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Physical Activity and Cardiovascular Disease

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Title: Physical Activity and Cardiovascular Disease


1
Physical Activity and Cardiovascular Disease
  • ANDREAS PITTARAS MD

2
Survival of the Fittest
  • in the last 15 years, many epidemiological
    studies have shown an unequivocal and robust
    relationship of fitness, physical activity, and
    exercise to reduce overall and CVD mortality.
  • Balady JG, New Engl J Med 2002346 (11)852-53

3
Coronary Heart Disease and Physical Activity of
WorkMorris JN, et al. Lancet 195321053-1120
  • Approximately 50 lower risk of CHD in those with
    physically demanding (i.e. mail carriers) vs
    those with sedentary occupations (i.e. desk
    clerks).

4
Physical Activity and the Incidence of Coronary
Heart Disease Powell KE, et al. Annu Rev
Public Health 1987 8253-87
  • 121 studies reviewed 43 were included.
  • The relationship between sedentary lifestyle and
    increase risk of CHD is likely to be causal.

5
Relative Risk for CAD
Ann Review Public Health 1987 8253-87
RR
Physical Inactivity
SBPgt150 mm Hg
TCgt268 mg/dL
Smoking gt1 pack
6
Population Attributable Risk by Risk Factor
Population Attributable Risk ()
7
It is Estimated that 250,000 Deaths/Year in the
USA are Attributable to Lack of Regular Physical
Activity Siegel PZ, at al., Weekly Reports 1991
8
Physical Activity Status in US Population
  • 20 - 22 - Exercise Regularly
  • 40 - 54 - Some Activity
  • 24 - 40 - Sedentary
  • 34 of pts are being counseled by
    physicians to begin or continue exercise.

9
AHA Position Statement Circulation
199186(1)340-44
  • Physical inactivity an as independent risk factor
    for the development of CHD equal in status to the
    traditional risk factors of HTN,
  • DM, Dyslipidemia and smoking.

10
Exercise Type ?
  • Most information is derived from aerobic exercise
    studies.
  • Some evidence from occupational studies support
    that repeated busts of high energy output may
    offer protection against premature coronary
    mortality.

11
Dynamic/Isotonic Exercise
High Intensity Anaerobic CHO as Fuel
Low Intensity Aerobic FFA as Fuel
-Walking -Jogging -Cycling
Strength Training
12
Physiologic Adaptations to Exercise Training
  • Chronic exercise of proper intensity, duration
    and frequency imposes a demand on the body.
  • Consequently, the body makes appropriate and
    specific changes to accommodate the imposed
    demand.

13
Cardiovascular Adaptations with Aerobic Exercise
  • Decrease
  • Rest HR BP
  • Rest Exercise RPP
  • Exercise HR BP (abs. WL)
  • ESV
  • Increase
  • LV Chamber
  • EDV
  • SV
  • CO
  • VO2 max

14
Cardiovascular Adaptations with Anaerobic Exercise
  • No Change
  • Rest HR BP
  • Rest Exercise RPP
  • Exercise HR BP (abs. WL)
  • ESV
  • No Change
  • LV Chamber ?
  • EDV ?
  • SV
  • CO
  • VO2 max

15
LVH with Aerobic and Anaerobic Exercise
  • Aerobic
  • Volume Load
  • Diastolic Stress
  • New Fibers in Series
  • Chamber size
  • Eccentric LVH
  • Anaerobic
  • Pressure Load
  • Systolic Stress
  • New fibers in parallel
  • Wall Thickness
  • Concentric LVH

16
CHD Death in Norwegian Men 40-59 years of Age
(N2,014)
Lie et al. Eur Heart J 85 147-57
Plt0.001
CHD Daeth in 7 yr/100
Fitness Quartiles
17
CVD Death in Men (N10,224)
Blair et al. JAMA1989 2622395-2401
CVD Death /10,000 person-years
METs
18
A Prospective Study of Walking as Compared with
Vigorous Exercise in the Prevention of CHD in
WomenManson JE, et al., NEJM 1999341650-8
  • N 72,488 Female Nurses
  • Age 40 to 65 yrs old in 1986
  • Free of CVD or Cancer
  • Follow-up 8 yrs
  • Incidence of Coronary Events 645 Fatal or
    Non-Fatal MI

19
Physical Activity RR Adjusted for Confounding
Factors (N72,488)
Mason JE, et al. NEJM99341650-8
Plt0.001
Physical Activity Quintiles
20
Relative Risk for Coronary Events and Walking
Pace (n72,488)
Mason JE, et al. NEJM99341650-8
Relative Risk
Walking Pace (min/mile)
21
Relative Risk for Coronary Events and Walking Time
Mason JE, et al. NEJM99341650-8
RR
Minutes Walking/Wk
22
Relative Risk for Coronary Events and Walking
Time in Women (n72,488)
Mason JE, et al. NEJM99341650-8
RR
Minutes Walking/Wk
23
F I N D I N G S
  • Brisk Walking for 100-200 min/week at a Pace of
    lt20 min/mile or lt13 min/km. Reduces the Risk for
    Coronary Events in Women by 30 to 40 Percent.
  • Similar Caloric Expenditure Yields Similar
    Reductions in Risk for Coronary Events.

24
Are Exercise Health Benefits Long-Lasting?
  • The Harvard Alumni study (n16,936) has shown
    that Ex-Varsity athletes retained lower risk for
    CHD only if they maintained a physically active
    lifestyle throughout life.
  • Paffenberger et al., Am J Epidemiol 1978
    108(3)161-175

25
Relative Risk of CHD Aerobic Activity in Men
(N51,529)
Tanasescu M, et al. JAMA022881994-2000
RR
Plt0.001
26
Survival for Fit Unfit Men (n9,777)
Blair et al, JAMA 19952731093-97
Survival Probability
Unfit to Fit
44 Reduction in Risk
Unfit to Unfit
27
How Much Physical Activity?
28
How Much Exercise?
  • Not an easy Question
  • Exercise Intensity, Duration and Frequency must
    be considered, as well as the interaction.
  • Caloric expenditure is one approach.
  • Intensity still may play an independent role.

29
Physical Activity and All Cause and CVD
Mortality in Women gt65 yrs
Gregg EW, et al. JAMA032892379--86
Relative Risk
CVD
Kcal/wk
30
Weekly Energy Expanded and Relative Risk of CHD
in Men (n7,337)
Lee, I-Min et al. Circulation 20031071110-16
Relative Risk

Kcal/Week
31
Age-adjusted First MI Rates by Physical Activity
(n16,963)
Paffenbarger et al., Am J Epidem.
1978108(3)161-75
MI/10,000 person-yrs
Total
Non-Fatal
Fatal
32
Exercise Intensity and Relative Risk of CHD in
Men (n7,337)
Lee I-Min, et al. Circulation 20031071110-16
Relative Risk
Kcal/Week
33
Exercise Intensity and Relative Risk of CHD in
Men (n7,337)
Lee I-Min, et al. Circulation 20031071110-16
Relative Risk
34
Relative Risk of All-Cause Death and Exercise
Capacity
Myers J et al. NEJM 2002346793-801
RR of Death
lt6 METS
6-7.9 METS
8-9.9 METS
10-12.9 METS
gt13 METS
Quintiles of Exercise Capacity
35
Survival Curves for Normal and CVD Patients
According to Exercise Capacity
Myers J et al. NEJM 2002346793-801
36
Conclusions
Myers J et al. NEJM 2002346793-801
  • Exercise Capacity is a more powerful predictor
    of mortality for CVD than other established risk
    factors.
  • A linear reduction in mortality. For each 1 MET
    increase in exercise capacity, a 12, decrease in
    mortality was observed.

37
Exercise Capacity and Risk of Death in Women
Gulati M, et al. Circulation 20031081554-59
Hazard Ratio of Death
3.1
1.9
38
Exercise Capacity and Risk of Death in Women
39
Conclusions
Gulati M, et al. Circulation 20031081554-59
  • Exercise capacity is a strong and independent
    predictor of all-cause mortality in asymptomatic
    women, even after adjusting for traditional
    cardiac risk factors.
  • For each 1 MET increase in exercise capacity, a
    17, decrease in mortality was observed.

40
Exercise Threshold for Health Benefits
  • METs lt 4 5 7 10
    ?
  • Threshold
  • Intensity Fast walk
    Running
  • 6 km/hr 10 km/hr
  • Kcal/wk 500 - 1000
    3,000
  • 120 min/wk 750 - 1050 1,500
  • 240 min/wk 1500-2100 3,000

41
Exercise in Patients with Risk factors and/or
Chronic Disease
42
Age-Adjusted CVD Death Rates CHD Risk Factors
(n26,980)
Blair, et al. JAMA 1996
51
Death Rate
Death Rate
27.5
46
12.6
Cardiorespiratory Fitness
43
Relative Risk of All-Cause Death and Exercise
Capacity
Myers J et al. 2002346793-801
RR of Death
gt8 Mets
lt5 Mets
5-8 Mets
44
CV Events and Physical Activity in Diabetic Women
(n5125)
Hu F, et al. Ann Intern Med 0113496-105
Relative Risk

Hours/Wk
45
Body Weight/ Obesity
46
Relative Risk for Physical Activity BMI,
Adjusted For Risk Factors
Mason JE, et al. NEJM99341650-8
RR
gt29
N72,488
lt29
Physical Activity Quintiles
47
F I N D I N G S
  • Brisk Walking for 100-200 min/week at a Pace of
    lt20 min/mile or lt13 min/km. Reduces the Risk for
    Coronary Events in Women by 30 to 40 Percent.
  • Similar Caloric Expenditure Yields Similar
    Reductions in Risk for Coronary Events.

48
Relative Risk of All-Cause Death and Exercise
Capacity
Myers J et al. 2002346793-801
RR of Death
CVD
Normal
lt6 METS
6-7.9 METS
8-9.9 METS
10-12.9 METS
gt13 METS
Quintiles of Exercise Capacity
49
Conclusions
Myers J et al. 2002346793-801
  • Exercise Capacity is a more powerful predictor
    of mortality for CVD than other established risk
    factors.
  • A linear reduction in mortality. For each 1 MET
    increase in exercise capacity, a 12, decrease in
    mortality was observed.

50
S T R O K E
51
The NIH Consensus Development Panel on Physical
Activity and CVDJAMA 96276241-46
  • Data are inadequate to determine whether stroke
    incidence is affected by physical activity or
    exercise training.

52
Physical Activity and Risk of Stroke in WomenHu
FB, et al , JAMA 20002832961-67
  • N72,488 Female Nurses with no CVD or Cancer
    at Baseline
  • Age 40-65 years
  • Follow-up 8 years (560,087 person-years)
  • 407 Strokes
  • 258 Ischemic
  • 67 Subarachnoid Hemorrhages
  • 42 Intracerebral 40 of Unknown type

53
Multivariate Relative Risk of Total Strokes
Relative Risk
P0.005
MET Quintiles
54
Multivariate RR for Ischemic Strokes
Relative Risk
P0.003
MET Quintiles
55
Multivariate Relative Risk of Total Strokes by
Walking Activity
Relative Risk
P0.01
METS
56
Multivariate Relative Risk of Ischemic Strokes by
Walking Activity
Relative Risk
p0.02
METS
57
RR of Total Strokes by Walking Pace
Relative Risk
Age-Adjusted
Multivariate
Plt0.001
58
Relative Risk of Hemorrhagic Strokes by Walking
Pace
Relative Risk
Plt0.02
Age-Adjusted
Multivariate
Plt0.06
59
Findings and Conclusions
  • Sedentary women who became active in middle to
    late adulthood had significantly lower risk for
  • Total Strokes 27 - Age-adjusted 20
    - Multivariate
  • Ischemic Strokes 38 - Age-adjusted 30
    - Multivariate

60
Findings and Conclusions
  • Walking pace is strongly associated with risk
    of stroke, Independent of the number of hours
    spent walking.
  • Comparable magnitudes of risk reduction with
    equivalent energy expenditures from walking and
    vigorous activity.

61
Cardiac Function
HTN
Dyslipidemia
Physical Activity
Body Fat
??
Endothelial Function
DM Type II
62
Hypertension
63
Kokkinos P., et al. Cardiology Clinics
200119(3)507-516
Average Reduction in BP Active 10.5/7.6
mm Hg Controls 3.8/1.3 mm Hg
64
BP Changes with Exercise
Kokkinos ,Pittaraset al. NEJM 19953331462-7
mm Hg
SBP
DBP
Plt0.05
16 weeks
32 weeks
65
BP Changes with Exercise
mm Hg
2 Wks
2 Wks
16 Wks
16 Wks
DBP
SBP
66
Relative Risk of All-Cause Death and Exercise
Capacity in Hypertensive Patients
Myers J et al. 2002346793-801
RR of Death
67
LVMI at Baseline and 16 Weeks
Kokkinos, Pittaras et al. NEJM 19953331462-7
plt0.05

Baseline
16 weeks
68
Wall Thickness at Baseline and 16 wks
Kokkinos, Pittaras et al. NEJM 19953331462-7
mm
plt0.05


69
Left ventricular hypertrophy is a powerful and
independent predictor of cardiovascular events in
patients with and without obstructive coronary
disease.
  • Ghali JK et al., 1992 Ann Intern Med
    1992117831-36 Koren MJ et al., 1991 Ann
    Intern Med 1991114345-52 Casale PN, et al.,
    Ann Intern Med 1986105173-78

70
LV Mass and Stroke
Rodriguez et al., JACC 200239(2)1482-8
Odds Ratio
Unadjusted
Adjusted
Quartiles of LV Mass
71
LVH, Physical Activity and Risk of Stroke
Rodriguez et al., JACC 200239(2)1482-8
Adjusted Odds Ratio
Active
4.79
3.92
3.53
3.29
2.9
72
LVH, Physical Activity Risk of Stroke
Rodriguez et al., JACC 200239(2)1482-8
Odds Ratio
Sedentary
Active
73
SBP Following Aerobic Training
Kokkinos et al, AJC 1997
plt0.01




74
May mitigate the hemodynamic load during daily
physical activities.
Attenuate the development and/or progression of
LVH.
75
Heart Failure
Skeletal Muscle Atrophy
Patient Adapts Sedentary Lifestyle
Diminished Aerobic Capacity
Muscular Changes
Neurohormonal Changes
Cardiorespiratory Changes
Kokkinos et al.. AHJ140(1) 2000
76
All Cardiac Event Survival for HF Patients
Belardinelli et al, Circulation 99991173-82
Trained
Untrained
77
Hospitalization for Heart Failure
Belardinelli et al, Circulation 99991173-82
Trained
Untrained
78
Cardiac Deaths for HF Patients
Belardinelli et al, Circulation 99991173-82
Trained
Untrained
79
Lipid Lipoprotein Metabolism
80
Changes in Lipids Lipoproteins with Exercise
and Diet in Men
Wood et al., NEJM 1991325461-6
Change
Control
Diet
DietEx
HDL-C
TG
LDL-C
81
Changes in Lipids Lipoproteins with Exercise
and Diet in Women
Wood et al., NEJM 1991325461-6
Change
Control
Diet
DietEx
TG
HDL-C
LDL-C
82
Is There A Dose-Response Relationship?
  • A dose-response relationship between HDL-C
    Levels and weekly distance run or weekly caloric
    expenditure is supported by most studies.

83
HDL-C and Km Run/WeekA dose-Response
Relationship
Kokkinos P., et al. Arch Intern Med 95155415-20
mg/dL

N2,906
plt0.001

Km/Week
84
Is There An Exercise Threshold?
  • The exercise-induced changes in lipid metabolism
    are likely the result of the interaction among
    exercise Intensity, Duration, Frequency and
    Length of Training.
  • It is also likely that an exercise threshold
    exists for each of these exercise components.

85
HDL-C and Weekly Distance
Kokkinos P., et al. Arch Intern Med 95155415-20
mg/dL
N2,906

plt0.001

Km/Week
86
Carbohydrate Metabolism
87
The Association between Cardiorespiratory
Fitness and Impaired Fasting Glucose and Type II
DM Wei M, et al., Ann Intern Med
199913089-96
  • N 8,633 Non-Diabetic Men
  • Age 30 to 79 yrs old
  • 7,511 Had Normal Fasting Blood Glucose
  • Follow-up 6 yrs
  • 149 Developed DM and 593 Developed Impaired
    Fasting Glucose

88
Cardiorespiratory Fitness Relative Risk for
Type II Diabetes
Wei M, et al. Ann Intern Med199913089-96
Relative Risk
plt0.001
Fitness Levels
89
Cardiorespiratory Fitness Relative Risk for
Impaired Fasting Glucose
Wei M, et al. Ann Intern Med9913089-96
Relative Risk
plt0.001
Fitness Levels
90
Cardiorespiratory Fitness RR for Impaired
Fasting Glucose Type II Diabetes in Women
(n338)
Relative Risk
plt0.001
Fitness Levels
91
Cumulative Incidence of Diabetes
Diabetes Prevention Program Research Group NEJM
346 (6) 393-403
Cumulative Incidence of DM ()
Placebo
Metformin
Lifestyle
92
Plasma Fasting Glucose
Diabetes Prevention Program Research Group NEJM
346 (6) 393-403
Plasma Glucose (mg/dl
Placebo
Metformin
Lifestyle
93
Glycosylated Hemoglobin
Diabetes Prevention Program Research Group NEJM
346 (6) 393-403
Glycosylated Hemoglobin ()
Placebo
Metformin
Lifestyle
94
Conclusions
  • Lifestyle changes and treatment with metformin
    both reduced the incidence of DM in persons at
    high risk.
  • Lifestyle intervention was more effective
    than metformin.
  • Number of pts need to be treated for 3 yrs to
    prevent 1 case of DM is 6.9 for the lifestyle
    intervention and 13.9 for metformin.

95
Plasma Glucose Levels Before After Aerobic
Training
Smutok et al. Metabolism 93
Plasma Glucose (mg/dl)
Pre-Training


Post-Training
Minutes After Glucose Ingestion
96
Plasma Glucose Levels Before After Strength
Training
Smutok et al. Metabolism 93
Plasma Glucose (mg/dl)
Pre-Training



Post-Training
Minutes After Glucose Ingestion
97
Plasma Insulin Levels Before After Aerobic
Training
Smutok et al. Metabolism 93
Plasma Insulin (?U/ml)
Pre-Training


Post-Training
Minutes After Glucose Ingestion
98
Plasma Insulin Levels Before After Strength
Training
Plasma Insulin (?U/ml)
Smutok et al. Metabolism 93
Pre-Training


Post-Training
Minutes After Glucose Ingestion
99
Body Weight/ Obesity
100
Relative Risk for Physical Activity BMI,
Adjusted For Risk Factors
Mason JE, et al. NEJM99341650-8
RR
N72,488
gt29
lt29
Physical Activity Quintiles
101
Cardiorespiratory Fitness CVD Mortality in Men
(N25,714)
Wei M, et al.JAMA99282(16)1547-53
Relative Risk
Fit
Unfit
(Normal)
(Obese)
(Over WT)
102
CVD Mortality Predictors in Normal WT Men (BMI
18.5-24.9)
Wei M, et al.JAMA99282(16)1547-53
Relative Risk
103
CVD Mortality Predictors in Overweight Men (BMI
25-29.9)
Wei M, et al.JAMA99282(16)1547-53
Relative Risk
104
CVD Mortality Predictors in Obese Men (BMI gt30)
Wei M, et al.JAMA99282(16)1547-53
Relative Risk
105
These findings suggest that it is as important
for a clinician to assess the fitness status of
patients, (especially obese) as it is to assess
blood glucose, TC, HTN and smoking habits.
106
Exercise Recommendations
  • Aerobic Activity 3-5 times/wk
  • Brisk Walk to Slow Jog
  • 60 to 80 of PMHR
  • 100 to 200 minutes/week
  • 1200 to 2400 Kcal/Wk

107
LVMI at Baseline and 16 Weeks in Patients with LVH
Kokkinos, Pittaras et al. New Engl J Med
19953331462-7
g/m2
plt0.05

Baseline
16 weeks
108
Wall Thickness at Baseline and 16 wks
Kokkinos, Pittaras et al. New Engl J Med
19953331462-7
mm
plt0.05


109
How Much Physical Activity ?
  • Do something
  • Choose something you enjoy
  • Start Low Progress Slowly
  • Increase duration by 1-2 min/wk
  • Be Consistent (2-5 times/week)
  • Goal 100-200 minutes/week

110
Exercise Training is Governed By Three Principles
  • Specificity
  • Overload
  • Reversibility

111
The Specificity Principle
  • Biological Systems will Make Specific Adaptations
    to Accommodate an Imposed Demand !

112
SPECIFICITY
  • Aerobic
  • Long Duration (gt10 min)
  • Low Intensity (lt85 of PMHR)
  • ATP via TCA Cycle
  • FFA as Fuel
  • Anaerobic
  • Short Duration (lt5 min)
  • High Intensity ( gt90 of PMHR)
  • ATP via Glycolysis
  • CHO as Fuel

113
The Overload Principle
  • The performance of a Biological System will
    Improve Only If the Demand Imposed upon it is
    Greater than the System is Currently Accustomed.

114
Overload Principle
  • Frequency, Duration
  • and/or Intensity Must be Increased Periodically.

115
Reversibility Principle
  • Training adaptations diminish
  • if stimulation (training)
  • is discontinued for a length of time (12 -90
    days).

116
Exercise Components
  • Frequency - Times/Wk
  • Duration - Min/Session
  • Intensity - How Hard
  • Length - How many Wks

117
Frequency
  • 2- 5 Times per Week
  • Exercise Every Other Day
  • Multiple Short Daily Sessions (5-10 min)
    for Those with Functional Capacity lt 3 METS

118
Duration
  • 20-60 Minutes/Session of Continuous Aerobic
    Activity
  • Multiple Daily Sessions ( 10 min) for Those
    with Functional Capacity lt 3 METs.
  • Slow, Progressive Increase

119
Length of Training
  • Most Exercise Benefits Are Evident Within 12
    Weeks of Consistent Training.

120
ACSM Exercise Intensity Classifications
  • METS PMHR
  • Low lt4 35-59
  • Moderate 4-6 60-79
  • High gt 6 gt 80

121
Exercise For Overweight Obese Patients
  • Exercise Modality that
  • does not Impose Excessive
  • Orthopedic Stress
  • (walking, stationary bike, aquatic exercises).

122
Exercise Intensity for Patients on Chronotropic
Medications
  • Base Exercise intensity on
  • 50 to 80 of Peak HR
  • achieved during ETT.

123
METs Kcal for 30 Minutes of Select Physical
Activities (80-kg person)
  • Activity METs Kcal
  • Fast Walk 5 200
  • Jog (12 min/mile) 8 320
  • Bike (Stationary) 7 280
  • Health Club 7 280
  • Dancing 5 200
  • Stair Climbing 5 200

124
Contraindications Recommendations for Exercise
  • Complete Physical
  • Resting BPlt 190/105 mm Hg
  • Exercise BP lt240/120 mm Hg
  • Exercise SBP drop gt10 mm Hg (baseline)
  • Unable to complete 5 METs (ETT) or climb a flight
    of stairs without severe SOB or symptoms.

Gill et al. JAMA 2000
125
Relative Risk of Onset of MI with Physical
Activity
126
Relative Risk of Onset of MI with Physical
Activity
127
The relative MI Risk for a 50-yr-old Non-smoking,
Non-diabetic Man during a given hour is 1 in 1
million. If this man were sedentary and engaged
in heavy physical exertion during that hour, his
risk would increase 100 times or 1 in 10,000.
Framingham Heart Study
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