DR SUBHASH DUKIYACARDIOLOGY, JIPMER

Refractory hypertension

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Resistant hypertension (RHTN) is defined as high blood pressure (BP) that requires 4 or more medications for treatment. As defined, RHTN includes patients whose BP is controlled or uncontrolled after use of 4 or more medications.

patients with RHTN who never achieve BP control in spite of maximum medical therapy (i.e., refractory hypertension) 

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What Is Resistant Hypertension?

In Compliant PatientOn life style change

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Prevalence of Resistant Hypertension*ALLHAT, CONVINCE, LIFE, INSIGHT

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Causes of Resistant Hypertension 7

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Strong Associates of Resistant Hypertension 9

Pseudo Resistant Hypertension

“White Coat” hypertension (not without risk) Uncompressible arteries of old age(Osler’s Pseudo HT) Measurement issues – small cuff (< 80% of arm) BP Recorded without 5-10 minutes of rest Non-compliance with drug treatment 40% patients discontinue Rx in the first year No life style modification practiced

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24 hr. Ambulatory BP Monitoring (ABPM)To distinguish white coat and pseudo hypertension, home BP and ABPM

Masked hypertension11

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Genetics and Resistant Hypertension

Mostly Polygenic

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Secondary and Resistant Hypertension 14

Whom We Should Watch for Sec HT? 15

Evaluation of Resistant Hypertension

Good blood pressure recording technique – cuff size Strict compliance with treatment recommendations Evaluation for secondary causes of resistant hypertension Ambulatory BP monitoring (ABPM) – to exclude “White Coat” Assessment for TOD – CKD, Retinopathy, LVH – is essential History of drug intake that can cause resistant hypertension Day time sleepiness, loud snoring, apnoeic spells - OSAS

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Common Causes of Secondary Hypertension 17

Relative Prevalence of Secondary Hypertension

Primary or Essential Hypertension 93-95%

Secondary Causes 5-7%

Renal Hypertension 3-5%

Parenchymal 2-3%

Reno vascular 1-2%

Endocrine: Conn’s, Cushing’s, Pheochromocytoma 0.3-1.0%

Oral Contraceptive Pills (OCP) 0.5%

Miscellaneous 0.5%

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Mechanisms for Secondary Hypertension 19

Secondary Hypertension: Renal Causes

Renal Artery Stenosis (RAS) Chronic Kidney Disease (CKD)

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Secondary Hypertension: Renal Causes

Mainly Tunica Media affected Intimal Atherosclerotic Plaques

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Renal Artery Stenosis (RAS) and RHT

Atherosclerotic (intimal) Reno vascular disease is 90% Fibro muscular (media) hyperplasia is 10% Duplex USG, MR angiography, Renal CT, Renal

Scintigraphy MR Angiography is highly sensitive for detecting RAS 15% of patients of CAG show asymptomatic RAS Renal revascularization, stenting are the Rx of choice

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Secondary Hypertension: Adrenal Causes

Excess Mineralocorticoid Activity Excess Glucocorticoid Activity

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Primary Aldosteronism and RHT

20% of cases of RHT have Primary Aldosteronism Suppression of Renin Activity, Low K+ and Mg++, Met Alkalosis

Higher 24 hour urinary aldosterone excretion In the background of higher dietary sodium intake General increase in R-A-S activity due to obesity AT II independent Aldosterone excess Stimulated by adipocyte derived secretagogues

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Cushing’s Syndrome and RHT

70% to 80% of patients with Cushing's have RHT Excessive stimulation of nonselective mineralocorticoid R IRS, DM and OSAS which coexist may contribute TOD is more severe in Cushing's syndrome Routine antihypertensive drugs are not effective MR Antagonist - Eplerenone or Spironolactone are effective Surgical excision of ACTH or Cortisol producing tumour

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Pheochromocytoma and RHT

Small but important cause of Secondary RHT Prevalence is 0.1% to 0.6% of hypertensives Increased BP variability – A CV risk factor by itself Episodic Hypertension, Palpitation, Headache and Sweating Dysglycemia and abnormal GTT are usually associated Has a diagnostic Specificity of 90% Plasma free metanephrine and normetanephrine Has 99% sensitivity and 89% specificity

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D.Dx. of Corticoid Induced Hypertension

Type of HT Serum K

Pl Renin

Aldosterone Increase in others

Primary Hyper Aldosteronism Low Low High

Glucocorticoid Remediable (GRA) Normal Low High 18 OH-C, THC in Urine

Mineralocorticoid Excess (apparent) Low Low Low THC+ 5THC in Urine

Deoxycorticosterone Low Low Low Pl Deoxycorticosterone

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Other Causes of Secondary Hypertension

Coarctation, PAN and Aortitis, PTHT Prolonged uses of External Agents

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Secondary Hypertension: Evaluations 29

Drug Treatment of Resistant Hypertension

If a correctable cause is found, treat that Aggressive drug therapy – Optimizing the current Rx. Effective Diuresis – Furosemide BID/Torsemide OD MRA antagonists, Spironolactone, Triamterene,

Amiloride Hydralazine or Minoxidil + β-Blocker and a diuretic Transdermal Clonidine

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Some Practical Points of Rx. of RHT 31

Future Options For Resistant Hypertension

Direct Renin Inhibitors (Aliskiren) Neutral Endopeptidase (NEP) Inhibitors (Omapatrilat) Aldosterone Synthase Inhibitors Clonidine Extended Release Endothelin Antagonists (Darusentan) Novel Combinations Algorithms

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Non Pharmacological Approaches

The following procedures are invasive and irreversible Implantable pulse generators – perivascular carotid

sinus leads to be surgically implanted Renal Denervation – particularly in those with renal

origin of the disease – Promising results

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Take home message

High prevalence gjmresistant HTNDrug adherenceR/O sec. causeLife style changesOptimize drugs

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Thank you

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