Hypertension What to do when you don’t know what to do! Fiona Stewart Auckland Heart Group Auckland City Hospital 2 nd Sept 2011

Essential HypertensionBP < 140/85 Hypertension with Diabetes BP < 130/80 Renal diseaseBP < 130/80 Proteinuria > 1g/dBP < 125/75 Age > 80BP < 150/

 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 Consider Repeat visit Nurse check (“white coat hypertension”) Home BP monitoring Ambulatory 24hr BP 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

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

 Linear increase in risk from BP 115/75  ↑20mmHg SBP or ↑10mmHg DBP doubles mortality from cardiovascular disease  BP /80-89 “prehypertension”

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

 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

 Chlorthalidone 12.5 – 25mg  Amlodipine  Lisinopril  Doxazosin

 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

 ACEI + Amlodipine  ACEI + Hydrochlorothiazide

 21% Reduction in CV death, MI, CVA over 3 years  NNT to prevent one major event = 77  37% were taking > 3 agents

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

 Patients aged > 80  SBP >160mmHg, DBP < 110mmHg  Indapamide 1.5mg + Perindopril 2-4mg vs placebo  Target BP 150/80

Blood pressure separation Median follow-up 1.8 years 15 mmHg 6 mmHg

All stroke (30% reduction) Placebo IndapamideSR ±perindopril Indapamide SR ±perindopril Placebo P=0.055

Total Mortality (21% reduction) Placebo Indapamide SR ±perindopril P=0.019 Placebo IndapamideSR ±perindopril

Fatal Stroke (39% reduction) Indapamide SR ±perindopril Placebo P=0.046 Placebo IndapamideSR ±perindopril

Heart Failure (64% reduction) P< Placebo IndapamideSR ±perindopril Placebo IndapamideSR ±perindopril

HR95% CI 0.70(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 mortality NCV/Unknown death CV Death Cardiac Death Heart Failure CV events ITT – Summary

 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

 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

Measurement ◦ Sitting ◦ DBP 4 th 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

Hypertrophy Arrhythmia Oxygen Consumption Vasoconstriction Atherosclerosis Insulin Resistance The kidney as origin of sympathetic drive carried centrally via renal afferent sympathetic nerves generating central sympathetic drive Renal Afferent Nerves ↑ Renin Release  RAAS activation ↑ Sodium Retention ↓ Renal Blood Flow ↑ Renin Release  RAAS activation ↑ Sodium Retention ↓ Renal Blood Flow Sleep Disturbances Renal Efferent Nerves

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: Symplicity HTN-1

Significant, Sustained BP Reduction BP change (mmHg) 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 SystolicDiastolic Symplicity HTN-2 Investigators. Lancet. 2010;376:1903.

Changes in Glucose Tolerance at 3 Months after Renal Denervation Mahfoud et al. European Society of Cardiology