Exercise Studies Where Walking is Better than Running: Does Intensity Matter?

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Exercise Studies Where Walking is Better than Running: Does Intensity Matter? Frontiers in Medicine The Forest 24 September 2018 William E. Kraus, M.D.

Exercise Intensity and Volume Effects: Confounded? ØTo really understand intensity effects, one must match for amount. ØEffects of exercise intensity, matched for amount on insulin sensitivity, serum triglycerides. ØEffects of intensity and amount on HDL cholesterol.

STRRIDE Studies of a Targeted Risk Reduction Intervention with Defined Exercise STRRIDE I STRRIDE AT/RT STRRIDE-PD NHLBI: HL-57453 NHLBI: HL-57453 NIDDK: DK-081559 NCT00200993 NCT00275145 NCT00962962

STRRIDE: Eligibility Criteria Age: 40-65 Body Composition: 25 BMI 35 Lipids: 130 LDL 190 or HDL 40 M and 45 W Glucose: fasting 140 mg%; fasting insulin 10 IU/ml Blood pressure: 160/90 mmhg Menstrual status: postmenopausal (FSH 40) HRT 6 months Demographics: equal genders, 30% minority Activity: sedentary, peak VO 2 ~ 29 ml/kg/min (8.3 METS) Medications: nothing that is known to influence skeletal muscle or exercise training responses (e.g. ACE inhibitors, b-blockers) and stable for 6 months

STRRIDE - Training Protocols Intensity Amount Time/wk (peak VO 2 ) (kcal/wk) (min per wk) Brisk Walking 13 miles/week 170 Jogging 13 miles/week 120 Jogging 22 miles/week 170 Inactive None None

STRRIDE - Training Protocols Intensity Amount Time/wk (peak VO 2 ) (kcal/wk) (min per wk) Int Brisk Walking 13 miles/week 170 Jogging 13 miles/week 120 Amt Jogging 22 miles/week 170 Inactive None None

STRRIDE - Study Design Months 0 3 6 9 10 12 Screening Ramp up Training Detraining Retraining (optional)

20 Percent Change Peak VO 2 15 10 5 d 0 Inactive Low Dose Moderate Low Dose Vigorous High Dose Vigorous Group

Percent Change Body Mass 2 1 0-1 -2 a Inactive Low Dose Moderate Group Low Dose Vigorous High Dose Vigorous

Triglycerides (mg/dl) 20-20 -60-100 120 Percent Change Si 100 80 60 40 20 0 d -20 Inactive Low Dose Low Dose Moderate Vigorous Group High Dose Vigorous

AUC Glucose by Group Glucose AUC Chg (mg/dl 120 min) 0-500 -1000-1500 -2000-2500 23.5% 51.3% 94.4% High Moderate High Vigorous Low Moderate 100% DPP-like Lifestyle

Glucose AUC Change (mg/dl 120 min) 0-500 -1000-1500 -2000 94.4 23.5% 51.3% 100% Insulin AUC Change (µu/ml 120 min) 0-1000 -2000-3000 -4000 62.9% 42.4 33.1% 100% -2500 16 KKW Mod- Intensity 16 KKW Vig- Intensity 10 KKW Mod- Intensity Clinical Lifestyle -5000 16 KKW Mod- Intensity 16 KKW Vig- Intensity 10 KKW Mod- Intensity Clinical Lifestyle Fasting Glucose Change (mg/dl) 2 0-2 -4-6 24.5% 100% Fasting Insulin Change (µu/ml) 0-1 -2-3 53.5% 39.6% 18% 100% -8 16 KKW Mod- Intensity 16 KKW Vig- Intensity 10 KKW Mod- Intensity Clinical Lifestyle -4 16 KKW Mod- Intensity 16 KKW Vig- Intensity 10 KKW Mod- Intensity Clinical Lifestyle

Responses of HDL to Various Exercise Regimens 0.15 Amount Effect HDL-C (mmol/l) 0.10 0.05 0.00-0.05-0.10 Inactive Intensity Effect Low Dose Moderate Low Dose Vigorous High Dose Vigorous Group

In general, both HDL cholesterol and serum TG reproducibly and favorably respond to changes in habitual physical activity, with increases in HDL cholesterol and decreases in serum TG, mostly related to the volume of exercise training and responding with threshold volumes in the range of 7 to 15 miles per week of regular exercise (equating to an approximate 600 to 800 MET-minutes). Physical Activity Guidelines Advisory Committee Science Report, DHHS, 2008

Exercise Intensity and Volume Effects: Confounded? ØTo really understand intensity effects, one must match for amount. ØEffects of exercise intensity, matched for amount on insulin sensitivity, serum triglycerides. ØEffects of intensity and amount on HDL cholesterol. ØIntensity is important, but different for different health benefits personalized exercise prescription.

Runners versus Walkers

Walking vs. Running Prospective Cohort Studies National Runners (33,060) and Walkers (15,945) Health Study Cohorts Energy expenditure quantified in METs/d Risk reductions in physician-diagnosed hypertension, hypercholesterolemia, diabetes and CHD over 6.2 years of follow-up No difference in risk reductions. Williams PT, Thompson PD. ATVB 33: 1085-91, 2013

Reduction in coronary heart disease (CHD) risks per metabolic equivant hours per day (METh/d) energy expended by walking or running at baseline. Paul T. Williams, and Paul D. Thompson Arterioscler Thromb Vasc Biol. 2013;33:1085-1091 Copyright American Heart Association, Inc. All rights reserved.

STRRIDE I 10-year Reunion

Reunion Protocol STRRIDE I participants that finished intervention period drop outs not invited back. 10 years following completion invited back for CPX test, blood work, assessment of BP, lipids, FBG, FI, waist circumference and weight, PA in last three months. Comparisons made to pre-intervention assessments.

Reunion Results 0 0 % Peak VO 2 (L/min) Fasting Insulin (uu/ml) -3-6 -9-12 -15 2 0-2 -4-6 -8 Inactive Control Inactive Low Low-Amt Amount Moderate moderate Low Low-Amt Amount Moderate moderate Low-Amt Amount High-Amt Amount vigorous Vigorous vigorous Vigorous Low-Amt Amount High High-Amt Amount vigorous Vigorous vigorous Vigorous Mean Arterial BP (mmhg) -2-4 -6-8 -10 Minimal Waist (cm) Inactive Inactive 8 6 4 2 0 Low Low-Amt Amount Low-Amt Amount High-Amt Amount Moderate moderate vigorous Vigorous vigorous Vigorous -2 Inactive Control Low Low-Amt Amount Low-Amt AmountHigh-Amt Moderate moderate vigorous Vigorous vigorous Vigorous

Change in Peak VO2

Change MAP controlled PA No Reg PA Reg PA D MAP controlled for weekly PA Last 3 Mo. 2 1 0-1 -2-3 -4-5 -6-7 -8-9 Inactive LAMI LAVI HAVI Inactive Low Amount Moderate Low Amount Vigorous High Amount Vigorous

A Weight Estimated Mean (kg) 100 98 96 94 92 90 0 0 1 2 3 4 5 6 7 8 9 10 Year Control Intervention Main effect, 4 (95% CI, 5 to 3) P<0.001 B Physical Fitness Estimated Mean (MET) 6.0 5.5 5.0 0.0 Intervention Control Main effect, 0.6 (95% CI, 0.5 to 0.8) P<0.001 0 1 2 3 4 5 6 7 8 9 10 Year C Waist Circumference Estimated Mean (cm) 114 112 110 108 Control Intervention D Glycated Hemoglobin Estimated Mean (%) 7.4 7.2 7.0 6.8 Control Intervention 106 0 Main effect, 3.2 (95% CI, 3.9 to 2.4) P<0.001 0 1 2 3 4 5 6 7 8 9 10 6.6 0.0 Main effect, 0.22 (95% CI, 0.28 to 0.16) P<0.001 0 1 2 3 4 5 6 7 8 9 10 Year Year The Look AHEAD Research Group n engl j med 369;2 nejm.org july 11, 2013

US Physical Activity Guidelines for Americans 2018 Overview and Highlights from the Physical Activity Guidelines Committee Frontiers in Medicine The Forest 24 September 2018 William E. Kraus, M.D.

Figure 1 MVPA & All-Cause Mortality in 654, 827 Men & Women age 21-90 10 years follow-up 82,465 deaths No lower threshold for benefit Steep early slope About 70% of benefit reached by 8.25 MET-hr/wk No apparent upper threshold No obvious best amount 150-300 Min MPA No evidence of increased risk at high end Moore, et al. PLOS Medicine, November 2012

Relative risks 1.0 0.9 Ischaemic stroke Ischaemic heart disease Diabetes Breast cancer Colon cancer 0.8 0.7 0 2 4 6 8 10 MET (minutes/week 000s) Fig 7 Continuous risk curves for association between Kyu HH,Bachman VF, Alexander L et al. Physical activity and risk of breast cancer, colon cancer, diabetes, ischemic heart disease, and ischemic stroke events: systematic review and dose-response meta-analysis for the Global Burden of Disease Study 2013 BMJ, 354.

Figure 2 Risk of selected health events by hours/week of moderate to vigorous physical activity all-cause mortality depression, dementia breast cancer diabetes colon cancer hip fracture CVD, CHD, stroke

Steps

Implications The measure of steps per day has the potential to significantly improve the translation of research findings into public health recommendations, policies, and programs. 32

Importance Steps are a basic unit of locomotion Easy to understand metric of ambulation Measuring step counts shown to motivate diverse samples of individuals to increase physical activity levels Self-assessment of steps through objective, readily obtainable technology Step counts per day provides a comparable denominator to caloric intake per day Tool for researchers and the public addressing a variety of health and physical activity issues Steps can be at light-, moderate-, and vigorous-intensity levels Range of exertion choice for the promotion of walking 33

NAVIGATOR Estimated 5-year event rate 0 08 0 06 0 04 0 02 95% confidence bound (adjusted for model 1) 0 6000 4000 2000 0 2000 4000 6000 Change in ambulatory activity (steps per day) Yates (2014) used Navigator data to show change in steps per day was associated with reduce risk for cardiovascular events, specifically, a yearly 2,000 steps per day increase resulted in an 8% yearly reduction in cardiovascular event rate. The doseresponse appeared linear. Baseline level of steps per day was inversely associated with cardiovascular event incidence, specifically at baseline each 2000 steps per day increment was associated with a 10% lower cardiovascular event rate. Figure: Relation between change in ambulatory activity and adjusted 5-year cardiovascular event rates Yates 2014 34

New Data Saint-Maurice, JAHA, 2018 NHANES, 2003-2006 wave >40 y 4840 individuals 700 deaths (31 Dec 2011) 100-759 cpm = light 760 cpm = MVPA 35

Do Bouts Matter? Whence did this whole idea originate?

New Data 1.00 1.00 Saint-Maurice, JAHA, 2018 Hazard ratio 1 0.9 0.8 0.7 0.6 0.5 0.4 0.3 0.2 0.1 0 1.00 0.43 0.42 0.44 0.39 Q1 (referent) Q2 Q3 Q4 Quartiles 0.24 0.27 0.26 0.28 0.35 Total MVPA 5min bouts 10min NHANES, 2003-2006 wave >40 y 4840 individuals 700 deaths (31 Dec 2011) 100-759 cpm = light 760 cpm = MVPA 37