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HypertensionHypertension

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Definition of Blood PressureThe pressure exerted by blood against the

artery through which it flows

Blood pressure = ca rdiac output X systemic vascular

resistance

CO X SVR = BP

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As the level of blood pressure As the level of blood pressure linked with a doubled increased linked with a doubled increased long-term risk for adverse eventslong-term risk for adverse events

Hypertension is ... “the level of Hypertension is ... “the level of blood pressure at which the blood pressure at which the benefits of action (i.e. therapeutic benefits of action (i.e. therapeutic intervention) exceed those of intervention) exceed those of inaction.”inaction.”

Evans and Rose Brit Med Bull Evans and Rose Brit Med Bull 1971;27:37-421971;27:37-42

Hypertension is defined:Hypertension is defined:

OROR

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Definition of Hypertension

Normal <120/<80

Prehypertension 120-139/80-89

Stage 1 140-159/90-99

Stage 2 >160/>100

Chobnian JAMA 2003;289:2560

Optimal <120/<80

Normal <130/<85

High Normal 130-139/85-89

Hypertension

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

JNC - VII BHS

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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

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JNC 6 Report

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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 Lack of treatment leads to serious complicationscomplications

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High Prevalence of Hypertension Worldwide

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3842

47 49 4955

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0

20

40

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Italy Sweden England Spain Finland Germany

Adults aged 35–64 y (data are age- and sex-adjusted), except* (adults aged ≥ 30 y) Hypertension defined as BP 140/90 mmHg or on treatment

Wolf-Maier et al. JAMA. 2003;289:23632369;Sekikawa, Hayakawa. J Hum Hypertens. 2004; 2004;18:911–912.

USA Japan*

Pre

vale

nce

of

hype

rten

sion

(%

)

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Prevalence of HypertensionPrevalence of Hypertension

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Awareness, Treatment and Control of Hypertension is Rather Low Worldwide

* BP < 140/90 mmHg

Wolf-Maier et al. Hypertension. 2004;43:10–17;Sekikawa, Hayakawa. J Hum Hypertens. 2004;18:911–912.

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

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BP Control Rates

Trends in awareness, treatment, and control of high blood pressure in adults ages 18–74

National Health and Nutrition Examination Survey, Percent

II1976–80

II(Phase 1)1988–91

II(Phase 2)1991–94 1999–2000

Awareness 51 73 68 70

Treatment 31 55 54 59

Control 10 29 27 34

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Benefits of Lowering BP

Average Percent Reduction

Stroke incidence 35–40%

Myocardial infarction 20–25%

Heart failure 50%

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Risk of CV Mortality Doubles With Each 20/10 mmHg BP Increase

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2

4

6

8

10

Fol

d in

crea

se in

re

lati

ve C

V r

isk

1-fold2-fold

4-fold

8-fold

115/75 135/85 155/95 175/105SBP/DBP (mmHg)

• Meta-analysis of 61 prospective, observational studies

• 1 million adults aged 40–69 y with BP > 115/75 mmHg

• 12.7 million person-years

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2 mmHg decrease in mean SBP

10% reduction in risk of stroke mortality

7% reduction in risk of IHD and other vascular disease mortality

Each 2 mmHg Decrease in SBP Reduces CV Risk by 7–10%

Lewington et al. Lancet. 2002;360:1903–1913.

• Meta-analysis of 61 prospective, observational studies

• 1 million adults aged 40–69 y with BP > 115/75 mmHg

• 12.7 million person-years

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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 mmHg doubles the risk of CVD across the entire BP range starting from 115/75 mmHg.

Prehypertension signals the need for increased education to reduce BP in order to prevent hypertension.

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Factors contribute to the development of primary HTN

1. Sympathetic nervous system hyperactivity

2. Renin-angiotensin-aldosterone system hyperactivity

3. Endothelial dysfunction

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Types of HTN?

Primary Primary • ?? ‘essential’idiopathic• Most common type

found in 90-95% of those with HTN

• Cause not well understood

• Salt sensitive• RAAS dependent

SecondarySecondary• Caused by some other

medical problem or condition:

• High-dose estrogen

• Renal artery stenosis

• Pregnancy (PET)

• Cushing’s syndrome

• pheochromocytoma

• Others?

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Renin level ??Renin level ??

ABPM ?ABPM ?

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What are the Symptoms?

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

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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 mmHg above initial radial pulse check If BP elevated, wait 2 minutes, recheck

• Check BP in other arm

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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 “white-coat” HTN. Absence of 10–20% BP decrease during sleep may indicate increased CVD risk. 130/80

Self-measurement Provides information on response to therapy. May help improve adherence to therapy and evaluate “white-coat” HTN. 135/85

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White Coat and Ambulatory BP monitoring ABPM White Coat and Ambulatory BP monitoring ABPM

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For persons over age 50, SBP is a more important than DBP as CVD risk factor.

Starting at 115/75 mmHg, CVD risk doubles with each increment of 20/10 mmHg throughout the BP range.

Persons who are normotensive at age 55 have a 90% lifetime risk for developing HTN.

Those with SBP 120–139 mmHg or DBP 80–89 mmHg should be considered prehypertensive who require health-promoting lifestyle modifications to prevent CVD.

Key MessagesKey Messages

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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 mmHg above goal, initiate therapy with two agents, one usually should be a thiazide-type diuretic.

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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.

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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

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Complications of Hypertension

Heart resistance

workload left ventricular hypertrophy

• CAD, angina, MI• Heart failure

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Complications of Hypertension

Brain Brain • Atherosclerosis,

stroke

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Complications of Hypertension

Peripheral vascular Peripheral vascular diseasedisease• Aortic aneurysm

or dissectionRetinal damageRetinal damage• damage to blood

vessels of the eye

Kidney diseaseKidney disease • vessels less

elastic decreased perfusion renal failure

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Acute Complications

Hypertensive Hypertensive Crisis:Crisis:Severe and abrupt elevation of BPDiastolic over 120mm hgHigh Mortality

Sx: papilledema, progressive renal failure, encephalopathyMost common cause is untreated hypertensionGoal: slowly decrease BP

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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• Especially brain

Hypertensive urgency:

BP is elevated but there is no evidence of target organ damage

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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

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What Reduces Risk of Complications?

REDUCING MODIFIABLE RISK REDUCING MODIFIABLE RISK FACTORS IS A KEY INTERVENTIONFACTORS IS A KEY INTERVENTION

Goal = Patient teaching to reduce risk factors

Drug therapy is initiated if lifestyle changes are not effective to control BP

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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

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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

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DASH Diet

http://www.nhlbi.nih.gov/health/public/heart/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

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Non-pharmacologic Management of Hypertension

Weight management• DASH

Low sodium-low fat dietSmoking cessationRestrict alcohol and caffeineRegular aerobic exerciseStress management • bio-feedback,

relaxation, yoga, Tai Chi

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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 blockersThree classes:• Cardioselective• Non-selective• Combined alpha-

beta-blockers

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Average number of antihypertensive medications1 2 3 4

Trial (SBP achieved)

ASCOT-BPLA (137 mmHg)

ALLHAT (138 mmHg)

IDNT (138 mmHg)

RENAAL (141 mmHg)

UKPDS (144 mmHg)

ABCD (132 mmHg)

MDRD (132 mmHg)

HOT (138 mmHg)

AASK (128 mmHg)

The Majority of Hypertensive Patients Need Combination Therapy to Achieve BP Goals

Bakris et al. Am J Med. 2004;116(5A):30S–38S;Dahlöf et al. Lancet. 2005;366:895–906.

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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)

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Pharmacologic Management of Hypertension

Angiotensin converting enzyme (ACE) inhibitors• Decrease effect of

RAA system: Capoten, Lisinopril

• Diabetes mellitus w/proteinuria, heart failure

Angiotensin II receptor blockers (ARB)• Prevent action of

angiotensin II and produce vasodilation

• losartan (Cozaar)

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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

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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

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Causes of Resistant Hypertension

Improper BP measurement Excess sodium intake Inadequate diuretic therapy Medication

• Inadequate doses• Drug actions and interactions (e.g., nonsteroidal anti-inflammatory

drugs (NSAIDs), illicit drugs, sympathomimetics, oral contraceptives)• Over-the-counter (OTC) drugs and herbal supplements

Excess alcohol intake Identifiable causes of HTN

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Summary Key Points

Two types of HTN: primary & secondaryInadequate BP control leads to serious complications including STROKEKey point: risk factor modificationTreatment focuses on lifestyle management and drug therapyJNC 7 provides the most current treatment guidelines for hypertension

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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

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Pheochromocytoma

0.01-0.1% of HTN population• Found in 0.5% of those screened

M = F3rd to 5th decades of lifeRare, 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)

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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

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Pheo: Paroxysms, ‘Spells’

10-60 min durationFrequency: daily to monthlySpontaneousPrecipitated:

• 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)

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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

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Plasma Metanephrines

Not postural dependent: can draw normally

Secreted continuously by pheo

SEN 99% SPEC 89%

False Positive: acetaminophen

Assay not widely available yet

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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%

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Renovascular HypertensionRenovascular Hypertension

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Endocrine Hypertension

Catecholamine producing tumours

Mineralocorticoid hypertension

Renin-dependent hypertension

Hyperthyroidism and hypothyroidism

Acromegaly

Hyperparathyroidism

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Typical clinical scenarios

Difficult hypertension with hypokalaemia, on polypharmacy- referred to endocrinologist for exclusion of 2ary hypertensionCoincidentaloma of adrenal with hypertension, on polypharmacyWhich drugs are permissible, and after how much delay should there be before investigation?

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Mineralocorticoid hypertension- in whom should it be suspected?

Diagnosis should be suspected in patient with hypertension, spontaneous hypokalaemia (<3.5mmol/l), and alkalosis.Severe hypokalaemia (<3.0) on diureticsInvestigate patient hypertension refractory to conventional therapy, or adrenal coincidentaloma Recent onset of hypertensionNormokalaemia present in >35% patients on low salt diet

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Clinical features of hyperaldosteronism

Mild to severe hypertensionSodium retention + intravascular vol exp mineralocorticoid escapeResetting 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 therapyNB minor mineralocorticoids DOC, compound B

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Imaging in 1ary hyperaldosteronism

High resolution CT scanning with thin (2-3mm) slicesBilateral 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 sideNon-tumorous side PAC = peripheral value because of suppressed PRA

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Glucocorticoid remediable hyperaldosteronism GRA (FH1)

Due to aberrant expression of chimeric gene formed by unequal recombination of promoter and initial parts of CYP11B1 and section of CYP11B2 with aldosterone synthase activityAldosterone under ACTH controlAutosomal dominant: FH of early onset BP↑ with CVA ,K+↓High levels of 18-hydroxy and 18-oxocortisolRx : chronic administration of low dose GC, spironolactone, or amiloride

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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

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Liddle's – low renin, low aldoLicorice and SAME -- low renin, low aldoRenal artery stenosis and renin-secreting tumors -- high renin, high aldoAdrenal hyperfunction -- low renin, high aldo

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Renin Aldo

Liddle low low

Licorice low low

RAS high high

Conn’s low high

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Renin-Angiotesnin-Aldosterone System

A drop in BP or blood volume causes kidneys to secrete reninrenin, a precursor to

angiotensin I

Angiotensin-converting enzyme turns angiotensin I into angiotensin I into angiotensin II,angiotensin II, a potent vasoconstrictor

Stimulates adrenal glands to release aldosteronealdosterone

This prompts the kidneys to retain sodium and water

The increased volume and vasoconstriction raise BP

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