Author's Accepted Manuscript

LONGITUDINAL CHANGES OF BLOOD PRES-SURE AFTER WEIGHT LOSS: FACTORS IN-VOLVED.

L Flores PhD, J Vidal PhD, I Núñez PhD, S RuedaMD, J Viaplana MD, E Esmatjes PhD

PII: S1550-7289(14)00198-1DOI: http://dx.doi.org/10.1016/j.soard.2014.04.028Reference: SOARD1994

To appear in: Surgery for Obesity and Related Diseases

Cite this article as: L Flores PhD, J Vidal PhD, I Núñez PhD, S Rueda MD, J ViaplanaMD, E Esmatjes PhD, LONGITUDINAL CHANGES OF BLOOD PRESSURE AFTERWEIGHT LOSS: FACTORS INVOLVED., Surgery for Obesity and Related Diseases,http://dx.doi.org/10.1016/j.soard.2014.04.028

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1

LONGITUDINAL CHANGES OF BLOOD PRESSURE AFTER WEIGHT LOSS:

FACTORS INVOLVED.

Authors: L Flores, PhD1,2

, J Vidal, PhD1,2,3

, I Núñez, PhD4, S Rueda, MD

1, J Viaplana, MD

3,

E Esmatjes, PhD2,3,5

.

Affiliations:

1 Obesity Unit, Department of Endocrinology and Nutrition, Hospital Clinic.

2 CIBERDEM: Spanish Biomedical Research Centre in Diabetes and Associated Metabolic

Disorders.

3 IDIBAPS:Institut d’Investigacions Biomèdiques August Pi i Sunyer.

4 Diagnostic Imaging Center, Hospital Clinic.

5 Diabetes Unit, Department of Endocrinology and Nutrition. Hospital Clinic i Provincial,

Barcelona, Spain.

Short title: Obesity: effect of weight loss on blood pressure.

Source of funding: This study received a grant (PI07/0124) from the Fondo de Investigación

Sanitaria (FIS) del Instituto de Salud Carlos III.

Correspondence to:

Dr Lilliam Flores, PhD, MD;

Obesity Unit; Department of Endocrinology and Nutrition;

Hospital Clinic i Universitari;

Villarroel, 170, Escalera 11, 2º piso. CP 08036, Barcelona, Spain.

Phone: 0034658023562; Fax: 0034934516638; e-mail: lflores@clinic.ub.es

Word Count: 2962; Tables: 5

Material Supplementary: Tables 4

2

LONGITUDINAL CHANGES OF BLOOD PRESSURE AFTER WEIGHT LOSS:

FACTORS INVOLVED.

Abstract

Background: The combination of obesity and hypertension (HT) places patients at a higher

risk for adverse cardiovascular outcomes and raises the need to establish the pathogenic

mechanisms of this relationship.

Objective: The aim of this study was to assess the effects of important weight loss on

longitudinal changes in blood pressure (BP) and investigate the pathogenic factors associated

with these changes.

Settings: Prospective study in patients undergoing bariatric surgery (BS) in 2010 at the

Hospital Clinic of Barcelona, Spain.

Material and Methods: We performed a prospective, open-label study including 37 obese

hypertensive patients (28 females, mean age 52±8 years) undergoing BS. Before BS, and at 4

and 12 months post-operatively, the body mass index (BMI), 24-h ambulatory BP, renin-

angiotensin-aldosterone system (RAAS: plasma rennin activity, aldosterone, angiotensin II,

angiotensin converting enzyme), sympathetic nervous system (SNS: metanephrines,

normetanephrines, norepinephrine) components, leptin, insulin and abdominal fat were

measured.

Results: Prior to BS, HT-duration was 6±6 years, the BMI 45±5 kg/m2 and excess body

weight (EBW) was 53±12 kg. At 12 months the EBMI loss was 14 kg/m2 and the EBW loss

was 70 %; HT remission was observed in 70 %; 24-h [systolic 19±13/diastolic 7±9 mmHg],

day and night BP levels and aldosterone, norepinephrine, leptin, insulin, subcutaneous and

visceral abdominal fat (VAT) significantly decreased (p<0.05). Mixed models for repeated

3

measures revealed that HT-duration, baseline BP, BMI and VAT area were the main variables

associated with longitudinal changes in BP.

Conclusions: These results demonstrate that the hypotensive response after weight loss in

severely hypertensive obese patients is mainly regulated by HT-duration, baseline BP, BMI

and VAT area, independently of suppression of hyperinsulinemia or changes in RAAS and

SNS components.

Keywords: Bariatric surgery, hypertension, dysfunctional adipose tissue, renin-angiotensin-

aldosterone system, sympathetic nervous system, visceral adipose tissue.

4

Introduction

The combination of obesity and hypertension (HT) places patients at a higher risk for adverse

cardiovascular outcomes and raises the need to establish the pathogenic mechanisms of this

relationship. The mechanisms through which obesity leads to HT are still an area of research,

although several overlapping mechanisms have been proposed. One of these mechanisms is

an alteration in the profile of adipokine secretion from dysfunctional adipose tissue present in

obesity. This change in adipokine secretion has important metabolic consequences such as a

chronic inflammatory state(1)

and hyperleptinemia(2-4)

that have been related to HT in the

obese. Other relevant mechanisms proposed include increased renin-angiotensin-aldosterone

system (RAAS)(5;6)

and sympathetic nervous system (SNS) activity(7-10)

, the development of

insulin resistance(6;8)

and endothelial dysfunction(11;12)

. However, none of these mechanisms

has been shown to fully explain this association, thereby suggesting that the mechanism of

obesity-related HT is multifactorial.

A number of studies have shown that non surgical weight reduction is associated with a

significant improvement or remission of HT(13;14)

. Therefore, the current guidelines related to

HT recommend a reduction in body weight to control BP(15)

. On the other hand, bariatric

surgery (BS) is currently the most effective therapy to achieve significant and long-term

weight loss in severely obese individuals. Several series of BS in hypertensive patients have

reported a remission or improvement in HT in more than 60% of the patients(16-21)

. However,

there is a dearth of data regarding the mechanisms by which BS induces HT remission.

Indeed, only 2 studies (using office BP as the reference method for diagnosing HT) on the

effect of BS on RAAS in hypertensive patients have been performed, showing a reduction in

plasma renin activity (PRA), aldosterone and angiotensin-converting enzyme (ACE) levels

after weight loss(22;23)

. Thus, the aim of this study was to determine the factors associated with

the longitudinal changes in BP obtained by 24 h ambulatory BP monitoring (ABPM) after BS.

5

Methods

Subjects

Patients with severe obesity and HT undergoing BS [laparoscopic Roux-en-Y gastric bypass

(LRYGB) or sleeve gastrectomy (SG)] in 2010 were invited to participate in this prospective,

open-label, 12-month study. The following inclusion criteria were used: age between 18 and

65 years, fulfillment of criteria for BS defined as body mass index (BMI) > 40 kg/m2 or 35-40

kg/m2 with major obesity-associated co-morbidities, anti-hypertensive treatment with 3 or less

hypotensor drugs and normal renal function (creatinine < 1.4 mg/dl in males or < 1.3 mg/dl in

females). Subjects were excluded if they had secondary HT or established cardiovascular

disease.

Study design

All patients were evaluated three times: before BS and at 4 and 12 months post-operatively.

All evaluations were performed after withdrawal of all antihypertensive treatment one week

before the clinical work up. The preoperative information obtained included: age, height (cm),

body weight [(kg), BW], BMI: (kg/m2), waist circumference (WC) gender, full medication

list, medical history and the percentage of excess BW (EBW), which was calculated

according to the ideal BW for a BMI of 25 kg/m2. Postoperatively, BW was measured and the

BMI, BW loss (BWL), excess BWL (EBWL) and excess BMI (EBMI) loss with excess > 25

kg/m2 were calculated.

Plasma and serum samples were collected under fasting conditions after 1 hour of rest in the

supine position to determine the different components of RAAS [PRA, aldosterone,

angiotensin II (Ang II), ACE] and SNS [metanephrine, normetanephrine, norepinephrine

(NE)]. In addition, glucose, insulin and leptin levels were also determined. BP was measured

by ABPM with an appropriate sized cuff (Spacelabs 90207) on a usual working day. All

patients underwent non-invasive 24-h ABPM using an oscillometric recorder (Spacelabs

6

90207, Redmond, WA, USA). They were asked to go to bed no later than 23:00 h and to arise

no earlier than 07:00 h. The device was programmed to measure BP every 20 min. over a 24-

h period. Only 24-h recordings including more than 80% of successful recordings were

accepted as valid. Finally, abdominal fat was evaluated by means of computed tomography to

assess visceral adipose tissue (VAT) and subcutaneous adipose tissue (SAT).

LRYGB and SG were performed as previously described(24;25)

. SG was mainly performed in

individuals with a BMI > 50 kg/m2, with an estimated operative risk, or the presence of an

enlarged liver, and the remaining patients underwent GB.

Definitions

Hypertension was defined as the permanent use of antihypertensive treatment and confirmed

by ABPM when the mean 24 h SBP and DBP were > 130/80 mmHg and remission of HT was

defined as a mean 24 h SBP and DBP < 130/80 mmHg associated with a discontinuation of

all antihypertensive drugs26

.

No protocol was established for the reduction or discontinuation of antihypertensive

medications. These drug adjustments were made at the discretion at the primary care

physician of each patient. The study was approved by the institutional review board. All

patients provided written informed consent to participate.

Analytical Determination

Plasma renin activity was measured by the RIA method (gamma Coat plasma renin activity,

Diasorin, Vercelli, Italy); Ang II was measured by RIA method (Angiotensin II RIA,

Búhlmann, Baseltrasse, Switzerland); aldosterone was measured by the RIA method (Coat A

count aldosterone, Siemens, Los Angeles, Ca); NE was measured by the RIA method

noradrenalin RIA, IBL-America, Minneapolis, USA); ACE was measured by enzymatic assay

(LTA); and nephrines were measured by ELISA (nephrines plasma ELISA fast-tract,

7

Diasource ImmunoAssay S.A, Louvain-La Neuve, Belgium). Plasma leptin was measured by

enzyme immunoassay (DBC Diagnostics, Biochem Canada, Inc; intraassay CV= 4.6%;

interassay CV=5.1%; sensitivity= 1 ng/ml).

Statistical Analysis

All analyses were performed using the SAS package (version 9.2 SAS Institute Inc., Cary,

North Caroline). The sample size was calculated based on an improvement of the SBP of 10

mmHg at 12 months. An error of 0.05 with a power of 90% was assumed. The final sample

size was calculated to be 37 patients. Data are expressed as means ± SD. Means of

anthropometric and biochemical parameters were compared with the paired and unpaired

Student’s t test as appropriate. Changes from baseline variables ( ) were calculated by

subtracting baseline from follow-up values.

To evaluate longitudinal changes in BP after BS, mixed models for repeated measures

(MMRM) were employed. Separate models were constructed for each of the SBP and DBP

baseline-adjusted measurements (24 h, day and night) obtained by ABPM. We first fitted a

univariate MMRM to estimate the coefficients ( ) and their 95% CI. Variables with P values

lower than 0.10 in this univariate analysis were selected for the final model using a forward

stepwise strategy selection.

8

Results

Participant characteristics

A total of 37 subjects were included in the study. The entire group was Caucasian, 31 patients

used ACE inhibitors or angiotensin receptor antagonists, 4 calcium channel blockers and 2

beta blockers, combined with diuretic treatment in 22 patients. Table 1 shows the clinical and

demographic characteristics of the study population at baseline.

Effect of BS on weight variables, HT remission, gender and type of surgery

Over the 12-month period after surgery, the BW decreased by a mean of 37 kg, the EBMI

decreased by 14 kg/m2, the WC decreased by 25 cm and the EBWL was 70%. Sixteen (43%)

patients reached a BMI ≤ 30 Kg/m2.

HT remission was observed in 26 (70%) patients. Prior to surgery, patients with HT remission

had a higher BMI, EBMI and EBW, used fewer antihypertensive drugs, and all BP parameters

were significantly lower compared to those without HT remission (Table 1). At the end of

follow-up the subjects with and without HT remission showed similar BMI values: 32 ± 4 vs.

30 ± 4 kg /m2, BWL: 39 ± 14 vs. 33 ± 7 kg and EBWL 69 ± 19 vs. 74 ± 17 %. Only in

patients without HT remission was the EBMI loss significantly lower: 15 ± 5 vs. 12 ± 2

kg/m2, p= 0.03, respectively.

With regard to gender, HT remission was achieved in 82 % of the women compared to only

33% of the males. Prior to BS, the only difference was that males had a higher WC than

females (137 ± 9 vs. 127 ± 10, p= 0.015). No further analyses were performed to attempt to

elucidate the mechanisms to explain the difference in HT resolution due to the small sample

size.

In relation to the type of surgery performed, before BS both age (50 ± 7 vs. 56 ± 9, p= 0.035)

as well as HT duration (5 ± 4 vs. 9 ± 7, p= 0.033) were significantly higher in those receiving

SG. After BS the BP response (24 h SBP 19 ± 14 vs. 15 ± 10 and 24 h DBP 7 ± 9 vs. 4 ± 6

9

mmHg] and weight loss achieved [BMI 31 ± 4 vs. 31 ± 5 kg/m2; BWL 39 ± 12 vs. 35 ± 12 kg

and EBWL 71 ± 17 vs. 70 ± 20 % in LRYGB and SG, respectively] were similar between the

two surgical approaches. In addition, we did not observe differences in HT remission between

the two types of surgery.

Effect of BS on BP, metabolic and hormonal parameters and body composition

All the BP parameters evaluated decreased significantly. With an EBWL of 51% (-26 Kg) at 4

months after surgery, the 24 h SBP and DBP decline was -18 and -7 mmHg, respectively,

representing a fall of 0.70 and 0.27 mmHg when expressed per kg of BWL. At 12 months

after BS, with an EBWL of 70% (-37 kg) the total 24 h SBP and DBP decline was -19 and -7

mmHg, respectively, representing a fall of 0.51 and 0.19 when expressed per kg of BWL. The

effect of weight loss on the BP parameters is presented in Table S1. The prevalence of non

dippers was similar prior to and 12 months after surgery (50 vs. 50 %), as was the mean night

SBP (9 vs. 9 mmHg) and DBP (14 vs. 11 mmHg) decline. After BS the nocturnal

hypertension (night SBP and DBP > 120/70 mmHg) decreased from 75 to 39% and the

pressure pulse (difference between the SBP and DBP readings) fell from 60 (7) to 47 (7)

mmHg, p <0.001.

As expected, all the metabolic parameters improved: glucose fell from 131 ± 55 to 95 ± 28

mg/dl, p< 0.001; fasting insulin from 30 ± 21 to 10 ± 4 mU/L, p< 0.001 and leptin: in males

from 43 ± 27 to 7 ± 9 and in females from 77 ± 23 to 25 ± 13 ng/ml, p< 0.001. Regarding

RAAS, all the components decreased as a mean, but only the reduction in aldosterone reached

statistical significance. In relation to SNS parameters only the decline in NE achieved

statistical significance (Table S2). Regarding adiposity measures, VAT and SAT areas

significantly decreased after surgery [211 ± 80 vs. 84 ± 46 cm2 p< 0.001 and 655 ± 186 vs.

375 ± 153 cm2, p<0.001, respectively].

10

Factors associated with the longitudinal changes in SBP and DBP

The exploratory analyses revealed that age and HT-duration were associated with higher

levels of 24-h, day and night SBP, whereas BW, BMI, WC, and EBW were associated with

lower levels of 24-h, day and night SBP. In relation to the RASS none of the components

achieved statistical significance in the univariate model. In relation to SNS components, only

NE showed an association with 24-h and night SBP levels, and concerning body composition,

the SAT area was associated with lower 24-h, day and night SBP levels whereas the VAT

area was associated with higher day-SBP levels (table 2). When we studied the follow-up

variables we observed that ∆ BMI and ∆ EBW were associated with lower 24-h SBP levels,

BWL with lower day SBP levels, and ∆ BMI, ∆ EBW and EBWL were associated with lower

night SBP levels (Table S3). None of the changes in the RASS and SNS components achieved

statistical significance to enter in the multivariate model.

In relation to DBP levels, the univariate analysis showed that the VAT area was associated

with higher 24-h and day DBP levels whereas BMI, EBW and SAT area were associated with

lower night DBP levels (Table 3). The analysis with the follow-up variables showed that ∆

BMI and ∆ EBW were associated with lower 24-h and night DBP levels whereas EBWL was

associated with higher 24-h and night DBP levels (Table S4). Again, none of the changes in

the RASS and SNS components achieved statistical significance to enter in the multivariate

model.

The results of the multivariate analysis showed that baseline factors associated with higher

SBP levels were HT-duration, SBP levels and VAT area whereas BMI was associated with

lower SBP levels (Table 4). In addition, baseline DBP levels and VAT area were associated

with higher DBP levels while the only factor associated with lower night DBP level was BMI.

No longitudinal changes in predictor variables were associated with longitudinal changes in

BP (Table 5).

11

Discussion:

We used a prospective design to measure the serial parameters related to different systems

reportedly involved in the obesity-HT relationship in an attempt to investigate the pathogenic

mechanisms involved in this relationship. In addition, we took advantage of the repeated

measurements of BP at each follow-up visit to characterize the longitudinal changes in BP

over time. Establishment of the pathophysiological modification that accompanies the

changes in BP after weight loss might indicate the sequence of alterations that leads to the

association of HT and obesity. In this sense, hypertensive patients undergoing BS represent an

ideal clinical model in which a significant weight loss is expected within a relatively short

time, thereby allowing evaluation of the changes in BP and the study of the pathogenic

mechanisms involved in these changes.

The present study has three main findings. First, the beneficial effect of weight loss on BP and

metabolic parameters in hypertensive severely obese subjects is confirmed, and similar to

other authors the remission rate of HT was 70%(17;18)

.

Second, we observed a sizeable decline in SBP and DBP after weight loss. This drop in BP

took place at an early stage following surgery (at 4 months). Further reductions in BW

occurred up to the last follow-up (at 12 months), albeit not accompanied by any notable

additional reductions in BP. Thus, the initial weight loss produced a greater fall in BP than

that observed after continued weight reduction. In concordance with prior results, in a group

of overweight and obesity young, stage 1, never-treated hypertensive patients followed for

more than 6 years Winnicki et al described that the association between long-term weight loss

and a subsequent decrease in BP is not linear and is limited to a decrease of up to 13% of the

initial BW. In agreement with these authors, our data indicate that 1 kg of weight loss is

associated with a decrease of approximately 0.70 mmHg for SBP and 0.27 mmHg for DBP,

but in our case the relationship held true for up to a 50% decrease of the initial BW(27)

. After

12

BS, Ahmed et al reported reductions in SBP (9 mmHg) and DBP (7 mmHg) as early as 1

week after surgery before presenting any significant weight loss (EBWL of 7%)(16)

and, in a

retrospective study Hinojosa et al reported that the maximal early BP fall occurred at 1

month(20)

. In our study BP was not monitored until 4 months after BS to avoid possible

confounders such as post-operative fluid status, severe caloric restriction and sodium intake.

Therefore, the maximal fall in BP might have been obtained earlier with even less BWL.

Indeed, our findings suggest that the impact of weight loss on BP does not require

achievement of an ideal body weight and that the target of BWL may even be set at a more

modest range of 50% of initial weight to achieve maximum benefits in BP.

Lastly, the novelty of the present study was to establish the factors associated with the

longitudinal changes in BP after weight loss, which we found to be HT-duration, baseline

levels of BP, BMI and VAT area. Interestingly, these variables are well known clinical risk

factors which, with the exception of VAT area, are easy to obtain with a simple clinical work

up. Indeed, we expected the VAT area to remain significantly associated with BP changes

since it has traditionally been considered the most pathogenic adipose tissue compartment and

in agreement with our findings, several authors have also shown a relationship between VAT

and HT even after adjustment for BMI and WC(28;29)

. Nonetheless, the relationship observed

between BMI and the changes in longitudinal BP deserves special mention; we observed that

patients with a higher BMI reached lower BP levels after weight loss suggesting that the

relationship between BP and BMI changes at very high degrees of obesity. In fact, at the end

of follow-up the BP in subjects with a high baseline BMI tertile (> 47.65 kg/m2) was 121.14

[116.55 to 125.72] mmHg compared to those with a lower BMI tertile (< 42.5 kg/m2) of

135.23 [130.61 to 139.86] mmHg. While it is true that a higher BMI is related to higher BP

levels, no studies have reported the rate of BP response after weight loss within different

ranges of BMI at these higher degrees of obesity. Mechanisms linking obesity and HT have

13

mainly emerged from studies including overweight subjects and individuals with obesity

grade 1, and thus, well-designed studies exploring how an increasing BMI modifies the

relationship of BP with different cardiovascular risk factors in severe obesity are necessary.

This study has limitations; one limitation of the study was that the sample size was calculated

for the expected changes in BP, which were achieved. This may represent a limitation for the

statistical power in the analysis of the data since other variables also involved in BP

regulation were analyzed and should have been taken into account. However, this sample size

was chosen because BP is the key parameter of our evaluation and it can be better ascertained

from the literature. Second, 24-h urinary excretion determination of many of the hormones

measured in this study could have been more representative than the plasma determination in

only one point in order to avoid circadian secretion and pulsatile problems which may be

frequent in plasma hormone determination. Finally, in this study we performed a wide range

of outcome measurements to achieve a better insight into the possible pathogenic mechanisms

of obesity-related HT. However, we did not address other mechanisms that could be

important, such as oxidative stress and endothelial dysfunction, and we did not measure other

adipokines such as adiponectin, the measurement of which could have helped to understand

the role of these mediators in obesity-related HT or how the decrease in the flow of free fatty

acid to the liver can influence hypotensive response after BS. As a consequence, our

conclusion is only one of the many hypotheses to explain the multifactorial nature of obesity-

related HT. Therefore, our results suggest that the mechanism responsible for the fall in BP

after weight loss should be sought in the early stages after BS before a significant weight loss

occurs (excess body weight loss 50%) and the maximum effect of BP has already taken place

(previous to 4 months after BS).

Conclusions

We observed that the hypotensive response after weight loss in hypertensive severely obese

subjects is mainly regulated by HT-duration, baseline BP, BMI and VAT area, independently

of the suppression of hyperinsulinemia or changes in RAAS and SNS components observed

after weight loss. Advances in the knowledge of the mechanisms associated with obesity-

related HT are important because of the relevance of HT as the most frequent co-morbidity of

obesity and the large healthcare costs involved.

Disclosure Statement: None

15

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Table 1. Demographic and clinical characteristics of the patients at baseline and according to

remission or not of hypertension after bariatric surgery.

Whole group HT remission HT no remission

Nº of patients 37 26 11

Age (years) 52 ± 8 52 ± 8 55 ±8

Sex (male/female) 9/28 3/23 6/5*

Weight (kg) 120 ± 16 121 ± 16 118 ± 16

BMI ( kg/m2) 45 ± 5 46 ± 4 41 ± 4*

EBW (kg) 53 ± 12 56 ± 12 47 ± 12*

WC (cm) 129 ± 11 130 ± 12 128 ± 9

HT evolution (years) 6 ± 6 6 ± 5 8 ± 8

Anti-HT treatment (1/2/3 drugs) 14/21/2 13/12/1 1/9/1*

Type 2 diabetes (yes/no) 14/23 8/18 6/5

Current smoker (yes/no) 7/30 4/22 3/8

Bariatric surgery (GBP/SG) 21/16 16/10 5/6

24 h SBP ( mmHg) 142 ± 8 134 ± 12 146 ± 6*

24 h DBP ( mmHg) 82 ± 9 76 ± 7 86 ± 10*

Abbreviations: HT: Hypertension; BMI: body mass index; EBW: excess body weight, WC:

waist circumference; GBP: gastric bypass; SG: sleeve gastrectomy; SBP: systolic blood

pressure; DBP: diastolic blood pressure.* p< 0.05 HT remission vs. HT not remission.

20

Table 2: Univariate baseline predictor estimates of change over follow-up in baseline-adjusted

SBP levels

24-h SBP

(mmHg)

p-

value

Day-SBP

(mmHg)

p-

value

Night-SBP

(mmHg)

p-

value

Gender (men)

3.01 [-5.41 to

11.43] 0.472

3.03 [-5.7 to

11.76] 0.485

2.65 [-6.79 to

12.08] 0.572

Age ( year)

0.48 [0.07 to

0.88] 0.024

0.53 [0.12 to

0.94] 0.014

0.5 [0.04 to

0.96] 0.035

HT-duration

(years)

0.65 [0.09 to

1.21] 0.024

0.73 [0.17 to

1.28] 0.012

0.66 [0.01 to

1.31] 0.046

Type of surgery

(GB)

4.75 [-2.37 to

11.86] 0.184

5 [-2.28 to

12.28] 0.172

3.19 [-4.9 to

11.29] 0.428

BMI (kg/m2)

-1.38 [-2.03 to -

0.73] 0.000

-1.27 [-2 to -

0.54] 0.001

-1.91 [-2.49 to -

1.32] 0.000

BW (kg)

-0.26 [-0.47 to -

0.05] 0.019

-0.27 [-0.48 to -

0.05] 0.018

-0.3 [-0.53 to -

0.06] 0.014

WC (cms)

-0.37 [-0.69 to -

0.05] 0.023

-0.33 [-0.66 to

0.01] 0.047

-0.43 [-0.79 to -

0.07] 0.020

EBW (kg)

-0.49 [-0.74 to -

0.24] 0.000

-0.48 [-0.74 to -

0.21] 0.001

-0.61 [-0.86 to -

0.36] 0.000

Aldosterone

(ng/dl)

0.65 [-0.63 to

1.93] 0.307

0.57 [-0.75 to

1.88] 0.386

0.82 [-0.57 to

2.22] 0.237

NE (pg/ml)

-0.05 [-0.11 to

0.01] 0.081

-0.04 [-0.1 to

0.02] 0.164

-0.07 [-0.13 to -

0.01] 0.035

VAT ( 100 cm2) 0.03 [-0.01 to 0.102 0.05 [0 to 0.09] 0.032 0.01 [-0.04 to 0.619

21

0.08] 0.06]

SAT (100 cm2)

-0.02 [-0.04 to

0] 0.040

-0.02 [-0.04 to

0] 0.068

-0.03 [-0.05 to

0] 0.018

The predictor variables were all measured at the baseline visit. The predictor estimates

indicate the estimated change [95%CI] in mmHg per either 1-unit change for continuous

variables or for being in the category referred in parenthesis. GB: gastric bypass vs. sleeve

gastrectomy; BMI: body mass index; BW: body weight; WC: waist circumference; EBW:

excess body weight; NE: norepinephrine; VAT: visceral adipose tissue; SAT: subcutaneous

adipose tissue. Values in red are statistically significant.

22

Table 3: Univariate baseline predictors estimates of change over follow-up in baseline-

adjusted DBP levels

24-h DBP

(mmHg)

p-

value

Day- DBP

(mmHg)

p-

value

Night- DBP

(mmHg)

p-

value

Gender (men)

2.76 [-2.42 to

7.93] 0.286

2.53 [-3.57 to

8.62] 0.405

2.3 [-2.77 to

7.36] 0.363

Age (years)

0.17 [-0.1 to

0.44] 0.212

0.19 [-0.13 to

0.51] 0.244

0.13 [-0.12 to

0.39] 0.297

Type of surgery

(GB)

2.21 [-2.22 to

6.65] 0.318

1.45 [-3.83 to

6.73] 0.580

0.86 [-3.44 to

5.17] 0.686

HT-duration

(years)

0.25 [-0.1 to

0.61] 0.160

0.33 [-0.09 to

0.74] 0.118

0.1 [-0.26 to

0.45] 0.578

BMI (kg/m2)

-0.31 [-0.78 to

0.16] 0.193

-0.35 [-0.91 to

0.21] 0.213

-0.53 [-0.97 to -

0.1] 0.017

WC (cms)

-0.1 [-0.31 to

0.1] 0.316

-0.11 [-0.35 to

0.14] 0.373

-0.16 [-0.36 to

0.04] 0.104

BW ( kg)

-0.03 [-0.17 to

0.11] 0.674

-0.04 [-0.2 to

0.12] 0.639

-0.04 [-0.17 to

0.09] 0.538

EBW (kg)

-0.09 [-0.27 to

0.09] 0.307

-0.1 [-0.31 to

0.1] 0.321

-0.14 [-0.31 to

0.03] 0.095

Aldosterone

(ng/dl)

0.49 [-0.35 to

1.32] 0.246

0.43 [-0.57 to

1.43] 0.389

0.61 [-0.13 to

1.35] 0.103

NE (pg/ml)

-0.01 [-0.05 to

0.02] 0.453

-0.01 [-0.05 to

0.03] 0.569

-0.02 [-0.06 to

0.01] 0.209

VAT (cm2) 0.03 [0.01 to 0.012 0.04 [0.01 to 0.015 0.02 [-0.01 to 0.247

23

0.06] 0.06] 0.04]

SAT (cm2)

-0.01 [-0.02 to

0] 0.135

-0.01 [-0.02 to

0] 0.173 -0.01 [-0.02 to 0] 0.055

The predictor variables were all measured at the baseline visit. The predictor estimates

indicate the estimated change [95%CI] in mmHg per either 1-unit change for continuous

variables or for being in the category referred between parentheses. GB: gastric bypass vs.

sleeve gastrectomy; BMI: body mass index; BW: body weight; WC: waist circumference;

EBW: excess body weight; NE: norepinephrine; VAT: visceral adipose tissue; SAT:

subcutaneous adipose tissue. Values in red are statistically significant.

24

Table 4. Baseline and follow-up multivariate* predictors of change over follow-up in

baseline-adjusted SBP levels.

24-h SBP

(mmHg)

p-

valu

e

Day- SBP (

mmHg)

p-

valu

e

Night-SBP

(mmHg)

p-

valu

e

Baseline SBP, per 1

mmHg increase

0.27 [0.03 to

0.51]

0.03

0

0.23 [0 to

0.46]

0.04

8

0.34 [0.13 to

0.55]

0.00

2

HT-duration, per 1 year

increase

0.47 [0.06 to

0.89]

0.02

5

0.53 [0.1 to

0.96]

0.01

7

0.43 [0.01 to

0.86]

0.04

3

BMI, per 1-unit increase

-1.49 [-2.06 to

-0.92]

0.00

0

-1.36 [-1.97 to

-0.75]

0.00

0

-1.94 [-2.5 to

-1.37]

0.00

0

VAT, per 100 cm2

increase

4.76 [1.78 to

7.75]

0.00

3

5.37 [2.26 to

8.48]

0.00

1

3.17 [0.11 to

6.23]

0.04

3

The model was constructed on a forward stepwise basis, including only variables significant

at the 10% two-sided alpha level. BMI: body mass index; VAT: visceral adipose tissue.

25

Table 5. Baseline and follow-up multivariate* predictors of change over follow-up in

baseline-adjusted DBP levels.

24-h DBP (

mmHg)

p-

valu

e

Day-DBP (

mmHg)

p-

valu

e

Night- DBP (

mmHg)

p-

valu

e

Baseline DBP, per 1

mmHg increase

0.53 [0.31 to

0.75]

0.00

0

0.45 [0.22 to

0.69]

0.00

0

0.54 [0.34 to

0.75]

0.00

0

HT-duration, per 1 year

increase - - -

BMI, per 1-unit increase - -

-0.63 [-1.07 to

-0.18]

0.00

7

VAT, per 100 cm2

increase

3.16 [0.76 to

5.56]

0.01

1

3.6 [0.76 to

6.44]

0.01

4

2.26 [-0.18 to

4.69]

0.06

8

The model was constructed on a forward stepwise basis, including only variables significant

at the 10% two-sided alpha level. BMI: body mass index; VAT: visceral adipose tissue.