effect of weight loss induced by energy restriction on measures of arterial compliance
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A systematic review and meta-analysis - K Petersen et al - Atherosclerosis Journal (2016)TRANSCRIPT
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Atherosclerosis 247 (2016) 7e20
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Effect of weight loss induced by energy restriction on measures ofarterial compliance: A systematic review and meta-analysis
K.S. Petersen a, b, P.M. Clifton a, N. Lister a, J.B. Keogh a, *
a School of Pharmacy and Medical Sciences, University of South Australia, GPO Box 2471, Adelaide, South Australia 5000, Australiab The George Institute for Global Health, University of Sydney, P.O. Box M201 Missenden Road, Camperdown, Sydney, New South Wales 2050, Australia
a r t i c l e i n f o
Article history:Received 12 September 2015Received in revised form13 January 2016Accepted 26 January 2016Available online 29 January 2016
Keywords:Meta-analysisWeight lossWeight reductionArterial stiffnessArterial compliance
Abbreviations: BMI, Body Mass Index; CAVI, CardiChronic Kidney Disease; CVD, Cardiovascular DiseasGastric Bypass; PWV, Pulse Wave Velocity; SMD, StSOS, Swedish Obesity Study; VBG, Vertical Banded Ga* Corresponding author.
E-mail addresses: [email protected]@unisa.edu.au (P.M. Clifton), [email protected]@unisa.edu.au (J.B. Keogh).
http://dx.doi.org/10.1016/j.atherosclerosis.2016.01.0420021-9150/© 2016 Elsevier Ireland Ltd. All rights rese
a b s t r a c t
Aim: To conduct a systematic review and meta-analysis of clinical trials involving adults, to determinethe effect of weight loss induced by energy restriction with or without exercise, anti-obesity drugs orbariatric surgery on measures of arterial stiffness and compliance.Methods: A systematic search of Pubmed, EMBASE, MEDLINE and the Cochrane Library was conducted tofind intervention trials (randomised/non-randomised) that aimed to achieve weight loss and includedthe following outcome measures: cardio-ankle vascular index (CAVI), direct measures of area/diameterrelated to pressure change (including b-stiffness index, brachial or carotid artery compliance, aortic,carotid or brachial artery distensibility and strain), measures derived from peripheral pulse wave analysis(including augmentation index, augmentation pressure, distal oscillatory, proximal capacitive and sys-temic compliance) and pulse pressure. Data were analysed using Comprehensive Meta Analysis V2 usingrandom effects analysis. Standardised mean difference (SMD) is reported with negative values indicatingan improvement.Results: A total of 43 studies, involving 4231 participants, were included in the meta-analysis. Meanweight loss was approximately 11% of initial body weight. Weight loss improved CAVI (SMD �0.48;p ¼ 0.04), b-stiffness index (SMD ¼ �0.98; p ¼ 0.001), arterial compliance (SMD ¼ �0.61; p ¼ 0.0001)and distensibility (SMD �1.10; p ¼ 0.005), distal oscillatory compliance (SMD ¼ �0.41; p ¼ 0.03),proximal capacitive compliance (SMD �0.66; p ¼ 0.009), systemic arterial compliance (SMD �0.71;p ¼ 0.003) and reflection time (SMD �0.51; p ¼ 0.001). Augmentation index, strain, augmentationpressure and pulse pressure were not significantly changed with weight loss.Conclusion: Weight loss induced by energy restriction improves some measures of arterial complianceand stiffness.
© 2016 Elsevier Ireland Ltd. All rights reserved.
1. Introduction
Cardiovascular disease (CVD) is the leading cause of deathworldwide [1]. Globally the prevalence of obesity has more thandoubled since 1980 [2]. Obesity increases the risk of CVD byapproximately two fold [3]. Longer exposure to adiposity inadulthood has been shown to have a cumulative adverse effect on
o-ankle Vascular Index; CKD,e; GB, Gastric Banding; GBP,andardised Mean Difference;stroplasty.
.edu.au (K.S. Petersen), peter.mail.unisa.edu.au (N. Lister),
rved.
cardiovascular risk factors in later life but individuals that loseweight in adulthood have a more favourable cardiovascular riskprofile than those that have never lost weight, even if weight loss isnot maintained [4]. Bariatric surgery reduces cardiovascular events[5]. However, moderate weight loss has not been shown to reducecardiovascular endpoints in randomised controlled trials, despitean improvement in cardiovascular risk factors [6,7]. Arterial stiff-ening is a risk factor for CVD [8,9] and overweight and obesity isassociated with increased stiffening [10] and a reduction in arterialcompliance [11,12].
Arterial stiffness is defined as a reduction in the capacity of anartery to expand and contract in response to a given pressurechange and can be measured in many different ways [13].Compliance, distensibility and strain are direct measures of arterialarea/diameter related to a given pressure change [14]. In a stiffartery change in the area/diameter per pressure change is reduced.
K.S. Petersen et al. / Atherosclerosis 247 (2016) 7e208
The consequence of increased stiffness is an increase in the prop-agation of the pressure wave through the vasculature. This can bemeasured by pulse wave velocity (PWV) and pulse wave analysisparameters including augmentation index. In healthy arteries, thespeed of the forward pressure wave is low and therefore the re-flected wave arrives back at the aortic root during diastole. How-ever, when arteries stiffen the speed of the forward pressure waveincreases and the reflected wave arrives back at the central arteriesearlier adding to the forward wave and augmenting systolic pres-sure [15].
Reduced arterial compliance measured by distensibility isassociated with increased risk of CVD and all-cause mortality [16].In addition, increased arterial stiffness determined by augmenta-tion index and PWV increases the risk of a cardiovascular event andtotal mortality [8,9].
We have previously shown in a meta-analysis of 20 studies thatmodest weight loss is associated with an improvement in PWV, thegold standard for determining arterial stiffness [17]. However, oftenother indices of arterial stiffness are measured and there has beenno quantitative assessment of the effect of weight loss on thesemeasures [12]. The aim is to conduct a meta-analysis of interven-tion trials (with or without a no weight loss control group) todetermine the effect of weight loss achieved with an energyrestricted diet with or without exercise, anti-obesity drugs or bar-iatric surgery on cardio-ankle vascular index (CAVI), direct mea-sures of area/diameter related to pressure change (including b-stiffness index, brachial or carotid artery compliance, aortic, carotidor brachial artery distensibility and strain), measures derived fromperipheral pulse wave analysis (including augmentation index,augmentation pressure, distal oscillatory, proximal capacitive andsystemic compliance) and pulse pressure.
2. Methods
2.1. Search strategy
A systematic literature search was conducted, from the indexdate of each database through toMarch 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 theintervention trials that have investigated the effect of weight losson measures of arterial compliance and arterial stiffness. SeeTable S1 for the search terms that were used. Reference lists of theidentified publications were searched for additional relevant arti-cles. Authors were not contacted to identify additional studies. Thesearch was restricted to studies published in English involvinghumans. The search was conducted by two independent re-searchers (KSP and NL).
2.2. Selection criteria
The search strategy was developed to identify all of the inter-vention trials that had investigated the effect of weight loss ach-ieved by an energy restricted diet with or without exercise, anti-obesity drugs or bariatric surgery on arterial compliance or arte-rial stiffness. We have recently published a meta-analysis on theeffect of weight loss on PWV [17] and so trials reporting on PWVwill not be reported on in this paper despite being included in thesystematic review. Intervention trials investigating the effect ofweight loss achievedwith an energy restricted diet with or withoutexercise, anti-obesity drugs or bariatric surgery on measures ofarterial compliance and stiffness in adults 18 years or older wereincluded. Studies identified by the search strategy were screened
by the title and abstract and excluded if they were not relevant tothe research question. The full text article of studies that were notexcluded based on the title or abstract were obtained and assessedagainst the inclusion criteria. Studies were excluded if weight losswas primarily achieved with physical activity or weight or bodymass index (BMI) was not reported pre or post intervention. Therewas no limit on the duration of the intervention; where measure-ments were provided for a number of time points during theintervention period, data from the greatest time since baselinewere used.
2.3. Outcomes
Outcomes includedwere CAVI, direct measures of area/diameterrelated to pressure change (including b-stiffness index, brachial orcarotid artery compliance, aortic, carotid or brachial artery disten-sibility and strain), measures derived from peripheral pulse waveanalysis (including augmentation index, augmentation pressure,distal oscillatory, proximal capacitive and systemic compliance)and pulse pressure. A description of each of these measurements isincluded in the online-only Data Supplement.
2.4. Data extraction
The data were extracted for each identified publication andentered by two independent researchers (KSP and NL) and cross-verified. Authors were contacted for additional information notreported in the publication. The demographic characteristics of thestudy population and details of the study protocol and methodol-ogy were also extracted from the included studies. For studies withmultiple treatment arms, treatments that did not meet the inclu-sion criteria were excluded.
2.5. Critical appraisal
The Newcastle-Ottawa Scale [18] was used to assess the qualityof the studies. Briefly studies are given a score out of 9 based onselection of the study groups, comparability of the groups, andascertainment of the outcome.
2.6. Statistical analysis
Statistical analysis was conducted using Comprehensive MetaAnalysis V2 (Eaglewood, NJ 07631). Data is reported as standardisedmean difference (SMD) and 95% confidence intervals. For all groupcomparisons significance was set at p < 0.05. Most studies did nothave a control group and therefore the change from baseline wasused. When there was a control group this was used for compari-son. Treatment effects were pooled when a study had two treat-ment arms or contributed data for more than onemeasure includedin a category. A study could contribute data for more than onemeasurement in different categories. Treatment effects weredetermined by calculating the SMD with negative values indicatingimprovement in the outcome measurement for consistency i.e. if apositive change in the outcome measure indicates improvementthe values were inverted so that a negative SMD was reflective ofimprovement. Random effects analysis was used. Heterogeneitybetween studies was examined by chi-square tests for significance,and measured inconsistency (I2) >50% indicated substantial het-erogeneity [19]. To explore the sources of heterogeneity subgroupanalysis was performed with p < 0.05 indicating a significant be-tween group difference. For continuous study characteristics (e.g.age, weight loss, sample size, study duration and baseline arterialstiffness/compliance measure) the median value for each arterialstiffness/compliance measurement category was used as the cut
K.S. Petersen et al. / Atherosclerosis 247 (2016) 7e20 9
point. Subgroup analysis was also performed by intervention type(diet, diet þ exercise, bariatric surgery,diet þ exercise þ medication) and study population (overweight/obese or overweight/obese with comorbidities). The number ofcomparisons available for each subgroup analysis is based on thenumber of study arms contributing data. If � 1 comparison wasavailable for a subgroup the analysis was not conducted. In addi-tion, subgroup analysis for baseline arterial compliance, distensi-bility, distal oscillatory compliance, proximal capacitive complianceand systemic compliancewere not completed because of the lack ofstandard measurement and reporting of these methods. Sensitivityanalysis was conducted to determine if an individual study wasresponsible for the observed effect and the risk of publication biaswas assessed by examining the funnel plots.
3. Results
3.1. Studies
The search strategy identified 7713 publications and 6119 wereexcluded based on the title and the abstract, and a further 382 wereexcluded after full text assessment (see Fig. S1). A total of 43 pub-lications met the inclusion criteria and were included in the meta-analysis [20e62]. The characteristics of the included studies aresummarised in Tables 1 and 2.
To examine the presence of publication bias studies weregrouped in the following way due to the small number of studiesthat examined each measure: direct measures of area/diameterrelated to pressure change, pulse wave analysis and pulse pressure.There was evidence of publication bias for measures derived frompulse wave analysis and pulse pressure as shown by examination ofthe funnel plots (online-only Data Supplement). Publication biaswas not detected for direct measures of area/diameter related topressure change (online-only Data Supplement).
3.2. Study quality
Four randomised controlled trials were included [21,27,32,40]and 5 studies used a per protocol analysis to group participantsaccording to whether or not weight loss was achieved[31,32,48,53,57]. The remainder of the studies were randomisedtrials or quasi-experimental trials without a no weight loss con-trol allocation. The NewcastleeOttawa Scale was used to assessthe quality of the studies and is presented in the online-only DataSupplement. The mean score was 4.7 (maximum attainable score9). The majority of studies included participants that wererepresentative of the population they were derived from with theexception of the study by Ahmadi et al. [20] that included BiggestLoser contestants. Only 4 studies were randomised controlledtrials and the control groups were drawn from the same popu-lation as the intervention group and the baseline characteristicsof the groups were comparable. The remaining studies were un-controlled and reported only before and after intervention dataand thus do not control for time related changes. All of the studieshad a follow-up time of greater than 1 month. Nineteen studieshad a follow-up rate of greater than 75% or were able todemonstrate that the characteristics of the participants lost tofollow-up were not different to the completers. Ten studies had aloss to follow-up rate greater than 25% which may introduce biasand 14 studies did not provide a statement about the attritionrate.
3.3. Cardio-ankle vascular index
Four studies [28,33,41,50], involving 381 participants, were
included in this section and overall there was a weak significanteffect of weight loss (SMD �0.48; 95% CI �0.94, �0.03; p ¼ 0.04;Q ¼ 23; p ¼ 0.0001; I2 ¼ 87%), see Fig. 1. Mean weight loss wasapproximately 8%. Sensitivity analysis showed that the removal ofeither of the following studies by Iguchi et al. [63] or Nagayamaet al. [64] resulted in a non-significant effect of weight loss on CAVI.
3.4. Direct measures of diameter/area related to pressure change
3.4.1. b-stiffness indexFive studies [21,27,34,37,58] measured b-stiffness index and
overall there was a significant effect of weight loss (SMD �0.98;95% CI �1.30, �0.66; p ¼ 0.0001; Q ¼ 6; p ¼ 0.22; I2 ¼ 30%), seeFig. S5. Sensitivity analysis showed no differential effect when eachstudy was individually excluded from the analysis.
3.4.2. ComplianceFive studies [23,26,27,37,58] measured arterial compliance (ca-
rotid or brachial) and weight loss was associated with animprovement in compliance (SMD �0.61; 95% CI �0.88, �0.34;p ¼ 0.0001; Q ¼ 5; p ¼ 0.26; I2 ¼ 24%), see Fig. S6. Sensitivityanalysis showed no differential effect when each study was indi-vidually excluded from the analysis.
3.4.3. DistensibilitySix studies [20,21,23,26,34,47] measured arterial distensibility
(carotid, brachial or aortic) and weight loss was associated with animprovement in distensibility (SMD �1.10; 95% CI �1.86, �0.33;p ¼ 0.005; Q ¼ 61; p ¼ 0.0001; I2 ¼ 92%), see Fig. S6. Sensitivityanalysis showed no differential effect when each study was indi-vidually excluded from the analysis.
3.4.4. StrainTwo studies [21,34] measured strain (carotid or aortic) and there
was no statistically significant change with weight loss (SMD 1.60;95% CI �3.60, 6.80; p ¼ 0.55; Q ¼ 57; p ¼ 0.001; I2 ¼ 98%).
3.5. Direct measures of diameter/area related to pressure change
When the 9 studies [20,21,23,26,27,34,37,47,58] that measuredb-stiffness, compliance, distensibility and strain were combinedweight loss was associated with an improvement in these directmeasures of arterial compliance (SMD �0.67; 95% CI �1.10, �0.25;p ¼ 0.002; Q ¼ 36; p ¼ 0.001; I2 ¼ 78%) (Fig. 2). When the studieswere grouped by the measurement site [aortic (SMD �0.94; 95%CI �1.79, �0.09; p ¼ 0.03; Q ¼ 18; p ¼ 0.001; I2 ¼ 94%), brachial(SMD�0.22; 95% CI�0.43,�0.01; p¼ 0.04; Q¼ 0, p¼ 0.63; I2¼ 0%)or carotid (SMD �0.93; 95% CI �1.31, �0.55; p ¼ 0.001; Q ¼ 23;p ¼ 0.001; I2 ¼ 78)] measurements at all of the sites were signifi-cantly improved with weight loss.
3.5.1. Augmentation indexTwelve studies [22,24,25,29,32,35,36,43,44,49,55,61] measured
augmentation index and there was no statistically significantchange in this outcomewith weight loss (SMD�0.10; 95% CI�0.20,0.01; p ¼ 0.063; Q ¼ 11; p ¼ 0.48; I2 ¼ 0), see Fig. S7. The meanweight loss achieved in these studies was approximately 10 kg.After individual removal of the studies by Park et al. [43], Skiltonet al. [55] andWycherley et al. [61] weight loss was associated witha significant improvement in augmentation index.
3.5.2. Augmentation pressureThree studies measured augmentation pressure and there was
no statistically significant improvement in augmentation pressurewith weight loss (SMD �0.23; 95% CI �0.55, 0.10; p ¼ 0.17; Q ¼ 5;
Table 1Summary of the studies included in the meta-analysis.
Study Population Studyduration(wks.)
Groups Completedn
Menn (%)
Dropouts n (%)
Baselineweight (kg)
Finalweight (kg)
Weight losskg (%)
Age (years)
Ahmadi 2011 [20] Morbidly obese 28 Energy restricteddiet þ exercise
14 7(50) 3 (18) 152.6 ± 37.4 92.4 ± 23.5 �60.2 ± 23.3 (�39.4%) 32 ± 11
Aizawa 2009 [21] High CVD risk 24 Energy restricteddiet þ exercise
34 15 (44) e 96.3 ± 18.0 94.0 ± 17.6 �2.3 ± 3.8 (�2.4%) 54 ± 9
Control 29 15 (52) e 84.6 ± 16.3 83.9 ± 16.4 �0.7 ± 3.6 (�0.8%) 54 ± 8Bakker 2013 [22] Obese with obstructive sleep
apnoea24 Bariatric surgery 12 2 (17) e 133.6 ± 23.7 99.2 ± 14.9 �34.4 ± 14.8 (�25.7%) 43 (37e49)*
Balkestein 1999 [23] Obese 12 Energy restricted diet 15 15 (100) 3 (17) 103.0 ± 12.0 88.0 ± 8.0 �15 ± 7.1 (�14.6%) 39 ± 7Energy restricteddiet þ exercise
19 19 (100) 0 (0) 102.0 ± 13.0 87.0 ± 9.0 �15.0 ± 8.0 (�14.7%)
Bradley 2009 [24] 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 2010 [25] Obese with type 2 diabetes 24 Energy restricteddiet ± Rimonabant therapy
27 ~45% 2 (7) 107.0 ± 21.0 104.0 ± 21.0 �3 ± 13.3 (�2.8%) 57 ± 11
Dengel 2006 [26] Overweight or obese 24 Energy restricted diet 12 3 (25) e 86.3 ± 4.1 79.5 ± 4.0 �6.8 ± 2.3 (�7.9%) 55 ± 4Dengo 2010 [27] Overweight and obese 12 Energy restricted diet 25 9 (36) e 84.6 ± 13 77.5 ± 11 �7.1 ± 7.8 (�8.4%) 61 ± 1
Control 11 6 (55) e 91.0 ± 15.9 90.4 ± 16.3 �0.6 ± 10.2 (�0.7%) 66 ± 2Elian 2012 [28] Romanian overweight and
obese24 Energy restricted
diet þ exercise135 31 (23) 75 (36) 96.6 ± 17.15 84.6 ± 16.0 �12.0 ± 6.2 (�12.4%) 38
Figueroa 2013 [29] Obese post-menopausal 12 Energy restricted diet 14 0 (0) e 92.2 ± 13.8 86.5 ± 13.5 �5.7 ± 8.6 (�6.2%) 55 ± 4Energy restricteddiet þ exercise (resistancetraining)
14 0 (0) e 86.8 ± 13.5 81.9 ± 13.1 �4.9 ± 8.4 (�5.6%) 54 ± 4
Goldberg 2009 [30] Obese (no exclusion forcomorbidities)
24 Energy restricted þ exercise 37 9 (24) e 95.7 ± 21.6 87.4 ± 20.7 �8.3 ± 6.3 (�8.7%) 55 ± 7
Hofsø 2010 [31] Morbidly obese including type2 diabetics
52 Bariatric surgery (Roux-en-Y) 76 23 (30) 4 (5) 137.0 ± 21.0 e �41.3 ± 13.1 (�30 ± 8%) 43 ± 11
Energy restricteddiet þ exercise
63 19 (30) 3 (5) 125.0 ± 20.0 e �10.7 ± 12.0 (�8 ± 9%) 47 ± 11
Howden 2013 [32] Stage 3e4 CKD þ 1 or moreuncontrolled CVD risk factors
52 Energy restricteddiet þ exercise
36 24 (67) 5 (12) 92.6 ± 22.5 e �1.8 ± 4.2 (2%) 60 ± 10
Control 36 21 (58) 6 (14) 92.7 ± 24.1 e 0.7 ± 3.7 (0.8%) 62 ± 8Iguchi 2013 [33] BMI BMI BMI
Japanese overweight or obesewith metabolic syndrome
12 Energy restricteddiet þ exercise (achieved <3%weight loss)
19 7 (37) 27 (45) 32.1 ± 5.7 32.4 ± 5.7 49 ± 12
Energy restricteddiet þ exercise (achieved >3%weight loss)
14 4 (29) 29.4 ± 4.1 27.2 ± 3.7 �2.2 kg/m2 (�0.7%) 54 ± 10
Ikonomidis 2007 [34] Morbidly obese (no exclusionfor comorbidities)
156 Bariatric surgery 60 15 (25) e 134.0 ± 24.0 87.0 ± 17.0 �47 ± 14.6 (�35.1%) 35 ± 11Control (no surgery) 20 4 (20) e 131.0 ± 22.0 134.0 ± 23.0 3.0 ± 14.3 (2.3%) 37 ± 12
Keogh 2007 [35] Overweight and obese 52 Energy restricted diet (33%CHO, 7% saturated fat)
13 ~32% 23 (64) 91.5 ± 10.5 e �4.6 ± 2.1 (�5%) 50 ± 1
Energy restricted diet (60%CHO, 20% fat)
97.6 ± 6.1 e �5.5 ± 1.2 (�6%) 47 ± 2
Keogh 2008 [36] Overweight and obese 8 Energy restricted diet (4% CHO,20% saturated fat)
52 e 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 e 3 (6) 97.0 ± 14.4 90.7 ± 13.8 �6.2 ± 2.9 (�6.4%) 49 ± 8
Miyaki 2012 [38] Premenopausal overweight orobese
12 Energy restricted diet þ wholebody vibration
12 0 (0) e 80.5 ± 14.2 71.8 ± 11.4 �8.7 ± 8.5 (�10.8%) 42 ± 7
Miyaki 2009 [37] 12 Energy restricted diet 12 12 (100) e 88.0 ± 10.4 80 ± 13.9 �8 ± 8.3 (�9.1%) 45 ± 7
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Overweight and obese withmetabolic syndrome
Moran 2010 [39] Overweight with polycysticovary syndrome
16 Energy restricted diet (16%protein, 27% fat, 57% CHO)
14 0 (0) 8 (36) 98.6 ± 17.2 91.7 ± 15.9 �6.9 ± 0.8 (�7%) 33 ± 4
Energy restricted diet (27%protein, 28% fat, 43% CHO)
14 0 (0) 10 (42) 104.2 ± 19.7 95.6 ± 17.3 �8.6 ± 1.1 (�8.3%) 32 ± 4
Murphy 2012 [40] Overweight 24 High pork diet (5e7 serves/wk.) 72 e 12 (14) 91.4 ± 17.8 90.6 ± 17.8 �0.8 ± 11.3 (�0.9%) 48 ± 12Control (<100 g pork/wk.) 72 e 8 (10) 92.8 ± 17.0 93.2 ± 17.0 0.4 ± 10.7 (0.4%)
Nagayama 2013 [41] Obese Japanese (n ¼ 34 hadtype 2 diabetes)
12 Energy restricteddiet þ exercise (anaerobic)
47 23 (49) e 90.1 ± 24.9 83.0 ± 21.7 �7.1 ± 15.0 (�7.9%) 46 ± 13
Nordstrand 2013 [42] Morbidly obese (BMI >40 or>35 with obesity related comorbidity)
28 Energy restricted diet 91 34 (37) 7 (7) 137.8 ± 22.4 e �9.4 ± 4.3 (�6.8%) 42 ± 10
Energy restricteddiet þ exercise
88 32 (36) 14 (14) 125.2 ± 20.4 �6.6 ± 3.5 (�5.3%) 45 ± 11
Park 2005 [43] Pre emenopausal obese 12 Energy restricteddiet þ exercise
36 0 (0) 6 (14) 74.3 ± 12.0 66.4 ± 10.0 - 8 ± 3.5 (11.0%) 34 ± 7
Phillips 2009 [44] Men, 30e70yrs, BMI 30e38,with moderate e severeobstructive sleep apnoea
24 Energy restricteddiet þ Sibutramine (10e15 mg/d) þ þ exercise
63 63 (100) 30 (32) 107.1 ± 12.4 99.1 ± 12.6 �7.9 ± 4.9 (�7.4%) 47 ± 9
Pieterse 2005 [45] Overweight or obese 6 Energy restricted diet including200 g/d avocado (30.6 g fat)
28 ~21% 3 (10) 91.3 ± 13.9 89.2 ± 13.9 �2.1 ± 8.8 (�2.3%) 41 ± 9
Energy restricted diet including30 g mixed dietary fat
27 ~21% 3 (10) 91.2 ± 14.4 88.5 ± 13.5 �2.7 ± 8.9 (�3.0%)
Randall 2005 [46] Obese African Americans (noexclusion for comorbidities)
12 Energy restricted diet (mealsprovided) þ exercise
~23% 190 (88) BMI BMI
25 42.8 ± 6.4 38.6 ± 5.9 �4.2 kg/m2 (�9.8%) 47 ± 11 (n ¼ 215)Rider 2009 [47] Obese 52 Bariatric surgery 13 6 (20) 7 (19) 113.0 ± 23.0 92.0 ± 18.0 �33.0 ± 13.0 44 ± 8
Energy restricted low GI diet 17 �12.0 ± 7.0Rudofsky 2011 [48] Obese 12 Meal replacement (OPTIFAST) 21 11 (52) e 119.7 ± 12.8 98.3 ± 11.6 �21.4 ± 6.8 (�17.9%) 43 ± 13Samaras 2012 [49] Obese with type 2 diabetes or
impaired glucose tolerance24 Energy restricted diet and
bariatric surgery at 12wks14 8 (47) 3 (18) 127.5 ± 21.3 109.4 ± 18.7 �18.1 ± 12.9 (�14.2%) 50 ± 10
Satoh 2008 [50] Japanese obese ± metabolicsyndrome
12 Energy restricteddiet þ 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 restricteddiet þ exercise (achieved <5%weight loss)
117 50 (43) 77.5 ± 16.2 77.7 ± 17.3 0.2 ± 10.7 (0.3%) 54 ± 14
Schneider 2005 [51] Obese normotensive 16 Orlistat (120 mg tds) þ Energyrestricted diet þ exercise
24 3 (13) e 89.5 ± 12 81.5 ± 9 �8.0 ± 7.2 (8.9%) 44 ± 11
Seligman 2011 [52] Metabolic syndrome, nodiabetic, 30e55yrs
12 Energy restricteddiet þ exercise (10 000 steps/d)
25 16 (64) 2 (8) 99.0 ± 14.0 90.0 ± 12.5 �9 ± 8.5 (�9.1%) 44 ± 7
Energy restricteddiet þ exercise (45minsmoderate intensity 3 times/week)
25 16 (64) 4 (16) 100.0 ± 9.0 89.0 ± 8.0 �11 ± 5.6 (�11.0%) 43 ± 8
Energy restricted diet (20%fat) þ exercise (1hr walking/d)
25 17 (68) 2 (8) 100.0 ± 12.0 92.0 ± 11.0 �8 ± 7.3 (�8.0%) 42 ± 8
Shargorodsky 2006[53]
Morbidly obese atlow or high risk of CVD
16 Bariatric surgery at high risk ofCVD
21 5 (24) 3 (7) 116.4 ± 17.5 95.2 ± 16.3 �21.2 ± 3.6 (�18.0%) 41
Bariatric surgery at low risk ofCVD
20 7 (35) 124.7 ± 21.3 100.5 ± 17.7 �24.3 ± 6.1 (�19.0%) 35
Sjostrom 2001 [54] Obese 286 Bariatric surgery 1157 359 (31) e e e GB �20.7 ± 16.6 (�17.0%)VBG �20.8 ± 13.1 (�17.0%)GBP-33.8 ± 18.1 (�27.0%)
47 ± 6
Non-surgical, conventionalobesity treatment
1031 340 (33) e e e 1.5 ± 10.2 (1.6%) 49 ± 6
Skilton 2008 [55] Obese 16e36 Energy restricteddiet þ exercise >5% weight loss
6 ~21% 22 (56) 122.5 ± 25.6 e �6.4 ± 6.2 (�5%) 44 ± 7
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Table 1 (continued )
Study Population Studyduration(wks.)
Groups Completedn
Menn (%)
Dropouts n (%)
Baselineweight (kg)
Finalweight (kg)
Weight losskg (%)
Age (years)
Energy restricteddiet þ exercise <5% weight loss
11 e �0.6 (�2.2 to 1.0)
Toto- Moukouo1986 [56]
Obese with sustainedessential hypertension
4 Energy restricted diet low insodium
9 9 (100) e 88 ± 9 e Aimed to 10e15%(wt. loss not reported)
42 ± 9
Van de Borne2000 [57]
Morbidly obese 16 Gastric restrictive surgery 28 5(18) e 117.0 ± 15.9 95.0 ± 15.9 �22 ± 10.0 (�18.8%) 34 ± 9
Werner 2013 [58] Stage 1 hypertension 12 Energy restricteddiet þ exercise
15 7 (47) e 95.6 ± 19.0 90.1 ± 19.8 �5.5 ± 12.3 (�5.8%) 53 ± 9
Wolfson 2010 [59] BMI BMI BMIObese (no exclusion forcomorbidities)
156 Energy restricteddiet þ exercise (BMImaintained or reduced after 6/12 intervention)
22 5 (23) 20 (30) 35.4 ± 6.7 32.2 ± 6.4 �3.2 ± 1.4 (�9%) 61 ± 9
Energy restricteddiet þ exercise (BMI increasedafter 6/12 intervention)
25 7 (28) 35.4 ± 7.2 34.4 ± 7.4 �0.9 ± 2.4 (�3%) 57 ± 9
Wong 2013 [60] Obese 16 Energy restricted diet 12 e 2 (7) 92.0 ± 13.9 89.0 ± 13.9 �3.6 ± 8.8 (�3.3%) 60 ± 20Wycherley 2010 [61] Overweight or obese 52 Energy restricted diet (4% CHO,
20% saturated fat)26 8 (31) 31 (54) 94.2 ± 16.3 e �14.9 ± 10.7 (�16%) 50 ± 9
Energy restricted diet (46%CHO, 30% fat)
23 9 (39) 38 (62) 97.5 ± 12.9 e �11.5 ± 7.2 (�12%) 50 ± 7
Yamashita 1998 [62] Overweight or obese 16 Energy restricted diet high inred meat (150 g/d, 5 days/week)
19 0 (0) 4 (10) 89.9 ± 14.4 82.1 ± 13.5 �7.8 ± 8.9 (�8.7%) 41 ± 9
Energy restricted diet high insoybeans (130 g dried weight)
17 0 (0) 80.2 ± 10.3 72.6 ± 9.2 �7.6 ± 6.3 (�9.5%) 40 ± 9
Data is presented as mean ± standard deviation unless otherwise specified; *interquartile range.
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Table 2Change in measures of arterial stiffness/compliance with weight loss.
Study Group Measure of arterial compliance/stiffness
Baseline Final Change
Cardio-ankle vascular indexElian 2012 [28] Energy restricted diet þ exercise Cardio-ankle vascular index (%) 7.92 ± 1.28 7.21 ± 1.08 �0.71 ± 0.77Iguchi 2013 [33] Energy restricted diet þ exercise
(achieved <3% weight loss)Cardio-ankle vascular index (%) 8.17 ± 1.31 8.2 ± 1.74 0.03 ± 1.05*
Energy restricted diet þ exercise(achieved >3% weight loss)
8.49 ± 1.12 7.98 ± 1.12 �0.51 ± 0.71*
Nagayama 2013 [41] Energy restricted diet þ exercise(anaerobic)
Cardio-ankle vascular index (%) 8.2 ± 1.3 7.9 ± 1.2 �0.3 ± 0.80
Satoh 2008 [50] Energy restricted diet þ exercise(achieved >5% weight loss)
Cardio-ankle vascular index (%) 7.84 ± 2.1 7.62 ± 1.4 �0.22 ± 1.3
Energy restricted diet þ exercise(achieved <5% weight loss)
8.07 ± 1.08 7.98 ± 1.08 �0.09 ± 4.0
Direct measures of diameter/area related to pressure changeb- stiffness indexIkonomidis 2007 [34] Bariatric surgery b- stiffness index, aortic (%)y 2.6 ± 2.1 4.2 ± 1.9 1.6 ± 1.3*
Control (no surgery) 2.64 ± 1.9 2.6 ± 1.8 �0.04 ± 1.2*Aizawa 2009 [21] Energy restricted diet þ exercise b- stiffness index, carotid (%) 12.5 ± 6.41 9.8 ± 6.41 �2.7 ± 4.1*
Control 10.9 ± 5.92 11.3 ± 5.92 0.5 ± 3.6*Dengo 2010 [27] Energy restricted diet b- stiffness index, carotid (%) 10.68 ± 2.9 9.44 ± 2.6 �1.24 ± 1.1
Control 11.73 ± 2.95 12.25 ± 2.7 0.52 ± 1.2Miyaki 2009 [37] Energy restricted diet b- stiffness index, carotid (%) 12.5 ± 4.85 9.8 ± 2.77 �2.7 ± 3.1*Werner 2013 [58] Energy restricted diet þ exercise b- stiffness index, carotid (%) 13.32 ± 4.49 11.48 ± 3.10 �1.87 ± 3.21Compliance, brachialBalkestein 1999 [23] Energy restricted diet Compliance, brachial cross sectional
(mm2/kPa)0.1 ± 0.08 0.11 ± 0.39 0.1 ± 0.33*
Energy restricted diet þ exercise 0.12 ± 0.044 0.14 ± 2.18 0.02 ± 1.18*Dengel 2006 [26] Energy restricted diet Compliance, brachial artery
(mm2/mmHg)0.116 ± 0.008 0.128 ± 0.012 0.012 ± 0.026*
Compliance, carotidBalkestein 1999 [23] Energy restricted diet Compliance, carotid cross sectional
(mm2/kPa)1.37 ± 0.39 1.54 ± 0.39 0.17 ± 0.24*
Energy restricted diet þ exercise 1.33 ± 0.44 1.43 ± 0.44 0.1 ± 0.28*Dengo 2010 [27] Energy restricted diet Compliance, carotid
(mm2/mmHg � 10�1)0.120 ± 0.07 0.133 ± 0.06 0.0125 ± 0.02
Control 0.126 ± 0.04 0.120 ± 0.03 �0.0056 ± 0.02Miyaki 2009 [37] Energy restricted diet Compliance, carotid
(mm2/mmHg � 10�1)0.89 ± 0.35 1.21 ± 0.52 0.32 ± 0.32*
Werner 2013 [58] Energy restricted diet þ exercise Compliance, carotid(mm2/mmHg � 10�1)
0.71 ± 0.18 0.92 ± 0.31 0.20 ± 0.23
Distensibility, aorticIkonomidis 2007 [34] Bariatric surgery Distensibility, aortic root
(cm2 � dyn�1 � 10�6)1.9 ± 1.5 4.3 ± 1.7 2.4 ± 1.03*
Control (no surgery) 1.8 ± 1.0 1.74 ± 1.05 �0.06 ± 0.65*Rider 2009 [47] Bariatric surgery Distensibility, abdominal arterial
(mmHg�1 � 10�3)1.5 ± 2.0
Energy restricted low GI diet 1.8 ± 1.8Rider 2009 [47] Bariatric surgery Distensibility, ascending arterial
(mmHg�1 � 10�3)1.2 ± 2.7
Energy restricted low GI diet 0.7 ± 2.3Rider 2009 [47] Bariatric surgery Distensibility, proximal descending
arterial (mmHg�1 � 10�3)1.9 ± 1.9
Energy restricted low GI diet 0.1 ± 1.5Distensibility, brachialBalkestein 1999 [23] Energy restricted diet Distensibility coefficient, brachial
(10�3/kPa)4.9 ± 3.87 4.7 ± 2.32 �0.2 ± 2.4*
Energy restricted diet þ exercise 5.0 ± 1.74 5.7 ± 2.18 0.7 ± 1.3*Dengel 2006 [26] Energy restricted diet Distensibility, brachial artery
(mm Hg�1)0.038 ± 0.001 0.041 ± 0.006 0.003 ± 0.018*
Distensibility, carotidAhmadi 2011 [20] Energy restricted diet þ exercise Distensibility index, carotid (%) 3.37 ± 1.71 7.83 ± 1.82 4.46 ± 1.13Aizawa 2009 [21] Energy restricted diet þ exercise Distensibility, carotid
(1/mmHg � 10�20.143 ± 0.06 0.191 ± 0.07 0.05 ± 0.04*
Control 0.179 ± 0.05 0.179 ± 0.04 0.005 ± 0.5*Balkestein 1999 [23] Energy restricted diet Distensibility coefficient, carotid
(10�3/kPa)28.1 ± 10.07 32.5 ± 11.62 4.4 ± 7.0*
Energy restricted diet þ exercise 26.9 ± 10.46 30.0 ± 10.46 3.1 ± 6.6*StrainAizawa 2009 [21] Energy restricted diet þ exercise Strain, carotid (%) 5.13 ± 1.44 6.27 ± 1.88 1.14 ± 1.13*
Control 5.53 ± 2.28 5.40 ± 1.86 �0.13 ± 1.37*Ikonomidis 2007 [34] Bariatric surgery Strain modulus, aortic pressure
(cm2 � dyn�1 � 10�6)1.44 ± 0.13 0.41 ± 0.19 �1.03 ± 0.12*
Control (no surgery) 1.11 ± 0.05 1.2 ± 0.08 0.09 ± 0.05*
(continued on next page)
K.S. Petersen et al. / Atherosclerosis 247 (2016) 7e20 13
Table 2 (continued )
Study Group Measure of arterial compliance/stiffness
Baseline Final Change
Ikonomidis 2007 [34] Bariatric surgery Strain, aortic (%) 5.55 ± 4.0 10.5 ± 3.5 4.95 ± 2.4*Control (no surgery) 5.24 ± 2.9 5.58 ± 4.0 0.34 ± 2.4*
Peripheral pulse wave analysisAugmentation indexBakker 2013 [22] Bariatric surgery Augmentation index (%) 23.0 ± 9.2 19.9 ± 10.6 �3.1 ± 6.4*Bradley 2009 [24] Energy restricted diet (20% fat, 60%
CHO)Augmentation index (%) 17.0 ± 14.4 13.3 ± 16.3 �3.75 ± 5.53
Energy restricted diet (20% CHO,60% fat)
12.3 ± 12.2 14.5 ± 11.9 2.17 ± 7.22
Chakera 2010 [25] Energy restricteddiet ± Rimonabant therapy (clinicaldecision)
Augmentation index (%) 28 ± 11 28 ± 10 0 ± 6.7*
Figueroa 2013 [29] Energy restricted diet Augmentation index (%) 31 ± 7.48 32 ± 7.48 1 ± 4.7*Energy restricted diet þ exercise(resistance training)
37 ± 7.48 34 ± 11.22 �3 ± 6.9*
Howden 2013 [32] Energy restricted diet þ exercise Augmentation index (%) 25.7 ± 10.4 �0.2 ± 8.5Control Augmentation index (%) 24.5 ± 8.1 �1.0 ± 8.5
Keogh 2007 [35] Energy restricted diet (33% CHO, 7%saturated fat)
Augmentation index (%) 26.5 ± 7.12 24.4 ± 5.61 �2.1 ± 4.3*
Energy restricted diet (60% CHO,20% fat)
21.0 ± 11.86 22.3 ± 11.98 1.3 ± 7.5*
Keogh 2008 [36] Energy restricted diet (4% CHO, 20%saturated fat)
Augmentation index (%) 29.4 ± 9.6 28.9 ± 10.2 �0.5 ± 6.3*
Energy restricted diet (46% CHO,<8% saturated fat)
28.1 ± 12.8 27.6 ± 9.4 �0.5 ± 7.7*
Park 2005 [43] Energy restricted diet þ exercise Augmentation index (%) 22.64 ± 11.25 22.92 ± 9.09 0.28 ± 6.8*Rudofsky 2011 [48] Meal replacement (OPTIFAST) pulse wave analysis, finger
photoplethysmography (m/s)7.8 ± 2.1 6.8 ± 1.4 �1 ± 1.3*
Wycherley 2010 [61] Energy restricted diet (4% CHO, 20%saturated fat)
Augmentation index (%) 29.6 ± 10.20 29.7 ± 11.22 0.1 ± 6.8*
Energy restricted diet (46% CHO,30% fat)
27.1 ± 10.07 28 ± 8.63 0.9 ± 6.1*
Augmentation index at HR 75Figueroa 2013 [29] Energy restricted diet Augmentation index, adjusted to
HR 75 (%)30 ± 7.48 26 ± 3.74 �4 ± 5.0*
Energy restricted diet þ exercise(resistance training)
33 ± 7.48 29 ± 7.48 �4 ± 4.7*
Phillips 2009 [44] Energy restricteddiet þ Sibutramine (10e15 mg/d) þ þ exercise
Augmentation index, adjusted toHR 75 (%)
16.2 ± 8.0 16.0 ± 8.1 �0.2 ± 5.1*
Samaras 2012 [49] Energy restricted diet and bariatricsurgery at 12wks
Augmentation index, adjusted toHR 75 (%)
25.5 ± 9.73 21.7 ± 5.61 �3.8 ± 6.2*
Skilton 2008 [55] Energy restricted diet þ exercise>5% weight loss
Augmentation index, adjusted toHR 75 (%)
24.8 ± 7.2 0.7 ± 0.7
Energy restricted diet þ exercise<5% weight loss
�0.8 ± 0.7
Augmentation pressureBradley 2009 [24] Energy restricted diet (20% CHO,
60% fat)Augmentation pressure (mmHg) 7.4 ± 7.1 8.4 ± 5.4 1 ± 4.3*
Energy restricted diet (20% fat, 60%CHO)
9.2 ± 7.4 8.3 ± 7.8 �0.9 ± 4.8*
Figueroa 2013 [29] Energy restricted diet Augmentation pressure (mmHg) 14 ± 3.74 13 ± 3.74 �1 ± 2.4*Energy restricted diet þ exercise(resistance training)
17 ± 3.74 15 ± 3.74 �2 ± 2.4*
Phillips 2009 [44] Energy restricteddiet þ Sibutramine (10e15 mg/d) þ þ exercise
Augmentation pressure, adjusted toHR 75 (mmHg)
7.8 ± 4.9 7.4 ± 4.0 �0.4 ± 2.9*
Compliance, distal oscillatoryGoldberg 2009 [30] Energy restricted þ exercise Compliance, distal oscillatory
(ml/mmHg �100)4.3 ± 2.3 5.5 ± 2.6 1.2 ± 1.6*
Moran 2010 [39] Energy restricted diet (16% protein,27% fat, 57% CHO)
Compliance, distal oscillatory(mL/mmHg � 100)
7.7 ± 2.0 10.0 ± 2.9 2.3 ± 1.8*
Energy restricted diet (27% protein,28% fat, 43% CHO)
7.9 ± 2.4 8.6 ± 3.1 0.7 ± 1.9*
Murphy 2012 [40] High pork diet (5e7 serves/wk) Compliance, distal oscillatory(ml/mmHg �10)
7.9 ± 3.39 8.1 ± 3.39 0.2 ± 2.2*
Control (<100 g pork/wk.) 8.3 ± 3.39 8.6 ± 4.24 0.3 ± 2.5*Schneider 2005 [51] Orlistat (120 mg tds) þ Energy
restricted diet þ exerciseCompliance, distal oscillatoryml/mmHg)
5.9 ± 3.2 5.9 ± 2.8 0 ± 1.9*
Shargorodsky 2006 [53] Bariatric surgery at high risk of CVD Compliance, distal oscillatory(ml/mmHg �100)
6.30 ± 2.74 7.25 ± 1.85 0.95 ± 1.9
Bariatric surgery at low risk of CVD 9.03 ± 5.11 8.67 ± 2.45 �0.34 ± 4.5Wolfson 2010 [59] Energy restricted diet þ exercise
(BMI maintained or reduced after 6/12 intervention)
Compliance, distal oscillatory(ml/mmHg �100)
3.5 ± 1.9 6.2 ± 2.9 2.7 ± 1.8*
K.S. Petersen et al. / Atherosclerosis 247 (2016) 7e2014
Table 2 (continued )
Study Group Measure of arterial compliance/stiffness
Baseline Final Change
Energy restricted diet þ exercise(BMI increased after 6/12intervention)
4.3 ± 2.0 4.6 ± 1.9 0.3 ± 1.2*
Wong 2013 [60] Energy restricted diet Compliance, distal oscillatory (ml/mmHg)
0.075 ± 0.03 0.071 ± 0.04 �0.004 ± 0.02
Compliance, proximal capacitiveGoldberg 2009 [30] Energy restricted þ exercise Compliance, proximal capacitive
(ml/mmHg � 10)12.0 ± 4.1 15.7 ± 4.7 3.7 ± 2.8*
Moran 2010 [39] Energy restricted diet (16% protein,27% fat, 57% CHO)
Compliance, proximal capacitive(mL/mmHg � 10)
13.8 ± 1.9 14.7 ± 4.3 0.9 ± 3.0*
Energy restricted diet (27% protein,28% fat, 43% CHO)
14.5 ± 3.0 17.1 ± 3.5 2.6 ± 2.1*
Murphy 2012 [40] High pork diet (5e7 serves/wk.) Compliance, proximal capacitive(ml/mmHg � 10)
17.1 ± 4.24 16.8 ± 4.24 �0.3 ± 2.7*
Control (<100 g pork/wk.) 16.7 ± 5.09 16.3 ± 4.24 �0.4 ± 3.1*Schneider 2005 [51] Orlistat (120 mg tds) þ Energy
restricted diet þ exerciseCompliance, proximal capacitive(ml/mmHg � 10)
13 ± 4 15.8 ± 3.6 2.8 ± 2.4*
Shargorodsky 2006 [53] Bariatric surgery at high risk of CVD Compliance, proximal capacitive(ml/mmHg � 10)
13.55 ± 4.71 13.82 ± 3.21 0.27 ± 4.1
Bariatric surgery at low risk of CVD 16.31 ± 6.21 15.66 ± 3.58 �0.65 ± 5.4Wolfson 2010 [59] Energy restricted diet þ exercise
(BMI maintained or reduced after 6/12 intervention)
Compliance, proximal capacitive(ml/mmHg � 10)
9.5 ± 2.9 13.9 ± 4.3 4.4 ± 2.6*
Energy restricted diet þ exercise(BMI increased after 6/12intervention)
12.3 ± 4.1 12.3 ± 4.0 0 ± 2.6*
Wong 2013 [60] Energy restricted diet Compliance, proximal capacitive(ml/mmHg)
1.46 ± 0.52 1.41 ± 0.35 �0.05 ± 0.45
Compliance, systemicPieterse 2005 [45] Energy restricted diet including
200 g/d avocado (30.6 g fat)Compliance, systemic arterial(mL/mmHg)
2.36 ± 0.54 2.44 ± 0.58 0.08 ± 0.4*
Energy restricted diet including30 g mixed dietary fat
2.44 ± 0.58 2.50 ± 2.62 0.06 ± 0.4*
Randall 2005 [46] Energy restricted diet (mealsprovided) þexercise
Compliance, systemic arterial(mL/mmHg)
1.3 ± 0.4 1.4 ± 0.4 0.1 ± 0.25*
Randall 2005 [46] Energy restricted diet (mealsprovided) þexercise
Compliance, systemic arterial(mL/mmHg/m2)
0.7 ± 0.2 0.8 ± 0.2 0.1 ± 0.13*
Toto- Moukouo 1986 [56] Energy restricted diet low insodium
Compliance, systemic arterial(ml/mmHg/m2)
0.86 ± 0.18 1.09 ± 0.24 0.23 ± 0.14*
Yamashita 1998 [62] Energy restricted diet high in redmeat (150 g/d, 5 days/week)
Compliance, systemic arterial(ml/mmHg/m2)
0.63 ± 0.21 0.8 ± 0.28 0.17 ± 0.17*
Energy restricted diet high insoybeans (130 g dried weight)
0.61 ± 0.32 0.78 ± 0.31 0.17 ± 0.20*
Reflection timeFigueroa 2013 [29] Energy restricted diet Reflection time (m/s) 138 ± 18.71 141 ± 11.22 3 ± 11.8*
Energy restricted diet þ exercise(resistance training)
131 ± 11.22 139 ± 11.22 8 ± 7.1*
Bradley 2009 [24] Energy restricted diet (20% CHO,60% fat)
Time to wave reflection (m/s) 151 ± 20 156 ± 25 5 ± 15*
Energy restricted diet (20% fat, 60%CHO)
152 ± 23 161 ± 29 9 ± 17.4*
Pulse pressurePulse pressure, aorticFigueroa 2013 [29] Energy restricted diet Pulse pressure, aortic (mmHg) 44 ± 7.48 39 ± 3.74 �4 ± 3.7*
Energy restricted diet þ exercise(resistance training)
46 ± 7.48 42 ± 3.74 �4 ± 7.5*
Pulse pressure, brachialDengo 2010 [27] Energy restricted diet Pulse pressure, brachial (mmHg) 52 ± 5 50 ± 10 �2 ± 6.7*
Control 58 ± 6.6 55 ± 9.9 �3 ± 6.1*Hofsø 2010 [31] Bariatric surgery (Roux-en-Y) Pulse pressure, brachial (mmHg) 51 ± 13 e �2 ± 14
Energy restricted diet þ exercise 52 ± 14 �4 ± 12Ikonomidis 2007 [34] Bariatric surgery Pulse pressure, brachial (mmHg) 48.2 ± 11.54 39 ± 11.3 �9.2 ± 7.2*
Control (no surgery) 47.3 ± 13.6 48.8 ± 13.1 1.5 ± 8.5*Miyaki 2009 [37] Energy restricted diet Pulse pressure, brachial (mmHg) 57 ± 13.86 50 ± 13.86 �7 ± 8.8*Miyaki 2012 [38] Energy restricted dietþwhole body
vibrationPulse pressure, brachial (mmHg) 51 ± 6.93 47 ± 10.39 �4 ± 6.4*
Nordstrand 2013 [42] Energy restricted diet Pulse pressure, brachial (mmHg) 58 ± 16 e �7 ± 14.6Energy restricted diet þ exercise 66 ± 16 e �6 ± 14.4
Randall 2005 [46] Energy restricted diet (mealsprovided) þexercise
Pulse pressure, brachial (mmHg) 52.7 ± 8.8 48.0 ± 7.3 �4.7 ± 5.3*
Seligman 2011 [52] Pulse pressure, brachial (mmHg) 52 ± 13 40 ± 7.5 �12 ± 8.2*
(continued on next page)
K.S. Petersen et al. / Atherosclerosis 247 (2016) 7e20 15
Table 2 (continued )
Study Group Measure of arterial compliance/stiffness
Baseline Final Change
Energy restricted diet þ exercise(10 000 steps/d)Energy restricted diet þ exercise(45mins moderate intensity 3times/week)
48 ± 13.5 38 ± 6 �10 ± 9.4*
Energy restricted diet (20%fat) þ exercise (1hr walking/d)
52 ± 14.5 44 ± 8.5 �8 ± 9.2*
Sjostrom 2001 [54] Bariatric surgery Pulse pressure, brachial (mmHg) e e 2.9 ± 13.9Non-surgical, conventional obesitytreatment
e e 4.7 ± 13.9
Wong 2013 [60] Energy restricted diet Pulse pressure, brachial (mmHg) 55 ± 6.93 53 ± 6.93 �1.6 ± 7.6Van de Borne 2000 [57] Gastric restrictive surgery Pulse pressure, brachial ambulatory
(mmHg)e e �5 ± 5.3
Pulse pressure, carotidDengo 2010 [27] Energy restricted diet Pulse pressure, carotid (mmHg) 40 ± 5 41 ± 5 1 ± 3.2*
Control 45 ± 6.6 43 ± 9.9 �2 ± 6.1*
Data is presented as mean ± standard deviation unless otherwise stated; *derived; ycalculated as In (systolic pressure/diastolic pressure) � (systolic diameter-diastolicdiameter)/diastolic diameter; For the purposes of the meta-analysis data were inverted so that a negative change in SMD was indicative of improvement regardless of themeasurement.
Study name Outcome Comparison Statistics for each study
Std diff Lower Upper in means limit limit p-Value
Elian 2012 Cardio-ankle vascular index (%) Diet+Exercise -0.922 -1.123 -0.721 0.000
Iguchi 2013 Cardio-ankle vascular index (%) Diet+Exercise -0.585 -1.290 0.119 0.104
Nagayama 2013 Cardio-ankle vascular index (%) Diet+Exercise -0.375 -0.671 -0.079 0.013
Satoh 2008 Cardio-ankle vascular index (%) Diet+Exercise -0.038 -0.371 0.296 0.824
-0.482 -0.936 -0.027 0.038
-2.00 -1.00 0.00 1.00 2.00
Favours weight loss Favours no weight loss
Fig. 1. Random effects meta-analysis for the effect of weight loss on cardio-ankle vascular index (%).
Study name Outcome Comparison Statistics for each study
Std diff Lower Upper in means limit limit p-Value
Ahmadi 2011 Carotid distensibility (%) Diet+Exercise -3.947 -5.500 -2.394 0.000
Aizawa 2009 Combined Diet+Exercise -0.659 -1.172 -0.146 0.012
Balkestein 1999 Combined Combined -0.364 -0.717 -0.012 0.043
Dengel 2006 Combined Diet -0.314 -0.897 0.268 0.291
Dengo 2010 Combined Diet -1.231 -1.999 -0.463 0.002
Ikonomidis 2007 Combined Bariatric surgery 1.163 0.172 2.155 0.021
Miyaki 2009 Combined Diet -0.935 -1.614 -0.257 0.007
Rider 2009 Combined Combined -0.570 -0.967 -0.173 0.005
Werner 2013 Combined Diet+Exercise -0.726 -1.297 -0.155 0.013
-0.674 -1.099 -0.249 0.002
-2.00 -1.00 0.00 1.00 2.00
Favours weight loss Favours no weight loss
Fig. 2. Random effects meta-analysis for the effect of weight loss on direct measures of arterial compliance.
K.S. Petersen et al. / Atherosclerosis 247 (2016) 7e2016
p ¼ 0.08; I2 ¼ 61%). Sensitivity analysis showed that after theremoval of each individual study there was no differential effect.
3.5.3. Distal oscillatory complianceDistal oscillatory compliance was measured in seven studies
[30,39,40,51,53,59,60] and weight loss (mean approximately 8 kg)was associated with a statistically significant improvement in thisoutcomemeasurement (SMD�0.41; 95% CI�0.76,�0.05; p¼ 0.03;Q¼ 31; p¼ 0.0001; I2¼ 81%), see Fig. 3. Sensitivity analysis showedthat individual removal of the following studies attenuated theeffect to non-significance Goldberg et al. [30], Moran et al. [39] and
Wolfson et al. [59].
3.5.4. Proximal capacitive complianceIn seven studies [30,39,40,51,53,59,60] proximal capacitive
compliance was measured and weight loss was associated with astatistically significant improvement (SMD �0.66; 95%CI �1.15, �0.17; p ¼ 0.009; Q ¼ 54; p ¼ 0.0001; I2 ¼ 89%), see Fig. 3.Sensitivity analysis showed no statistically significant difference inthe effect sizes when each studywas individually removed from theanalysis.
Fig. 3. Random effects meta-analysis for the effect of weight loss on A) distal oscillatory compliance and B) proximal capacitive compliance.
K.S. Petersen et al. / Atherosclerosis 247 (2016) 7e20 17
3.5.5. Systemic arterial complianceIn 4 studies [45,46,56,62] systemic arterial compliance was
measured and there was an improvement following weight loss(SMD �0.71, 95% CI �1.18, �0.25; p ¼ 0.003; Q ¼ 14; p ¼ 0.004;I2 ¼ 78%), see Fig. S8. Sensitivity analysis showed the effect per-sisted after removal of each study individually.
3.5.6. Reflection timeTwo studies reported reflection time and there was an
improvement with weight loss (SMD �0.51; 95% CI �0.80, �0.20;p ¼ 0.001; Q ¼ 0.3; p ¼ 0.57; I2 ¼ 0%).
3.5.7. Pulse pressureTwelve studies [27,29,31,34,37,38,42,46,52,54,57,60], including
2814 participants, measured pulse pressure. There was no signifi-cant effect of weight loss on pulse pressure (SMD �0.23; 95%CI �1.60, 1.10; p ¼ 0.74; Q ¼ 2858; p ¼ 0.0001; I2 ¼ 100). Afterremoval of the Sjostrom et al. [54] study weight loss was associatedwith an improvement in pulse pressure (SMD e 0.66; 95%CI �0.91, �0.41; p ¼ 0.0001; Q ¼ 51; p ¼ 0.0001; I2 ¼ 81).
3.5.8. Subgroup analysisThere was significant heterogeneity (I2>50%) for the majority of
arterial stiffness/compliance measurement categories thereforesubgroup analysis was conducted to explore the potential sourcesheterogeneity. Table S3 in the supplementary material shows theresults of this analysis. This analysis could not be completed forstrain, augmentation pressure and reflection time because of thesmall number of studies reporting these outcomes. The subgroupanalysis showed that for distal oscillatory compliance there was asignificant difference in the magnitude of the effect size based onthe study population, with an improvement in this measureobserved for overweight/obese subjects with comorbidities only.There was also a statistically significant difference in the effect size
for proximal capacitive compliance based on the type of interven-tion used, with a diet and exercise intervention associated with agreater effect. There was no significant between group difference inthe effect size based on the type of intervention used for any of theother measures of arterial stiffness or compliance. When weightloss was above the median (>16 kg) the magnitude of the effect ofweight loss on distensibility was significantly greater than whenweight loss was below the median although with lower weight lossthere was no heterogeneity (I2 ¼ 0). Consistent sources of hetero-geneity across the categories of arterial stiffness/compliance mea-surements could not be identified.
4. Discussion
This meta-analysis shows that weight loss of approximately 11%improves CAVI, b-stiffness index, arterial compliance and disten-sibility, distal oscillatory compliance, proximal capacitive compli-ance, systemic arterial compliance and reflection time.Augmentation index, strain, augmentation pressure and pulsepressure were not significantly improved with weight loss. Thisanalysis suggests arterial stiffness and compliance are improvedwith modest weight loss, however because of the quality of thestudies included in this meta-analysis and the significant hetero-geneity, the results should be interpreted as hypothesis generating.
In this meta-analysis we included studies that measured a rangeof different arterial compliance and stiffness measures and this hasnot been done previously. It was shown that CAVI, a measure ofarterial stiffness that is independent of blood pressure at the time ofmeasurement but is affected by hypertensive status [65] wasimproved with weight loss. Blood pressure is a well-establishedpredictor of PWV [66], the gold standard for determining arterialstiffness, and it is unclear whether blood pressure reduction lowersPWV or is a result of lowered PWV. It is likely that a bidirectionalrelationship exists between arterial stiffening and blood pressure
K.S. Petersen et al. / Atherosclerosis 247 (2016) 7e2018
such that elevated blood pressure causes damage to the vasculatureand increases arterial stiffening [67]. In contrast, arterial stiffeningmay precede hypertension [68,69]. b-stiffness index is anothermeasure of arterial stiffness that is less dependent on blood pres-sure [14]. In this meta-analysis weight loss improved b-stiffnessindex. This suggests that weight loss improves arterial stiffnessindependently of blood pressure but well-designed randomisedcontrolled trials are required to confirm this.
Proximal capacitive compliance and distal oscillatory compli-ance, measures of systemic arterial compliance derived from pe-ripheral pulse wave analysis were improved with weight loss.Subgroup analysis showed a greater effect of weight loss on distaloscillatory compliance in overweight and obese people withcomorbidities. In addition, subgroup analysis showed that weightloss achieved with a diet plus exercise intervention produced agreater improvement in proximal capacitive compliance.
Proximal capacitive compliance and distal oscillatory compli-ance are derived from peripheral pulse wave analysis and volumechange is not directly measured. Therefore the finding that weightloss improves these measures could have been because of areduction in pressure rather than a change in the compliance of theartery. However, arterial compliance measured by the change indiameter (or area) divided by the pressure change was also shownto improve with weight loss in this meta-analysis. This suggeststhat weight loss affects the mechanical properties of the arteryrather than just reducing arterial pressure. In addition, the findingthat regardless of the location where the arterial compliancemeasurement was taken (aortic, brachial or carotid) weight losswas associated with an improvement suggests that although thesemeasurements may be physiologically different weight loss has nodifferential effect based on measurement site.
Weight loss of approximately 10 kg was associated with a non-significant reduction in augmentation index. However, after indi-vidual removal of the studies by Park et al. [43], Skilton et al. [55]and Wycherley et al. [61] weight loss was associated with a sig-nificant improvement in augmentation index. It is not clear whyeach of these studies attenuated the effect to non-significance asthere are no unique qualities to these studies. In addition, subgroupanalysis showed that the effect of weight loss on augmentationindex could not be explained by any of the study characteristics. Alimitation is that a gender analysis could not be conducted becausethe data was not reported, although none of the papers reported asignificant gender effect. Some studies have suggested that theremay be a gender effect such that in males obesity is positivelyassociated with augmentation index and in women the oppositehas been shown76, 78.
Augmentation index is not strictly a measure of arterial stiffnessas it is influenced by the timing and magnitude of the wavereflection [70] as evidenced by the effect of heart rate onaugmentation index [71]. Only 4 studies included in this meta-analysis adjusted augmentation index to a heart rate of 75 andweight loss was still non-significantly associated with augmenta-tion index when only studies that adjusted for heart rate wereincluded. We were unable to adjust for heart rate in the analysisbecause of a lack of reporting of heart rate in the included papers.
Pulse pressure is a measure of arterial stiffness and also cardiacoutput and wave reflection [14]. This meta-analysis showed thatpulse pressure was not associated with weight reduction. However,after removal of the data from the Swedish Obesity Study (SOS)[54], weight loss significantly reduced pulse pressure. The SOSfollowed up participants after 10 years, which is a greater follow-uptime than the other included studies (range 3e36 months). SOS isunusual compared with all of the other weight loss studies becauseof its lack of persistent blood pressure reduction.
All but two studies included in this meta-analysis measured
peripheral pulse pressure and it is know that amplification of thewaveform occurs from the aorta to the periphery and thereforeperipheral pulse pressure cannot be used as a surrogate for centralpulse pressure [15]. This is particularly true in younger individuals(<50 years) because of the age related decline in pulse pressureamplification [72]. The mean age of the participants in the includedstudies was 47 years therefore it is possible that an improvement inpulse pressure with weight loss was not shown because of the in-fluence of pressure amplification.
Limitations of this meta-analysis include the low quality of theincluded studies as only 4 studies were randomised controlledtrials and the methods of randomisation and blinding were notreported. Significant heterogeneity was observed between thestudies and although this was explored the analysis was limited byour inability to perform the subgroup analysis after stratificationfor weight loss (above/below median) due to the small number ofcomparisons in each group. In addition, there was evidence ofpublication bias. Therefore, the evidence provided by this meta-analysis is of a low quality and can only be interpreted as hypoth-esis generating.
This meta-analysis shows that weight loss induced by energyrestriction improves CAVI, b-stiffness index, arterial complianceand distensibility, distal oscillatory compliance, proximal capacitivecompliance, systemic arterial compliance and reflection time. Dueto the poor quality of the included trials and the lack of well-designed randomised controlled trials the results can only beused as hypothesis generating and in the future well-designedrandomised controlled trials should be conducted to determinethe effect of weight loss on measures of arterial compliance andstiffness.
Acknowledgements
JBK is a Fellow of the South Australian Cardiovascular ResearchDevelopment Program funded by the Heart Foundation and theGovernment of South Australia. PMC is supported by a NHMRCPrincipal Research Fellowship. KSP was funded by an AustralianPostgraduate Award þ UniSA Rural and Isolated Top-up Scholar-ship. Natalie Lister was funded by a University of South AustraliaPostgraduate Award. This research was jointly funded throughthese fellowships and the University of South Australia.
Appendix A. Supplementary data
Supplementary data related to this article can be found at http://dx.doi.org/10.1016/j.atherosclerosis.2016.01.042.
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