Association of physical activity with body mass index, waist circumference and incidence of obesity in older adults

Association of physical activity with body mass index, waist circumference and incidence of... Abstract Background There is limited, and inconsistent, data on the prospective association between physical activity and surrogate markers of adiposity in older adults. We aim to determine the prospective association of leisure time physical activity (LTPA) with body mass index (BMI), waist circumference (WC) and the incidence of obesity. Methods This prospective analysis included 7144 individuals with a mean age of 67 ± 6.2 years, from the PREvención con DIeta MEDiterránea (PREDIMED) study. BMI and WC were measured and LTPA was recorded using the Minnesota Leisure Time Physical Activity Questionnaire. Exposure and outcome variables were calculated as cumulative average of repeated measurements. Results Total LTPA was inversely associated (P < 0.001) with BMI and WC. The difference in BMI and WC between extreme quintiles of LTPA (Q1–Q5) was 2.1 kg/m2 (95% confidence interval (CI) 1.68; 2.49, P < 0.001) and 4.8 cm (CI 2.28; 7.25, P < 0.001), respectively. Low-intensity LTPA was inversely associated with BMI but not with WC, while moderate/vigorous LTPA showed an inverse relationship with BMI and WC. The hazard of general and abdominal obesity incidence decreased across quintiles of total and moderate/vigorous LTPA (P < 0.001 for both), whereas low-intensity LTPA was inversely associated with the incidence of general obesity (P < 0.001). Conclusion LTPA was inversely associated with BMI, WC and incidence of general and abdominal obesity. The finding that low-intensity LTPA was inversely related to BMI and the incidence of obesity is of particular importance because this level of physical activity could be a feasible option for many older adults. Introduction Among the elderly population, obesity is related to numerous adverse health outcomes, including frailty, disability, weakness and chronic diseases.1–4 In developed countries, the prevalence of obesity has increased in all age groups, including adults older than 60 years. In Spain, the Seniors ENRICA study found that half of this population was overweight, 30% with obesity but 57% with abdominal obesity.2 Similarly, the EXERNET study indicates that >56% of the Spanish elderly population has central obesity.5 It is widely known that physical activity improves the health of elderly individuals;6–11 however, studies are inconsistent regarding the effect of physical activity on obesity in this age group. A meta-analysis showed that physical activity was inversely associated with body mass index (BMI) and waist circumference (WC) in the short term,12 but recent randomized trials found that physical activity without dietary interventions did not significantly reduce BMI in 12–18 months.13–15 Intervention studies usually assess the effect of moderate and vigorous intensity physical activity, including strength exercises and aerobics, on fat indicators. However, performing these kinds of activities on a daily basis or adhering to a long-term program can be challenging for older adults, a population that experiences a reduction in physical capacities over time.16 There is limited, and inconsistent, evidence on the prospective association between physical activity and surrogate markers of adiposity in older adults.17,18 The aim of the present study was to determine the prospective association of leisure-time physical activity (LTPA) at total, light, moderate and vigorous levels of intensity with BMI, WC and the incidence of general and abdominal obesity in older Spanish adults at high risk of cardiovascular disease. Methods This study was a prospective cohort analysis within the framework of the PREDIMED study (PREvención con DIeta MEDiterránea). The complete protocol of the PREDIMED trial has been reported elsewhere19 and in www.predimed.es. In brief, a multicenter, randomized, 3-arm trial focused on cardiovascular primary prevention in older adults was carried out between 2003 and 2013 in Spain. The recruitment was performed in 11 recruiting centers between 2003 and 2009. Participants were randomly allocated to one of three groups: a Mediterranean diet supplemented with extra virgin olive oil, a Mediterranean diet supplemented with nuts, and a control group with a low-fat diet. Energy restriction or physical activity was not part of the PREDIMED intervention. The primary end point included a composite of myocardial infarction, stroke and cardiovascular death. The Institutional Review Boards for all recruiting centers approved the study protocol and the trial was conducted under the principles of the Declaration of Helsinki. The trial is registered at http://www.controlled-trials.com/ISRCTN35739639. Eligible participants were 3165 men (aged 55–80 years old) and 4282 women (aged 60–80 years old). Individuals were free of cardiovascular disease but had either type II diabetes or at least three of the following cardiovascular risk factors: current smoking, hypertension, increased low-density lipoprotein, decreased high-density lipoprotein, overweight/obesity or family history of premature heart disease. Signed informed consent was obtained from all participants. After excluding those individuals with missing data on any of the variables used in the present study, a total of 7144 participants (3039 men and 4105 women) with a mean age of 67.0 ± 6.2 years were included in the present analysis. Anthropometric measures were taken directly by nurses trained and certified according to the PREDIMED protocol. A calibrated beam scale and a wall-mounted calibrated stadiometer was used to measure weight and height, respectively, with the participant barefoot and wearing light clothing. WC was measured midway between the lowest rib and the iliac crest using an anthropometric tape. All anthropometric variables were measured annually. BMI was calculated by dividing the weight (kg) by the square of the height (m2). General obesity was defined by a BMI equal to or >30 kg/m2 and abdominal obesity by a WC exceeding 88 cm in women and 102 cm in men. The cumulative averages of BMI and WC were calculated. Mean follow-up of the study was 6.8 years. Average annual measures of BMI, WC and LTPA were 5170, 4795 and 4773, respectively. The amount and intensity of LTPA was estimated by the Minnesota Leisure Time Physical Activity Questionnaire, which was initially created to assess the protective effect that exercise could have on the cardiovascular system. It was designed to quantify the amount of energy expended in LTPA and to classify activity on an intensity scale. A Spanish version, consisting of 67 activities organized in nine sections, has been validated for men and women.20,21 The participants were asked to complete the form, indicating the number of days and minutes/day they had performed those activities during the previous week and year. The unit used to quantify physical activity was metabolic equivalent task per minutes per day (METs·min/day). This unit was calculated by multiplying the METs assigned to each activity and its mean duration (in minutes per day). LTPA was classified as light LTPA (intensity below 4 METs; such as walking), moderate LTPA (intensity 4–5.5 METs; such as brisk walking) and vigorous (intensity ≥6 METs; such as jogging). This questionnaire was completed at a baseline visit and annually thereafter. As 47.6% of the participants reported a median (IQR = interquartile range) of 0 (0–30) METs·min/day for vigorous LTPA, we combined moderate and vigorous intensity LTPA into one category. A general questionnaire collected data on smoking status and education level at baseline. Blood pressure was measured in triplicate with a validated semiautomatic oscillometer (HEM705CP; Omron). The mean of these three measures was used to diagnose hypertension (systolic blood pressure ≥ 140 mm Hg, a diastolic blood pressure ≥ 90 mm Hg or taking antihypertensive medication). Participants were considered to have hypercholesterolemia or diabetes if they had previously been diagnosed as such and/or were being treated with lipid-lowering or antidiabetic agents, respectively. Data on energy intake and diet quality, measured by adherence to the Mediterranean diet, were recorded annually on a validated food frequency questionnaire22 and a validated 14-point Mediterranean diet adherence screener.23 Information about changes in smoking habits and any new medical diagnoses was collected using an annual follow-up questionnaire. To minimize within-person variation in long-term LTPA (categorized as total, low intensity and moderate/vigorous intensity), energy intake, adherence to the Mediterranean diet, BMI and WC, we calculated the cumulative average of these annual measurements, based on valid assessments from baseline to the end of follow-up. Moderate and vigorous intensity levels were combined into one category for purposes of analysis, as described in the results section. General linear modelling procedures were used to compare general characteristics of the study population according to quintile distribution of the cumulative average of total LTPA. Polynomial contrasts were used to determine p for linear trend for continuous variables, with a post hoc Bonferroni correction for multiple comparisons. Chi squared tests were used to determine p for linear trend for categorical variables. We fitted general linear models of cumulative averages of (i) total LTPA, (ii) low-intensity LTPA and (iii) moderate/vigorous LTPA as fixed factors and cumulative averages of BMI and WC as dependent variables. Final models were adjusted for sex, age, smoking, educational level, intervention group, hypertension, diabetes, dyslipidemia and cumulative averages of energy intake and adherence to the Mediterranean diet. Sensitivity analyses were undertaken to test the robustness of the results. Effect modification between total LTPA and sex, age, intervention group and adherence to the Mediterranean diet was tested. The association of total LTPA with BMI and WC was stratified by sex, age (<70 and ≥70 years), intervention group and body mass categories [normal weight (BMI = 18.5–24.9 kg/m2), overweight (BMI = 25.0–29.9 kg/m2) and obesity (BMI >29.9 kg/m2)]. Cox models for interval-censored data were fitted to determine the relationship between LTPA (total, low intensity and moderate/vigorous intensity) and incidence of general and abdominal obesity. Incidence between 1-year questionnaire cycles was related to cumulative average of total, low intensity and moderate/vigorous intensity LTPA calculated from all preceding LTPA measures. Participants with general and abdominal obesity at baseline were excluded correspondingly. All models were adjusted for sex, age, smoking, educational level, hypertension, dyslipidemia, diabetes, cumulative average of energy intake and cumulative average of adherence to the Mediterranean diet. The R function ‘ic_sp’ from ‘icenReg’ package was used to fit Cox models for interval-censored data.24 Finally, we conducted multiple linear regression analysis with cubic spline modeling to determine dose-response associations between the cumulative average of moderate/vigorous LTPA and those of BMI and WC using the ‘gam’ package in R version 3.0.2. The lower cut-off of the recommended amount of moderate/vigorous LTPA of 500 METs·min/week was set as the reference value. Associations were considered significant if P < 0.05. The SPSS for Windows version 22 (SPSS, Inc., Chicago, IL, United States) was used for all statistical analysis, except discrete-time Cox regression and dose-response analysis (described above). Results The median (IQR) of the cumulative average LTPA was 198 (104–323) METs·min/day, stratified in men and women as 276 (157–442) METs·min/day and 154 (80–250) METs·min/day, respectively. The median (IQR) was 90 (35–159) METs·min/day) and 58 (8–178) METs·min/day for light and moderate/vigorous LTPA, respectively. More than half (54.1%) of the population did not meet the minimum recommended level of moderate/vigorous intensity physical activity of 500 METs·min/week. The incidence of obesity and abdominal obesity was 14.1% (n = 536/3793) and 31.4% (n = 680/2167), respectively. Positive associations were found between LTPA and higher levels of education, proportion of men, smoking prevalence, energy intake, adherence to the Mediterranean diet and levels of light and moderate/vigorous LTPA. Age, WC, BMI and prevalence of hypertension decreased across quintiles of LTPA (table 1). Table 1 Population characteristics across quintiles of total leisure-time physical activity (METs·min/day)a Characteristic  1st  2nd  3rd  4th  5th  P for    <82  82–157  157–239  239–367  >367  trend  Men, n  363 (25.4%)  397 (27.8%)  537 (37.6%)  695 (48.6%)  1047 (73.3%)  <0.001  Age, years  67.7 (67.4–68.0)  67.5 (67.2–67.8)  67.1 (66.8–67.4)  66.7 (66.3–67.0)  65.9 (65.6–66.2)  <0.001  Type-2 diabetes, nb  727 (50.9%)  658 (46.0%)  667 (46.7%)  671 (47.0%)  724 (50.7%)  0.888  Dyslipidemia, nc  1030 (72.1%)  1046 (73.1%)  1051 (73.6%)  1054 (73.8%)  996 (69.7%)  0.279  Lipid-lowering treatment, n  704 (49.3%)  708 (49.5%)  728 (51.0%)  726 (50.8%)  661 (46.3%)  0.266  Hypertension, nd  1230 (86.1%)  1201 (84.0%)  1195 (83.7%)  1164 (81.5%)  1120 (78.4%)  <0.001  Current smokers, n  183 (12.8%)  157 (11.0%)  193 (13.5%)  195 (13.6%)  272 (19.0%)  <0.001  Intervention group            <0.001      Olive oil, n  452 (31.6%)  474 (33.1%)  483 (33.8%)  521 (36.5%)  515 (36.1%)        Nuts, n  433 (30.3%)  435 (30.4%)  500 (35.0%)  483 (33.8%)  520 (36.4%)        Low-fat diet, n  544 (38.1%)  521 (36.4%)  445 (31.2%)  425 (29.7%)  393 (27.5%)    More than basic education, n  293 (20.5%)  282 (19.7%)  323 (22.6%)  369 (25.8%)  342 (23.9%)  <0.001  BMI, kg/m2e  31.2 (31.0–31.4)  30.5 (30.3–30.7)  29.8 (29.6–30.0)  29.0 (28.8–29.2)  28.8 (28.6–29.0)  <0.001  WC, cm  104.5 (103.3–105.6)  102.3 (101.14–103.4)  101.7 (100.6–102.9)  99.9 (98.8–101.1)  102.2 (101.1–103.4)  <0.001  LTPA, METs·min/day                  Light  21 (0–45)  84 (53–110)  130 (77–170)  142 (72–212)  152 (69–271)  <0.001      Moderate/vigorous  2 (0–19)  27 (3–61)  60 (15–117)  144 (70–229)  340 (203–472)  <0.001  Energy intake, kcal.d  2185 (2162–2207)  2144 (2121–2166)  2169 (2146–2191)  2209 (2187–2232)  2320 (2298–2343)  <0.001  Med scoref  9.1 (9.0–9.1)  9.5 (9.4–9.5)  9.6 (9.6–9.7)  9.9 (9.9–10.0)  10.2 (10.1–10.2)  <0.001  Characteristic  1st  2nd  3rd  4th  5th  P for    <82  82–157  157–239  239–367  >367  trend  Men, n  363 (25.4%)  397 (27.8%)  537 (37.6%)  695 (48.6%)  1047 (73.3%)  <0.001  Age, years  67.7 (67.4–68.0)  67.5 (67.2–67.8)  67.1 (66.8–67.4)  66.7 (66.3–67.0)  65.9 (65.6–66.2)  <0.001  Type-2 diabetes, nb  727 (50.9%)  658 (46.0%)  667 (46.7%)  671 (47.0%)  724 (50.7%)  0.888  Dyslipidemia, nc  1030 (72.1%)  1046 (73.1%)  1051 (73.6%)  1054 (73.8%)  996 (69.7%)  0.279  Lipid-lowering treatment, n  704 (49.3%)  708 (49.5%)  728 (51.0%)  726 (50.8%)  661 (46.3%)  0.266  Hypertension, nd  1230 (86.1%)  1201 (84.0%)  1195 (83.7%)  1164 (81.5%)  1120 (78.4%)  <0.001  Current smokers, n  183 (12.8%)  157 (11.0%)  193 (13.5%)  195 (13.6%)  272 (19.0%)  <0.001  Intervention group            <0.001      Olive oil, n  452 (31.6%)  474 (33.1%)  483 (33.8%)  521 (36.5%)  515 (36.1%)        Nuts, n  433 (30.3%)  435 (30.4%)  500 (35.0%)  483 (33.8%)  520 (36.4%)        Low-fat diet, n  544 (38.1%)  521 (36.4%)  445 (31.2%)  425 (29.7%)  393 (27.5%)    More than basic education, n  293 (20.5%)  282 (19.7%)  323 (22.6%)  369 (25.8%)  342 (23.9%)  <0.001  BMI, kg/m2e  31.2 (31.0–31.4)  30.5 (30.3–30.7)  29.8 (29.6–30.0)  29.0 (28.8–29.2)  28.8 (28.6–29.0)  <0.001  WC, cm  104.5 (103.3–105.6)  102.3 (101.14–103.4)  101.7 (100.6–102.9)  99.9 (98.8–101.1)  102.2 (101.1–103.4)  <0.001  LTPA, METs·min/day                  Light  21 (0–45)  84 (53–110)  130 (77–170)  142 (72–212)  152 (69–271)  <0.001      Moderate/vigorous  2 (0–19)  27 (3–61)  60 (15–117)  144 (70–229)  340 (203–472)  <0.001  Energy intake, kcal.d  2185 (2162–2207)  2144 (2121–2166)  2169 (2146–2191)  2209 (2187–2232)  2320 (2298–2343)  <0.001  Med scoref  9.1 (9.0–9.1)  9.5 (9.4–9.5)  9.6 (9.6–9.7)  9.9 (9.9–10.0)  10.2 (10.1–10.2)  <0.001  Note: WC, waist circumference; LTPA, leisure time physical activity; MET, Metabolic Equivalent of Task. a Values are presented as means (confidence interval) or median (interquartile range) for continuous variables and n (%) for categorical variables. b Diabetes was defined as using antidiabetic medication or fasting glucose >126 mg/dl or casual glucose >200 mg/dl with polyuria, polydipsia or unexplained weight loss or glucose >200 mg/dl in two measurements after an oral glucose tolerance test. c Dyslipidemia: LDL-cholesterol ≥160 mg/dl and HDL-cholesterol ≤ 40 mg/dl in men or ≤ 50 mg/dl in women. d Hypertension was defined as systolic blood pressure ≥140 mm Hg or diastolic blood pressure ≥90 mm Hg or taking antihypertensive medication. e BMI, body mass index was calculated dividing the weight in kilograms by the square of the height in meters. f Adherence to the Mediterranean diet (Score 0 indicates minimum adherence and score 14 maximum adherence). Table 1 Population characteristics across quintiles of total leisure-time physical activity (METs·min/day)a Characteristic  1st  2nd  3rd  4th  5th  P for    <82  82–157  157–239  239–367  >367  trend  Men, n  363 (25.4%)  397 (27.8%)  537 (37.6%)  695 (48.6%)  1047 (73.3%)  <0.001  Age, years  67.7 (67.4–68.0)  67.5 (67.2–67.8)  67.1 (66.8–67.4)  66.7 (66.3–67.0)  65.9 (65.6–66.2)  <0.001  Type-2 diabetes, nb  727 (50.9%)  658 (46.0%)  667 (46.7%)  671 (47.0%)  724 (50.7%)  0.888  Dyslipidemia, nc  1030 (72.1%)  1046 (73.1%)  1051 (73.6%)  1054 (73.8%)  996 (69.7%)  0.279  Lipid-lowering treatment, n  704 (49.3%)  708 (49.5%)  728 (51.0%)  726 (50.8%)  661 (46.3%)  0.266  Hypertension, nd  1230 (86.1%)  1201 (84.0%)  1195 (83.7%)  1164 (81.5%)  1120 (78.4%)  <0.001  Current smokers, n  183 (12.8%)  157 (11.0%)  193 (13.5%)  195 (13.6%)  272 (19.0%)  <0.001  Intervention group            <0.001      Olive oil, n  452 (31.6%)  474 (33.1%)  483 (33.8%)  521 (36.5%)  515 (36.1%)        Nuts, n  433 (30.3%)  435 (30.4%)  500 (35.0%)  483 (33.8%)  520 (36.4%)        Low-fat diet, n  544 (38.1%)  521 (36.4%)  445 (31.2%)  425 (29.7%)  393 (27.5%)    More than basic education, n  293 (20.5%)  282 (19.7%)  323 (22.6%)  369 (25.8%)  342 (23.9%)  <0.001  BMI, kg/m2e  31.2 (31.0–31.4)  30.5 (30.3–30.7)  29.8 (29.6–30.0)  29.0 (28.8–29.2)  28.8 (28.6–29.0)  <0.001  WC, cm  104.5 (103.3–105.6)  102.3 (101.14–103.4)  101.7 (100.6–102.9)  99.9 (98.8–101.1)  102.2 (101.1–103.4)  <0.001  LTPA, METs·min/day                  Light  21 (0–45)  84 (53–110)  130 (77–170)  142 (72–212)  152 (69–271)  <0.001      Moderate/vigorous  2 (0–19)  27 (3–61)  60 (15–117)  144 (70–229)  340 (203–472)  <0.001  Energy intake, kcal.d  2185 (2162–2207)  2144 (2121–2166)  2169 (2146–2191)  2209 (2187–2232)  2320 (2298–2343)  <0.001  Med scoref  9.1 (9.0–9.1)  9.5 (9.4–9.5)  9.6 (9.6–9.7)  9.9 (9.9–10.0)  10.2 (10.1–10.2)  <0.001  Characteristic  1st  2nd  3rd  4th  5th  P for    <82  82–157  157–239  239–367  >367  trend  Men, n  363 (25.4%)  397 (27.8%)  537 (37.6%)  695 (48.6%)  1047 (73.3%)  <0.001  Age, years  67.7 (67.4–68.0)  67.5 (67.2–67.8)  67.1 (66.8–67.4)  66.7 (66.3–67.0)  65.9 (65.6–66.2)  <0.001  Type-2 diabetes, nb  727 (50.9%)  658 (46.0%)  667 (46.7%)  671 (47.0%)  724 (50.7%)  0.888  Dyslipidemia, nc  1030 (72.1%)  1046 (73.1%)  1051 (73.6%)  1054 (73.8%)  996 (69.7%)  0.279  Lipid-lowering treatment, n  704 (49.3%)  708 (49.5%)  728 (51.0%)  726 (50.8%)  661 (46.3%)  0.266  Hypertension, nd  1230 (86.1%)  1201 (84.0%)  1195 (83.7%)  1164 (81.5%)  1120 (78.4%)  <0.001  Current smokers, n  183 (12.8%)  157 (11.0%)  193 (13.5%)  195 (13.6%)  272 (19.0%)  <0.001  Intervention group            <0.001      Olive oil, n  452 (31.6%)  474 (33.1%)  483 (33.8%)  521 (36.5%)  515 (36.1%)        Nuts, n  433 (30.3%)  435 (30.4%)  500 (35.0%)  483 (33.8%)  520 (36.4%)        Low-fat diet, n  544 (38.1%)  521 (36.4%)  445 (31.2%)  425 (29.7%)  393 (27.5%)    More than basic education, n  293 (20.5%)  282 (19.7%)  323 (22.6%)  369 (25.8%)  342 (23.9%)  <0.001  BMI, kg/m2e  31.2 (31.0–31.4)  30.5 (30.3–30.7)  29.8 (29.6–30.0)  29.0 (28.8–29.2)  28.8 (28.6–29.0)  <0.001  WC, cm  104.5 (103.3–105.6)  102.3 (101.14–103.4)  101.7 (100.6–102.9)  99.9 (98.8–101.1)  102.2 (101.1–103.4)  <0.001  LTPA, METs·min/day                  Light  21 (0–45)  84 (53–110)  130 (77–170)  142 (72–212)  152 (69–271)  <0.001      Moderate/vigorous  2 (0–19)  27 (3–61)  60 (15–117)  144 (70–229)  340 (203–472)  <0.001  Energy intake, kcal.d  2185 (2162–2207)  2144 (2121–2166)  2169 (2146–2191)  2209 (2187–2232)  2320 (2298–2343)  <0.001  Med scoref  9.1 (9.0–9.1)  9.5 (9.4–9.5)  9.6 (9.6–9.7)  9.9 (9.9–10.0)  10.2 (10.1–10.2)  <0.001  Note: WC, waist circumference; LTPA, leisure time physical activity; MET, Metabolic Equivalent of Task. a Values are presented as means (confidence interval) or median (interquartile range) for continuous variables and n (%) for categorical variables. b Diabetes was defined as using antidiabetic medication or fasting glucose >126 mg/dl or casual glucose >200 mg/dl with polyuria, polydipsia or unexplained weight loss or glucose >200 mg/dl in two measurements after an oral glucose tolerance test. c Dyslipidemia: LDL-cholesterol ≥160 mg/dl and HDL-cholesterol ≤ 40 mg/dl in men or ≤ 50 mg/dl in women. d Hypertension was defined as systolic blood pressure ≥140 mm Hg or diastolic blood pressure ≥90 mm Hg or taking antihypertensive medication. e BMI, body mass index was calculated dividing the weight in kilograms by the square of the height in meters. f Adherence to the Mediterranean diet (Score 0 indicates minimum adherence and score 14 maximum adherence). Total LTPA was inversely associated with BMI and WC in sex- and age-adjusted models (table 2). Further adjustment for diabetes, hypercholesterolemia, lipid-lowering treatment, hypertension, smoking, intervention group, education level, energy intake and adherence to the Mediterranean diet did not affect the direction and magnitude of these associations. The difference in BMI and WC between the bottom and top quintiles of total LTPA was 2.1 kg/m2 and 4.7 cm, respectively (P < 0.001 for both). Table 2 Association of BMI and waist circumference with quintiles of total leisure-time physical activity (LTPA) and intensity levels (light and moderate/vigorous LTPA)a     BMI, kg/m2b   WC, cm   LTPA, METs·min/day  N = 7144  Model 1  Model 2  Model 1  Model 2  Total      1st <82  1429  31.2 (31.0–31.4)  31.1 (30.9–31.3)  105.7 (104.5–106.8)  105.2 (104.1–106.4)      2nd 82–157  1430  30.4 (30.2–30.6)  30.3 (30.2–30.5)  103.3 (102.2–104.5)  103.1 (102.0–104.3)      3rd 157–239  1428  29.8 (29.6–30.0)  29.8 (29.6–30.0)  102.1 (100.9–103.2)  102.0 (100.9–103.1)      4th 239–367  1429  29.1 (28.9–29.2)  29.1 (28.9–29.3)  99.5 (98.3–100.6)  99.7 (98.6–100.8)      5th >367  1428  28.9 (28.7–29.1)  29.0 (28.8–29.2)  100.0 (98.8–101.2)  100.5 (99.3–101.7)      P for trend    <0.001  <0.001  <0.001  <0.001  Light      1st <27  1441  30.5 (30.3–30.7)  30.4 (30.2–30.6)  103.3 (102.1–104.4)  103.1 (102.0–104.3)      2nd 27–68  1418  30.1 (29.9–30.3)  30. 1 (29.9–30.3)  102.1 (101.0–103.3)  102.0 (100.9–103.1)      3rd 68–115  1428  29.8 (29.6–30.0)  29.8 (29.6–29.9)  101.4 (100.3–102.6)  101.5 (100.4–102.6)      4th 115–178  1429  29.7 (29.5–29.9)  29.8 (29.7–30.0)  101.5 (100.3–102.6)  101.6 (100.5–102.7)      5th >178  1428  29.2 (29.0–29.4)  29.2 (29.0–29.4)  102.3 (101.2–103.5)  102.4 (101.2–103.5)      P for trend    <0.001  <0.001  0.146  0.290  Moderate/vigorous      1st <2  1443  30.7 (30.5–30.9)  30.6 (30.4–30.8)  106.7 (105.6–107.9)  106.3 (105.1–107.5)      2nd 2–32  1418  30.6 (30.4–30.8)  30.6 (30.4–30.8)  103.7 (102.6–104.9)  103.5 (102.4–104.7)      3rd 32–94  1427  29.9 (29.7–30.1)  29.9 (29.7–30.1)  102.2 (101.0–103.3)  102.1 (101.0–103.2)      4th 94–219  1428  29.3 (29.1–29.5)  29. 4 (29.2–29.6)  99.9 (98.8–101.0)  100.1 (99.0–101.3)      5th >219  1428  28.8 (28.6–29.0)  28.9 (28.7–29.1)  98.0 (96.9–99.2)  98.5 (97.3–99.7)      P for trend    <0.001  <0.001  <0.001  <0.001      BMI, kg/m2b   WC, cm   LTPA, METs·min/day  N = 7144  Model 1  Model 2  Model 1  Model 2  Total      1st <82  1429  31.2 (31.0–31.4)  31.1 (30.9–31.3)  105.7 (104.5–106.8)  105.2 (104.1–106.4)      2nd 82–157  1430  30.4 (30.2–30.6)  30.3 (30.2–30.5)  103.3 (102.2–104.5)  103.1 (102.0–104.3)      3rd 157–239  1428  29.8 (29.6–30.0)  29.8 (29.6–30.0)  102.1 (100.9–103.2)  102.0 (100.9–103.1)      4th 239–367  1429  29.1 (28.9–29.2)  29.1 (28.9–29.3)  99.5 (98.3–100.6)  99.7 (98.6–100.8)      5th >367  1428  28.9 (28.7–29.1)  29.0 (28.8–29.2)  100.0 (98.8–101.2)  100.5 (99.3–101.7)      P for trend    <0.001  <0.001  <0.001  <0.001  Light      1st <27  1441  30.5 (30.3–30.7)  30.4 (30.2–30.6)  103.3 (102.1–104.4)  103.1 (102.0–104.3)      2nd 27–68  1418  30.1 (29.9–30.3)  30. 1 (29.9–30.3)  102.1 (101.0–103.3)  102.0 (100.9–103.1)      3rd 68–115  1428  29.8 (29.6–30.0)  29.8 (29.6–29.9)  101.4 (100.3–102.6)  101.5 (100.4–102.6)      4th 115–178  1429  29.7 (29.5–29.9)  29.8 (29.7–30.0)  101.5 (100.3–102.6)  101.6 (100.5–102.7)      5th >178  1428  29.2 (29.0–29.4)  29.2 (29.0–29.4)  102.3 (101.2–103.5)  102.4 (101.2–103.5)      P for trend    <0.001  <0.001  0.146  0.290  Moderate/vigorous      1st <2  1443  30.7 (30.5–30.9)  30.6 (30.4–30.8)  106.7 (105.6–107.9)  106.3 (105.1–107.5)      2nd 2–32  1418  30.6 (30.4–30.8)  30.6 (30.4–30.8)  103.7 (102.6–104.9)  103.5 (102.4–104.7)      3rd 32–94  1427  29.9 (29.7–30.1)  29.9 (29.7–30.1)  102.2 (101.0–103.3)  102.1 (101.0–103.2)      4th 94–219  1428  29.3 (29.1–29.5)  29. 4 (29.2–29.6)  99.9 (98.8–101.0)  100.1 (99.0–101.3)      5th >219  1428  28.8 (28.6–29.0)  28.9 (28.7–29.1)  98.0 (96.9–99.2)  98.5 (97.3–99.7)      P for trend    <0.001  <0.001  <0.001  <0.001  Notes: LTPA, total leisure time physical activity; MET, Metabolic Equivalent of Task. a Values are mean (confidence interval). Model 1 was adjusted by sex and age. Model 2 was adjusted for sex, age, diabetes, dyslipidemia, lipid-lowering treatment, hypertension, smoking, intervention group, education level, energy intake and level of adherence to Mediterranean diet. Additionally, light and moderate/vigorous LTPA were also adjusted for each other. b BMI, body mass index was calculated dividing the weight in kilograms by the square of the height in meters. Table 2 Association of BMI and waist circumference with quintiles of total leisure-time physical activity (LTPA) and intensity levels (light and moderate/vigorous LTPA)a     BMI, kg/m2b   WC, cm   LTPA, METs·min/day  N = 7144  Model 1  Model 2  Model 1  Model 2  Total      1st <82  1429  31.2 (31.0–31.4)  31.1 (30.9–31.3)  105.7 (104.5–106.8)  105.2 (104.1–106.4)      2nd 82–157  1430  30.4 (30.2–30.6)  30.3 (30.2–30.5)  103.3 (102.2–104.5)  103.1 (102.0–104.3)      3rd 157–239  1428  29.8 (29.6–30.0)  29.8 (29.6–30.0)  102.1 (100.9–103.2)  102.0 (100.9–103.1)      4th 239–367  1429  29.1 (28.9–29.2)  29.1 (28.9–29.3)  99.5 (98.3–100.6)  99.7 (98.6–100.8)      5th >367  1428  28.9 (28.7–29.1)  29.0 (28.8–29.2)  100.0 (98.8–101.2)  100.5 (99.3–101.7)      P for trend    <0.001  <0.001  <0.001  <0.001  Light      1st <27  1441  30.5 (30.3–30.7)  30.4 (30.2–30.6)  103.3 (102.1–104.4)  103.1 (102.0–104.3)      2nd 27–68  1418  30.1 (29.9–30.3)  30. 1 (29.9–30.3)  102.1 (101.0–103.3)  102.0 (100.9–103.1)      3rd 68–115  1428  29.8 (29.6–30.0)  29.8 (29.6–29.9)  101.4 (100.3–102.6)  101.5 (100.4–102.6)      4th 115–178  1429  29.7 (29.5–29.9)  29.8 (29.7–30.0)  101.5 (100.3–102.6)  101.6 (100.5–102.7)      5th >178  1428  29.2 (29.0–29.4)  29.2 (29.0–29.4)  102.3 (101.2–103.5)  102.4 (101.2–103.5)      P for trend    <0.001  <0.001  0.146  0.290  Moderate/vigorous      1st <2  1443  30.7 (30.5–30.9)  30.6 (30.4–30.8)  106.7 (105.6–107.9)  106.3 (105.1–107.5)      2nd 2–32  1418  30.6 (30.4–30.8)  30.6 (30.4–30.8)  103.7 (102.6–104.9)  103.5 (102.4–104.7)      3rd 32–94  1427  29.9 (29.7–30.1)  29.9 (29.7–30.1)  102.2 (101.0–103.3)  102.1 (101.0–103.2)      4th 94–219  1428  29.3 (29.1–29.5)  29. 4 (29.2–29.6)  99.9 (98.8–101.0)  100.1 (99.0–101.3)      5th >219  1428  28.8 (28.6–29.0)  28.9 (28.7–29.1)  98.0 (96.9–99.2)  98.5 (97.3–99.7)      P for trend    <0.001  <0.001  <0.001  <0.001      BMI, kg/m2b   WC, cm   LTPA, METs·min/day  N = 7144  Model 1  Model 2  Model 1  Model 2  Total      1st <82  1429  31.2 (31.0–31.4)  31.1 (30.9–31.3)  105.7 (104.5–106.8)  105.2 (104.1–106.4)      2nd 82–157  1430  30.4 (30.2–30.6)  30.3 (30.2–30.5)  103.3 (102.2–104.5)  103.1 (102.0–104.3)      3rd 157–239  1428  29.8 (29.6–30.0)  29.8 (29.6–30.0)  102.1 (100.9–103.2)  102.0 (100.9–103.1)      4th 239–367  1429  29.1 (28.9–29.2)  29.1 (28.9–29.3)  99.5 (98.3–100.6)  99.7 (98.6–100.8)      5th >367  1428  28.9 (28.7–29.1)  29.0 (28.8–29.2)  100.0 (98.8–101.2)  100.5 (99.3–101.7)      P for trend    <0.001  <0.001  <0.001  <0.001  Light      1st <27  1441  30.5 (30.3–30.7)  30.4 (30.2–30.6)  103.3 (102.1–104.4)  103.1 (102.0–104.3)      2nd 27–68  1418  30.1 (29.9–30.3)  30. 1 (29.9–30.3)  102.1 (101.0–103.3)  102.0 (100.9–103.1)      3rd 68–115  1428  29.8 (29.6–30.0)  29.8 (29.6–29.9)  101.4 (100.3–102.6)  101.5 (100.4–102.6)      4th 115–178  1429  29.7 (29.5–29.9)  29.8 (29.7–30.0)  101.5 (100.3–102.6)  101.6 (100.5–102.7)      5th >178  1428  29.2 (29.0–29.4)  29.2 (29.0–29.4)  102.3 (101.2–103.5)  102.4 (101.2–103.5)      P for trend    <0.001  <0.001  0.146  0.290  Moderate/vigorous      1st <2  1443  30.7 (30.5–30.9)  30.6 (30.4–30.8)  106.7 (105.6–107.9)  106.3 (105.1–107.5)      2nd 2–32  1418  30.6 (30.4–30.8)  30.6 (30.4–30.8)  103.7 (102.6–104.9)  103.5 (102.4–104.7)      3rd 32–94  1427  29.9 (29.7–30.1)  29.9 (29.7–30.1)  102.2 (101.0–103.3)  102.1 (101.0–103.2)      4th 94–219  1428  29.3 (29.1–29.5)  29. 4 (29.2–29.6)  99.9 (98.8–101.0)  100.1 (99.0–101.3)      5th >219  1428  28.8 (28.6–29.0)  28.9 (28.7–29.1)  98.0 (96.9–99.2)  98.5 (97.3–99.7)      P for trend    <0.001  <0.001  <0.001  <0.001  Notes: LTPA, total leisure time physical activity; MET, Metabolic Equivalent of Task. a Values are mean (confidence interval). Model 1 was adjusted by sex and age. Model 2 was adjusted for sex, age, diabetes, dyslipidemia, lipid-lowering treatment, hypertension, smoking, intervention group, education level, energy intake and level of adherence to Mediterranean diet. Additionally, light and moderate/vigorous LTPA were also adjusted for each other. b BMI, body mass index was calculated dividing the weight in kilograms by the square of the height in meters. To determine the independent association of different intensities of LTPA with BMI and WC, we fitted models mutually adjusted for LTPA intensities (table 2). Low-intensity LTPA was inversely associated with BMI but not WC. In contrast, moderate/vigorous LTPA showed a strong inverse relationship with WC (8 cm difference between bottom and top quintiles) in addition to BMI. Tests of interaction revealed that sex—but not age, intervention group or adherence to the Mediterranean diet—had a significant effect modification on the association of total LTPA with BMI and WC. The effect size of these associations was stronger in women than in men. Sensitivity analysis revealed no difference in the direction of the associations between total LTPA and BMI or WC regardless of sex, age and intervention group (Supplementary table S4). However, the magnitude of the association was stronger in women, participants aged ≥70 years and the low-fat diet intervention group compared to men, participants younger than 70 and the olive oil and nuts intervention groups, respectively. Stratified by BMI category, BMI and WC decreased with increasing total LTPA in the presence of obesity but not overweight or normal weight. The association of total, low-intensity and moderate/vigorous intensity LTPA with the incidence of general and abdominal obesity is shown in table 3. Total LTPA was inversely associated with the incidence of general and abdominal obesity. High levels of low-intensity LTPA decreased the risk of general (HR hazard ratio 0.67, P = 0.012 bottom vs. top quintile) but not abdominal obesity incidence. In contrast, moderate/vigorous intensity LTPA was inversely associated with the incidence of abdominal (P linear trend < 0.001) and general obesity (P linear trend = 0.005). Table 3 Hazard ratios for the incidence of general and abdominal obesity by quintiles of total leisure-time physical activity (LTPA) and intensity levels (light and moderate/vigorous LTPA)a   General obesityb     Abdominal obesityc   LTPA, METs·min/day  N  Model 1  Model 2  LTPA, METs·min/day    Model 1  Model 2  Total      1st 0–107  759  Reference  Reference  1st 0–137  434  Reference  Reference      2nd 108–190  759  0.75 (0.56–1.01)  0.76 (0.57–1.02)  2nd 138–226  433  0.91 (0.73–1.13)  0.92 (0.70–1.19)      3rd 191–275  758  0.64 (0.48–0.84)  0.65 (0.50–0.85)  3rd 227–320  435  0.69 (0.54–0.86)  0.72 (0.57–0.91)      4th 276–407  759  0.57 (0.43–0.74)  0.59 (0.46–0.77)  4th 321–468  432  0.69 (0.54–0.89)  0.72 (0.54–0.97)      5th >407  758  0.54 (0.40–0.74)  0.58 (0.44–0.76)  5th >468  433  0.55 (0.43–0.70)  0.59 (0.45–0.77)      P for trend    <0.001  0.001  P for trend    <0.001  <0.001  Light      1st 0–30  759  Reference  Reference  1st 0–30  434  Reference  Reference      2nd 31–75  759  0.85 (0.64–1.13)  0.84 (0.64–1.11)  2nd 31–78  433  1.14 (0.89–1.46)  1.15 (0.83–1.60)      3rd 76–125  758  0.87 (0.65–1.16)  0.86 (0.65–1.13)  3rd 79–130  434  1.07 (0.82–1.40)  1.08 (0.81 to1.45)      4th 126–190  759  0.97 (0.74–1.27)  0.96 (0.74–1.25)  4th 131–202  433  1.23 (0.97–1.56)  1.25 (0.93–1.67)      5th >190  758  0.67 (0.49–0.92)  0.67 (0.49–0.92)  5th >202  433  0.94 (0.71–1.23)  0.95 (0.71–1.27)      P for trend    0.067  0.110  P for trend    0.989  0.960  Moderate/vigorous      1st 0–7  759  Reference  Reference  1st 0–15  434  Reference  Reference      2nd 8–48  759  0.82 (0.62–1.08)  0.82 (0.62–1.08)  2nd 16–76  433  0.96 (0.78–1.18)  0.94 (0.74–1.19)      3rd 49–121  758  0.86 (0.64–1.16)  0.89 (0.69–1.15)  3rd 77–173  434  0.90 (0.70–1.16)  0.91 (0.70–1.19)      4th 122–256  759  0.59 (0.45–0.79)  0.63 (0.46–0.85)  4th 174–313  433  0.65 (0.52–0.82)  0.68 (0.54–0.87)      5th >256  758  0.61 (0.45–0.83)  0.65 (0.48–0.87)  5th >313  433  0.57 (0.43–0.75)  0.60 (0.46–0.77)      P for trend    <0.001  0.005  P for trend    <0.001  <0.001    General obesityb     Abdominal obesityc   LTPA, METs·min/day  N  Model 1  Model 2  LTPA, METs·min/day    Model 1  Model 2  Total      1st 0–107  759  Reference  Reference  1st 0–137  434  Reference  Reference      2nd 108–190  759  0.75 (0.56–1.01)  0.76 (0.57–1.02)  2nd 138–226  433  0.91 (0.73–1.13)  0.92 (0.70–1.19)      3rd 191–275  758  0.64 (0.48–0.84)  0.65 (0.50–0.85)  3rd 227–320  435  0.69 (0.54–0.86)  0.72 (0.57–0.91)      4th 276–407  759  0.57 (0.43–0.74)  0.59 (0.46–0.77)  4th 321–468  432  0.69 (0.54–0.89)  0.72 (0.54–0.97)      5th >407  758  0.54 (0.40–0.74)  0.58 (0.44–0.76)  5th >468  433  0.55 (0.43–0.70)  0.59 (0.45–0.77)      P for trend    <0.001  0.001  P for trend    <0.001  <0.001  Light      1st 0–30  759  Reference  Reference  1st 0–30  434  Reference  Reference      2nd 31–75  759  0.85 (0.64–1.13)  0.84 (0.64–1.11)  2nd 31–78  433  1.14 (0.89–1.46)  1.15 (0.83–1.60)      3rd 76–125  758  0.87 (0.65–1.16)  0.86 (0.65–1.13)  3rd 79–130  434  1.07 (0.82–1.40)  1.08 (0.81 to1.45)      4th 126–190  759  0.97 (0.74–1.27)  0.96 (0.74–1.25)  4th 131–202  433  1.23 (0.97–1.56)  1.25 (0.93–1.67)      5th >190  758  0.67 (0.49–0.92)  0.67 (0.49–0.92)  5th >202  433  0.94 (0.71–1.23)  0.95 (0.71–1.27)      P for trend    0.067  0.110  P for trend    0.989  0.960  Moderate/vigorous      1st 0–7  759  Reference  Reference  1st 0–15  434  Reference  Reference      2nd 8–48  759  0.82 (0.62–1.08)  0.82 (0.62–1.08)  2nd 16–76  433  0.96 (0.78–1.18)  0.94 (0.74–1.19)      3rd 49–121  758  0.86 (0.64–1.16)  0.89 (0.69–1.15)  3rd 77–173  434  0.90 (0.70–1.16)  0.91 (0.70–1.19)      4th 122–256  759  0.59 (0.45–0.79)  0.63 (0.46–0.85)  4th 174–313  433  0.65 (0.52–0.82)  0.68 (0.54–0.87)      5th >256  758  0.61 (0.45–0.83)  0.65 (0.48–0.87)  5th >313  433  0.57 (0.43–0.75)  0.60 (0.46–0.77)      P for trend    <0.001  0.005  P for trend    <0.001  <0.001  Notes: LTPA, total leisure time physical activity; MET, Metabolic Equivalent of Task. a Values are hazard ratios (confidence interval). Model 1 was adjusted by sex and age and model 2 was adjusted for sex, age, diabetes, dyslipidemia, lipid-lowering treatment, hypertension, smoking, intervention group, education level, energy intake and level of adherence to Mediterranean diet. Additionally, light and moderate/vigorous LTPA were mutually adjusted. b General obesity was defined by a BMI above or equal to 30 km/m2. c Abdominal obesity was defined by a waist circumference above 88 cm in women and above 102 cm in men. Table 3 Hazard ratios for the incidence of general and abdominal obesity by quintiles of total leisure-time physical activity (LTPA) and intensity levels (light and moderate/vigorous LTPA)a   General obesityb     Abdominal obesityc   LTPA, METs·min/day  N  Model 1  Model 2  LTPA, METs·min/day    Model 1  Model 2  Total      1st 0–107  759  Reference  Reference  1st 0–137  434  Reference  Reference      2nd 108–190  759  0.75 (0.56–1.01)  0.76 (0.57–1.02)  2nd 138–226  433  0.91 (0.73–1.13)  0.92 (0.70–1.19)      3rd 191–275  758  0.64 (0.48–0.84)  0.65 (0.50–0.85)  3rd 227–320  435  0.69 (0.54–0.86)  0.72 (0.57–0.91)      4th 276–407  759  0.57 (0.43–0.74)  0.59 (0.46–0.77)  4th 321–468  432  0.69 (0.54–0.89)  0.72 (0.54–0.97)      5th >407  758  0.54 (0.40–0.74)  0.58 (0.44–0.76)  5th >468  433  0.55 (0.43–0.70)  0.59 (0.45–0.77)      P for trend    <0.001  0.001  P for trend    <0.001  <0.001  Light      1st 0–30  759  Reference  Reference  1st 0–30  434  Reference  Reference      2nd 31–75  759  0.85 (0.64–1.13)  0.84 (0.64–1.11)  2nd 31–78  433  1.14 (0.89–1.46)  1.15 (0.83–1.60)      3rd 76–125  758  0.87 (0.65–1.16)  0.86 (0.65–1.13)  3rd 79–130  434  1.07 (0.82–1.40)  1.08 (0.81 to1.45)      4th 126–190  759  0.97 (0.74–1.27)  0.96 (0.74–1.25)  4th 131–202  433  1.23 (0.97–1.56)  1.25 (0.93–1.67)      5th >190  758  0.67 (0.49–0.92)  0.67 (0.49–0.92)  5th >202  433  0.94 (0.71–1.23)  0.95 (0.71–1.27)      P for trend    0.067  0.110  P for trend    0.989  0.960  Moderate/vigorous      1st 0–7  759  Reference  Reference  1st 0–15  434  Reference  Reference      2nd 8–48  759  0.82 (0.62–1.08)  0.82 (0.62–1.08)  2nd 16–76  433  0.96 (0.78–1.18)  0.94 (0.74–1.19)      3rd 49–121  758  0.86 (0.64–1.16)  0.89 (0.69–1.15)  3rd 77–173  434  0.90 (0.70–1.16)  0.91 (0.70–1.19)      4th 122–256  759  0.59 (0.45–0.79)  0.63 (0.46–0.85)  4th 174–313  433  0.65 (0.52–0.82)  0.68 (0.54–0.87)      5th >256  758  0.61 (0.45–0.83)  0.65 (0.48–0.87)  5th >313  433  0.57 (0.43–0.75)  0.60 (0.46–0.77)      P for trend    <0.001  0.005  P for trend    <0.001  <0.001    General obesityb     Abdominal obesityc   LTPA, METs·min/day  N  Model 1  Model 2  LTPA, METs·min/day    Model 1  Model 2  Total      1st 0–107  759  Reference  Reference  1st 0–137  434  Reference  Reference      2nd 108–190  759  0.75 (0.56–1.01)  0.76 (0.57–1.02)  2nd 138–226  433  0.91 (0.73–1.13)  0.92 (0.70–1.19)      3rd 191–275  758  0.64 (0.48–0.84)  0.65 (0.50–0.85)  3rd 227–320  435  0.69 (0.54–0.86)  0.72 (0.57–0.91)      4th 276–407  759  0.57 (0.43–0.74)  0.59 (0.46–0.77)  4th 321–468  432  0.69 (0.54–0.89)  0.72 (0.54–0.97)      5th >407  758  0.54 (0.40–0.74)  0.58 (0.44–0.76)  5th >468  433  0.55 (0.43–0.70)  0.59 (0.45–0.77)      P for trend    <0.001  0.001  P for trend    <0.001  <0.001  Light      1st 0–30  759  Reference  Reference  1st 0–30  434  Reference  Reference      2nd 31–75  759  0.85 (0.64–1.13)  0.84 (0.64–1.11)  2nd 31–78  433  1.14 (0.89–1.46)  1.15 (0.83–1.60)      3rd 76–125  758  0.87 (0.65–1.16)  0.86 (0.65–1.13)  3rd 79–130  434  1.07 (0.82–1.40)  1.08 (0.81 to1.45)      4th 126–190  759  0.97 (0.74–1.27)  0.96 (0.74–1.25)  4th 131–202  433  1.23 (0.97–1.56)  1.25 (0.93–1.67)      5th >190  758  0.67 (0.49–0.92)  0.67 (0.49–0.92)  5th >202  433  0.94 (0.71–1.23)  0.95 (0.71–1.27)      P for trend    0.067  0.110  P for trend    0.989  0.960  Moderate/vigorous      1st 0–7  759  Reference  Reference  1st 0–15  434  Reference  Reference      2nd 8–48  759  0.82 (0.62–1.08)  0.82 (0.62–1.08)  2nd 16–76  433  0.96 (0.78–1.18)  0.94 (0.74–1.19)      3rd 49–121  758  0.86 (0.64–1.16)  0.89 (0.69–1.15)  3rd 77–173  434  0.90 (0.70–1.16)  0.91 (0.70–1.19)      4th 122–256  759  0.59 (0.45–0.79)  0.63 (0.46–0.85)  4th 174–313  433  0.65 (0.52–0.82)  0.68 (0.54–0.87)      5th >256  758  0.61 (0.45–0.83)  0.65 (0.48–0.87)  5th >313  433  0.57 (0.43–0.75)  0.60 (0.46–0.77)      P for trend    <0.001  0.005  P for trend    <0.001  <0.001  Notes: LTPA, total leisure time physical activity; MET, Metabolic Equivalent of Task. a Values are hazard ratios (confidence interval). Model 1 was adjusted by sex and age and model 2 was adjusted for sex, age, diabetes, dyslipidemia, lipid-lowering treatment, hypertension, smoking, intervention group, education level, energy intake and level of adherence to Mediterranean diet. Additionally, light and moderate/vigorous LTPA were mutually adjusted. b General obesity was defined by a BMI above or equal to 30 km/m2. c Abdominal obesity was defined by a waist circumference above 88 cm in women and above 102 cm in men. Supplementary figures S1 and S2 show the dose-effect association of moderate/vigorous LTPA and BMI and WC, respectively, adjusted for sex, age, diabetes, hypercholesterolemia, lipid lowering treatment, hypertension, smoking, intervention group, educational level, cumulative average of energy intake, cumulative average of the Mediterranean diet adherence score and correspondingly adjusted for BMI and WC. We chose the minimum recommended level of moderate/vigorous LTPA of 500 METs·min/week (71.4 METs·min/day) as the reference value. β coefficients for differences (95% confidence interval) in BMI decrease linearly until 400 METs·min/day, where it starts to slightly increase. WC decreases linearly reaching a plateau at 600 METs·min/day. Discussion This prospective study showed that higher levels of total LTPA were consistently associated with lower BMI, WC and incidence of abdominal and general obesity. Moderate/vigorous-intensity LTPA showed similar results. Light-intensity LTPA was inversely associated with BMI and incidence of general obesity, but not with WC or incidence of abdominal obesity. Prospective evidence in populations younger than 60 years indicates a favorable impact of physical activity on controlling BMI and WC.25–27 A study with 288 498 individuals from 10 European countries evaluated the association between baseline total physical activity (categorized as inactive, moderately inactive, moderately active and active) and annual change in body weight, for a mean follow-up of 5.1 years. In individuals aged 50 years and older, they found that women with obesity, but not normal or overweight, who had a higher physical activity category at baseline had less weight gain. This association was not observed for men in any BMI category.25 The stronger effect size of physical activity on weight development in individuals with obesity was also found in the present study and is in concordance with other reports.27,28 This finding is especially relevant because obesity is associated with high risk of cardiometabolic disease,29 and these individuals would benefit the most from physical activity. A recent prospective study on 3670 British government employees with a mean age of 56 years showed that individuals classified in the top tertile of moderate/vigorous LTPA at baseline had a reduction in the incidence of obesity at 5 and 10 years of 30% and 33%, respectively, compared with the bottom baseline tertile.26 The magnitude of this risk reduction is comparable with that of the present study. Hamer et al.27 found that participants who meet the physical activity recommendations at all measurement points during follow-up have a lower BMI (−0.43 kg/m2) and WC (−2.50 cm), compared to those who infrequently meet it. The effect size of these observed associations was considerably lower than that of the present study. Findings from cross-sectional studies suggest an inverse association of BMI and WC30,31 with total and moderate/vigorous LTPA in older individuals; however, there is little prospective evidence. A 6 year follow-up study in 8352 postmenopausal women has provided evidence for the protective impact of physical activity on weight development in older populations.17 In participants aged 50–69 years, higher levels of LTPA were associated with less gain in fat mass, whereas in those aged 60–69 years it was associated with a greater loss in fat mass. Interestingly, in women aged 70–79 years, the loss in fat mass occurring in all categories was not associated with physical activity. The authors concluded that efforts to encourage physical activity in postmenopausal women may be more effective at younger ages. Additionally, a 13-year follow-up study in 34 079 women found that participants aged 55–64 years who were categorized in the lowest LTPA group gained significantly more weight than those in the highest LTPA category. This trend was not observed in women aged 65 years or older.18 In the present study, more than half of the individuals (54.1%) reported <500 METs of moderate/vigorous LTPA per week. This represents a high, but not exceptional32 prevalence of individuals not meeting the current recommendation for physical activity. Cross-sectional analyses have demonstrated that older individuals meeting the activity recommendations have a lower BMI and WC compared to those who did not.28,32 Prospective evidence from the present study shows a linear dose-effect relationship of moderate/vigorous LTPA with BMI and WC, which reached a point where it started to increase or formed a plateau, respectively. The increase in BMI after reaching 400 METs·min/day, as reported by 7% of the participants might have been due to gains in muscle mass. Frailty associated with older ages33 might impede many older individuals from engaging in moderate/vigorous physical activity. In fact, in the current study, individuals classified in the first three quintiles of total LTPA reported higher levels of light LTPA than moderate/vigorous LTPA, and only in the fifth quintile were the amounts of moderate/vigorous LTPA higher than light LTPA. Low-intensity physical activity may be a feasible physical activity selection for older adults. Therefore, it is important to note that low-intensity LTPA was associated with a considerable decrease in BMI and incidence of general obesity in the present study. Cross-sectional data on this relationship are inconsistent.30,34 Furthermore, a recent review, mostly of randomized clinical trials on the effect of low intensity physical activity on cardiovascular risk factors, found no improvement in body composition.35 The short-term intervention and generally only fair study design might explain this finding. The inverse association between LTPA (total and moderate/vigorous) with surrogate markers of body fat remained significant after adjustment for diet quality and energy intake. Since weight is directly affected by the balance of energy expenditure vs. energy consumed,36 these findings might be partially explained by the increase in carbohydrate and fat oxidation in the muscle that takes place during exercise.37 Studies including exercise interventions have suggested that higher intensity exercise decreases subcutaneous and visceral fat to a greater extent than exercises carried out at lower intensities.38,39 This could illustrate the greater association between moderately/vigorous LTPA and anthropometric measures, compared to light LTPA. Studies have also suggested that women with increasing exercise duration could have a greater capacity to oxidize intramyocellular lipids than men, and that women could rely to a greater extent on the use of plasma free fatty acids for fuel.40 This mechanism could explain why the inverse association of physical activity with BMI and WC was greater in women. The strengths of this study are the relatively large sample size of older adults, and the yearly measurement of anthropometric variables, diet and physical activity throughout the follow up. Furthermore, physical activity and dietary data were recorded using validated questionnaires. However, all instruments measuring past engagement in physical activity are vulnerable to measurement errors. Furthermore, measurement error of self-reported physical activity by the Minnesota Leisure Time Physical Activity Questionnaire is random, which may attenuate the results. The present study showed an inverse association between LTPA and BMI, WC and incidence of general and abdominal obesity, in older individuals at high cardiovascular risk. Moderate/vigorous LTPA was negatively associated with all four outcomes, whereas light-intensity LTPA was associated with BMI and the incidence of general obesity. The latter finding is of particular importance because light-intensity physical activity could be a feasible option for many older adults. Supplementary data Supplementary data are available at EURPUB online. Acknowledgement We appreciate the English revision by Elaine M. Lilly, PhD. Funding Centro de Investigación Biomédica en Red Fisiopatología de la Obesidad y Nutrición (CIBEROBN) and Epidemiologia y Salud Publica (CIBERESP) are an initiative of the Instituto de Salud Carlos III (ISCIII) of Spain which is supported by FEDER funds (CB06/03). This study was supported by the official funding agency for biomedical research of the Spanish government, ISCIII, through grants provided to research networks specifically developed for the trial (RTIC G03/140 and RD 06/0045) through CIBEROBN, and by grants from Centro Nacional de Investigaciones Cardiovasculares (CNIC 06/2007), Fondo de Investigación Sanitaria–Fondo Europeo de Desarrollo Regional (PI04–2239, PI05/2584, CP06/00100, PI07/0240, PI07/1138, PI07/0954, PI 07/0473, PI10/01407, PI10/02658, PI11/01647 and PI11/02505; PI13/00462), Ministerio de Ciencia e Innovación (AGL-2009-13906-C02 and AGL2010-22319-C03), Fundación Mapfre 2010, Consejería de Salud de la Junta de Andalucía (PI0105/2007), Public Health Division of the Department of Health of the Autonomous Government of Catalonia, Generalitat Valenciana (ACOMP06109, GVA-COMP2010-181, GVACOMP2011-151, CS2010-AP-111 and CS2011-AP-042), and the Navarra Regional Government (27/2011). The Fundación Patrimonio Comunal Olivarero and Hojiblanca SA (Málaga, Spain), California California Walnut Commission (Sacramento, CA), Borges SA (Reus, Spain) and Morella Nuts SA (Reus, Spain) donated the olive oil, walnuts, almonds and hazelnuts, respectively, used in the study. Conflicts of interest: E.R. and J.S.-S. are consultants for the California Walnut Commission and International Nut Council, respectively. None of the other authors reported a conflict of interest related to the study. Key points Total and moderate/vigorous leisure time physical activities were inversely associated with body mass index, waist circumference and incidence of general and abdominal obesity in older Spanish adults. Light- intensity leisure time physical activity showed an inverse association with body mass index and general obesity. 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Google Scholar CrossRef Search ADS PubMed  16 Milanovic Z, Pantelic S, Trajkovic N, et al.   Age-related decrease in physical activity and functional fitness among elderly men and women. Clin Interv Aging  2013; 8: 549– 56. Google Scholar CrossRef Search ADS PubMed  17 Sims ST, Kubo J, Desai M, et al.   Changes in physical activity and body composition in postmenopausal women over time. Med Sci Sports Exerc  2013; 45: 1486– 92. Google Scholar CrossRef Search ADS PubMed  18 Lee I, Djousse L, Sesso HD, et al.   Physical activity and weight gain prevention. JAMA  2010; 303: 1173– 9. Google Scholar CrossRef Search ADS PubMed  19 Martínez- González MÁ, Corella D, Salas-Salvado J, et al.   Cohort profile: design and methods of the PREDIMED study. Int J Epidemiol  2012; 41: 377– 85. Google Scholar CrossRef Search ADS PubMed  20 Elosua R, Marrugat J, Molina L, et al.   Validation of the Minnesota leisure time physical activity questionnaire in Spanish men. The MARATHOM investigators. Am J Epidemiol  1994; 139: 1197– 209. Google Scholar CrossRef Search ADS PubMed  21 Elosua R, Garcia M, Aguilar A, et al.   Validation of the Minnesota leisure time physical activity questionnaire in spanish women. Med Sci Sport Exerc  2000; 32: 1431– 7. Google Scholar CrossRef Search ADS   22 De la Fuente-Arrillaga C, Vázquez Ruiz Z, Bes-Rastrollo M, et al.   Reproducibility of an FFQ validated in Spain. Public Health Nutr  2010; 13: 1364– 72. Google Scholar CrossRef Search ADS PubMed  23 Schroder H, Fitó M, Estruch R, et al.   A short screener is valid for assessing mediterranean diet adherence among older spanish men and women. J Nutr Nutr Epidemiol  2011; 141: 1140– 5. 24 Pan W. Extending the iterative convex minorant algorithm to the cox model for interval-censored data. J Comput Graph Stat  1999; 8: 109– 20. 25 Ekelund U, Besson H, Luan J, et al.   Physical activity and gain in abdominal adiposity and body weight: prospective cohort study in 288 498 men and women. 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Severity of obesity and cardiometabolic risk factors in adults: sex differences and role of physical activity. The HERMEX study. Int J Cardiol  2016; 223: 352– 9. Google Scholar CrossRef Search ADS PubMed  30 Jefferis BJ, Parsons TJ, Sartini C, et al.   Does duration of physical activity bouts matter for adiposity and metabolic syndrome? A cross-sectional study of older British men. Int J Behav Nutr Phys Act  2016; 13: 13– 36. Google Scholar CrossRef Search ADS PubMed  31 Rosique-Esteban N, Díaz-Ló Pez AS, Martínez-González MA, et al.   Leisure-time physical activity, sedentary behaviors, sleep, and cardiometabolic risk factors at baseline in the PREDIMED-PLUS intervention trial: a cross-sectional analysis. PLoS One  2017; 12: e0172253. Google Scholar CrossRef Search ADS PubMed  32 Loprinzi PD, Lee H, Cardinal BJ. Evidence to Support Including Lifestyle Light-Intensity Recommendations in Physical Activity Guidelines for Older Adults. Am J Heal Promot  2015; 29: 277– 84. Google Scholar CrossRef Search ADS   33 Hajek A, Brettschneider C, Posselt T, et al.   Predictors of frailty in old age: results of a longitudinal study. J Nutr Heal Aging  2016; 20: 952– 7. Google Scholar CrossRef Search ADS   34 Blaum CS, Xue QL, Michelon E, et al.   The association between obesity and the frailty syndrome in older women: the Women’s Health and Aging Studies. J Am Geriatr Soc  2005; 53: 927– 34. Google Scholar CrossRef Search ADS PubMed  35 Batacan RB, Duncan MJ, Dalbo VJ, et al.   Effects of light intensity activity on CVD risk factors: a systematic review of intervention studies. Biomed Res Int  2015; 2015: 1. Google Scholar CrossRef Search ADS   36 Thomas DM, Bouchard C, Church T, et al.   Why do individuals not lose more weight from an exercise intervention at a defined dose? An energy balance analysis. Obes Rev  2012; 13: 835– 47. Google Scholar CrossRef Search ADS PubMed  37 Martin WH, Klein S. Use of endogenous carbohydrate and fat as fuels during exercise. Proc Nutr Soc  1998; 57: 49– 54. Google Scholar CrossRef Search ADS PubMed  38 Tremblay A, Simoneau JA, Bouchard C. Impact of exercise intensity on body fatness and skeletal muscle metabolism. Metabolism  1994; 43: 814– 8. Google Scholar CrossRef Search ADS PubMed  39 Irving B. a, Ph D, Davis CK, et al.   Effect of exercise training intensity on abdominal visceral fat and body composition. Med Sci Sport  2008; 40: 1863– 72. 40 Devries MC. Sex-based differences in endurance exercise muscle metabolism: impact on exercise and nutritional strategies to optimize health and performance in women. Exp Physiol  2016; 101: 243– 9. Google Scholar CrossRef Search ADS PubMed  © The Author(s) 2018. Published by Oxford University Press on behalf of the European Public Health Association. All rights reserved. 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Oxford University Press
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© The Author(s) 2018. Published by Oxford University Press on behalf of the European Public Health Association. All rights reserved.
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Abstract

Abstract Background There is limited, and inconsistent, data on the prospective association between physical activity and surrogate markers of adiposity in older adults. We aim to determine the prospective association of leisure time physical activity (LTPA) with body mass index (BMI), waist circumference (WC) and the incidence of obesity. Methods This prospective analysis included 7144 individuals with a mean age of 67 ± 6.2 years, from the PREvención con DIeta MEDiterránea (PREDIMED) study. BMI and WC were measured and LTPA was recorded using the Minnesota Leisure Time Physical Activity Questionnaire. Exposure and outcome variables were calculated as cumulative average of repeated measurements. Results Total LTPA was inversely associated (P < 0.001) with BMI and WC. The difference in BMI and WC between extreme quintiles of LTPA (Q1–Q5) was 2.1 kg/m2 (95% confidence interval (CI) 1.68; 2.49, P < 0.001) and 4.8 cm (CI 2.28; 7.25, P < 0.001), respectively. Low-intensity LTPA was inversely associated with BMI but not with WC, while moderate/vigorous LTPA showed an inverse relationship with BMI and WC. The hazard of general and abdominal obesity incidence decreased across quintiles of total and moderate/vigorous LTPA (P < 0.001 for both), whereas low-intensity LTPA was inversely associated with the incidence of general obesity (P < 0.001). Conclusion LTPA was inversely associated with BMI, WC and incidence of general and abdominal obesity. The finding that low-intensity LTPA was inversely related to BMI and the incidence of obesity is of particular importance because this level of physical activity could be a feasible option for many older adults. Introduction Among the elderly population, obesity is related to numerous adverse health outcomes, including frailty, disability, weakness and chronic diseases.1–4 In developed countries, the prevalence of obesity has increased in all age groups, including adults older than 60 years. In Spain, the Seniors ENRICA study found that half of this population was overweight, 30% with obesity but 57% with abdominal obesity.2 Similarly, the EXERNET study indicates that >56% of the Spanish elderly population has central obesity.5 It is widely known that physical activity improves the health of elderly individuals;6–11 however, studies are inconsistent regarding the effect of physical activity on obesity in this age group. A meta-analysis showed that physical activity was inversely associated with body mass index (BMI) and waist circumference (WC) in the short term,12 but recent randomized trials found that physical activity without dietary interventions did not significantly reduce BMI in 12–18 months.13–15 Intervention studies usually assess the effect of moderate and vigorous intensity physical activity, including strength exercises and aerobics, on fat indicators. However, performing these kinds of activities on a daily basis or adhering to a long-term program can be challenging for older adults, a population that experiences a reduction in physical capacities over time.16 There is limited, and inconsistent, evidence on the prospective association between physical activity and surrogate markers of adiposity in older adults.17,18 The aim of the present study was to determine the prospective association of leisure-time physical activity (LTPA) at total, light, moderate and vigorous levels of intensity with BMI, WC and the incidence of general and abdominal obesity in older Spanish adults at high risk of cardiovascular disease. Methods This study was a prospective cohort analysis within the framework of the PREDIMED study (PREvención con DIeta MEDiterránea). The complete protocol of the PREDIMED trial has been reported elsewhere19 and in www.predimed.es. In brief, a multicenter, randomized, 3-arm trial focused on cardiovascular primary prevention in older adults was carried out between 2003 and 2013 in Spain. The recruitment was performed in 11 recruiting centers between 2003 and 2009. Participants were randomly allocated to one of three groups: a Mediterranean diet supplemented with extra virgin olive oil, a Mediterranean diet supplemented with nuts, and a control group with a low-fat diet. Energy restriction or physical activity was not part of the PREDIMED intervention. The primary end point included a composite of myocardial infarction, stroke and cardiovascular death. The Institutional Review Boards for all recruiting centers approved the study protocol and the trial was conducted under the principles of the Declaration of Helsinki. The trial is registered at http://www.controlled-trials.com/ISRCTN35739639. Eligible participants were 3165 men (aged 55–80 years old) and 4282 women (aged 60–80 years old). Individuals were free of cardiovascular disease but had either type II diabetes or at least three of the following cardiovascular risk factors: current smoking, hypertension, increased low-density lipoprotein, decreased high-density lipoprotein, overweight/obesity or family history of premature heart disease. Signed informed consent was obtained from all participants. After excluding those individuals with missing data on any of the variables used in the present study, a total of 7144 participants (3039 men and 4105 women) with a mean age of 67.0 ± 6.2 years were included in the present analysis. Anthropometric measures were taken directly by nurses trained and certified according to the PREDIMED protocol. A calibrated beam scale and a wall-mounted calibrated stadiometer was used to measure weight and height, respectively, with the participant barefoot and wearing light clothing. WC was measured midway between the lowest rib and the iliac crest using an anthropometric tape. All anthropometric variables were measured annually. BMI was calculated by dividing the weight (kg) by the square of the height (m2). General obesity was defined by a BMI equal to or >30 kg/m2 and abdominal obesity by a WC exceeding 88 cm in women and 102 cm in men. The cumulative averages of BMI and WC were calculated. Mean follow-up of the study was 6.8 years. Average annual measures of BMI, WC and LTPA were 5170, 4795 and 4773, respectively. The amount and intensity of LTPA was estimated by the Minnesota Leisure Time Physical Activity Questionnaire, which was initially created to assess the protective effect that exercise could have on the cardiovascular system. It was designed to quantify the amount of energy expended in LTPA and to classify activity on an intensity scale. A Spanish version, consisting of 67 activities organized in nine sections, has been validated for men and women.20,21 The participants were asked to complete the form, indicating the number of days and minutes/day they had performed those activities during the previous week and year. The unit used to quantify physical activity was metabolic equivalent task per minutes per day (METs·min/day). This unit was calculated by multiplying the METs assigned to each activity and its mean duration (in minutes per day). LTPA was classified as light LTPA (intensity below 4 METs; such as walking), moderate LTPA (intensity 4–5.5 METs; such as brisk walking) and vigorous (intensity ≥6 METs; such as jogging). This questionnaire was completed at a baseline visit and annually thereafter. As 47.6% of the participants reported a median (IQR = interquartile range) of 0 (0–30) METs·min/day for vigorous LTPA, we combined moderate and vigorous intensity LTPA into one category. A general questionnaire collected data on smoking status and education level at baseline. Blood pressure was measured in triplicate with a validated semiautomatic oscillometer (HEM705CP; Omron). The mean of these three measures was used to diagnose hypertension (systolic blood pressure ≥ 140 mm Hg, a diastolic blood pressure ≥ 90 mm Hg or taking antihypertensive medication). Participants were considered to have hypercholesterolemia or diabetes if they had previously been diagnosed as such and/or were being treated with lipid-lowering or antidiabetic agents, respectively. Data on energy intake and diet quality, measured by adherence to the Mediterranean diet, were recorded annually on a validated food frequency questionnaire22 and a validated 14-point Mediterranean diet adherence screener.23 Information about changes in smoking habits and any new medical diagnoses was collected using an annual follow-up questionnaire. To minimize within-person variation in long-term LTPA (categorized as total, low intensity and moderate/vigorous intensity), energy intake, adherence to the Mediterranean diet, BMI and WC, we calculated the cumulative average of these annual measurements, based on valid assessments from baseline to the end of follow-up. Moderate and vigorous intensity levels were combined into one category for purposes of analysis, as described in the results section. General linear modelling procedures were used to compare general characteristics of the study population according to quintile distribution of the cumulative average of total LTPA. Polynomial contrasts were used to determine p for linear trend for continuous variables, with a post hoc Bonferroni correction for multiple comparisons. Chi squared tests were used to determine p for linear trend for categorical variables. We fitted general linear models of cumulative averages of (i) total LTPA, (ii) low-intensity LTPA and (iii) moderate/vigorous LTPA as fixed factors and cumulative averages of BMI and WC as dependent variables. Final models were adjusted for sex, age, smoking, educational level, intervention group, hypertension, diabetes, dyslipidemia and cumulative averages of energy intake and adherence to the Mediterranean diet. Sensitivity analyses were undertaken to test the robustness of the results. Effect modification between total LTPA and sex, age, intervention group and adherence to the Mediterranean diet was tested. The association of total LTPA with BMI and WC was stratified by sex, age (<70 and ≥70 years), intervention group and body mass categories [normal weight (BMI = 18.5–24.9 kg/m2), overweight (BMI = 25.0–29.9 kg/m2) and obesity (BMI >29.9 kg/m2)]. Cox models for interval-censored data were fitted to determine the relationship between LTPA (total, low intensity and moderate/vigorous intensity) and incidence of general and abdominal obesity. Incidence between 1-year questionnaire cycles was related to cumulative average of total, low intensity and moderate/vigorous intensity LTPA calculated from all preceding LTPA measures. Participants with general and abdominal obesity at baseline were excluded correspondingly. All models were adjusted for sex, age, smoking, educational level, hypertension, dyslipidemia, diabetes, cumulative average of energy intake and cumulative average of adherence to the Mediterranean diet. The R function ‘ic_sp’ from ‘icenReg’ package was used to fit Cox models for interval-censored data.24 Finally, we conducted multiple linear regression analysis with cubic spline modeling to determine dose-response associations between the cumulative average of moderate/vigorous LTPA and those of BMI and WC using the ‘gam’ package in R version 3.0.2. The lower cut-off of the recommended amount of moderate/vigorous LTPA of 500 METs·min/week was set as the reference value. Associations were considered significant if P < 0.05. The SPSS for Windows version 22 (SPSS, Inc., Chicago, IL, United States) was used for all statistical analysis, except discrete-time Cox regression and dose-response analysis (described above). Results The median (IQR) of the cumulative average LTPA was 198 (104–323) METs·min/day, stratified in men and women as 276 (157–442) METs·min/day and 154 (80–250) METs·min/day, respectively. The median (IQR) was 90 (35–159) METs·min/day) and 58 (8–178) METs·min/day for light and moderate/vigorous LTPA, respectively. More than half (54.1%) of the population did not meet the minimum recommended level of moderate/vigorous intensity physical activity of 500 METs·min/week. The incidence of obesity and abdominal obesity was 14.1% (n = 536/3793) and 31.4% (n = 680/2167), respectively. Positive associations were found between LTPA and higher levels of education, proportion of men, smoking prevalence, energy intake, adherence to the Mediterranean diet and levels of light and moderate/vigorous LTPA. Age, WC, BMI and prevalence of hypertension decreased across quintiles of LTPA (table 1). Table 1 Population characteristics across quintiles of total leisure-time physical activity (METs·min/day)a Characteristic  1st  2nd  3rd  4th  5th  P for    <82  82–157  157–239  239–367  >367  trend  Men, n  363 (25.4%)  397 (27.8%)  537 (37.6%)  695 (48.6%)  1047 (73.3%)  <0.001  Age, years  67.7 (67.4–68.0)  67.5 (67.2–67.8)  67.1 (66.8–67.4)  66.7 (66.3–67.0)  65.9 (65.6–66.2)  <0.001  Type-2 diabetes, nb  727 (50.9%)  658 (46.0%)  667 (46.7%)  671 (47.0%)  724 (50.7%)  0.888  Dyslipidemia, nc  1030 (72.1%)  1046 (73.1%)  1051 (73.6%)  1054 (73.8%)  996 (69.7%)  0.279  Lipid-lowering treatment, n  704 (49.3%)  708 (49.5%)  728 (51.0%)  726 (50.8%)  661 (46.3%)  0.266  Hypertension, nd  1230 (86.1%)  1201 (84.0%)  1195 (83.7%)  1164 (81.5%)  1120 (78.4%)  <0.001  Current smokers, n  183 (12.8%)  157 (11.0%)  193 (13.5%)  195 (13.6%)  272 (19.0%)  <0.001  Intervention group            <0.001      Olive oil, n  452 (31.6%)  474 (33.1%)  483 (33.8%)  521 (36.5%)  515 (36.1%)        Nuts, n  433 (30.3%)  435 (30.4%)  500 (35.0%)  483 (33.8%)  520 (36.4%)        Low-fat diet, n  544 (38.1%)  521 (36.4%)  445 (31.2%)  425 (29.7%)  393 (27.5%)    More than basic education, n  293 (20.5%)  282 (19.7%)  323 (22.6%)  369 (25.8%)  342 (23.9%)  <0.001  BMI, kg/m2e  31.2 (31.0–31.4)  30.5 (30.3–30.7)  29.8 (29.6–30.0)  29.0 (28.8–29.2)  28.8 (28.6–29.0)  <0.001  WC, cm  104.5 (103.3–105.6)  102.3 (101.14–103.4)  101.7 (100.6–102.9)  99.9 (98.8–101.1)  102.2 (101.1–103.4)  <0.001  LTPA, METs·min/day                  Light  21 (0–45)  84 (53–110)  130 (77–170)  142 (72–212)  152 (69–271)  <0.001      Moderate/vigorous  2 (0–19)  27 (3–61)  60 (15–117)  144 (70–229)  340 (203–472)  <0.001  Energy intake, kcal.d  2185 (2162–2207)  2144 (2121–2166)  2169 (2146–2191)  2209 (2187–2232)  2320 (2298–2343)  <0.001  Med scoref  9.1 (9.0–9.1)  9.5 (9.4–9.5)  9.6 (9.6–9.7)  9.9 (9.9–10.0)  10.2 (10.1–10.2)  <0.001  Characteristic  1st  2nd  3rd  4th  5th  P for    <82  82–157  157–239  239–367  >367  trend  Men, n  363 (25.4%)  397 (27.8%)  537 (37.6%)  695 (48.6%)  1047 (73.3%)  <0.001  Age, years  67.7 (67.4–68.0)  67.5 (67.2–67.8)  67.1 (66.8–67.4)  66.7 (66.3–67.0)  65.9 (65.6–66.2)  <0.001  Type-2 diabetes, nb  727 (50.9%)  658 (46.0%)  667 (46.7%)  671 (47.0%)  724 (50.7%)  0.888  Dyslipidemia, nc  1030 (72.1%)  1046 (73.1%)  1051 (73.6%)  1054 (73.8%)  996 (69.7%)  0.279  Lipid-lowering treatment, n  704 (49.3%)  708 (49.5%)  728 (51.0%)  726 (50.8%)  661 (46.3%)  0.266  Hypertension, nd  1230 (86.1%)  1201 (84.0%)  1195 (83.7%)  1164 (81.5%)  1120 (78.4%)  <0.001  Current smokers, n  183 (12.8%)  157 (11.0%)  193 (13.5%)  195 (13.6%)  272 (19.0%)  <0.001  Intervention group            <0.001      Olive oil, n  452 (31.6%)  474 (33.1%)  483 (33.8%)  521 (36.5%)  515 (36.1%)        Nuts, n  433 (30.3%)  435 (30.4%)  500 (35.0%)  483 (33.8%)  520 (36.4%)        Low-fat diet, n  544 (38.1%)  521 (36.4%)  445 (31.2%)  425 (29.7%)  393 (27.5%)    More than basic education, n  293 (20.5%)  282 (19.7%)  323 (22.6%)  369 (25.8%)  342 (23.9%)  <0.001  BMI, kg/m2e  31.2 (31.0–31.4)  30.5 (30.3–30.7)  29.8 (29.6–30.0)  29.0 (28.8–29.2)  28.8 (28.6–29.0)  <0.001  WC, cm  104.5 (103.3–105.6)  102.3 (101.14–103.4)  101.7 (100.6–102.9)  99.9 (98.8–101.1)  102.2 (101.1–103.4)  <0.001  LTPA, METs·min/day                  Light  21 (0–45)  84 (53–110)  130 (77–170)  142 (72–212)  152 (69–271)  <0.001      Moderate/vigorous  2 (0–19)  27 (3–61)  60 (15–117)  144 (70–229)  340 (203–472)  <0.001  Energy intake, kcal.d  2185 (2162–2207)  2144 (2121–2166)  2169 (2146–2191)  2209 (2187–2232)  2320 (2298–2343)  <0.001  Med scoref  9.1 (9.0–9.1)  9.5 (9.4–9.5)  9.6 (9.6–9.7)  9.9 (9.9–10.0)  10.2 (10.1–10.2)  <0.001  Note: WC, waist circumference; LTPA, leisure time physical activity; MET, Metabolic Equivalent of Task. a Values are presented as means (confidence interval) or median (interquartile range) for continuous variables and n (%) for categorical variables. b Diabetes was defined as using antidiabetic medication or fasting glucose >126 mg/dl or casual glucose >200 mg/dl with polyuria, polydipsia or unexplained weight loss or glucose >200 mg/dl in two measurements after an oral glucose tolerance test. c Dyslipidemia: LDL-cholesterol ≥160 mg/dl and HDL-cholesterol ≤ 40 mg/dl in men or ≤ 50 mg/dl in women. d Hypertension was defined as systolic blood pressure ≥140 mm Hg or diastolic blood pressure ≥90 mm Hg or taking antihypertensive medication. e BMI, body mass index was calculated dividing the weight in kilograms by the square of the height in meters. f Adherence to the Mediterranean diet (Score 0 indicates minimum adherence and score 14 maximum adherence). Table 1 Population characteristics across quintiles of total leisure-time physical activity (METs·min/day)a Characteristic  1st  2nd  3rd  4th  5th  P for    <82  82–157  157–239  239–367  >367  trend  Men, n  363 (25.4%)  397 (27.8%)  537 (37.6%)  695 (48.6%)  1047 (73.3%)  <0.001  Age, years  67.7 (67.4–68.0)  67.5 (67.2–67.8)  67.1 (66.8–67.4)  66.7 (66.3–67.0)  65.9 (65.6–66.2)  <0.001  Type-2 diabetes, nb  727 (50.9%)  658 (46.0%)  667 (46.7%)  671 (47.0%)  724 (50.7%)  0.888  Dyslipidemia, nc  1030 (72.1%)  1046 (73.1%)  1051 (73.6%)  1054 (73.8%)  996 (69.7%)  0.279  Lipid-lowering treatment, n  704 (49.3%)  708 (49.5%)  728 (51.0%)  726 (50.8%)  661 (46.3%)  0.266  Hypertension, nd  1230 (86.1%)  1201 (84.0%)  1195 (83.7%)  1164 (81.5%)  1120 (78.4%)  <0.001  Current smokers, n  183 (12.8%)  157 (11.0%)  193 (13.5%)  195 (13.6%)  272 (19.0%)  <0.001  Intervention group            <0.001      Olive oil, n  452 (31.6%)  474 (33.1%)  483 (33.8%)  521 (36.5%)  515 (36.1%)        Nuts, n  433 (30.3%)  435 (30.4%)  500 (35.0%)  483 (33.8%)  520 (36.4%)        Low-fat diet, n  544 (38.1%)  521 (36.4%)  445 (31.2%)  425 (29.7%)  393 (27.5%)    More than basic education, n  293 (20.5%)  282 (19.7%)  323 (22.6%)  369 (25.8%)  342 (23.9%)  <0.001  BMI, kg/m2e  31.2 (31.0–31.4)  30.5 (30.3–30.7)  29.8 (29.6–30.0)  29.0 (28.8–29.2)  28.8 (28.6–29.0)  <0.001  WC, cm  104.5 (103.3–105.6)  102.3 (101.14–103.4)  101.7 (100.6–102.9)  99.9 (98.8–101.1)  102.2 (101.1–103.4)  <0.001  LTPA, METs·min/day                  Light  21 (0–45)  84 (53–110)  130 (77–170)  142 (72–212)  152 (69–271)  <0.001      Moderate/vigorous  2 (0–19)  27 (3–61)  60 (15–117)  144 (70–229)  340 (203–472)  <0.001  Energy intake, kcal.d  2185 (2162–2207)  2144 (2121–2166)  2169 (2146–2191)  2209 (2187–2232)  2320 (2298–2343)  <0.001  Med scoref  9.1 (9.0–9.1)  9.5 (9.4–9.5)  9.6 (9.6–9.7)  9.9 (9.9–10.0)  10.2 (10.1–10.2)  <0.001  Characteristic  1st  2nd  3rd  4th  5th  P for    <82  82–157  157–239  239–367  >367  trend  Men, n  363 (25.4%)  397 (27.8%)  537 (37.6%)  695 (48.6%)  1047 (73.3%)  <0.001  Age, years  67.7 (67.4–68.0)  67.5 (67.2–67.8)  67.1 (66.8–67.4)  66.7 (66.3–67.0)  65.9 (65.6–66.2)  <0.001  Type-2 diabetes, nb  727 (50.9%)  658 (46.0%)  667 (46.7%)  671 (47.0%)  724 (50.7%)  0.888  Dyslipidemia, nc  1030 (72.1%)  1046 (73.1%)  1051 (73.6%)  1054 (73.8%)  996 (69.7%)  0.279  Lipid-lowering treatment, n  704 (49.3%)  708 (49.5%)  728 (51.0%)  726 (50.8%)  661 (46.3%)  0.266  Hypertension, nd  1230 (86.1%)  1201 (84.0%)  1195 (83.7%)  1164 (81.5%)  1120 (78.4%)  <0.001  Current smokers, n  183 (12.8%)  157 (11.0%)  193 (13.5%)  195 (13.6%)  272 (19.0%)  <0.001  Intervention group            <0.001      Olive oil, n  452 (31.6%)  474 (33.1%)  483 (33.8%)  521 (36.5%)  515 (36.1%)        Nuts, n  433 (30.3%)  435 (30.4%)  500 (35.0%)  483 (33.8%)  520 (36.4%)        Low-fat diet, n  544 (38.1%)  521 (36.4%)  445 (31.2%)  425 (29.7%)  393 (27.5%)    More than basic education, n  293 (20.5%)  282 (19.7%)  323 (22.6%)  369 (25.8%)  342 (23.9%)  <0.001  BMI, kg/m2e  31.2 (31.0–31.4)  30.5 (30.3–30.7)  29.8 (29.6–30.0)  29.0 (28.8–29.2)  28.8 (28.6–29.0)  <0.001  WC, cm  104.5 (103.3–105.6)  102.3 (101.14–103.4)  101.7 (100.6–102.9)  99.9 (98.8–101.1)  102.2 (101.1–103.4)  <0.001  LTPA, METs·min/day                  Light  21 (0–45)  84 (53–110)  130 (77–170)  142 (72–212)  152 (69–271)  <0.001      Moderate/vigorous  2 (0–19)  27 (3–61)  60 (15–117)  144 (70–229)  340 (203–472)  <0.001  Energy intake, kcal.d  2185 (2162–2207)  2144 (2121–2166)  2169 (2146–2191)  2209 (2187–2232)  2320 (2298–2343)  <0.001  Med scoref  9.1 (9.0–9.1)  9.5 (9.4–9.5)  9.6 (9.6–9.7)  9.9 (9.9–10.0)  10.2 (10.1–10.2)  <0.001  Note: WC, waist circumference; LTPA, leisure time physical activity; MET, Metabolic Equivalent of Task. a Values are presented as means (confidence interval) or median (interquartile range) for continuous variables and n (%) for categorical variables. b Diabetes was defined as using antidiabetic medication or fasting glucose >126 mg/dl or casual glucose >200 mg/dl with polyuria, polydipsia or unexplained weight loss or glucose >200 mg/dl in two measurements after an oral glucose tolerance test. c Dyslipidemia: LDL-cholesterol ≥160 mg/dl and HDL-cholesterol ≤ 40 mg/dl in men or ≤ 50 mg/dl in women. d Hypertension was defined as systolic blood pressure ≥140 mm Hg or diastolic blood pressure ≥90 mm Hg or taking antihypertensive medication. e BMI, body mass index was calculated dividing the weight in kilograms by the square of the height in meters. f Adherence to the Mediterranean diet (Score 0 indicates minimum adherence and score 14 maximum adherence). Total LTPA was inversely associated with BMI and WC in sex- and age-adjusted models (table 2). Further adjustment for diabetes, hypercholesterolemia, lipid-lowering treatment, hypertension, smoking, intervention group, education level, energy intake and adherence to the Mediterranean diet did not affect the direction and magnitude of these associations. The difference in BMI and WC between the bottom and top quintiles of total LTPA was 2.1 kg/m2 and 4.7 cm, respectively (P < 0.001 for both). Table 2 Association of BMI and waist circumference with quintiles of total leisure-time physical activity (LTPA) and intensity levels (light and moderate/vigorous LTPA)a     BMI, kg/m2b   WC, cm   LTPA, METs·min/day  N = 7144  Model 1  Model 2  Model 1  Model 2  Total      1st <82  1429  31.2 (31.0–31.4)  31.1 (30.9–31.3)  105.7 (104.5–106.8)  105.2 (104.1–106.4)      2nd 82–157  1430  30.4 (30.2–30.6)  30.3 (30.2–30.5)  103.3 (102.2–104.5)  103.1 (102.0–104.3)      3rd 157–239  1428  29.8 (29.6–30.0)  29.8 (29.6–30.0)  102.1 (100.9–103.2)  102.0 (100.9–103.1)      4th 239–367  1429  29.1 (28.9–29.2)  29.1 (28.9–29.3)  99.5 (98.3–100.6)  99.7 (98.6–100.8)      5th >367  1428  28.9 (28.7–29.1)  29.0 (28.8–29.2)  100.0 (98.8–101.2)  100.5 (99.3–101.7)      P for trend    <0.001  <0.001  <0.001  <0.001  Light      1st <27  1441  30.5 (30.3–30.7)  30.4 (30.2–30.6)  103.3 (102.1–104.4)  103.1 (102.0–104.3)      2nd 27–68  1418  30.1 (29.9–30.3)  30. 1 (29.9–30.3)  102.1 (101.0–103.3)  102.0 (100.9–103.1)      3rd 68–115  1428  29.8 (29.6–30.0)  29.8 (29.6–29.9)  101.4 (100.3–102.6)  101.5 (100.4–102.6)      4th 115–178  1429  29.7 (29.5–29.9)  29.8 (29.7–30.0)  101.5 (100.3–102.6)  101.6 (100.5–102.7)      5th >178  1428  29.2 (29.0–29.4)  29.2 (29.0–29.4)  102.3 (101.2–103.5)  102.4 (101.2–103.5)      P for trend    <0.001  <0.001  0.146  0.290  Moderate/vigorous      1st <2  1443  30.7 (30.5–30.9)  30.6 (30.4–30.8)  106.7 (105.6–107.9)  106.3 (105.1–107.5)      2nd 2–32  1418  30.6 (30.4–30.8)  30.6 (30.4–30.8)  103.7 (102.6–104.9)  103.5 (102.4–104.7)      3rd 32–94  1427  29.9 (29.7–30.1)  29.9 (29.7–30.1)  102.2 (101.0–103.3)  102.1 (101.0–103.2)      4th 94–219  1428  29.3 (29.1–29.5)  29. 4 (29.2–29.6)  99.9 (98.8–101.0)  100.1 (99.0–101.3)      5th >219  1428  28.8 (28.6–29.0)  28.9 (28.7–29.1)  98.0 (96.9–99.2)  98.5 (97.3–99.7)      P for trend    <0.001  <0.001  <0.001  <0.001      BMI, kg/m2b   WC, cm   LTPA, METs·min/day  N = 7144  Model 1  Model 2  Model 1  Model 2  Total      1st <82  1429  31.2 (31.0–31.4)  31.1 (30.9–31.3)  105.7 (104.5–106.8)  105.2 (104.1–106.4)      2nd 82–157  1430  30.4 (30.2–30.6)  30.3 (30.2–30.5)  103.3 (102.2–104.5)  103.1 (102.0–104.3)      3rd 157–239  1428  29.8 (29.6–30.0)  29.8 (29.6–30.0)  102.1 (100.9–103.2)  102.0 (100.9–103.1)      4th 239–367  1429  29.1 (28.9–29.2)  29.1 (28.9–29.3)  99.5 (98.3–100.6)  99.7 (98.6–100.8)      5th >367  1428  28.9 (28.7–29.1)  29.0 (28.8–29.2)  100.0 (98.8–101.2)  100.5 (99.3–101.7)      P for trend    <0.001  <0.001  <0.001  <0.001  Light      1st <27  1441  30.5 (30.3–30.7)  30.4 (30.2–30.6)  103.3 (102.1–104.4)  103.1 (102.0–104.3)      2nd 27–68  1418  30.1 (29.9–30.3)  30. 1 (29.9–30.3)  102.1 (101.0–103.3)  102.0 (100.9–103.1)      3rd 68–115  1428  29.8 (29.6–30.0)  29.8 (29.6–29.9)  101.4 (100.3–102.6)  101.5 (100.4–102.6)      4th 115–178  1429  29.7 (29.5–29.9)  29.8 (29.7–30.0)  101.5 (100.3–102.6)  101.6 (100.5–102.7)      5th >178  1428  29.2 (29.0–29.4)  29.2 (29.0–29.4)  102.3 (101.2–103.5)  102.4 (101.2–103.5)      P for trend    <0.001  <0.001  0.146  0.290  Moderate/vigorous      1st <2  1443  30.7 (30.5–30.9)  30.6 (30.4–30.8)  106.7 (105.6–107.9)  106.3 (105.1–107.5)      2nd 2–32  1418  30.6 (30.4–30.8)  30.6 (30.4–30.8)  103.7 (102.6–104.9)  103.5 (102.4–104.7)      3rd 32–94  1427  29.9 (29.7–30.1)  29.9 (29.7–30.1)  102.2 (101.0–103.3)  102.1 (101.0–103.2)      4th 94–219  1428  29.3 (29.1–29.5)  29. 4 (29.2–29.6)  99.9 (98.8–101.0)  100.1 (99.0–101.3)      5th >219  1428  28.8 (28.6–29.0)  28.9 (28.7–29.1)  98.0 (96.9–99.2)  98.5 (97.3–99.7)      P for trend    <0.001  <0.001  <0.001  <0.001  Notes: LTPA, total leisure time physical activity; MET, Metabolic Equivalent of Task. a Values are mean (confidence interval). Model 1 was adjusted by sex and age. Model 2 was adjusted for sex, age, diabetes, dyslipidemia, lipid-lowering treatment, hypertension, smoking, intervention group, education level, energy intake and level of adherence to Mediterranean diet. Additionally, light and moderate/vigorous LTPA were also adjusted for each other. b BMI, body mass index was calculated dividing the weight in kilograms by the square of the height in meters. Table 2 Association of BMI and waist circumference with quintiles of total leisure-time physical activity (LTPA) and intensity levels (light and moderate/vigorous LTPA)a     BMI, kg/m2b   WC, cm   LTPA, METs·min/day  N = 7144  Model 1  Model 2  Model 1  Model 2  Total      1st <82  1429  31.2 (31.0–31.4)  31.1 (30.9–31.3)  105.7 (104.5–106.8)  105.2 (104.1–106.4)      2nd 82–157  1430  30.4 (30.2–30.6)  30.3 (30.2–30.5)  103.3 (102.2–104.5)  103.1 (102.0–104.3)      3rd 157–239  1428  29.8 (29.6–30.0)  29.8 (29.6–30.0)  102.1 (100.9–103.2)  102.0 (100.9–103.1)      4th 239–367  1429  29.1 (28.9–29.2)  29.1 (28.9–29.3)  99.5 (98.3–100.6)  99.7 (98.6–100.8)      5th >367  1428  28.9 (28.7–29.1)  29.0 (28.8–29.2)  100.0 (98.8–101.2)  100.5 (99.3–101.7)      P for trend    <0.001  <0.001  <0.001  <0.001  Light      1st <27  1441  30.5 (30.3–30.7)  30.4 (30.2–30.6)  103.3 (102.1–104.4)  103.1 (102.0–104.3)      2nd 27–68  1418  30.1 (29.9–30.3)  30. 1 (29.9–30.3)  102.1 (101.0–103.3)  102.0 (100.9–103.1)      3rd 68–115  1428  29.8 (29.6–30.0)  29.8 (29.6–29.9)  101.4 (100.3–102.6)  101.5 (100.4–102.6)      4th 115–178  1429  29.7 (29.5–29.9)  29.8 (29.7–30.0)  101.5 (100.3–102.6)  101.6 (100.5–102.7)      5th >178  1428  29.2 (29.0–29.4)  29.2 (29.0–29.4)  102.3 (101.2–103.5)  102.4 (101.2–103.5)      P for trend    <0.001  <0.001  0.146  0.290  Moderate/vigorous      1st <2  1443  30.7 (30.5–30.9)  30.6 (30.4–30.8)  106.7 (105.6–107.9)  106.3 (105.1–107.5)      2nd 2–32  1418  30.6 (30.4–30.8)  30.6 (30.4–30.8)  103.7 (102.6–104.9)  103.5 (102.4–104.7)      3rd 32–94  1427  29.9 (29.7–30.1)  29.9 (29.7–30.1)  102.2 (101.0–103.3)  102.1 (101.0–103.2)      4th 94–219  1428  29.3 (29.1–29.5)  29. 4 (29.2–29.6)  99.9 (98.8–101.0)  100.1 (99.0–101.3)      5th >219  1428  28.8 (28.6–29.0)  28.9 (28.7–29.1)  98.0 (96.9–99.2)  98.5 (97.3–99.7)      P for trend    <0.001  <0.001  <0.001  <0.001      BMI, kg/m2b   WC, cm   LTPA, METs·min/day  N = 7144  Model 1  Model 2  Model 1  Model 2  Total      1st <82  1429  31.2 (31.0–31.4)  31.1 (30.9–31.3)  105.7 (104.5–106.8)  105.2 (104.1–106.4)      2nd 82–157  1430  30.4 (30.2–30.6)  30.3 (30.2–30.5)  103.3 (102.2–104.5)  103.1 (102.0–104.3)      3rd 157–239  1428  29.8 (29.6–30.0)  29.8 (29.6–30.0)  102.1 (100.9–103.2)  102.0 (100.9–103.1)      4th 239–367  1429  29.1 (28.9–29.2)  29.1 (28.9–29.3)  99.5 (98.3–100.6)  99.7 (98.6–100.8)      5th >367  1428  28.9 (28.7–29.1)  29.0 (28.8–29.2)  100.0 (98.8–101.2)  100.5 (99.3–101.7)      P for trend    <0.001  <0.001  <0.001  <0.001  Light      1st <27  1441  30.5 (30.3–30.7)  30.4 (30.2–30.6)  103.3 (102.1–104.4)  103.1 (102.0–104.3)      2nd 27–68  1418  30.1 (29.9–30.3)  30. 1 (29.9–30.3)  102.1 (101.0–103.3)  102.0 (100.9–103.1)      3rd 68–115  1428  29.8 (29.6–30.0)  29.8 (29.6–29.9)  101.4 (100.3–102.6)  101.5 (100.4–102.6)      4th 115–178  1429  29.7 (29.5–29.9)  29.8 (29.7–30.0)  101.5 (100.3–102.6)  101.6 (100.5–102.7)      5th >178  1428  29.2 (29.0–29.4)  29.2 (29.0–29.4)  102.3 (101.2–103.5)  102.4 (101.2–103.5)      P for trend    <0.001  <0.001  0.146  0.290  Moderate/vigorous      1st <2  1443  30.7 (30.5–30.9)  30.6 (30.4–30.8)  106.7 (105.6–107.9)  106.3 (105.1–107.5)      2nd 2–32  1418  30.6 (30.4–30.8)  30.6 (30.4–30.8)  103.7 (102.6–104.9)  103.5 (102.4–104.7)      3rd 32–94  1427  29.9 (29.7–30.1)  29.9 (29.7–30.1)  102.2 (101.0–103.3)  102.1 (101.0–103.2)      4th 94–219  1428  29.3 (29.1–29.5)  29. 4 (29.2–29.6)  99.9 (98.8–101.0)  100.1 (99.0–101.3)      5th >219  1428  28.8 (28.6–29.0)  28.9 (28.7–29.1)  98.0 (96.9–99.2)  98.5 (97.3–99.7)      P for trend    <0.001  <0.001  <0.001  <0.001  Notes: LTPA, total leisure time physical activity; MET, Metabolic Equivalent of Task. a Values are mean (confidence interval). Model 1 was adjusted by sex and age. Model 2 was adjusted for sex, age, diabetes, dyslipidemia, lipid-lowering treatment, hypertension, smoking, intervention group, education level, energy intake and level of adherence to Mediterranean diet. Additionally, light and moderate/vigorous LTPA were also adjusted for each other. b BMI, body mass index was calculated dividing the weight in kilograms by the square of the height in meters. To determine the independent association of different intensities of LTPA with BMI and WC, we fitted models mutually adjusted for LTPA intensities (table 2). Low-intensity LTPA was inversely associated with BMI but not WC. In contrast, moderate/vigorous LTPA showed a strong inverse relationship with WC (8 cm difference between bottom and top quintiles) in addition to BMI. Tests of interaction revealed that sex—but not age, intervention group or adherence to the Mediterranean diet—had a significant effect modification on the association of total LTPA with BMI and WC. The effect size of these associations was stronger in women than in men. Sensitivity analysis revealed no difference in the direction of the associations between total LTPA and BMI or WC regardless of sex, age and intervention group (Supplementary table S4). However, the magnitude of the association was stronger in women, participants aged ≥70 years and the low-fat diet intervention group compared to men, participants younger than 70 and the olive oil and nuts intervention groups, respectively. Stratified by BMI category, BMI and WC decreased with increasing total LTPA in the presence of obesity but not overweight or normal weight. The association of total, low-intensity and moderate/vigorous intensity LTPA with the incidence of general and abdominal obesity is shown in table 3. Total LTPA was inversely associated with the incidence of general and abdominal obesity. High levels of low-intensity LTPA decreased the risk of general (HR hazard ratio 0.67, P = 0.012 bottom vs. top quintile) but not abdominal obesity incidence. In contrast, moderate/vigorous intensity LTPA was inversely associated with the incidence of abdominal (P linear trend < 0.001) and general obesity (P linear trend = 0.005). Table 3 Hazard ratios for the incidence of general and abdominal obesity by quintiles of total leisure-time physical activity (LTPA) and intensity levels (light and moderate/vigorous LTPA)a   General obesityb     Abdominal obesityc   LTPA, METs·min/day  N  Model 1  Model 2  LTPA, METs·min/day    Model 1  Model 2  Total      1st 0–107  759  Reference  Reference  1st 0–137  434  Reference  Reference      2nd 108–190  759  0.75 (0.56–1.01)  0.76 (0.57–1.02)  2nd 138–226  433  0.91 (0.73–1.13)  0.92 (0.70–1.19)      3rd 191–275  758  0.64 (0.48–0.84)  0.65 (0.50–0.85)  3rd 227–320  435  0.69 (0.54–0.86)  0.72 (0.57–0.91)      4th 276–407  759  0.57 (0.43–0.74)  0.59 (0.46–0.77)  4th 321–468  432  0.69 (0.54–0.89)  0.72 (0.54–0.97)      5th >407  758  0.54 (0.40–0.74)  0.58 (0.44–0.76)  5th >468  433  0.55 (0.43–0.70)  0.59 (0.45–0.77)      P for trend    <0.001  0.001  P for trend    <0.001  <0.001  Light      1st 0–30  759  Reference  Reference  1st 0–30  434  Reference  Reference      2nd 31–75  759  0.85 (0.64–1.13)  0.84 (0.64–1.11)  2nd 31–78  433  1.14 (0.89–1.46)  1.15 (0.83–1.60)      3rd 76–125  758  0.87 (0.65–1.16)  0.86 (0.65–1.13)  3rd 79–130  434  1.07 (0.82–1.40)  1.08 (0.81 to1.45)      4th 126–190  759  0.97 (0.74–1.27)  0.96 (0.74–1.25)  4th 131–202  433  1.23 (0.97–1.56)  1.25 (0.93–1.67)      5th >190  758  0.67 (0.49–0.92)  0.67 (0.49–0.92)  5th >202  433  0.94 (0.71–1.23)  0.95 (0.71–1.27)      P for trend    0.067  0.110  P for trend    0.989  0.960  Moderate/vigorous      1st 0–7  759  Reference  Reference  1st 0–15  434  Reference  Reference      2nd 8–48  759  0.82 (0.62–1.08)  0.82 (0.62–1.08)  2nd 16–76  433  0.96 (0.78–1.18)  0.94 (0.74–1.19)      3rd 49–121  758  0.86 (0.64–1.16)  0.89 (0.69–1.15)  3rd 77–173  434  0.90 (0.70–1.16)  0.91 (0.70–1.19)      4th 122–256  759  0.59 (0.45–0.79)  0.63 (0.46–0.85)  4th 174–313  433  0.65 (0.52–0.82)  0.68 (0.54–0.87)      5th >256  758  0.61 (0.45–0.83)  0.65 (0.48–0.87)  5th >313  433  0.57 (0.43–0.75)  0.60 (0.46–0.77)      P for trend    <0.001  0.005  P for trend    <0.001  <0.001    General obesityb     Abdominal obesityc   LTPA, METs·min/day  N  Model 1  Model 2  LTPA, METs·min/day    Model 1  Model 2  Total      1st 0–107  759  Reference  Reference  1st 0–137  434  Reference  Reference      2nd 108–190  759  0.75 (0.56–1.01)  0.76 (0.57–1.02)  2nd 138–226  433  0.91 (0.73–1.13)  0.92 (0.70–1.19)      3rd 191–275  758  0.64 (0.48–0.84)  0.65 (0.50–0.85)  3rd 227–320  435  0.69 (0.54–0.86)  0.72 (0.57–0.91)      4th 276–407  759  0.57 (0.43–0.74)  0.59 (0.46–0.77)  4th 321–468  432  0.69 (0.54–0.89)  0.72 (0.54–0.97)      5th >407  758  0.54 (0.40–0.74)  0.58 (0.44–0.76)  5th >468  433  0.55 (0.43–0.70)  0.59 (0.45–0.77)      P for trend    <0.001  0.001  P for trend    <0.001  <0.001  Light      1st 0–30  759  Reference  Reference  1st 0–30  434  Reference  Reference      2nd 31–75  759  0.85 (0.64–1.13)  0.84 (0.64–1.11)  2nd 31–78  433  1.14 (0.89–1.46)  1.15 (0.83–1.60)      3rd 76–125  758  0.87 (0.65–1.16)  0.86 (0.65–1.13)  3rd 79–130  434  1.07 (0.82–1.40)  1.08 (0.81 to1.45)      4th 126–190  759  0.97 (0.74–1.27)  0.96 (0.74–1.25)  4th 131–202  433  1.23 (0.97–1.56)  1.25 (0.93–1.67)      5th >190  758  0.67 (0.49–0.92)  0.67 (0.49–0.92)  5th >202  433  0.94 (0.71–1.23)  0.95 (0.71–1.27)      P for trend    0.067  0.110  P for trend    0.989  0.960  Moderate/vigorous      1st 0–7  759  Reference  Reference  1st 0–15  434  Reference  Reference      2nd 8–48  759  0.82 (0.62–1.08)  0.82 (0.62–1.08)  2nd 16–76  433  0.96 (0.78–1.18)  0.94 (0.74–1.19)      3rd 49–121  758  0.86 (0.64–1.16)  0.89 (0.69–1.15)  3rd 77–173  434  0.90 (0.70–1.16)  0.91 (0.70–1.19)      4th 122–256  759  0.59 (0.45–0.79)  0.63 (0.46–0.85)  4th 174–313  433  0.65 (0.52–0.82)  0.68 (0.54–0.87)      5th >256  758  0.61 (0.45–0.83)  0.65 (0.48–0.87)  5th >313  433  0.57 (0.43–0.75)  0.60 (0.46–0.77)      P for trend    <0.001  0.005  P for trend    <0.001  <0.001  Notes: LTPA, total leisure time physical activity; MET, Metabolic Equivalent of Task. a Values are hazard ratios (confidence interval). Model 1 was adjusted by sex and age and model 2 was adjusted for sex, age, diabetes, dyslipidemia, lipid-lowering treatment, hypertension, smoking, intervention group, education level, energy intake and level of adherence to Mediterranean diet. Additionally, light and moderate/vigorous LTPA were mutually adjusted. b General obesity was defined by a BMI above or equal to 30 km/m2. c Abdominal obesity was defined by a waist circumference above 88 cm in women and above 102 cm in men. Table 3 Hazard ratios for the incidence of general and abdominal obesity by quintiles of total leisure-time physical activity (LTPA) and intensity levels (light and moderate/vigorous LTPA)a   General obesityb     Abdominal obesityc   LTPA, METs·min/day  N  Model 1  Model 2  LTPA, METs·min/day    Model 1  Model 2  Total      1st 0–107  759  Reference  Reference  1st 0–137  434  Reference  Reference      2nd 108–190  759  0.75 (0.56–1.01)  0.76 (0.57–1.02)  2nd 138–226  433  0.91 (0.73–1.13)  0.92 (0.70–1.19)      3rd 191–275  758  0.64 (0.48–0.84)  0.65 (0.50–0.85)  3rd 227–320  435  0.69 (0.54–0.86)  0.72 (0.57–0.91)      4th 276–407  759  0.57 (0.43–0.74)  0.59 (0.46–0.77)  4th 321–468  432  0.69 (0.54–0.89)  0.72 (0.54–0.97)      5th >407  758  0.54 (0.40–0.74)  0.58 (0.44–0.76)  5th >468  433  0.55 (0.43–0.70)  0.59 (0.45–0.77)      P for trend    <0.001  0.001  P for trend    <0.001  <0.001  Light      1st 0–30  759  Reference  Reference  1st 0–30  434  Reference  Reference      2nd 31–75  759  0.85 (0.64–1.13)  0.84 (0.64–1.11)  2nd 31–78  433  1.14 (0.89–1.46)  1.15 (0.83–1.60)      3rd 76–125  758  0.87 (0.65–1.16)  0.86 (0.65–1.13)  3rd 79–130  434  1.07 (0.82–1.40)  1.08 (0.81 to1.45)      4th 126–190  759  0.97 (0.74–1.27)  0.96 (0.74–1.25)  4th 131–202  433  1.23 (0.97–1.56)  1.25 (0.93–1.67)      5th >190  758  0.67 (0.49–0.92)  0.67 (0.49–0.92)  5th >202  433  0.94 (0.71–1.23)  0.95 (0.71–1.27)      P for trend    0.067  0.110  P for trend    0.989  0.960  Moderate/vigorous      1st 0–7  759  Reference  Reference  1st 0–15  434  Reference  Reference      2nd 8–48  759  0.82 (0.62–1.08)  0.82 (0.62–1.08)  2nd 16–76  433  0.96 (0.78–1.18)  0.94 (0.74–1.19)      3rd 49–121  758  0.86 (0.64–1.16)  0.89 (0.69–1.15)  3rd 77–173  434  0.90 (0.70–1.16)  0.91 (0.70–1.19)      4th 122–256  759  0.59 (0.45–0.79)  0.63 (0.46–0.85)  4th 174–313  433  0.65 (0.52–0.82)  0.68 (0.54–0.87)      5th >256  758  0.61 (0.45–0.83)  0.65 (0.48–0.87)  5th >313  433  0.57 (0.43–0.75)  0.60 (0.46–0.77)      P for trend    <0.001  0.005  P for trend    <0.001  <0.001    General obesityb     Abdominal obesityc   LTPA, METs·min/day  N  Model 1  Model 2  LTPA, METs·min/day    Model 1  Model 2  Total      1st 0–107  759  Reference  Reference  1st 0–137  434  Reference  Reference      2nd 108–190  759  0.75 (0.56–1.01)  0.76 (0.57–1.02)  2nd 138–226  433  0.91 (0.73–1.13)  0.92 (0.70–1.19)      3rd 191–275  758  0.64 (0.48–0.84)  0.65 (0.50–0.85)  3rd 227–320  435  0.69 (0.54–0.86)  0.72 (0.57–0.91)      4th 276–407  759  0.57 (0.43–0.74)  0.59 (0.46–0.77)  4th 321–468  432  0.69 (0.54–0.89)  0.72 (0.54–0.97)      5th >407  758  0.54 (0.40–0.74)  0.58 (0.44–0.76)  5th >468  433  0.55 (0.43–0.70)  0.59 (0.45–0.77)      P for trend    <0.001  0.001  P for trend    <0.001  <0.001  Light      1st 0–30  759  Reference  Reference  1st 0–30  434  Reference  Reference      2nd 31–75  759  0.85 (0.64–1.13)  0.84 (0.64–1.11)  2nd 31–78  433  1.14 (0.89–1.46)  1.15 (0.83–1.60)      3rd 76–125  758  0.87 (0.65–1.16)  0.86 (0.65–1.13)  3rd 79–130  434  1.07 (0.82–1.40)  1.08 (0.81 to1.45)      4th 126–190  759  0.97 (0.74–1.27)  0.96 (0.74–1.25)  4th 131–202  433  1.23 (0.97–1.56)  1.25 (0.93–1.67)      5th >190  758  0.67 (0.49–0.92)  0.67 (0.49–0.92)  5th >202  433  0.94 (0.71–1.23)  0.95 (0.71–1.27)      P for trend    0.067  0.110  P for trend    0.989  0.960  Moderate/vigorous      1st 0–7  759  Reference  Reference  1st 0–15  434  Reference  Reference      2nd 8–48  759  0.82 (0.62–1.08)  0.82 (0.62–1.08)  2nd 16–76  433  0.96 (0.78–1.18)  0.94 (0.74–1.19)      3rd 49–121  758  0.86 (0.64–1.16)  0.89 (0.69–1.15)  3rd 77–173  434  0.90 (0.70–1.16)  0.91 (0.70–1.19)      4th 122–256  759  0.59 (0.45–0.79)  0.63 (0.46–0.85)  4th 174–313  433  0.65 (0.52–0.82)  0.68 (0.54–0.87)      5th >256  758  0.61 (0.45–0.83)  0.65 (0.48–0.87)  5th >313  433  0.57 (0.43–0.75)  0.60 (0.46–0.77)      P for trend    <0.001  0.005  P for trend    <0.001  <0.001  Notes: LTPA, total leisure time physical activity; MET, Metabolic Equivalent of Task. a Values are hazard ratios (confidence interval). Model 1 was adjusted by sex and age and model 2 was adjusted for sex, age, diabetes, dyslipidemia, lipid-lowering treatment, hypertension, smoking, intervention group, education level, energy intake and level of adherence to Mediterranean diet. Additionally, light and moderate/vigorous LTPA were mutually adjusted. b General obesity was defined by a BMI above or equal to 30 km/m2. c Abdominal obesity was defined by a waist circumference above 88 cm in women and above 102 cm in men. Supplementary figures S1 and S2 show the dose-effect association of moderate/vigorous LTPA and BMI and WC, respectively, adjusted for sex, age, diabetes, hypercholesterolemia, lipid lowering treatment, hypertension, smoking, intervention group, educational level, cumulative average of energy intake, cumulative average of the Mediterranean diet adherence score and correspondingly adjusted for BMI and WC. We chose the minimum recommended level of moderate/vigorous LTPA of 500 METs·min/week (71.4 METs·min/day) as the reference value. β coefficients for differences (95% confidence interval) in BMI decrease linearly until 400 METs·min/day, where it starts to slightly increase. WC decreases linearly reaching a plateau at 600 METs·min/day. Discussion This prospective study showed that higher levels of total LTPA were consistently associated with lower BMI, WC and incidence of abdominal and general obesity. Moderate/vigorous-intensity LTPA showed similar results. Light-intensity LTPA was inversely associated with BMI and incidence of general obesity, but not with WC or incidence of abdominal obesity. Prospective evidence in populations younger than 60 years indicates a favorable impact of physical activity on controlling BMI and WC.25–27 A study with 288 498 individuals from 10 European countries evaluated the association between baseline total physical activity (categorized as inactive, moderately inactive, moderately active and active) and annual change in body weight, for a mean follow-up of 5.1 years. In individuals aged 50 years and older, they found that women with obesity, but not normal or overweight, who had a higher physical activity category at baseline had less weight gain. This association was not observed for men in any BMI category.25 The stronger effect size of physical activity on weight development in individuals with obesity was also found in the present study and is in concordance with other reports.27,28 This finding is especially relevant because obesity is associated with high risk of cardiometabolic disease,29 and these individuals would benefit the most from physical activity. A recent prospective study on 3670 British government employees with a mean age of 56 years showed that individuals classified in the top tertile of moderate/vigorous LTPA at baseline had a reduction in the incidence of obesity at 5 and 10 years of 30% and 33%, respectively, compared with the bottom baseline tertile.26 The magnitude of this risk reduction is comparable with that of the present study. Hamer et al.27 found that participants who meet the physical activity recommendations at all measurement points during follow-up have a lower BMI (−0.43 kg/m2) and WC (−2.50 cm), compared to those who infrequently meet it. The effect size of these observed associations was considerably lower than that of the present study. Findings from cross-sectional studies suggest an inverse association of BMI and WC30,31 with total and moderate/vigorous LTPA in older individuals; however, there is little prospective evidence. A 6 year follow-up study in 8352 postmenopausal women has provided evidence for the protective impact of physical activity on weight development in older populations.17 In participants aged 50–69 years, higher levels of LTPA were associated with less gain in fat mass, whereas in those aged 60–69 years it was associated with a greater loss in fat mass. Interestingly, in women aged 70–79 years, the loss in fat mass occurring in all categories was not associated with physical activity. The authors concluded that efforts to encourage physical activity in postmenopausal women may be more effective at younger ages. Additionally, a 13-year follow-up study in 34 079 women found that participants aged 55–64 years who were categorized in the lowest LTPA group gained significantly more weight than those in the highest LTPA category. This trend was not observed in women aged 65 years or older.18 In the present study, more than half of the individuals (54.1%) reported <500 METs of moderate/vigorous LTPA per week. This represents a high, but not exceptional32 prevalence of individuals not meeting the current recommendation for physical activity. Cross-sectional analyses have demonstrated that older individuals meeting the activity recommendations have a lower BMI and WC compared to those who did not.28,32 Prospective evidence from the present study shows a linear dose-effect relationship of moderate/vigorous LTPA with BMI and WC, which reached a point where it started to increase or formed a plateau, respectively. The increase in BMI after reaching 400 METs·min/day, as reported by 7% of the participants might have been due to gains in muscle mass. Frailty associated with older ages33 might impede many older individuals from engaging in moderate/vigorous physical activity. In fact, in the current study, individuals classified in the first three quintiles of total LTPA reported higher levels of light LTPA than moderate/vigorous LTPA, and only in the fifth quintile were the amounts of moderate/vigorous LTPA higher than light LTPA. Low-intensity physical activity may be a feasible physical activity selection for older adults. Therefore, it is important to note that low-intensity LTPA was associated with a considerable decrease in BMI and incidence of general obesity in the present study. Cross-sectional data on this relationship are inconsistent.30,34 Furthermore, a recent review, mostly of randomized clinical trials on the effect of low intensity physical activity on cardiovascular risk factors, found no improvement in body composition.35 The short-term intervention and generally only fair study design might explain this finding. The inverse association between LTPA (total and moderate/vigorous) with surrogate markers of body fat remained significant after adjustment for diet quality and energy intake. Since weight is directly affected by the balance of energy expenditure vs. energy consumed,36 these findings might be partially explained by the increase in carbohydrate and fat oxidation in the muscle that takes place during exercise.37 Studies including exercise interventions have suggested that higher intensity exercise decreases subcutaneous and visceral fat to a greater extent than exercises carried out at lower intensities.38,39 This could illustrate the greater association between moderately/vigorous LTPA and anthropometric measures, compared to light LTPA. Studies have also suggested that women with increasing exercise duration could have a greater capacity to oxidize intramyocellular lipids than men, and that women could rely to a greater extent on the use of plasma free fatty acids for fuel.40 This mechanism could explain why the inverse association of physical activity with BMI and WC was greater in women. The strengths of this study are the relatively large sample size of older adults, and the yearly measurement of anthropometric variables, diet and physical activity throughout the follow up. Furthermore, physical activity and dietary data were recorded using validated questionnaires. However, all instruments measuring past engagement in physical activity are vulnerable to measurement errors. Furthermore, measurement error of self-reported physical activity by the Minnesota Leisure Time Physical Activity Questionnaire is random, which may attenuate the results. The present study showed an inverse association between LTPA and BMI, WC and incidence of general and abdominal obesity, in older individuals at high cardiovascular risk. Moderate/vigorous LTPA was negatively associated with all four outcomes, whereas light-intensity LTPA was associated with BMI and the incidence of general obesity. The latter finding is of particular importance because light-intensity physical activity could be a feasible option for many older adults. Supplementary data Supplementary data are available at EURPUB online. Acknowledgement We appreciate the English revision by Elaine M. Lilly, PhD. Funding Centro de Investigación Biomédica en Red Fisiopatología de la Obesidad y Nutrición (CIBEROBN) and Epidemiologia y Salud Publica (CIBERESP) are an initiative of the Instituto de Salud Carlos III (ISCIII) of Spain which is supported by FEDER funds (CB06/03). This study was supported by the official funding agency for biomedical research of the Spanish government, ISCIII, through grants provided to research networks specifically developed for the trial (RTIC G03/140 and RD 06/0045) through CIBEROBN, and by grants from Centro Nacional de Investigaciones Cardiovasculares (CNIC 06/2007), Fondo de Investigación Sanitaria–Fondo Europeo de Desarrollo Regional (PI04–2239, PI05/2584, CP06/00100, PI07/0240, PI07/1138, PI07/0954, PI 07/0473, PI10/01407, PI10/02658, PI11/01647 and PI11/02505; PI13/00462), Ministerio de Ciencia e Innovación (AGL-2009-13906-C02 and AGL2010-22319-C03), Fundación Mapfre 2010, Consejería de Salud de la Junta de Andalucía (PI0105/2007), Public Health Division of the Department of Health of the Autonomous Government of Catalonia, Generalitat Valenciana (ACOMP06109, GVA-COMP2010-181, GVACOMP2011-151, CS2010-AP-111 and CS2011-AP-042), and the Navarra Regional Government (27/2011). The Fundación Patrimonio Comunal Olivarero and Hojiblanca SA (Málaga, Spain), California California Walnut Commission (Sacramento, CA), Borges SA (Reus, Spain) and Morella Nuts SA (Reus, Spain) donated the olive oil, walnuts, almonds and hazelnuts, respectively, used in the study. Conflicts of interest: E.R. and J.S.-S. are consultants for the California Walnut Commission and International Nut Council, respectively. None of the other authors reported a conflict of interest related to the study. Key points Total and moderate/vigorous leisure time physical activities were inversely associated with body mass index, waist circumference and incidence of general and abdominal obesity in older Spanish adults. Light- intensity leisure time physical activity showed an inverse association with body mass index and general obesity. 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The European Journal of Public HealthOxford University Press

Published: Mar 15, 2018

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