Prof. Jamal Al WakeelHead, Nephrology DivisionDepartment of Medicine

Case

47 year old man came to your clinic with headache for 3 weeks. The nurse measure his Blood Pressure and was found to be 150/95 mmHg:

1.Does he have Hypertension?2. What is the stage of Hypertension?3.What investigation should you perform?4.What could be your management on his case?5.Is their any possible prevention to his disease and its complication?

The objective of this Lecture is:

1.To be able to recognize the definition of hypertension2.To be able to identify the Stages of Hypertension3.To find out the complication of Hypertension4.To learn how to measure blood pressure5.To familiarize with the test done for Hypertension6.To acquire knowledge on how to measure hypertension

Reference: Current Medical Therapy and Diagnosis 2007

The 4th most common cause of death world-wide

Directly and indirectly responsible for >20% of all deaths

29-30% incidence of hypertension in the 18 year and older population of the United States

9.1% and 8.7% the population of Saudi Arabia with hypertension 160/95 mmHg

HYPERTENSION

Onset stage 25-55 years mainly in 40-50y occurs over 30%of persons older than 65 y

Only 34% of persons with hypertension have their blood pressure under control

HYPERTENSION

PREVALENCE OF HYPERTENSIONIN THE UNITED STATES*

6%

16%

31%

48%

65%

78%

0%

20%

40%

60%

80%

100%

18-34 35-44 45-54 55-64 65-74 75+

†

*Based on NHANES 19992000 data. Hypertension is defined as blood pressure 140/90 mmHg or antihypertensive treatment.†Low reliability due to large relative error.

Fields et al. Hypertension. 2004:44;398-404.

Hyp

ert

en

sio

nP

revale

nce

Age

BP CONTROL RATESTrends in awareness, treatment, and control of high blood pressure in adults ages 18–74

National Health and Nutrition Examination Survey, Percent

II

1976–80

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

Sources: Unpublished data for 1999–2000 computed by M. Wolz, National Heart, Lung, and Blood Institute; JNC 6.

In 95% of cases no cause can be found primary hypretension (essential)

Secondary hpertension 5-10%

HYPERTENSION

ESSENTIAL (PRIMARY) HYPERTENSION

Pathogenesis Sympathetic neural hyperactivity,insensitivity

baroreflex Increased angiotensin II activity and

mineralocortoid excess Genetic factors Reduced adult nephron mass may predispose to

hypertension Abnormal cardiovascular devolopment Intracellular Na &Ca Defect in natriuresis

Essential HTN• Risk factors

– Obesity---metabolic syndrome– Excessive salt intake---low potassium intake– Excessive alcohol intake – Polycythimia– Lack of exercise

– Nonsteroid anti-iflammatery drugs– Family history of essential HTN

• Caffeine and smoking increase the BP acutely but are not risk factors for the development of chronic essential HTN

Primary renal disease Oral contraceptives Sleep apnea syndrome Pheochromocytoma Primary hyperaldosteronism Renovascular disease Cushing’s syndrome Other endocrine disorders Coarctation of the aorta

SECONDARY HYPERTENSION

U.S. Department of Health and Human

Services

National Institutes of Health

National Heart, Lung, and Blood Institute

The Seventh Report of the Joint National Committee

Prevention, Detection, Evaluation, and Treatment of High

Blood Pressure (JNC 7) on

The Seventh Report of the Joint National Committee

Prevention, Detection, Evaluation, and Treatment of High

Blood Pressure (JNC 7) on

National Heart, Lung, and Blood National Heart, Lung, and Blood InstituteInstitute

National High Blood Pressure National High Blood Pressure Education ProgramEducation Program

National Heart, Lung, and Blood National Heart, Lung, and Blood InstituteInstitute

National High Blood Pressure National High Blood Pressure Education ProgramEducation Program

BLOOD PRESSURE CLASSIFICATION

Normal <120 and <80

Prehypertension 120–139 or 80–89

Stage 1 Hypertension

140–159 or 90–99

Stage 2 Hypertension

>160 or >100

BP Classification SBP mmHg DBP mmHg

Optimal blood pressure : systolic <120 mmHg and diastolic <80 mmHg

Normal: systolic 120-129 mmHg and/or diastolic 80-84 mmHg

High normal: systolic 130-139 mmHg and/or diastolic 85-89 mmHg

Hypertension: Grade 1: systolic 140-159 mmHg and/or diastolic 90-

99 mmHg Grade 2: systolic 160-179 mmHg and/or diastolic 100-

109 mmHg Grade 3: systolic ≥180 mmHg and/or diastolic ≥110

mmHg Isolated systolic hypertension: systolic ≥140 mmHg

and ≥90 mmHg

DIFFERENT DEFINITIONS ACCORDING TO EUROPEAN SOCIETIES OF HYPERTENSION

AND CARDIOLOGY :

apply to adults on no antihypertensive medications and who are not acutely ill

If there is a disparity in category between the systolic and diastolic pressures, the higher value determines the severity of the hypertension

BLOOD PRESSURE CLASSIFICATION

Patient should be seated with the back straight and the arm supported at heart level

The patient should rest for 5 minutes The bladder of the pressure cuff should

encircle at least 80% of the upper arm Use the average of two or more readings on

at least two occasions

MEASUREMENT:

Measurement:

The diagnosis of mild hypertension should not be made until the blood pressure has been measured on at least three to six visits

Average of 10 to 15 mmHg decrease between visits 1 and three

Approximately 20 to 25% of patients with mild office hypertension

More common in elderly

Infrequent in patients with office diastolic pressures ≥105 mmHg

WHITE COAT HYPERTENSION

Peripheral vascular disease

hyprtensife

Emergency

And

emergencies Morbidity

Disability

Renal disease

CAD .ECG,

ARRTHYM MI .SUDDEN DEATH

CHFLVH

Aorticdissection

Stroke

Ischemia

Hemorrage

Alzaheimer COGNETIVE

Hypertension

COMPLICATION

19/04/23 21

This left ventricle is very thickened (slightly over 2 cm in thickness), but the rest of the heart is not greatly

enlarged. This is typical for hypertensive heart disease. The hypertension creates a greater pressure

load on the heart to induce the hypertrophy.

The left ventricle is markedly thickened in this patient with severe hypertension that was untreated for many

years. The myocardial fibers have undergone hypertrophy.

HYPERTENSIVE EMERGENCY

HYPERTENSIVE URGENCYSevere hypertension (diastolic blood pressure above

120 mmHg) in asymptomatic patients There is no proven benefit from rapid reduction in

BP in asymptomatic patients who have no evidence of acute end-organ and are little short-term risk

Severe hypertension (diastolic blood pressure above 120 mmHg) in endorgan dammage(MI,STROKE,AKI,CHF)

Marked hypertension with encephapapathy& retinal hemorrhages, exudates, or papilledema

Associated with a diastolic pressure above 120 mmHg

MALIGNANT HYPERTENSION

HYPERTENSIVE RETINOPATHYGRADE 4

Papilledema from malignant hypertension. There is blurring of the borders of the optic disk with hemorrhages (yellow arrows) and exudates (white arrow)

Screening:Asympatomatic- headache.chestheavance,Symptomof

cmplications

Every two years for persons with systolic and diastolic pressures below 120 mmHg and 80 mmHg

Yearly for persons with a systolic pressure of 120 to 139 mmHg OR

Diastolic pressure of 80-89 mmHg

DIAGNOSIS HYPERTENSION

Presence of precipitating or aggravating factors Natural course of the blood pressure Extent of target organ damage Presence scondry HTN of other risk factors for

cardiovascular disease

HISTORY

To evaluate for signs of end-organ damage

For evidence of a cause of secondary hypertension

PHYSICAL EXAMINTAION

HYPERTENSIVE RETINOPATHYGRADE 2

Arteriovenous nicking in association with

hypertension Grade 2

(yellow arrow)

HYPERTENSIVE RETINOPATHYGRADE 3

Flame-shaped hemmorhage in association with

severe hypertension Grade

3 (yellow arrow)

LABORATORY TESTS

Routine Tests• Electrocardiogram • Urinalysis • Blood glucose, and hematocrit • Serum potassium, creatinine, or the corresponding estimated GFR, and calcium• Lipid profile, after 9- to 12-hour fast, that includes high-density and low-density lipoprotein cholesterol, and triglycerides

Optional tests • Measurement of urinary albumin excretion or albumin/creatinine ratio

More extensive testing for identifiable causes is not generally indicated unless BP control is not achieved

Who should be treated?

Persistently elevated blood pressure after three to six visits over a several month period

If the systolic pressure is persistently ≥140 mmHg and/or the diastolic pressure is persistently ≥90 mmHg

Systolic pressure is persistently above 130 mmHg and/or the diastolic pressure is above 80 mmHg in patients with cardiovascular disease,. post-myocardial infarction, heart failure,ckd & DM

Recommend a goal blood pressure ≤130/80 mmHg

Patients with office hypertension, normal values at home, and no evidence of end-organ damage should undergo ambulatory blood pressure monitoring

TREATMENT OF HYPERTENSION

LIFESTYLE MODIFICATIONS

• DRUG THERAPY

BENEFITS OF LOWERING BP

Average Percent Reduction

Stroke incidence 35–40%

Myocardial infarction

20–25%

Heart failure 50%

Renal Failure 35-50%

LIFESTYLE MODIFICATION

Modification Approximate SBP reduction (range)

Weight reduction 5–20 mmHg/10 kg weight loss

Adopt DASH eating 8–14 mmHg

Dietary sodium 2–8 mmHg

Physical activity 4–9 mmHg

Moderation of alcohol consumption

2–4 mmHg

CLASSIFICATION AND MANAGEMENT OF BP FOR ADULTS

BP classificatio

n

SBP* mmHg

DBP* mmHg

Lifestyle modifica

tion

Initial drug therapy

Without compelling indication

With compelling indications

Normal <120 & <80 Encourage

Prehypertension 120–139 or 80–89 Yes No antihypertensive drug indicated.

Drug(s) for compelling indications. ‡

Stage 1 Hypertension

140–159 or 90–99 Yes Thiazide-type diuretics for most. May consider ACEI, ARB, BB,

CCB, or combination. Drug(s) for the compelling indications.‡

Other antihypertensive drugs (diuretics, ACEI,

ARB, BB, CCB) as needed.

Stage 2 Hypertension

>160 or >100 Yes Two-drug combination for most† (usually thiazide-type diuretic

and ACEI or ARB or BB or CCB).

*Treatment determined by highest BP category.†Initial combined therapy should be used cautiously in those at risk for orthostatic hypotension.‡Treat patients with chronic kidney disease or diabetes to BP goal of <130/80 mmHg.

COMPELLING INDICATIONS FOR INDIVIDUAL DRUG CLASSES

Compelling Indication

Initial Therapy

THIAZ, BB, ACEI, ARB, ALDO ANT

BB, ACEI, ALDO ANT

THIAZ, BB, ACE, CCB

Heart failure

Postmyocardialinfarction

High CAD risk

COMPELLING INDICATIONS FOR INDIVIDUAL DRUG CLASSES

Compelling Indication

Initial Therapy Options

Diabetes THIAZ, BB, ACE, ARB, CCB

Chronic kidney disease

ACEI, ARB

Recurrent stroke

prevention

THIAZ, ACEI

FOLLOW-UP AND MONITORING

Patients should return for follow-up after4weaks and adjustment of medications until the BP goal is reached.

More frequent visits for stage 2 HTN or with complicating comorbid conditions.

Serum potassium and creatinine monitored 1–2 times per year.

A low dose of initial drug should be used, slowly titrating upward.

Optimal formulation should provide 24-hour efficacy with once-daily dose.

Combination therapies may provide additional efficacy with fewer adverse effects.

DRUG THERAPY

DRUG THERAPY

•Diuretics•β-Adrenergic Blocking Agents•Angiotensin-Converting Enzyme Inhibitors•Angiotensin II Receptor Blockers•Calcium Channel Blocking Agents•α-Adrenoceptor Antagonists•Drugs with Central Sympatholytic Action•Arteriolar Dilators

ACE inhibitors and diuretics Angiotensin II receptor antagonists and diuretics Calcium antagonists and ACE inhibitors Angiotensin II receptor antagonists &-adrenergic

blockers NOT RECOMENDED Other combinations (-adrenergic blockers and

diuretics)

COMBINATION THERAPIES

ANTIHYPERTENSIVE DRUGS: DIURETICS

THIAZIDES AND RELATED DIURETICSHydrochlorothiazide

Chlorthalidone

Metolazone

Indapamide

LOOP DIURETICSFurosemide

Ethacrynic acid

Bumetanide

Torsemide

ALDOSTERONE RECEPTOR BLOCKERSSpironolactone

Amiloride

Eplerenone

COMBINATION PRODUCTSHydrochlorothiazide and triamterene

Hydrochlorothiazide and amiloride

Hydrochlorothiazide and spironolactone

Thiazide Indapamine Hydrochlorothiazid

• Commonly the first line treatment in mild-moderate hypertension

• Often used in combination with other antihypertensive agents(ACEI.ARB,C .B block

• Proven benefit in stoke and myocardial infarction reduction

Diuretics

– Mechanism decrease plasma volum(inhabet Na absorbation in DCT)&reduce perpheral resistance

– Full antihypertensive effect may take 6-8week

– At the doses used side effect low

Adverse effects:

- Idiosyncratic reactions (rashes - may be photosensitiv, purp)• impotence- Metabolic and electrolyte changes

HyponatremiaHypokalemia

(combine with potassium-sparing diuretics)

HypomagnesemiaHyperuricemia (most diuretics reduce urate clearance)

Hyperglycemia Hypercalcemia

(thiazides reduce urinary calcium ion clearance precipitate clinically significant hypercalcemia in hypertensive patients withhyperparathyroidism)

Hypercholesterolemia (a small in plasma cholesterol concentration)

ANTIHYPERTENSIVE DRUGS: β-ADRENERGIC BLOCKING AGENTS

Acebutolol

Atenolol

Betaxolol

Bisoprolol

Carteolol

Carvedilol

Labetalol

Metoprolol

Nadolol

Penbutolol

Pindolol

Propranolol

Timolol

cardio-selective: blocker: atenolol,metoprolol,Betxolol/bisoprololblockers with ISA :acebutolblockers:labetalol, carvedilol

cardio non-selective:blockers:nadolol, propranolol,

blockers with ISA:pindolol,

-adrenoreceptor antagonists

Note: Partial agonist activity (intrinsic sympathomimetic activity – ISA) - may be an advantage in treating patients with asthma because these drugs will cause bronchodilation; they have moderate (lower) effect on lipid metabolism, cause lesser vasospasms and negative inotropic effect

2. Drugs influencing sympathetic nerves

Beta-adrenoceptor antagonists

ATENOLOL ,Bisoprolol, Betaxolol ,, Metoprolol

• Cardioselective beta-blockers are preferable• Mechanism of action may involve

– reduction in peripheral resistance– inhibition of renin release– Reduce heart rate

• NOT Recomended used as first line therapy

• When used alone effective in 50-60% of patients

• When used in conjunction with a diuretic increase response rate to 60-80%

• Contraindications– Asthma– Decompanstated Heart failure,

Bradycardia– Raynauds

Adverse Drug Reactions

– Tiredness – Breadycarbia– Cold hands and feet– Muscle fatigue– There is concern that -blockers

precipitate diabetes mellitus when used with thiazide diuretics

RENIN ANGIOTENSIN ALDOSTERONE SYSTEM

Bradykinin

Nitric Oxide

Prostacyclin

Inactive Metabolites

Angiotensinogen

Angiotensin I

Angiotensin II

A C E+ +

Activation of AT-1 receptors &Aldosterone

Renin

Chymase

60% ACE Dependent

40% ChymaseDependent

ACE-I

ARB

Angiotensin Converting Enzymes

ENALAPRIL, LISINOPRIL, RAMIPRIL,perindperil

• Competitively inhibit the actions of angiotensin converting enzyme (ACE)

• ACE converts angiotensin I to active angiotensin II

• Angiotensin II is a potent vasoconstrictor and

hypertrophogenic agent &produce aldosterone

Contraindications– Bilateral Renal artery stenosis– Renal failure– Hyperkalaemia

Adverse Drug reactions– Cough 10-15% – hyperkalemia– first dose hypertension– taste disturbance– renal impairment in renal artery stenosis– Angioneurotic oedema

ANGIOTENSIN II RECEPTOR BLOCKERS

Candesartan cilexitil

Candesartan cilexitil/HCTZ

Eprosartan

Eprosartan/HCTZ

Irbesartan

Irbesartan and hydrochlorothiazide

Losartan

Losartan and hydrochlorothiazide

Olmesartan

Olmesartan and hydrochlorothiazide

Telmisartan

Telmisartan and hydrochlorothiazide

Valsartan

Valsartan and hydrochlorothiazide

Angiotensin II Antagonists

LOSARTAN, VALSARTAN, CANDESARTAN, IRBESARTAN

• angiotensin II antagonists competitively block the actions of angiotensin II at the angiotensin AT1 receptor

• Advantage over ACE inhibitors – Cough2%-5% – -less hyperkalemia

calcium channel blocking agents

NONDIHYDROPYRIDINE AGENTSDiltiazem

Verapamil

DIHYDROPYRIDINESAmlodipine

Felodipine

Isradipine

Nicardipine

Nifedipine

Nisoldipine

Calcium Channel Blockers

AMLODIPINE, VERAPAMIL, diltiazem & nifedipine,felodipine

• “ short acting dihydropyridines should not be used as first line therapy to treat hypertension.”

Mechanism

– relaxing large and small arteries and reducing peripheral resistance

– reducing cardiac output

Contraindications– Acute MI– Heart failure, bradycardia

VERAPAMIL,DILTIAZEM

Averse Drug Reactions– Flushing– Headache– Ankle oedema– Indigestion and reflux oesophagitis

Rate limiting VERAPAMIL, DILTIAZEM agents also cause

– Bradycardia– Constipation

Α-ADRENOCEPTOR ANATAGONISTS

Prazosin Terazosin Doxazosin

Alpha-adrenoceptor antagonists

Prazosin, DOXAZOSIN,Terazosin– Selectively block post synaptic 1-

adrenoceptors– reduce vascular smooth muscle contraction

in arteries

Adverse Drug Reactions– First dose hypotension– Dizziness – Dry mouth– Headache

CENTRAL SYMPATHOLYTICSClonidine

Guanabenz

Guanfacine

Methyldopa

PERIPHERAL NEURONAL ANTAGONISTS

Reserpine

DIRECT VASODILATORSHydralazine

Minoxidil

CONTINUATION

c) Centrally acting drugs

stimulating alpha-adrenergic receptors in the central nervous system

Methyldopafalse transmitter

Clonidine, Moxonidinedirect a2-agonist, imidazol receptor agonists

- limited use in the treatment of hypertension. - methyldopa hypertension during pregnancy- methyldopa causes symptoms of drowsiness and fatigue that are intolerable to many adult patients in long-term use- they are seldom used to treat essential hypertension- clonidine is potent but poorly tolerated (rebound hypertension, if it is discontinued abruptly, is an uncommon but severe problem)