Obesity and Hypertension. Manish Sinha Evelina London Children s Hospital

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1 Obesity and Hypertension Manish Sinha Evelina London Children s Hospital Manchester 30 th June 2017

2 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

3 Definition of obesity - BMI There are several definitions around for overweight and obesity Clinical cut-offs - 85 th and 95 th percentile Health policy - 91 st and 98 th percentile (NICE/ DoH) International Obesity Task force (IOTF) - 88 th /90 th and 99 th corresponds with adult BMI cut offs at 25 kg/m 2 and 30 kg/m 2

5 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:

6 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

7 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:

8 and how common is hypertension in obese children?

9 Prevalence of hypertension and prehypertension in US (NHANES) Hypertension: SBP and/or DBP on 3 occasions 95 th percentile Prevalence 1-2%, age 8-17 Prehypertension: SBP and/or DBP 90 th percentile, < 95 th percentile or BP >120/80 mmhg Prevalence about 5% age % age 13-17

10 Prevalence of hypertension and prehypertension in US (NHANES) JAMA Pediatr. 2015;169(3): doi: /jamapediatrics

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

12 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): , 2016.

13 Major issue - several OTHER problems Type 2 diabetes mellitus Dyslipidaemia Non-alcoholic fatty liver (steatohepatitis) Obstructive sleep apnea Orthopaedic problems

14 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) % 16% 16% 20% 20% 11% < Age Franklin et al. Hypertension 2001;37:

15 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) % 16% 16% 20% 20% 11% < Age Sorof et al. J Pediatr 2002;140: Franklin et al. Hypertension 2001;37:

16 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

17 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 Pathophysiology - 2

18 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

19 Do obese hypertensive children exhibit TOD? Obesity increased clustering of CV risk factors Increased carotid intima medial thickness (cimt) and LVH described in children with essential hypertension cimt and LV mass correlate with blood pressure and BMI elevated BMI, SBP and serum triglyceride and LDL-C Berenson GS et al. N Engl J Med 1998;338:

20 The Journal of Clinical Hypertension Volume 18, Issue 7, pages

22 Value of current BMI and BP? Normal BMI and blood pressure tracks during childhood tracking Probability of overweight at age 35 y predicted from childhood BMI at the 95th percentile 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

23 Value of current BP SBP and DBP tracking correlation coefficients against follow-up period Xiaoli Chen, and Youfa Wang Circulation. 2008;117: Copyright American Heart Association, Inc. All rights reserved.

24 Childhood Adiposity, Adult Adiposity, and Cardiovascular Risk Factors Juonala M et al. N Engl J Med 2011;365: 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)

27 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): doi: /j.jacc Figure Legend: 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 Date mmof Hg download: and DBP 85 to 89 mm Hg, SBP 130 Copyright to 139 mm The Hg American and DBP <85 College mm Hg, of Cardiology. or SBP <130 mm Hg and DBP 85 to 89 mm Hg); 5/25/2015 salmon, optimal-normal BP (SBP <130 mm Hg and DBP All <85 rights mm reserved. Hg). The log-rank was used to calculate p values. IDH = isolated diastolic hypertension; ISH = isolated systolic hypertension; SDH = systolic diastolic hypertension.

28 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

29 Tertiary One stop hypertension clinic for service evaluation at ELCH of since June 2009 hypertension in children - single visit 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 management 29

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 -

30 Tertiary clinic-2 The service is now well established with over 450 patients seen in the past 7-years see 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

31 Case 1 DO 12 year old boy, african origin - headaches & chest pain No cardiac cause identified hence referred to the clinic cm (2 nd -9 th percentile) and 42.7 kg (75 th percentile) BMI 23.2 kg/m 2 (95 th percentile) clinical excess weight 126/78 mmhg clinic (95 th percentile 119/78) - confirmed on ambulatory BP 126/67 mmhg - ISH concentric LVH with increased microalbuminuria 7g of sodium in 24-hour urine specimen

32 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 cm and 46kg - BMI 24.0 kg/m 2 (97 th percentile) Very few snacks - 5g equivalent of sodium in 24- hour urine LVMI improved 44 g/m 2.7

33 Normal blood pressure values for boys Height percentile 50 th 75 th 90 th 95 th 12 year 95 th BP percentile 13 year 95 th BP percentile 123/81 125/82 127/82 127/83 126/81 128/82 129/83 130/83

36 Staging of Hypertension Stage 1: 95 th 99 th percentile Stage 2: >99 th percentile +5mmHg Clinical urgency symptomatic or incidental finding? Life threatening hypertension 36

Improve clinical practice - 1 Must measure BP in children >3 years Copies of the normal BP tables in boys and girls from the Fourth report, should be

37 Improve clinical practice - 1 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 Cardio Z iphone app from ELCH calculation of a user-defined 'target centile' blood pressure

38 Case 1 DO 2017 Ongoing weight gain and ill-sustained lifestyle changes Amlodipine and Lisinopril 4 years later BP 130/72 mmhg asymptomatic cm and 62.8kg - BMI 26.9 kg/m 2 (98 th percentile) - no change few snacks on history Increased indexed LV mass 65.6 g/m 2.7 ; concentric LVH

39 Case 2 NW 16 years 2 monh old boy, african origin feels unwell, headache 177 cm (25 th -50 th percentile) and 75 kg; BMI: 23.9 kg/m 2 (92 nd percentile) - clinical excess weight 170/62 mmhg clinic; (95 th percentile 136/86) confirmed on ambulatory BP 142/64 mmhg - ISH 7.9g of sodium in 24-hour eccentric LVH with increased microalbuminuria

40 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

43 Case 3 PM 15 year old girl, Caucasian headaches and breathlessness High BP detected whilst on holiday cm (50 th percentile) and 96.2 kg BMI: 31.8 kg/m2 (99 th percentile) - obese 143/104 mmhg clinic; (95 th 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

44 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

45 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

46 Salt intake and blood pressure Quanhe Yang et al. Pediatrics 2012;130:

47 Case 4 DA 15 year old boy, african origin asymptomatic High BP detected when joining gymnasium cm and kg BMI: 29.7 kg/m2 (99 th 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!

48 Weight (Kg) Blood pressure (mmhg) Case 4 DA Weight SBP DBP Re-presented with even worse BP 163/100 mmhg o asymptomatic cannot understand the fuss; weight 119.8kg Continuing poor adherence to diet and medication Transitioned to adults - no change o o o Age in years Asymptomatic; 132.1kg and increasing; BMI 99 th percentile Concentric LVH but with preserved biventricular systolic function On 3-anti-hypertensives (Amlodipine, Lisinopril and Hydrochorthiazide)

49 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 (50 th -75 th centile) and weight 119 kg BMI 38.1 kg/m 2 (>99 th percentile) morbidly obese 160/86 mmhg - confirmed on ABPM 151/74 mmhg - ISH HTN clinic kg! and BP improved as well!! Clinic - 124/62 mmhg clinic; ambulatory BP 110/66 mmhg on no medication No evidence of LVH

50 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

51 Management Non-pharmacological: weight reduction and exercise together most effective at least early (>6-month) compliance major issue target BMI <85 th 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

52 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 1/3 rd 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

53 Acknowledgments Kings College London Guy s & St Thomas Charity British Heart Foundation 53

54 THANK YOU

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