Atherosclerosis 234 (2014) 366e372
Contents lists available at ScienceDirect
Atherosclerosis journal homepage: www.elsevier.com/locate/atherosclerosis
Relationship between objectively measured physical activity and vascular structure and function in adults Manuel A. Gomez-Marcos a, b, c, *, José I. Recio-Rodríguez a, b, Maria C. Patino-Alonso a, b, d, Cristina Agudo-Conde a, b, Lourdes Lasaosa-Medina e, f, Emiliano Rodriguez-Sanchez a, b, c, José A. Maderuelo-Fernandez a, b, Luis García-Ortiz a, b, c, for the EVIDENT Group1 a
Primary Care Research Unit, The Alamedilla Health Center, Castilla and León Health ServiceeSACYL Salamanca, Spain REDIAPP, IBSAL, Spain Medicine Department, University of Salamanca, Salamanca, Spain d Statistics Department, University of Salamanca, Salamanca, Spain e CAP Passeig de Sant Joan, Barcelona, Spain f REDIAPP, Spain b c
a r t i c l e i n f o
a b s t r a c t
Article history: Received 26 November 2013 Received in revised form 27 February 2014 Accepted 28 February 2014 Available online 18 March 2014
Objectives: To analyze the relationship between regular physical activity, as assessed by accelerometer and 7-day physical activity recall (PAR) with vascular structure and function based on carotid intimamedia thickness, pulse wave velocity, central and peripheral augmentation index and the ambulatory arterial stiffness index in adults. Methods: This study analyzed 263 subjects who were included in the EVIDENT study (mean age 55.85 12.21 years; 59.30% female). Physical activity was assessed during 7 days using the Actigraph GT3X accelerometer (counts/minute) and 7-day PAR (metabolic equivalents (METs)/hour/week). Carotid ultrasound was used to measure carotid intima media thickness (IMT). The SphygmoCor System was used to measure pulse wave velocity (PWV), and central and peripheral augmentation index (CAIx and PAIx). The B-pro device was used to measure ambulatory arterial stiffness index (AASI). Results: Median counts/minute was 244.37 and mean METs/hour/week was 11.49. Physical activity showed an inverse correlation with PAIx (r ¼ 0.179; p < 0.01) and vigorous activity day time with IMT (r ¼ 0.174), CAIx (r ¼ 0.217) and PAIx (r ¼ 0.324) (p < 0.01, all). Sedentary activity day time was correlated positively with CAIx (r ¼ 0.103; p < 0.05). In multiple regression analysis, after adjusting for confounding factors, the inverse association of CAIx with counts/minute and the time spent in moderate and vigorous activity were maintained as well as the positive association with sedentary activity day time (p < 0.05). Conclusion: Physical activity, assessed by counts/minute, and the amount of time spent in moderate, vigorous/very vigorous physical activity, showed an inverse association with CAIx. Likewise, the time spent in sedentary activity was positively associated with the CAIx. Trial registration: Clinical Trials.gov Identifier: NCT01083082. Ó 2014 Elsevier Ireland Ltd. All rights reserved.
Keywords: Physical activity Vascular structure Vascular function
1. Introduction * Corresponding author. Research Unit, The Alamedilla Centre for Health, 37003 Salamanca, Spain. Tel.: þ34 923 290900x53552; fax: þ34 923 123644. E-mail addresses: [email protected] (M.A. Gomez-Marcos), donrecio@ gmail.com (J.I. Recio-Rodríguez), [email protected] (M.C. Patino-Alonso), [email protected] (C. Agudo-Conde), [email protected] (L. LasaosaMedina), [email protected] (E. Rodriguez-Sanchez), jmaderuelo@ saludcastillayleon.es (J.A. Maderuelo-Fernandez), [email protected] (L. García-Ortiz). 1 EVIDENT Group. redIAPP: Research Network on Preventive Activities and Health Promotion, Spain. http://dx.doi.org/10.1016/j.atherosclerosis.2014.02.028 0021-9150/Ó 2014 Elsevier Ireland Ltd. All rights reserved.
Participation in regular physical activity and/or aerobic exercise is associated with a decrease in all-cause, cardiovascular and cancer mortality [1e3], and a reduced risk of fatal and non-fatal coronary events in healthy individuals over a wide age range [4]. A sedentary lifestyle is one of the major risk factors for cardiovascular disease [5]. Physical inactivity is associated to an increased carotid intima media thickness (IMT) [6]. The RISC study [7] concluded that the
M.A. Gomez-Marcos et al. / Atherosclerosis 234 (2014) 366e372
proportion of time dedicated to sedentary activities was directly associated to baseline common carotid artery IMT, independently of age and established atherosclerotic risk factors. In the DNASCO study [8], aerobic physical exercise did not attenuate the progression of atherosclerosis. The studies that have analyzed the relationship between arterial stiffness and physical activity conclude that moderate physical activity in elderly people reduces the pulse wave velocity (PWV), particularly in hypertensive subjects [9]. Edwards et al. [10] found physical activity to be associated to PWV and to the central augmentation index (CAIx) in adolescents and young adults. RecioRodriguez et al. [11] published the time spent watching television to be directly correlated to the peripheral augmentation index (PAIx) in adults. On the other hand, Madura et al. [12] showed that the changes in arterial stiffness parameters due to aerobic exercise are reversible. Despite the predominant involvement of physical activity in cardiovascular prevention and rehabilitation strategies, the role of vascular structure and function has been less investigated. We therefore aimed to analyze the relationship between regular physical activity, as assessed by accelerometer and 7 physical activity recall (PAR)-day, with vascular structure and function based on carotid IMT, PWV, CAIx and peripheral augmentation index (PAIx), and the ambulatory arterial stiffness index (AASI) in adults. 2. Methods 2.1. Study design This study analyzed 263 subjects who were included in the EVIDENT study (NCT01083082) [13]. 2.2. Study population Subjects for the study were selected by stratified random sampling, including individuals ranging from 20 to 80 years of age who agreed to participate. The exclusion criteria for the study were: known coronary or cerebrovascular atherosclerotic disease, heart failure, moderate or severe chronic obstructive pulmonary disease, musculoskeletal disease that limited walking, advanced respiratory, renal, or hepatic disease, severe mental disease, treated oncological disease diagnosed in the 5 years before the start of the study, terminal disease, and pregnancy. Recruitment and data collection for the study were carried out from January 2011 to December 2011. The 263 participants with measures of vascular structure and function were sufficient to detect a difference of 0.05 mm in IMT between two of the three tertiles of physical activity evaluated as counts/minute in a two-sided test, assuming a common standard deviation (SD) of 0.10 mm with a significance level of 95% and a power of 80%. The study was approved by an independent ethics committee of Salamanca University Hospital, and all participants gave written informed consent according to the general recommendations of the Declaration of Helsinki [14]. 2.3. Measurements A detailed description has been published elsewhere regarding how the clinical data were collected, the anthropometric measurements were made and the analytical parameters were obtained [13]. 2.3.1. Physical activity Physical activity was estimated by accelerometer and the 7-day physical activity recall (PAR).
367
The ActiGraph GT3X accelerometers (ActiGraph, Shalimar, FL, USA), which have been previously validated [15e17]. ActiGraph is a monitor that uses a piezoelectric acceleration sensor to filter and convert the signals produced from the sensor in samples collected at a preset frequency in hertz. The samples are summed over a userspecified time sampling interval, called an “epoch”. Activity “counts” are recorded to the internal memory of accelerometers by converting acceleration units over a given epoch [18]. Subjects wore the accelerometer fastened with an elastic strap to the right side of the waist for 7 consecutive days involving regular physical activity, except for bathing and performing activities in the water. All subjects were verbally instructed on how to use the accelerometer. The accelerometer was set to record physical activity data every minute. The MAHUFFE software, available from: http://www. mrc-epid.cam.ac.uk/research/resources/materials-transferdisclaimer/physical-activity-downloads/(accessed: 30/12/2013), will be used to analyze the data. Sequences of 10 or more consecutive zero counts were considered non-wearing time and were excluded from the analyses. Inclusion criteria were a minimum of four days of recording, including at least one weekend day, and at least 600 registered minutes per day. The main outcome variable from the activity monitor was the average intensity of physical activity (counts/minute), calculated with equal weighting given to each day (regardless of registered time per day). The intensity of physical activity was determined according to the cut-off points proposed by Freedson [19], sedentary (5724 counts/minute), and very vigorous (>9498 counts/minute). Moderate-vigorous activity was considered as activity accumulated from all bouts lasting at least 1 min. The 7-day PAR is a general measure of physical activity, which has been recognized as a valid and reliable tool in recent years and is widely used in epidemiological, clinical and behavioral change studies [20]. It consists of a semi-structured interview (10e15 min) in which participants provide an estimate of the number of hours dedicated to physical or occupational activities that required at least a moderate effort over the previous 7 days. The dose of physical activity was estimated in mean metabolic equivalents (METs)/hour/week, and active persons were considered as those doing at least 30 min of moderate activity for five days a week or at least 20 min of hard activity for 3 days a week. Persons not reaching this level of physical activity were considered sedentary [21]. Reliability between 7-day PAR and accelerometer data was evaluated by correlation coefficient (CC) between METs/hour/week and counts/minute (r ¼ 0.397; p < 0.001). 2.3.2. Anthropometric measurements Body weight was determined on two occasions using a homologated electronic scale (Seca 770) following calibration (precision 0.1 kg), with the patient wearing light clothing and no shoes. Height in turn was measured with a portable system (Seca 222), recording the average of two readings. Body mass index (BMI) was calculated as weight (kg) divided by height squared (m2). A value of >30 kg/m2 was taken to define obesity. Finally, waist circumference was measured using a flexible graduated measuring tape with the patient in the standing position without clothing. 2.3.3. Office blood pressure Office blood pressure (BP) was calculated as the average of the last two of three measurements of sistolic blood pressure (SBP) and diastolic blood pressure (DBP) made with a validated sphygmomanometer (OMRON Model M10-IT). Measurements were made on the right upper arm of participants in the seated position after at least 5 min of rest, with a cuff of appropriate size as determined by
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M.A. Gomez-Marcos et al. / Atherosclerosis 234 (2014) 366e372
measurement of the upper-arm circumference, and following the recommendations of the European Society of Hypertension [22]. 2.3.4. Ambulatory blood pressure monitoring Ambulatory BP monitoring (ABPM) was done through radial artery tonometry on a day of standard activity in each patient. The instrument used for this purpose was a radial artery pulse-wave acquisition device (BPro, HealthSTATS International, Singapore) validated according to the protocol of the European Society of Hypertension, the Association for the Advancement of Medical Instrumentation, and the British Hypertension Society [23,24]. Records in which valid readings constituted 80% of all readings were considered acceptable. Valid registries were required to fulfill a series of pre-established criteria, including 80% successful SBP and DBP recordings during the day time and nighttime periods, 24h duration, and 1 BP measurement per hour. The monitor was programmed to obtain BP measurements every 15 min during the day time and nighttime. The ambulatory arterial stiffness index (AASI) for evaluating vascular function was defined as 1 minus the regression slope of DBP over SBP readings obtained from individual 24-h blood pressure recordings with the BPro device. The stiffer the arterial tree, the closer the regression slope and AASI were to 0 and 1, respectively [25]. 2.3.5. Pulse wave velocity (PWV) and peripheral (PAIx) and central augmentation index (CAIx) These parameters were estimated using the SphygmoCor System (AtCor Medica lPty Ltd., Head Office, West Ryde, Australia). The central augmentation index (CAIx) is a composite index that integrates the amount of the wave that is reflected back to the aorta depending on the tone of the resistance arteries, which are the main peripheral reflecting sites. The contribution of the backward wave to pulse pressure is related to the timing of its superimposition onto the forward wave, as well as to its magnitude and shape. Conditions of markedly increased arterial stiffness are characterized by an early superimposition of backward waves onto the forward wave, causing an increase in central SBP [26]. Assessment of CAIx has, thus, been proposed as a simple approach to quantify the role of wave reflection in determining an elevation of central blood pressure values. The Augmentation index value decreases as BMI increases and increases with the age [26e28]. Using the above system (Px Pulse Wave Analysis) with the patient in the sitting position and resting the arm on a rigid surface, pulse wave analysis was performed with a sensor in the radial artery, using mathematical transformation to estimate the aortic pulse wave. The reliability of these measurements was evaluated before the study using the CAIx intra-class correlation coefficient, which showed values of 0.97 (95% CI: 0.94e0.99) for intra-observer agreement on repeated measurements in 22 subjects. According to the BlandAltman analysis, the mean difference for intraobserver agreement (95% limits of agreement) was 0.45 (9.88e10.79). From the morphology of the aortic wave, CAIx was estimated using the following formula: increase in central pressure 100/pulse pressure. We adjusted CAIx to 75 bpm heart rate. The peripheral augmentation index (PAIx) is a measurement taken directly from the late systolic shoulder of the peripheral arterial waveform, and is defined as the ratio of the difference in amplitude between the second peak and diastolic pressure to the difference between the first peak and diastolic pressure [29]. The PAIx was calculated as second peak SBP (SBP2) e DBP/first peak SBPeDBP 100, to yield a percent (%) value. Because PAIx is affected by heart rate (HR), its values were standardized to an HR of 75 bpm according to the following equation: PAIx75 ¼ PAIx (HR/75).
Using the SphygmoCor System, and with the patient in the supine position, the pulse waves of the carotid and femoral arteries were analyzed, estimating the delay with respect to the ECG wave and calculating PWV. Distance measurements were taken with a measuring tape from the sternal notch to the carotid and femoral arteries at the sensor location [30]. 2.3.6. Assessment of vascular structure by carotid intima media thickness (IMT) Carotid ultrasound to assess carotid IMT was performed by two investigators trained for this purpose before starting the study. The reliability of such recordings was evaluated before the study, using the intra-class correlation coefficient, which showed values of 0.97 (95%CI: 0.94e0.99) for intra-observer agreement on repeated measurements in 20 subjects, and 0.90 (95%CI: 0.74e0.96) for interobserver agreement. According to the Bland-Altman analysis, the mean difference for interobserver agreement (95% limits of agreement) was 0.01 (0.03e0.06). A Sonosite Micromax ultrasound device paired with a 5e10 MHz multi-frequency high-resolution linear transducer with Sonocal software was used for performing automatic measurements of IMT in order to optimize reproducibility. Measurements were made of the common carotid after the examination of a 10-mm longitudinal section at a distance of 1 cm from the bifurcation, performing measurements in the anterior or proximal wall, and in the posterior or distal wall in the lateral, anterior and posterior projections, following an axis perpendicular to the artery to discriminate two lines: one for the intimaeblood interface and the other for the media-adventitious interface. A total of 6 measurements were obtained of the right carotid, with another 6 measurements of the left carotid, using average values (average IMT) automatically calculated by the software [31]. The measurements were obtained with the subject lying down, with the head extended and slightly turned opposite to the examined carotid artery. The individuals performing the different tests were blinded to the clinical data of the patient. All organ damage assessments were made within a period of 10 days. 3. Statistical analysis Continuous variables were expressed as the mean standard deviation for normally distributed continuous data, the median (interquartile range, IQR) for asymmetrically distributed continuous data, and the frequency distribution for categorical data. Statistical normality was tested using the KolmogoroveSmirnov test. A Spearman’s correlation was used to analyze the relationship between asymmetrically distributed continuous data. We performed 5 multiple linear regression analyses, one for each of the dependent variables, IMT 100 (to facilitate interpretation), PAIx, CAIx, AASI 100 (to facilitate interpretation) and PWV as dependent variables, and six models one for each of the independent (counts/minute, sedentary activity day time, light activity day time, moderate activity day time, vigorous or very vigorous activity intensity and METs/hour/week), based on a multivariate general lineal model (GLM). We adjusted the models by age, sex, smoking status, SBP, waist circumference, presence of diabetes mellitus, antihypertensive drugs and lipid-lowering drugs. The statistical differences between counts/minute in tertiles of dependent variables were assessed using multivariate analysis of variance (MANOVA). The Scheffé method was used to adjust for multiple pairwise comparisons. The data were analyzed using the Statistical Package for the Social Sciences version 20.0 (SPSS, Chicago, IL, USA). A value of p < 0.05 was considered statistically significant.
M.A. Gomez-Marcos et al. / Atherosclerosis 234 (2014) 366e372
4. Results
Table 2 Physical exercise assessment by accelerometer.
We studied 263 subjects with a mean age of 55.85 12.21 years, of which 59.30% were females. Table 1 shows the demographic and clinical characteristics and mean values of the parameters used for evaluating the vascular structure and function of the study patients. The evaluation of physical exercise made with the accelerometer yielded a median of 244.37 counts/minute (195.48e325.48), 54.16 27.31 min/day of moderate physical activity, and 2.63 10.26 min/day of vigorous or very vigorous activity, and with the 7 day PAR yielded a mean of 11.49 23.35 METs/hour/week. The percentage of sedentary subjects was 80.2% (Table 2). Subjects performing vigorous or very vigorous physical activity had lower mean values in all parameters of vascular structure and function analyzed, compared to the group that does not perform vigorous activity, especially in the CAIx_75 and PAIx_75 (p < 0.01), (Table 3). Table 4 shows the correlations of the parameters that evaluate physical activity with the variables used to assess vascular structure and function. Physical activity, as assessed by counts/minute, showed an inverse correlation with PAIx (r ¼ 0.179; p < 0.01) and AASI (r ¼ 0.142; p < 0.05) and assessed by METs/hour/week, with PAIx (r ¼ 0.132; p < 0.05) and a positive correlation with AASI (r ¼ 0.168; p < 0.01). Likewise sedentary activity time showed a positive correlation with CAIx (r ¼ 0.103; p < 0.05) and with PWV (r ¼ 0.171; p < 0.01). Light activity time showed a positive correlation with PWV (r ¼ 0.184; p < 0.01) and Moderate activity time with AASI (r ¼ 0.186; p < 0.01). Finally, vigorous activity day time showed an inverse correlation with IMT (r ¼ 0.174), CAIx (r ¼ 0.217) and PAIx (r ¼ 0.324) (p < 0.01, all).
Table 1 Baseline demographic and clinical characteristics of patients.
Age. (years) Female. n (%) Smoking. n (%) Body mass index. (kg/m2) Waist circumference, cm Obesity. n (%) Office SBP. (mmHg) Office DBP. (mmHg) Hypertension. n (%) SBP 24 h hours. (mmHg) DBP 24 h hours. (mmHg) Antihypertensive Drugs. n (%) Fasting glucose. (mg/dL) Diabetes. n (%) Oral antidiabetic drugs. n (%) Total cholesterol. (mg/dL) Triglycerides. (mg/dL) HDL-cholesterol. (mg/dL) LDL-cholesterol. (mg/dL) Dyslipidemia. n (%) Lipid lowering drugs. n (%) Carotid mean IMT. (mm) CAIx 75HR. (%) PAIx 75HR (%) PWV. (m/s) AASI
369
Mean/median/number
SD/IQR/ (%)
55.85 146 54 26.74 92 54 120 77 105 116 77 76 85 18 12 213 91 56 132 72 43 0.68 27.91 81.15 7.10 0.42
12.21 (59.30) (20.50) 24.16e29.54 86.00e98.25 (20.50) 17 11 (39.90) 18 12 (28.90) 80e93 (6.80) (4.60) 38 67e133 47e68 33 (27.40) 16.30 0.10 11.51 71.16e92.01 6.20e8.60 0.05
Values are means (standard deviations (SD)) for normally distributed continuous data and medians (interquartile range (IQR)) for asymmetrically distributed continuous data and number and proportions for categorical data. SBP: Systolic Blood Pressure. DBP: Diastolic Blood Pressure. HDL: High Density Lipoprotein. LDL: Low Density Lipoprotein. IMT: Intima Media Thickness. CAIx: Central Augmentation Index corrected for heart rate; PAIx: Peripheral Augmentation Index corrected for heart rate. PWV: Pulse Wave Velocity. AASI: Ambulatory Arterial Stiffness Index.
Accelerometer
Mean/Median
SD/IQR
Counts/min. Sedentary activity. (min/day) Sedentary activity/awake. (min/day) Low activity. (min/day) Moderate activity. (min/day) Vigorous intensity activity (min/day) 7-day-PAR METs/hour/week Sedentary n (%) Active n (%)
244.37 1073.52 655.92 314.12 54.16 2.63
195.48e325.48 97.75 97.75 91.57 27.31 10.26
11.49 211 52
23.35 80.2 19.8
Values are medians and interquartile range (IQR). min: minute. The intensity of physical activity was determined according to the cut-off points proposed by Freedson: Sedentary (5724 counts min) and very vigorous (>9498 counts min). Vigorous intensity activity include vigorous and very vigorous. METs: metabolic equivalent. Active were considered as those doing at least 30 min of moderate activity, five days a week, or at least 20 min of hard activity, 3 days a week.
Fig. 1 represents the parameters of vascular function and structure in relation to the physical activity tertiles according to counts/minute. The values of PAIx, CAIx, AASI and PWV had lower values in the tertiles that perform more physical activity. A multiple linear regression analysis was carried out. CAIx maintained the inverse association with the counts/minute (b ¼ 0.007; p < 0.01), and with the time spent in moderate (b ¼ 0.015; p ¼ 0.04) and in vigorous/very vigorous intensity activity (b ¼ 0.127; p ¼ 0.05). Likewise, CAIx maintained the positive association with the time spent in sedentary activity (b ¼ 0.015; p ¼ 0.03). Furthermore, an inverse association was observed of AASI with the METs/hour/week (b ¼ 0.039; p ¼ 0.01) and the time spent in moderate intensity activity (b ¼ 0.041; p ¼ 0.01) (Table 5). 5. Discussion In this study, physical activity, assessed by counts/minute, and the time spent in moderate and vigorous/very vigorous activity showed an inverse association with the CAIx. Likewise, the time spent in sedentary activity, showed a positive association with the CAIx. In summary, increased physical activity and more time spent in activities of moderate, vigorous/very vigorous intensity the CAIx was lower. Likewise the longer time spent in sedentary activities the CAIx was greater. Our results are consistent with those published by Edwards et el [10]. in adolescents and young adults. In this study, and after
Table 3 Parameters of vascular structure and function according to the intensity of physical activity performed. Vigorous or very vigorous physical activity Carotid IMT. (mm) CAIx_75. (%) PAIx_75. (%) PWV. (m/s) AASI
No
Yes
0.69
0.66
30.54 88.35 7.83 0.427
24.95 75.97 7.34 0.416
p value 0.05 0 9498 counts min). IMT: Intima Media Thickness. CAIx: Central Augmentation Index corrected for heart rate; PAIx: Peripheral Augmentation Index corrected for heart rate. PWV: Pulse Wave Velocity. AASI: Ambulatory Arterial Stiffness Index. METs: metabolic equivalent. P-values by Spearman correlation and Pearson correlation. *p < 0.05, **p < 0.01.
adjusting for demographic variables and other cardiovascular risk factors, physical activity showed an inverse association with the augmentation index. The studies that have analyzed the relationship between arterial stiffness and physical activity concluded that moderate physical activity in elderly people reduces PWV, particularly in hypertensive subjects [10]. On the other hand, in adolescents and young adults, Edwards et al. [10] found PWV to be greater in the tertile performing less physical activity, with the description of an independent association only among the participants with type 2 diabetes mellitus (DM2). Sakuragi et al. [32], in a study of 573 children in Australia in which physical activity was measured with a pedometer, found an inverse correlation with PWV. These results agree with the findings of our own study, in which the different measures used to assess arterial stiffness (PWV and AASI) showed greater values in the tertile of individuals with less physical activitye though significance was lost on adjusting for confounding factors. However, Tanaka et al. [33] found no association between PWV and physical activity in 53 adult women. van de Laar RJ et al. [34] and Sugawara et al. [35] only recorded this association in those who performed intense or very intense activity, in contrast to the findings of our study. The different publications that have analyzed the relationship between vascular function and physical activity have not produced uniform results. This suggests that the relationship can be
Fig. 1. Values corresponding to ambulatory arterial stiffness index; peripheral augmentation index corrected for heart rate; central augmentation index corrected for heart rate; pulse wave velocity and intima-media thickness according to the count/minute by tertiles: (T1 < 210.98; T2: 210.99e292.97; T3 > 292.98).
M.A. Gomez-Marcos et al. / Atherosclerosis 234 (2014) 366e372 Table 5 Multiple Regression Analysis with vascular structure and function parameters as dependent variable and physical activity as independent variable. Dependent variable: IMT mean
b
IC 95%
Physical activity counts/minute Physical activity METs/hour/week Sedentary activity day time Light activity day time Moderate activity day time Vigorous activity day time PAIX/75HR Physical activity Counts/minute Physical activity METs/hour/week Sedentary activity day time Light activity day time Moderate activity day time Vigorous activity day time CAIX/75HR Physical activity counts/minute Physical activity METs/hour/week Sedentary activity day time Light activity day time Moderate activity day time Vigorous activity day time AASI Physical activity counts/minute Physical activity METs/hour/week Sedentary activity day time Light activity day time Moderate activity day time Vigorous activity day time PWV Physical activity counts/minute Physical activity METs/hour/week Sedentary activity day time Light activity day time Moderate activity day time Vigorous activity day time
0.004 0.028 0.006 0.005 0.016 0.068
0.001 0.013 0.017 0.006 0.020 0.030
0.008 0.068 0.004 0.016 0.053 0.165
0.10 0.18 0.24 0.37 0.38 0.17
0.007 0.012 0.015 0.005 0.070 0.142
0.018 0.106 0.010 0.031 0.156 0.372
0.003 0.083 0.039 0.022 0.016 0.088
0.16 0.81 0.24 0.72 0.11 0.22
0.007 0.017 0.015 0.009 0.015 0.127
0.013 0.037 0.001 0.040 0.030 0.257
0.001 0.071 0.029 0.059 0.000 0.004
Contents lists available at ScienceDirect
Atherosclerosis journal homepage: www.elsevier.com/locate/atherosclerosis
Relationship between objectively measured physical activity and vascular structure and function in adults Manuel A. Gomez-Marcos a, b, c, *, José I. Recio-Rodríguez a, b, Maria C. Patino-Alonso a, b, d, Cristina Agudo-Conde a, b, Lourdes Lasaosa-Medina e, f, Emiliano Rodriguez-Sanchez a, b, c, José A. Maderuelo-Fernandez a, b, Luis García-Ortiz a, b, c, for the EVIDENT Group1 a
Primary Care Research Unit, The Alamedilla Health Center, Castilla and León Health ServiceeSACYL Salamanca, Spain REDIAPP, IBSAL, Spain Medicine Department, University of Salamanca, Salamanca, Spain d Statistics Department, University of Salamanca, Salamanca, Spain e CAP Passeig de Sant Joan, Barcelona, Spain f REDIAPP, Spain b c
a r t i c l e i n f o
a b s t r a c t
Article history: Received 26 November 2013 Received in revised form 27 February 2014 Accepted 28 February 2014 Available online 18 March 2014
Objectives: To analyze the relationship between regular physical activity, as assessed by accelerometer and 7-day physical activity recall (PAR) with vascular structure and function based on carotid intimamedia thickness, pulse wave velocity, central and peripheral augmentation index and the ambulatory arterial stiffness index in adults. Methods: This study analyzed 263 subjects who were included in the EVIDENT study (mean age 55.85 12.21 years; 59.30% female). Physical activity was assessed during 7 days using the Actigraph GT3X accelerometer (counts/minute) and 7-day PAR (metabolic equivalents (METs)/hour/week). Carotid ultrasound was used to measure carotid intima media thickness (IMT). The SphygmoCor System was used to measure pulse wave velocity (PWV), and central and peripheral augmentation index (CAIx and PAIx). The B-pro device was used to measure ambulatory arterial stiffness index (AASI). Results: Median counts/minute was 244.37 and mean METs/hour/week was 11.49. Physical activity showed an inverse correlation with PAIx (r ¼ 0.179; p < 0.01) and vigorous activity day time with IMT (r ¼ 0.174), CAIx (r ¼ 0.217) and PAIx (r ¼ 0.324) (p < 0.01, all). Sedentary activity day time was correlated positively with CAIx (r ¼ 0.103; p < 0.05). In multiple regression analysis, after adjusting for confounding factors, the inverse association of CAIx with counts/minute and the time spent in moderate and vigorous activity were maintained as well as the positive association with sedentary activity day time (p < 0.05). Conclusion: Physical activity, assessed by counts/minute, and the amount of time spent in moderate, vigorous/very vigorous physical activity, showed an inverse association with CAIx. Likewise, the time spent in sedentary activity was positively associated with the CAIx. Trial registration: Clinical Trials.gov Identifier: NCT01083082. Ó 2014 Elsevier Ireland Ltd. All rights reserved.
Keywords: Physical activity Vascular structure Vascular function
1. Introduction * Corresponding author. Research Unit, The Alamedilla Centre for Health, 37003 Salamanca, Spain. Tel.: þ34 923 290900x53552; fax: þ34 923 123644. E-mail addresses: [email protected] (M.A. Gomez-Marcos), donrecio@ gmail.com (J.I. Recio-Rodríguez), [email protected] (M.C. Patino-Alonso), [email protected] (C. Agudo-Conde), [email protected] (L. LasaosaMedina), [email protected] (E. Rodriguez-Sanchez), jmaderuelo@ saludcastillayleon.es (J.A. Maderuelo-Fernandez), [email protected] (L. García-Ortiz). 1 EVIDENT Group. redIAPP: Research Network on Preventive Activities and Health Promotion, Spain. http://dx.doi.org/10.1016/j.atherosclerosis.2014.02.028 0021-9150/Ó 2014 Elsevier Ireland Ltd. All rights reserved.
Participation in regular physical activity and/or aerobic exercise is associated with a decrease in all-cause, cardiovascular and cancer mortality [1e3], and a reduced risk of fatal and non-fatal coronary events in healthy individuals over a wide age range [4]. A sedentary lifestyle is one of the major risk factors for cardiovascular disease [5]. Physical inactivity is associated to an increased carotid intima media thickness (IMT) [6]. The RISC study [7] concluded that the
M.A. Gomez-Marcos et al. / Atherosclerosis 234 (2014) 366e372
proportion of time dedicated to sedentary activities was directly associated to baseline common carotid artery IMT, independently of age and established atherosclerotic risk factors. In the DNASCO study [8], aerobic physical exercise did not attenuate the progression of atherosclerosis. The studies that have analyzed the relationship between arterial stiffness and physical activity conclude that moderate physical activity in elderly people reduces the pulse wave velocity (PWV), particularly in hypertensive subjects [9]. Edwards et al. [10] found physical activity to be associated to PWV and to the central augmentation index (CAIx) in adolescents and young adults. RecioRodriguez et al. [11] published the time spent watching television to be directly correlated to the peripheral augmentation index (PAIx) in adults. On the other hand, Madura et al. [12] showed that the changes in arterial stiffness parameters due to aerobic exercise are reversible. Despite the predominant involvement of physical activity in cardiovascular prevention and rehabilitation strategies, the role of vascular structure and function has been less investigated. We therefore aimed to analyze the relationship between regular physical activity, as assessed by accelerometer and 7 physical activity recall (PAR)-day, with vascular structure and function based on carotid IMT, PWV, CAIx and peripheral augmentation index (PAIx), and the ambulatory arterial stiffness index (AASI) in adults. 2. Methods 2.1. Study design This study analyzed 263 subjects who were included in the EVIDENT study (NCT01083082) [13]. 2.2. Study population Subjects for the study were selected by stratified random sampling, including individuals ranging from 20 to 80 years of age who agreed to participate. The exclusion criteria for the study were: known coronary or cerebrovascular atherosclerotic disease, heart failure, moderate or severe chronic obstructive pulmonary disease, musculoskeletal disease that limited walking, advanced respiratory, renal, or hepatic disease, severe mental disease, treated oncological disease diagnosed in the 5 years before the start of the study, terminal disease, and pregnancy. Recruitment and data collection for the study were carried out from January 2011 to December 2011. The 263 participants with measures of vascular structure and function were sufficient to detect a difference of 0.05 mm in IMT between two of the three tertiles of physical activity evaluated as counts/minute in a two-sided test, assuming a common standard deviation (SD) of 0.10 mm with a significance level of 95% and a power of 80%. The study was approved by an independent ethics committee of Salamanca University Hospital, and all participants gave written informed consent according to the general recommendations of the Declaration of Helsinki [14]. 2.3. Measurements A detailed description has been published elsewhere regarding how the clinical data were collected, the anthropometric measurements were made and the analytical parameters were obtained [13]. 2.3.1. Physical activity Physical activity was estimated by accelerometer and the 7-day physical activity recall (PAR).
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The ActiGraph GT3X accelerometers (ActiGraph, Shalimar, FL, USA), which have been previously validated [15e17]. ActiGraph is a monitor that uses a piezoelectric acceleration sensor to filter and convert the signals produced from the sensor in samples collected at a preset frequency in hertz. The samples are summed over a userspecified time sampling interval, called an “epoch”. Activity “counts” are recorded to the internal memory of accelerometers by converting acceleration units over a given epoch [18]. Subjects wore the accelerometer fastened with an elastic strap to the right side of the waist for 7 consecutive days involving regular physical activity, except for bathing and performing activities in the water. All subjects were verbally instructed on how to use the accelerometer. The accelerometer was set to record physical activity data every minute. The MAHUFFE software, available from: http://www. mrc-epid.cam.ac.uk/research/resources/materials-transferdisclaimer/physical-activity-downloads/(accessed: 30/12/2013), will be used to analyze the data. Sequences of 10 or more consecutive zero counts were considered non-wearing time and were excluded from the analyses. Inclusion criteria were a minimum of four days of recording, including at least one weekend day, and at least 600 registered minutes per day. The main outcome variable from the activity monitor was the average intensity of physical activity (counts/minute), calculated with equal weighting given to each day (regardless of registered time per day). The intensity of physical activity was determined according to the cut-off points proposed by Freedson [19], sedentary (5724 counts/minute), and very vigorous (>9498 counts/minute). Moderate-vigorous activity was considered as activity accumulated from all bouts lasting at least 1 min. The 7-day PAR is a general measure of physical activity, which has been recognized as a valid and reliable tool in recent years and is widely used in epidemiological, clinical and behavioral change studies [20]. It consists of a semi-structured interview (10e15 min) in which participants provide an estimate of the number of hours dedicated to physical or occupational activities that required at least a moderate effort over the previous 7 days. The dose of physical activity was estimated in mean metabolic equivalents (METs)/hour/week, and active persons were considered as those doing at least 30 min of moderate activity for five days a week or at least 20 min of hard activity for 3 days a week. Persons not reaching this level of physical activity were considered sedentary [21]. Reliability between 7-day PAR and accelerometer data was evaluated by correlation coefficient (CC) between METs/hour/week and counts/minute (r ¼ 0.397; p < 0.001). 2.3.2. Anthropometric measurements Body weight was determined on two occasions using a homologated electronic scale (Seca 770) following calibration (precision 0.1 kg), with the patient wearing light clothing and no shoes. Height in turn was measured with a portable system (Seca 222), recording the average of two readings. Body mass index (BMI) was calculated as weight (kg) divided by height squared (m2). A value of >30 kg/m2 was taken to define obesity. Finally, waist circumference was measured using a flexible graduated measuring tape with the patient in the standing position without clothing. 2.3.3. Office blood pressure Office blood pressure (BP) was calculated as the average of the last two of three measurements of sistolic blood pressure (SBP) and diastolic blood pressure (DBP) made with a validated sphygmomanometer (OMRON Model M10-IT). Measurements were made on the right upper arm of participants in the seated position after at least 5 min of rest, with a cuff of appropriate size as determined by
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measurement of the upper-arm circumference, and following the recommendations of the European Society of Hypertension [22]. 2.3.4. Ambulatory blood pressure monitoring Ambulatory BP monitoring (ABPM) was done through radial artery tonometry on a day of standard activity in each patient. The instrument used for this purpose was a radial artery pulse-wave acquisition device (BPro, HealthSTATS International, Singapore) validated according to the protocol of the European Society of Hypertension, the Association for the Advancement of Medical Instrumentation, and the British Hypertension Society [23,24]. Records in which valid readings constituted 80% of all readings were considered acceptable. Valid registries were required to fulfill a series of pre-established criteria, including 80% successful SBP and DBP recordings during the day time and nighttime periods, 24h duration, and 1 BP measurement per hour. The monitor was programmed to obtain BP measurements every 15 min during the day time and nighttime. The ambulatory arterial stiffness index (AASI) for evaluating vascular function was defined as 1 minus the regression slope of DBP over SBP readings obtained from individual 24-h blood pressure recordings with the BPro device. The stiffer the arterial tree, the closer the regression slope and AASI were to 0 and 1, respectively [25]. 2.3.5. Pulse wave velocity (PWV) and peripheral (PAIx) and central augmentation index (CAIx) These parameters were estimated using the SphygmoCor System (AtCor Medica lPty Ltd., Head Office, West Ryde, Australia). The central augmentation index (CAIx) is a composite index that integrates the amount of the wave that is reflected back to the aorta depending on the tone of the resistance arteries, which are the main peripheral reflecting sites. The contribution of the backward wave to pulse pressure is related to the timing of its superimposition onto the forward wave, as well as to its magnitude and shape. Conditions of markedly increased arterial stiffness are characterized by an early superimposition of backward waves onto the forward wave, causing an increase in central SBP [26]. Assessment of CAIx has, thus, been proposed as a simple approach to quantify the role of wave reflection in determining an elevation of central blood pressure values. The Augmentation index value decreases as BMI increases and increases with the age [26e28]. Using the above system (Px Pulse Wave Analysis) with the patient in the sitting position and resting the arm on a rigid surface, pulse wave analysis was performed with a sensor in the radial artery, using mathematical transformation to estimate the aortic pulse wave. The reliability of these measurements was evaluated before the study using the CAIx intra-class correlation coefficient, which showed values of 0.97 (95% CI: 0.94e0.99) for intra-observer agreement on repeated measurements in 22 subjects. According to the BlandAltman analysis, the mean difference for intraobserver agreement (95% limits of agreement) was 0.45 (9.88e10.79). From the morphology of the aortic wave, CAIx was estimated using the following formula: increase in central pressure 100/pulse pressure. We adjusted CAIx to 75 bpm heart rate. The peripheral augmentation index (PAIx) is a measurement taken directly from the late systolic shoulder of the peripheral arterial waveform, and is defined as the ratio of the difference in amplitude between the second peak and diastolic pressure to the difference between the first peak and diastolic pressure [29]. The PAIx was calculated as second peak SBP (SBP2) e DBP/first peak SBPeDBP 100, to yield a percent (%) value. Because PAIx is affected by heart rate (HR), its values were standardized to an HR of 75 bpm according to the following equation: PAIx75 ¼ PAIx (HR/75).
Using the SphygmoCor System, and with the patient in the supine position, the pulse waves of the carotid and femoral arteries were analyzed, estimating the delay with respect to the ECG wave and calculating PWV. Distance measurements were taken with a measuring tape from the sternal notch to the carotid and femoral arteries at the sensor location [30]. 2.3.6. Assessment of vascular structure by carotid intima media thickness (IMT) Carotid ultrasound to assess carotid IMT was performed by two investigators trained for this purpose before starting the study. The reliability of such recordings was evaluated before the study, using the intra-class correlation coefficient, which showed values of 0.97 (95%CI: 0.94e0.99) for intra-observer agreement on repeated measurements in 20 subjects, and 0.90 (95%CI: 0.74e0.96) for interobserver agreement. According to the Bland-Altman analysis, the mean difference for interobserver agreement (95% limits of agreement) was 0.01 (0.03e0.06). A Sonosite Micromax ultrasound device paired with a 5e10 MHz multi-frequency high-resolution linear transducer with Sonocal software was used for performing automatic measurements of IMT in order to optimize reproducibility. Measurements were made of the common carotid after the examination of a 10-mm longitudinal section at a distance of 1 cm from the bifurcation, performing measurements in the anterior or proximal wall, and in the posterior or distal wall in the lateral, anterior and posterior projections, following an axis perpendicular to the artery to discriminate two lines: one for the intimaeblood interface and the other for the media-adventitious interface. A total of 6 measurements were obtained of the right carotid, with another 6 measurements of the left carotid, using average values (average IMT) automatically calculated by the software [31]. The measurements were obtained with the subject lying down, with the head extended and slightly turned opposite to the examined carotid artery. The individuals performing the different tests were blinded to the clinical data of the patient. All organ damage assessments were made within a period of 10 days. 3. Statistical analysis Continuous variables were expressed as the mean standard deviation for normally distributed continuous data, the median (interquartile range, IQR) for asymmetrically distributed continuous data, and the frequency distribution for categorical data. Statistical normality was tested using the KolmogoroveSmirnov test. A Spearman’s correlation was used to analyze the relationship between asymmetrically distributed continuous data. We performed 5 multiple linear regression analyses, one for each of the dependent variables, IMT 100 (to facilitate interpretation), PAIx, CAIx, AASI 100 (to facilitate interpretation) and PWV as dependent variables, and six models one for each of the independent (counts/minute, sedentary activity day time, light activity day time, moderate activity day time, vigorous or very vigorous activity intensity and METs/hour/week), based on a multivariate general lineal model (GLM). We adjusted the models by age, sex, smoking status, SBP, waist circumference, presence of diabetes mellitus, antihypertensive drugs and lipid-lowering drugs. The statistical differences between counts/minute in tertiles of dependent variables were assessed using multivariate analysis of variance (MANOVA). The Scheffé method was used to adjust for multiple pairwise comparisons. The data were analyzed using the Statistical Package for the Social Sciences version 20.0 (SPSS, Chicago, IL, USA). A value of p < 0.05 was considered statistically significant.
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4. Results
Table 2 Physical exercise assessment by accelerometer.
We studied 263 subjects with a mean age of 55.85 12.21 years, of which 59.30% were females. Table 1 shows the demographic and clinical characteristics and mean values of the parameters used for evaluating the vascular structure and function of the study patients. The evaluation of physical exercise made with the accelerometer yielded a median of 244.37 counts/minute (195.48e325.48), 54.16 27.31 min/day of moderate physical activity, and 2.63 10.26 min/day of vigorous or very vigorous activity, and with the 7 day PAR yielded a mean of 11.49 23.35 METs/hour/week. The percentage of sedentary subjects was 80.2% (Table 2). Subjects performing vigorous or very vigorous physical activity had lower mean values in all parameters of vascular structure and function analyzed, compared to the group that does not perform vigorous activity, especially in the CAIx_75 and PAIx_75 (p < 0.01), (Table 3). Table 4 shows the correlations of the parameters that evaluate physical activity with the variables used to assess vascular structure and function. Physical activity, as assessed by counts/minute, showed an inverse correlation with PAIx (r ¼ 0.179; p < 0.01) and AASI (r ¼ 0.142; p < 0.05) and assessed by METs/hour/week, with PAIx (r ¼ 0.132; p < 0.05) and a positive correlation with AASI (r ¼ 0.168; p < 0.01). Likewise sedentary activity time showed a positive correlation with CAIx (r ¼ 0.103; p < 0.05) and with PWV (r ¼ 0.171; p < 0.01). Light activity time showed a positive correlation with PWV (r ¼ 0.184; p < 0.01) and Moderate activity time with AASI (r ¼ 0.186; p < 0.01). Finally, vigorous activity day time showed an inverse correlation with IMT (r ¼ 0.174), CAIx (r ¼ 0.217) and PAIx (r ¼ 0.324) (p < 0.01, all).
Table 1 Baseline demographic and clinical characteristics of patients.
Age. (years) Female. n (%) Smoking. n (%) Body mass index. (kg/m2) Waist circumference, cm Obesity. n (%) Office SBP. (mmHg) Office DBP. (mmHg) Hypertension. n (%) SBP 24 h hours. (mmHg) DBP 24 h hours. (mmHg) Antihypertensive Drugs. n (%) Fasting glucose. (mg/dL) Diabetes. n (%) Oral antidiabetic drugs. n (%) Total cholesterol. (mg/dL) Triglycerides. (mg/dL) HDL-cholesterol. (mg/dL) LDL-cholesterol. (mg/dL) Dyslipidemia. n (%) Lipid lowering drugs. n (%) Carotid mean IMT. (mm) CAIx 75HR. (%) PAIx 75HR (%) PWV. (m/s) AASI
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Mean/median/number
SD/IQR/ (%)
55.85 146 54 26.74 92 54 120 77 105 116 77 76 85 18 12 213 91 56 132 72 43 0.68 27.91 81.15 7.10 0.42
12.21 (59.30) (20.50) 24.16e29.54 86.00e98.25 (20.50) 17 11 (39.90) 18 12 (28.90) 80e93 (6.80) (4.60) 38 67e133 47e68 33 (27.40) 16.30 0.10 11.51 71.16e92.01 6.20e8.60 0.05
Values are means (standard deviations (SD)) for normally distributed continuous data and medians (interquartile range (IQR)) for asymmetrically distributed continuous data and number and proportions for categorical data. SBP: Systolic Blood Pressure. DBP: Diastolic Blood Pressure. HDL: High Density Lipoprotein. LDL: Low Density Lipoprotein. IMT: Intima Media Thickness. CAIx: Central Augmentation Index corrected for heart rate; PAIx: Peripheral Augmentation Index corrected for heart rate. PWV: Pulse Wave Velocity. AASI: Ambulatory Arterial Stiffness Index.
Accelerometer
Mean/Median
SD/IQR
Counts/min. Sedentary activity. (min/day) Sedentary activity/awake. (min/day) Low activity. (min/day) Moderate activity. (min/day) Vigorous intensity activity (min/day) 7-day-PAR METs/hour/week Sedentary n (%) Active n (%)
244.37 1073.52 655.92 314.12 54.16 2.63
195.48e325.48 97.75 97.75 91.57 27.31 10.26
11.49 211 52
23.35 80.2 19.8
Values are medians and interquartile range (IQR). min: minute. The intensity of physical activity was determined according to the cut-off points proposed by Freedson: Sedentary (5724 counts min) and very vigorous (>9498 counts min). Vigorous intensity activity include vigorous and very vigorous. METs: metabolic equivalent. Active were considered as those doing at least 30 min of moderate activity, five days a week, or at least 20 min of hard activity, 3 days a week.
Fig. 1 represents the parameters of vascular function and structure in relation to the physical activity tertiles according to counts/minute. The values of PAIx, CAIx, AASI and PWV had lower values in the tertiles that perform more physical activity. A multiple linear regression analysis was carried out. CAIx maintained the inverse association with the counts/minute (b ¼ 0.007; p < 0.01), and with the time spent in moderate (b ¼ 0.015; p ¼ 0.04) and in vigorous/very vigorous intensity activity (b ¼ 0.127; p ¼ 0.05). Likewise, CAIx maintained the positive association with the time spent in sedentary activity (b ¼ 0.015; p ¼ 0.03). Furthermore, an inverse association was observed of AASI with the METs/hour/week (b ¼ 0.039; p ¼ 0.01) and the time spent in moderate intensity activity (b ¼ 0.041; p ¼ 0.01) (Table 5). 5. Discussion In this study, physical activity, assessed by counts/minute, and the time spent in moderate and vigorous/very vigorous activity showed an inverse association with the CAIx. Likewise, the time spent in sedentary activity, showed a positive association with the CAIx. In summary, increased physical activity and more time spent in activities of moderate, vigorous/very vigorous intensity the CAIx was lower. Likewise the longer time spent in sedentary activities the CAIx was greater. Our results are consistent with those published by Edwards et el [10]. in adolescents and young adults. In this study, and after
Table 3 Parameters of vascular structure and function according to the intensity of physical activity performed. Vigorous or very vigorous physical activity Carotid IMT. (mm) CAIx_75. (%) PAIx_75. (%) PWV. (m/s) AASI
No
Yes
0.69
0.66
30.54 88.35 7.83 0.427
24.95 75.97 7.34 0.416
p value 0.05 0 9498 counts min). IMT: Intima Media Thickness. CAIx: Central Augmentation Index corrected for heart rate; PAIx: Peripheral Augmentation Index corrected for heart rate. PWV: Pulse Wave Velocity. AASI: Ambulatory Arterial Stiffness Index. METs: metabolic equivalent. P-values by Spearman correlation and Pearson correlation. *p < 0.05, **p < 0.01.
adjusting for demographic variables and other cardiovascular risk factors, physical activity showed an inverse association with the augmentation index. The studies that have analyzed the relationship between arterial stiffness and physical activity concluded that moderate physical activity in elderly people reduces PWV, particularly in hypertensive subjects [10]. On the other hand, in adolescents and young adults, Edwards et al. [10] found PWV to be greater in the tertile performing less physical activity, with the description of an independent association only among the participants with type 2 diabetes mellitus (DM2). Sakuragi et al. [32], in a study of 573 children in Australia in which physical activity was measured with a pedometer, found an inverse correlation with PWV. These results agree with the findings of our own study, in which the different measures used to assess arterial stiffness (PWV and AASI) showed greater values in the tertile of individuals with less physical activitye though significance was lost on adjusting for confounding factors. However, Tanaka et al. [33] found no association between PWV and physical activity in 53 adult women. van de Laar RJ et al. [34] and Sugawara et al. [35] only recorded this association in those who performed intense or very intense activity, in contrast to the findings of our study. The different publications that have analyzed the relationship between vascular function and physical activity have not produced uniform results. This suggests that the relationship can be
Fig. 1. Values corresponding to ambulatory arterial stiffness index; peripheral augmentation index corrected for heart rate; central augmentation index corrected for heart rate; pulse wave velocity and intima-media thickness according to the count/minute by tertiles: (T1 < 210.98; T2: 210.99e292.97; T3 > 292.98).
M.A. Gomez-Marcos et al. / Atherosclerosis 234 (2014) 366e372 Table 5 Multiple Regression Analysis with vascular structure and function parameters as dependent variable and physical activity as independent variable. Dependent variable: IMT mean
b
IC 95%
Physical activity counts/minute Physical activity METs/hour/week Sedentary activity day time Light activity day time Moderate activity day time Vigorous activity day time PAIX/75HR Physical activity Counts/minute Physical activity METs/hour/week Sedentary activity day time Light activity day time Moderate activity day time Vigorous activity day time CAIX/75HR Physical activity counts/minute Physical activity METs/hour/week Sedentary activity day time Light activity day time Moderate activity day time Vigorous activity day time AASI Physical activity counts/minute Physical activity METs/hour/week Sedentary activity day time Light activity day time Moderate activity day time Vigorous activity day time PWV Physical activity counts/minute Physical activity METs/hour/week Sedentary activity day time Light activity day time Moderate activity day time Vigorous activity day time
0.004 0.028 0.006 0.005 0.016 0.068
0.001 0.013 0.017 0.006 0.020 0.030
0.008 0.068 0.004 0.016 0.053 0.165
0.10 0.18 0.24 0.37 0.38 0.17
0.007 0.012 0.015 0.005 0.070 0.142
0.018 0.106 0.010 0.031 0.156 0.372
0.003 0.083 0.039 0.022 0.016 0.088
0.16 0.81 0.24 0.72 0.11 0.22
0.007 0.017 0.015 0.009 0.015 0.127
0.013 0.037 0.001 0.040 0.030 0.257
0.001 0.071 0.029 0.059 0.000 0.004
