HypertensionWhat to do when you don’t know what to do!

Fiona StewartAuckland Heart GroupAuckland City Hospital

2nd Sept 2011

Essential Hypertension BP < 140/85

Hypertension withDiabetes BP < 130/80Renal disease BP < 130/80Proteinuria > 1g/d BP < 125/75

Age > 80 BP < 150/

HypertensionNZ Heart Foundation Recommendations

Correct cuff size Sitting x2 at 2 minute intervals Standing

BUT in patients with borderline BPs Single recordings are unreliable Multiple clinic recordings correlate poorly with ABU Home BP monitoring is not much better

ConsiderRepeat visitNurse check (“white coat hypertension”)Home BP monitoringAmbulatory 24hr BP monitoring

Blood Pressure Measurement

Home BP Measurements

Ambulatory Blood Pressure Monitoring

History◦ Other illnesses (cardiovascular disease,

diabetes, renal disease, gout)◦ Family history

Lifestyle assessment◦ Smoking, alcohol (max 1-2/d) salt intake,

liquorice ingestion, weight, exercise, stress Basic tests

◦ FBC, U + E, urate, creat, eGFR, gluc, lipids, MSU◦ ECG

Blood Pressure Review

Indication◦ Abnormal screening tests◦ Young ◦ BP severe or hard to control

Renin, aldosterone, cortisol 24h U metanephrines Renal scan and doppler study Echocardiogram – LVH, ascending aorta

Blood Pressure ReviewAdditional Tests

Linear increase in risk from BP 115/75 ↑20mmHg SBP or ↑10mmHg DBP doubles

mortality from cardiovascular disease BP 120-139/80-89 “prehypertension”

Prehypertension

Weight Salt intake (including soya sauce) Liquorice ingestion Alcohol Stress Exercise Contributing drugs (NSAIDs)

Prehypertension Management

Systolic BP better predictor of adverse cardiovascular events especially in elderly

Persistent BP > 140/85 → treat Over 80 years – aim for SBP<150

◦ Always check standing BP

Hypertension - Treatment

Chlorthalidone 12.5 – 25mg Amlodipine Lisinopril Doxazosin

Which Antihypertensive is Best?ALLHAT Trial

Doxazosin or Chlorthalidone?ALLHAT Trial

ALLHAT TrialDoxazosin and Chlorthalidone

ALLHAT TrialBP Control

Target BP < 140/90 67% achieved target 2/3 were taking 2+ agents 1/4 were taking 3+ agents

Expect to need multiple medications to control BP

ALLHAT Trial

ALLHAT TrialFatal Cardiac Event and Nonfatal MI

ACEI + Amlodipine ACEI + Hydrochlorothiazide

ACCOMPLISH Trial

ACCOMPLISH Trial

ACCOMPLISH Trial Cardiovascular Events

21% Reduction in CV death, MI, CVA over 3 years

NNT to prevent one major event = 77

37% were taking > 3 agents

ACCOMPLISH Trial

Assess comorbidity. Multiple drugs are usually necessary

First Line◦ Thiazides◦ ACEI/ARB◦ CCB

Second Line- Beta blockers

Third Line◦ Spironolactone◦ Alpha blockers◦ Clonidine

Fourth Line◦ Ardian radiofrequency ablation of renal artery

Statin

HypertensionTreatment Choice

Patients aged > 80 SBP >160mmHg, DBP < 110mmHg Indapamide 1.5mg + Perindopril 2-4mg

vs placebo Target BP 150/80

Treatment of Hypertension in the Very Elderly > 80

HYVET trial

Blood pressure separation

70

80

90

100

110

120

130

140

150

160

170

180

0 1 2 3 4 5Follow-up (years)

Blo

od P

ress

ure

(mm

Hg)

Placebo

Indapamide SR +/-perindoprilIMedian follow-up 1.8

years

15 mmHg

6 mmHg

All stroke(30% reduction)

PlaceboIndapamideSR ±perindopril

Indapamide

SR

±perindopril

Placebo

P=0.055

Total Mortality(21% reduction)

Placebo

Indapamide

SR

±perindopril

P=0.019

PlaceboIndapamideSR ±perindopril

Fatal Stroke(39% reduction)

Indapamide

SR

±perindopril

Placebo

P=0.046

PlaceboIndapamideSR ±perindopril

Heart Failure(64% reduction)

P<0.0001

Placebo

IndapamideSR

±perindopril

PlaceboIndapamideSR ±perindopril

0 20.50.20.1

HR 95% CI0.70 (0.49, 1.01)0.61 (0.38, 0.99)0.79 (0.65, 0.95)0.81 (0.62, 1.06)0.77 (0.60, 1.01)0.71 (0.42, 1.19)0.36 (0.22, 0.58)0.66 (0.53, 0.82)

All Stroke

Stroke Death

All cause mortalityNCV/Unknown deathCV Death

Cardiac Death

Heart Failure

CV events

ITT – Summary

Starting Antihypertensive Treatment

Change only one medication at a time Arrange follow up BP measurements (L+S) Check electrolytes with diuretics Escalate early to a second agent Feedback results to the patient

Confirm hypertension with 24hr monitor Check for secondary causes

◦ Renal scan ? Renal artery stenosis◦ Cortisol, renin, aldosterone, metanephrines

Lifestyle adjustments – stress, salt Compliance Optimal medication dose and frequency

BP Remains Elevated

Thiazides◦ Chlorthalidone more effective than HCZ

ACEI◦ Cilazapril and lisinopril – daily dose◦ Enalapril and quinapril – bd dose

Angiotensin II Blockers◦ Titrate dose to 32mg candesartan, 100mg

losartan CCBs

◦ Amlodipine and felodipine 10mg

Optimising Medication

Measurement◦ Sitting◦ DBP 4th Korotkoff sound

DBP <90mmHg from conception to 20/40 is strongly correlated with lower rates of pre-eclampsia

ACEI and ARB are contraindicated from 6 weeks gestation. ACEI are safe with breast feeding.

Metoprolol, oxprenolol and labetalol are associated with a better fetal outcome than other beta-blockers

Methydopa has a long record of safety in pregnancy

CCBs are well tolerated in pregnancy

Chronic Hypertension and Pregnancy

HypertrophyArrhythmiaOxygen Consumption

VasoconstrictionAtherosclerosis

InsulinResistance

The kidney as origin of sympathetic drive carried centrally via renal afferent sympathetic nerves generating central

sympathetic drive

Renal AfferentNerves

↑ Renin Release RAAS activation↑ Sodium Retention↓ Renal Blood Flow

Sleep Disturbances

Renal EfferentNerves

Radiofrequency energy can ablate the renal sympathetic nerves

• First-in-man, non-randomized• 45 patients with resistant HTN (SBP ≥160 mmHg on

≥3 anti-HTN drugs, including a diuretic) Expanded cohort of patients (n=153)

• 24-month follow-up

Lancet. 2009;373:1275

35

Symplicity HTN-1

Significant, Sustained BP Reduction

BP change(mmHg)

1 M(n=138)

3 M(n=135)

6 M(n=86)

12 M(n=64)

18 M(n=36)

24 M(n=18)

-50

-40

-30

-20

-10

0

10

-20 -24 -25 -23 -26 -32-10 -11 -11 -11 -14 -14

Systolic Diastolic

36

Primary Endpoint: 6-Month Office BP

∆ from Baseline

to 6 Months (mmHg)

33/11 mmHg difference between RDN and Control

(p<0.0001)

• 84% of RDN patients had ≥ 10 mmHg reduction in SBP• 10% of RDN patients had no reduction in SBP

37

Systolic

Diastolic

Systolic Diastolic

Symplicity HTN-2 Investigators. Lancet. 2010;376:1903.

Changes in Glucose Toleranceat 3 Months after Renal Denervation

Mahfoud et al. European Society of Cardiology. 2010.