Determinants of Cardiorespiratory Fitness in Men Aged 42 to 60 Years With and Without Cardiovascular Disease

Determinants of Cardiorespiratory Fitness in Men Aged 42 to 60 Years With and Without Cardiovascular Disease Jari Antero Laukkanen, MD, PhDa,b,f,*, David Laaksonen, MD, PhDd, Timo Antero Lakka, MD, PhDa,c, Kai Savonen, MD, PhDa,e, Rainer Rauramaa, MD, PhDa,e, Timo Mäkikallio, MD, PhDf,g, and Sudhir Kurl, MDb Good cardiorespiratory fitness has been found to protect against cardiovascular diseases and type 2 diabetes. The purpose of this study was to investigate determinants of directly measured cardiorespiratory fitness (maximal oxygen uptake [VO2max]), including age, body composition, prevalent diseases, cardiovascular and pulmonary functions, biochemical factors, physical activity, nutrition, smoking, and alcohol consumption, in a populationbased study of 936 men 42 to 60 years of age. Variables that had the strongest direct associations with VO2max (milliliters per minute) in a linear multivariate step-up regression model were body weight, heart rate at maximal exercise, mean intensity and frequency of conditioning physical activity, intake of carbohydrates, blood hemoglobin, and forced expiratory volume in 1 second. The strongest inverse associations with VO2max were heart rate at rest, age, fasting serum insulin, waist-to-hip ratio, coronary heart disease, and asthma. This model accounted for 67% of the variation of VO2max. In conclusion, mean intensity, frequency, and duration of conditioning physical activity were associated directly with VO2max. However, measurements of the function of pulmonary and cardiovascular systems, carbohydrate intake, and body composition were powerful determinants of cardiorespiratory fitness, especially in older middle-aged men. © 2009 Elsevier Inc. (Am J Cardiol 2009;103:1598 –1604)

Cardiorespiratory fitness has been related to several factors, such as age,1–5 gender,4,5 heredity,6,7 prevalent cardiovascular disease,4,5 use of medications,8 quantity and quality of physical activity,1,5 cigarette smoking,1,9,10 obesity,3 and nutrition.1 Furthermore, maximal oxygen uptake (VO2max) is an accurate measurement of the functional capacity of the cardiovascular system.8 Indeed, small stroke volume, low maximal heart rate, and small arteriovenous oxygen difference at exercise have partly explained lower cardiorespiratory fitness.8,11 However, little information is available on determinants of cardiorespiratory fitness in populationbased samples.12 We therefore studied determinants of directly measured cardiorespiratory fitness, including age, chronic diseases, use of medications, biochemical factors, body weight, and several health habits such as physical activity, cigarette smoking, alcohol consumption, and nutrition, in a population-based sample of middle-aged men, and whether the relative importance of these factors differs with respect to age and health status. a Kuopio Research Institute of Exercise Medicine, bSchool of Public Health and Clinical Nutrition and cInstitute of Biomedicine and Physiology, University of Kuopio, Departments of dMedicine and eClinical Physiology and Nuclear Medicine, Kuopio University Hospital, Kuopio, fLapland Central Hospital, Rovaniemi, and gDivision of Cardiology, Department of Internal Medicine, University of Oulu, Oulu, Finland. Manuscript received November 16, 2008; revised manuscript received and accepted January 31, 2009. This work was supported by grants from the Finnish Academy, the Ministry of Education of Finland, and the town of Kuopio, Finland. *Corresponding author: Fax 358-71-162936. E-mail address: [email protected] (J.A. Laukkanen).

0002-9149/09/$ – see front matter © 2009 Elsevier Inc. doi:10.1016/j.amjcard.2009.01.371

Methods Subjects were participants in the Kuopio Ischaemic Heart Disease Risk Factor Study (KIHD), which was designed to investigate risk factors for cardiovascular disease, carotid atherosclerosis, and related outcomes in a random population-based sample of men. Of the 3,433 men 42 to 60 years of age who resided in the town of Kuopio, Finland, or its surrounding rural communities, 198 were excluded because of death, serious disease, or migration away from the area, and of the remainder, 2,682 (82%) agreed to participate in the study. Baseline examinations were conducted from March 1984 to December 1989. In the first cohort men were 54 years old and in the second cohort men were 42 to 60 years old. Complete data on cardiorespiratory fitness and its determinants were available for 936 men. Data were limited due to assessment of pulmonary function, which was limited to only the second cohort that included men 42 to 60 years old. Those men who underwent exercise testing and assessment of cardiorespiratory fitness and pulmonary function were from the second cohort and that cohort with different age groups was included in the study. Cardiorespiratory fitness was assessed with a maximal, symptom-limited exercise-tolerance test on an electrically braked bicycle ergometer. The testing protocol consisted of a linear increase in workload by 20 W/min (400 L bicycle ergometer, Medical Fitness Equipment, Mearn, The Netherlands). Respiratory gas exchange was measured by the breath-by-breath method, using a MGC 2001 analyzer (Medical Graphics, St. Paul, Minnesota). The MGC 2001 analyzer expressed VO2max as the average of values recorded over 8 seconds. VO2max was defined as the highest www.AJConline.org

Miscellaneous/Cardiorespiratory Fitness and Determinants

value for or the plateau on oxygen uptake. Electrocardiogram was monitored continuously during and 8 minutes after the test. Heart rates at rest and during exercise were recorded. The most common reasons for stopping the exercise test were leg fatigue (574 men), exhaustion (117 men), breathlessness (64 men), and pain in the leg muscles, joints, or back (56 men). The test was discontinued in 86 men because of cardiorespiratory symptoms or abnormalities such as dyspnea (48 men), chest pain (26 men), ischemic electrocardiographic changes (4 men), arrhythmias (3 men), a marked change in systolic or diastolic blood pressure (2 men), and dizziness (3 men). Leisure-time physical activity was assessed using the KIHD 12-month leisure-time physical activity questionnaire.13–15 The checklist included the most common leisuretime physical activities of middle-aged Finnish men, selected based on a previous population study in Finland.13–15 For each activity performed, subjects were asked to record the frequency (number of sessions per month), average duration (hours and minutes per session), and intensity (scored as 0 for recreational activity, 1 for conditioning activity, 2 for brisk conditioning activity, 3 for strenuous exercise). Mean intensity of physical activity was expressed in METs. The 4 categories of intensity of activity (range of possible scores 0 to 3) were assigned their own MET values, revised based on a synthesis of available empiric data.15 A MET is the ratio of metabolic rate during exercise to metabolic rate at rest. One MET corresponds to an energy expenditure of approximately 1 kcal/kg of body weight per hour, or an oxygen uptake of 3.5 ml/kg/min. Physical activity was categorized according to type: (1) conditioning physical activity—walking (mean intensity 4.3 METs, range 3.0 to 7.0), jogging (10.2 METs, 7.0 to 12.5), skiing (9.6 METs, 7.0 to 12.5), bicycling (5.9 METs, 4.0 to 9.0), swimming (5.4 METs, 4.0 to 10.0), rowing (5.4 METs, 3.0 to 10.0), ball games (6.7 METs, 4.9 to 9.0), and gymnastics, dancing, or weight lifting (4.9 METs, 3.0 to 8.0); (2) nonconditioning physical activity— crafts, repairs, or building (2.7 METs, 2.0 to 6.0), yard work, gardening, farming, or snow shoveling (4.3 METs, 3.0 to 7.0), hunting, picking berries, or gathering mushrooms (3.6 METs, 3.0 to 7.0), fishing (2.4 METs, 2.0 to 5.0), and forestry (7.6 METs, 3.0 to 10.0); and (3) walking (3.5 METs, 3.0 to 6.0) or bicycling (5.2 METs, 4.0 to 7.0) to work. Lifelong exposure to smoking (cigarette pack-years) was estimated as the product of the number of years spent smoking and the number of tobacco products smoked daily at time of examination. Number of cigarettes, cigars, and pipefuls of tobacco currently smoked daily and duration of regular smoking in years were recorded using a self-administered questionnaire. Consumption of alcohol in the previous 12 months was assessed with the Nordic Alcohol Consumption Inventory.16 Consumption of foods was assessed when blood was sampled by recording intake over 4 days with a questionnaire, which was checked at the interview.16 History of diseases (coronary heart disease [CHD], cardiac insufficiency, cardiomyopathy, stroke, claudication, asthma, chronic bronchitis, pulmonary tuberculosis, and diabetes mellitus), family history of diseases, and use of

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Table 1 Distributions of maximal oxygen uptake, conditioning physical activity, other determinants, and diseases in men in eastern Finland (n ⫽ 936) VO2max (ml/min) 2,538 ⫾ 687 (465–5,034) VO2max (ml/kg/min) 31.6 ⫾ 8.4 (6.4–58.3) Conditioning physical activity Duration (h/wk) 2.13 ⫾ 2.34 (0–21.74) Frequency (sessions/wk) 2.40 ⫾ 2.34 (0.02–21.12) Mean intensity (METs)* 5.84 ⫾ 1.74 (3.0–12.5) Age (yrs) 51.0 ⫾ 6.6 (42.0–61.1) Height (cm) 173.6 ⫾ 6.1 (156.5–193.7) Weight (kg) 80.9 ⫾ 11.3 (51.7–132.1) Waist-to-hip circumference ratio 0.94 ⫾ 0.06 (0.75–1.51) 6.76 ⫾ 14.80 (0.00–144.00) Cigarette smoking (pack-years)† Heart rate at rest (beats/min) 63 ⫾ 11 (18–109) Heart rate at maximal exercise (beats/min) 161 ⫾ 24 (73–210) Systolic blood pressure (mm Hg) 132 ⫾ 15 (93–203) Hemoglobin (g/dl) 14.7 ⫾ 0.9 (10.3–18.1) Hematocrit 0.43 ⫾ 0.02 (0.33–0.51) Blood leukocytes (1 ⫻ 109/L) 5.71 ⫾ 1.61 (2.8–18.9) Serum insulin (mU/L) 11.2 ⫾ 6.8 (1.0–67.8) Intake of carbohydrate (g/day) 258.9 ⫾ 73.2 (78.6–538.9) FVC (L) 4.52 ⫾ 0.89 (0.70–7.16) FEV1 (L) 3.75 ⫾ 0.80 (0.62–6.62) FEV1% ⫽ (FEV1/FVC) ⫻ 100 83.2 ⫾ 8.52 (42.0–100.0) CHD 20.5% 6.2% Cardiac insufficiency‡ Cardiomyopathy§ 1.5% Left ventricular hypertrophy 1.2% Stroke 1.6% Claudication 3.3% Asthma 3.5% Chronic bronchitis 7.2% Pulmonary tuberculosis 2.6% Diabetes mellitus 4.2% Use of any ␤ blocker 14.4% Values are means ⫾ SDs (ranges) or percentages of patients. * A metabolic unit is the ratio of metabolic rate during physical activity to metabolic rate at rest. One MET corresponds to an energy expenditure of approximately 1 kcal/kg of body weight per hour and an oxygen uptake of 3.5 ml/kg/min. † Pack-years denotes lifelong exposure to smoking, which was estimated as the product of years smoked and the number of tobacco products smoked daily at time of examination. ‡ Defined as a diagnosis of heart failure based on clinical findings and symptoms. § Includes dilated and hypertrophied cardiomyopathies diagnosed based on echocardiographic findings and symptoms.

medicines were recorded using a self-administered questionnaire, which was checked by an interviewer. A physician reinterviewed subjects regarding their medical histories. Prevalent CHD was defined as a history of myocardial infarction or angina pectoris, a positive finding for angina pectoris on effort based on the London School of Hygiene cardiovascular questionnaire, or use of nitroglycerin tablets for chest pain ⱖ1 time/week. A family history of CHD was defined as positive when the father, mother, sister, or brother of a subject had a myocardial infarction, angina pectoris, or CHD. Diabetes mellitus was defined as a fasting blood glucose level ⱖ6.7 mmol/L or a clinical diagnosis of diabetes with dietary, oral, or insulin treatment. Blood pressure at rest was measured by 1 nurse with a random 0 mercury sphygmomanometer (Hawksley, United

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Figure 1. (A) Duration, (B) frequency, and (C) mean intensity of conditioning physical activity and (D) VO2max in a population-based sample of middle-aged men.

Kingdom; from 8:00 to 10:00 A.M.). The measuring protocol included, after a supine rest of 5 minutes, 3 measurements in the supine position, 1 measurement in the standing position, and 2 measurements in the sitting position at 5-minute intervals. The mean of 6 systolic and diastolic pressures was used in these analyses.17 Pulmonary function was measured using a Medikro 101 spirometer. Three measurements were used to assess pulmonary function: (1) forced vital capacity (FVC), (2) forced expiratory volume in 1 second (FEV1), and (3) percentage of FEV1 from FVC. Body mass index was calculated by diving a subject’s weight in kilograms by his height in square meters. Waistto-hip ratio was computed as the ratio of waist circumference to hip circumference. Main lipoprotein fractions were separated from fresh serum samples by ultracentrifugation and precipitation.18 Cholesterol and triglyceride contents of all lipoprotein fractions were measured enzymatically (Boehringer Mannheim, Mannheim, Germany). Blood glucose was derived from

venous blood samples that were taken after a 12-hour fast. Serum insulin was determined with a Novo Biolabin radioimmunoassay kit (Novo Nordisk, Bagsvaerd, Denmark). Plasma fibrinogen was determined from fresh samples with a coagulometer based on clotting of extra fibrin (Amelung KC4, Heinrich Amelung, Lemgo, Germany). Blood hemoglobin was measured photometrically (Gilford Stasar III, Gilford Instrument Laboratories, Oberlin, Ohio) using the cyanmethemoglobin method within a few hours of blood sampling.19 Blood hematocrit was determined using a hematocrit centrifuge. Blood leukocyte count was measured using a Coulter Counter (Coulter Counter Electronics, Luton, United Kingdom). Several possible determinants of cardiorespiratory fitness (VO2max), including history of diseases, family history of diseases, medications, physical activity, cigarette smoking, alcohol consumption, dietary intake of nutrients, biochemical factors, such as serum lipids and lipoproteins, serum insulin, blood glucose, plasma fibrinogen, blood hemoglobin, hematocrit and leukocyte count, blood pressure, body

Miscellaneous/Cardiorespiratory Fitness and Determinants

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Table 2 Strongest determinants of maximal oxygen uptake (n ⫽ 936)* Variable

VO2max (ml/min) Univariate Model

Heart rate at maximal exercise (beats/min) Weight (kg) Heart rate at rest (beats/min) Age (yrs) Intensity of conditioning physical activity (METs)‡ Intake of carbohydrates (g/day) Fasting serum insulin (mU/L) Waist-to-hip circumference ratio CHD (yes vs no) Frequency of conditioning physical activity (session/week) Asthma (yes vs no) Hemoglobin (g/dl) FEV1

Multivariate Model

Crude r Value

p Value

Standardized

In Original Units

p Value

0.624 0.281 ⫺0.071 ⫺0.508 0.345 0.196 ⫺0.118 ⫺0.146 ⫺0.392† 0.031

⬍0.001 ⬍0.001 0.031 ⬍0.001 ⬍0.001 ⬍0.001 0.001 ⬍0.001 ⬍0.001 NS

0.455 0.422 ⫺0.189 ⫺0.166 0.163 0.130 ⫺0.101 ⫺0.084 ⫺0.081 0.069

13.116 25.792 ⫺11.904 ⫺17.275 64.245 1.217 ⫺10.200 ⫺999.6 ⫺137.792 20.257

⬍0.001 ⬍0.001 ⬍0.001 ⬍0.001 ⬍0.001 ⬍0.001 ⬍0.001 ⬍0.001 ⬍0.001 ⬍0.001

⫺0.115† 0.025 0.479

⬍0.001 NS ⬍0.001

⫺0.070 0.051 0.060

⫺249.460 3.838 51.460

⬍0.001 0.009 0.011

* Determinants of VO2max were selected from a step-up multivariate regression model based on their statistical significance (p ⬍0.05). Spearman correlation coefficient. ‡ A metabolic unit is the ratio of metabolic rate during physical activity to metabolic rate at rest. One MET corresponds to an energy expenditure of approximately 1 kcal/kg of body weight per hour and an oxygen uptake of 3.5 ml/kg/min. †

mass index, and waist-to-hip circumference ratio, were entered into a step-up linear multivariate regression model. Separate regression models were done for men 42 to 48 years old (n ⫽ 502) and 54 to 60 years old (n ⫽ 434) and for healthy (n ⫽ 536) and unhealthy men with any disease that could lower VO2max (n ⫽ 400). Determinants of VO2max were selected based on their statistical significance (p ⬍0.05) from these models. Crude correlations of VO2max with the determinants were estimated with Pearson correlation coefficients (Spearman coefficient for dichotomous variables). Regression of determinants on VO2max were estimated and tested for statistical significance with linear multivariate regression analysis. To study how much each variable independently accounted for variation of VO2max, these variables were dropped out 1 by 1 from the multivariate regression model. All statistical analyses were conducted with procedures from SPSS 14.0 for Windows (SPSS, Inc., Chicago, Illinois). Results Means ⫾ SDs (ranges) or prevalences of VO2max and its determinants in the present study population are listed in Table 1. Distributions of duration, frequency, and mean intensity of conditioning physical activity and VO2max in the study population are presented in Figure 1. The strongest determinants of VO2max without and after adjustment for other determinants are listed in Table 2. VO2max had direct crude correlations with heart rate at maximal exercise, body weight, mean intensity of conditioning physical activity, intake of carbohydrates, and FEV1 and inverse crude correlations with heart rate at rest, age, fasting serum insulin, waist-to-hip ratio, prevalent CHD, and prevalent asthma. After adjustment for all factors listed in Table 2, VO2max was directly associated with body weight, heart rate at maximal exercise, mean intensity of conditioning physical

activity, intake of carbohydrates, frequency of conditioning physical activity, blood hemoglobin, and FEV1 and inversely with heart rate at rest, age, fasting serum insulin, waist-to-hip circumference ratio, prevalent CHD, and asthma. Determinants listed in Table 2 altogether accounted for 67% of the variation of VO2max. Body weight accounted independently for 12%, heart rate at maximal exercise for 12%, heart rate at rest for 3.0%, mean intensity of conditioning physical activity for 2.5%, age for 2.2%, intake of carbohydrates for 1.7%, fasting serum insulin for 0.8%, FEV1 for 0.4%, prevalent asthma for 1.9%, prevalent CHD for 0.5%, waist-to-hip ratio for 0.5%, frequency of conditioning physical activity for 0.4%, and blood hemoglobin for 0.2% of the variation of VO2max. VO2max decreased by 53 ml/min (0.61 ml/kg/min) per year of age without adjustment and by 19 ml/min (0.22 ml/kg/min) after adjustment for all determinants listed in Table 2. There was a 136 ml/min (1.96 ml/kg/min) decrease in VO2max per 1-MET decrease of mean intensity of conditioning physical activity without adjustment and a 66 ml/ min (0.86 ml/kg/min) decrease after adjustment for other determinants. Of different types of leisure-time physical activity, duration of jogging (crude r ⫽ 0.205, standardized multivariate regression coefficient beta 0.133, p ⬍0.001), cross-country skiing (r ⫽ 0.256, beta 0.138, p ⬍0.001), leisure-time bicycling (r ⫽ 0.058, beta 0.070, p ⬍0.001), bicycling to work (r ⫽ 0.013, beta 0.064, p ⬍0.01), ball games (r ⫽ 0.191, beta 0.060, p ⬍0.01), and rowing (r ⫽ 0.083, beta 0.056, p ⬍0.01) were associated directly with VO2max after adjustment for the determinants listed in Table 2 excluding other variables of leisure-time physical activity. VO2max also had direct crude correlations with mean intensity of total leisure-time physical activity (r ⫽ 0.347, p ⬍0.001), FVC (r ⫽ 0.412, p ⬍0.001), FEV1 (r ⫽ 0.479, p ⬍0.001), body height (r ⫽ 0.427, p ⬍0.001), and diastolic blood pres-

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Table 3 Strongest determinants of maximal oxygen uptake (milliliters per minute) in age groups Variable

Weight (kg) Heart rate at maximal exercise (beats/min) Heart rate at rest (beats/min) Intensity of conditioning physical activity (METs)† Intake of carbohydrates (g/day) Fasting serum insulin (mU/L) CHD (yes vs no) Duration of conditioning physical activity (h/wk) Waist-to-hip ratio FEV1 Asthma (yes vs no) Blood hemoglobin (g/dl) Cardiomyopathy (yes vs no)‡

42–48 yrs

54–60 yrs

Standardized

In Original Units

p Value

Standardized

In Original Units

p Value

0.563 0.430 ⫺0.243 0.204 0.167 ⫺0.130 ⫺0.092 0.087 ⫺0.083 * ⫺0.062 * *

30.926 14.917 ⫺14.234 73.433 1.343 ⫺12.597 ⫺178.380 28.499 ⫺884.061 * ⫺248.250 * *

⬍0.001 ⬍0.001 ⬍0.001 ⬍0.001 ⬍0.001 ⬍0.001 0.005 0.004 0.020 * 0.037 * *

0.395 0.540 ⫺0.179 0.129 0.102 ⫺0.085 ⫺0.085 * ⫺0.121 0.989 ⫺0.101 0.099 ⫺0.065

21.282 12.786 ⫺9.466 44.745 0.905 ⫺7.083 ⫺108.839 * ⫺1,274.426 80.495 ⫺281.878 6.072 ⫺302.345

⬍0.001 ⬍0.001 ⬍0.001 ⬍0.001 0.001 0.019 0.014 * 0.002 0.005 0.001 0.002 0.036

* These variables did not enter into the step-up multivariate regression model because of their statistical nonsignificance (p ⬍0.05). A metabolic unit is the ratio of metabolic rate during physical activity to metabolic rate at rest. One MET corresponds to an energy expenditure of approximately 1 kcal/kg of body weight per hour and an oxygen uptake of 3.5 ml/kg/min. ‡ Includes dilated and hypertrophied cardiomyopathies diagnosed based on echocardiographic findings and symptoms. †

sure (r ⫽ 0.074, p ⫽ 0.023) and inverse crude correlations with prevalent cardiac insufficiency (r ⫽ ⫺0.206, p ⬍0.001), left ventricular hypertrophy (r ⫽ ⫺0.104, p ⫽ 0.002), stroke (r ⫽ ⫺0.067, p ⫽ 0.005), claudication (r ⫽ ⫺0.203, p ⬍0.001), chronic bronchitis (r ⫽ ⫺0.074, p ⫽ 0.023), and diabetes mellitus (r ⫽ ⫺0.092, p ⫽ 0.005), use of any ␤ blockers (r ⫽ ⫺0.326, p ⬍0.001), cigarette smoking (r ⫽ ⫺0.163, p ⬍0.001), blood leukocyte count (r ⫽ ⫺0.180, p ⬍0.001), and fasting blood glucose (r ⫽ ⫺0.180, p ⬍0.001). However, none of these variables was associated with VO2maxafter adjustment for other determinants. Prevalent pulmonary tuberculosis, use of medications other than ␤ blockers, systolic blood pressure, body height, alcohol consumption, duration of conditioning physical activity, mean intensity, frequency, and duration of nonconditioning physical activity, and alcohol consumption were not associated with VO2max. Table 3 lists determinants of VO2max separately in men 42 to 48 years old and in men 54 to 60 years old after adjustment for other determinants. The association of mean intensity of conditioning physical activity with VO2max was stronger in the younger than in the older men and duration of conditioning physical activity was related to VO2max only in the younger men. Durations of jogging, cross-country skiing, and bicycling to work were associated with VO2max in the 2 age groups, duration of leisure-time bicycling and ball games only in the older men, and duration of rowing only in the younger men. Waist-to-hip ratio had a stronger inverse association with VO2max in the older men. Blood hemoglobin and FEV1 were related directly and prevalent cardiomyopathy inversely to VO2max only in the older men. The association of mean intensity of conditioning physical activity with VO2max was stronger in healthy men (beta 0.218, p ⬍0.001) than in unhealthy men with any disease that could lower VO2max (CHD, cardiac insufficiency, cardiomyopathy, left ventricular hypertrophy, stroke, claudication, asthma, chronic bronchitis, pulmonary tuberculosis, diabetes, and cancer, beta 0.095, p ⫽ 0.001) after adjust-

ment for determinants listed in Table 2. Duration of conditioning physical activity (beta 0.129, p ⬍0.001) waist-to-hip ratio (beta⫽ ⫺0.139, p ⬍0.001), and blood hemoglobin (beta 0.069, p ⫽ 0.016) were associated independently with VO2max only in healthy men, whereas prevalent CHD (beta⫽ ⫺0.117, p ⬍0.001) and asthma (beta⫽ ⫺0.100, p ⬍0.001) were related independently to VO2max in unhealthy men. Discussion Heart rate at maximal exercise, intensity, frequency, and duration of conditioning physical activity, intake of carbohydrates, body weight, and blood hemoglobin were directly related to cardiorespiratory fitness, whereas age, heart rate at rest, prevalent CHD and asthma, central obesity, and fasting serum insulin were inversely associated. These variables accounted for 67% of the variation of VO2max. The present study in middle-aged men from eastern Finland is 1 of the few reported studies concerning determinants of cardiorespiratory fitness in unselected population samples.9,11,20,21 We used directly measured VO2max as a measurement of cardiorespiratory fitness, which is considered the most accurate method for assessing cardiorespiratory capacity. Few previous studies concerning determinants of cardiorespiratory fitness in population samples have applied this method.12,21 Quantitive 12-month leisure-time physical activity history, the reproducibility and validity of which have been shown previously,15 enabled us to investigate associations of different components of leisure-time physical activity with VO2max. In contrast, biological determinants and diseases can be measured more accurately than most health habits, including physical activity, dietary factors, and alcohol consumption, which may underestimate observed associations of health habits as determinants of cardiorespiratory fitness. In our study, intensity and frequency of conditioning physical activity were associated directly with VO2max. Intensity of conditioning physical activity had a stronger as-

Miscellaneous/Cardiorespiratory Fitness and Determinants

sociation with VO2max, especially in the younger men. Physical activity can markedly increase VO2max in sedentary middle-aged subjects.22 The VO2max-improving effect of physical activity depends strongly on its frequency, duration,23 and especially intensity.1,22,23 Unfit subjects may require lower amounts of physical activity than fit subjects to improve their cardiorespiratory fitness. For example, 2 times/week of physical activity improved VO2max in subjects with a low initial VO2max, but ⬎3 times/week was needed in subjects with a high VO2max.23 Furthermore, lower-intensity physical activity appears sufficient to improve cardiorespiratory fitness in older unfit subjects compared to younger and fit subjects.23 In population-based studies, however, the association between physical activity and cardiorespiratory fitness has been relatively weak and physical activity has accounted for only a small part of the variance of VO2max.1,12,20 Heredity may in part explain interindividual differences in cardiorespiratory fitness and its sensitivity to endurance training.6,7 The genetic component of cardiorespiratory fitness has been estimated to be 25% to 40%.6,7,24 We found that heart rate at maximal exercise had a strong direct relation and that blood hemoglobin, which transports oxygen to tissues, had a weak direct relation to VO2max. Furthermore, pulmonary expiratory capacity was related directly to VO2max. VO2max is an indicator of the oxygen transport capacity of the body, limited primarily by cardiac output, pulmonary gas exchange, peripheral circulation, extraction of oxygen in muscles, and migration of oxygen to mitochondria.25 These components are determined by age, genetic factors, diseases, medications, and health habits. Exercise training decreases heart rate and blood pressure at rest and submaximal work load, increases cardiac output and maximal aerobic capacity, muscle capillarization, and mitochondrial oxidative enzyme activity.25 The main reason for the decrease in VO2max with age is lowering of cardiac output at maximal exercise.11,26 The observed mean decrease of VO2max per year of age was 53 ml/min, which is of the same order as shown previously.3,27 Previous studies have shown an average decrease in VO2max of 5% to 15% per decade in men 20 to 75 years old,28 with the smallest decrease in younger groups. However, VO2max is higher in physically active than inactive subjects, whatever the age. Also, cardiorespiratory fitness seems to decrease at a slower rate in physically active subjects.28 Little information is available on the associations of various diseases with VO2max.4 The relative importance of health status as a determinant of VO2max is greater in older subjects because of a higher prevalence of chronic diseases that limit cardiorespiratory capacity in these subjects. Based on our analyses, CHD and asthma are the most important diseases associated with low VO2max in middle-aged men. In older men, prevalent cardiomyopathy and left ventricular hypertrophy also explained some of the variation in VO2max. We found that waist-to-hip ratio was inversely associated with VO2max, especially in older healthy men. Large adipose tissue mass and low fat-free weight have been associated with low VO2max in older populations.3,11 However, in our study total body weight had a direct association with VO2max as expressed in liters per minute, most likely because heavier and more obese men also have a larger fat-free

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mass, including skeletal muscle. Thus, total oxygen uptake may be greater than in lighter men, although their functional capacity and VO2max per kilogram of body weight or fat-free mass may be lower. Cardiorespiratory fitness was associated directly with intake of carbohydrates and inversely with fasting serum insulin. These relations may to some extent reflect the improved use of carbohydrates and insulin sensitivity in men with good cardiorespiratory fitness. The metabolic capacity of the body during endurance exercise is closely related to VO2max.25 Exercise increases the rate of use of all metabolic fuels and muscle oxidative enzyme activities. Dietary carbohydrates are potentially significant substrates to increase endurance performance and may increase VO2max by maintaining the ability to oxidize carbohydrates at high rates.29 Based on this cross-sectional population-based study, frequency, duration, and especially intensity of conditioning physical activity are associated directly with VO2max in middle-aged men. This is in line with our previous findings showing the strong prognostic value of cardiorespiratory fitness.13,30 However, factors other than physical activity, such as age, body composition, prevalent heart disease and obstructive pulmonary disease, cardiovascular and pulmonary functions, and carbohydrate use, appear to account for the variance in VO2max. The relative importance of physical activity was higher in younger and healthy men, whereas other factors were more important in older men. Acknowledgment: We thank the staff of the Kuopio Research Institute of Exercise Medicine, the Research Institute of Public Health, and University of Kuopio, Kuopio, Finland, for data collection in the study. 1. Leon AS, Jacobs DR, DeBacker G, Taylor HL. Relationship of physical characteristics and life habits to treadmill exercise capacity. Am J Epidemiol 1981;113:653– 660. 2. Kohl HW, Blair SN, Paffenbarger RS Jr, Macera CA, Kronenfeld JJ. A mail survey of physical activity habits as related to measured physical fitness. Am J Epidemiol 1988;127:1228 –1239. 3. Jackson AS, Beard EF, Wier LT, Ross RM, Stuteville JE, Blair SN. Changes in aerobic power of men ages 25–70 yr. Med Sci Sports Exerc 1995;27:113–120. 4. Bruce RA, Kusumi F, Hosmer D. Maximal oxygen intake and nomographic assessment of functional aerobic impairment in cardiovascular disease. Am Heart J 1973;85:546 –562. 5. Fletcher GF, Balady GJ, Amsterdam EA, Chaitman B, Eckel R, Fleg J, Froelicher VF, Leon AS, Piña IL, Rodney R, et al. Exercise standards for testing and training: a statement for healthcare professionals from the American Heart Association. Circulation 2001;104:1694 – 1740. 6. Bouchard C, Boulay MR, Simoneau JA, Bouchard C, Boulay MR, Simoneau JA. Heredity and trainability of aerobic and anaerobic performances. An update. Sports Med 1988;5:69 –73. 7. Rankinen T, Perusse L, Rauramaa R, Rivera MA, Wolfarth B, Bouchard C. The human gene map for performance and health-related fitness phenotypes. Med Sci Sports Exerc 2001;33:855– 867. 8. Penny WJ, Mir MA. Cardiorespiratory response to exercise before and after acute beta-adrenoreceptor blockade in nonsmokers and smokers. Int J Cardiol 1986;11:293–304. 9. Blair SN, Kannel WB, Kohl HW, Goodyear N, Wilson PW. Surrogate measures of physical activity and physical fitness. Evidence for sedentary traits of resting tachycardia, obesity, and low vital capacity. Am J Epidemiol 1989;129:1145–1156.

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10. Sandvik L, Erikssen G, Thaulow E. Long term effects of smoking on physical fitness and lung function: a longitudinal study of 1393 middle aged Norwegian men for seven years. BMJ 1995;311:715–718. 11. Ogawa T, Spina RJ, Martin WH III, Kohrt WM, Schechtman KB, Holloszy JO, Ehsani AA. Effects of aging, sex, and physical training on cardiovascular response to exercise. Circulation 1992;86:494 –503. 12. Tager IB, Hollenberg M, Satariano WA. Association between selfreported leisure-time physical activity and measures of cardiorespiratory fitness in an elderly population. Am J Epidemiol 1998;147:921– 931. 13. Lakka TA, Venäläinen JM, Rauramaa R, Salonen R, Tuomilehto J, Salonen JT. Relation of physical activity and cardiorespiratory fitness to the risk of acute myocardial infarction in men. N Eng J Med 1994;330:1549 –1554. 14. Salonen JT, Lakka TA. Intra-person variability of various physical activity assessments in the Kuopio Ischaemic Heart Disease Risk Factor Study. Int J Epidemiol 1992;21:467– 472. 15. Lakka TA, Salonen JT. The physical activity questionnaires of the Ischaemic Heart Disease Study (KIHD). Med Sci Sports Exerc 1997; 29:S46 –S59. 16. Kauhanen J, Julkunen J, Salonen JT. Coping with inner feelings and stress: heavy alcohol use in the context of alexithymia. Behav Med 1992;18:121–126. 17. Laukkanen JA, Kurl S, Rauramaa R, Lakka TA, Venäläinen JM, Salonen JT. Systolic blood pressure response to exercise testing is related to the risk of acute myocardial infarction in middle-aged men. Eur J Cardiovas Prev Rehabil 2006;13:421– 428. 18. Salonen JT, Salonen R, Seppanen K, Rauramaa R, Tuomilehto J. HDL, HDL2, HDL3 subfractions, and the risk of acute myocardial infarction: a prospective population study in eastern Finnish men. Circulation 1991;84:129 –139. 19. Salonen JT, Nyyssonen K, Korpela H, Tuomilehto J, Seppänen R, Salonen R. High stored iron levels are associated with excess risk of

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