprotein; NS = not significant;

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i

= increase;

J, = decrease.

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Coronary Heart Disease Risk Factors

uals have familial hypercholesterolaemia, which is a genetic defect, where a gene that controls the production of the lipid receptors is defective. These patients have only half the number of receptors and it may not be surprising that the effect of training in these individuals is the same as that in individuals having normal levels of lipids. However, data are still too scarce to conclude. In addition, some studies have shown beneficial effects of physical activity on haemostatic factors (decreased fibrinogen and coagulation factor VII level and platelet adhesiveness). While there are too few studies to conclude, and not all studies are significant, most point in the same directionP8]

Obesity is inversely associated with activity level.[32] Exercise training improves body composition in obese individuals, however, intervention studies are rarely successful in decreasing bodyweight unless a strict diet is also followed. [33] More important than bodyweight is the fat distribution (i.e. abdominaUvisceral fat) and its relationship to insulin resistance (metabolic syndrome, see section 1.5). 1.4 Smoking

Smoking is an important CHD risk factor. Physical activity and smoking are negatively related, and physically active persons are less likely to start smoking, just like smokers are more likely to drop out of exercise programmes than nonsmokers.[34,35] However, training studies have not shown changes in smoking habitsp6] The negative association between smoking and physical activity is probably due to a clustering of unhealthy habits. 1.5 Hormones

Both noradrenaline (norepinephrine) release rate, insulin sensitivity and sympathetic nervous activity are affected by training.[30] These changes are probably very important, as both increased insulin sensitivity and a lower level of noradrenaline positively affect blood pressure, blood lipids, periphUm~ed.

2. Exercise Type, IntenSity, Dose-Response and Threshold 2.1 Exercise Modality

1.3 Obesity

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eral resistance and fat storage. In fact, non-insulindependant diabetes mellitus is commonly associated with hypertension, and the link between these diseases is hyperinsulinaemia (metabolic syndrome))3!] Training improves tissue sensitivity to insulin. The hormonal changes are probably related to changes in maximum oxygen uptake (V02max ), which might suggest that fitness is a more powerful predictor of risk of CHD than physical activity itself.

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There are improvements in many CHD risk factors with aerobic training, and trained individuals have a better risk profile compared with sedentary individuals. Even in studies using low intensity exercise, improvements have been found both in blood lipids and blood pressure. However, because of a very low initial fitness level in the individuals, improvements were also found in fitness level.[37,38] It is not possible to determine if improvements are linked to an increase in aerobic fitness level. Few studies have measured both physical activity and fitness. The relationship between CHD risk factors and physical activity disappears after adjustment for fitness levelp5,26] In a cross-sectional study of more than 6000 17-year-olds, Andersen[39] found a negatively graded relationship between aerobic fitness and blood pressure. However, no relationship was found between the amount of sports activity and other measures of physical fitness, such as strength, muscle endurance and flexibility, and blood pressure (figs I and 2). Two explanations were given: (i) the use of insensitive methods, or more likely, (ii) the benefit was linked to the aerobic fitness level. Only high intensity physical activity, which is a small part of the total physical activity, would have an effect on the fitness level in a relatively fit population. These findings might suggest an upper threshold in fitness level above which no further decrease in blood pressure was found. Sports Med. 1996 Oct; 22 (4)

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Andersen & Hippe

and Holly,[43] circuit weight training was found to lower blood pressure in borderline hypertensive individuals, however, an additional increase was found in aerobic fitness.[43] Compared with aerobic training, risk reductions in blood pressure and blood lipids are lower in resistive training studies, but both training modalities seem to increase insulin sensitivity.l44,45]

94 93 92 91 90 OJ I

E

.s ~ ::>

89

2.2 Intensity

88

(/) (/)

~

C. "0

0 0

:c

92

ro 91

c


90 89 88 87 86

~

85 84

10

20

30

40

50

60

70

80

90

Few training studies have compared the effect of different relative exercise intensities on CHD risk factors. Hicks et al.[46] found that acute changes in high density lipoprotein were positively correlated to the intensity of the exercise. However, Duncan et aU 37 ] found no relationship between the increase in fitness level and the increase in high density lipoprotein in 3 training groups walking at different speeds. The relationship may not exist, but the lack of significance could also be caused by a great daily variation in cholesterol or by changes in dietary intake with training.

Percentiles (%) of V02max (ml/kg/min)

Fig. 1. Mean values and standard errors of mean for resting blood pressure in 17-year-old boys (n = 2256) [top] and girls (n = 3234) [bottom] in percentiles of maximum oxygen uptake (V02max ) [ml/kg/min]. The 50% percentile corresponds to 53 ml/kg/min in boys and 42 ml/kg/min in girls (reproduced from Andersen,[391 with permission).

Little evidence exists on the benefit of strength training on CHD risk factors. Several investigators have reported favourable changes in blood lipids, but data are not conclusive. [40] Kohl et aJ.l41] found an adverse association of muscular strength on lipid status, whereas Tucker[42] found a substantial lower risk of hypercholesterolaemia in strengthtrained compared with sedentary individuals. One reason might be that strength is related to body size, and body size is also related positively to blood lipids and blood pressure. Therefore, it may be more meaningful to relate the risk factors to strength per kg bodyweight or height 2. In the study of Harris © Adis International Limited. All rights reserved.

3. Future Research Clinical exercise studies, where variations in relative intensity, total energy expenditure, exercise modality and baseline fitness level are separately controlled, are still needed before final conclusions can be drawn concerning specific recommendations of exercise for maximal benefit. Cross-sectional studies should not only be used to describe populations at risk, but also to describe relationships between variables. Also, studies of how best to motivate the population to become and remain active are needed. This is a complex task, because the type, intensity and quantity of physical activity which is good for health may change with age. The importance of the content of the physical education lessons in schools must be emphasised. In many countries, physical education lessons are compulsory and there may be a chance of motivating the sedentary if activities are chosen with care. Sports Med. 1996 Oct; 22 (4)

217

Coronary Heart Disease Risk Factors

92

+

412 Ol 91 J:

391

E

.s ~

453

90

+

::J

!J) !J)

~ a.

89

"C

0 0

:is c

:::

88 617

os Q) 87 ::2: 86

0-0.5

Boys 306

575

710

791

2

0.5-2

2-4

4-7

Girls 269

1 >7

Participation in sport (hours/week) Fig. 2. Mean values and standard error of mean for blood pressure in 17-year-old boys (n = 1.957) and girls (n = 2.962) in relation to weekly hours of sports participation. The numbers above each data point represent the number of participants in each group (reproduced from Andersen,[39] with permission).

4. Conclusions The benefit of being physically active is multifaceted. There is benefit achieved independently of the effect on risk factors, and furthermore, most known CHD risk factors are favourably altered by physical activity. Part of the benefit is coupled to acute changes in risk factors, but also hormonal changes in insulin and (nor)adrenaline may playa role, as well as other changes in the cardiovascular system (more capillaries and lower peripheral resistance). Some physical activity, independent of modality, is better than none, but aerobic exercise probably alters CHD risk factors more than other types of exercise. An aerobic type of exercise sufficient to increase the fitness level may be most beneficial to CHD risk factors. However, there may be an upper level of fitness above which no further change in risk factors occurs.

References I. Powell KE, Thompson PD, Caspersen CJ, et al. Physical activity and the incidence of coronary heart disease. Ann Rev Public Health 1987; 8: 253-87 2. Pate RR, Pratt M, Blair SN, et al. Physical activity and public health. JAMA 1995; 273: 402-7 3. Vuori I, Fentem P, Andersen LB, et al. The significance of sport for society. Counsil of Europe Press, 1995

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4. Morris IN, Clayton DG, Everitt MG, et al. Exercise in leisure time: coronary attack and death rates. Br Heart J 1990; 63: 325-34 5. Wannamethee G, Shaper AG. Physical activity and stroke in British middle-aged men. BMJ 1992; 304: 601-5 6. Paffenbarger RS, Hale WE. Work activity and coronary heart mortality. N Engl J Med 1975; 292: 545-50 7. Paffenbarger RS, Hyde RT, Wing AL, et al. Physical activity, all-cause mortality, and longevity of college alumni. N Engl J Med 1986; 314: 605-13 8. Leon AS, Connett J. Physical activity and 10.5 year mortality in the Multiple Risk Factor Intervention Trial (MRFIT). Int J Epidemiol 1991; 20: 690-7 9. Blair SN, Kohl HW, Paffenbarger RS, etal. Physical fitness and all-cause mortality: a prospective study of healthy men and women. JAMA 1989; 262: 2392-401 10. Hein HO, Saudicani P, Sorensen H, et al. Changes in physical activity level and risk of ischaemic heart disease: a six year follow-up in the Copenhagen Male Study. Scand J Med Sci Sports 1994; 4: 57-64 II. Paffenbarger RS, Kampert JB, Lee I-M, et aI. Changes in physical activity and other Iifeway patterns influencing longevity. Med Sci Sports Exerc 1994; 26: 857-65 12. Blair SN, Kohl HW, Barlow CE, et al. Changes in physical fitness and all-cause mortality. JAMA 1995; 273: 1093-8 \3. Kannel WB, Dawber TR. Atherosclerosis as a pediatric problem. J Pediatr 1972; 80: 544-54 14. Kemper HCG, Snel J, Verschuur R, et al. Tracking of health and risk indicators of cardiovascular diseases from teenager to adult: the Amsterdam Growth and Health study. Prev Med 1990; 19: 642-55 15. Andersen LB, Haraldsdottir J. Tracking of cardiovascular disease risk factors including maximal oxygen uptake and physical activity from late teenage to adulthood: an 8-year follow-up study. J Int Med Res 1993; 234: 309-15 16. Arroll B, Beaglehole R. Does physical activity lower blood pressure: a critical review of the clinical trials. J Clin Epidemiol 1992; 45: 439-47 17. Kelley G, McClellan P. Antihypertensive effects of aerobic exercise. Am J Hypertens 1994; 7: 115-9 18. Fagard RH. Prescription and results of physical activity. J Cardiovasc Pharmacol 1995; 25 Suppl. I: s20-s27 19. Hansen HS, Froberg K, Hyldebrandt N, et al. A controlled study of eight months of physical training and reduction of blood pressure in children: the Odense schoolchild study. BMJ 1991; 303: 682-5 20. Hagberg JM, Goldring D, Ehsani AA, et ai. Effect of exercise training on the blood pressure and hemodynamic features of hypertensive adolescents. Am J Cardiol 1983; 52: 763-8 21. Braith RW, Pollock ML, Lowenthal DT, et al. Moderate- and high-intensity exercise lowers blood pressure in normotensive subjects 60 to 79 years of age. Am J Cardiol 1994; 73: 1124-8 22. Gordon NF, Scott CB, Wilkinson WJ, et al. Exercise and mild essential hypertension: recommendations for adults. Sports Med 1990; 10: 390-404 23. Paffenbarger RS, Jung DL, Leung RW, et al. Physical activity and hypertension: an epidemiological view. Ann Med 1991; 23: 319-27 24. Blair SN, Goodyear NN, Gibbons LW, et al. Physical fitness and incidence of hypertension in healthy normotensive men and women. JAMA 1984; 252: 487-90 25. L¢chen M-L, Rasmussen K. The Troms¢ Study: physical fitness, self reported physical activity, and their relationship to

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Lim~ed.

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Correspondence and reprints: Dr Lars Bo Andersen, Institute of Preventive Medicine, Komtnunehospitalet, DK-1399,

Copenhagen K, Denmark.

Sports Med. 1996 Oct; 22 (4)