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The association of physical activity with all-cause, cardiovascular, and cancer mortalities among older adults
YPMED-04188; No of Pages 7 Preventive Medicine xxx (2015) xxx–xxx
Contents lists available at ScienceDirect
Preventive Medicine journal homepage: www.elsevier.com/locate/ypmed
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Chen-Yi Wu a,b,c, Hsiao-Yun Hu a,d, Yi-Chang Chou a,d, Nicole Huang d,e, Yiing-Jenq Chou a, Chung-Pin Li f,g,⁎
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Available online xxxx
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Keywords: Physical activity All-cause mortality Cardiovascular mortality Cancer mortality Older adults
Institute of Public Health, Department of Public Health, National Yang Ming University, Taipei, Taiwan Department of Dermatology, Taipei Veterans General Hospital, No. 201, Sec. 2, Shih-Pai Road, Taipei, Taiwan Department of Dermatology, Taipei City Hospital, Heping Fuyou Branch, Taipei, Taiwan d Department of Education and Research, Taipei City Hospital, Taipei, Taiwan e Institute of Hospital and Health Care Administration, National Yang-Ming University, Taipei, Taiwan f Division of Gastroenterology, Department of Medicine, Taipei Veterans General Hospital, Taipei, Taiwan g National Yang-Ming University School of Medicine, Taipei, Taiwan
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The association of physical activity with all-cause, cardiovascular, and cancer mortality among older adults
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Objective. To evaluate the association of physical activity with all-cause, cardiovascular, and cancer mortality among older adults. Methods. A study sample consisting of 77,541 community-dwelling Taipei citizens aged ≥ 65 years was selected based on data obtained from the government-sponsored Annual Geriatric Health Examination Program between 2006 and 2010. Subjects were asked how many times they had physical activity for ≥30 min during the past 6 months. Mortality was determined by matching cohort identifications with national death files. Results. Compared to subjects with no physical activity, those who had 1–2 times of physical activity per week had a decreased risk of all-cause mortality [hazard ratio (HR): 0.77; 95% confidence interval (CI): 0.71–0.85). Subjects with 3–5 times of physical activity per week had a further decreased risk of all-cause mortality (HR: 0.64; 95% CI: 0.58–0.70). An inverse dose–response relationship was observed between physical activity and all-cause, cardiovascular, and cancer mortality. According to stratified analyses, physical activity was associated with a decreased risk of mortality in most subgroups. Conclusions. Physical activity had an inverse association with all-cause, cardiovascular, and cancer mortality among older adults. Furthermore, most elderly people can benefit from an active lifestyle. © 2014 Elsevier Inc. All rights reserved.
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Introduction
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The health benefits of physical activity, including increased longevity or postponed premature mortality, have been supported by evidences from many epidemiological studies (Bellavia et al., 2013; Moore et al., 2012; Nocon et al., 2008; Wannamethee and Shaper, 2001; Wannamethee et al., 2001). Low cardiorespiratory fitness, which is closely related to physical activity, was observed to be responsible for the highest proportion of deaths in a large longitudinal study across age groups (Stofan et al., 1998; Sui et al., 2007; Sui et al., 2013). Although the association between physical activity and mortality has been examined extensively in the past years, most of the evidence has been derived from studies involving a combination of middle-aged and elderly subjects (Arrieta and Russell, 2008; Autenrieth et al., 2011; Bellavia et al., 2013; Moore et al., 2012; Nocon et al., 2008; Oguma
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⁎ Corresponding author at: Division of Gastroenterology, Department of Medicine, Taipei Veterans General Hospital, No. 201, Sec. 2, Shih-Pai Road, Taipei 112, Taiwan. Fax: +886 2 2873 9318. E-mail address: [email protected] (C.-P. Li).
et al., 2002; Wen et al., 2011). Fewer studies have been conducted to focus on only the older population (Balboa-Castillo et al., 2011; Bembom et al., 2009; Knoops et al., 2004; Schooling et al., 2006; Sundquist et al., 2004; Ueshima et al., 2010). Although physical activity may result in favorable physiological changes in all age groups, the association of physical activity and mortality among the elderly remains inconsistent. Furthermore, the magnitude of benefit for postponing premature mortality is unknown. Possible adverse effects of physical activity have been reported (Maron, 2000). The benefit of exercise has been reported to be attenuated in those aged 75 years or older who are extremely active (Sherman et al., 1994). Given the aging populations worldwide, the survival of older adults would be a major concern to caregivers and can also pose a burden to public health. Many studies have been conducted to evaluate the association of physical activity with all-cause mortality. However, the evidence regarding the association between physical activity and cardiovascular disease (CVD) and cancer mortality remains limited. Autenrieth et al. revealed that physical activity has a protective effect on all-cause, CVD, and cancer mortality among participants aged 25–74 years (Autenrieth et al., 2011). However, Ueshima et al. observed that
http://dx.doi.org/10.1016/j.ypmed.2014.12.023 0091-7435/© 2014 Elsevier Inc. All rights reserved.
Please cite this article as: Wu, C.-Y., et al., The association of physical activity with all-cause, cardiovascular, and cancer mortality among older adults, Prev. Med. (2015), http://dx.doi.org/10.1016/j.ypmed.2014.12.023
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C.-Y. Wu et al. / Preventive Medicine xxx (2015) xxx–xxx
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hemoglobin levels were obtained. These measures of health were referred to 136 as the clinical characteristics of the participants. 137
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Outcome variables
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Endpoints of this study included mortality data obtained between May 1, 2006 and December 31, 2010. Vital statistics of the participants were obtained by matching cohort identifications with computerized national death files. Information on the cause of deaths was coded according to 2 versions of the International Classification of Diseases (ICD); the 9th version was used for data from 2006 to 2008 (ICD-9 codes: 001–998) and the 10th version was used for data from 2009 to 2010 (ICD-10 codes: A00–Z99). Deaths attributed to CVD (ICD-9 codes: 390–459; ICD-10 codes: I00–I99) and cancer (ICD-9 codes: 140–239; ICD-10 codes: C00–D49) were coded as cause-specific.
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Methods
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Study population
98 99 100 101 102 103 104 105 106 Q14 107 108 109 110 111 112 113
Data for this study were obtained from the Taipei Geriatric Health Examination Database. A cohort consisting of 77,541 participants aged ≥ 65 years, including 39,365 men and 38,176 women, was evaluated. The participants were enrolled in the annual physical examination program for older adults, which is managed by the Taipei City Government, between May 1, 2006 and December 31, 2010. Participants voluntarily took part in the physical examination program and were encouraged to participate in the program on a yearly basis for a routine physical examination; however, only the results from the initial visit were used for analyses. Demographic informations, including marital status, educational level, smoking history, and alcohol consumption, were collected through self-administered questionnaires. During the medical check-up, measurements of height, body weight, and blood pressure were obtained in addition to a blood sample used for laboratory analyses. Identification data of the participants were encrypted before being analyzed by the researchers. The study was approved by the institutional review board of Taipei City Hospital (IRB No.: TCHIRB-1020417-E).
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Measurement of physical activity
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Physical activity data were collected through self-administered questionnaires. The participants were asked the number of times (0 times/week, 1–2 times/week, and 3–5 times/week) they performed physical activity for ≥30 min during the past 6 months.
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Controlled variables
120 121 122 123 124 125 126 127 128 129 130 131 132 133 134 135
Baseline data, including age, sex, marital status (single, married/cohabiting), educational level (none, 1–6 years, 7–12 years, N 12 years), smoking (frequently, occasionally, none), and alcohol consumption (frequently, occasionally, none), were collected. BMI was calculated as weight in kilograms divided by height in meters squared. The World Health Organization BMI categories were used for categorizing participants who were underweight (15–18.4 kg/m2), normal (18.5–24.9 kg/m2), overweight (25–29.9 kg/m2), and obese (≥ 30 kg/m2). Cognitive impairment was measured by the Short Portable Mental Status Questionnaire (SPMSQ), a widely used 10-item cognitive screening instrument (Pfeiffer, 1975; Wu et al., 2014). The 5-item Brief Symptom Rating Scale was used to screen subjects for possible depression and anxiety (Lung and Lee, 2008; Wu et al., 2014). Height, weight, systolic blood pressure (SBP), and diastolic blood pressure (DBP) were measured. Laboratory data, including fasting blood sugar (FBS), total cholesterol (TC), triglycerides (TG), aspartate transaminase (AST), alanine transaminase (ALT), albumin, creatinine, blood urea nitrogen (BUN), and
Results
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The baseline characteristics of all participants are shown in Table 1. There were 77,541 participants with a mean age of 73.1 (SD = 6.6) years. The 5-year study period consisted of 254,211 person-years of observation with an average follow-up of 3.28 (SD = 1.30) years. Participants with more physical activity were likely to have the following characteristics: younger, male, married/cohabiting, higher educational level, non-smoker, drinker, normal weight, no cognitive impairment, and no depression. The clinical characteristics of the participants for each physical activity level are presented in Table 2. Participants who had more physical activity had a lower SBP, DBP, FBS, TC, TG, and BUN and higher AST, ALT, albumin, and hemoglobin levels. According to the Kaplan–Meier analysis, a reduction in survival probability was associated with a lower level of physical activity (Fig. 1). The 4-year survival rates for participants with 0 times/week, 1–2 times/week, and 3–5 times/week of physical activity were 89.7%, 93.6%, and 95.1%, respectively (log-rank test for equality of survivor functions, P b 0.001). The results of the Cox proportional hazards model for all-cause mortality risk are shown in Table 3. As observed in model 1, participants with higher physical activity levels had a significantly lower risk of mortality compared to those without any physical activity. The association of physical activity on mortality, which attenuated after adjusting for demographics, socioeconomics, lifestyle, and clinical characteristics, was included in models 2 and 3. In the Cox regression analysis of model 3, participants who engaged in physical activity 1–2 times/week had a decreased mortality risk compared to those who had no physical activity (HR: 0.77; 95% confidence interval [CI], 0.71–0.85); participants who had physical activity 3–5 times/week had a further decrease in the mortality risk (HR: 0.64;
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Baseline characteristics were presented as means and standard deviations (SD) for continuous variables. Categorical variables were expressed as relative frequencies and compared with Chi square tests. Trend analysis was used to examine differences in clinical characteristics among physical activity levels. A Cox proportional hazards model was used to calculate the hazard ratios (HRs) for mortality. The proportional hazards assumption was proven to be sufficient after being tested by inspection [log ((−log)event) vs. log of event times]. The time of entry was the initial examination date (between May 1, 2006 and December 31, 2010), and the time of exit was the end of the follow-up period (December 31, 2010) or the date of death, whichever was earlier. The HR for different physical activity levels was calculated using a reference group (i.e., no physical activity group). Possible effect modification was assessed using further stratified analyses to evaluate the mortality risk of subgroups. HRs were also calculated to examine the association between physical activity level and cause-specific death from CVD and cancer, after controlling for demographics, socioeconomic data, lifestyle factors, and health status. All analyses were conducted using the SAS 9.3 (SAS Institute Inc., Cary, NC, USA) and STATA 12.0 (STATA Corp., College Station, TX, USA) statistical software packages.
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Statistical analyses
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and cancer mortality remains unclear (Ueshima et al., 2010). Further studies are needed to examine the possible effects of physical activity 78 on cancer mortality among older adults. 79 Older population has a higher incidence of multiple chronic diseases, 80 which consists of a heterogeneous group of risk factors for mortality. It 81 might be appropriate to evaluate them by using subgroups of diverse 82 clinical characteristics. Furthermore, the clinical characteristics of 83 Q13 older adults with different physical activity levels remain an interesting 84 topic to investigate. 85 In this study, we analyzed a large cohort of 77,541 elderly people 86 who were enrolled in the Annular Geriatric Health Examinations 87 Program using detailed information regarding demographic, lifestyle, 88 body mass index (BMI), cognitive and mood status, blood pressure, 89 and laboratory data. We followed-up on the participants' vital status 90 for 5 years, which totals 254,211 person-years of observation. The 91 objective of this study was to evaluate the association of physical 92 activity with all-cause, CVD, and cancer mortality among older adults. 93 Furthermore, the large sample size of 77,541 older adults allowed us 94 to focus on older people and perform stratified analyses to investigate 95 the associations among each clinical characteristic subgroup.
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74 physical activity among older adults had an inverse association with all75 Q12 cause and CVD mortality, but the association between physical activity
Please cite this article as: Wu, C.-Y., et al., The association of physical activity with all-cause, cardiovascular, and cancer mortality among older adults, Prev. Med. (2015), http://dx.doi.org/10.1016/j.ypmed.2014.12.023
170 171 172 173 174 175 176 177 178 179 180 181 182 183 184 185 186 187 188 189 190 191 192 193 194 195 196 197 198
C.-Y. Wu et al. / Preventive Medicine xxx (2015) xxx–xxx
All participants
Physical activity
Number (%)
Number (%)
Number (%)
77,541 (100) 3842 (5.0) 73.1 ± 6.6
8487 (11.0) 688 (17.9) 74.3 ± 7.2
28,780 (37.1) 1551 (40.4) 73.2 ± 6.6
40,274 (51.9) 1603 (41.7) 72.9 ± 6.4
b0.001
39,365 (50.8) 38,176 (49.2)
3473 (8.8) 5014 (13.1)
13,746 (34.9) 15,034 (39.4)
22,146 (56.3) 18,128 (47.5)
b0.001
20,323 (26.2) 57,218 (73.8)
2983 (14.7) 5504 (9.6)
7650 (37.6) 21,130 (36.9)
9690 (47.7) 30,584 (53.5)
b0.001
6859 (8.9) 21,492 (27.7) 27,664 (35.7) 21,526 (27.8)
1284 (18.7) 2999 (14.0) 2754 (10.0) 1450 (6.7)
2518 (36.7) 7862 (36.6) 10,652 (38.5) 7748 (36.0)
788 (1.0) 6061 (7.8) 70,692 (91.2)
190 (24.1) 900 (14.9) 7397 (10.5)
306 (38.8) 2352 (38.8) 26,122 (37.0)
1804 (2.3) 13,317 (17.2) 62,420 (80.5)
220 (12.2) 1020 (7.7) 7247 (11.6)
2708 (3.5) 44,842 (57.8) 25,896 (33.4) 4095 (5.3)
411 (15.2) 4454 (9.9) 2901 (11.2) 721 (17.6)
74,954 (96.7) 1414 (1.8) 1173 (1.5)
7682 (10.3) 361 (25.5) 444 (37.9)
69,841 (90.1) 5913 (7.6) 1787 (2.3)
7306 (10.5) 870 (14.7) 311 (17.4)
SD: standard deviation; BMI: body mass index.
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95% CI, 0.58–0.70). We observed an inverse dose–response relationship between physical activity and all-cause mortality. In model 3, other factors that resulted in a decreased risk included married/cohabiting, higher educational levels, occasional drinker, higher BMI, and a TC level ≥ 200 mg/dL. Increased mortality risk was associated with older age, male gender, smoker, underweight, cognitive impairment, mild depression, FBS ≥126 mg/dL, ALT ≥43 U/L, creatinine ≥1.4 mg/dL, albumin b3.5 g/dL, and hemoglobin b 12 g/dL.
t2:1 t2:2
Table 2 Clinical characteristic of participants by physical activity level.
t2:3 t2:4
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Variables
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t2:5 t2:6 t2:7 t2:8 t2:9 t2:10 t2:11 t2:12 t2:13 t2:14 t2:15 t2:16 t2:17
Systolic blood pressure (mm Hg) Diastolic blood pressure (mm Hg) Fasting blood sugar (mg/dL) Total cholesterol (mg/dL) Triglyceride (mg/dL) AST (U/L) ALT (U/L) Albumin (g/dL) Creatinine (mg/dL) BUN (mg/dL) Hemoglobin (g/dL)
All participants
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Number (%)
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b0.001
3057 (44.6) 10,631 (49.5) 14,258 (51.5) 12,328 (57.3)
b0.001
292 (37.1) 2809 (46.4) 37,173 (52.6)
b0.001
534 (29.6) 4578 (34.3) 23,668 (37.9)
1050 (58.2) 7,7191 (58.0) 31,505 (50.5)
b0.001
1039 (38.4) 16,367 (36.5) 9717 (37.5) 1657 (40.5)
1258 (46.5) 24,021 (53.6) 13,278 (51.3) 1717 (41.9)
b0.001
27,763 (37.0) 567 (40.1) 450 (38.4)
39,509 (52.7) 486 (34.4) 279 (23.8)
b0.001
25,801 (36.9) 2225 (37.6) 754 (42.2)
36,734 (52.6) 2818 (47.7) 722 (40.4)
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Total Mortality Age (mean ± SD) Sex Male Female Marital status Single Married/cohabiting Education (year) None 1–6 6–12 N12 Smoker Frequently Occasionally None Drinker Frequently Occasionally None BMI (kg/m2) Underweight (15.0–18.4) Normal (18.5–24.9) Overweight (25–29.9) Obesity (≥30) Cognitive impairment None Mild Moderate-to-severe Depression None Mild Moderate-to-severe
3–5 times/week
T
t1:6 t1:7 t1:8 t1:9 t1:10 t1:11 t1:12 t1:13 t1:14 t1:15 t1:16 t1:17 t1:18 t1:19 t1:20 t1:21 t1:22 t1:23 t1:24 t1:25 t1:26 Q2 t1:27 t1:28 t1:29 t1:30 t1:31 t1:32 t1:33 t1:34 t1:35 t1:36 t1:37 t1:38 t1:39 t1:40
1–2 times/week
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Variables
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Table 1 Baseline characteristic of participants and numbers of deaths by physical activity levels.
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Multivariate stratified analyses revealed that light physical activity (1–2 times/week) was associated with a reduced risk of all-cause mortality in most subgroups (Fig. 2). In general, the patients with lower risks–non-smokers, non- or occasional drinkers, those with normal weight, those with no or mild cognitive impairment, those without depression, and those with normal blood sugar–had the greatest reduction in the risk of all-cause mortality. Similar trends were observed for heavy physical activity (3–5 times/week) according
Physical Activity
P
None
1–2 times/week
3–5 times/week
Mean ± SD
Mean ± SD
Mean ± SD
Mean ± SD
135.3 ± 19.7 76.2 ± 11.7 106.0 ± 27.8 199.0 ± 36.7 126.8 ± 85.0 25.1 ± 14.7 23.4 ± 19.7 4.3 ± 0.3 1.0 ± 0.5 17.6 ± 6.4 13.6 ± 1.4
135.9 ± 20.5 76.3 ± 12.2 107.9 ± 31.8 200.5 ± 38.0 137.4 ± 90.8 25.1 ± 14.3 23.1 ± 18.7 4.3 ± 0.3 1.0 ± 0.6 18.1 ± 7.2 13.3 ± 1.5
135.8 ± 19.9 76.3 ± 11.6 106.3 ± 28.5 200.7 ± 38.0 130.7 ± 93.3 25.1 ± 14.7 23.3 ± 19.6 4.3 ± 0.3 1.0 ± 0.5 17.5 ± 6.7 13.6 ± 1.4
134.9 ± 19.4 76.1 ± 11.6 105.4 ± 26.3 197.6 ± 35.3 121.8 ± 76.8 25.2 ± 14.9 23.6 ± 19.9 4.4 ± 0.3 1.0 ± 0.5 17.5 ± 6.1 13.7 ± 1.4
b0.001 0.01 0.002 b0.001 b0.001 b0.001 b0.001 b0.001 0.56 0.04 b0.001
AST: aspartate transaminase; ALT: alanine transaminase; BUN: blood urea nitrogen.
Please cite this article as: Wu, C.-Y., et al., The association of physical activity with all-cause, cardiovascular, and cancer mortality among older adults, Prev. Med. (2015), http://dx.doi.org/10.1016/j.ypmed.2014.12.023
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During the 5 years of follow-up, a total of 3842 deaths were identified, which included 877 and 1438 deaths related to CVD and cancer, respectively. Increased physical activity was inversely associated with all-cause, CVD, and cancer mortality (Table 4).
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Discussion
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In this study, we were able to observe that the risk for all-cause, CVD, and cancer mortality among older adults decreased substantially with physical activity, as indicated by a distinct dose–response relationship and across the majority of subgroups. Healthy adults have been recommended to engage in physical activity to improve and maintain health treatment; according to one study, this recommendation may apply to older adults as well (Haskell et al., 2007). Moreover, an inverse association between mortality and physical activity was observed in participants who had only 1–2 times of physical activity per week. In accordance with previous studies, we have provided evidence that a low frequency of physical activity, albeit less than the recommended amount of physical activity on most days of the week (Nelson et al., 2007), also has health benefits for older adults.
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Table 3 Predictive factors of all-cause mortality. Variables
Model 1
t3:49
0.59 0.45
0.54–−0.65 0.41–0.49
C E R R O C
N
Physical activity (none) 1–2 times/week 3–5 times/week Age (years) Sex (female) Male Marital status (single) Married/cohabiting Education (year) (none) 1–6 6–12 N12 Smoker (none) Occasionally Frequently Drinker (none) Occasionally Frequently BMI (18.5–24.9 kg/m2) Underweight (15.0–18.4 kg/m2) Overweight (25–29.9 kg/m2) Obesity (≥30 kg/m2) Cognitive impairment (none) Mild Moderate-to-severe Depression (none) Mild Moderate-to-severe Systolic blood pressure (normal) ≥140 mm Hg Fasting blood sugar (normal) ≥126 mm Hg Total cholesterol (normal) ≥200 mg/dL Triglyceride (normal) ≥200 mg/dL ALT (normal) ≥43 U/L Creatinine (normal) ≥1.4 mg/dL Albumin (normal) b3.5 g/dL Hemoglobin (normal) b12 g/dL
95% CI
U
t3:5 t3:6 Q3 t3:7 t3:8 t3:9 t3:10 t3:11 t3:12 t3:13 t3:14 t3:15 t3:16 t3:17 t3:18 t3:19 t3:20 t3:21 t3:22 t3:23 t3:24 t3:25 t3:26 t3:27 t3:28 t3:29 t3:30 t3:31 t3:32 t3:33 t3:34 t3:35 t3:36 t3:37 t3:38 t3:39 t3:40 t3:41 t3:42 t3:43 t3:44 t3:45 t3:46 t3:47 t3:48
Model 2
HR
T
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to subgroups (Fig. 2). Moreover, the dose–response relationships were apparent. These observations further confirmed the association between physical activity and an attenuated risk of all-cause mortality in older patients.
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Fig. 1. Overall survival.
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Model 3
HR
95% CI
HR
95% CI
0.75 0.61 1.09
0.69–0.83 0.55–0.66 1.09–1.10
0.77 0.64 1.08
0.71–0.85 0.58–0.70 1.08–1.09
2.11
1.95–2.28
2.01
1.85–2.18
0.88
0.82–0.95
0.91
0.85–0.98
0.96 0.84 0.68
0.86–1.07 0.76–0.94 0.60–0.76
0.96 0.88 0.72
0.86–1.07 0.79–0.98 0.64–0.81
1.49 1.69
1.35–1.65 1.32–2.17
1.52 1.79
1.38–1.69 1.40–2.30
0.70 0.91
0.63–0.77 0.76–1.10
0.75 0.98
0.68–0.83 0.81–1.19
1.75 0.84 0.92
1.56–1.97 0.78–0.90 0.78–1.08
1.69 0.82 0.84
1.50–1.89 0.76–0.89 0.72–0.99
1.76 2.90
1.51–2.06 2.54–3.30
1.67 2.47
1.43–1.95 2.17–2.83
1.19 1.22
1.06–1.33 1.00–1.48
1.18 1.19
1.05–1.32 0.98–1.44
1.07
1.00–1.14
1.38
1.27–1.51
0.84
0.79–0.90
0.98
0.89–1.09
1.29
1.13–1.46
1.81
1.65–1.97
2.40
2.01–2.87
1.96
1.81–2.13
HR: hazard ratio; CI: confidence interval; BMI: body mass index; ALT: alanine transaminase.
Please cite this article as: Wu, C.-Y., et al., The association of physical activity with all-cause, cardiovascular, and cancer mortality among older adults, Prev. Med. (2015), http://dx.doi.org/10.1016/j.ypmed.2014.12.023
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Fig. 2. Subgroup analysis.
t4:1 t4:2
Table 4 Causes of death.
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A false association from reverse causation is almost unavoidable in an observational study because unhealthy people are more likely to be inactive compared to healthy people. The reverse causation can be reduced by restricting the participants to healthy people (Rockhill et al., 2001). Our cohort most likely represented a healthier population because 89% of our participants engaged in at least 1–2 times of physical
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t4:3
Cause
Death (n, %)
Physical activity
(n, %)
HRa
t4:4 t4:5 t4:6 t4:7 t4:8 t4:9 t4:10 t4:11 t4:12
All-cause
3842 (100)
None 1–2 times/week 3–5 times/week None 1–2 times/week 3–5 times/week None 1–2 times/week 3–5 times/week
688 (17.9) 1551 (40.4) 1603 (41.7) 150 (17.1) 350 (39.9) 377 (43.0) 215 (15.0) 568 (39.5) 655 (45.6)
1 0.77 0.64 1 0.82 0.72 1 0.82 0.72
t4:13 t4:14
Cardiovascular
Cancer
877 (22.8)
1438 (37.4)
HR: hazard ratio; CI: confidence interval. a Adjusted with variables similarly to model 3.
95% CI 0.71–0.85 0.58–0.70 0.67–1.00 0.59–0.88 0.70–0.96 0.61–0.84
activity per week. Therefore, we believe that our study population would be suitable for investigating this subject. A lower mortality rate can be associated in people who maintain their physical activity levels, which can be due to various mechanisms, including improved cardiorespiratory fitness (Nelson et al., 2007), reduction in cardiovascular risk factors and events (Nelson et al., 2007), changes in steroid hormones or insulin/insulin-like growth factors, alterations in free radical generation, changes in body composition or weight (Westerlind, 2003), and prevention of falls, osteoporotic fractures, and disability (Gregg et al., 1998). Mortality reductions have been reported to be more pronounced in women in a meta-analysis study, which was not confined to older adults (Samitz et al., 2011). In contrast to a previous study, we did not observe a more beneficial association of physical activity for women in comparison to men. The beneficial effect of physical activity among women was proposed to be associated with changes in hormone levels, estrogen metabolism, and body fat distribution (Lara et al., 2010), which may not be relevant to women aged N65 years. It has been reported that physical activity lowers blood pressure (MacAuley et al., 1996), which is consistent with our observations. We observed that participants with higher physical activity levels had
Please cite this article as: Wu, C.-Y., et al., The association of physical activity with all-cause, cardiovascular, and cancer mortality among older adults, Prev. Med. (2015), http://dx.doi.org/10.1016/j.ypmed.2014.12.023
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This study was supported by the Taiwan Ministry of Education through its “Aim for the Top University Plan”, and by grants from the Department of Health of the Taipei City Government (10301-62-001), Taipei Veterans General Hospital (V103C-201), and the National Science Council Taiwan (NSC 98-2314-B-075-029). This study was based on data from the Taipei City Public Health Database, which was provided by the Department of Health of the Taipei City Government and managed by the Databank for Public Health Analysis. The interpretations and conclusions contained herein do not represent those of the Department of Health of the Taipei City Government or the Databank for Public Health Analysis.
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Physical activity was observed to have an inverse association with all-cause, CVD, and cancer mortality among older adults. Furthermore, older adults can benefit from an active lifestyle; including a minimal amount of physical activity to one's daily routine (i.e., 30 min once or twice per week) may increase longevity. Preventive resources for older adults should include more opportunities for physical activity.
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The authors declare that there are no conflicts of interests.
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Lee et al., 2000 References
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Healthcare professionals should also encourage older adults to be 327 physically active for at least 1–2 times/week. 328
Arrieta, A., Russell, L.B., 2008. Effects of leisure and non-leisure physical activity on mortality in U.S. adults over two decades. Ann. Epidemiol. 18, 889–895. Autenrieth, C.S., Baumert, J., Baumeister, S.E., et al., 2011. Association between domains of physical activity and all-cause, cardiovascular and cancer mortality. Eur. J. Epidemiol. 26, 91–99. Balboa-Castillo, T., Guallar-Castillon, P., Leon-Munoz, L.M., Graciani, A., Lopez-Garcia, E., Rodriguez-Artalejo, F., 2011. Physical activity and mortality related to obesity and functional status in older adults in Spain. Am. J. Prev. Med. 40, 39–46. Bellavia, A., Bottai, M., Wolk, A., Orsini, N., 2013. Physical activity and mortality in a prospective cohort of middle-aged and elderly men — a time perspective. Int. J. Behav. Nutr. Phys. Act. 10, 94. Bembom, O., van der Laan, M., Haight, T., Tager, I., 2009. Leisure-time physical activity and all-cause mortality in an elderly cohort. Epidemiology 20, 424–430. Burchfiel, C.M., Sharp, D.S., Curb, J.D., et al., 1995. Physical activity and incidence of diabetes: the Honolulu Heart Program. Am. J. Epidemiol. 141, 360–368. Gregg, E.W., Cauley, J.A., Seeley, D.G., Ensrud, K.E., Bauer, D.C., 1998. Physical activity and osteoporotic fracture risk in older women. Study of Osteoporotic Fractures Research Group. Ann. Intern. Med. 129, 81–88. Haskell, W.L., Lee, I.M., Pate, R.R., et al., 2007. Physical activity and public health: updated recommendation for adults from the American College of Sports Medicine and the American Heart Association. Med. Sci. Sports Exerc. 39, 1423–1434. Knoops, K.T., de Groot, L.C., Kromhout, D., et al., 2004. Mediterranean diet, lifestyle factors, and 10-year mortality in elderly European men and women: the HALE project. JAMA 292, 1433–1439. Lara, S., Casanova, G., Spritzer, P.M., 2010. Influence of habitual physical activity on body composition, fat distribution and metabolic variables in early postmenopausal women receiving hormonal therapy. Eur. J. Obstet. Gynecol. Reprod. Biol. 150, 52–56. Lee, I.M., Sesso, H.D., Paffenbarger Jr., R.S., 2000. Physical activity and coronary heart disease risk in men: does the duration of exercise episodes predict risk? Circulation 102, 981–986. Lung, F.W., Lee, M.B., 2008. The five-item Brief-Symptom Rating Scale as a suicide ideation screening instrument for psychiatric inpatients and community residents. BMC Psychiatry 8, 53. MacAuley, D., McCrum, E.E., Stott, G., et al., 1996. Physical activity, physical fitness, blood pressure, and fibrinogen in the Northern Ireland health and activity survey. J. Epidemiol. Community Health 50, 258–263. Maron, B.J., 2000. The paradox of exercise. N. Engl. J. Med. 343, 1409–1411. Moore, S.C., Patel, A.V., Matthews, C.E., et al., 2012. Leisure time physical activity of moderate to vigorous intensity and mortality: a large pooled cohort analysis. PLoS Med. 9, e1001335. Nelson, M.E., Rejeski, W.J., Blair, S.N., et al., 2007. Physical activity and public health in older adults: recommendation from the American College of Sports Medicine and the American Heart Association. Circulation 116, 1094–1105. Nocon, M., Hiemann, T., Muller-Riemenschneider, F., Thalau, F., Roll, S., Willich, S.N., 2008. Association of physical activity with all-cause and cardiovascular mortality: a systematic review and meta-analysis. Eur. J. Cardiovasc. Prev. Rehabil. 15, 239–246. Oguma, Y., Sesso, H.D., Paffenbarger Jr., R.S., Lee, I.M., 2002. Physical activity and all cause mortality in women: a review of the evidence. Br. J. Sports Med. 36, 162–172. Pedersen, J.O., Heitmann, B.L., Schnohr, P., Gronbaek, M., 2008. The combined influence of leisure-time physical activity and weekly alcohol intake on fatal ischaemic heart disease and all-cause mortality. Eur. Heart J. 29, 204–212.
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lower SBP and DBP. The benefit of physical activity tends to be more prominent in participants with higher blood pressures, which is also consistent with a previous study that evaluated a combination of middle-aged and elderly participants (Autenrieth et al., 2011). An important role of physical activity for preventing type 2 diabetes mellitus has been reported (Burchfiel et al., 1995). In our study, participants who were more physically active had lower FBS levels, which might suggest a protective role of physical activity on blood sugar levels. In our study, physical activity significantly reduced mortality in participants who had a normal weight and also presented a likely lower mortality among the underweight, overweight, and obese groups. Our findings are in agreement with a previous report, which concluded that older adults with obesity can benefit from an active lifestyle (Balboa-Castillo et al., 2011). Similarly to a previous study involving younger participants, the inverse association between physical activity and all-cause mortality tended to be stronger for occasional drinkers (Pedersen et al., 2008). The patients with higher risks–smokers, frequent drinkers, and obese patients–may have clouded the beneficial effects of physical activity, and may have had a less obvious reduction in the risk of all-cause mortality. Our study had several strengths. The sample size of this study was large enough to allow us to perform stratified analyses to investigate associations among diverse subgroups. A wide-ranging baseline data, including lifestyle and detailed clinical characteristics obtained during the physical examination, which covered multiple domains of health enabled us to evaluate heterogeneity among older adults. The period of follow-up was short, which contributed to fewer errors that may have occurred due to changes in physical activity levels. Our study also contained several limitations. Physical activity levels were determined from questions that were designed to obtain sufficient information for broad ranking. Nevertheless, physical activity levels had a distinct dose–response relationship. Furthermore, simple questions can maximize the reliability and validity of physical activity assessment (Shephard, 2003). Another limitation was that physical activity was not objectively assessed, but self-reported, and was just monitored for 6 months. Therefore, a certain degree of exposure misclassification was inevitable. However, this would be considered non-differential misclassification and make our findings conservative. Thirdly, we did not assess physical activity through a validated physical activity questionnaire, and had no information regarding the intensity of physical activity or the level of physical fitness of the participants. The questionnaires do not assess physical activities that were not conducted during leisure time (i.e., household-related activities), which might contribute to biases in our results and the total amount of physical activity would be underestimated. Fourthly, this study was conducted during an annual physical examination for older adults. The voluntary participants of this study may not represent the general population. However, the observed relative risk may be a reasonable estimate for the general population because the risks were evaluated using internal comparisons. Fifthly, this report does not include time-dependent analyses. The amount of physical activity was recorded at baseline, making it impossible to report changes in exercise patterns over time. Sixthly, we did not consider preexisting diseases or the severity of these diseases in the participants. Baseline measures of clinical characteristics obtained during the initial physical examination were used for performing adjustments in the models.
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Sundquist, K., Qvist, J., Sundquist, J., Johansson, S.E., 2004. Frequent and occasional physical activity in the elderly: a 12-year follow-up study of mortality. Am. J. Prev. Med. 27, 22–27. Ueshima, K., Ishikawa-Takata, K., Yorifuji, T., et al., 2010. Physical activity and mortality risk in the Japanese elderly: a cohort study. Am. J. Prev. Med. 38, 410–418. Wannamethee, S.G., Shaper, A.G., 2001. Physical activity in the prevention of cardiovascular disease: an epidemiological perspective. Sports Med. 31, 101–114. Wannamethee, S.G., Shaper, A.G., Walker, M., 2001. Physical activity and risk of cancer in middle-aged men. Br. J. Cancer 85, 1311–1316. Wen, C.P., Wai, J.P., Tsai, M.K., et al., 2011. Minimum amount of physical activity for reduced mortality and extended life expectancy: a prospective cohort study. Lancet 378, 1244–1253. Westerlind, K.C., 2003. Physical activity and cancer prevention-mechanisms. Med. Sci. Sports Exerc. 35, 1834–1840. Wu, C.Y., Chou, Y.C., Huang, N., Chou, Y.J., Hu, H.Y., Li, C.P., 2014. Cognitive impairment assessed at annual geriatric health examinations predicts mortality among the elderly. Prev. Med.
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Pfeiffer, E., 1975. A short portable mental status questionnaire for the assessment of organic brain deficit in elderly patients. J. Am. Geriatr. Soc. 23, 433–441. Rockhill, B., Willett, W.C., Manson, J.E., et al., 2001. Physical activity and mortality: a prospective study among women. Am. J. Public Health 91, 578–583. Samitz, G., Egger, M., Zwahlen, M., 2011. Domains of physical activity and all-cause mortality: systematic review and dose–response meta-analysis of cohort studies. Int. J. Epidemiol. 40, 1382–1400. Schooling, C.M., Lam, T.H., Li, Z.B., et al., 2006. Obesity, physical activity, and mortality in a prospective Chinese elderly cohort. Arch. Intern. Med. 166, 1498–1504. Shephard, R.J., 2003. Limits to the measurement of habitual physical activity by questionnaires. Br. J. Sports Med. 37, 197–206 (discussion 06). Sherman, S.E., D'Agostino, R.B., Cobb, J.L., Kannel, W.B., 1994. Does exercise reduce mortality rates in the elderly? Experience from the Framingham Heart Study. Am. Heart J. 128, 965–972. Stofan, J.R., DiPietro, L., Davis, D., Kohl 3rd, H.W., Blair, S.N., 1998. Physical activity patterns associated with cardiorespiratory fitness and reduced mortality: the Aerobics Center Longitudinal Study. Am. J. Public Health 88, 1807–1813. Sui, X., LaMonte, M.J., Laditka, J.N., et al., 2007. Cardiorespiratory fitness and adiposity as mortality predictors in older adults. JAMA 298, 2507–2516. Sui, X., Li, H., Zhang, J., Chen, L., Zhu, L., Blair, S.N., 2013. Percentage of deaths attributable to poor cardiovascular health lifestyle factors: findings from the Aerobics Center Longitudinal Study. Epidemiol. Res. Int. 2013.
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Preventive Medicine journal homepage: www.elsevier.com/locate/ypmed
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Chen-Yi Wu a,b,c, Hsiao-Yun Hu a,d, Yi-Chang Chou a,d, Nicole Huang d,e, Yiing-Jenq Chou a, Chung-Pin Li f,g,⁎
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Keywords: Physical activity All-cause mortality Cardiovascular mortality Cancer mortality Older adults
Institute of Public Health, Department of Public Health, National Yang Ming University, Taipei, Taiwan Department of Dermatology, Taipei Veterans General Hospital, No. 201, Sec. 2, Shih-Pai Road, Taipei, Taiwan Department of Dermatology, Taipei City Hospital, Heping Fuyou Branch, Taipei, Taiwan d Department of Education and Research, Taipei City Hospital, Taipei, Taiwan e Institute of Hospital and Health Care Administration, National Yang-Ming University, Taipei, Taiwan f Division of Gastroenterology, Department of Medicine, Taipei Veterans General Hospital, Taipei, Taiwan g National Yang-Ming University School of Medicine, Taipei, Taiwan
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The association of physical activity with all-cause, cardiovascular, and cancer mortality among older adults
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Objective. To evaluate the association of physical activity with all-cause, cardiovascular, and cancer mortality among older adults. Methods. A study sample consisting of 77,541 community-dwelling Taipei citizens aged ≥ 65 years was selected based on data obtained from the government-sponsored Annual Geriatric Health Examination Program between 2006 and 2010. Subjects were asked how many times they had physical activity for ≥30 min during the past 6 months. Mortality was determined by matching cohort identifications with national death files. Results. Compared to subjects with no physical activity, those who had 1–2 times of physical activity per week had a decreased risk of all-cause mortality [hazard ratio (HR): 0.77; 95% confidence interval (CI): 0.71–0.85). Subjects with 3–5 times of physical activity per week had a further decreased risk of all-cause mortality (HR: 0.64; 95% CI: 0.58–0.70). An inverse dose–response relationship was observed between physical activity and all-cause, cardiovascular, and cancer mortality. According to stratified analyses, physical activity was associated with a decreased risk of mortality in most subgroups. Conclusions. Physical activity had an inverse association with all-cause, cardiovascular, and cancer mortality among older adults. Furthermore, most elderly people can benefit from an active lifestyle. © 2014 Elsevier Inc. All rights reserved.
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Introduction
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The health benefits of physical activity, including increased longevity or postponed premature mortality, have been supported by evidences from many epidemiological studies (Bellavia et al., 2013; Moore et al., 2012; Nocon et al., 2008; Wannamethee and Shaper, 2001; Wannamethee et al., 2001). Low cardiorespiratory fitness, which is closely related to physical activity, was observed to be responsible for the highest proportion of deaths in a large longitudinal study across age groups (Stofan et al., 1998; Sui et al., 2007; Sui et al., 2013). Although the association between physical activity and mortality has been examined extensively in the past years, most of the evidence has been derived from studies involving a combination of middle-aged and elderly subjects (Arrieta and Russell, 2008; Autenrieth et al., 2011; Bellavia et al., 2013; Moore et al., 2012; Nocon et al., 2008; Oguma
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⁎ Corresponding author at: Division of Gastroenterology, Department of Medicine, Taipei Veterans General Hospital, No. 201, Sec. 2, Shih-Pai Road, Taipei 112, Taiwan. Fax: +886 2 2873 9318. E-mail address: [email protected] (C.-P. Li).
et al., 2002; Wen et al., 2011). Fewer studies have been conducted to focus on only the older population (Balboa-Castillo et al., 2011; Bembom et al., 2009; Knoops et al., 2004; Schooling et al., 2006; Sundquist et al., 2004; Ueshima et al., 2010). Although physical activity may result in favorable physiological changes in all age groups, the association of physical activity and mortality among the elderly remains inconsistent. Furthermore, the magnitude of benefit for postponing premature mortality is unknown. Possible adverse effects of physical activity have been reported (Maron, 2000). The benefit of exercise has been reported to be attenuated in those aged 75 years or older who are extremely active (Sherman et al., 1994). Given the aging populations worldwide, the survival of older adults would be a major concern to caregivers and can also pose a burden to public health. Many studies have been conducted to evaluate the association of physical activity with all-cause mortality. However, the evidence regarding the association between physical activity and cardiovascular disease (CVD) and cancer mortality remains limited. Autenrieth et al. revealed that physical activity has a protective effect on all-cause, CVD, and cancer mortality among participants aged 25–74 years (Autenrieth et al., 2011). However, Ueshima et al. observed that
http://dx.doi.org/10.1016/j.ypmed.2014.12.023 0091-7435/© 2014 Elsevier Inc. All rights reserved.
Please cite this article as: Wu, C.-Y., et al., The association of physical activity with all-cause, cardiovascular, and cancer mortality among older adults, Prev. Med. (2015), http://dx.doi.org/10.1016/j.ypmed.2014.12.023
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hemoglobin levels were obtained. These measures of health were referred to 136 as the clinical characteristics of the participants. 137
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Endpoints of this study included mortality data obtained between May 1, 2006 and December 31, 2010. Vital statistics of the participants were obtained by matching cohort identifications with computerized national death files. Information on the cause of deaths was coded according to 2 versions of the International Classification of Diseases (ICD); the 9th version was used for data from 2006 to 2008 (ICD-9 codes: 001–998) and the 10th version was used for data from 2009 to 2010 (ICD-10 codes: A00–Z99). Deaths attributed to CVD (ICD-9 codes: 390–459; ICD-10 codes: I00–I99) and cancer (ICD-9 codes: 140–239; ICD-10 codes: C00–D49) were coded as cause-specific.
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Methods
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Study population
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Data for this study were obtained from the Taipei Geriatric Health Examination Database. A cohort consisting of 77,541 participants aged ≥ 65 years, including 39,365 men and 38,176 women, was evaluated. The participants were enrolled in the annual physical examination program for older adults, which is managed by the Taipei City Government, between May 1, 2006 and December 31, 2010. Participants voluntarily took part in the physical examination program and were encouraged to participate in the program on a yearly basis for a routine physical examination; however, only the results from the initial visit were used for analyses. Demographic informations, including marital status, educational level, smoking history, and alcohol consumption, were collected through self-administered questionnaires. During the medical check-up, measurements of height, body weight, and blood pressure were obtained in addition to a blood sample used for laboratory analyses. Identification data of the participants were encrypted before being analyzed by the researchers. The study was approved by the institutional review board of Taipei City Hospital (IRB No.: TCHIRB-1020417-E).
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Physical activity data were collected through self-administered questionnaires. The participants were asked the number of times (0 times/week, 1–2 times/week, and 3–5 times/week) they performed physical activity for ≥30 min during the past 6 months.
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Baseline data, including age, sex, marital status (single, married/cohabiting), educational level (none, 1–6 years, 7–12 years, N 12 years), smoking (frequently, occasionally, none), and alcohol consumption (frequently, occasionally, none), were collected. BMI was calculated as weight in kilograms divided by height in meters squared. The World Health Organization BMI categories were used for categorizing participants who were underweight (15–18.4 kg/m2), normal (18.5–24.9 kg/m2), overweight (25–29.9 kg/m2), and obese (≥ 30 kg/m2). Cognitive impairment was measured by the Short Portable Mental Status Questionnaire (SPMSQ), a widely used 10-item cognitive screening instrument (Pfeiffer, 1975; Wu et al., 2014). The 5-item Brief Symptom Rating Scale was used to screen subjects for possible depression and anxiety (Lung and Lee, 2008; Wu et al., 2014). Height, weight, systolic blood pressure (SBP), and diastolic blood pressure (DBP) were measured. Laboratory data, including fasting blood sugar (FBS), total cholesterol (TC), triglycerides (TG), aspartate transaminase (AST), alanine transaminase (ALT), albumin, creatinine, blood urea nitrogen (BUN), and
Results
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The baseline characteristics of all participants are shown in Table 1. There were 77,541 participants with a mean age of 73.1 (SD = 6.6) years. The 5-year study period consisted of 254,211 person-years of observation with an average follow-up of 3.28 (SD = 1.30) years. Participants with more physical activity were likely to have the following characteristics: younger, male, married/cohabiting, higher educational level, non-smoker, drinker, normal weight, no cognitive impairment, and no depression. The clinical characteristics of the participants for each physical activity level are presented in Table 2. Participants who had more physical activity had a lower SBP, DBP, FBS, TC, TG, and BUN and higher AST, ALT, albumin, and hemoglobin levels. According to the Kaplan–Meier analysis, a reduction in survival probability was associated with a lower level of physical activity (Fig. 1). The 4-year survival rates for participants with 0 times/week, 1–2 times/week, and 3–5 times/week of physical activity were 89.7%, 93.6%, and 95.1%, respectively (log-rank test for equality of survivor functions, P b 0.001). The results of the Cox proportional hazards model for all-cause mortality risk are shown in Table 3. As observed in model 1, participants with higher physical activity levels had a significantly lower risk of mortality compared to those without any physical activity. The association of physical activity on mortality, which attenuated after adjusting for demographics, socioeconomics, lifestyle, and clinical characteristics, was included in models 2 and 3. In the Cox regression analysis of model 3, participants who engaged in physical activity 1–2 times/week had a decreased mortality risk compared to those who had no physical activity (HR: 0.77; 95% confidence interval [CI], 0.71–0.85); participants who had physical activity 3–5 times/week had a further decrease in the mortality risk (HR: 0.64;
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Baseline characteristics were presented as means and standard deviations (SD) for continuous variables. Categorical variables were expressed as relative frequencies and compared with Chi square tests. Trend analysis was used to examine differences in clinical characteristics among physical activity levels. A Cox proportional hazards model was used to calculate the hazard ratios (HRs) for mortality. The proportional hazards assumption was proven to be sufficient after being tested by inspection [log ((−log)event) vs. log of event times]. The time of entry was the initial examination date (between May 1, 2006 and December 31, 2010), and the time of exit was the end of the follow-up period (December 31, 2010) or the date of death, whichever was earlier. The HR for different physical activity levels was calculated using a reference group (i.e., no physical activity group). Possible effect modification was assessed using further stratified analyses to evaluate the mortality risk of subgroups. HRs were also calculated to examine the association between physical activity level and cause-specific death from CVD and cancer, after controlling for demographics, socioeconomic data, lifestyle factors, and health status. All analyses were conducted using the SAS 9.3 (SAS Institute Inc., Cary, NC, USA) and STATA 12.0 (STATA Corp., College Station, TX, USA) statistical software packages.
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and cancer mortality remains unclear (Ueshima et al., 2010). Further studies are needed to examine the possible effects of physical activity 78 on cancer mortality among older adults. 79 Older population has a higher incidence of multiple chronic diseases, 80 which consists of a heterogeneous group of risk factors for mortality. It 81 might be appropriate to evaluate them by using subgroups of diverse 82 clinical characteristics. Furthermore, the clinical characteristics of 83 Q13 older adults with different physical activity levels remain an interesting 84 topic to investigate. 85 In this study, we analyzed a large cohort of 77,541 elderly people 86 who were enrolled in the Annular Geriatric Health Examinations 87 Program using detailed information regarding demographic, lifestyle, 88 body mass index (BMI), cognitive and mood status, blood pressure, 89 and laboratory data. We followed-up on the participants' vital status 90 for 5 years, which totals 254,211 person-years of observation. The 91 objective of this study was to evaluate the association of physical 92 activity with all-cause, CVD, and cancer mortality among older adults. 93 Furthermore, the large sample size of 77,541 older adults allowed us 94 to focus on older people and perform stratified analyses to investigate 95 the associations among each clinical characteristic subgroup.
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Please cite this article as: Wu, C.-Y., et al., The association of physical activity with all-cause, cardiovascular, and cancer mortality among older adults, Prev. Med. (2015), http://dx.doi.org/10.1016/j.ypmed.2014.12.023
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Physical activity
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Number (%)
Number (%)
77,541 (100) 3842 (5.0) 73.1 ± 6.6
8487 (11.0) 688 (17.9) 74.3 ± 7.2
28,780 (37.1) 1551 (40.4) 73.2 ± 6.6
40,274 (51.9) 1603 (41.7) 72.9 ± 6.4
b0.001
39,365 (50.8) 38,176 (49.2)
3473 (8.8) 5014 (13.1)
13,746 (34.9) 15,034 (39.4)
22,146 (56.3) 18,128 (47.5)
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20,323 (26.2) 57,218 (73.8)
2983 (14.7) 5504 (9.6)
7650 (37.6) 21,130 (36.9)
9690 (47.7) 30,584 (53.5)
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6859 (8.9) 21,492 (27.7) 27,664 (35.7) 21,526 (27.8)
1284 (18.7) 2999 (14.0) 2754 (10.0) 1450 (6.7)
2518 (36.7) 7862 (36.6) 10,652 (38.5) 7748 (36.0)
788 (1.0) 6061 (7.8) 70,692 (91.2)
190 (24.1) 900 (14.9) 7397 (10.5)
306 (38.8) 2352 (38.8) 26,122 (37.0)
1804 (2.3) 13,317 (17.2) 62,420 (80.5)
220 (12.2) 1020 (7.7) 7247 (11.6)
2708 (3.5) 44,842 (57.8) 25,896 (33.4) 4095 (5.3)
411 (15.2) 4454 (9.9) 2901 (11.2) 721 (17.6)
74,954 (96.7) 1414 (1.8) 1173 (1.5)
7682 (10.3) 361 (25.5) 444 (37.9)
69,841 (90.1) 5913 (7.6) 1787 (2.3)
7306 (10.5) 870 (14.7) 311 (17.4)
SD: standard deviation; BMI: body mass index.
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95% CI, 0.58–0.70). We observed an inverse dose–response relationship between physical activity and all-cause mortality. In model 3, other factors that resulted in a decreased risk included married/cohabiting, higher educational levels, occasional drinker, higher BMI, and a TC level ≥ 200 mg/dL. Increased mortality risk was associated with older age, male gender, smoker, underweight, cognitive impairment, mild depression, FBS ≥126 mg/dL, ALT ≥43 U/L, creatinine ≥1.4 mg/dL, albumin b3.5 g/dL, and hemoglobin b 12 g/dL.
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Table 2 Clinical characteristic of participants by physical activity level.
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t1:41
t2:5 t2:6 t2:7 t2:8 t2:9 t2:10 t2:11 t2:12 t2:13 t2:14 t2:15 t2:16 t2:17
Systolic blood pressure (mm Hg) Diastolic blood pressure (mm Hg) Fasting blood sugar (mg/dL) Total cholesterol (mg/dL) Triglyceride (mg/dL) AST (U/L) ALT (U/L) Albumin (g/dL) Creatinine (mg/dL) BUN (mg/dL) Hemoglobin (g/dL)
All participants
F
Number (%)
E
b0.001
3057 (44.6) 10,631 (49.5) 14,258 (51.5) 12,328 (57.3)
b0.001
292 (37.1) 2809 (46.4) 37,173 (52.6)
b0.001
534 (29.6) 4578 (34.3) 23,668 (37.9)
1050 (58.2) 7,7191 (58.0) 31,505 (50.5)
b0.001
1039 (38.4) 16,367 (36.5) 9717 (37.5) 1657 (40.5)
1258 (46.5) 24,021 (53.6) 13,278 (51.3) 1717 (41.9)
b0.001
27,763 (37.0) 567 (40.1) 450 (38.4)
39,509 (52.7) 486 (34.4) 279 (23.8)
b0.001
25,801 (36.9) 2225 (37.6) 754 (42.2)
36,734 (52.6) 2818 (47.7) 722 (40.4)
b0.001
O
Total Mortality Age (mean ± SD) Sex Male Female Marital status Single Married/cohabiting Education (year) None 1–6 6–12 N12 Smoker Frequently Occasionally None Drinker Frequently Occasionally None BMI (kg/m2) Underweight (15.0–18.4) Normal (18.5–24.9) Overweight (25–29.9) Obesity (≥30) Cognitive impairment None Mild Moderate-to-severe Depression None Mild Moderate-to-severe
3–5 times/week
T
t1:6 t1:7 t1:8 t1:9 t1:10 t1:11 t1:12 t1:13 t1:14 t1:15 t1:16 t1:17 t1:18 t1:19 t1:20 t1:21 t1:22 t1:23 t1:24 t1:25 t1:26 Q2 t1:27 t1:28 t1:29 t1:30 t1:31 t1:32 t1:33 t1:34 t1:35 t1:36 t1:37 t1:38 t1:39 t1:40
1–2 times/week
C
t1:5
P
None
R O
Variables
t1:4
P
t1:3
Table 1 Baseline characteristic of participants and numbers of deaths by physical activity levels.
D
t1:1 t1:2 Q1
3
Multivariate stratified analyses revealed that light physical activity (1–2 times/week) was associated with a reduced risk of all-cause mortality in most subgroups (Fig. 2). In general, the patients with lower risks–non-smokers, non- or occasional drinkers, those with normal weight, those with no or mild cognitive impairment, those without depression, and those with normal blood sugar–had the greatest reduction in the risk of all-cause mortality. Similar trends were observed for heavy physical activity (3–5 times/week) according
Physical Activity
P
None
1–2 times/week
3–5 times/week
Mean ± SD
Mean ± SD
Mean ± SD
Mean ± SD
135.3 ± 19.7 76.2 ± 11.7 106.0 ± 27.8 199.0 ± 36.7 126.8 ± 85.0 25.1 ± 14.7 23.4 ± 19.7 4.3 ± 0.3 1.0 ± 0.5 17.6 ± 6.4 13.6 ± 1.4
135.9 ± 20.5 76.3 ± 12.2 107.9 ± 31.8 200.5 ± 38.0 137.4 ± 90.8 25.1 ± 14.3 23.1 ± 18.7 4.3 ± 0.3 1.0 ± 0.6 18.1 ± 7.2 13.3 ± 1.5
135.8 ± 19.9 76.3 ± 11.6 106.3 ± 28.5 200.7 ± 38.0 130.7 ± 93.3 25.1 ± 14.7 23.3 ± 19.6 4.3 ± 0.3 1.0 ± 0.5 17.5 ± 6.7 13.6 ± 1.4
134.9 ± 19.4 76.1 ± 11.6 105.4 ± 26.3 197.6 ± 35.3 121.8 ± 76.8 25.2 ± 14.9 23.6 ± 19.9 4.4 ± 0.3 1.0 ± 0.5 17.5 ± 6.1 13.7 ± 1.4
b0.001 0.01 0.002 b0.001 b0.001 b0.001 b0.001 b0.001 0.56 0.04 b0.001
AST: aspartate transaminase; ALT: alanine transaminase; BUN: blood urea nitrogen.
Please cite this article as: Wu, C.-Y., et al., The association of physical activity with all-cause, cardiovascular, and cancer mortality among older adults, Prev. Med. (2015), http://dx.doi.org/10.1016/j.ypmed.2014.12.023
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C.-Y. Wu et al. / Preventive Medicine xxx (2015) xxx–xxx
During the 5 years of follow-up, a total of 3842 deaths were identified, which included 877 and 1438 deaths related to CVD and cancer, respectively. Increased physical activity was inversely associated with all-cause, CVD, and cancer mortality (Table 4).
219 220
Discussion
223
In this study, we were able to observe that the risk for all-cause, CVD, and cancer mortality among older adults decreased substantially with physical activity, as indicated by a distinct dose–response relationship and across the majority of subgroups. Healthy adults have been recommended to engage in physical activity to improve and maintain health treatment; according to one study, this recommendation may apply to older adults as well (Haskell et al., 2007). Moreover, an inverse association between mortality and physical activity was observed in participants who had only 1–2 times of physical activity per week. In accordance with previous studies, we have provided evidence that a low frequency of physical activity, albeit less than the recommended amount of physical activity on most days of the week (Nelson et al., 2007), also has health benefits for older adults.
224 225
Table 3 Predictive factors of all-cause mortality. Variables
Model 1
t3:49
0.59 0.45
0.54–−0.65 0.41–0.49
C E R R O C
N
Physical activity (none) 1–2 times/week 3–5 times/week Age (years) Sex (female) Male Marital status (single) Married/cohabiting Education (year) (none) 1–6 6–12 N12 Smoker (none) Occasionally Frequently Drinker (none) Occasionally Frequently BMI (18.5–24.9 kg/m2) Underweight (15.0–18.4 kg/m2) Overweight (25–29.9 kg/m2) Obesity (≥30 kg/m2) Cognitive impairment (none) Mild Moderate-to-severe Depression (none) Mild Moderate-to-severe Systolic blood pressure (normal) ≥140 mm Hg Fasting blood sugar (normal) ≥126 mm Hg Total cholesterol (normal) ≥200 mg/dL Triglyceride (normal) ≥200 mg/dL ALT (normal) ≥43 U/L Creatinine (normal) ≥1.4 mg/dL Albumin (normal) b3.5 g/dL Hemoglobin (normal) b12 g/dL
95% CI
U
t3:5 t3:6 Q3 t3:7 t3:8 t3:9 t3:10 t3:11 t3:12 t3:13 t3:14 t3:15 t3:16 t3:17 t3:18 t3:19 t3:20 t3:21 t3:22 t3:23 t3:24 t3:25 t3:26 t3:27 t3:28 t3:29 t3:30 t3:31 t3:32 t3:33 t3:34 t3:35 t3:36 t3:37 t3:38 t3:39 t3:40 t3:41 t3:42 t3:43 t3:44 t3:45 t3:46 t3:47 t3:48
Model 2
HR
T
t3:4
D
t3:3
R O
t3:1 t3:2
P
218
to subgroups (Fig. 2). Moreover, the dose–response relationships were apparent. These observations further confirmed the association between physical activity and an attenuated risk of all-cause mortality in older patients.
216 217
E
215
O
F
Fig. 1. Overall survival.
4
Model 3
HR
95% CI
HR
95% CI
0.75 0.61 1.09
0.69–0.83 0.55–0.66 1.09–1.10
0.77 0.64 1.08
0.71–0.85 0.58–0.70 1.08–1.09
2.11
1.95–2.28
2.01
1.85–2.18
0.88
0.82–0.95
0.91
0.85–0.98
0.96 0.84 0.68
0.86–1.07 0.76–0.94 0.60–0.76
0.96 0.88 0.72
0.86–1.07 0.79–0.98 0.64–0.81
1.49 1.69
1.35–1.65 1.32–2.17
1.52 1.79
1.38–1.69 1.40–2.30
0.70 0.91
0.63–0.77 0.76–1.10
0.75 0.98
0.68–0.83 0.81–1.19
1.75 0.84 0.92
1.56–1.97 0.78–0.90 0.78–1.08
1.69 0.82 0.84
1.50–1.89 0.76–0.89 0.72–0.99
1.76 2.90
1.51–2.06 2.54–3.30
1.67 2.47
1.43–1.95 2.17–2.83
1.19 1.22
1.06–1.33 1.00–1.48
1.18 1.19
1.05–1.32 0.98–1.44
1.07
1.00–1.14
1.38
1.27–1.51
0.84
0.79–0.90
0.98
0.89–1.09
1.29
1.13–1.46
1.81
1.65–1.97
2.40
2.01–2.87
1.96
1.81–2.13
HR: hazard ratio; CI: confidence interval; BMI: body mass index; ALT: alanine transaminase.
Please cite this article as: Wu, C.-Y., et al., The association of physical activity with all-cause, cardiovascular, and cancer mortality among older adults, Prev. Med. (2015), http://dx.doi.org/10.1016/j.ypmed.2014.12.023
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226 227 228 229 230 231 232 233 234 235 236
5
R
R
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C
T
E
D
P
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O
F
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Fig. 2. Subgroup analysis.
t4:1 t4:2
Table 4 Causes of death.
240 241
U
242
A false association from reverse causation is almost unavoidable in an observational study because unhealthy people are more likely to be inactive compared to healthy people. The reverse causation can be reduced by restricting the participants to healthy people (Rockhill et al., 2001). Our cohort most likely represented a healthier population because 89% of our participants engaged in at least 1–2 times of physical
238 239
t4:3
Cause
Death (n, %)
Physical activity
(n, %)
HRa
t4:4 t4:5 t4:6 t4:7 t4:8 t4:9 t4:10 t4:11 t4:12
All-cause
3842 (100)
None 1–2 times/week 3–5 times/week None 1–2 times/week 3–5 times/week None 1–2 times/week 3–5 times/week
688 (17.9) 1551 (40.4) 1603 (41.7) 150 (17.1) 350 (39.9) 377 (43.0) 215 (15.0) 568 (39.5) 655 (45.6)
1 0.77 0.64 1 0.82 0.72 1 0.82 0.72
t4:13 t4:14
Cardiovascular
Cancer
877 (22.8)
1438 (37.4)
HR: hazard ratio; CI: confidence interval. a Adjusted with variables similarly to model 3.
95% CI 0.71–0.85 0.58–0.70 0.67–1.00 0.59–0.88 0.70–0.96 0.61–0.84
activity per week. Therefore, we believe that our study population would be suitable for investigating this subject. A lower mortality rate can be associated in people who maintain their physical activity levels, which can be due to various mechanisms, including improved cardiorespiratory fitness (Nelson et al., 2007), reduction in cardiovascular risk factors and events (Nelson et al., 2007), changes in steroid hormones or insulin/insulin-like growth factors, alterations in free radical generation, changes in body composition or weight (Westerlind, 2003), and prevention of falls, osteoporotic fractures, and disability (Gregg et al., 1998). Mortality reductions have been reported to be more pronounced in women in a meta-analysis study, which was not confined to older adults (Samitz et al., 2011). In contrast to a previous study, we did not observe a more beneficial association of physical activity for women in comparison to men. The beneficial effect of physical activity among women was proposed to be associated with changes in hormone levels, estrogen metabolism, and body fat distribution (Lara et al., 2010), which may not be relevant to women aged N65 years. It has been reported that physical activity lowers blood pressure (MacAuley et al., 1996), which is consistent with our observations. We observed that participants with higher physical activity levels had
Please cite this article as: Wu, C.-Y., et al., The association of physical activity with all-cause, cardiovascular, and cancer mortality among older adults, Prev. Med. (2015), http://dx.doi.org/10.1016/j.ypmed.2014.12.023
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323 324 325 326
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This study was supported by the Taiwan Ministry of Education through its “Aim for the Top University Plan”, and by grants from the Department of Health of the Taipei City Government (10301-62-001), Taipei Veterans General Hospital (V103C-201), and the National Science Council Taiwan (NSC 98-2314-B-075-029). This study was based on data from the Taipei City Public Health Database, which was provided by the Department of Health of the Taipei City Government and managed by the Databank for Public Health Analysis. The interpretations and conclusions contained herein do not represent those of the Department of Health of the Taipei City Government or the Databank for Public Health Analysis.
332 Q19 333
Uncited reference
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Sponsor's role
O
Physical activity was observed to have an inverse association with all-cause, CVD, and cancer mortality among older adults. Furthermore, older adults can benefit from an active lifestyle; including a minimal amount of physical activity to one's daily routine (i.e., 30 min once or twice per week) may increase longevity. Preventive resources for older adults should include more opportunities for physical activity.
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The authors declare that there are no conflicts of interests.
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Conflict of interest
Lee et al., 2000 References
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Conclusion
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Healthcare professionals should also encourage older adults to be 327 physically active for at least 1–2 times/week. 328
Arrieta, A., Russell, L.B., 2008. Effects of leisure and non-leisure physical activity on mortality in U.S. adults over two decades. Ann. Epidemiol. 18, 889–895. Autenrieth, C.S., Baumert, J., Baumeister, S.E., et al., 2011. Association between domains of physical activity and all-cause, cardiovascular and cancer mortality. Eur. J. Epidemiol. 26, 91–99. Balboa-Castillo, T., Guallar-Castillon, P., Leon-Munoz, L.M., Graciani, A., Lopez-Garcia, E., Rodriguez-Artalejo, F., 2011. Physical activity and mortality related to obesity and functional status in older adults in Spain. Am. J. Prev. Med. 40, 39–46. Bellavia, A., Bottai, M., Wolk, A., Orsini, N., 2013. Physical activity and mortality in a prospective cohort of middle-aged and elderly men — a time perspective. Int. J. Behav. Nutr. Phys. Act. 10, 94. Bembom, O., van der Laan, M., Haight, T., Tager, I., 2009. Leisure-time physical activity and all-cause mortality in an elderly cohort. Epidemiology 20, 424–430. Burchfiel, C.M., Sharp, D.S., Curb, J.D., et al., 1995. Physical activity and incidence of diabetes: the Honolulu Heart Program. Am. J. Epidemiol. 141, 360–368. Gregg, E.W., Cauley, J.A., Seeley, D.G., Ensrud, K.E., Bauer, D.C., 1998. Physical activity and osteoporotic fracture risk in older women. Study of Osteoporotic Fractures Research Group. Ann. Intern. Med. 129, 81–88. Haskell, W.L., Lee, I.M., Pate, R.R., et al., 2007. Physical activity and public health: updated recommendation for adults from the American College of Sports Medicine and the American Heart Association. Med. Sci. Sports Exerc. 39, 1423–1434. Knoops, K.T., de Groot, L.C., Kromhout, D., et al., 2004. Mediterranean diet, lifestyle factors, and 10-year mortality in elderly European men and women: the HALE project. JAMA 292, 1433–1439. Lara, S., Casanova, G., Spritzer, P.M., 2010. Influence of habitual physical activity on body composition, fat distribution and metabolic variables in early postmenopausal women receiving hormonal therapy. Eur. J. Obstet. Gynecol. Reprod. Biol. 150, 52–56. Lee, I.M., Sesso, H.D., Paffenbarger Jr., R.S., 2000. Physical activity and coronary heart disease risk in men: does the duration of exercise episodes predict risk? Circulation 102, 981–986. Lung, F.W., Lee, M.B., 2008. The five-item Brief-Symptom Rating Scale as a suicide ideation screening instrument for psychiatric inpatients and community residents. BMC Psychiatry 8, 53. MacAuley, D., McCrum, E.E., Stott, G., et al., 1996. Physical activity, physical fitness, blood pressure, and fibrinogen in the Northern Ireland health and activity survey. J. Epidemiol. Community Health 50, 258–263. Maron, B.J., 2000. The paradox of exercise. N. Engl. J. Med. 343, 1409–1411. Moore, S.C., Patel, A.V., Matthews, C.E., et al., 2012. Leisure time physical activity of moderate to vigorous intensity and mortality: a large pooled cohort analysis. PLoS Med. 9, e1001335. Nelson, M.E., Rejeski, W.J., Blair, S.N., et al., 2007. Physical activity and public health in older adults: recommendation from the American College of Sports Medicine and the American Heart Association. Circulation 116, 1094–1105. Nocon, M., Hiemann, T., Muller-Riemenschneider, F., Thalau, F., Roll, S., Willich, S.N., 2008. Association of physical activity with all-cause and cardiovascular mortality: a systematic review and meta-analysis. Eur. J. Cardiovasc. Prev. Rehabil. 15, 239–246. Oguma, Y., Sesso, H.D., Paffenbarger Jr., R.S., Lee, I.M., 2002. Physical activity and all cause mortality in women: a review of the evidence. Br. J. Sports Med. 36, 162–172. Pedersen, J.O., Heitmann, B.L., Schnohr, P., Gronbaek, M., 2008. The combined influence of leisure-time physical activity and weekly alcohol intake on fatal ischaemic heart disease and all-cause mortality. Eur. Heart J. 29, 204–212.
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lower SBP and DBP. The benefit of physical activity tends to be more prominent in participants with higher blood pressures, which is also consistent with a previous study that evaluated a combination of middle-aged and elderly participants (Autenrieth et al., 2011). An important role of physical activity for preventing type 2 diabetes mellitus has been reported (Burchfiel et al., 1995). In our study, participants who were more physically active had lower FBS levels, which might suggest a protective role of physical activity on blood sugar levels. In our study, physical activity significantly reduced mortality in participants who had a normal weight and also presented a likely lower mortality among the underweight, overweight, and obese groups. Our findings are in agreement with a previous report, which concluded that older adults with obesity can benefit from an active lifestyle (Balboa-Castillo et al., 2011). Similarly to a previous study involving younger participants, the inverse association between physical activity and all-cause mortality tended to be stronger for occasional drinkers (Pedersen et al., 2008). The patients with higher risks–smokers, frequent drinkers, and obese patients–may have clouded the beneficial effects of physical activity, and may have had a less obvious reduction in the risk of all-cause mortality. Our study had several strengths. The sample size of this study was large enough to allow us to perform stratified analyses to investigate associations among diverse subgroups. A wide-ranging baseline data, including lifestyle and detailed clinical characteristics obtained during the physical examination, which covered multiple domains of health enabled us to evaluate heterogeneity among older adults. The period of follow-up was short, which contributed to fewer errors that may have occurred due to changes in physical activity levels. Our study also contained several limitations. Physical activity levels were determined from questions that were designed to obtain sufficient information for broad ranking. Nevertheless, physical activity levels had a distinct dose–response relationship. Furthermore, simple questions can maximize the reliability and validity of physical activity assessment (Shephard, 2003). Another limitation was that physical activity was not objectively assessed, but self-reported, and was just monitored for 6 months. Therefore, a certain degree of exposure misclassification was inevitable. However, this would be considered non-differential misclassification and make our findings conservative. Thirdly, we did not assess physical activity through a validated physical activity questionnaire, and had no information regarding the intensity of physical activity or the level of physical fitness of the participants. The questionnaires do not assess physical activities that were not conducted during leisure time (i.e., household-related activities), which might contribute to biases in our results and the total amount of physical activity would be underestimated. Fourthly, this study was conducted during an annual physical examination for older adults. The voluntary participants of this study may not represent the general population. However, the observed relative risk may be a reasonable estimate for the general population because the risks were evaluated using internal comparisons. Fifthly, this report does not include time-dependent analyses. The amount of physical activity was recorded at baseline, making it impossible to report changes in exercise patterns over time. Sixthly, we did not consider preexisting diseases or the severity of these diseases in the participants. Baseline measures of clinical characteristics obtained during the initial physical examination were used for performing adjustments in the models.
E
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Please cite this article as: Wu, C.-Y., et al., The association of physical activity with all-cause, cardiovascular, and cancer mortality among older adults, Prev. Med. (2015), http://dx.doi.org/10.1016/j.ypmed.2014.12.023
334 335 336 Q20 337 338 339 340 341 342 Q21
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Sundquist, K., Qvist, J., Sundquist, J., Johansson, S.E., 2004. Frequent and occasional physical activity in the elderly: a 12-year follow-up study of mortality. Am. J. Prev. Med. 27, 22–27. Ueshima, K., Ishikawa-Takata, K., Yorifuji, T., et al., 2010. Physical activity and mortality risk in the Japanese elderly: a cohort study. Am. J. Prev. Med. 38, 410–418. Wannamethee, S.G., Shaper, A.G., 2001. Physical activity in the prevention of cardiovascular disease: an epidemiological perspective. Sports Med. 31, 101–114. Wannamethee, S.G., Shaper, A.G., Walker, M., 2001. Physical activity and risk of cancer in middle-aged men. Br. J. Cancer 85, 1311–1316. Wen, C.P., Wai, J.P., Tsai, M.K., et al., 2011. Minimum amount of physical activity for reduced mortality and extended life expectancy: a prospective cohort study. Lancet 378, 1244–1253. Westerlind, K.C., 2003. Physical activity and cancer prevention-mechanisms. Med. Sci. Sports Exerc. 35, 1834–1840. Wu, C.Y., Chou, Y.C., Huang, N., Chou, Y.J., Hu, H.Y., Li, C.P., 2014. Cognitive impairment assessed at annual geriatric health examinations predicts mortality among the elderly. Prev. Med.
N C O
R
R
E
C
T
E
D
P
R O
O
F
Pfeiffer, E., 1975. A short portable mental status questionnaire for the assessment of organic brain deficit in elderly patients. J. Am. Geriatr. Soc. 23, 433–441. Rockhill, B., Willett, W.C., Manson, J.E., et al., 2001. Physical activity and mortality: a prospective study among women. Am. J. Public Health 91, 578–583. Samitz, G., Egger, M., Zwahlen, M., 2011. Domains of physical activity and all-cause mortality: systematic review and dose–response meta-analysis of cohort studies. Int. J. Epidemiol. 40, 1382–1400. Schooling, C.M., Lam, T.H., Li, Z.B., et al., 2006. Obesity, physical activity, and mortality in a prospective Chinese elderly cohort. Arch. Intern. Med. 166, 1498–1504. Shephard, R.J., 2003. Limits to the measurement of habitual physical activity by questionnaires. Br. J. Sports Med. 37, 197–206 (discussion 06). Sherman, S.E., D'Agostino, R.B., Cobb, J.L., Kannel, W.B., 1994. Does exercise reduce mortality rates in the elderly? Experience from the Framingham Heart Study. Am. Heart J. 128, 965–972. Stofan, J.R., DiPietro, L., Davis, D., Kohl 3rd, H.W., Blair, S.N., 1998. Physical activity patterns associated with cardiorespiratory fitness and reduced mortality: the Aerobics Center Longitudinal Study. Am. J. Public Health 88, 1807–1813. Sui, X., LaMonte, M.J., Laditka, J.N., et al., 2007. Cardiorespiratory fitness and adiposity as mortality predictors in older adults. JAMA 298, 2507–2516. Sui, X., Li, H., Zhang, J., Chen, L., Zhu, L., Blair, S.N., 2013. Percentage of deaths attributable to poor cardiovascular health lifestyle factors: findings from the Aerobics Center Longitudinal Study. Epidemiol. Res. Int. 2013.
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419 420 421 422 423 424 425 426 427 428 429 430 431 Q23 432 433 434 435 Q24