Characterizing Differences in Mortality at the Low End of the Fitness Spectrum

Sandra Mandic; Jonathan N. Myers; Ricardo B. Oliveira; Joshua P. Abella; Victor F. Froelicher


Med Sci Sports Exerc. 2009;41(8):1573-1579. 

In This Article


Experimental Design and Approach

The study population consisted of 4384 veterans (200 women) referred for treadmill testing for clinical reasons at the Long Beach and VA Palo Alto Health Care System (Palo Alto, CA) from 1987 to 2006. Detailed clinical history, current medications, risk factors, and cardiovascular disease were recorded prospectively on computerized forms.[5,6] The study was approved by the Stanford Investigational Review Board, and all subjects signed written informed consent.

All subjects had normal exercise test results and no history of cardiovascular disease. We excluded individuals with a history of cardiovascular disease, chronic obstructive pulmonary disease, cancer, chronic renal insufficiency, endocrine, liver, or neurological disease, or abnormal exercise test results (defined as exercise-induced angina and/or ST-segment depression ≥1 mm that was horizontal or downsloping during exercise, in recovery, or both).

The population was divided into quintiles of fitness on the basis of metabolic equivalents (METs) achieved. Cutoff points between the categories were set at approximately every 20th percentile of the population to yield similar sample sizes in each quintile.

Exercise Testing

After providing written informed consent, the subjects underwent symptom-limited treadmill testing according to standardized graded[29] or individualized ramp[15] treadmill protocols. Before testing, exercise capacity was estimated by a questionnaire that allowed individualization of the ramp protocol such that maximal exercise capacity was achieved within 8 to 12 min in most subjects.[16] Subjects were encouraged to exercise until volitional fatigue in the absence of symptoms or other signs of ischemia. The use of handrails during exercise was discouraged. Target heart rate (HR) were not used as predetermined end points. A 12-lead ECG was monitored throughout the test. After exercise, subjects were placed in a supine position. Medications were not changed or stopped before testing. The exercise tests were performed, analyzed, and reported according to a standardized protocol and with the use of a computerized database.[22]

Peak exercise capacity (in METs) was estimated on the basis of the speed and grade of the treadmill.[1] One MET is defined as the energy expended sitting quietly, which is equivalent to an oxygen consumption of approximately 3.5 mL·kg-1 body weight per minute for an average adult. Normal standards for age-predicted exercise capacity were derived from regression equations developed from veterans referred for exercise testing [14] using the equation [18.0 - (0.15 × age)]. The percentage of normal exercise capacity achieved was defined as follows: [(achieved exercise capacity/predicted exercise capacity) × 100]. Age-predicted maximal HR was calculated as 187 - (0.85 × age).[14]

Physical Activity Questionnaire

Physical activity data were collected between 1993 and 2006, depending on the availability of research assistants during that period, and were available in a subgroup of 802 subjects. Physical activity was quantified by a five-page questionnaire modified from the Harvard Alumni studies of Paffenbarger et al.[19] and has been previously described in detail.[17] Examples of physical activities included walking (leisurely or briskly), jogging (slowly or briskly), swimming, gardening, carpentry, weight lifting, and playing golf (carrying clubs or using power cart, etc.). Metabolic costs of lifetime and recent recreational physical activities were computed, and energy expenditure was expressed in kilocalories per week (kcal·wk-1). Subjects were categorized as sedentary (< 1000 kcal·wk-1), moderately active (1000-1999 kcal·wk-1), and active (>2000 kcal·wk-1). Cut points for categories of physical activity were determined on the basis of previously published observational studies showing that an energy expenditure of ≥1000 kcal·wk-1 in physical activity (approximating 30 min or more of moderate-intensity physical activity on ≥5 d·wk-1) is widely recommended to promote health and prevent chronic disease.[7,20,25] An energy expenditure of ≥2000 kcal·wk-1 was considered "active" (approximating 1 h or more of moderate-intensity activity 5 to 7 d·wk-1); this amount has been used as a benchmark for risk reduction.[19]


The Social Security Death Index was used to match all individuals to their records according to name and Social Security number. Vital status was determined as of October 2007. Causes of death were determined independently by two physicians, and any disagreement was resolved by consensus. Cardiovascular death was defined as death due to stroke or cardiac reasons.

Statistical Analysis

NCSS software (Kayesville, UT) was used for all statistical analyses. ANOVA with Bonferroni post hoc multiple comparisons and χ2 tests were used to compare differences between the quintiles of exercise capacity for continuous and discrete variables, respectively. Clinical characteristics of Q1 and Q2 were compared using unpaired t-tests and χ2 tests where appropriate. All-cause and cardiovascular mortalities were used as the end points for Kaplan-Meier survival analysis. Cox proportional hazards analysis was used to determine which variables were independently and significantly associated with time to death in multivariate models. Analyses were adjusted for age in years as a continuous variable. The relative risks of both all-cause and cardiovascular mortalities were calculated for each fitness category. Continuous variables are presented as mean ± SD, whereas categorical variables are expressed as absolute and relative (%) frequencies. P < 0.05 were considered statistically significant.


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