ObesityandHypertensionDror Dicker MD, Internal Medicine D & Obesity Clinic Hasharon Hospital-Rabin Medical CenterSackler School Of Medicine Tel Aviv University, Israel.Co-Chair Obesity Management Task Force, EASO

• John works as an accountant in a big company

• He is married with 2 children and he loves to cook for his family

• John is a former smoker who has been diagnosed with hypertension (5 years ago) and Type 2 Diabetes (4 years ago)

• 1 year ago he had acute coronary event and stent implantation in his LAD artery

• Lately he complains on effort dyspnoea

• His BMI is 35 kg/m2, latest HbA1c is 8.5% and his latest eGFR was 85mL/min/1.73 m2

• John is taking an ACE inhibitor for his blood pressure

• He is on metformin 1 g twice daily and sitagliptin 100 mg once daily.

Case Study : John, uncontrolled on dual therapy

Obesity Hypertension - epidemiology

Relative risk of hypertension for a five-unit increment in body mass index

Jayedi A, obesity reviews, 2018

• Fifty-seven prospective cohort studies were included

• 1.49 (95% [CI]: 1.41, 1.58;) for a five-unitincrement in body mass index.

• 1.16 (95%CI:1.09, 1.23;) for weight gain equal to a one-unit increment in BMI

Mechanisms by which obesity induces hypertension

HallJEet.al,Circulation Res 2015

Schematic of candidate mechanisms of leptin-induced hypertension in men and women

weight loss effective in lowering BP in the long run

Life Style

An average net weight reduction of 5.1 kg by means of energy restriction, increased physical activity, or the combined intervention was associated with a significant reduction in SBP of 4.44 mm Hg (95% CI, 5.93 to 2.95) and a significant reduction in DBP of 3.57 mm Hg (95% CI, 4.88 to 2.25). When expressed per kilogram of weight loss, reductions in SBP and DBP were 1.05 mm Hg (95% CI, 1.43 to 0.66) and 0.92 mm Hg (95% CI, 1.28 to 0.55) Respectively

Influence of Weight Reduction on Blood Pressure A Meta-Analysis of Randomized Controlled Trials

Neter JE. Hypertension. 2003

Long-Term Weight Loss and Changes in Blood Pressure: Results of the Trials of Hypertension Prevention, Phase II

• individual counseling session, followed by 14 weekly group meetings

• After this 14-week-six biweekly group meetings and then monthly group meetings.

• It was suggested that men not consume less than 1500kcal/d and women not less than 1200 kcal/d.

• physical activity goal was 30 to 45 minutes per day, four to five days per week.

StevensVJ,AnnInternMed . 2001

Long-Term Weight Loss and Changes in Blood Pressure: Results of the Trials of Hypertension Prevention, Phase II

StevensVJ,AnnInternMed . 2001

-8.8 kg

-2.6 kg -0.1 kg 2.6 kg 7.3 kg

Di Sy

118

119

120

121

122

123

124

125

Baseline Year 1 Year 2 Year 3

Syst

olic

blo

od p

ress

ure

(mm

Hg)

Placebo Metformin Intensive lifestyle intervention

Intensive Lifestyle Intervention Reduces Blood Pressure, Diabetes Prevention Program(N=3234)

29 3033

39

3033

35

40

3026

29 29

05

1015202530354045

Baseline Year 1 Year 2 Year 3

Patie

nts

(%)

PlaceboMetforminIntensive lifestyle intervention

• BloodPressureChange • HypertensionPrevalence

DPP Research Group. Diabetes Care. 2005

P<0.001

Changes in Weight, Physical Fitness and Blood Pressure during 10 Years of Follow-up in Look AHEAD.

Wing RR, NEJM, 2013

The difference in cardiovascular risk factors between intervention groups diminished over time, with hemoglobin A1c and systolic blood pressure showing the most sustained differences

weight loss effective in lowering BP in the long run

Pharmacotherapy

SCALE Obesity and Prediabetes: Trial design

Inclusion criteria:• BMI: ≥30 kg/m2, or ≥27 kg/m2 + comorbidities

• Stable body weight, and preceding failed dietary effort

0.6 mg1.2 mg

1.8 mg2.4 mg

16040–2Week

Screening

Liraglutide 3.0 mg/day

Placebo

Randomisation2:1 (liraglutide:placebo)

Dose escalation

56

End oftrial

68

Liraglutide 3.0 mg/day

Placebo

Liraglutide 3.0 mg/day

Placebo

Withoutprediabetes

With Prediabetes

0.6 mg1.2 mg

1.8 mg2.4 mg Off-drug

follow-up

172

All arms included lifestyle intervention: −500 kcal/day hypocaloric diet + 150 min/week increased physical activity

Off-drug follow-up

70

End oftreatment

Pi-Sunyer et al. NEJM 2015;373:11–22.

SCALE Obesity and Prediabetes – Weight Loss

leRouxCW,Lancet2017

SCALE Obesity and Prediabetes – Systolic Blood Pressure

leRouxCW,Lancet2017

SCALE Obesity and Prediabetes – Diastolic Blood Pressure

leRouxCW,Lancet2017

Gutzwiller etal,JCEM2004

Urinevolume

7006005004003002001000

Volu

me

(ml/1

80 m

in)

Placebo GLP-1

Urine osmolality

Excretion of sodium

8007006005004003002001000

Osm

olal

ity (m

osm

ol/l)

Placebo GLP-1

2.82.42.01.61.20.80.40

Fe N

a+(%

)

Placebo GLP-1

Fractional excretion of

sodium

160140120100806040200

Na+

excr

etio

n (m

mol

/180

min

)

Placebo GLP-1GLP-1

0.375 pmol/kg/min

1.5 pmol/kg/min

p < 0.001

p < 0.001p < 0.002

GLP-1 Increases Urine Volume and Sodium Excretion in Healthy Subjects

Glp-1A Effects on Hypertension

Pharmacological treatment of obesity-induced hypertension

Kotsis V et al Journal of Hypertension 2018

4. Lorcaserin 10 mg

Pharmacological treatment of obesity-induced diabetes

Kotsis V et al Journal of Hypertension 2018

weight loss effective in lowering BP in the long run

Bariatric Surgery

Bariatric Surgery

RecoveryfromDiabetes,LipidDisturbances,Hypertension,andHyperuricemiaover2and10YearsinSurgicallyTreatedSubjectsandTheirObeseControls

Sjostrom,L.etal.NEngl JMed2004;351:2683-2693

Mean Percent Change in Body Weight from Baseline to Years 2,6, and 12 in the Surgery Group

Adams TD, NEJM 2017

Unadjusted Mean Baseline and 12-Year Follow-up Values for Clinical Variables, According to Study Group

Adams TD, NEJM 2017

What are the Mechanisms that improve blood pressure Control After Bariatric Surgery ?– Weight loss– volume and urinary sodium excretion– Increase in Gut Hormone (GLP-1)

Summery Life Style • Weight Loss is effective in lowering Blood Pressure in the long run !

– Weight loss is maintained– Regular Physical activity (200-300 min/w)

Pharmacotherapy Weight Loss is effective in lowering Blood Pressure in the long run !– Using Anti Obesity Medication

• ( GLP-1, liraglutide)• Increasing ANP• volume and urinary sodium excretion &vasodilatation

• LorcaserinBariatric Surgery

Weight Loss is effective in lowering Blood Pressure in the long run !– Bariatric Surgery

• Weight loss• volume and urinary sodium excretion• Increase in Gut Hormone (GLP-1)