Resistant Hypertension

1. 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

2. Essential Hypertension • Uncontrolled Hypertension • Pseudo Resistant Hypertension • Resistant Hypertension • Refractory Hypertension • Secondary Hypertension • Reno Vascular Hypertension • Malignant Hypertension Understand These KEY Words

3. Sitting and standing recording of BP, Contralateral • Two readings five minutes apart, rarely lower limb BP • After resting, preferably same time of day – morning • Korotkoff’s phase V – disappearance for diastolic • Standard cuff size -12 x 26 cm, Large cuff 13 x 36 cm • Calibration of the instrument from time to time • Cuff should encircle 80% of the arm - very thin clothing • Quite environment, relaxed doctor and patient • No smoking, alcohol or caffeine by the patient • Auscultatory gap, recollect Korotkoff’s phases, Phase IV? B.P Measurement Issues Revisited

4. Non DM DM, CKD The Target Blood Pressure (JNC7)

5. “White Coat” hypertension (not without risk) • TOD is minimal in White Coat hypertension • 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 • Be cautious to a patient as label pseudo hypertension Pseudo Resistant Hypertension

6. 24 hr. Ambulatory BP Monitoring (ABPM) To distinguish white coat and pseudo hypertension, home BP and ABPM Masked hypertension

7. Hypertension in most patients is asymptomatic • TOD and complications are often occult • Side effects of the drugs, Cost, Combinations • Complexity of the regimens, timings • Multiple 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

8. How to Evaluate for Non Compliance

9. In Compliant Patient On life style change What Is Resistant Hypertension?

10. 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

11. 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

12. Mostly Polygenic Genetics and Resistant Hypertension

13. Whom We Should Watch for Sec HT?

14. Causes of Resistant Hypertension

15. Strong Associates of Resistant Hypertension

16. Problems of Resistant Hypertension

17. 30% 5% Secondary and Resistant Hypertension

18. Common Causes of Secondary Hypertension

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

20. Relative Prevalence of Secondary Hypertension

21. Mechanisms for Secondary Hypertension

22. Chronic Kidney Disease (CKD) Renal Artery Stenosis (RAS) Secondary Hypertension: Renal Causes

23. Intimal Atherosclerotic Plaques Mainly Tunica Media affected Secondary Hypertension: Renal Causes

24. 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 Renal Artery Stenosis (RAS) and RHT

25. Fibro Muscular Dysplasia (FMD)

26. FMD Treated with Angioplasty

27. Atherosclerotic RAS Treated with Angioplasty

28. 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

29. Excess Glucocorticoid Activity Excess Mineralocorticoid Activity Secondary Hypertension: Adrenal Causes

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

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

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

33. D.Dx. of Corticoid Induced Hypertension

34. Prolonged uses of External Agents Coarctation, PAN and Aortitis, PTHT Other Causes of Secondary Hypertension

35. 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 Physical Examination in Hypertension

36. 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 Evaluation of Resistant Hypertension

37. Secondary Hypertension: Evaluations

38. Salt Restriction • Weight Loss • Physical Activity • Smoking Cessation • Alcohol Abstinence • Glycaemia and Lipid Control Life Style Principles for Hypertension

39. 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 Drug Treatment of Resistant Hypertension

40. Some Practical Points of Rx. of RHT

41. Anti hypertensive drugs - interactions

42. 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

43. 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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