Mr. AMF 62 years presented with central chest pain on exertion for last 4 monthsHypertension(BP-220/120 mmHg) for last 4 years,  taking 4 anti hypertensives.Diabetes for last 5 years (HbA1c-9.3%).Smoking for 8 years.Dyslipedemic for 3 years. H/o 5 times hospital admissions due to heart failure in last 3 years.ECG-Anterior wall ischemiaEF-58%During careful clinical exam- renal bruit on left side.Coronary angiogram done and revealed DVD. Renal angiogram showed significant left renal artery stenosis. Coronary angioplasty and left renal artery angioplasty done. Mr AMF now have no chest pain on exertion after 3 months of coronary angioplasty. Now BP is controlled (130/85 mm Hg), taking B blockers and ARB due to intolerance of ACE inhibitors. No hospital admission during this period. Diabetes and serum lipids are controlled.

1. A 45 years old gentleman presented with
BP 190/105 mmHg and getting 3
antihypertensives including a diuretics.
How will you manage this case?
Cardiology Round
Spreaker:
Professor Dr Md Toufiqur Rahman
Professor of Cardiology, CMMC, Manikganj

2. drtoufiq19711@yahoo.com
Cardiology Round
Resistant Hypertension
(Case based and Evidence based)
Dr. Md.Toufiqur Rahman
MBBS, FCPS, MD, FACC, FESC, FRCP, FSCAI,
FCCP,FAPSC, FAPSIC, FAHA,FACP
Professor of Cardiology
CMMC,Manikganj
Consultant, Medinova, Malbagh branch.

3. Cardiology Round
Mr. AMF 62 years presented with
central chest pain on exertion for last 4 months
Hypertension(BP-220/120 mmHg) for last 4 years,
taking 4 anti hypertensives.
Diabetes for last 5 years (HbA1c-9.3%).
Smoking for 8 years.
Dyslipedemic for 3 years.
H/o 5 times hospital admissions due to heart failure in last 3 years.
ECG-Anterior wall ischemia
EF-58%
During careful clinical exam- renal bruit on left side.
Coronary angiogram done and revealed DVD. Renal
angiogram showed significant left renal artery stenosis.
Coronary angioplasty and left renal artery angioplasty done.

4. Follow up
• Mr AMF now have no chest pain on exertion after
3 months of coronary angioplasty.
• Now BP is controlled (130/85 mm Hg), taking B
blockers and ARB due to intolerance of ACE
inhibitors.
• No hospital admission during this period.
• Diabetes and serum lipids are controlled.
Cardiology Round

5. From: 2018 ESC/ESH Guidelines for the management of arterial hypertension
Eur Heart J. 2018;39(33):3021-3104. doi:10.1093/eurheartj/ehy339
Cardiology Round

6. drtoufiq19711@yahoo.com
Cardiology Round

7. Cardiology Round
Medications and other substances that may increase blood presssure

8. • Hypertension is defined as resistant to treatment
when the recommended treatment strategy fails to
lower office SBP and DBP values to <140 mmHg
and/or <90 mmHg, respectively, and the inadequate
control of BP is confirmed by ABPM or HBPM in
patients whose adherence to therapy has been
confirmed.
• The recommended treatment strategy should include
appropriate lifestyle measures and treatment with
optimal or best-tolerated doses of three or more
drugs, which should include a diuretic, typically an
ACE inhibitor or an ARB, and a CCB.
• Pseudo-resistant hypertension and secondary causes
of hypertension should also have been excluded.
Cardiology Round

9. • Prevalence rates range from 5–30% in patients
with treated hypertension.
• After applying a strict definition and having
excluded causes of pseudoresistant
hypertension , the true prevalence of resistant
hypertension is likely to be <10% of treated
patients.
• Patients with resistant hypertension are at
higher risk of HMOD, CKD, and premature CV
events.
Cardiology Round

10. causes of pseudo-resistant hypertension
• (1) Poor adherence to prescribed medicines is a frequent cause of pseudo-
resistant hypertension, occurring in <_50% of patients assessed by
therapeutic drug monitoring, and is directly related to the number of
tablets prescribed .
• (2) White-coat phenomenon (in which office BP is elevated but BP is
controlled at ABPM or HBPM) is not uncommon in these patients, hence
the recommendation to confirm office hypertension with ABPM or HBPM
before confirming the diagnosis of resistant hypertension.
• (3) Poor office BP measurement technique, including the use of cuffs that
are too small relative to the arm circumference, can result in a spurious
elevation of BP.
• (4) Marked brachial artery calcification, especially in older patients with
heavily calcified arteries.
• (5) Clinician inertia, resulting in inadequate doses or irrational
combinations of BP-lowering drug therapies.
Cardiology Round
Pseudo-resistant hypertension

11. Other causes of resistant hypertension
• (1) Lifestyle factors, such as obesity or large gains in
weight, excessive alcohol consumption, and high
sodium intake.
• (2) Intake of vasopressor or sodium-retaining
substances, drugs prescribed for conditions other than
hypertension, some herbal remedies, or recreational
drug use (cocaine, anabolic steroids, etc.)
• (3) Obstructive sleep apnoea (usually, but not
invariably, associated with obesity).
• (4) Undetected secondary forms of hypertension.
• (5) Advanced HMOD, particularly CKD or large-artery
stiffening.
Cardiology Round

12. Resistant hypertension is associated with
older age (especially >75 years), male sex,
black African origin, higher initial BP at
diagnosis of hypertension, highest BP ever
reached during the patient’s lifetime,
frequent outpatient visits, obesity,
diabetes, atherosclerotic disease and
HMOD, CKD, and a Framingham 10 year
coronary risk score >20%.
Cardiology Round

13. • (1) The patient’s history, including lifestyle characteristics,
alcohol and dietary sodium intake, interfering drugs or
substances, and sleep history.
• (2) The nature and dosing of the antihypertensive
treatment.
• (3) A physical examination, with a particular focus on
determining the presence of HMOD and signs of secondary
hypertension.
• (4) Confirmation of treatment resistance by out-of-office BP
measurements (i.e. ABPM or HBPM). Laboratory tests to
detect electrolyte abnormalities (hypokalaemia), associated
risk factors (diabetes), organ damage (advanced renal
dysfunction), and secondary hypertension.
• (6) Confirmation of adherence to BP-lowering therapy.
Cardiology Round
Diagnostic approach to resistant hypertension

14. • Patients should be screened for a secondary cause of
hypertension, especially primary aldosteronism or
atherosclerotic renal artery stenosis, particularly in older
patients or patients with CKD.
• Poor adherence to treatment should be considered, but its
identification may be challenging in routine clinical practice.
Some methods are easy to use but of limited value (e.g.
standardized questionnaires), whereas others, such as drug
screening of urine or blood, show considerable promise but
are not yet widely available.
• Other methods include the measurement of BP after
directly observed treatment intake, which has been used in
clinical trials, but may be more difficult to implement in
routine clinical practice.
Cardiology Round
Diagnostic approach to resistant hypertension

15. Cardiology Round

16. Cardiology Round

17. Cardiology Round

18. Cardiology Round

19. Cardiology Round

20. Physical Examination in Hypertension
• BP measurement (contralateral, all arms)
• Weight, waist circumference, BMI
• Peripheral pulses, ABI, bruits (Carotid)
• Thyroid examination – Hypo and hyper features
• Cardiovascular system examination
• Abdomen: masses, bruit, aortic pulsation
• Fundus examination for retinopathy
Cardiology Round

21. What Is Resistant Hypertension?
BP not on target
Three drugs used
One is a diuretic
At optimal dosage
In Compliant Patient
On life style change
Cardiology Round

22. • Advancing age
• High Base line Blood Pressure
• Obesity and Over Weight
• Excessive Dietary Salt Intake, Alcoholism
• Chronic Kidney Disease (CKD)
• Diabetes Mellitus (Type II)
• Left Ventricular Hypertrophy (LVH)
• Black Race, Female Gender
Clinical Markers for Resistant Hypertension
Cardiology Round

23. • Non narcotic analgesics, NSAIDs, Aspirin
• Selective COX-2 inhibitors (Celecoxib)
• Sympathomimetic agents (decongestants)
• Diet pills, Cocaine, Ephedrine
• Stimulants (Methylphenidate, Amphetamine)
• Alcohol (binge drinking, >30 ml/day)
• Oral Contraceptive Pills (OCP), Steroids, Anabolics
• Cyclosporine, Erythropoietin
• Liquorice, herbal compounds (ephedra)
Medications Interaction for BP control
Cardiology Round

24. Patient Related
High Sodium Intake
Poor adherence to Rx. plan
Intake of Drugs that raise BP
Lack of Life Style Adherence
Physician Related
Sub Clinical Volume Over Load
Inadequate Use of Diuretics
Progressive Renal Insufficiency
Unsuspected Secondary Cause
Causes of Resistant Hypertension
Cardiology Round

25. • AHI >20• BMI >30
• Creat.
>1.5
• HbA1c >
9.0
T2DM CKD
OSASLVH
Strong Associates of Resistant Hypertension
Cardiology Round

26. Systolic BP difficult control
Diastolic BP in old age
Problems of Resistant Hypertension
Cardiology Round

27. Hypertension
Resistant
Secondary
Secondary and Resistant Hypertension
Cardiology Round

28. In General Population - Low
In Specialized Clinics -15%
In Clinical Trials* - 30%
*ALLHAT, CONVINCE, LIFE, INSIGHT
Prevalence of Resistant Hypertension
Cardiology Round

29. • 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
Cardiology Round

30. • 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
Primary Aldosteronism and RHT
Cardiology Round

31. • 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
Cushing’s Syndrome and RHT
Cardiology Round

32. • 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
Pheochromocytoma and RHT
Cardiology Round

33. • 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
Evaluation of Resistant Hypertension
Cardiology Round

34. • 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
• Day time sleepiness, loud snoring, apnoeic spells - OSAS
Drug Treatment of Resistant Hypertension
Cardiology Round

35. Some Practical Points of Rx. of RHT
Cardiology Round
Consider Plasma Renin Measurement
Adding Doxazosin to regimen
Spironolactone, Eplerenone

36. Direct Renin Inhibitors (Aliskiren)
Neutral Endopeptidase (NEP) Inhibitors (Omapatrilat)
New Aldosterone Antagonists (Eplerenone)
Aldosterone Synthase Inhibitors
Clonidine Extended Release
Endothelin Antagonists (Darusentan)
Novel Combinations Algorithms
Future Options For Resistant Hypertension
Cardiology Round

37. • 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
Cardiology Round

38. Cardiology Round

39. Technique of Hypertension Measurement
drtoufiq19711@yahoo.com
Cardiology Round

40. Cardiology Round
Causes of Resistant Hypertension
Improper blood pressure measurement
Volume overload and pseudotolerance
Excess sodium intake
Volume retention from kidney disease
Inadequate diuretic therapy)
Drug-induced or other causes
Nonadherence
Inadequate doses
Inappropriate combinations
Nonsteroidal anti-inflammatory drugs; cyclooxygenase 2 inhibitors
Cocaine, amphetamines, other illicit drugs
Sympathomimetics (decongestants, anorectics)
Oral contraceptives
Adrenal steroids
Cyclosporine and tacrolimus
Erythropoietin Licorice (including some chewing tobacco)
Selected over-the-counter dietary supplements and medicines (eg,
ephedra, ma haung, bitter orange)
Associated conditions
Obesity ,Excess alcohol intake ,Identifiable causes of hypertension

41. Cardiology Round