Effect of Weight Loss on Pulse Wave...

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Globally, cardiovascular disease (CVD) is the leading cause of death accounting for 31% in 2008.1 Obesity

is an independent predictor of CVD and weight loss has been shown to improve many obesity-related risk factors.2 However, there are few studies investigating the effect of weight loss on cardiovascular end points. The Trial of Non-pharmacological Interventions in the Elderly enrolled sub-jects >60 years with hypertension to investigate the effect of weight loss on blood pressure and cardiovascular out-comes.3 After a median follow-up of 29 months, the hazard ratio (HR) for a cardiovascular end point or diagnosis of high blood pressure in the weight reduction group was 0.64 (95% confidence interval [CI], 0.49, 0.85; P=0.002).4 More recently, the Look AHEAD trial (n=5145) failed to show a benefit of weight reduction on cardiovascular end points in subjects with type 2 diabetes mellitus after a median follow-up of 9.6 years.5 In the Look AHEAD trial, the mean weight loss in the intervention group was 6%, compared with 3.5% in the control group.

Carotid femoral pulse wave velocity (cfPWV) is consid-ered the gold standard method for measuring arterial stiff-ness because it measures the propagation of the forward pressure at the level of the aorta.6 A meta-analysis of indi-vidual participant data from 17 studies (17 635 participants) showed that cfPWV was an independent predictor of coro-nary heart disease (HR, 1.23; 95% CI, 1.11 to 1.35), stroke (HR, 1.28; 95% CI, 1.16 to 1.42), CVD (HR, 1.30; 1.18 to 1.43), CVD mortality (HR, 1.28; 95% CI, 1.15 to 1.43), and all-cause mortality (HR, 1.17; 1.11 to 1.22), after adjustment for established risk factors. Furthermore, the addition of cfPWV to conventional Framingham risk factors improved 10-year CVD risk prediction by 13% in those at intermediate risk of CVD.7

Many studies indicate that weight loss may improve pulse wave velocity (PWV), although in about half of the studies the change is not statistically significant. A meta-analysis has not been conducted to assess the overall effect of weight loss. The primary aim of this meta-analysis of intervention trials is

© 2014 American Heart Association, Inc.

Arterioscler Thromb Vasc Biol is available at http://atvb.ahajournals.org DOI: 10.1161/ATVBAHA.114.304798

Objective—To conduct a systematic review and meta-analysis of clinical trials involving adults, to determine the effect of weight loss induced by energy restriction with or without exercise, antiobesity drugs or bariatric surgery on pulse wave velocity (PWV) measured at all arterial segments.

Approach and Results—A systematic search of Pubmed (1966 to 2014), EMBASE (1947 to 2014), MEDLINE (1946 to 2014), and the Cochrane Library (1951 to 2014) was conducted and the reference lists of identified articles were searched to find intervention trials (randomized/nonrandomized) that aimed to achieve weight loss and included PWV as an outcome. The search was restricted to human studies. Two independent researchers extracted the data. Data were analyzed using Comprehensive Meta Analysis version 2 using random effects analysis. A total of 22 studies were included in the qualitative synthesis and 20 studies (3 randomized controlled trials), involving 1259 participants, were included in the meta-analysis. The standardized mean difference for the overall effect of weight loss on PWV measured at all sites was −0.32 (95% confidence interval, −0.41, −0.24; P=0.0001). Carotid femoral pulse wave velocity (standardized mean difference, −0.35; 95% confidence interval, −0.44, −0.26; P=0.0001; 16 studies) and brachial ankle PWV (standardized mean difference, −0.48; 95% confidence interval, −0.78, −0.18; P=0.002; 5 studies) were improved with weight loss. Meta-regression showed that change in blood pressure was a predictor of change in PWV (P<0.01).

Conclusion—Modest weight loss (mean 8% of initial body weight) achieved with diet and lifestyle measures improved PWV. The results of this meta-analysis suggest that weight loss may reduce PWV, although future research is required. (Arterioscler Thromb Vasc Biol. 2015;35:243-252. DOI: 10.1161/ATVBAHA.114.304798.)

Key Words: arterial stiffness ◼ meta-analysis ◼ weight loss ◼ weight reduction

Received on: August 24, 2014; final version accepted on: October 27, 2014.From the School of Pharmacy and Medical Science, University of South Australia, Adelaide, Australia.The online-only Data Supplement is available with this article at http://atvb.ahajournals.org/lookup/suppl/doi:10.1161/ATVBAHA.114.304798/-/DC1.Correspondence to Peter M. Clifton, GPO Box 2471, Adelaide SA 5000, Australia. E-mail [email protected]

Effect of Weight Loss on Pulse Wave VelocitySystematic Review and Meta-Analysis

Kristina S. Petersen, Natalie Blanch, Jennifer B. Keogh, Peter M. Clifton

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244 Arterioscler Thromb Vasc Biol January 2015

to determine the effect of weight loss, achieved by an energy restricted diet with or without exercise, antiobesity drugs or bariatric surgery on PWV measured at all arterial segments in adults.

Materials and MethodsMaterials and Methods are available in the online-only Data Supplement.

ResultsStudiesThe search strategy identified 7713 publications and 6119 were excluded based on the title and the abstract, and a fur-ther 403 were excluded after full text assessment (online-only Data Supplement). A total of 22 publications met the inclu-sion criteria and were included in the qualitative synthesis (Table 1).8–27 One study reported the results as median (inter-quartile range) and was excluded from the meta-analysis.28 The results of the Slow Adverse Vascular Effects trial were reported in 2 articles by Cooper et al29 and Hughes et al.19 In the Cooper et al29 article, 12-month results were reported as median (interquartile) and therefore, this article is not included in the meta-analysis but is included in the qualita-tive synthesis. The 6-month results, reported by Hughes et

Nonstandard Abbreviations and Acronyms

cfPWV carotid femoral pulse wave velocity

CVD cardiovascular disease

PWV pulse wave velocity

SMD standardized mean difference

Table 1. Summary of the Intervention Studies Included in the Meta-Analysis

Study Population

Study Duration

(wk) GroupsCompleted

nMen

n, (%)Drop-Outs

n (%)Baseline Weight Final Weight Weight Loss Age

Barinas-Mitchell et al23

Type 2 diabetes mellitus 52 Energy restricted diet+exercise +Orlistat

17 NR 14 (27) 97.0±15.1 86.9±13 −10.1±9.1 (−10.4%)

50±2

Energy restricted diet+exercise+placebo

21 NR 101.8±19.3 92.4±16.4 −9.4±11.6 (−9.2%)

52±2

Blumenthal et al24

RCT

Overweight or obese unmedicated with Pre or

stage 1 hypertension

Energy restricted DASH diet+exercise

46 ≈31% 3 (6) 93.9±14.0 84.5 −9.4 (−10.0%) 52±10

Usual diet control 48 ≈31% 1 (2) 92.6±15.0 94.1 0.9 (+2.0%) 52±9

Bradley et al10

Overweight or obese 8 Energy restricted diet (20% CHO, 60% fat)

12 5 (42) 3 (11) 97.7±14.4 90.3±12.9 −7.4±8.6 (−7.6%)

37±9

Energy restricted diet (20% fat, 60% CHO)

12 4 (33) 91.5±11.1 85.0±11.2 −6.5 (−7.1%) 41±10

Chakera et al11 Obese with type 2 diabetes mellitus

24 Energy restricted diet±Rimonabant therapy

27 ≈45% 2 (7) 107.0±21.0 104.0±21.0 −3±13.3 (−2.8%)

57±11

Clifton et al25 Overweight with TG >2 mmol/L

12 Meal replacements 26 17 (65) 7 (21) 94.4±12.2 88.4±11.9 6.0±4.2 (−6.4%) 49±9

Energy restricted diet (low fat, high CHO)

29 15 (52) 4 (12) 96.4±12.9 89.7±12.1 6.6±3.35 (−6.9%)

47±10

Cooper et al29 25–45 y Overweight or obese

52 Energy restricted diet + exercise

255 ≈23% 89 (26) 92.2±14.9 85.5±15.1 −6.7 (−7.1%) 38±6

Dengo et al9 Overweight and obese 12 Energy restricted diet 25 9 (36) NR 84.6±13 77.5±11 −7.1±7.8 (−8.4%)

61±1

RCT Control 11 6 (55) NR 91.0±15.9 90.4±16.3 −0.6±10.2 (−0.7%)

66±2

Figueroa et al18 Overweight or obese postmenopausal women

with pre or stage 1 hypertension

12 Energy restricted diet 13 0 (0) 4(9) 89.0±15.9 83.4±16.6 −5.6±10.3 (−6.3%)

54±4

Energy restricted diet + exercise (resistance

training)

14 0 (0) 86.7±10.1 81.9±9.4 −4.8±6.2 (−5.5%)

54±4

Howden et al12 Stage 3–4 CDK+1 or more uncontrolled CVD

risk factors

52 Energy restricted diet+exercise

36 24 (67) 5 (12) 92.6±22.5 NR −1.8±4.2 (2%) 60±10

RCT Control 36 21 (58) 6 (14) 92.7±24.1 NR 0.7±3.7 (0.8%) 62±8

Hughes et al19 25–45 y, Overweight or obese

24 Energy restricted diet+exercise

272 NR 67 (20) 92.2±15 85.7±15 −7.0±5.9 (−7.6%)

38±6

(Continued )



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Petersen et al Weight Loss and PWV: Meta-Analysis 245

al19 are included in the meta-analysis. Therefore, 20 studies, involving 1259 participants, are included in the meta-analysis (Table 2).

Study QualityThe Newcastle-Ottawa Scale30 was used to assess the quality of the studies and the mean score was 5 (online-only Data

Keogh et al13 Overweight and obese 52 Energy restricted diet (33% CHO, 7% saturated

fat)

13 ≈32% 23 (64) 91.5±10.5 NR −4.6±2.1 (−5%)

50±1

Energy restricted diet (60% CHO, 20% fat)

97.6±6.1 NR −5.5±1.2 (−6%)

47±2

Keogh et al14 Overweight and obese 8 Energy restricted diet (4% CHO, 20% saturated fat)

52 NR 5 (9) 94.0±15.3 87.0±13.9 −7.5±2.6 (−8%)

51±8

Energy restricted diet (46% CHO, <8%

saturated fat)

47 NR 3 (6) 97.0±14.4 90.7±13.8 −6.2±2.9 (−6.4%)

49±8

Maeda et al20 Overweight and obese men

12 Energy restricted diet+exercise (aerobic)

17 17 (100) NR 87.6±10.3 75.3±9.1 −12.3±6.2 (−14.0%)

35–63†

Miyaki21 Premenopausal overweight or obese

12 Energy restricted diet+whole body

vibration

12 0 (0) NR 80.5±14.2 71.8±11.4 −8.7±8.5 (−10.8%)

42±7

Miyaki et al17 Overweight and obese 12 Energy restricted diet 12 12 (100) NR 88.0±10.4 80±13.9 (−8±8.3) −9.1%

45±7

Nordstrand et al26

Morbidly obese (BMI >40 or >35

with obesity-related comorbidity)

28 Energy restricted diet 91 34 (37) 7 (7) 137.8±22.4 NR −9.4±4.3 (−6.8%)

42±10

Energy restricted diet+exercise

88 32 (36) 14 (14) 125.2±20.4 −6.6±3.5 (−5.3%)

45±11

Philippou et al28

Men, 35–65 y, with ≥1 CHD risk factor

24 Energy restricted low GI diet

22 22 (100) 18 (32) NR NR −2.2±3.6 NR

Energy restricted high GI diet

16 16 (100) NR NR −3.0±4.2 NR

Pirro et al27 Hypercholesterolemic 8 Isocaloric diet low in cholesterol (<200 mg/d),

low saturated fat (5%)

35 NR NR 66.0±11.0 64.0±11.0 −2.0±7.0 (3.0%)

58±14

Rider et al8 Obese 52 Energy restricted low glycemic index

diet or bariatric surgery

27 ≈24% 23 (46) 114.0±23.0 93.0±17.0 −21±13.9 (−18.4%)

43±9

Samaras et al16

Obese with type 2 diabetes mellitus or impaired glucose

tolerance

24 Energy restricted diet and bariatric surgery at 12 wk

14 8 (47) 3 (18) 127.5±21.3 109.4±18.7 −18.1±12.9 (−14.2%)

50±10

Satoh et al22 Obese 12 Energy restricted diet + exercise (achieved >5%

weight loss)

49 21 (43) 0 80.2±17.5 73.8±15.4 −6.4±10.6 (−8.0%)

53±14

Energy restricted diet + exercise (achieved <5%

weight loss)

117 50 (43) 77.5±16.2 77.7±17.3 0.2±10.7 (0.3%)

54±14

Wycherley et al15

Overweight or obese 52 Energy restricted diet (4% CHO, 20% saturated fat)

26 8 (31) 31 (54) 94.2±16.3 NR −14.9±10.7 (−16%)

50±9

Energy restricted diet (46% CHO,

30% fat)

23 9 (39) 38 (62) 97.5±12.9 NR −11.5±7.2 (−12%)

50±7

BMI indicates body mass index; CKD, chronic kidney disease; CVD, cardiovascular disease; DASH, dietary approaches to stop hypertension; NR, not reported; and RCT, randomized controlled trials.

*Median (interquartile range).†Range.

Table 1. Continued

Study Population

Study Duration

(wk) GroupsCompleted

nMen

n, (%)Drop-Outs

n (%)Baseline Weight Final Weight Weight Loss Age



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Table 2. Change in Pulse Wave Velocity After Weight Loss

Study Group Type of PWV Measurement Baseline Final Change

Pulse wave velocity, aortic

Dengo et al9 Energy restricted diet PWV, aortic (m/s) 8.33±1.75 7.06±1.25 −1.27±1.06

Control 8.18±1.79 8.83±2.06 0.65±1.24

Rider et al8 Energy restricted low glycemic index diet or

bariatric surgery

PWV, aortic arch (MRI; m/s) 10.3±7.2 10.1±7.7 −0.2±4.7*


bariatric surgery

PWV, ascending aorta to abdominal aorta (MRI; (m/s)

5.8±2.0 5.0±1.0 −0.8±1.3*


bariatric surgery

PWV, descending aorta (MRI; m/s)

6.2±8.3 4.3±1.4 −1.9±7.2*

Pulse wave velocity, brachial ankle

Cooper et al29 SAVE trial (12-mo results)


PWV, brachial ankle (m/s) 12.05 (9.0, 15.5)† 11.99 (9.25, 15.25)† −0.33 (−140.5, 84.5)†

Figueroa et al18* Energy restricted diet PWV, brachial ankle (m/s) 13.88±3.46 12.61±1.8 −1.30±2.3

Energy restricted diet+exercise (resistance

training)

13.95±1.3 13.35±1.01 −0.6±0.8

Hughes et al19 SAVE trial (6-mo results)


PWV, brachial ankle (m/s) 12.08±1.32 … −0.12±0.92

Maeda et al20 Energy restricted diet+exercise (aerobic)

PWV, brachial ankle (m/s) 13.5±2.06 12.5±1.72 −1.0±1.4*

Miyaki et al21 Energy restricted diet+whole body vibration


Satoh et al22 Energy restricted diet+exercise (achieved

>5% weight loss)


Energy restricted diet+exercise (achieved

<5% weight loss)

14.19±2.7 14.16±2.7 −0.03±1.7*

Pulse wave velocity, carotid femoral

Barinas-Mitchell et al23 Energy restricted diet+exercise±Orlistat

PWV, carotid femoral (m/s) 8.17±0.63 6.80±0.20 −1.37±0.5*

Blumenthal et al24 Energy restricted DASH diet+exercise

PWV, carotid femoral (m/s) … 7.0±1.8 …

Usual diet control … 7.7±1.6 …

Chakera et al11 Energy restricted diet±Rimonabant therapy

(clinical decision)


Clifton et al25 Meal replacement PWV, carotid femoral (m/s) 7.43±2.68 6.18±1.66 −1.24±2.11

Energy restricted diet (low fat, high CHO)

7.26±3.18 6.24±1.29 −1.02±2.66

Cooper et al29 SAVE trial (12-mo results)


PWV, carotid femoral (m/s) 8.19 (5.42, 12.92† 7.78 (5.0, 12.50)† −0.026±0.974

Dengo et al9 Energy restricted diet PWV, carotid femoral (m/s) 11.55±2.30 9.68±1.8 −1.87±1.38

Control 11.76±2.52 11.90±2.55 0.14±1.60

Figueroa et al18 Energy restricted diet PWV, carotid femoral (m/s) 11.75±3.38 11.25±2.28 −0.5±0.95


training)

11.81±1.57 11.30±1.12 −0.51±0.95

Howden et al12 Energy restricted diet+exercise

PWV, carotid femoral (m/s) 9.2±2.1 … 0.4±1.4

Control 9.8±2.3 … 0.1±2.0

(Continued )



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Supplement). The majority of studies8–16,19,22–27,29 used par-ticipants that were representative of the population they were drawn from, that is, overweight, obese, had type 2 diabetes mellitus, or chronic kidney disease. Five studies17,18,20,21,28 only included men or women and therefore are only somewhat representative of the population they were drawn from.31Only

3 studies9,12,24 were randomized controlled trials and the con-trol groups were drawn from the same population because the intervention group and the baseline characteristics of the groups were comparable. The other 17 studies8,10,11,13–23,25–27 were uncontrolled and reported only before and after inter-vention data and thus do not control for time-related changes.

Hughes et al19 Energy restricted diet+exercise

PWV, carotid femoral (m/s) 8.8±2.57 … −0.52±3.03

Keogh et al13 Energy restricted diet (33% CHO, 7% saturated fat)

PWV, carotid femoral (m/s) 9.5±1.3 9.5±1.4 0±1.7


8.9±1.0 9.8±0.5 0.9±3.8

Keogh et al14 Energy restricted diet (4% CHO, 20% saturated fat)


Energy restricted diet (46% CHO, <8% saturated fat)

11.1±2.9 9.5±1.5 −1.6±1.9*

Miyaki et al17 Energy restricted diet PWV, carotid femoral (m/s) 9.79±1.56 9.18±1.0 0.60±0.97*

Miyaki et al21 Energy restricted diet + whole body vibration


Nordstrand et al26 Energy restricted diet PWV, carotid femoral (m/s) 8.7±1.7 8.5±0.7 −0.2±0.97

Energy restricted diet + exercise

8.6±1.8 8.1±0.7 −0.6±0.96

Philippou et al28 Energy restricted low GI diet

PWV, carotid femoral (m/s) 10.3(10.0 to 10.9)† 9.7 (9.3 to 10.3)† −0.4(−1.4 to 0.0)†

Energy restricted high GI diet

9.9(9.2 to 10.6)† 9.4 (9.0 to 10.5)† −0.3(−0.6 to 0.5)†

Pirro et al27 Isocaloric diet low in cholesterol (<200 mg/d)/

low saturated fat (5%)


Samaras et al16 Energy restricted diet and bariatric surgery at 12 wk


Wycherley et al15 Energy restricted diet (4% CHO, 20% saturated fat)

PWV, carotid femoral (m/s) 10.7±3.06 9.3±1.53 −1.4±2.1


11.0±2.88 9.5±2.4 −1.5±1.7

Pulse wave velocity, carotid radial

Bradley et al10 Energy restricted diet (20% CHO, 60% fat)

PWV, brachial (m/s) 8.3±0.6 8.2±0.7 −0.1±0.4*

Energy restricted diet (20% fat, 60% CHO)

8.1±1.7 8.1±1.5 0.0±1.0*

Chakera et al11 Energy restricted diet±Rimonabant therapy

(clinical decision)

PWV, brachial (m/s) 8.3±1.0 8.4±1.0 0.1±0.6*

Pulse wave velocity, femoral ankle

Figueroa et al18 Energy restricted diet PWV, femoral ankle (m/s) 10.17±1.19 9.41±0.69 −0.78±0.8


training)

10.32±0.67 10.17±0.71 −0.15±0.4

Hughes et al19 Energy restricted diet+exercise

PWV, femoral ankle (m/s) 9.46±1.03 0.06±0.92

DASH indicates dietary approaches to stop hypertension.*Calculated change.†Median (interquartile range).

Table 2. Continued

Study Group Type of PWV Measurement Baseline Final Change



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The randomized intervention trials did not report the method of randomization or blinding. All the studies had a follow-up time of >1 month. Twelve studies10–12,14,16,18,19,22–26 had a follow-up rate of >75% or were able to demonstrate that the characteristics of the participants lost to follow-up were not different to the completers. Five studies8,13,15,28,29 had a loss to follow-up rate of >25% and 5 studies did not provide a statement about participant flow.9,17,20,21,27 The loss to follow-up rate was the main difference between the studies and when a sensitivity analysis was conducted to compare studies with a follow-up rate >75% to studies that had a lower follow-up rate or the participants flow was not reported there was no statistically significant difference in the standardized mean difference (SMD).

Pulse Wave VelocityTwenty studies, including 1259 participants, were included in the meta-analysis. Weight loss (mean 8% of initial body weight) significantly improved PWV (SMD, −0.32; 95% CI, −0.41, −0.24; P=0.0001; Q=35; P=0.11; I2=26%; Figure 1). Sensitivity analysis showed that no 1 study was responsible for the observed effect and significance was maintained after the removal of each individual study. Examination of the fun-nel plot showed evidence of publication bias (Eggers test P=0.08l; Figure 2).

There were 10 studies that used an energy restricted diet to achieve weight loss and 8 studies that had a diet and exer-cise intervention. Both types of weight loss interventions were associated with a significant reduction in PWV and the effect was nonsignificantly larger (Q=0.19; P=0.66) for weight loss achieved with an energy restricted diet (SMD, –0.36; 95% CI, −0.47, −0.25; P=0.0001; Q=15; P=0.38; I2=7; mean weight loss 8% of initial body weight) compared with energy restriction plus exercise (SMD, −0.32; 95% CI, −0.49, −0.15; P=0.0001; Q=14; P=0.045; I2=51%; mean weight loss 8% of initial body weight). There was a nonsignificantly (Q=2; P=0.17) larger effect on PWV when >10% of initial body weight was lost (SMD, −0.44; 95% CI, −0.63, −0.25; P=0.0001; Q=7; P=0.29; I2=19%) compared with <10% of initial body weight (SMD, −0.29; 95% CI, −0.38, −0.20; P=0.001; Q= 24; P=0.18; I2=22%).

When the different types of PWV measurements were looked at, there was no statistically significant difference in the response to weight loss (Q=8; P=0.11). Carotid femoral PWV (SMD, −0.35; 95% CI, −0.44, −0.26; P=0.0001; Q=29; P=0.11; I2=28%; 16 studies) and brachial ankle pulse wave velocity (SMD, −0.48; 95% CI, −0.78, −0.18; P=0.002; Q=16; P=0.002; I2=69%; 5

Study name Outcome Comparison Statistics for each study Std diff in means and 95% CI

Std diff Lower Upper in means limit limit p-Value

Barinas- Mitchell 2006 Carotid femoral PWV (ms) Diet+Exercise+drugs -0.455 -0.789 -0.121 0.008Blumenthal 2010 Carotid femoral PWV (ms) Diet+Exercise -0.642 -1.048 -0.236 0.002Bradley 2009 Carotid radial PWV (ms) Diet -0.152 -0.721 0.417 0.602Bradley 2009 Carotid radial PWV (ms) Diet -0.004 -0.569 0.562 0.990Chakera 2010 Carotid femoral PWV (ms) Diet+drugs -0.173 -0.540 0.193 0.354Clifton 2005 Carotid femoral PWV (ms) Diet -0.384 -0.790 0.022 0.064Clifton 2005 Carotid femoral PWV (ms) Diet -0.589 -1.089 -0.089 0.021Dengo 2010 Carotid femoral PWV (ms) Diet -0.900 -1.639 -0.161 0.017Figueroa 2013b Carotid femoral PWV (ms) Diet -0.424 -0.991 0.144 0.143Figueroa 2013b Carotid femoral PWV (ms) Diet+Exercise -0.421 -0.968 0.125 0.131Howden 2013 Carotid femoral PWV (ms) Diet+Exercise 0.174 -0.289 0.637 0.462Hughes 2012 Carotid femoral PWV (ms) Diet+Exercise -0.171 -0.291 -0.051 0.005Keogh 2007 Carotid femoral PWV (ms) Diet 0.237 -0.574 1.048 0.567Keogh 2007 Carotid femoral PWV (ms) Diet 0.000 -0.800 0.800 1.000Keogh 2008 Carotid femoral PWV (ms) Diet -0.291 -0.568 -0.013 0.040Keogh 2008 Carotid femoral PWV (ms) Diet -0.637 -0.950 -0.323 0.000Maeda 2013 Brachial ankle PWV (ms) Diet+Exercise -0.708 -1.240 -0.177 0.009Miyaki 2009 Carotid femoral PWV (ms) Diet -0.639 -1.260 -0.018 0.044Miyaki 2012 Carotid femoral PWV (ms) Diet+Exercise -0.640 -1.261 -0.019 0.043Nordstrand 2013 Carotid femoral PWV (ms) Diet -0.197 -0.404 0.011 0.063Nordstrand 2013 Carotid femoral PWV (ms) Diet+Exercise -0.363 -0.579 -0.147 0.001Pirro 2004 Carotid femoral PWV (ms) Diet -0.413 -0.758 -0.068 0.019Rider 2010 Aortic arch PWV (MRI) (ms) Diet/surgery -0.027 -0.404 0.350 0.889Samaras 2012 Carotid femoral PWV (ms) Bariatric surgery -0.289 -0.823 0.246 0.290Satoh 2008 Brachial ankle PWV (ms) Diet+Exercise -0.189 -0.523 0.145 0.267Wycherley 2010 Carotid femoral PWV (ms) Diet -0.458 -0.862 -0.054 0.026Wycherley 2010 Carotid femoral PWV (ms) Diet -0.521 -0.957 -0.086 0.019

-0.324 -0.409 -0.239 0.000

-2.00 -1.00 0.00 1.00 2.00

Favours weight loss Favours no weight loss

Figure 1. Random effects meta-analysis of the effect of weight loss on pulse wave velocity. CI indicates confidence interval; and PWV, pulse wave velocity.

-2.0 -1.5 -1.0 -0.5 0.0 0.5 1.0 1.5 2.0

0.0

0.1

0.2

0.3

0.4

0.5

Stan

dard

Err

or

Std diff in means

Funnel Plot of Standard Error by Std diff in means

Figure 2. Funnel plot for pulse wave velocity.



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studies) were significantly reduced by weight loss. Carotid radial, aortic, and femoral ankle PWV were not significantly reduced by weight loss (Figure 3). The combined SMD was −0.35 (95% CI, −0.44, −0.26; P=0.0001; Q=32; P=0.0.11; I2= 28%) when only studies that measured cfPWV or brachial ankle pulse wave veloc-ity were included (online-only Data Supplement).

Meta-regression showed that the change in systolic (P=0.002) and diastolic blood pressure (P<0.001) were cor-related with the change in PWV (Figures 4 and 5). Weight loss (kg), baseline weight, intervention period, and percent-age weight loss did not correlate with the change in PWV ( online-only Data Supplement).

Study name Group byoutcome categor ies

Comparison Statistics for each study Std diff in means and 95% CI

Std diff Lower Upper in means limit limit p-Value

Dengo 2010 Aortic PWV Diet -1.142 -1.899 -0.385 0.003Rider 2010 Aortic PWV Diet/surgery -0.027 -0.404 0.350 0.889

Aortic PWV -0.534 -1.623 0.554 0.336Figueroa 2013b Brachial ankle PWV Diet -0.983 -1.645 -0.321 0.004Figueroa 2013b Brachial ankle PWV Diet+Exercise -0.829 -1.436 -0.221 0.007Hughes 2012 Brachial ankle PWV Diet+Exercise -0.127 -0.246 -0.007 0.037Maeda 2013 Brachial ankle PWV Diet+Exercise -0.708 -1.240 -0.177 0.009Miyaki 2012 Brachial ankle PWV Diet+Exercise -0.626 -1.245 -0.008 0.047Satoh 2008 Brachial ankle PWV Diet+Exercise -0.189 -0.523 0.145 0.267

Brachial ankle PWV -0.483 -0.784 -0.182 0.002Barinas- Mitchell 2006 Carotid femoral PWV Diet+Exercise+drugs -0.455 -0.789 -0.121 0.008Blumenthal 2010 Carotid femoral PWV Diet+Exercise -0.642 -1.048 -0.236 0.002Chakera 2010 Carotid femoral PWV Diet+drugs -0.173 -0.540 0.193 0.354Clifton 2005 Carotid femoral PWV Diet -0.384 -0.790 0.022 0.064Clifton 2005 Carotid femoral PWV Diet -0.589 -1.089 -0.089 0.021Dengo 2010 Carotid femoral PWV Diet -0.900 -1.639 -0.161 0.017Figueroa 2013b Carotid femoral PWV Diet -0.424 -0.991 0.144 0.143Figueroa 2013b Carotid femoral PWV Diet+Exercise -0.421 -0.968 0.125 0.131Howden 2013 Carotid femoral PWV Diet+Exercise 0.174 -0.289 0.637 0.462Hughes 2012 Carotid femoral PWV Diet+Exercise -0.171 -0.291 -0.051 0.005Keogh 2007 Carotid femoral PWV Diet 0.237 -0.574 1.048 0.567Keogh 2007 Carotid femoral PWV Diet 0.000 -0.800 0.800 1.000Keogh 2008 Carotid femoral PWV Diet -0.291 -0.568 -0.013 0.040Keogh 2008 Carotid femoral PWV Diet -0.637 -0.950 -0.323 0.000Miyaki 2009 Carotid femoral PWV Diet -0.639 -1.260 -0.018 0.044Miyaki 2012 Carotid femoral PWV Diet+Exercise -0.640 -1.261 -0.019 0.043Nordstrand 2013 Carotid femoral PWV Diet -0.197 -0.404 0.011 0.063Nordstrand 2013 Carotid femoral PWV Diet+Exercise -0.363 -0.579 -0.147 0.001Pirro 2004 Carotid femoral PWV Diet -0.413 -0.758 -0.068 0.019Samaras 2012 Carotid femoral PWV Bariatric surgery -0.289 -0.823 0.246 0.290Wycherley 2010 Carotid femoral PWV Diet -0.458 -0.862 -0.054 0.026Wycherley 2010 Carotid femoral PWV Diet -0.521 -0.957 -0.086 0.019

Carotid femoral PWV -0.347 -0.439 -0.255 0.000Bradley 2009 Carotid radial PWV Diet -0.152 -0.721 0.417 0.602Bradley 2009 Carotid radial PWV Diet -0.004 -0.569 0.562 0.990Chakera 2010 Carotid radial PWV Diet+drugs 0.100 -0.265 0.465 0.591

Carotid radial PWV 0.020 -0.250 0.290 0.886Figueroa 2013b Femoral ankle PWV Diet -0.821 -1.450 -0.192 0.010Figueroa 2013b Femoral ankle PWV Diet+Exercise -0.454 -1.005 0.096 0.106Hughes 2012 Femoral ankle PWV Diet+Exercise 0.063 -0.056 0.182 0.298

Femoral ankle PWV -0.340 -0.904 0.224 0.237

-2.00 -1.00 0.00 1.00 2.00


Figure 3. Random effects meta-analysis of the effect of weight loss on pulse wave velocity measured at the different arterial segments. CI indicates confidence interval; and PWV, pulse wave velocity.

Regression of change systolic blood pressure on Std diff in means

change systolic blood pressure

Std

diff

in m

eans

-18.11 -15.70 -13.29 -10.87 -8.46 -6.05 -3.64 -1.23 1.19 3.60 6.01

0.40

0.26

0.12

-0.02

-0.16

-0.30

-0.44

-0.58

-0.72

-0.86

-1.00

Regression co-efficient= 0.02; p=0.002; tau-squared= 0.0

Figure 4. Meta-regression of the effect of change in systolic blood pressure on change in pulse wave velocity.

Regression of change diastolic blood pressure on Std diff in means

change diastolic blood pressure

Std

diff

in m

eans

-10.95 -9.69 -8.43 -7.17 -5.91 -4.65 -3.39 -2.13 -0.87 0.39 1.65

0.40

0.26

0.12

-0.02

-0.16

-0.30

-0.44

-0.58

-0.72

-0.86

-1.00

Regression co-efficient = 0.05; p= 0.0001; tau squared 0.0

Figure 5. Meta-regression of the effect of change in diastolic blood pressure on change in pulse wave velocity.



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DiscussionThis meta-analysis shows that modest weight loss (8% of initial body weight) achieved with diet and lifestyle inter-ventions seems to improve PWV. Carotid femoral PWV and brachial ankle pulse wave velocity, robust indirect mea-sures of arterial stiffness that are predictive of cardiovas-cular events and mortality,7,32 were improved with weight loss. In addition, meta-regression showed that the change in systolic and diastolic blood pressure was correlated with the change in PWV. To the authors knowledge, this is the first systematic review and meta-analysis to be conducted on the topic.

A previous meta-analysis of the effect of bariatric surgery on cardiovascular risk factors and measures of cardiac struc-ture and function showed that the Framingham Risk Score was reduced and left ventricular ejection fraction and left ventricu-lar mass were improved after bariatric surgery.33 The weighted mean excessive weight loss was 54% in the meta-analysis by Vest et al.33 PWV was not included in this meta-analysis. The results of the current meta-analysis show that an improvement in PWV can be seen with more modest weight loss (8%), which can be achieved with diet and lifestyle measures.

In this meta-analysis, weight loss of >10% of initial body weight was associated with an improvement in cfPWV of ≈0.8 m/s. A previous meta-analysis of longitudinal stud-ies, with a mean follow-up time of 7.7 years, showed that with a 1 m/s lower cfPWV the risk of a cardiovascular event was reduced by 14%.34 Furthermore, a recent meta-analysis showed that arterial stiffness was improved with antioxi-dant supplementation (SMD, −0.17; 95% CI, −0.26, −0.08; P<0.001)35 and Pase et al36 showed that omega 3 supplemen-tation (SMD Hedges g, 0.33; 95% CI, 0.11, 0.56; P=0.044) reduced PWV. In both of these meta-analyses, the effect sizes were similar to what we observed with weight loss (SMD −0.32). These findings together suggest that weight loss may be an effective way to improve vascular health but this needs to be confirmed by a well-designed placebo-con-trolled randomized trial.

Meta-regression showed that the change in systolic and diastolic blood pressure was correlated with the change in PWV. A systematic review of observational studies showed that blood pressure was an independent predictor of PWV in 90% of published studies involving the 2 outcomes.37 The results of the meta-regression showed that the change in blood pressure was correlated with the change in PWV, although the direction of the causality cannot be established. Many epide-miological studies have shown a positive association between body mass index and PWV, independent of age and blood pressure, which becomes evident as early as childhood.38–40 It was shown by Weisbrod et al41 that when mice were fed a high fat, high sucrose diet that significantly increased their body weight, PWV was increased by 2.4-fold after 1 month, compared with a normal diet. An increase in systolic blood pressure was not observed until 6 months and diastolic blood pressure remained unchanged. This study concluded that arte-rial stiffness preceded hypertension.41 An analysis from the Framingham Offspring Study supported this finding as it was found that blood pressure measured between 1998 and 2001

did not predict PWV measured between 2005 and 2008.42 PWV has been found to predict systolic blood pressure in both the Framingham Offspring Study and the Baltimore Longitudinal Study of Aging.42,43 These studies together sug-gest that the reduction in PWV caused by the weight loss may reduce the risk of systolic hypertension.

The reduction in PWV seen with weight loss may also be explained by a reduction in vascular remodelling and inflam-matory molecules. In the study by Weisbrod et al,41 after 2 months of hypercaloric feeding the greatest increase in PWV was observed and this was accompanied by a reduction in endothelial nitric oxide function. In addition, activity of tis-sue transglutaminase-2 enzyme, which increases extracel-lular matrix cross-linking, was increased. When the mice were put back onto a normal diet they lost 12.5% of body weight (returned to control weight) within 2 weeks and PWV was reduced to control measurements within 2 months.41 After diet reversal inflammatory gene expression was nor-malized and a reduction in extracellular matrix cross-links were observed. A study of healthy adults showed that metal-loproteinase-9 and serum elastase activity were positively associated with PWV, indicating a role for elastin changes in arterial stiffening.44 This suggests that obesity causes arte-rial stiffening as a result of an increase in inflammation and vascular remodelling molecules and a change in endothelial function.

Limitations of this analysis include the low quality of the included studies because only 3 studies were random-ized controlled trials and the methods of randomization and blinding were not reported. In addition, there was evidence of publication bias. Therefore, the evidence provided by this meta-analysis is of a low quality and can only be inter-preted as hypothesis generating. A subgroup analysis for dietary composition was unable to be performed because the macro-nutrient composition was not reported in many articles.

In this meta-analysis of 20 studies, including data from 1259 participants, it was shown that when modest weight loss (8% of initial body weight) was achieved, PWV was reduced (SMD, −0.32; 95% CI, −0.41, −0.24; P=0.0001). In addition, the change in PWV was correlated with the change in systolic and diastolic blood pressure. However, because of the low methodological quality of the included studies, well-designed randomized controlled trials are required to confirm this finding. The results of this meta-analysis sug-gest that weight loss may improve PWV, although future research is required.

Sources of FundingJ. Keogh is a Fellow of the South Australian Cardiovascular Research Development Program funded by the Heart Foundation and the Government of South Australia. P.M. Clifton is supported by a National Health and Medical Research Centre Principal Research Fellowship. K.S. Petersen is funded by an Australian Postgraduate Award+UniSA Rural and Isolated Top-up Scholarship. N. Blanch is funded by a University of South Australia Postgraduate Award. This research was jointly funded through these fellowships and the University of South Australia.



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DisclosuresNone.

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Arterial stiffness is an independent risk factor for cardiovascular disease. There has been no quantitative synthesis of the effect of weight loss on pulse wave velocity. Here we report on a meta-analysis of 20 studies, including data from 1259 participants, which shows that modest weight loss (mean 8% of total body weight), achieved with diet and lifestyle changes seems to improve pulse wave velocity. The results of this meta-analysis suggest that weight loss may improve pulse wave velocity, although well-designed randomized placebo-controlled trials are required to confirm this finding.

Significance



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Kristina S. Petersen, Natalie Blanch, Jennifer B. Keogh and Peter M. CliftonEffect of Weight Loss on Pulse Wave Velocity: Systematic Review and Meta-Analysis

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1

Methods

Search strategy

A systematic literature search was conducted, from the index date of each database through to March 2014 using PubMed (http://www.ncbi.nlm.nih.gov/pubmed, since 1966), EMBASE (http://embase.com, since 1947), MEDLINE (http://www.nlm.nih.gov/bsd/pmresources.html, since 1946) and the Cochrane Library (http://www.thecochranelibrary.com, since 1951) to identify all of the intervention trials that have investigated the effect of weight loss on arterial compliance. See Table 1 for the search terms that were used. Reference lists of the identified publications were searched for additional relevant articles. Authors were not contacted to identify additional studies. The search was restricted to studies of humans.

Selection criteria

The search strategy was developed to identify all of the intervention trials that had investigated the effect of weight loss on arterial compliance. However, only trials reporting on weight loss and PWV will be reported on in this paper. Intervention trials investigating the effect of weight loss induced by an energy restricted diet with or without exercise, anti-obesity drug or bariatric surgery on PWV in adults of 18 years or older were included. Studies identified by the search strategy were screened by the title and abstract and excluded if they were not relevant to the research question. The full text article of studies that were not excluded based on the title or abstract were obtained and assessed against the inclusion criteria. Studies were excluded if weight loss was primarily achieved with physical activity or weight or body mass index was not reported pre or post intervention. Studies reporting median and interquartile range were not included in the meta-analysis, however were included in the qualitative synthesis. There was no limit on the duration of the intervention; where measurements were provided for a number of time points during the intervention period, data from the greatest time since baseline were used.

Outcomes

The outcome was PWV measured at the following sites carotid-femoral, femoral- ankle, brachial- ankle and carotid- radial and aortic. PWV is calculated as distance (meters) divided by time delay (seconds) and is determined by measuring the waveforms at two sites (carotid-femoral, femoral- ankle, brachial- ankle and carotid- radial) using applanation tonometry and the ratio of the distance between the sites to the time delay is calculated. Alternatively, a Doppler probe may be used to record arterial waveforms with a simultaneous ECG recording to calculate the time between the R- wave and the upstroke of each waveform.1

Aortic PWV may be directly measured (in m/s) using MRI. In the paper by Dengo et al2 aortic PWV was calculated by measuring the waveform at the carotid and femoral arteries and using an equation developed to estimate the direct distance between the sites.3

Data extraction

http://www.ncbi.nlm.nih.gov/pubmed

http://embase.com/

http://www.nlm.nih.gov/bsd/pmresources.html

http://www.thecochranelibrary.com/

2

The data was extracted for each identified publication and entered by two independent researchers and cross-verified. Authors were contacted for additional information not reported in the publication. The demographic characteristics of the study population and details of the study protocol and methodology were also extracted from the included studies. For studies with multiple treatment arms, treatments that did not meet the inclusion criteria were excluded. In studies with multiple treatment arms and only one control group the sample size of the control group was divided by the number of treatment groups to avoid duplication of the control group sample size.

Critical appraisal

The Newcastle-Ottawa Scale4 was used to assess the quality of the studies.

Statistical analysis

Statistical analysis was conducted using Comprehensive Meta Analysis V2 (Eaglewood, NJ 07631). Data is reported as standardised mean difference (SMD) and 95% confidence intervals. To estimate the effect size (m/s) for PWV the difference in means was calculated. For all group comparisons significance was set at p<0.05. Most studies did not have a control group and therefore the change from baseline was used. When there was a control group this was used for comparison. Treatment effects were pooled and the SMD was calculated. When a study reported on more than one measure of PWV, only one measure was included in the pooled analysis and precedence was given to carotid femoral PWV. Random effects analysis was used as significant heterogeneity was observed. Heterogeneity between studies was examined by chi-square tests for significance, and the measured inconsistency (I2) statistics with a measurement >50% indicating substantial heterogeneity.5 Meta-regression was performed using the random effect model (method of moments). Possible confounders were not adjusted for in the meta-regressions. Sensitivity analysis was conducted to determine if any individual study was responsible for the observed effect and the risk of publication bias was assessed by examining the funnel plots and Egger’s test.

Table 1: Search strategy

Terms

Search 1: weight reduction/

Search 2: caloric restriction/

Search 3: diet* restrict*.mp

Search 4: energy restrict*. mp

Search 5: obesity/

Search 6: bariatric surgery/

Search 7: 1 or 2 or 3 or 4 or 5 or 6

Search 8: arterial stiffness/

Search 9: artery compliance/

Search 10: pulse pressure/

Search 11: augmentation index/

Search 12: pulse wave/

3

Search 13: pulse wave velocity.mp.

Search 14: central pressure.mp.

Search 15: arterial elasticity.mp.

Search 16: 8 or 9 or 10 or 11 or 12 or 13 or 14 or 15

Search 17: 7 and 16

Search 18: limit 17 to (human)

*The search strategy identified in this table was designed for EMBASE (http://embase.com); equivalent terms were used for MEDLINE (http://www.nlm.nih.gov/bsd/pmresources.html), PubMed (http://www.ncbi.nlm.nih.gov/pubmed) and the Cochrane Library (http://www.thecochranelibrary.com).

References

1. Laurent S, Cockcroft J, Van Bortel L, Boutouyrie P, Giannattasio C, Hayoz D, Pannier B, Vlachopoulos C, Wilkinson I,Struijker-Boudier H. Expert consensus document on arterial stiffness: methodological issues and clinical applications. Eur Heart J. 2006; 27:2588-2605.

2. Dengo AL, Dennis EA, Orr JS, Marinik EL, Ehrlich E, Davy BM,Davy KP. Arterial destiffening with weight loss in overweight and obese middle-aged and older adults. Hypertension. 2010; 55:855-61.

3. Vermeersch SJ, Rietzschel ER, De Buyzere ML, Van Bortel LM, Gillebert TC, Verdonck PR, Laurent S, Segers P,Boutouyrie P. Distance measurements for the assessment of carotid to femoral pulse wave velocity. J Hypertens. 2009; 27:2377-2385.

4. Wells G, Shea B, O'Connell D, Peterson J, Welch V, Losos M,Tugwell P, The Newcastle-Ottawa Scale (NOS) for assessing the quality of nonrandomised studies in meta-analyses. DOI: http://www.ohri.ca/programs/clinical_epidemiology/oxford.asp.

5. Gagnier J, Morgenstern H, Altman D, Berlin J, Chang S, McCulloch P, Sun X,Moher D. Consensus-based recommendations for investigating clinical heterogeneity in systematic reviews. BMC Med Res Methodol. 2013; 13:106.

http://embase.com/

http://www.nlm.nih.gov/bsd/pmresources.html

http://www.ncbi.nlm.nih.gov/pubmed

http://www.thecochranelibrary.com/

http://www.ohri.ca/programs/clinical_epidemiology/oxford.asp

Records identified through

database searching

(n = 7712)

PubMed n= 3360

EMBASE n=1940

MEDLINE n=338

Cochrane Library n=2074

Scre

enin

g In

clu

ded

El

igib

ility

Id

enti

fica

tio

n

Additional records identified

through other sources

(n = 1)

Records after duplicates removed

(n =6544 )

Records screened

(n = 6544)

Records excluded

(n = 6119)

Full-text articles assessed

for eligibility

(n = 425)

Full-text articles

excluded, with reasons

(n = 403)

PWV not a reported

outcome n=393

Not a weight loss study

n=8

Repeated data from

another study n=1

Weight loss exercise

induced n=1

Studies included in

qualitative synthesis

(n = 22)

Studies included in

quantitative synthesis

(meta-analysis)

(n = 20, 3 controlled

trials)

Supplement Material

Figure I: PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-analysis) Flowchart.

Figure II: Random effects meta-analysis of the effect of weight loss on carotid femoral and brachial ankle pulse wave velocity

S tudy nam e Outcom e Com par ison S tatistics for each study S td diff in m eans and 95% C I S ubgr oup within study

S td diff Lower Upper in means limit limit p-Value

B arinas- Mitchell 2006 Carotid femoral P WV (ms) Diet+E xercise+drugs -0.455 -0.789 -0.121 0.008 E nergy restricted diet + exercise + Orlistat -8

B lumenthal 2010 Carotid femoral P WV (ms) Diet+E xercise -0.642 -1.048 -0.236 0.002 E nergy restricted DA S H diet + exercise -10

Chakera 2010 Carotid femoral P WV (ms) Diet+drugs -0.173 -0.540 0.193 0.354 E nergy restricted diet +/- Rimonabant therapy (clinical decision) -3

Clifton 2005 Carotid femoral P WV (ms) Diet -0.384 -0.790 0.022 0.064 E nergy restricted diet (low fat diet, high CHO) -7

Clifton 2005 Carotid femoral P WV (ms) Diet -0.589 -1.089 -0.089 0.021 Meal replacement -6

Dengo 2010 Carotid femoral P WV (ms) Diet -0.900 -1.639 -0.161 0.017 E nergy restricted diet -8

Figueroa 2013b Carotid femoral P WV (ms) Diet -0.424 -0.991 0.144 0.143 E nergy restricted diet -6

Figueroa 2013b Carotid femoral P WV (ms) Diet+E xercise -0.421 -0.968 0.125 0.131 E nergy restricted diet + exercise (resistance training) -6

Howden 2013 Carotid femoral P WV (ms) Diet+E xercise 0.174 -0.289 0.637 0.462 E nergy restricted diet + exercise -2

Hughes 2012 Carotid femoral P WV (ms) Diet+E xercise -0.171 -0.291 -0.051 0.005 E nergy restricted diet + exercise -8

K eogh 2007 Carotid femoral P WV (ms) Diet 0.237 -0.574 1.048 0.567 E nergy restricted diet ( 60% CHO, 20% fat) -6

K eogh 2007 Carotid femoral P WV (ms) Diet 0.000 -0.800 0.800 1.000 E nergy restricted diet (33% CHO, 7% saturated fat) -5

K eogh 2008 Carotid femoral P WV (ms) Diet -0.291 -0.568 -0.013 0.040 E nergy restricted diet (4% CHO, 20% saturated fat) -8

K eogh 2008 Carotid femoral P WV (ms) Diet -0.637 -0.950 -0.323 0.000 E nergy restricted diet (46% CHO, <8% saturated fat) -6

Maeda 2013 B rachial ankle P WV (ms) Diet+E xercise -0.708 -1.240 -0.177 0.009 E nergy restricted diet + exercise (aerobic) -14

Miyaki 2009 Carotid femoral P WV (ms) Diet -0.639 -1.260 -0.018 0.044 E nergy restricted diet -9

Miyaki 2012 Carotid femoral P WV (ms) Diet+E xercise -0.640 -1.261 -0.019 0.043 E nergy restricted diet + whole body vibration -11

Nordstrand 2013 Carotid femoral P WV (ms) Diet -0.197 -0.404 0.011 0.063 E nergy restricted diet -7

Nordstrand 2013 Carotid femoral P WV (ms) Diet+E xercise -0.363 -0.579 -0.147 0.001 E nergy restricted diet + exercise -5

P irro 2004 Carotid femoral P WV (ms) Diet -0.413 -0.758 -0.068 0.019 Iso-caloric diet low in cholesterol (<200mg/d)/low saturated fat (5% ) -3

S amaras 2012 Carotid femoral P WV (ms) B ariatric surgery -0.289 -0.823 0.246 0.290 E nergy restricted diet + bariatric surgery -13

S atoh 2008 B rachial ankle P WV (ms) Diet+E xercise -0.189 -0.523 0.145 0.267 E nergy restricted diet + exercise -8

W ycherley 2010 Carotid femoral P WV (ms) Diet -0.458 -0.862 -0.054 0.026 E nergy restricted diet (4% CHO, 20% saturated fat) -16

W ycherley 2010 Carotid femoral P WV (ms) Diet -0.521 -0.957 -0.086 0.019 E nergy restricted diet (46% CHO, 30% fat) -12

-0.348 -0.437 -0.259 0.000

-2.00 -1.00 0.00 1.00 2.00


Regression co-efficient= -0.003; p=0.82; tau-squared=0.01

Figure III: Meta-regression of the effect of weight loss (kg) on change in PWV

Regression of Weight loss (kg) on Std diff in means

Weight loss (kg)

Std

dif

f in

me

an

s

0.10 2.38 4.66 6.94 9.22 11.50 13.78 16.06 18.34 20.62 22.90

0.40

0.26

0.12

-0.02

-0.16

-0.30

-0.44

-0.58

-0.72

-0.86

-1.00

Regression co-efficient= 0.003; p=0.29; tau-squared=0.01

Figure IV: Meta-regression of the effect of baseline weight on change in PWV

Regression of Baseline weight on Std diff in means

Baseline weight

Std

dif

f in

me

an

s

58.82 67.44 76.05 84.67 93.28 101.90 110.52 119.13 127.75 136.36 144.98

0.40

0.26

0.12

-0.02

-0.16

-0.30

-0.44

-0.58

-0.72

-0.86

-1.00

Regression co-efficient =- 0.002; p= 0.88; tau- squared = 0.01

Figure V: Meta-regression of the effect of percentage weight loss on change in PWV

Regression of Percentage weight loss on Std diff in means

Percentage weight loss

Std

dif

f in

me

an

s

1.50 3.30 5.10 6.90 8.70 10.50 12.30 14.10 15.90 17.70 19.50

0.40

0.26

0.12

-0.02

-0.16

-0.30

-0.44

-0.58

-0.72

-0.86

-1.00

Regression co-efficient = 0.006; p= 0.63; tau squared 0.01

Figure VI: Meta- regression of the effect of the intervention period on change in PWV

Regression of Intervention period (months) on Std diff in means

Intervention period (months)

Std

dif

f in

me

an

s

-0.10 1.22 2.54 3.86 5.18 6.50 7.82 9.14 10.46 11.78 13.10

0.40

0.26

0.12

-0.02

-0.16

-0.30

-0.44

-0.58

-0.72

-0.86

-1.00

Table I: Assessment of the quality of the included studies using the Newcastle-Ottawa Scale

Study Selection Comparability Outcome Overall score Representativeness

of the intervention group

Representativeness of the control group

Ascertainment of weight loss

Demonstration that outcome of interest was not present at start of study

Comparability of intervention and control group at baseline

Measurement of PWV

Adequate follow-up time

Adequacy of follow up of cohorts

a) truly representative of the population the sample is derived from b) somewhat representative of the population the sample is derived from c) selected group of the population that is not representative d) no description of the study population

a) drawn from the same community as the intervention group b) drawn from a different source c) no description of the derivation of the intervention group NA not relevant to the study

a) measured b) self-reported c) no description

a) yes b) no NA not relevant to the study

a) intervention and control group matched at baseline b) Differences in baseline characteristics of the intervention and control group NA not relevant to the study

a) independent blind assessment b) performed by a trained operator c) self-report d) no description

a) yes (>1 month) b) no (<1 month)

a) complete follow up b) subjects lost to follow up unlikely to introduce bias (<25% or explanation provided that the people lost to follow-up are not different from the completers) (description provided of those lost) c) loss to follow up rate likely to introduce bias >25%

(no description of those lost provided) d) no statement

Barinas-Mitchell 20061

(a) NA (a) NA NA (a) (a) (b) 5

Blumenthal 20102

(a) (a) (a) NA (a) (a) (a) (b) 7

Bradley 20093

(a) NA (a) NA NA (a) (a) (b) 5

Chakera 20104

(a) NA (a) NA NA (a) (a) (b) 5

Clifton 20055

(a) NA (a) NA NA (a) (a) (b) 5

Cooper 20126

(a) NA (a) NA NA (a) (a) (c) 4

Dengo 20107

(a) (a) (a) NA (a) (b) (a) (d) 6

Figueroa 20138

(b) NA (a) NA NA (a) (a) (b) 5

Howden 20139

(a) (a) (a) NA (a) (b) (a) (b) 6

Hughes 201210

(a) NA (a) NA NA (a) (a) (b) 5

Keogh 200711

(a) NA (a) NA NA (a) (a) (c) 4

Keogh 200812

(a) NA (a) NA NA (a) (a) (b) 5

Maeda (b) NA (a) NA NA (a) (a) (d) 4

1. Barinas-Mitchell E, Kuller LH, Sutton-Tyrrell K, Hegazi R, Harper P, Mancino J,Kelley DE. Effect of weight loss and nutritional intervention on arterial stiffness in type 2 diabetes. Diabetes Care. 2006; 29:2218-2222.

2. Blumenthal JA, Babyak MA, Hinderliter A, Watkins LL, Craighead L, Lin PH, Caccia C, Johnson J, Waugh R,Sherwood A. Effects of the DASH diet alone and in combination with exercise and weight loss on blood pressure and cardiovascular biomarkers in men and women with high blood pressure: the ENCORE study. Arch Intern Med. 2010; 170:126-35.

3. Bradley U, Spence M, Courtney CH, McKinley MC, Ennis CN, McCance DR, McEneny J, Bell PM, Young IS,Hunter SJ. Low-fat versus low-carbohydrate weight reduction diets - Effects on weight loss, insulin resistance, and cardiovascular risk: A randomized control trial. Diabetes. 2009; 58:2741-2748.

4. Chakera A, Bunce S, Heppenstall C,Smith JC. The effects of weight loss using dietary manipulation and rimonabant therapy on arterial stiffness in type 2 diabetes. Artery Research. 2010; 4:47-51.

201313

Miyaki 201214

(b) NA (a) NA NA (a) (a) (d) 4

Miyaki 200915

(b) NA (a) NA NA (a) (a) (d) 4

Nordstrand 201316

(a) NA (a) NA NA (a) (a) (b) 5

Philippou 200917

(b) NA (a) NA NA (a) (a) (c) 4

Pirro 200418

(a) NA (a) NA NA (a) (a) (d) 4

Rider 201019

(a) NA (a) NA NA (a) (a) (c) 4

Samaras 201220

(a) NA (a) NA NA (a) (a) (b) 5

Satoh 200821

(a) NA (a) NA NA (a) (a) (a) 5

Wycherley 201022

(a) NA (a) NA NA (a) (a) (c) 4

5. Clifton PM, Keogh JB, Foster PR,Noakes M. Effect of weight loss on inflammatory and endothelial markers and FMD using two low-fat diets. Int J Obes (Lond). 2005; 29:1445-51.

6. Cooper JN, Buchanich JM, Youk A, Brooks MM, Barinas-Mitchell E, Conroy MB,Sutton-Tyrrell K. Reductions in arterial stiffness with weight loss in overweight and obese young adults: potential mechanisms. Atherosclerosis. 2012; 223:485-90.

7. Dengo AL, Dennis EA, Orr JS, Marinik EL, Ehrlich E, Davy BM,Davy KP. Arterial destiffening with weight loss in overweight and obese middle-aged and older adults. Hypertension. 2010; 55:855-61.

8. Figueroa A, Vicil F, Sanchez-Gonzalez MA, Wong A, Ormsbee MJ, Hooshmand S,Daggy B. Effects of diet and/or low-intensity resistance exercise training on arterial stiffness, adiposity, and lean mass in obese postmenopausal women. Am J Hypertens. 2013; 26:416-423.

9. Howden EJ, Leano R, Petchey W, Coombes JS, Isbel NM,Marwick TH. Effects of exercise and lifestyle intervention on cardiovascular function in CKD. Clin J Am Soc Nephrol. 2013; 8:1494-1501.

10. Hughes TM, Althouse AD, Niemczyk NA, Hawkins MS, Kuipers AL,Sutton-Tyrrell K. Effects of weight loss and insulin reduction on arterial stiffness in the SAVE trial. Cardiovasc Diabetol. 2012; 11.

11. Keogh JB, Brinkworth GD,Clifton PM. Effects of weight loss on a low-carbohydrate diet on flow-mediated dilatation, adhesion molecules and adiponectin. Br J Nutr. 2007; 98:852-859.

12. Keogh JB, Brinkworth GD, Noakes M, Belobrajdic DP, Buckley JD,Clifton PM. Effects of weight loss from a very-low-carbohydrate diet on endothelial function and markers of cardiovascular disease risk in subjects with abdominal obesity. Am J Clin Nutr. 2008; 87:567-576.

13. Maeda S, Miyaki A, Kumagai H, Eto M, So R, Tanaka K,Ajisaka R. Lifestyle modification decreases arterial stiffness and plasma asymmetric dimethylarginine level in overweight and obese men. Coron Artery Dis. 2013; 24:583-588.

14. Miyaki A, Maeda S, Choi Y, Akazawa N, Tanabe Y, So R, Tanaka K,Ajisaka R. The addition of whole-body vibration to a lifestyle modification on arterial stiffness in overweight and obese women. Artery Research. 2012; 6:85-91.

15. Miyaki A, Maeda S, Yoshizawa M, Misono M, Saito Y, Sasai H, Endo T, Nakata Y, Tanaka K,Ajisaka R. Effect of weight reduction with dietary intervention on arterial distensibility and endothelial function in obese men. Angiology. 2009; 60:351-357.

16. Nordstrand N, Gjevestad E, Hertel JK, Johnson LK, Saltvedt E, Roislien J,Hjelmesaeth J. Arterial stiffness, lifestyle intervention and a low-calorie diet in morbidly obese patients - A nonrandomized clinical trial. Obesity. 2013; 21:690-697.

17. Philippou E, Bovill-Taylor C, Rajkumar C, Vampa ML, Ntatsaki E, Brynes AE, Hickson M,Frost GS. Preliminary report: the effect of a 6-month dietary glycemic index manipulation in addition to healthy eating advice and weight loss on arterial compliance and 24-hour ambulatory blood pressure in men: a pilot study. Metabolism. 2009; 58:1703-8.

18. Pirro M, Schillaci G, Savarese G, Gemelli F, Mannarino MR, Siepi D, Bagaglia F,Mannarino E. Attenuation of inflammation with short-term dietary intervention is associated with a reduction of arterial stiffness in subjects with hypercholesterolaemia. Eur J Cardiovasc Prev Rehabil. 2004; 11:497-502.

19. Rider OJ, Tayal U, Francis JM, Ali MK, Robinson MR, Byrne JP, Clarke K,Neubauer S. The effect of obesity and weight loss on aortic pulse wave velocity as assessed by magnetic resonance imaging. Obesity. 2010; 18:2311-2316.

20. Samaras K, Viardot A, Lee PN, Jenkins A, Botelho NK, Bakopanos A, Lord RV,Hayward CS. Reduced arterial stiffness after weight loss in obese type 2 diabetes and impaired glucose tolerance: The role of immune cell activation and insulin resistance. Diab Vasc Dis Res. 2013; 10:40-48.

21. Satoh N, Shimatsu A, Kato Y, Araki R, Koyama K, Okajima T, Tanabe M, Ooishi M, Kotani K,Ogawa Y. Evaluation of the cardio-ankle vascular index, a new indicator of arterial stiffness independent of blood pressure, in obesity and metabolic syndrome. Hypertens Res. 2008; 31:1921-1930.

22. Wycherley TP, Brinkworth GD, Keogh JB, Noakes M, Buckley JD,Clifton PM. Long-term effects of weight loss with a very low carbohydrate and low fat diet on vascular function in overweight and obese patients: Original Article. J Intern Med. 2010; 267:452-461.

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