Sports Med DOI 10.1007/s40279-014-0165-y

SYSTEMATIC REVIEW

Effect of Aerobic Exercise Training on Arterial Stiffness in Obese Populations A Systematic Review and Meta-Analysis David Montero • Christian K. Roberts • Agne`s Vinet

Ó Springer International Publishing Switzerland 2014

Abstract Background and Objective Controversy exists as to whether aerobic exercise training decreases arterial stiffness in obese subjects. The aim of this study was to systematically review and quantify the effect of aerobic exercise training on arterial stiffness in obese populations. Methods MEDLINE, Cochrane, Scopus, and Web of Science were searched up until May 2013 for trials assessing the effect of aerobic training interventions lasting 8 weeks or more on arterial stiffness in obese populations (body mass index C30 kg/m2). Standardized mean difference (SMD) in arterial stiffness parameters (augmentation index, b-stiffness, distensibility, pulse wave velocity, arterial waveforms) was calculated using a random-effects model. Subgroup and meta-regression analyses were used to study potential moderating factors. Results Eight trials, comprising a total of 235 subjects with an age range of 49–70 years, met the inclusion criteria. Arterial stiffness was not significantly reduced by aerobic training (SMD -0.17; 95 % confidence interval (CI) -0.39, 0.06, P = 0.14). Similarly, post-intervention arterial stiffness was similar between the aerobic-trained and control obese groups (SMD 0.02; 95 % CI -0.28, 0.32, P = 0.88). Neither heterogeneity nor publication bias were Electronic supplementary material The online version of this article (doi:10.1007/s40279-014-0165-y) contains supplementary material, which is available to authorized users. D. Montero (&)
A. Vinet Avignon University, LAPEC EA4278, 84000 Avignon, France e-mail: [email protected] C. K. Roberts Exercise and Metabolic Disease Research Laboratory, Translational Sciences Section, School of Nursing, University of California, Los Angeles, CA, USA

detected in these analyses. In subgroup analyses, arterial stiffness was significantly reduced in aerobic-trained subgroups having below median values in post- minus preintervention systolic blood pressure (SBP) (P \ 0.01), exercise intensity rating score (P \ 0.01), and methodological quality score (P \ 0.01). Equivalent results were obtained in meta-regression analyses. Conclusion Based on current published trials, arterial stiffness is generally not reduced in middle-aged and older obese populations in response to aerobic training. However, in studies using low-intensity aerobic training and yielding a decrease in SBP, arterial stiffness may decrease. Long-term studies are needed to assess the prognostic value of these findings.

1 Introduction The prevalence of obesity has almost doubled since 1980 [1]. Approximately 500 million adults worldwide are currently obese (defined as a body mass index (BMI) C30 kg/ m2) [1] and that number is projected to reach 1 billion by 2030 [2], representing an important global public health issue. Obese subjects are likely to present, independently of blood pressure level, with an increase in central and peripheral arterial stiffness [3, 4], which plays an important role in the development of cardiovascular disease [5], considered to be the principal cause of obesity-related morbidity and mortality [6, 7]. There are several potential factors that may contribute to increased arterial stiffness in obesity. Among them, high circulatory levels of free fatty acids (FFAs), insulin, leptin, and proinflammatory cytokines, all of which are commonly reported in obese subjects, may promote arterial stiffening through the

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stimulation of vascular smooth muscle proliferation, endothelial dysfunction, and increased sympathetic activity [3, 5]. Aerobic exercise training is known to reduce stiffness of central and peripheral arteries in non-obese healthy [8–12] and mild hypertensive adults [13, 14]. Arterial remodeling, improved endothelial function, and decreased sympathetic tonus have been suggested as mechanisms underlying the direct beneficial effect of aerobic training on arterial distensibility [8]. Current recommendations by major health organizations include moderate-to-high intensity aerobic exercise in young and older adults [15, 16]. However, in obese populations, previous trials that have measured the effect of aerobic training on arterial stiffness have yielded variable results [17–25], leading to some uncertainty of the effects of aerobic exercise on arterial stiffness. Therefore, the main objective of this study was to use the meta-analysis procedure to systematically review the effect of aerobic training on arterial stiffness in obese populations.

2 Methods This study is reported according to the Preferred Reporting Items for Systematic reviews and Meta-Analyses (PRISMA) guidelines [26]. 2.1 Data Sources and Searches The search strategy was developed to identify all relevant studies assessing the effect of aerobic exercise interventions on arterial stiffness in obese populations. Our systematic search included MEDLINE, Cochrane, Scopus, and Web of Science, from their inceptions until May 2013. We used combinations of the subject headings ‘obesity’, ‘arterial stiffness’, ‘arterial compliance’, ‘arterial distensibility’, ‘aerobic exercise’, and ‘physical activity’; the search strategy for MEDLINE is shown in Figure S1, Electronic Supplementary Material. We also performed hand searching in reference citations of identified reviews and original research articles selected for full-text retrieval. 2.2 Study Selection To be included in our analysis, an original research article had to meet the following criteria: (1) the research had to be a trial involving an obese group(s) (mean BMI C30 kg/ m2); (2) arterial stiffness values had to be reported at baseline and after an aerobic exercise intervention; (3) the duration of the aerobic exercise intervention had to be C8 weeks. An aerobic training intervention was defined as a deliberate and supervised program of aerobic physical activity, described within the corresponding manuscript.

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Studies following the above criteria but including, concurrent with aerobic exercise, other interventions deemed likely to influence arterial stiffness were excluded. In the event of multiple publications pertaining to the same research, the first published or more comprehensive study was used. Inclusion of studies in our analysis was not limited by publication status or language. 2.3 Data Extraction and Quality Assessment The following variables were abstracted into a preformatted spreadsheet: authors, year of publication, characteristics of study participants (n, age, % females, weight, BMI, brachial systolic blood pressure (SBP), brachial diastolic blood pressure (DBP), fitness level, health status, co-morbidities, medication status), vascular region assessed, vascular technique, arterial stiffness (augmentation index, b-stiffness, distensibility, pulse wave velocity, arterial waveforms), and aerobic training characteristics (type, frequency, intensity, bout duration, duration of the intervention, total accumulated time). Exercise intensity was included as a numeric effect having an integer value of 1 (easy walking) through 5 (aerobic exercise [80 % maximum oxygen consumption) [27]. Furthermore, if data were unclear or were not available in the published articles, we contacted the corresponding and/or first author by e-mail to request this information. The methodological quality of each included trial was evaluated using a validated 10-point scale to rate intervention trials [28–30]. Study selection, data extraction, and quality assessment were performed independently and in duplicate by two investigators (D.M.) and (A.V.). Discrepancies on inclusion/ exclusion were solved by consensus or through consultation with a third reviewer (C.K.R.). 2.4 Data Synthesis and Analysis The meta-analysis and statistical analyses were performed using Review Manager software (RevMan 5.2; Cochrane Collaboration, Oxford, UK) and Comprehensive Metaanalysis software (Version 2; Biostat, Englewood, NJ, USA). In each trial, the size of the effect of the intervention was calculated by the difference between post- and preintervention arterial stiffness in aerobic-trained obese groups. For controlled trials, the size of the effect of the intervention was also calculated by the difference in arterial stiffness between the aerobic-trained and control groups at the end of the intervention period. Each mean difference (paired and unpaired) was weighted according to the inverse variance method [31]. Because arterial stiffness was assessed by techniques using different scales, the mean differences were standardized by dividing them by the within-group standard deviation. The standardized mean

Aerobic Training and Arterial Stiffness in Obesity Fig. 1 Flow diagram of the process of study selection

difference (SMD) in each study was pooled with a randomeffects model [32] and effect sizes were interpreted according to Cohen guidelines [33]. Heterogeneity between studies was assessed using I2 statistics. Potential moderating factors were evaluated by subgroup analysis comparing studies grouped by dichotomous or continuous variables potentially influencing arterial stiffness. Median values of continuous variables were used as cut-off values for grouping studies. Changes in potential moderating factors were expressed and analyzed as post- minus pre-intervention values. Meta-regression analysis was performed to further explore which variables best predicted the SMD between post- and pre-intervention arterial stiffness. In all meta-regression models, studies were weighted by the inverse variance of the dependent

variable [31]. Potential moderating factors were entered as independent variables in regressions models with the SMD between post- and pre-intervention arterial stiffness as the dependent variable. Publication bias was evaluated by estimating Begg and Mazumdar’s funnel plot asymmetry and Egger’s weighted regression test [34]. A P value of less than 0.05 was considered statistically significant.

3 Results 3.1 Study Selection and Characteristics The flow diagram of the process of study selection is shown in Fig. 1. The search of MEDLINE, Cochrane,

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D. Montero et al. Table 1 Main clinical characteristics of studies included in the meta-analysis References

n Ctrl

EXE

$ (%)

Age (years)

Weight (kg)

BMI (kg/m2)

SBP, DBP

Reported comorbidities

Medication status

Kitzman et al. [21]

20

23

72

70

N/A

32.2

146.0, 82.0

HF

At least 66 % of subjects on aHTN

Ho et al. [20]

16

15

80

55

91.9

32.7

119.9, 67.4

None

Excluded subjects on LLD and/or b-blockers. 1 subject on aHTN

McNeilly et al. [22]

–

11

46

49

89.0

32.4

145.4, 94.5

IGT

Excluded subjects on LLD and/or aHTN

Vinet et al. [24]

–

10

0

51

100.3

33.2

127.8, 81.4

None

Excluded subjects on any drugs influencing vascular function

Waib et al. [25]

24

55

55

49

N/A

30.0

141.1, 90.0

Stage 1 HTN

aHTN withdrawn 1 month before initial screening

Miyaki et al. [23] Aizawa et al. [17]

– –

21 8

0 78

50 68

87.2 86.6

30.1 32.7

145.0, 87.0 154.2, 81.2

None Stage 1 HTN

Excluded subjects on any drugs All subjects on aHTN

Hill et al. [19]

18

14

57

51

96.0

32.6

132.4, 75.9

Stage 1 HTN and/or DLP

Excluded subjects on LLD and/or aHTN

Data are mean, or n aHTN antihypertensive drugs, BMI body mass index, Ctrl control group, DBP diastolic blood pressure, DLP dyslipidemia, EXE aerobic exercisetrained group, HF heart failure, HTN hypertension, IGT impaired glucose tolerance, LLD lipid-lowering drugs, N/A data not available, SBP systolic blood pressure All characteristics refer to the EXE group

Scopus, and Web of Science and our manual review of articles cited in the identified and related publications retrieved 349 articles, with 169 remaining after removal of duplicates. Of these, 134 were excluded because they were review articles or letters (n = 51), cross-sectional studies (n = 50), studies not involving exercise interventions (n = 18), irrelevant to our present meta-analysis (n = 12), or animal studies (n = 3). We obtained and reviewed the full text of the remaining 35 articles and excluded 27 for the following reasons: 17 articles included an additional intervention, five did not report arterial stiffness, two did not involve obese populations [35, 36], for two no data were provided in response to our requests to the authors [37, 38], and for one article the exercise intervention lasted \8 weeks [18]. Finally, eight articles were included in the meta-analysis. Table 1 shows the main clinical characteristics of the resulting eight trials, comprising a total of 235 subjects, of whom 157 were assigned to aerobic-trained groups and 78 to control groups. The total sample size range was 8–79. The mean age range was 49–70 years. The mean weight and BMI range was 86.6–100.3 kg and 30.0–33.2 kg/m2, respectively. The mean SBP and DBP range was 119.9–154.2 mmHg and 67.4–94.5 mmHg, respectively. Regarding the characteristics of the exercise interventions (Table 2), all trials consisted of conventional land-based exercise such as walking and/or running, while three trials also included cycling exercise [17, 21, 24] and arm ergometry [21]. They all had a mean of 3.9 sessions per week, 45.5 min per session, and 13.1 weeks of duration, resulting in 2,330 min on average in total. The intensity of aerobic

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exercise was moderate, having a mean intensity rating of 2.6 out of 5. Arterial stiffness was assessed by four trials in central arteries, three trials evaluated it in peripheral arteries (none of them in predominantly trained limbs), and one trial evaluated it in both central and peripheral arteries. 3.2 Quality Assessment and Potential Bias The quality of the trials, according to a previously validated scale [28–30] was moderate. The mean (SD) score was 4.3 ± 1.8 out of a possible 10 points (Table S1, Electronic Supplementary Material). Four out of eight trials were randomized controlled trials [19–21, 25]. Six trials had adequately described dropouts [17, 19–21, 24, 25], while the rest did not comment on dropouts. As for the evaluation of potential bias, the Begg and Mazumdar’s plot for the SMD between post- and pre-intervention arterial stiffness in aerobic-trained obese groups did not show asymmetry, suggesting the absence of significant publication bias (P = 0.11). Egger’s significance test also showed no significant publication bias (P = 0.09). 3.3 Arterial Stiffness Arterial stiffness was determined in all of the included trials by previously validated techniques in central and peripheral arteries (Table 2) [39]. After data pooling, SMD between post- and pre-intervention arterial stiffness in aerobic-trained obese populations did not reach statistical significance [-0.17; 95 % confidence interval (CI) -0.39, 0.06, P = 0.13 (paired), P = 0.14 (unpaired)] (Fig. 2).

Aerobic Training and Arterial Stiffness in Obesity Table 2 Characteristics of aerobic exercise interventions and arterial stiffness assessment in studies included in the meta-analysis References

Kitzman et al. [21]

Aerobic exercise intervention

Arterial stiffness assessment

Type

Frequency (week-1)

Bout duration (min)

Duration (weeks)

Total time (min)

Intensity ratinga

Intensity description

Vascular region assessed

Technique

W, C, A

3

60

16

2,880

3.5

70 % HRR

Central

b-Stiffness and distensibilityb

Ho et al. [20]

T

5

30

12

1,800

3

60 % HRR

Central

Augmentation Index

McNeilly et al. [22]

W

5

30

12

1,800

2

65 % HRmax

Peripheral

PWV

Vinet et al. [24]

W, C

3

45

8

1080

1.5

LIPOXmax (60 % HRmax)

Central

Distensibility

Waib et al. [25]

T

5

60

12.9

3,858

3

50–70 % VO2max

Peripheral

Arterial waveforms

Miyaki et al. [23]

W, J

3

40–60

12

1,800

2

11–15 (Borg’s scale)

Central

b-stiffness and distensibilityb

Aizawa et al. [17]

T, C

4.3

44.2

20

3,801

3

*64 % VO2max

Central, peripheral

b-stiffness and distensibilityb

Hill et al. [19]

W, R

3

45

12

1,620

3

75 % HRmax

Peripheral

Arterial waveforms

Data are mean A arm ergometry, C cycling, J jogging, HRmax maximum heart rate, HRR heart rate reserve (estimated as: HRmax - resting heart rate [64]), LIPOXmax maximal lipid oxidation, PWV pulse wave velocity, R running, T treadmill, VO2max maximal oxygen consumption, W walking a

Based on Snowling et al. [27] and validated equivalences between HRmax and VO2max in adults [65]

b

b-Stiffness and distensibility were similarly modified by the aerobic exercise intervention. b-Stiffness was used in the meta-analysis

Fig. 2 Standardized mean difference (SMD) between post and preintervention arterial stiffness in aerobic exercise-trained obese groups. Squares represent the SMD for each trial. Diamonds represents the pooled SMD across trials. Because the SMD method does not correct

for differences in the direction of the scale, mean values of some trials were multiplied by -1 to ensure that all the scales pointed in the same direction. Art arterial, IV inverse variance, SD standard deviation, SMD standardized mean difference, Std standardized

Post-intervention arterial stiffness was similar between the aerobic exercise-trained and control groups (four trials, SMD 0.02; 95 % CI -0.28, 0.32, P = 0.88) (Fig. 3). No heterogeneity was detected (I2 = 0) in either of these analyses.

trained obese subgroups below the median value in change in BMI after intervention (SMD -0.56 (-1.06, -0.06), P = 0.03), change in DBP after intervention (SMD -0.49 (-0.94, -0.05), P = 0.03), and baseline weight (SMD -0.49 (-0.94, -0.05), P = 0.03), which was not observed in their complementary subgroups; however, there was no significant differences between complementary subgroups (P = 0.10; P = 0.11; P = 0.40; respectively). Arterial stiffness was also significantly reduced in aerobic-trained obese subgroups below the median value in change in weight after intervention (SMD -0.61 (-1.05, -0.17), P \ 0.01), change in SBP after intervention (SMD -0.61

3.4 Subgroup and Meta-Regression Analyses Subgroup analyses were conducted to study the influence of potential moderating factors on arterial stiffness in studies included in the meta-analysis (Table 3). A significant decrease in arterial stiffness was detected in aerobic-

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Fig. 3 Standardized mean difference (SMD) in post-intervention arterial stiffness between aerobic exercise-trained and control obese groups. Squares represent the SMD for each trial. Diamonds represents the pooled SMD across trials. Because the SMD method does not correct for differences in the direction of the scale, mean

values of some trials were multiplied by -1 to ensure that all the scales pointed in the same direction. Art arterial, IV inverse variance, SD standard deviation, SMD standardized mean difference, Std standardized

(-1.05, -0.17), P \ 0.01), exercise intensity rating score (SMD -0.61 (-1.05, -0.17), P \ 0.01), and methodological quality score (SMD -0.55 (-0.95, -0.15), P \ 0.01), but not in their complementary subgroups; significant differences were found between complementary subgroups (P = 0.02; P = 0.02; P = 0.03; P = 0.02; respectively). No other potential clinical (age, sex, health, and medication status), exercise-related (baseline fitness level, frequency, bout duration, intervention duration, total accumulated time), or methodological (vascular technique, vascular region assessed) moderating factor significantly influenced arterial stiffness by subgroup analysis. In the meta-regression analysis (Fig. 4), significant associations were detected between the SMD between postand pre-intervention arterial stiffness in aerobic-trained groups and changes in SBP after intervention (B = 0.05, P = 0.03), exercise intensity rating score (B = 0.44, P = 0.02), and methodological quality score (B = 0.14, P = 0.03). None of the other potential moderating factors aforementioned predicted the SMD between post- and preintervention arterial stiffness in aerobic-trained obese groups.

populations. This is in contrast to the beneficial effects of aerobic exercise interventions on arterial distensibility reported in non-obese healthy [8–12] and mild hypertensive adults [13, 14]. Likewise, significant reductions in arterial stiffness were found in obese populations following combined aerobic training and nutrition interventions [40– 42]. Several factors may explain, in part, these results. First, the lack of systematic improvement in estimates of arterial stiffness could be because of the highly variable baseline blood pressures (Table 1). The baseline mean SBP range was 120–154 mmHg and the baseline DBP range was 67–95 mmHg. Thus, one might hypothesize that the lack of effect in total may be related to this high baseline blood pressure variability, resulting in lack of change in arterial stiffness on subjects with normal baseline blood pressure. Nevertheless, we did not detect significant differences in arterial stiffness between subgroups according to baseline blood pressures (Table 3), weakening this hypothesis. Second, chronically elevated levels of SBP, as in subjects with isolated systolic hypertension, may limit the enhancement of arterial distensibility [43–45]. Alternatively, arterial stiffness may be, in addition to a consequence, a cause of the lack of reduction in SBP. In this regard, we noted a decrease in arterial stiffness in obese subgroups showing concurrent systolic blood pressure reduction following aerobic exercise (Table 3; Fig. 4). Third, weight-bearing exercise training could hamper arterial stiffness improvements in obese subjects because of excessive arterial wall stress [46]. Indeed, extra weight carrying may require intense muscle contractions leading to high intramuscular pressure, which concurrently with the increased sympathetic activity and baroreflex impairment described in obesity [47], can produce high peaks of wall stress in vasodilated arteries. Consequently, arteries may respond by enhancing their smooth muscle content, thus restricting distensibility. This hypothesis might be, in part, supported by the decrease in arterial stiffness detected in aerobic-trained obese subgroups below, but not above, the

4 Discussion In this systematic review and meta-analysis, we pooled and analyzed data from eight trials evaluating the effects of aerobic exercise training interventions on arterial stiffness in obese populations. Overall, the results suggest that arterial stiffness is not improved with aerobic training. However, subgroup and meta-regression analyses revealed that low-intensity aerobic training accompanied by a reduction in SBP could result in decreased arterial stiffness in obese populations. Compared with the inconsistent findings of previous trials [17–25], the meta-analysis indicated that aerobic training alone does not reduce arterial stiffness in obese

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Aerobic Training and Arterial Stiffness in Obesity Table 3 Subgroup analyses assessing potential moderating factors for arterial stiffness in studies included in the meta-analysis Subgroup

Studies Number

Arterial stiffness a

References

SMD (95 % CI)

I2Heterogeneity

P value

PDifference

Clinical characteristics Age (years) C51.15

4

[17, 20, 21, 24]

-0.18 (-0.56, 0.19)

0

0.33

\51.15

4

[19, 22, 23, 25]

-0.19 (-0.52, 0.14)

19

0.25

0.98

Sex C55.85 % women

4

[17, 19–21]

-0.06 (-0.42, 0.29)

0

0.73

\55.85 % women Baseline weight (kg)

4

[22–25]

-0.35 (-0.76, 0.07)

41

0.10

C90.45

3

[19, 20, 24]

-0.22 (-0.67, 0.23)

0

0.34

\90.45

3

[17, 22, 23]

-0.49 (-0.94, -0.05)

0

0.03

0.31

0.40

Baseline BMI (kg/m2) C32.5

4

[17, 19, 20, 24]

-0.22 (-0.63, 0.19)

0

0.29

\32.5

4

[21–23, 25]

-0.17 (-0.49, 0.14)

21

0.27

0.86

Baseline SBP (mmHg) C143.05

4

[17, 21–23]

-0.32 (-0.67, 0.03)

0

0.08

\143.05

4

[19, 20, 24, 25]

-0.07 (-0.35, 0.22)

0

0.65

0.28

Baseline DBP (mmHg) C81.70

4

[21–23, 25]

-0.17 (-0.49, 0.14)

21

0.27

\81.70

4

[17, 19, 20, 24]

-0.22 (-0.63, 0.19)

0

0.29

0.86

Change in weight (kg) C-1.4

4

[17, 19, 20, 25]

-0.01 (-0.30, 0.28)

0

0.95

3

[21–23]

-0.61 (-1.05, -0.17)

0

\0.01

C-0.5

5

[17, 19, 20, 24, 25]

-0.08 (-0.35, 0.20)

0

0.58

\-0.5

2

[22, 23]

-0.56 (-1.06, -0.06)

0

0.03

\-1.4 Change in BMI (kg)

0.02

0.10

Change in SBP (mmHg) C-7.6

4

[17, 19, 20, 25]

-0.01 (-0.30, 0.28)

0

0.95

\-7.6

3

[22–24]

-0.61 (-1.05, -0.17)

0

\0.01

0.02

Change in DBP (mmHg) C-2.8

4

[19, 20, 24, 25]

-0.07 (-0.35, 0.22)

0

0.65

\-2.8

3

[17, 22, 23]

-0.49 (-0.94, -0.05)

0

0.03

0.11

Health status Co-morbidities/high BP

6

[17, 19, 21–23, 25]

-0.14 (-0.38, 0.10)

0

0.26

Healthy

2

[20, 24]

-0.35 (-1.05, 0.35)

33

0.33

0.58

Medication status LLD or aHTN

3

[17, 20, 21]

-0.07 (-0.47, 0.34)

0

0.75

No medication

5

[19, 22–25]

-0.27 (-0.59, 0.06)

24

0.11

0.46

Exercise characteristics Baseline maximum oxygen consumptionb Good

1

[17]

-0.22 (-1.21, 0.76)

–

0.66

Very poor

4

[21, 23–25]

-0.22 (-0.58, 0.14)

37

0.23

1

Frequency (week-1) C3.65

4

[17, 20, 22, 25]

-0.07 (-0.36, 0.23)

0

0.66

\3.65

4

[19, 21, 23, 24]

-0.30 (-0.65, 0.04)

3

0.09

0.31

Session length (min) C45

5

[19, 21, 23–25]

-0.17 (-0.46, 0.12)

17

0.24

\45

3

[17, 20, 22]

-0.24 (-0.72, 0.24)

0

0.32

0.81

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D. Montero et al. Table 3 continued Subgroup

Studies

Arterial stiffness

Numbera

References

SMD (95 % CI)

I2Heterogeneity

C12

7

[17, 19–23, 25]

-0.13 (-0.36, 0.10)

0

0.27

\12

1

[24]

-0.77 (-1.69, 0.15)

–

0.10

P value

PDifference

Duration (weeks) 0.18

Total time (min) C1,800

6

[17, 20–23, 25]

-0.14 (-0.38, 0.10)

0

0.26

\1,800

2

[19, 24]

-0.36 (-1.06, 0.35)

31

0.32

0.56

Intensity rating C3

5

[17, 19–21, 25]

-0.01 (-0.27, 0.24)

0

0.92

\3

3

[22–24]

-0.61 (-1.05, -0.17)

0

\0.01

0.02

Arterial stiffness assessment Vascular technique Including BP

7

[17, 19–21, 23–25]

-0.14 (-0.37, 0.09)

0

0.23

Not-including BP

1

[22]

-0.54 (-1.39, 0.32)

–

0.22

0.38

Vascular region assessed Central

5

[17, 20, 21, 23, 24]

-0.29 (-0.61, 0.03)

0

0.08

Peripheral

3

[19, 22, 25]

-0.05 (-0.36, 0.26)

0

0.74

C4 points

4

[19–21, 25]

0.00 (-0.27, 0.27)

0

0.99

\4 points

4

[17, 22–24]

-0.55 (-0.95, -0.15)

0

\0.01

0.30

Methodological quality 0.03

Subgroup analyses are performed on SMD between post- and pre-intervention arterial stiffness in aerobic exercise-trained obese groups. Median values of continuous variables were used as cut-off values for grouping studies aHTN antihypertensive drugs, BMI body mass index, BP blood pressure, CI confidence interval, DBP diastolic blood pressure, LLD lipidlowering drugs, Pdifference P value of the difference between subgroups, SBP systolic blood pressure, SMD standardized mean difference a

Certain enrolled studies were not included because the value used for the subgroup analysis was not reported in them

b

According to maximum oxygen consumption reference values depending on sex and age status [66]

median value in baseline weight (Table 3). Otherwise, in a recent meta-analysis comprising trials in normal-weight normotensive and hypertensive subjects, a neutral-tointensifying effect on arterial stiffness was described for resistance training [48], which has been associated with increased sympathetic activity [49] and intermittent extreme elevations of blood pressure [50]. In this respect, weight-bearing aerobic exercise could be hypothesized to cause resistance-like effects in obese subjects, thereby limiting arterial stiffness reduction. Finally, dietary interventions might be necessary to decrease arterial stiffness in obese subjects. Improvements in arterial distensibility following hypocaloric diets and/or nutritional modifications alone [51–57], some of them reported along with decreases in inflammatory markers [54, 55], in obese populations supports that hypothesis. Likewise, in our meta-analysis, weight loss was associated with decreased arterial stiffness (Table 3), though this result was not confirmed in metaregression analyses. Taking together, this meta-analysis suggests the need for further evaluation of the previously assumed benefit of aerobic training [15, 16] on arterial stiffness in obese populations.

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Despite the overall negative pooled results, this study found a distinct effect of aerobic training on arterial stiffness in obese populations according to the exercise intensity and the magnitude of the reduction in SBP. Lowintensity aerobic-trained obese subgroups presented above the median reduction in SBP and improved arterial stiffness, whereas no change in arterial stiffness was observed for moderate-to-high intensity, which showed a below median reduction in SBP. Meta-regression analysis confirmed the moderator effect of exercise intensity and SBP reduction on the change in arterial stiffness (Fig. 4). While speculative, these findings might be linked to the aforementioned hypotheses regarding chronically elevated SBP and high peaks of wall stress as a result of weight-bearing exercise in obese subjects. In this way, animal studies demonstrated that low, but not high-intensity, aerobic exercise could partially counterbalance those obesity-related adverse effects by decreasing sympathetic tone, cardiac output, blood pressure, resting heart rate, and tachycardic response during progressive exercise [58, 59], which might explain the favorable effect of low-intensity aerobic exercise on arterial stiffness. As an additional explanation, in

Aerobic Training and Arterial Stiffness in Obesity

Fig. 4 Meta-regression plots of standardized mean difference (SMD) between post- and pre-intervention arterial stiffness in aerobic-trained obese groups according to the post minus pre-intervention change in systolic blood pressure (SBP) (B = 0.05, P = 0.03) (a), exercise

intensity rating score (B = 0.44, P = 0.02) (b) and the methodological quality score (B = 0.14, P = 0.03) (c). The size of each circle is proportional to the study’s weight. SBP systolic blood pressure, SMD standardized mean difference

obese men, three months of low intensity [40 % maximal oxygen consumption (VO2max)] aerobic exercise enhanced mobilization and oxidation of FFAs [60], which have been related to arterial stiffness plausibly by increasing oxidative stress [61], whereas high-intensity (70 % VO2max) aerobic exercise diminished plasma oxidation of FFAs at rest [60]. Furthermore, high, but not mild or moderateintensity, aerobic exercise has been associated with increased oxidative stress markers in healthy normalweight adults [62]. Ultimately, our results suggest that lowintensity aerobic exercise interventions associated with a decrease in SBP may, in fact, have a positive impact on arterial stiffness in obese populations. Long-term, largescale exercise trials should determine whether a reduction in arterial stiffness has significant prognostic value in terms of clinical endpoints such as morbidity and mortality, which, to date, is largely unknown [39]. There are some limitations in the present meta-analysis worthy of consideration. First, the mean age of included trials was 49–70 years, hence our findings cannot be applied to younger obese populations in which both duration of and co-morbidities associated with obesity may be less determining. Likewise, age per se is related to the development of arterial stiffness [63], therefore, the age

status of our study population could have contributed, independently of obesity, to the overall lack of improvement in arterial stiffness with aerobic training. Yet, obesity may be considered to play a role in our study because aerobic training has been frequently associated with reduced arterial stiffness in normal-weight populations over 50 years of age [9, 11, 12]. Second, there were methodological differences among the techniques used to evaluate arterial stiffness in the analyzed trials. Although we did not detect a significant impact of such methodological variables on arterial stiffness (Table 3), some of these analyses could have been underpowered. Third, because the number of trials including a non-exercise obese control group was relatively small [19, 20, 22, 25], we chose to study potential moderating factors for arterial stiffness assessed by the SMD between post- and preintervention arterial stiffness in trained obese groups. Nonetheless, both meta-analyses of controlled and noncontrolled trials revealed similar effect size and null heterogeneity among trials. Fourth, given that different estimates of arterial stiffness were used in the analyzed trials and only one of these included a non-obese control group [24], we could not compare the baseline degree of arterial stiffness in obese populations between trials, which might

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be a potential moderating factor. Finally, according to heterogeneity analyses, the effect size could have been overestimated in trials with low methodological quality, although there was no significant publication bias.

5 Conclusions The current meta-analysis suggests that aerobic exercise training interventions do not reduce arterial stiffness in middle-aged and older obese populations. However, arterial stiffness decreases in obese subgroups with lowintensity training associated with SBP reduction. Further studies are needed to understand the mechanisms underlying changes in arterial stiffness in response to exercise training and the effects of different training modalities in obese individuals. Acknowledgments No sources of funding were used to assist in the preparation of this review. C.K.R. was supported by the National Heart, Lung and Blood Institute (P50HL105188) during the writing of this paper. The authors have no potential conflicts of interest that are directly relevant to the content of this review.

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