Resistant Hypertension
Prof. Dr. Sarma VSN Rachakonda
M.D (Internal Medicine)., M.Sc., (Canada), FCGP,
FICP, FIMSA, FRCP (G), FCCP (USA), FACP (USA)
Hon. National Professor of Medicine, IMA – CGP, India
Senior Consultant Physician & Cardio-metabolic Specialist
Adjunct Professor, Tamilnadu Dr. MGR Medical University, Chennai
www.drsarma.in
 Essential
Hypertension
 Uncontrolled
 Pseudo
Hypertension
Resistant Hypertension
 Resistant
Hypertension
 Refractory
Hypertension
 Secondary
Hypertension
 Reno
Vascular Hypertension
 Malignant
Hypertension
Understand These KEY Words
 Sitting
 Two
and standing recording of BP, Contralateral
readings five minutes apart, rarely lower limb BP
 After
resting, preferably same time of day – morning
 Korotkoff’s
 Standard
phase V – disappearance for diastolic
cuff size -12 x 26 cm, Large cuff 13 x 36 cm
 Calibration
 Cuff
should encircle 80% of the arm - very thin clothing
 Quite
 No
of the instrument from time to time
environment, relaxed doctor and patient
smoking, alcohol or caffeine by the patient
 Auscultatory
gap, recollect Korotkoff’s phases, Phase IV?
B.P Measurement Issues Revisited
SBP
DBP
140
90
130
80
The Target Blood Pressure (JNC7)
 “White
 TOD
Coat” hypertension (not without risk)
is minimal in White Coat hypertension
 Uncompressible
 Measurement
 BP
arteries of old age(Osler’s Pseudo HT)
issues – small cuff (< 80% of arm)
Recorded without 5-10 minutes of rest
 Non-compliance
 40%
with drug treatment
patients discontinue Rx in the first year
 No
life style modification practiced
 Be
cautious to a patient as label pseudo hypertension
Pseudo Resistant Hypertension
To distinguish white coat and pseudo hypertension, home BP and ABPM
24 hr. Ambulatory BP Monitoring (ABPM)
Masked hypertension
 Hypertension
in most patients is asymptomatic
 TOD
and complications are often occult
 Side
effects of the drugs, Cost, Combinations
 Complexity
 Multiple
of the regimens, timings
medications for comorbidities
 Lack
of understanding of gravity of the disease, TOD
 False
belief that hypertension got “cured”
 Social,
economic and personal factors
Non Compliance for Rx. of Hypertension
Stop and
Start Drugs
Admit and
Administer
How to Evaluate for Non Compliance
In Compliant Patient
On life style change
BP not on target
Three drugs used
One is a diuretic
At optimal dosage
What Is Resistant Hypertension?
 Advancing
 High
Base line Blood Pressure
 Obesity
and Over Weight
 Excessive
 Chronic
Dietary Salt Intake, Alcoholism
Kidney Disease (CKD)
 Diabetes
 Left
age
Mellitus (Type II)
Ventricular Hypertrophy (LVH)
 Black
Race, Female Gender
Clinical Markers for Resistant Hypertension
 Non
narcotic analgesics, NSAIDs, Aspirin
 Selective
COX-2 inhibitors (Celecoxib)
 Sympathomimetic
 Diet
pills, Cocaine, Ephedrine
 Stimulants
 Alcohol
 Oral
agents (decongestants)
(Methylphenidate, Amphetamine)
(binge drinking, >30 ml/day)
Contraceptive Pills (OCP), Steroids, Anabolics
 Cyclosporine,
 Liquorice,
Erythropoietin
herbal compounds (ephedra)
Medications Interaction for BP control
Mostly Polygenic
ACE Gene
CYP3A5
Most Esta.
ENaC β,γ
Liddle’s
Genetics and Resistant Hypertension
Young Hypertensive
First Time Hypertension after 60 yrs.
Well Controlled - Now out of control
Whom We Should Watch for Sec HT?
Patient Related
Physician Related
High Sodium Intake
Sub Clinical Volume Over Load
Poor adherence to Rx. plan
Inadequate Use of Diuretics
Intake of Drugs that raise BP
Progressive Renal Insufficiency
Lack of Life Style Adherence
Unsuspected Secondary Cause
Causes of Resistant Hypertension
•HbA1c
> 9.0
•BMI >30
•Creat.
>1.5
T2DM
CKD
LVH
OSAS
•AHI >20
Strong Associates of Resistant Hypertension
Systolic BP difficult control
Diastolic BP in old age
Problems of Resistant Hypertension
Hypertension
Resistant
Secondary
Secondary and Resistant Hypertension
Primary Aldosteronism
Pheochromocytoma
SHT
Cushing's Syndrome
RAS & Renal Disease
Common Causes of Secondary Hypertension
In General Population - Low
In Specialized Clinics -15%
In Clinical Trials* - 30%
Prevalence of Resistant Hypertension
*ALLHAT, CONVINCE, LIFE, INSIGHT
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%
Relative Prevalence of Secondary Hypertension
1
• Increased Vascular Tone
2
• Na and Water Retention
3
• Abnormal SNS activation
4
• Abnormal R-A-S activation
5
• Endothelial NO mismatch
Mechanisms for Secondary Hypertension
Renal Vascular
Renal Parenchymal
Renal Artery Stenosis (RAS)
Chronic Kidney Disease (CKD)
Atherosclerotic RAS
Unilateral: Reflux, Tumour
Fibro Muscular Dysplasia (FMD)
Bilateral: CGN, CPN, Cysts, APKD
Arteritis, Dissection, Thrombosis
Renin Secreting Tumours
Takayasu Syndrome (Indians)
HT may be the effect or cause
Secondary Hypertension: Renal Causes
Fibro Muscular Dysplasia
Atherosclerotic RAS
Mainly Tunica Media affected
Intimal Atherosclerotic Plaques
Young age
Elderly, Male, Smoker, Abd. Bruit,
Female gender
Severe recent HT & CKD together
Good response to Angioplasty
Flash Pulmonary Oedema,  Chol.
Takayasu Syndrome (Indians)
Worsening with ACE, Other CVD
Secondary Hypertension: Renal Causes
 Atherosclerotic
 Fibro
muscular (media) hyperplasia is 10%
 Duplex
 MR
(intimal) Reno vascular disease is 90%
USG, MR angiography, Renal CT, Renal Scintigraphy
Angiography is highly sensitive for detecting RAS
 15%
of patients of CAG show asymptomatic RAS
 Renal
revascularization, stenting are the Rx of choice
Renal Artery Stenosis (RAS) and RHT
Fibro Muscular Dysplasia (FMD)
FMD Treated with Angioplasty
Atherosclerotic RAS Treated with Angioplasty
 CKD
is a common cause and complication of RHT
 Serum
creatinine of >1.5 mg% can cause RHT
 Increased
sodium and fluid retention
 Expansion
of intravascular volume – fluid overload
 CKD
is strong predictor of poor outcomes and RHT
Renal Parenchymal Disease and RHT
Glucocorticoid
Mineralocorticoid
Excess Mineralocorticoid Activity
Excess Glucocorticoid Activity
Primary Hyperaldosteronism
Primary  in Cortisol – Cushing’s Syn.
Glucocorticoid Remediable Aldost.
ACTH Excess – Cushing’s Disease
11β OHSD Deficiency
 Production of Catecholamines
Hyperdeoxycorticosteronism
Pheochromocytoma
Secondary Hypertension: Adrenal Causes
 20%
of cases of RHT have Primary Aldosteronism
 Suppression
 Higher
 In
of Renin Activity, Low K+ and Mg++, Met Alkalosis
24 hour urinary aldosterone excretion
the background of higher dietary sodium intake
 General
 AT
increase in R-A-S activity due to obesity
II independent Aldosterone excess
 Stimulated
by adipocyte derived secretagogues
Primary Aldosteronism and RHT
 70%
to 80% of patients with Cushing's have RHT
 Excessive
 IRS,
DM and OSAS which coexist may contribute
 TOD
is more severe in Cushing's syndrome
 Routine
 MR
stimulation of nonselective mineralocorticoid R
antihypertensive drugs are not effective
Antagonist - Eplerenone or Spironolactone are effective
 Surgical
excision of ACTH or Cortisol producing tumour
Cushing’s Syndrome and RHT
 Small
but important cause of Secondary RHT
 Prevalence
 Increased
 Episodic
is 0.1% to 0.6% of hypertensives
BP variability – A CV risk factor by itself
Hypertension, Palpitation, Headache and Sweating
 Dysglycemia
 Has
a diagnostic Specificity of 90%
 Plasma
 Has
and abnormal GTT are usually associated
free metanephrine and normetanephrine
99% sensitivity and 89% specificity
Pheochromocytoma and RHT
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+ 5THC in Urine
Deoxycorticosterone
Low
Low
Low
Pl Deoxycorticosterone
D.Dx. of Corticoid Induced Hypertension
Biological
Exogenous
Coarctation, PAN and Aortitis, PTHT
Prolonged uses of External Agents
Obstructive Sleep Apnoea - OSAS
Exogenous Glucocorticoid Admin.
Liddle’s Syndrome: ENaC Receptor
Excess Liquorice (11 β OHSD inhibit)
Acromegaly, Met Syndrome, PCOD
Excess Alcohol: > 30 ml/day
 Or  Thyroid, Hyperparathyroidism
NSAIDs, Cyclosporine, OCP
Other Causes of Secondary Hypertension
 BP
measurement (contralateral, all arms)
 Weight,
waist circumference, BMI
 Peripheral
 Thyroid
pulses, ABI, bruits (Carotid)
examination – Hypo and hyper features
 Cardiovascular
 Abdomen:
 Fundus
system examination
masses, bruit, aortic pulsation
examination for retinopathy
Physical Examination in Hypertension
 Good
 Strict
blood pressure recording technique – cuff size
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
 Day
of drug intake that can cause resistant hypertension
time sleepiness, loud snoring, apnoeic spells - OSAS
Evaluation of Resistant Hypertension
Angiography, DSA
MRI, CT, USG, Colour D
Nuclear Medicine
Secondary Hypertension: Evaluations
 Salt
Restriction
 Weight
Loss
 Physical
Activity
 Smoking
Cessation
 Alcohol
Abstinence
 Glycaemia
and Lipid Control
Life Style Principles for Hypertension
 If
a correctable cause is found, treat that
 Aggressive
 Effective
 MRA
drug therapy – Optimizing the current Rx.
Diuresis – Furosemide BID/Torsemide OD
antagonists, Spironolactone, Triamterene, Amiloride
 Hydralazine
or Minoxidil + β-Blocker and a diuretic
 Transdermal
Clonidine
Drug Treatment of Resistant Hypertension
Consider
Plasma Renin Measurement
Adding Doxazosin to regimen
Spironolactone, Eplerenone
Some Practical Points of Rx. of RHT
Antihypertensive Drug
Interacting Drug
Hydrochlorothiazide
Cholestyramine
Propranolol
Rifampicin
Guanethadine
Tricyclics
ACE Inhibitors
Indomethacin
Diuretics
Indomethacin
All Drugs
Cocaine, Tricyclics
Most of the BP Drugs
Phenylpropanolamine
Anti hypertensive drugs - interactions
 Direct
Renin Inhibitors (Aliskiren)
 Neutral
 New
Endopeptidase (NEP) Inhibitors (Omapatrilat)
Aldosterone Antagonists (Eplerenone)
 Aldosterone
 Clonidine
Extended Release
 Endothelin
 Novel
Synthase Inhibitors
Antagonists (Darusentan)
Combinations Algorithms
Future Options For Resistant Hypertension
 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
 Neurovascular
decompensation – may be temporary
Non Pharmacological Approaches
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