epi exam two chapters 5&6

physical activity guidelines advisory committee 2008 findings - threshold of about _______ kcal/week

750-1000

CHD mortality protective threshold window

750-2000 kcal/week; moderate PA (3-6 METS)

primary ischemic or thromboembolic stroke

85% of all strokes; results from clotting or stenosis (70%) or embolism (5-10%)

___________ deaths attributed to some form of CVD

864,000

Aerobics Center Longitudinal Study description

max treadmill time and mortality in 10,000 men and 3,000 women over about 8 years; outcome was age adjusted all-cause mortality

__________ new coronary attacks

700,000

Changes in fitness level and all-cause mortality - ACLS cohort

- men (9000) - 2 exams (1970 to 1987) - mortality for five years after the 2nd exam - each minute increase in treadmill time = 8% lower risk

cardiovascular disease: _______ in direct and indirect costs in 2007

$475 billion

ACLS changes in fitness

- 10,000 men from ACLS - fitness measure at two time points (5 years) - CVD mortality 5 yrs after 2nd exam - risk related to change in fitness level - 8-10% reduction in risk for each minute treadmill time increased from T1 to T2 for both health and unhealthy men

fitness versus physical activity - myers et al. 2004

- 1000 men - 6-10 years follow-up - fitness overall better predictor of morality - nice dose response for fitness and PA - evidence for consistency

CHD mortality

- 20 of 31 observational studies prior to 1996 found a dose-response gradient for a 50% reduction in risk of CHD mortality for higher levels of PA - Updated in 2008 (subsequent slide) - Newer studies do a better job at getting rid of residual confounders

exercise and recurrent heart attack risk: meta-analysis

- 22 RCTs of 4,554 patients - mortality OR = .80 - CVD mortality OR = .78 - fatal heart attack OR = .75 - sudden death OR = .63 - better survival but no effect on RHA

Physical Activity and Stroke: Chiuve et al., Circulation 2008

- 25% reduction in risk for the women - 25% reduction in risk for the men - Focus on ischemic stroke

exercise and recurrent heart attack risk: national exercise and heart disease project

- 3 year RCT of 651 men 30-64 y followed 19 years - 8%-14% drop in CVD and all-cause mortality with each 1 MET increase in fitness

Physical Activity and Ischemic Stroke: Northern Manhattan Stroke Study, New York City (Sacco et al, 1998)

- 369 cases of first stroke - 678 controls - mean age 70 years - very diverse study - broad spectrum of folks - dose response in both conditions (no exercise vs light to moderate vs vigorous AND <2 h/wk vs <5 h/wk vs 5+ h/wk) - gets on cusp of consistency

PA and stroke risk: 15 studies published by 2001

- 4 focused on women - 13 were cohort studies ranging from 5 to 26 years - Half reported a significant reduction (30-60%) in risk of stroke or stroke death among active - Just six showed dose-response - Most studies adjusted for confounders and found reduced risk in U.S. and Europe regardless of age, ethnicity, and sex

Physical Activity and Stroke: U.S. Health Professionals Study Cohort (Chiuve et al., 2008)

- 43,685 men - free of CVD in 1986 - 40-65 years of age - 994 incident cases of stroke during 16 years of follow up - independent of age, smoking, BMI, history of hypertension - dose response w/moderate-vigorous PA

Intensity? health professionals' follow-up study

- 45,000 men - PA every 2 years from 1986 to 1998 - controlling for major CVD risk and volume of activity - walk speed increase = better off - dose response w/intensity increase and walk speed increase

exercise testing and mortality risk: stanford, CA study (myers et al., 2002)

- 6,213 men at different fit levels - Dose-response - Lighter the bar the lower the fitness level; darkest bar is most fit - Higher the fitness the lower the risk - The average reduction is 1 MET increase in exercise capacity increased survival by 12% - Everybody in elevated risk groups is being benefitted by PA - Activity is modifying the risk in all of the conditions (hypertension, COPD, diabetes, smoking, high BMI, cholesterol)

CHD mortality updated by PA Guidelines Advisory Committee 2008

- 60 prospective cohort studies since 1996 found a linear reduction in CHD mortality risk of 30-40% with higher levels of physical activity during middle age in both men and women - negatively accelerating

Physical Activity and Stroke: U.S. Nurses Health Study Cohort (Hu et al. 2000)

- 72,488 women - free of CVD in 1986 - 40-65 years of age - 407 incident cases of stroke during 8 years of follow up - independent of age, smoking, BMI, history of hypertension) - Dose response for all but hemorrhagic stroke (dose response until risk went back up in group doing the most) - Exercise may increase risk for hemorrhagic in the most active - Anti-clotting effect of exercise (may not be true but is a way to think about an alternative explanation for things)

changes in fitness - harvard alumni study

- PA stayed the same or increased - Risk is reduced at all ages in those who are increasing their activity - Not showing a third level (people who were active and became less active)

Physical Activity and Stroke: U.S. Physician's Health Study Cohort (lee at al., 1999)

- RR of stroke among 21,823 men - 40-80 years of age - 533 cases of stroke during 11 years of follow up - independent of age, smoking, alcohol intake, history of angina, parental history of MI - not independent of hypertension, BMI, high cholesterol, diabetes - No dose response; any frequency of vigorous exercise during the week means you're protected compared to someone doing none

Physical Activity and Stroke: Harvard Alumni Study Cohort (Paffenbarger, Hyde, Wing and Steinmetz 1984)

- Rates and RR of first stroke - More than 10,000 men - Entered college in 1916-1950 - Followed up in the 1960s & 1978 - Independent of blood pressure, age, smoking, body weight, and family history of CVD - nice dose response

stroke plausibility

- Reduced risk of atherosclerosis and thrombosis (see ch 5, p. 112-114). - Reduced blood pressure - Vessel injury and plaque formation - Clotting factors • 4-year follow up of 854 Finnish men 42-60 years: after adjusting for age and smoking, maximal aerobic power was inversely related to the surface roughness and thickness of the interior lining of the carotid artery; remained after further adjustment for blood pressure, diabetes, apo B, and plasma fibrinogen. - Brain neurotrophins

the women's lifestyle and health cohort (trolls-lagerros et al. 2005)

- Risk if women was active when she was 14 or when she enrolled in this study as an adult woman - No activity is blue - that's the risky comparison - Enrollment age has nice dose response - At age 14 (done by recall - did you play sports as a girl etc) - kind of a dose response except the most vigorous group was no better off than those who did nothing - Suggests that what you're doing in your recent health is more important than what you did when you were young - If a woman decreased her activity level, risk was the same as someone who was inactive her whole life

how does exercise protect for CHD: increase electrical stability of myocardium

- decrease local ischemia during rest and submax exercise - decrease myocardial catecholamines, beta-adreno receptors or cAMP - increase ventricular fibrillation threshold

how does exercise protect for CHD: decrease myocardial work and oxygen demand

- decrease resting and sub maximal heart rate - decrease resting and submaximal systolic and mean arterial blood pressure - decrease submax cardiac output during exercise - decrease resting and exercise plasma catecholamines - decrease adiposity

how does exercise protect for CHD: maintain or increase myocardial oxygen

- delay, retard or reduce plaque ( improve lipoprotein profile, improve CHO metabolism, decrease platelet stickiness, increase fibrinolysis) - increase coronary collaterals - increase myocardial perfusion or distribution

stroke potentially controllable risk factors

- history of stroke (50%/5 yr) - history of TIA (33%/5 yr) - hypertension - heart diseases - carotid and peripheral vascular disease - hyperlipidemia - type II diabetes/obesity - smoking - alcohol abuse

how does exercise protect for CHD: increase myocardial function

- increase myocardial hypertrophy and contractility - increase resting and exercise ejection fraction - decrease afterload - increase resting and sub maximal stroke volume

Cardiovascular Health Study on PA and all-cause mortality (6000 men and women; 65+)

- kind of a dose response - 5 year mortality (646 deaths) - most protected group is expending close to 2000 kcals/week - adjusted means ruled out other confounders; data has been statistically adjusted to rule out other risk factors - results for PA/fitness are independent of other factors

cardiovascular disease: _____ million people in US have one or more types ( ______% of the population)

70; 34

stroke uncontrollable risk factors

- over age 55 years (2/3 over 65 years) - type 1 diabetes - african american race (2x risk) - sickle cell disease - females? (higher risk, but more stroke survivors; men die from other causes sooner) - family Hx

Nurse's health study

- relative risk of coronary events - 72,488 female nurses - walking and total PA risk reduction is very similar; explanation: most of their activity is walking

major risk factors for CHD that can be modified

- tobacco smoke (22.5%) - blood cholesterol levels - high blood pressure (32%) - physical inactivity (25-60%) - obesity and overweight (65%)(30% obese) - diabetes mellitus (6.7%) RR of HD death = 2-4

leading causes of death US, 2006: deaths in thousands - heart disease

720

cost of stroke in US 2010

73.7 billion

leading causes of death US, 2006: deaths in thousands - diabetes

75

ACLS changes in fitness RR fit/fit

.22

Aerobics Center Longitudinal Study: 8 year follow-up (25,000 men and 7,000 women) - high fit (top 20%) had RR = ________ compared to low fit women (adjusted for age, year, smoking, chronic disease)

.37

ACLS changes in fitness RR unfit/fit

.48

Aerobics Center Longitudinal Study: 8 year follow-up (25,000 men and 7,000 women) - high fit (top 20%) had RR = ________ compared to low fit men (adjusted for age, year, smoking, chronic disease)

.49

high CRF

.64 (.68-.76)

moderate CRF

.68 (.52-.66)

physical activity guidelines advisory committee 2008 findings

67 of 73 observational studies since 1996 found a linear reduction in all-cause mortality risk of 31% with higher levels of physical activity; similar in men and women

about ________ of the 4.5 million US stroke survivors are disabled

67%

cost of stroke in US 2007

69 billion

atherogenesis steps

1. oxidized LDL 2. macrophages/inflammation 3. foam cells 4. plaque growth/muscle infiltration 5. plaque rupture

Samitz et al. study showed _____% decrease for each hour per week of vigorous PA

10

leading causes of death US, 2006: deaths in thousands - unintentional injuries

100

leading causes of death US, 2006: deaths in thousands - chronic lower respiratory disease

125

Samitz et al study showed 150 min of MVPA lead to a _____% decrease

14

CHD primary prevention (sattlemair et al. 2011) 9 of 33 prospective cohort studies gave quantitative data on PA exposure: 150 min/wk of moderate intensity leisure-time physical activity resulted in ________ lower CHD risk compared with people reporting no PA

14% (RR .86)

leading causes of death US, 2006: deaths in thousands - stroke

144

only ____% of heart attacks and strokes are the result of occlusion

15

primary hemorrhagic stroke

15% of strokes; results from bleeding on (5%) or in (10%) brain

each year about _________ die from a stroke-related event

160,000

CHD cost in 2007

165 billion

____________ adults in the US have CHD

17.6 million (about 935,000 heart attacks each year)

CHD cost in 2010

177 billion

percentage breakdown of deaths from CVD diseases: stroke

18%

each year about ____________ have a recurrent stroke

185,000

physical activity guidelines advisory committee 2008 findings - about _______ of moderate PA such as walking

2 to 2.5 hours/week

physical activity and all-cause mortality number

2.4 million

CHD primary prevention (sattlemair et al. 2011) 9 of 33 prospective cohort studies gave quantitative data on PA exposure: 300 min/week of moderate-intensity leisure-time PA resulted in ______ lower CHD risk

20% (RR .80)

death decline rate of stroke since 1950

2006 death rate of 45/100,000 has dropped from 89/100,000 since 1950

PA and all-cause mortality US 2006: ______% of all deaths cancer

23.1

Physical Activity and Recurrent Stroke: Birmingham, England (Shinton and Sagar, 1993)

25 cases who had a stroke 198 controls; adjusted for age and sex. Reduced risk for vigorous exercise remained around .40 after further adjustments

Physical Activity Guidelines for Americans Advisory Committee concluded that active men and women have _______ lower risk of stroke incidence or stroke mortality

25%-30%

Samitz et al study showed 300 min of MVPA lead to a ______% decrease

26 (so it's better to do five hours a week than two hours)

Samitz et al., 2011 meta-analysis of 80 observational studies of 1.33 million adults: leisure PA

26% (.30-.33%) decrease

smoking, AA, 65 years stroke risk

2x (double)

the women's lifestyle and health cohort (trolls-lagerros et al. 2005) - those women that stayed active or became active had about ______ reduction in risk

30%

PA and all-cause mortality US 2006: ______% of all deaths CVD (heart and stroke)

31.7

Samitz et al., 2011 meta-analysis of 80 observational studies of 1.33 million adults: total PA

35% (.40-.29%) decrease

__________% of all deaths are CVD

38

stroke is the ___ leading cause of death in the US

3rd (136,000 died in 2007 - 54,000 men and 82,000 women)

Aerobics Center Longitudinal Study - low fit all-cause mortality ______ rate compared to most fit group (men)

3x

diabetes stroke risk

3x

Samitz et al. study showed _____% decrease for each hour per week of moderate PA

4

stroke magnitude 1990

4.4 million/yr deaths worldwide, 2nd only to 6.3 million CHD deaths

CHD deaths

425-450,000

Aerobics Center Longitudinal Study - low fit all-cause mortality ______ rate compared to most fit group (women)

4x

percentage breakdown of deaths from CVD diseases: high blood pressure

5%

stroke magnitude 2000

5.4 million/yr deaths worldwide, 2nd only to 7.06 million CHD deaths

percentage breakdown of deaths from CVD diseases: coronary heart disease

53%

leading causes of death US, 2006: deaths in thousands - cancer

575

over the last 50 years CHD death rates have decreased by

59%

_________ ever had a stroke

6.4 million (2.4% ; 2.5 million men and 3.9 million women)

each year about __________ adults have a first stroke

610,000

#1 killer in US every year since 1900 (except 1918)

CVD

St James Women Take Heart Project - Chicago

For each 1 MET increase in treadmill exercise endurance there was a 17% reduction in all-cause mortality adjusted for other risk factors

the first physical activity epidemiologist

James Easton (1799)

why is CVD risk higher for older women than older men?

More older women than older men so women risk is higher at older ages (Occam's razor)

women's health study (mora et al., circulation 2007)

PA lowered CVD risk by 59%

exercise testing and mortality risk: lipid research clinics prevalence study (mora et al., JAMA 2003)

RR of CVD and all-cause mortality among almost 3000 asymptomatic women independent of age, smoking, BMI, diabetes, family history of CH, high LDL, high triglycerides, low HDL, hypertension; nice dose response

temporal sequence

exposure to the risk factor must precede development of the disease with sufficient time to account for disease progression

thrombotic stroke causes

abnormal hemostasis

embolic stroke causes

aortic placques, atrial fibrillation, SA node and valve disorders, MI, heart inflammation, heart tumors

"a stroke of God's hands;" derived from the Greek word for thunderstruck

apoplexy (modern usage" a cerebrovascular accident)

hazards of alcohol take home message

being active modifies the risk (particularly of cancers) of death at different drinking levels

regulation of blood clotting

blood viscosity, coagulation factors, platelet stickiness, fibrinogenesis, fibrinolysis

single largest killer of american males and females

coronary heart disease

metabolic component of physical fitness (bouchard and shephard)

glucose tolerance insulin sensitivity ratio of lipid to CHO oxidation (RER)

__________ is one of the highest stroke risk factors

high blood pressure (6x risk of stroke)

PA and stroke risk: Meta Analysis of 13 prospective cohort studies with average follow-up of 14 years (Diep et al., 2010)

highly active: 19% lower risk moderately active: 11% lower risk

PA and stroke risk: meta analysis of 18 cohort studies (11 from the U.S. and 1 each from England, the Netherlands, Italy, Norway, Iceland, Sweden, and Japan) (Lee, Folsom, Blair, 2003)

highly active: 25% lower risk moderately active: 17% lower risk

Aerobics Center Longitudinal Study: older adults (60-89); 1800 men, 800 women; 10 yr follow up adjusted for age, year, BMI, cholesterol, smoking, high BP, diabetes

in women age 70-89 being in the highest fitness group was worse than being in the moderate one; however in the rest of the group deaths per 1,000 all decreased more with improved fitness levels (dose response); biggest difference going from low fitness to moderate fitness

major risk factors for CHD that cannot be changed

increasing age, male gender, heredity (including race)

women's health study (mora et al., circulation 2007) proportions of reduced risk for each biomarker

inflammatory and hemostatic biomarkers contributed the most, followed by blood pressure, then LDL/HDL/total cholesterol, then apolipoproteins A1 and B100, then BMI, and finally hemoglobin A1c/diabetes

clotting

platelet stickiness is higher in morning; increased by catecholamines; decreased by aspirin, ethanol, and flavanoids

types of strokes

primary hemorrhagic and primary ischemic or thromboembolic

lacunar stroke causes

stenosis of carotid and deep arteries by occlusion from atherosclerotic plaques, cholesterol emboli, clots from heart inflammation, and arteriosclerosis

all-cause mortality (kodama et al., 2009)

summary of 33 studies in more than 100,,000 people; 13% REDUCTION IN RISK FOR EACH 1 MET ELEVEVATION IN CRF

consistency

the observed association is always observed if the risk factor is present regardless of sex, race, age or methods of measurement

biological plausibliity

the observed association is explainable by existing knowledge about possible biological mechanisms of the disease, which may be alterable (e.g. by physical activity)

dose response

the risk of disease associated with the risk factor is greater with stronger exposure to the risk factor

strength of association

there is a large and clinically meaningful difference in disease risk between those exposed and those not exposed to the risk factor

the only acute therapy (i.e., within 3 hours of symptom onset) that is approved by the FDA for ischemic stroke

thrombolysis using intravenous injection of tissue plasminogen activator (t-PA); it improves clinical outcomes (OR = 1.7 (95% CI 1.2 to 2.6), but not mortality rates, at 3 months after stroke (Marler et al., 2000).