Role of Exercise in Chronic Disease Management

Urho Kujala, MD, PhD

Professor of Sports & Exercise Medicine

Department of Health Sciences

University of Jyväskylä, Finland

E-mail: urho.kujala@sport.jyu.fi

Where does the evidence originate in

Sports and Exercise Medicine Relationships between physical activity,

fitness and health/disease

Epidemiological designs

Studies invesigating

the mechanismsvia which

exercise modifiesdisease

progression

RCTsand systematic

reviews

Physical inactivity and health: What kind of scientific knowledge and

evidence do we have/need?

• Prevention; Observational studies to give general advice for healthy people? (Problem: cause and effect evaluation?)

• Studies on the effects of exercise on the mechanisms of disease (Problem: effect on true prognosis?)

• Treatment of patients with chronic disease using resourches of health care; intervention studies, preferably RCTs, are needed? (Problem: shortem trials, specific patient groups etc.)

• Risks of complications/safety rules

Problems of observational studies:Heritability of physical activity

0

10

20

30

40

50

60

70

80

Heritability % by country

Australia

Netherlands

GB

Sweden

Finland

Denmark

(Stubbe et al. Plos One 2006)

Problems of observational studies:GENETIC SELECTION BIAS

FAVOURABLE GENES

HIGH FITNESS LEVEL,EASY TO EXERCISE

LOW MORBIDITY

FAVOURABLE RISK FACTOR PROFILE

See Kujala et al. Am J Epidemiol 2002;156:985-993

Waist circumference & PA

Among twin pairs (n=42) consistently discordant for physical activity for 30 years active co-twins had 8.4 cm smaller waist than inactive co-twins

(Waller et al. Int J Obesity 2008;32:353-361.)

Mechanisms by which physical exercise prevents from disease, disease progression or death

• Physical fitness • Blood pressure levels • Obesity, visceral fat • HDL cholesterol • Insulin sensitivity • Heart function • Heart electrical stability • Bone mineral density

• Sympaticus-parasympaticus balance

• Endothelium dependent vasodilatation

• Inflammation • Platelet aggregation • Per-oxidized LDL • Homocystein

NOTE: Compare with ”monotherapies” using drugs

Randomised Controlled Trial (RCT)

Patient group

Exercise(+usual care)

Control/Placebo(+ usual care)

Randomisation

Measurement of outcomes so that assessors are blinded to treatment group, and all subjects are included into

the ’intention-to-treat’ -analysis

”Review of Systematic Reviews”:Quantitative meta-analysis or

Qualitative analysis

• Inclusion criteria:

- Contrast for exercise only

- Treatment of disease

- At least two RCT:s (randomized controlled trials)

Statistical methods of meta-analyses

• Dichotomous (or binary) data; odds ratios (OR), relative risks (or relative effects), risk differences as well as absolute measures, such as the number needed to treat (NNT).

• For continuous data; weighted mean difference (WMD) is preferable when outcomes measured in a standard way. In case continuous outcomes are conceptually the same but measured in different ways, standardized mean differences (SMD).

• Heterogeneity between different studies; fixed effect vs. random effects analysis methods

EVIDENCE CATEGORIES

A: Randomized controlled trials (rich body of data)

B: Randomized controlled trials (limited body of data)

C: Nonrandomized trials (observational studies)

D: Committee consensus judgement

Exercise for overweight and obesity

• Diet better than exercise (in the beginning)• More intensive exercise better than low intensity

exerciseExercise also lowers diastolic blood pressure,

triglyceride levels and fasting blood glucose(Shaw et al. Cochrane Syst Rev)

NOTE: Exercise reduces waist also without an effect on weight (Ohkawara et al. Int J Obesity 2008)

Exercise training and blood lipid profile

-6

-4

-2

0

2

4

6

HDL-C Trigly LDL-C

% change caused by exercisetraining(WMD, 51 controlledtrials)

(Leon & Sanchez. Review. Med Sci Sports Exerc 2001)

Exercise-based rehabilitation for coronary heart disease

• RCTs show that exercise in the rehabilitation of documented coronary heart disease can reduce all cause mortality by 27% (data from 12 trials including 2845 subjects and at least six-month follow-up) and total cardiac mortality by 31% (4 trials), but not the occurrence of non-fatal myocardial infarction.

(Jolliffe et al. Cochrane Database Syst Rev)

CHD – Contrast; ExerciseOutcome; Total mortality

CHD – Contrast; ExerciseOutcome; Cardiac deaths

Heart failure

• Based on 11 RCTs physical exercise training (729 patients) risk of death was 29% lower among exercise groups compared to controls

(Smart et al. Am J Med 2004;10:693-706.)

(+ increase in fitness/function)

Exercise for intermittent claudication

• RCTs report that training increases maximal walking time in a treadmill test (weighted mean difference 6.51 min; 95%CI 4.36-8.66).

• Adverse effects are rare.• In the reports method of randomization was

usually not explained, but there were either no or minimal loses to follow-up.

(Leng et al. Cochrane Database Syst Rev)

Intermittent claudication- Contrast; exercise Outcome; max walking time

Blood pressure/hypertension and endurance training

• Endurance training reduces blood pressure – by -6.9/-4.9 mmHg in hypertensives– by -1.9/-1.6 mmHg in normotensives

(Cornelissen & Fagard 2005)

• The effect is seen within some weeks

Exercise and glycemic control in type 2 diabetes

• Thomas et al. Cochrane Syst Reviews 2006 (14 RCTs):

Weighted mean difference in reducing glycosylated hemoglobin percent (HbA1c) -0.63% (95% CI -0.9, -0.3)

• Boule et al. Diabetologia 2003;46:1071-1081:

Standardized mean difference in increasing maximal oxygen uptake 0.53 (95% CI 0.18-0.88)

Resistance training in the treatment of type 2 diabetes

Three-month individualized progressive resistance training program

Inverse correlation between HbA1c and knee extensor muscle cross-sectional area at follow-up (r=-0.73)

7,9

8

8,1

8,28,3

8,4

8,5

8,68,7

8,8

HbA1c

Baseline

Follow-up

P < 0.05

(Eriksson et al. Int J Sports Med 1997;18:242-246)

Asthma – Contrast; Exercise Outcome; Maximal oxygen uptake

Asthma

• Cardiorespiratory fitness can be increased by physical training (5 trials; physical training caused an increase in maximal oxygen uptake by 5.6 ml/kg/min; 95% CI 3.9-7.2; p<0.00001)

• No evidence of an effect on measures of resting pulmonary function.

(Ram et al. Cochrane Database Syst Rev)

Rehabilitation of COPD patients

• COPD patients of rehabilitation groups (20 trials; 979 patients) did significantly better than control groups on walking test (standardized effect size (ES) 0.71; 95% CI 0.43 to 0.99).

(Salman et al. J Gen Intern Med 2003)

Rehabilitation of COPD patients

• COPD patients of rehabilitation groups (12 trials; 723 patients) that used the Chronic Respiratory Disease Questionnaire had less shortness of breath than did the control groups (ES 0.62; 95% CI, 0.35 to 0.89).

(Salman et al. J Gen Intern Med 2003)

Rehabilitation of COPD patients

• Trials that used respiratory muscle training only showed no significant difference between rehabilitation and control groups, whereas trials that used at least lower extremity training showed that rehabilitation groups did significantly better than control groups on walking test and shortness of breath.

Osteoarthritis – Contrast; ExerciseOutcome; Pain

(Fransen et al. Cochrane Database Syst Rev)

Osteoarthritis – Contrast; ExerciseOutcome; Physical function

(Fransen et al. Cochrane Database Syst Rev)

Osteoarthritis• Based on 17 RCTs, land-based therapeutic exercise

(with manual therapy or balance training in some studies) improved self-reported pain (SMD 0.39, 95% CI 0.30-0.47) and self-reported physical function (SMD 0.31, 95% CI 0.23-0.39)

• Home programs improved pain less than other individual treatments or group-based exercise classes

• When outcome assessor was blinded the improvements were smaller

(Fransen et al. Cochrane Database Syst Rev)

Rheumatoid arthritis:Exercise therapy

• Dynamic exercise therapy is effective at increasing aerobic capacity and muscle strength (6 RCTs, due to heterogeneity in outcome measures the results not pooled).

• No detrimental effects on disease activity and pain.

(Van den Ende et al. Cochrane Database Syst Rev; Kettunen & Kujala. Exercise therapy for people with rheumatoid arthritis and osteoarthritis. Scand J Med Sci Sports 2004;14:138-142.)

Low back pain

• Acute back pain – Exercise does not help (strong evidence); subacute back pain – no help

• Chronic low back pain; effect on pain based on 43 RCTs 7.3 units (95% CI 3.7-10.9) on a scale from 0 to 100.

• Effect on function is smaller (target group has an effect) • Exercise may be helpful for chronic LBP patients to

increase return to normal daily activities and work.(Hayden et al. Ann Intern Med 2005;142:765-775,van Tulder et al. Cochrane Database Syst Rev)

Best exercise programme for LBP?

• Indirect comparisons using Bayesian multivariable random-effects meta-regression (Hayden et al. Ann Intern Med 2005;142:776-786)

• Compared to non-supervised home exercises the improvements were higher for:

Individually designed programs 5.4 points Supervised home exercise 6.1 p. Group and individually supervised program 5.9 p.

Depression

• Based on 9 low quality RCTs exercise treatment decreased Beck depression inventory score (weighted mean difference -7.3 (95% CI -10.0 to -4.6)

(Lawlor and Hopker. BMJ 2001;322:763-767)

Cognitive impairment and dementia

• Exercise training increases fitness, physical function and cognitive function in people with dementia

(Heyn et al. Arch Phys med Rehabil 2004;85:1694-1704)

Effects of exercise therapy based on RCTs

HDL cholesterol↑

Risk of death↓

Str

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Mo

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Ind

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?Risk of myocardial infarction↓Risk of coronary heart disease↓

Physical fitness↑(Aerobic fitnessand muscular strength)

Risk of type 2 diabetes mellitus↓

Blood pressure↓

Inflammation↓

Glycemic control↑

Insulin sensitivity↑

Obesity↓Visceral fat↓

Parasympatic tone↑

Electrical stability of heart↑

Heart function↑

Endothelium dependent vasolidatation?

Platelet aggregation↓

Bone mineral content↑

Exercise therapy for chronic diseases: Conclusions from RCTs

• There is accumulating evidence that people with chronic disease can maintain or increase their fitness without documented increases in complications (this has effects on some quality of life parameters)

• Beneficial effects on disease outcomes are documented only in some diseases (CHD, heart failure); indirect support from RCTs investigating different risk factors

(Kujala et al. Scand J Med Sci Sports 2004;14:339-45.)

Exercise therapy for chronic diseases: Conclusions from RCTs

When interpreting the results from RCTs we have to remember:

• In RCTs the participants have been examined by specialist physicians and exercise levels have been controlled to fit the disease severity of the participants

• To avoid complications, in many cases, exercise programs have to be tailored individually by professionals

(Kujala et al. Scand J Med Sci Sports 2004;14:339-45.)

Criticism: Evidence b(i)ased medicine??

• RCT is more like a standardized laboratory experient than a clinical situation?

• RCT does not measure the effect of a treatment but the ”effect of an intervention compared to another treatment” (NNT figures)

• There are many good treatments which efficacy has not been shown in RCTs

Conclusion

• In the treatment of chronic disease exercise therapy (using correct therapeutic dose) has many positive effects

• No compareable drug therapies (with many simultaneous positive effects) are available

• It is a challenge to increase the knowledge of health care professionals on the correct use of exercise therapy in chronically ill patients and build collaboration between exercise and health care professionals