The Role of Exercise in Medicine

Exercise Is a Relatively New Scientific Discipline:

It Has Important Foundations in Scandaniva

Beginnings of Exercise Science Exercise scientists have won the

Nobel Prize• August Krogh—1920

Capillary regulation

• A. V. Hill and Otto Meyerhof—1922 Muscle metabolism

Early leaders in exercise science in Scandinavia• Erik Christensen • P.O. Astrand• Erik Assmussen • Marti Karvonnen

Articles/Period—Web of SciencePhysical Activity or Physical Fitness and

Cardiovascular Disease# of Articles

Years

Ranking of selected risk factors: 6 leading causes of death by income group, estimates for 2004

Percentage of total (total: 1.53 billion)

World Health Organization. http://www.who.int/healthinfo/global_burden_disease/global_health_risks/en/index.htm

Risk Factors for Stroke in 22 Countries: INTERSTROKE Study

O’Donnell MJ et al. Lancet 2010; 376(9735):112-123

Adjusted for age, sex, and region

Self-reported Physical Activity Underestimates the True Effect

• 31,818 men and 10,555 women

• 1492 deaths in men during average follow-up of 14.6 years, and 230 deaths in women during average follow-up of 12.8 years

• PA mortality trends not significant after adj for CRF

• CRF trends significant after adj for PA

Phys Act CRFLee DC, et al. BJSM; pub online April 23, 2010

Aerobics Center Longitudinal Study

Design of the ACLS

1970 More than 80,000 patients 2005

Mortality surveillance to 2003More than 4000 deaths

Cooper Clinic examinations--includinghistory and physical exam, clinical tests,body composition, EBT, and CRF

1982 ‘86 ‘90 ‘95 ’99 ‘04Mail-back surveys for case finding and monitoring habits and other characteristics

All-Cause Death Rates by CRF Categories—3120 Women and

10 224 Men—ACLS

0

10

20

30

40

50

60

70

Ag

e ad

j dea

th r

ate/

10,0

00 P

Y

Low Moderate High

Women

Men

Blair SN. JAMA 1989

Does Changing Cardiorespiratory Fitness

Reduce Mortality Risk?

Fitness Change Categories Unfit was defined as the least fit 20% of men

in each age group Men were classified as fit or unfit at both

examinations Change categories

• unfit at both examinations = never fit• unfit at first, fit at second = improvers• fit at both examinations = always fit

Blair SN et al. JAMA 1995; 273:1093-8

Age-Adjusted Death Rates by Fitness Change Groups, Men, ACLS

Age-adjusted Death Rates/10,000 Man-years

Fitness Groups

CVD All-cause

Never fit 65 122

Improvers 31 68

Always fit 14 40

Blair SN et al. JAMA 1995; 273:1093-8

CRF and Risk of Incident Hypertension, ACLS Women

4,884 healthy women examined at the Cooper Clinic, 1970-1998

157 women developed hypertension during average follow-up of 5 years

Risk adjusted for age, exam year, alcohol intake, smoking, BP, family history of hypertension, waist girth, glucose, & triglycerides

FitnessGroups

Risk of Developing Hypertension

Barlow CE et al. Am J Epidemiol 2006; 163:142-50

P for trend <0.01

CRF and Digestive System Cancer Mortality

•38,801 men, ages 20-88 years•283 digestive system cancer deaths in 17 years of follow-up

CRF was inversely associated with death after adjustment for age, examination year, body mass index, smoking, drinking, family history of cancer, personal history of diabetes•Fit men had lower risk of colon, colorectal, and liver cancer deaths

High Fit

Moderately Fit

Low Fit

Peel JB et al. Cancer Epidemiol Biomarkers Prev 2009; 18:1111

CRF and Breast Cancer Mortality

•14,551 women, ages 20-83 years•Completed exam 1970-2001•Followed for breast cancer mortality to 12/31/2003•68 breast cancer deaths in average follow-up of 16 years•Odds ration adjusted for age, BMI, smoking, alcohol intake, abnormal ECT, health status, family history, & hormone use

Odds Ratio

p for trend=0.04

Sui X et al. MSSE 2009; 41:742

Activity, Fitness, and Mortality in Older Adults

Cardiorespiratory Fitness and All-Cause Mortality, Women and Men ≥60 Years of Age

4060 women and men ≤60 years

989 died during ~14 years of follow-up

~25% were women Death rates adjusted

for age, sex, and exam year

0

5

10

15

20

25

30

35

40

45

60-69 70-79 80+

Low

Moderate

High

All-Cause death rates/1,000 PY

Age Groups

Sui M et al. JAGS 2007.

Physical Activity as Treatment for Chronic Disease

Exercise Is Medicine!

Cardiorespiratory Fitness and Health Outcomes in Various

Population SubgroupsSuch as People Who Are Overweight or Obese or

Those with Chronic Disease

Cardiorespiratory Fitness, Risk Factors and All-Cause Mortality, Men,

ACLS

0

10

20

30

40

50

60

De

ath

s/1

0,0

00

MY

*

Low Mod High

01

2 or 3

# of risk factors

Risk Factorscurrent smokingSBP >140 mmHgChol >240 mg/dl

Cardiorespiratory Fitness Groups*Adjusted for age, exam year, and other risk factors

Blair SN et al. JAMA 1996; 276:205-10

CVD Mortality Risk* by Fitness and BMI Categories, 2316 Men with Diabetes,

179 CVD Deaths

0

1

2

3

4

5

6

7

8

9

10

Ris

k o

f C

VD

Mo

rta

lity

18.5 < BMI <25.0 25.0 ≤ BMI <30.0 30.0 ≤ BMI < 35.0

Re

fere

nc

e

Church TS et al. Arch Int Med 2005; 165:2114*Adj for age and examination year

p for trend <0.0001p for trend <0.0001 p for trend <0.002

0

2

4

6

8

10

12

14

16

18

LowModerateHigh

Controlled HTN Stage 1 HTN Stage 2 HTN

Severity of HTN

P <.001 P <.001 P =.048

CRF:

Age and exam year adjusted rates of total CVD events by levels of CRF and severity of HTN in

8147 hypertensive men

Sui X et al. Am J Hyptertension. 2007

CVD incidence/1000 man-years

Multivariate + % Body Fat adjusted HR of All-Cause Mortality by Fitness Groups,

ACLS, 2603 Adults 60+

0

0.2

0.4

0.6

0.8

1

1.2

Q1 Q2 Q3 Q4 Q5

Adjusted HR

p for trend <0.001

Cardiorespiratory Fitness

106 deaths

98 deaths95 deaths

90 deaths61 deaths

*Adjusted for age, exam year, smoking, abnormal exercise ECG, baseline health conditions, and percent body fat Sui M et al. JAMA 2007; 298:2507-16

Joint Associations of CRF and % Body Fat with All-cause Mortality, ACLS Adults 60+

0

10

20

30

40

Fit Unfit

Normal

Obese

Death rate/1,000 person-years

Rates adjusted for age, sex and exam year

Deaths 151 190 29 72

Sui M et al. JAMA 2007; 298:2507-16

Muscular Strength and Mortality

Thirds of Muscle Strength and Thirds of Muscle Strength and Mortality, 8762 Men--ACLSMortality, 8762 Men--ACLS

0

5

10

15

20

25

30

35

40

Age adj death rate/10,000

MY

All-Cause CVD

Low

Middle

High

503 deaths (145 CVD) during average follow-up of 18.9 years

Ruiz J et al. BMJ 2008

Strength, Adiposity, and Cancer Mortality•8,677 men, 20-82 years•18.8 years of follow-up, 211 cancer deaths•Muscular strength assessed by 1-RM bench press and leg press •Significant trend across strength categories remained after further adjustment for BMI, % body fat, waist circumference, and cardiorespiratory fitness Thirds of Strength

Odds of Cancer Death*

*Adj for age, exam yr, smokingalcohol intake, and health status

P for trend=0.003

Ruiz J et al. Cancer Epidemiol Biomarkers Prev 2009; 18:1468

Attributable Fractions (%) forAll-Cause Deaths

40,842 Men & 12,943 Women, ACLS40,842 Men & 12,943 Women, ACLS

02468

1012141618

Low CRF

Obese

Smoker

Hypertension

High Chol

Diabetes

MenWomen

Blair SN. Br J Sports Med 2009; 43:1-2.

Yes, But Those Are Observational Studies, and

We Require Randomized Clinical Trial Evidence

Reduction in Risk of Developing Diabetes in Comparison with Controls,

DPP

58%

31%

0

20

40

60

80

100

Ris

k re

du

ctio

n (

%)

*Moderate intensity exercise of 150 min/week; low calorie, low fat diet

Lifestyle Intervention* Metformin

DPP Research Group. NEJM 2002; 346:393-403

Cost Effectiveness of Diabetes Prevention-DPP

The lifestyle and metformin groups cost $2,250 more/year than placebo

As implemented in the DPP and from a societal perspective, lifestyle was more cost effective than metformin

$0$10,000$20,000$30,000$40,000$50,000$60,000$70,000$80,000$90,000

$100,000

Per C

aseD

elayed/P

rev

Per Q

AL

YG

ained

Lifestyle

Metformin

DPP Res Group. Diab Care 2003; 26:2518

8.58.7

7.57.98.0

6

7

8

9

10

0 6 12

Sco

re

Physical activitySuccessful aging

P<0.001

mo mo

Means estimated from repeated measures ANCOVA adjusted for gender, field center and baseline values

LIFE-P SPPB Score

J Gerontol Biol Sci Med Sci 2006;61:1157

Physical activityN=213

Successful agingN=211

p

Death 0.9% 0.9% >0.99Life threatening event 1.4% 1.4% >0.99Hospitalization 20.7% 20.9% >0.99Significant lab exam 2.8% 3.8% 0.60Any SAE 22.5% 23.7% 0.82

LIFE-P Serious adverse events

J Gerontol Biol Sci Med Sci 2006;61:1157

Exercise Is Medicinewww.exerciseismedicine.org

Exercise Is Medicine World Congress

Denver, COMay 31-June 2, 2010

What should I do in my clinical practice to promote

physical activity?

Physician Competencies for Prescribing Lifestyle Medicine “The leading causes of death for

adults in the United States are related to lifestyle—tobacco use, poor diet, physical inactivity, and excessive alcohol consumption”

“The enormous potential effects of health behavior change on mortality, morbidity, and health care costs provide ample motivation for the concept of lifestyle medicine…”

Lianov & Johnson. JAMA 2010; 304:202-3.

Physician Competencies for Prescribing Lifestyle Medicine

Lifestyle change is recommended therapy, but often not done…• 36% of obese patients are advised to

lose weight during an examination• 28% of smokers report that clinicians

offered them assistance to quit smoking Physicians lack confidence of their

knowledge and skill for lifestyle counseling

Lianov & Johnson. JAMA 2010; 304:202-3.

Physician Competencies for Prescribing Lifestyle Medicine Lifestyle medicine competencies

for primary care physicians• Leadership• Knowledge• Assessment skills• Management skills• Use of office and community

support

Lianov & Johnson. JAMA 2010; 304:202-3.

Risk of all-cause mortality decreases with number of positive health factors

Prospective study of 38,110 men, age 20-84 yrs

Positive health factors• Moderate to high CRF (top two-thirds

CRF)• Physically active (moderate to high

LTPA)• BMI (18.5 – 25.0 kg/m2)• Smoking (not current smoker)• Alcohol consumption (1-14

drinks/week) Average follow-up of 16.1 yrs, and 2,642

deaths

Byun et al. MSSE 2010; 42(9):1632-1638

HR* According to the Number of Positive Health Factors for All-Cause Mortality

Byun et al. MSSE 2010; 42(9):1632-1638

P for trend <0.001

*Adjusted for age, examination year, hypertension, diabetes, and hypercholesterolemia

Physical Activity Interventions in Clinical

Practice

Karolinska Institute• 101 participants 68-years old

with low PA, overweight and abdominal obesity

• Randomized to physical activity on prescription (PAP) or a minimal intervention

• Physical activity, anthropometric parameters, body composition and cardiometabolic risk factors

Kallings L et al. Euro.J.Cardio.Preven.Rehab. 2009. 16:80-84.

Karolinska Institute• Favorable changes in

anthropometrics, body composition, S-glucose, glycosolated hemoglobin, blood lipids and apolipoproteins were seen in the PAP group

Kallings L et al. Euro.J.Cardio.Preven.Rehab. 2009. 16:80-84.

Where Do We Go from Here?

Behavioral Approaches to Physical Activity Interventions

Theoretical foundations• Social Learning Theory• Stages of Change Model• Environmental/Ecological Model

Methods• Problem solving• Self-monitoring• Goal setting• Social support• Cognitive restructuring• Incremental changes• Manipulating the environment

Track Record of Lifestyle PA Interventions

Successfully implemented in many different populations and settings• Men and women of all ages• African-American men and women,

Hispanic women• Prostate cancer survivors• Worksites, YMCA’s, public heath

departments, recreation facilities, senior centers, churches

Lessons Learned from Physical Activity Intervention Studies

Individuals who use cognitive and behavioral strategies are more likely to be active at 24 months than individuals who do not use these strategies

Approximately 25-30% of initially sedentary persons who participate in Active Living will be meeting consensus public health guidelines for physical activity at 24 months

Using Modern Technology to Promote Healthful

Lifestyles

How to Achieve Lifestyle Change

Counseling by a PhD level behavioral psychologist

Counseling by B.A. level health educators

Counseling by mail and telephone

Counseling by electronic communications

Telehealth and Weight Change•87 participants (73 women & 14 men)•Mean age 50 years•Treatment groups (Quasi-experimental design)

•Traditional class•Telehealth—interaction with RD via web and email•Control

•No difference in satisfaction between traditional and telehealth•Telehealth more convenient than traditional (p<0.0001)

Kg change at 6 mo

Traditional Telehealth Control

p <0.05

Haugen HA et al. Obes 2007; 15:3067-77

Promoting PA via PDA 37 healthy, inactive adults, ≥50 years of

age 8-week RCT PDA intervention (93% had not used

PDAs)• Questions about amount and type of PA • Alerted at 2 PM and 9 PM to complete PA

assessment• Gave motivational and behavioral tips

Controls—standard written materials

King AC et al. Am J Prev Med 2007; 34:138-42

Promoting PA via PDA Intervention participants completed 68%

of the 112 PDA entries available After adjusting for baseline differences

• PDA group reported 310.6 minutes of moderate to vigorous PA/week

• Control group reported 125.5 minutes/week• p=0.048 for group comparison

78.6% of PDA group reported enjoying using the device

King AC et al. Am J Prev Med 2007; 34:138-42

The SenseWear Armband (SWA)The SenseWearTM Armband

(BodyMedia, Pittsburgh, PA) Lightweight monitor worn on the

upper left arm Four sensors (skin temp,

galvanic skin response, heat flux, tri-axial accelerometer)

Estimates energy expenditure Physical activity – duration &

intensity

Effects across time for weight. Estimates adjust for age, gender, race, education, and wave.

Standard Care

GWL

GWL=Group Weight LossSWA=SenseWear Armband

Shuger S et al. In review

Summary Physical inactivity and low fitness

are highly prevalent in modern societies

Inactivity and low fitness are strong determinants of morbidity and mortality due to chronic disease

Comprehensive programs to increase activity are crucial to the public’s health

Physicians and other health care professionals can make a difference via Exercise Is Medicine

Acknowledgements Co-investigators

• Xuemei Sui• Tim Church• James Hebert• Greg Hand• Ian Janssen• Francisco Ortega• Jonatan Ruiz• Steve Hooker• Michael Beets• Sara Wilcox• Chris Riddoch• Andrew Jackson• Paul McAuley• Susumu Sawada• Andy Ness

Post-doctoral scholars• D.C. Lee• Meghan Baruth• Jongkyu Kim• Enrique Artero

PhD students• Amanda Paluch• John Sieverdes• Vaughn Barry• Jonathan Mitchell• Won Byun• Tatiana Warren• Andrea Maslow• Will Lyely

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