Manchester 30th June 2017

Obesity and Hypertension

Manish Sinha

Evelina London Children’s Hospital

Scope of Talk

• Trends of childhood obesity in the UK

• Prevalence of hypertension in obese children

• Pathophysiology of hypertension in obesity

• Relevance – does it matter during childhood and as

young adults with ‘childhood onset’ obesity

• Cases from our hypertension clinic

Definition of obesity - BMI

• There are several definitions around for overweight

and obesity

– Clinical cut-offs - 85th and 95th percentile

– Health policy - 91st and 98th percentile (NICE/ DoH)

– International Obesity Task force (IOTF) - 88th /90th and 99th

• corresponds with adult BMI cut offs at 25 kg/m2 and 30 kg/m2

Prevalence of overweight and obesity by study year and age group in boys and girls

Cornelia H M van Jaarsveld, and

Martin C Gulliford Arch Dis

Child 2015;100:214-219

Trends in childhood obesity

• Stabilising of the prevalence of childhood overweight and obesity• similar trends in the

US, Netherlands and Australia

• Reasons in the UK• public health

campaigns <11 year olds

• Physical Education in schools

• Active School Travel policies

Prevalence of obesity by study year and age group in boys and girls

Cornelia H M van Jaarsveld, and

Martin C Gulliford Arch Dis

Child 2015;100:214-219

and how common is hypertension in obese children?

Prevalence of hypertension and prehypertension in US(NHANES)

• Hypertension: SBP and/or DBP on 3 occasions ≥

95th percentile

– Prevalence 1-2%, age 8-17

• Prehypertension: SBP and/or DBP ≥ 90th

percentile, < 95th percentile or BP >120/80

mmHg

– Prevalence about 5% age 8 – 12 14% age 13-17

JAMA Pediatr. 2015;169(3):272-279. doi:10.1001/jamapediatrics.2014.3216

Prevalence of hypertension and prehypertension in US(NHANES)

Hypertension in obese children-2Sorof J et al. J Pediatr. 2002; 140: 660–666.

Obese children display clustering of cardiometabolic risk factors

• In a cohort of n=611 obese youth

– hyperinsulinism (30.8%), lipid abnormalities (12.9%) and high BP (10.5%)

– in addition to obesity, one risk factor was present in 39%, two risk factors in 16.5% and three risk factors in 2.8%

Blood pressure in children and adolescents: current insights.Lurbe, Empar; Ingelfinger, Julie

Journal of Hypertension. 34(2):176-183, 2016.

Major issue - several OTHER problems

• Type 2 diabetes mellitus

• Dyslipidaemia

• Non-alcoholic fatty liver (steatohepatitis)

• Obstructive sleep apnea

• Orthopaedic problems

Frequency of systolic and diastolic hypertension

ISH (SBP ³140 mm Hg and DBP <90 mm Hg)

SDH (SBP ³140 mm Hg and DBP ³90 mm Hg)

IDH (SBP <140 mm Hg and DBP ³90 mm Hg)

Franklin et al.

Hypertension 2001;37:

869-874.

Age

<40 40-49 50-59 60-69 70-79 80+

17% 16% 16% 20% 20% 11%

0

20

40

60

80

100

Frequency of systolic and diastolic hypertension

ISH (SBP ³140 mm Hg and DBP <90 mm Hg)

SDH (SBP ³140 mm Hg and DBP ³90 mm Hg)

IDH (SBP <140 mm Hg and DBP ³90 mm Hg)

Franklin et al.

Hypertension 2001;37:

869-874.

Age

<40 40-49 50-59 60-69 70-79 80+

17% 16% 16% 20% 20% 11%

0

20

40

60

80

100

12-16

Sorof et al. J Pediatr

2002;140: 660-6.

Pathophysiology - 1

• Blood pressure - balance between CO and peripheral resistance

• In adults - CO maintained but peripheral resistance goes up as arterioles have smooth muscle cells

Pathophysiology - 2

Mechanisms that link obesity with peripheral vascular resistance• Autonomic nervous

system activation• Renal mechanisms:

impaired pressure natriuresis; RAS

• Hormones: insulin resistance, Leptin

• Endothelial dysfunction: a state of inflammation

Summary-1

• Excess weight including obesity remain highly prevalent and continue

to rise in those >11 years

– absence of any specific long term programme

• Hypertension in obesity is common but only one of several CV risk

factors present in this cohort

– Often asymptomatic and this makes it difficult for the patient to understand

– no national blood pressure measurement programmes

• Pathophysiology of hypertension in obese children is poorly

understood

– few recent data

• Increased carotid intima medial thickness (cIMT) and LVH described in children with essential hypertension

• cIMT and LV mass correlate with blood pressure and BMI

Do obese hypertensive children exhibit TOD?Obesity – increased clustering of CV risk factors

Berenson GS et al. N Engl J Med 1998;338:1650-1656.

elevated BMI, SBP and serum triglyceride and

LDL-C

The Journal of Clinical Hypertension

Volume 18, Issue 7, pages 625-633

•Normal BMI and blood pressure tracks during childhood –‘tracking’

• Similarly, abnormal BMI and BP have been shown to increase to higher percentiles over time

Guo S S , and Chumlea W C Am J Clin Nutr 1999;70:145s-

148s

Probability of overweight at age 35 y predicted

from childhood BMI at the 95th percentile

Value of current BMI and BP?

Value of current BPSBP and DBP tracking correlation coefficients against follow-up period

Xiaoli Chen, and Youfa Wang Circulation. 2008;117:3171-

3180

Copyright © American Heart Association, Inc. All rights reserved.

Childhood Adiposity, Adult Adiposity, and Cardiovascular Risk Factors

• Four prospective cohort studies

– Bogalusa Heart Study (BOGA)

– Muscatine Study (MUSC)

– Childhood Determinants of Adult Health (CDAH) study

– Cardiovascular Risk in Young Finns Study (YFS)

Juonala M et al. N Engl J Med 2011;365:1876-1885

Date of download:

5/25/2015

Copyright © The American College of Cardiology.

All rights reserved.

From: Isolated Systolic Hypertension in Young and Middle-Aged Adults and 31-Year Risk for Cardiovascular

Mortality: The Chicago Heart Association Detection Project in Industry Study

J Am Coll Cardiol. 2015;65(4):327-335. doi:10.1016/j.jacc.2014.10.060

Hypertension Subtype and Cardiovascular Mortality: Kaplan-Meier Curves of the Cumulative Incidence of CVD Mortality by Sex

Sex-specific cumulative incidence rate of cardiovascular disease (CVD) mortality for each hypertension subtype is shown. The

definition of each color line is as follows: periwinkle, systolic diastolic hypertension (systolic blood pressure [SBP] ≥140 mm Hg and

diastolic blood pressure [DBP] ≥90 mm Hg); gold, isolated diastolic hypertension (SBP <140 mm Hg and DBP ≥90 mm Hg); violet,

isolated systolic hypertension (SBP ≥140 mm Hg and DBP <90 mm Hg); green, high-normal blood pressure (BP) (SBP 130 to 139

mm Hg and DBP 85 to 89 mm Hg, SBP 130 to 139 mm Hg and DBP <85 mm Hg, or SBP <130 mm Hg and DBP 85 to 89 mm Hg);

salmon, optimal-normal BP (SBP <130 mm Hg and DBP <85 mm Hg). The log-rank was used to calculate p values. IDH = isolated

diastolic hypertension; ISH = isolated systolic hypertension; SDH = systolic diastolic hypertension.

Figure Legend:

Summary-2

• Current BMI and BP levels - track and predict

• There is strong association of obesity and hypertension with surrogate markers of CV disease during childhood and

• Young obese adults with ‘childhood onset’ obesity display the highest risk of developing CV risk factors

• Emerging longitudinal data regarding CV mortality related to elevated BP levels in young adults

Tertiary hypertension service at ELCHsince June 2009

90% with normal renal function

▪ Family history & investigation work-up completed

▪ Out of office evaluation including interpretation of results

▪ dietary assessment for salt and calories

▪ 24-hour urine specimen for measurement of sodium

▪ cardiac (and vascular) assessment

▪ monitoring following commencement of therapy

▪ shared care management29

‘One stop’ clinic for evaluation of

hypertension in children - single visit

Tertiary clinic-2

• The service is now well established with over 450 patients seen in the past 7-years– see 80-90 new referrals per year

• Patients being referred from primary, secondary – primary care - General Practitioners - rarely

– secondary care – Consultant Paediatricians – majority

– tertiary care – Consultant sub-specialists (cardiologist, endocrine)

• What are their age ranges? – 14% <2years; 11% 2-5 years; 75% >5years

Case 1 DO

• 12 year old boy, african origin - headaches & chest pain

• No cardiac cause identified hence referred to the clinic– 135.7 cm (2nd-9th percentile) and 42.7 kg (75th

percentile)– BMI 23.2 kg/m2 (95th percentile) – clinical excess

weight

– 126/78 mmHg clinic (95th percentile 119/78) -confirmed on ambulatory BP 126/67 mmHg - ISH

– concentric LVH with increased microalbuminuria– 7g of sodium in 24-hour urine specimen

Case 1 DO

• Future management• Commenced on amlodipine whilst actively

modifying lifestyle & diet• 12 months later BP 112/70 mmHg

– asymptomatic but now performing regular physical exercise

– 138.5 cm and 46kg - BMI 24.0 kg/m2 (97th

percentile) – Very few snacks - 5g equivalent of sodium in 24-

hour urine– LVMI – improved 44 g/m2.7

Normal blood pressure values for boys

Height

percentile50th 75th 90th 95th

12 year

95th BP

percentile

123/81 125/82 127/82 127/83

13 year

95th BP

percentile

126/81 128/82 129/83 130/83

Staging of Hypertension

• Stage 1: 95th–99th percentile

• Stage 2: >99th percentile +5mmHg

• Clinical urgency – symptomatic or incidental finding?

– Life threatening hypertension

36

Improve clinical practice - 1

‘Cardio Z’ iphone app from ELCH

http://www.ubqo.com/cardioz

• Must measure BP in children >3 years

• Copies of the normal BP tables in boys and girls from the ‘Fourth report’, should be available to all clinicians in clinic rooms

calculation of a user-defined 'target centile' blood pressure

Case 1 DO –2017

• Ongoing weight gain and ill-sustained lifestyle changes• Amlodipine and Lisinopril

• 4 years later BP 130/72 mmHg– asymptomatic– 153.4 cm and 62.8kg - BMI 26.9 kg/m2 (98th

percentile) - no change– few snacks on history – Increased indexed LV mass 65.6 g/m2.7 ; concentric

LVH

Case 2 NW

• 16 years 2 monh old boy, african origin – feels unwell, headache

– 177 cm (25th-50th percentile) and 75 kg;

– BMI: 23.9 kg/m2 (92nd percentile) - clinical excess weight

– 170/62 mmHg clinic; (95th percentile 136/86) confirmed on ambulatory BP 142/64 mmHg - ISH

– 7.9g of sodium in 24-hour– eccentric LVH with increased microalbuminuria

Case 2 NW

• Future management - 9 months later• Initially on two but now on single agent - ACEi -

BP 122/64 mmHg - asymptomatic• Modified diet - no snacks, family modified diet

Case 3 PM

• 15 year old girl, Caucasian – headaches and breathlessness

– High BP detected whilst on holiday

– 170.9 cm (50th percentile) and 96.2 kg

– BMI: 31.8 kg/m2 (99th percentile) - obese

– 143/104 mmHg clinic; (95th percentile 131/80) confirmed on ambulatory BP 142/68 mmHg - ISH

– 12.5g of sodium in 24-hour; normal renal function

– no evidence of LVH; indexed LV mass 26.8 g.m2.7

Case 3 PM

• Family history of hypertension and hypercholesterolaemia

• normal lipid profile

• Difficult to convince need to take medications – will take medications for short period and stop once BP level better!

• Good response to medications but no weight improvement or change in diet

90

92

94

96

98

100

102

104

106

14 15 16 17 18

Daily recommended salt in children

• 1 to 3 years – 2g salt a day (0.8g sodium)

• 4 to 6 years – 3g salt a day (1.2g sodium)

• 7 to 10 years – 5g salt a day (2g sodium)

• 11 years and over – 6g salt a day (2.4g sodium)

• Food labels only give the figure for sodium

Salt (mg)= sodium (mg) x 2.5

http://www.nhs.uk/livewell/goodfood/pages/salt.aspx

Salt intake and blood pressure

Quanhe Yang et al. Pediatrics

2012;130:611-619

Case 4 DA

• 15 year old boy, african origin – asymptomatic– High BP detected when joining gymnasium – 186.6 cm and 103.8 kg– BMI: 29.7 kg/m2 (99th percentile) – obese

• Hyperuricaemia and dyslipidaemia– 159/77 mmHg clinic; – confirmed on ambulatory BP 154/92 mmHg - SDH– 11.5g of sodium in 24-hour; normal renal function– Concentric LVH; indexed LV mass 46.6 g.m2.7 – Commenced on Amlodipine with some improvement

• Felt better - so stopped medication and missed two appointments!

Case 4 DA

• Re-presented with even worse BP 163/100 mmHgo asymptomatic – cannot understand the fuss; weight 119.8kg

• Continuing poor adherence to diet and medication• Transitioned to adults - no change

o Asymptomatic; 132.1kg and increasing; BMI 99th percentile o Concentric LVH but with preserved biventricular systolic functiono On 3-anti-hypertensives (Amlodipine, Lisinopril and Hydrochorthiazide)

50

100

150

200

50

75

100

125

150

14.0 14.5 15.0 15.5 16.0 16.5 17.0 17.5 18.0 18.5 19.0

Blo

od

pre

ssu

re (

mm

Hg)

Wei

ght

(Kg)

Age in years

Weight SBP DBP

Case 5 JB

• 16 years 9 months boy, causcasian – intermittent headaches– High BP detected at the time of check entry to health

club– DGH - height 176.8 (50th -75th centile) and weight 119

kg– BMI 38.1 kg/m2 (>99th percentile) – morbidly obese– 160/86 mmHg - confirmed on ABPM 151/74 mmHg -

ISH– HTN clinic - 112.3 kg! and BP improved as well!!

• Clinic - 124/62 mmHg clinic; ambulatory BP 110/66 mmHg on no medication

– No evidence of LVH

Case 5 JB

• Future management

– Took up boxing – 18 months later – 83.5kg & very

well - discharged

– Dynamap 143/71 but Aneroid measurements

112/68 mmHg

Management

• Non-pharmacological: weight reduction and exercise – together most effective at least early (>6-month)

– compliance major issue

– target BMI <85th percentile, 40-min exercise 3-5 days a week

• Diet – need to cut down on salt intake– This needs to be demonstrated to families often as convinced salt

intake not high!

• Pharmacotherapy generally reserved for– symptomatic hypertension +/- evidence of end-organ damage

– elevated BP unresponsive to conservative treatment

51

Summary-3 some findings from the hypertension clinic

• Isolated systolic hypertension 80%-85%– males, adolescents, increased BMI and poor diet

– No identifiable cause – renal, cardiac, other

– mostly asymptomatic;

– High salt intake and excessive sodium in 24-hour urine even in those with normal BMI

• In confirmed cases of hypertension– less than a 1/3rd have LVH (+/-micro Alb) – often eccentric

• Most effective treatment measures that have improved BP– Reduction of salt intake

– CCB, ACEi and diuretics in some

52

Acknowledgments

• Kings College London

• Guy’s & St Thomas’ Charity

• British Heart Foundation

53

THANK YOU