Impact of Body Mass Index, Physical Activity, and Other Clinical Factors on Cardiorespiratory Fitness (from the Cooper Center Longitudinal Study) Susan G. Lakoski, MD, MSa,*, Carolyn E. Barlow, MSb, Stephen W. Farrell, PhDb, Jarett D. Berry, MD, MSa, James R. Morrow, Jr., PhDc, and William L. Haskell, PhDd Cardiorespiratory fitness (CRF) is widely accepted as an important reversible cardiovas- cular risk factor. In the present study, we examined the nonmodifiable and modifiable determinants of CRF within a large healthy Caucasian population of men and women. The study included 20,239 patients presenting to Cooper Clinic (Dallas, Texas) for a compre- hensive medical examination from 2000 through 2010. CRF was determined by maximal treadmill exercise testing. Physical activity categories were 0 metabolic equivalent tasks (METs)/min/week (no self-reported moderate or vigorous intensity physical activity), 1 to 449 METs/min/week (not meeting physical activity guideline), 450 to 749 METs/min/week (meeting guideline), and 750 METs/min/week (exceeding guideline). Linear regression modeling was used to determine the most robust clinical factors associated with achieved treadmill time. Age, gender, body mass index (BMI), and physical activity were the most important factors associated with CRF, explaining 56% of the variance (R2 0.56). The addition of all other factors combined (current smoking, systolic blood pressure, blood glucose, high-density and low-density lipoprotein cholesterol, health status) were associ- ated with CRF (p 0.05) but additively only improved R2 by 2%. There was a significant interaction between BMI and physical activity on CRF, such that normal-weight (BMI 25 kg/m2) subjects achieved higher CRF for a given level of physical activity compared to obese subjects (BMI 30 kg/m2). Percent body fat, not lean body mass, was the key factor driving this interaction. In conclusion, BMI was the most important clinical risk factor associated with CRF other than nonmodifiable risk factors age and gender. For a similar amount of physical activity, normal-weight subjects achieved a higher CRF level compared to obese subjects. These data suggest that obesity may offset the benefits of physical activity on achieved CRF, even in a healthy population of men and women. © 2011 Elsevier Inc. All rights reserved. (Am J Cardiol 2011 108:34–39) Cardiorespiratory fitness (CRF) is a strong predictor of cardiovascular and all-cause mortality1–8 and provides prognostic value beyond traditional risk factor assessment.9 Because CRF is a composite of several nonmodifiable and modifiable clinical risk factors,10,11 understanding the im- portance of these factors on CRF estimates is critical when assigning recommendations concerning healthy lifestyles. The primary goal of the present study was to determine the key factors that explain CRF in generally healthy men and women. Second, we explored the interplay between 2 known modifiable factors (physical activity and body mass index [BMI]) on CRF. Third, we assessed whether meeting the American College of Sports Medicine and American Heart Association guidelines for physical activity12 was associated with higher CRF estimates in normal-weight, overweight, and obese men and women. To achieve this goal, we used the Cooper Center Longitudinal Study (CCLS), the largest United States population database of CRF estimates with concomitant risk factor capture. Methods The CCLS is a prospective study composed of patients who received preventive medical examinations at the Cooper Clinic in Dallas, Texas. Most were referred by their personal physicians, employers, or were self-re- ferred for examination. The present study included 20,329 Caucasian men and women, 20 to 90 years of age, who completed a comprehensive medical examination from 2000 through 2010 and achieved 85% of their maximum predicted heart rate during exercise treadmill testing.8 We excluded subjects seen at the Cooper Clinic before 2000 to avoid potential confounding owing to temporal population shifts in cardiovascular risk factors (i.e., smoking, BMI). We also excluded nonwhite sub- jects to improve our internal validity and to make direct comparisons between CCLS and National Health and Nutrition Examination Survey (NHANES) fitness esti- aDepartment of Internal Medicine/Cardiology, University of Texas Southwestern Medical School, Dallas, Texas bThe Cooper Institute, Dal- las, Texas cDepartment of Kinesiology, Health Promotion and Recreation University of North Texas, Denton, Texas dStanford Prevention Research Center, Stanford University, Palo Alto, California. Manuscript received November 23, 2010 revised manuscript received and accepted February 16, 2011. *Corresponding author: Tel: 214-648-1400 fax: 214-648-1450. E-mail address: susan.lakoski@utsouthwestern.edu (S.G. Lakoski). 0002-9149/11/$ – see front matter © 2011 Elsevier Inc. All rights reserved. www.ajconline.org doi:10.1016/j.amjcard.2011.02.338

mates among non-Hispanic whites.13 All subjects pro- vided written informed consent to participate in research. Personal medical history, body composition, laboratory measurements, and assessment of CRF by maximal exercise treadmill tests were performed at the first visit to the Cooper Clinic. Information regarding age, gender, ethnicity, and medical history were obtained by questionnaires. A history of hypertension, current smoking, diabetes, or other pre- existing medical condition was verified by a physician dur- ing the clinic visit. Health status was a categorical value assigned as normal or abnormal, with abnormal defined as a personal history of heart attack, stroke, diabetes, hyperten- sion or cancer, or an abnormal electrocardiogram at rest of during exercise based on ST segment abnormalities, as previously described.14 BMI was calculated from measured weight and height during the clinic visit. BMI was treated as continuous vari- able and categorized as normal weight ( 25 kg/m2), over- weight ( 25 to 30 kg/m2), and obese ( 30 kg/m2). Waist circumference was measured by trained staff and reported in centimeters. Skinfold measurements at 7 sites or underwater weighing measurements were used to estimate percent body fat. Lean body mass was calculated by the following equa- tion: lean body mass (body weight [kilograms] [1 – {percent body fat/100}]). Blood pressure at rest was re- corded using standard auscultatory methods after the patient had been seated for 5 minutes. Systolic and diastolic blood pressures were recorded at the first and fifth Korotkoff sounds, respectively. Fasting venous blood samples were obtained and plasma concentrations of lipids and glucose were determined with automated bioassays in the Cooper Clinic laboratory that meet quality control standards of the Centers for Disease Control and Prevention Lipid Standard- ization Program. Physical activity was assessed by self-reported participa- tion in recreational or leisure-time activities during the pre- vious month. For each activity, number of sessions per week (frequency) and average duration per session were reported. From these data, we converted frequency and duration to minutes of activity per week. Each activity value was then weighted by multiplying minutes of activity by an estimated metabolic equivalent task (MET) value yielding MET min- utes per week. MET values for physical activity were based on average intensity of each activity using the compendium of physical activities developed by Ainsworth et al.15 METs per minute per week groups were created based on Amer- ican College of Sports Medicine guidelines.12 Categories were 0 METs/min/week (no self-reported moderate or vig- orous intensity physical activity), 1 to 449 METs/min/week (not meeting guideline for physical activity), 450 to 749 METs/min/week (meeting guidelines), and 750 METs/ min/week (exceeding guideline for physical activity). An alternative definition of physical activity was also explored, categorizing subjects into 4 groups: 0 no organized phys- ical activity 1 nonrunning activities 2 0 to 10 miles/ week of running 3 11 to 20 miles/week running and 4 20 miles/week of running.16 CRF was determined using a maximal treadmill exercise test and a modified Balke protocol as previously described.8 Treadmill speed was set initially at 88 m/min. The grade was 0% during the first minute, 2% during the second minute, and increased 1% each minute until 25 minutes. After 25 minutes, the grade did not change and speed was increased 5.4 m/min each minute until test termination. Time achieved on a treadmill has previously been shown to be highly correlated with measured maximal oxygen uptake in men and women.17,18 For the present study, CRF was defined (1) as a continuous variable expressed as total time Table 1 Relation between clinical risk factors and quintiles of cardiorespiratory fitness Fitness Quintiles Quintile 1 (n 3,968) Quintile 2 (n 3,995) Quintile 3 (n 4,174) Quintile 4 (n 4,059) Quintile 5 (n 4,133) METs 9.0 9.0–10.2 10.3–11.2 11.3–12.5 12.6 Age (years) 53.2 (10.6) 49.5 (9.5) 46.8 (8.9) 45.2 (8.7) 42.7 (7.9) Men 1,564 (39.4%) 2,174 (54.4%) 2,900 (69.5%) 3,197 (78.7%) 3,624 (87.7%) Body mass index (kg/m2) Women 27.5 5.5 23.9 3.4 22.8 3.0 21.7 2.5 21.0 2.1 Men 32.5 5.7 29.7 4.0 28.1 3.2 26.8 2.9 25.3 2.5 Reports no organized physical activity 1,653 (41.7%) 1,098 (27.5%) 919 (22.0%) 572 (14.1%) 283 (6.9%) Meets guideline for physical activity* 1,834 (46.2%) 2,452 (61.4%) 2,935 (70.3%) 3,246 (80.0%) 3,747 (90.7%) Current smoker 484 (12.8%) 458 (12.1%) 546 (13.7%) 508 (13.2%) 388 (10.0%) Self-reported hypertension 1,085 (29.1%) 761 (20.1%) 616 (15.6%) 475 (12.3%) 298 (7.6%) Self-reported diabetes 180 (4.9%) 76 (2.0%) 51 (1.3%) 25 (0.7%) 15 (0.4%) Systolic blood pressure (mm Hg) 124.8 16.6 121.2 14.9 120.2 14.0 120.1 13.5 119.1 12.2 Diastolic blood pressure (mm Hg) 82.7 10.2 81.8 10.1 81.6 9.7 81.4 9.7 79.8 8.9 Glucose (mg/dl) 101.0 22.9 96.9 15.7 95.8 12.6 95.0 11.2 93.6 9.7 Low-density lipoprotein cholesterol (mg/dl) 120.1 34.0 118.5 33.1 119.1 33.9 118.9 32.0 114.3 30.4 High-density lipoprotein cholesterol (mg/dl) Women 61.9 16.8 66.9 16.4 67.1 15.3 69.3 15.6 71.5 15.2 Men 43.8 11.7 44.4 10.4 46.3 11.3 48.9 11.6 52.8 12.4 * American College of Sports Medicine and American Heart Association guidelines for physical activity.12 Moderate intensity activity 5 times for 30 min/week or 450 METs/min/week. 35 Preventive Cardiology/The Clinical Determinants of Cardiorespiratory Fitness