1 Hypertension Definition of Blood Pressure The pressure

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Hypertension

Definition of Blood Pressure The pressure exerted by blood against the artery through which it flows Blood pressure = cardiac output X systemic vascular resistance CO X SVR = BP 3

Hypertension is defined: Ø As the level of blood pressure linked with a doubled increased longterm risk for adverse events OR Hypertension is. . . “the level of blood pressure at which the benefits of action (i. e. therapeutic intervention) exceed those of inaction. ” Evans and Rose Brit Med Bull 1971; 27: 37 -42 4

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Definition of Hypertension JNC - VII BHS Normal <120/<80 Optimal <120/<80 Prehypertension 120 -139/80 -89 Normal <130/<85 Stage 1 140 -159/90 -99 High Normal 130 -139/85 -89 Stage 2 >160/>100 Hypertension Chobnian JAMA 2003; 289: 2560 Grade 1 140 -159/90 -99 Grade 2 160 -179/100 -109 Grade 3 >180/>110 Isolated syst. hypertension Grade 1 140 -159/<90 Grade 2 >160/<90 Williams BMJ 2004; 328; 634 7

What guidelines are used to categorize HTN? The Joint Committee on Prevention, Evaluation, and Treatment of High Blood Pressure (JNC 7) guidelines provide the most current guidelines http: //www. nhlbi. nih. gov/hbp/detect/categ. htm 8

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JNC 6 Report 10

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Prevalence 65 million Americans have hypertension (HTN) Of those diagnosed with HTN < 50% have their blood pressure under control Lack of treatment leads to serious complications 12

Prevalence of hypertension (%) High Prevalence of Hypertension Worldwide USA Italy Sweden England Spain Finland Adults aged 35– 64 y (data are age- and sex-adjusted), except* (adults aged ≥ 30 y) Hypertension defined as BP 140/90 mm. Hg or on treatment 13 Wolf-Maier et al. JAMA. 2003; 289: 2363 2369; Sekikawa, Hayakawa. J Hum Hypertens. 2004; 18: 911– 912. Japan* Germany

Prevalence of Hypertension 14

Awareness, Treatment and Control of Hypertension is Rather Low Worldwide Proportion of patients in the population (%) Country Aware Treated Controlled* Japan 16. 0 – 4. 1 England 35. 8 24. 8 10. 0 Germany 36. 5 26. 1 7. 8 Spain 38. 9 26. 8 5. 0 Sweden 48. 0 26. 2 5. 5 Italy 51. 8 32. 0 9. 0 USA 69. 3 52. 5 28. 6 * BP < 140/90 mm. Hg 15 Wolf-Maier et al. Hypertension. 2004; 43: 10– 17; Sekikawa, Hayakawa. J Hum Hypertens. 2004; 18: 911– 912. 15

BP Control Rates Trends in awareness, treatment, and control of high blood pressure in adults ages 18– 74 Awareness Treatment Control National Health and Nutrition Examination Survey, Percent II II II (Phase 1) (Phase 2) 1976– 80 1988– 91 1991– 94 1999– 2000 51 73 68 70 31 55 54 59 10 29 27 34 16

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Benefits of Lowering BP Average Percent Reduction Stroke incidence 35– 40% Myocardial infarction 20– 25% Heart failure 50% 19

Risk of CV Mortality Doubles With Each 20/10 mm. Hg BP Increase • Meta-analysis of 61 prospective, observational studies • 1 million adults aged 40– 69 y with BP > 115/75 mm. Hg • 12. 7 million person-years Fold increase in relative CV risk 8 -fold 4 -fold 2 -fold 115/75 135/85 155/95 SBP/DBP (mm. Hg) 175/105 20

Each 2 mm. Hg Decrease in SBP Reduces CV Risk by 7– 10% • Meta-analysis of 61 prospective, observational studies • 1 million adults aged 40– 69 y with BP > 115/75 mm. Hg • 12. 7 million person-years 2 mm. Hg decrease in mean SBP 21 Lewington et al. Lancet. 2002; 360: 1903– 1913. 7% reduction in risk of IHD and other vascular disease mortality 10% reduction in risk of stroke mortality 21

CVD Risk § HTN prevalence ~ 50 million people in the United States. § The BP relationship to risk of CVD is continuous, consistent, and independent of other risk factors. § Each increment of 20/10 mm. Hg doubles the risk of CVD across the entire BP range starting from 115/75 mm. Hg. § Prehypertension signals the need for increased education to reduce BP in order to prevent hypertension. 22

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Factors contribute to the development of primary HTN 1. 2. 3. Sympathetic nervous system hyperactivity Renin-angiotensin-aldosterone system hyperactivity Endothelial dysfunction 25

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Types of HTN? Primary • ? ? ‘essential’idiopathic • Most common type found in 90 -95% of those with HTN • Cause not well understood • Salt sensitive • RAAS dependent Secondary • Caused by some other medical problem or condition: • • • High-dose estrogen Renal artery stenosis Pregnancy (PET) Cushing’s syndrome pheochromocytoma Others? 27

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ABPM ? Renin level ? ? 29

What are the Symptoms? Symptoms may or may not be present • • Dizziness (unsteadiness) Early morning headache activity tolerance Malaise, fatigue Blurring of vision Spontaneous nosebleed Palpitations, angina, dyspnea Early signs/symptoms are often missed 30

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BP measurement Physical assessment • Height & weight • Blood pressure Measuring BP accurately: • No smoking or caffeine 30 minutes before • Rest for 5 minutes prior to BP • Apply cuff to bare arm • Proper size cuff applied 1 inch above brachial artery • Inflate cuff to 30 mm. Hg above initial radial pulse check If BP elevated, wait 2 minutes, recheck • Check BP in other arm 34

BP Measurement Techniques Method Brief Description In-office Two readings, 5 minutes apart, sitting in chair. Confirm elevated reading in contralateral arm. 140/90 Ambulatory BP monitoring Indicated for evaluation of “whitecoat” HTN. Absence of 10– 20% BP decrease during sleep may indicate increased CVD risk. 130/80 Provides information on response to therapy. May help improve adherence to therapy and evaluate “white-coat” HTN. 135/85 35 Self-measurement

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White Coat and Ambulatory BP monitoring ABPM 37

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Key Messages § For persons over age 50, SBP is a more important than DBP as CVD risk factor. § Starting at 115/75 mm. Hg, CVD risk doubles with each increment of 20/10 mm. Hg throughout the BP range. § Persons who are normotensive at age 55 have a 90% lifetime risk for developing HTN. § Those with SBP 120– 139 mm. Hg or DBP 80– 89 mm. Hg should be considered prehypertensive who require health 40 promoting lifestyle modifications to prevent CVD.

Key Messages (Continued) § Thiazide-type diuretics should be initial drug therapy for most, either alone or combined with other drug classes. § Certain high-risk conditions are compelling indications for other drug classes. § Most patients will require two or more antihypertensive drugs to achieve goal BP. § If BP is >20/10 mm. Hg above goal, initiate therapy with two agents, one usually should be a thiazide-type diuretic. 41

Key Messages (Continued) § The most effective therapy prescribed by the careful clinician will control HTN only if patients are motivated. § Motivation improves when patients have positive experiences with, and trust in, the clinician. § Empathy builds trust and is a potent motivator. § The responsible physician’s judgment remains paramount. 42

Complications of HTN The higher the BP and the longer an individual has hypertension, the higher the risk of complications which include: • • • Hypertensive heart disease Cerebrovascular disease Peripheral vascular disease Kidney disease Retinal damage 43

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Complications of Hypertension Heart • resistance workload left ventricular hypertrophy • CAD, angina, MI • Heart failure 46

Complications of Hypertension Brain • Atherosclerosis, stroke 47

Complications of Hypertension Peripheral vascular disease • Aortic aneurysm or dissection Retinal damage • damage to blood vessels of the eye Kidney disease • vessels less elastic decreased perfusion renal failure 48

Acute Complications Hypertensive Crisis: Severe and abrupt elevation of BP Diastolic over 120 mm hg High Mortality Sx: papilledema, progressive renal failure, encephalopathy Most common cause is untreated hypertension Goal: slowly decrease BP 49

Classifications Hypertensive Crisis Hypertensive crisis is categorized by the degree of organ damage Hypertensive emergency: BP is severely elevated and there is evidence of target organ damage Hypertensive urgency: BP is elevated but there is no evidence of target organ damage • Especially brain 50

GOAL: Reduce Complications JNC 7 guidelines recommend a target BP of less than 140/90 Patients with renal disease or diabetes need BP less than 130/80 51

What Reduces Risk of Complications? REDUCING MODIFIABLE RISK FACTORS IS A KEY INTERVENTION Goal = Patient teaching to reduce risk factors Drug therapy is initiated if lifestyle changes are not effective to control BP 52

Management of Hypertension Depends on risk group Lifestyle modifications Drug therapy is initiated if lifestyle modifications do not achieve goal Add or change drugs if goal not achieved 53

TREATMENT: Lifestyle Modification Lose excess weight Cut back on salt Exercise regularly Cease alcohol intake Adopt the DASH eating plan to decrease cholesterol intake STOP smoking 54

DASH Diet http: //www. nhlbi. nih. gov/health/public/h eart/hbp/dash/ Dietary Approaches to Stop Hypertension = DASH • A diet rich in fruits, vegetables and low-fat dairy products with reduced fat content • Limits sodium intake to 2. 4 g/day 55

Non-pharmacologic Management of Hypertension Weight management • DASH Low sodium-low fat diet Smoking cessation Restrict alcohol and caffeine Regular aerobic exercise Stress management • bio-feedback, relaxation, yoga, Tai Chi 56

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Drug Therapy for HTN Diuretics • Flush excess water and sodium from the body • Thiazide diuretics • Loop diuretics: furosemide (Lasix) • Potassium sparing: Aldactone Beta adrenergic blockers Three classes: • Cardioselective • Non-selective • Combined alphabeta-blockers 58

The Majority of Hypertensive Patients Need Combination Therapy to Achieve BP Goals Trial (SBP achieved) ASCOT-BPLA (137 mm. Hg) ALLHAT (138 mm. Hg) IDNT (138 mm. Hg) RENAAL (141 mm. Hg) UKPDS (144 mm. Hg) ABCD (132 mm. Hg) MDRD (132 mm. Hg) HOT (138 mm. Hg) AASK (128 mm. Hg) 1 59 Bakris et al. Am J Med. 2004; 116(5 A): 30 S– 38 S; Dahlöf et al. Lancet. 2005; 366: 895– 906. 2 3 4 Average number of antihypertensive medications

Pharmacologic Management of Hypertension Alpha-adrenergic blockers • Suppress nerve impulses to blood vessels, which allows blood to pass more easily so BP goes ↓ • prazosin (Minipress) Calcium channel blockers • decrease the influx of Ca++ into muscle cells • Act on vascular smooth muscles (primary arteries) to decrease spasm and promote vasodilation • Amlodipine (Norvasc); felodipine (Plendil) 60

Pharmacologic Management of Hypertension Angiotensin converting enzyme (ACE) inhibitors Angiotensin II receptor blockers (ARB) • Decrease effect of • Prevent action of RAA system: Capoten, Lisinopril • Diabetes mellitus w/proteinuria, heart failure angiotensin II and produce vasodilation • losartan (Cozaar) 61

Pharmacologic Management of Hypertension Vasodilators • Direct arterial vasodilation • Sodium nitroprusside (Nipride) • Often used in hypertensive crisis Alpha-receptor agonists • Clonidine • Acts on central nervous system • Lowers peripheral vascular resistance 62

Why don’t some patients respond to therapy? Non-adherence to therapy • Patients don’t take their HTN meds → complications!!! • Cost, inadequate teaching, side effects, inconvenient dosing Drug related causes Other conditions Secondary hypertension Volume overload 63

Causes of Resistant Hypertension § Improper BP measurement § Excess sodium intake § Inadequate diuretic therapy § Medication • Inadequate doses • Drug actions and interactions (e. g. , nonsteroidal antiinflammatory drugs (NSAIDs), illicit drugs, sympathomimetics, oral contraceptives) • Over-the-counter (OTC) drugs and herbal supplements § Excess alcohol intake 64 § Identifiable causes of HTN

Summary Key Points Two types of HTN: primary & secondary Inadequate BP control leads to serious complications including STROKE Key point: risk factor modification Treatment focuses on lifestyle management and drug therapy JNC 7 provides the most current treatment guidelines for hypertension 65

Identifiable Causes of Hypertension § Sleep apnea § Drug-induced or related causes § Chronic kidney disease § Primary aldosteronism § Renovascular disease § Chronic steroid therapy and Cushing’s syndrome § Pheochromocytoma § Coarctation of the aorta § Thyroid or parathyroid disease 66

Pheochromocytoma 0. 01 -0. 1% of HTN population • Found in 0. 5% of those screened M=F 3 rd to 5 th decades of life Rare, investigate only if clinically suspicion: • • • Signs or Symptoms Severe HTN, HTN crisis Refractory HTN (> 3 drugs) HTN present @ age < 20 or > 50 ? Adrenal lesion found on imaging (ex. Incidentaloma) 67

Pheo: Signs & Symptoms The five P’s: • • • Pressure (HTN) 90% Pain (Headache) 80% Perspiration 71% Palpitation 64% Pallor 42% • Paroxysms (the sixth P!) The Classical Triad: • Pain (Headache), Perspiration, Palpitations • Lack of all 3 virtually excluded diagnosis of pheo in a series of > 21, 0000 patients 68

Pheo: Paroxysms, ‘Spells’ 10 -60 min duration Frequency: daily to monthly Spontaneous Precipitated: • Diagnostic procedures, I. A. Contrast (I. V. is OK) • Drugs (opiods, unopposed -blockade, anesthesia induction, histamine, ACTH, glucagon, metoclopramide) • Strenuous exercise, movement that increases intra-abdo pressure (lifting, straining) • Micturition (bladder paraganlgioma) 69

Pheo: ‘Rule of 10’ 10% extra-adrenal (closer to 15%) 10% occur in children 10% familial (closer to 20%) 10% bilateral or multiple (more if familial) 10% recur (more if extra-adrenal) 10% malignant 10% discovered incidentally 70

Plasma Metanephrines Not postural dependent: can draw normally Secreted continuously by pheo SEN 99% SPEC 89% False Positive: acetaminophen Assay not widely available yet 71

Localization: Imaging CT abdomen • Adrenal pheo SEN 93 -100% • Extra-adrenal pheo SEN 90% MRI • > SEN than CT for extra-adrenal pheo MIBG Scan • SEN 77 -90% SPEC 95 -100% 72

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Renovascular Hypertension 74

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Endocrine Hypertension Catecholamine producing tumours Mineralocorticoid hypertension Renin-dependent hypertension Hyperthyroidism and hypothyroidism Acromegaly Hyperparathyroidism 76

Typical clinical scenarios Difficult hypertension with hypokalaemia, on polypharmacy- referred to endocrinologist for exclusion of 2 ary hypertension Coincidentaloma of adrenal with hypertension, on polypharmacy Which drugs are permissible, and after how much delay should there be before investigation? 77

Mineralocorticoid hypertension- in whom should it be suspected? Diagnosis should be suspected in patient with hypertension, spontaneous hypokalaemia (<3. 5 mmol/l), and alkalosis. Severe hypokalaemia (<3. 0) on diuretics Investigate patient hypertension refractory to conventional therapy, or adrenal coincidentaloma Recent onset of hypertension Normokalaemia present in >35% patients on low salt diet 78

Clinical features of hyperaldosteronism Mild to severe hypertension Sodium retention + intravascular vol exp mineralocorticoid escape Resetting of osmostat (thirst provoked at higher [Na+]) K+ loss (kaliuresis) +/- low serum K+ (unprovoked: rule out diuretics, laxatives, vomiting, herbal supplements) Suppression of renin generation (rule out drugs, excessive dietary sodium intake) Polyuria, nocturia, fatigue, cramps, Mg++↓ Exclude liquorice abuse / carbenoxolone therapy NB minor mineralocorticoids DOC, compound B 79

Imaging in 1 ary hyperaldosteronism High resolution CT scanning with thin (2 -3 mm) slices Bilateral adrenal venous catheter (measure cortisol, adrenaline + aldosterone) remains gold standard – operator dependent: right adrenal notoriously difficult to cannulate. Give iv ACTH (2μg/min) during sampling to magnify difference between tumour and non-tumorous side Non-tumorous side PAC = peripheral value because of suppressed PRA 80

Glucocorticoid remediable hyperaldosteronism GRA (FH 1) Due to aberrant expression of chimeric gene formed by unequal recombination of promoter and initial parts of CYP 11 B 1 and section of CYP 11 B 2 with aldosterone synthase activity Aldosterone under ACTH control Autosomal dominant: FH of early onset BP↑ with CVA , K+↓ High levels of 18 -hydroxy and 18 -oxocortisol Rx : chronic administration of low dose GC, spironolactone, or amiloride 81

Liddle syndrome Familial BP↑, unprovoked K+↓, PRA↓, and undetectable PAC Autosomal dominant, caused by constitutive activation of distal renal epithelial sodium channel (β, γ C-terminal subunit mutations prevent trafficking of channel) Treated by amiloride 82

Liddle's – low renin, low aldo Licorice and SAME -- low renin, low aldo Renal artery stenosis and renin-secreting tumors -- high renin, high aldo Adrenal hyperfunction -- low renin, high aldo 83

Renin Aldo Liddle low Licorice low RAS high Conn’s low high 84

Renin-Angiotesnin. Aldosterone System A drop in BP or blood volume causes kidneys to secrete renin, renin a precursor to angiotensin I Angiotensin-converting enzyme turns angiotensin I into angiotensin II, a potent vasoconstrictor Stimulates adrenal glands to release aldosterone This prompts the kidneys to retain sodium and water The increased volume and vasoconstriction raise BP 85

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