hypertension

Dr. Fuad Farooq

Consultant Cardiologist

Key ConceptsKey Concepts

• Hypertension is common disorderHypertension is common disorder

• Hypertension increases cardiovascular Hypertension increases cardiovascular riskrisk

• Effective treatment confers benefitEffective treatment confers benefit

• Compelling indications for certain Compelling indications for certain antihypertensive agents and blood antihypertensive agents and blood pressure targetspressure targets

Definition of Hypertension

Causes of Hypertension

• Primary – 90-95% of cases – also termed “essential” of “idiopathic”

• Secondary – about 5% of cases– Renal or renovascular disease– Endocrine disease

• Pheochomocytoma• Cushing’s syndrome• Conn’s syndrome• Acromegaly and hypothyroidism

– Coarctation of the aorta– Iatrogenic

• Hormonal / oral contraceptive• NSAIDs

Prevalence

• Children - 4% mostly secondary

• Middle age - 11-21%

• 50-59 years - 44%

• 60-69 years old - 54 %

• >70 years old - ≥ 64 %

Risk Factors

• Age is the major risk factor– Blood pressure increases with age in both men and women– The lifetime risk for hypertension is nearly 90%– The risks for high blood pressure increases in men over age

45 and women over age 55

• Family History– People with parents or other close relatives who have high

blood pressure have an increased risk of developing it themselves

Risk Factors

• Obesity– About a third of patients with high blood pressure are

overweight– BMI ≥ 35kg/m2 double the risk of hypertension than people

with normal weights

• Obstructive Sleep Apnea• Lifestyle Factors

– Smoking– High Salt (Na) and low Potassium intake– Chronic Alcohol intake– Physical Inactivity– Stress

Mortality Due to CHD per Quartile Mortality Due to CHD per Quartile of Usual SBPof Usual SBP

van den Hoogen et al. N Engl J Med 2000;342:1.

USA

Japan

Relationship Between Hypertension and IHD Mortality

Lewington S, et al. Lancet 2002; 360:1903–13

Key Message

Above 115/75 mmHg, CVD risk doubles with each BP increase of 20/10 mmHg

Role of blood pressure in cardiovascular morbidity and mortality. Prog Cardiovasc Dis. 1974;17:5-2.

* Treat patients with chronic kidney disease or diabetes to BP goal of <130/80 mm Hg

Blood Pressure Classification and Management

Normal <120 and <80 Encourage

Pre HTN 120-139 or 80-89 Yes NoYes*

Stage 1 HTN 140-159 or 90-99 Yes YesYes

Stage 2 HTN >160 or >100 Yes YesYes

Life- Initial Drug Therapy BP SBP DBP style Compelling Indications Classification mm Hg mm Hg Changes Without With

Life- Initial Drug Therapy BP SBP DBP style Compelling Indications Classification mm Hg mm Hg Changes Without With

JNC VII. JAMA 2003;289:2560.

Factors Contributing to Poor Blood Pressure Control

Took no action

Increased dose

Changed drug

Prescribed add-on therapy

18%

Taylor Nelson Healthcare, Epson, Surrey England - Cardiomonitor 1992

Goals of the Hypertensive EvaluationGoals of the Hypertensive Evaluation

• Does the patient have primary or Does the patient have primary or secondary (reversible) hypertension? secondary (reversible) hypertension?

• Is target organ damage present?Is target organ damage present?

• Are other cardiovascular (CV) risk Are other cardiovascular (CV) risk factors present?factors present?

Routine Work-up

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

"The Goal is to Get to Goal!”

Hypertension-PLUS-

Diabetes or Renal Disease

< 140/90 mmHg < 130/80 mmHg

Lifestyle Modification

Modification Approximate SBP Reduction (range)

Weight reduction 5-20 mmHg/ 10 kg weight loss

Adopt DASH eating plan 8-14 mmHg

Dietary sodium reduction 2-8 mmHg

Physical activity 4-9 mmHg

Moderation of alcohol consumption

2-4 mmHg

JNC 7 Express. JAMA. 2003 Sep 10; 290(10):1314

Impact of a 5 mmHg Reduction

Overall Reduction

Stroke 14%

Coronary Heart Disease 9%

All Cause Mortality 7%

Hypertension 2003;289:2560-2572.

Dietary

Approaches to

Stop

Hypertension

• Lowers systolic BP – In normotensive patients

by an average of 3.5 mm Hg

– In hypertensive patients by 11.4 mm Hg

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

http://www.nhlbi.nih.gov/health/public/heart/hbp/dash/new_dash.pdf

DASH Eating Plan

• Low in saturated fat, cholesterol, and total fat• Emphasizes fruits, vegetables, and low fat

diary products• Reduced red meat, sweets, and sugar

containing beverages• Rich in magnesium, potassium, calcium,

protein, and fiber• 1.5-3 gm sodium per day• Can reduce BP in 2 weeks

Sacks FM. NEJM. 2001; 344:3-10.

Classes of Antihypertensive

Classes

1. Diuretics

2. β-blockers

3. ACE Inhibitors

4. Blockers of AT1 receptors (ARB)

5. Calcium channel blockers

6. α1-antagonists

7. α2-Agonists

8. Direct vasodilators

Diuretics

Carboanhydrase inhibitors (acetazolamide) – not used in the treatment of hypertension

Carboanhydrase Inhibitors

Loop Diuretics

Loop diuretics (furosemide, etacrynic acid, bumetanide)– Strong short-lasting effect– Ability to excrete to 25 % of Na+ from filtrate– Block active reabsorption of Na+, Cl-, K+ from ascending

limb of Henle´s loop– Rarely used as antihypertensive – only furosemide in low

dosage – if simultaneously is very much reduced Glomerular filtration

– They aren´t suitable for long-lasting application

Thiazide diuretics (hydrochlorothiazide, chlorthalidone, clopamide)– Block reabsorption of Na+ and Cl- from distal tubulus– Effect is weaker then loop diuretics – they excrete about 5 %

from Na+ filtrate– Most suitable diuretics for long–lasting treatment of

hypertension– The most is used hydrochlorothiazide – daily dose 12.5 – 25

mg

Thiazide Diuretics

K+ Sparing Diuretics

K-sparing diuretics - Spironolactone (aldosterone antagonist), Amiloride, Triamterene– Only in resistant hypertension and to assistant

drugs in combinations to correct hypokalemia

Side Effects of Diuretics

DVERSE EFFECT DIURETICS SYMPTOMS

1. HypovolemiaLoop diuretic

Thiazides

LassitudeThirst

Muscle crampsHypotension

2. HypokalemiaAcetazolamidesLoop diuretics

Thiazides

Muscle weaknessParalysis

Arrhythmia

3. HyperkalemiaAmilorides

TriamterenesSpironolactone

ArrhythmiaMuscle cramps

Paralysis


4. HyponatremiaThiazides

FurosemidesCNS symptoms

Coma

5. Metabolic alkalosisLoop diuretics

ThiazidesArrhythmia

CNS symptoms

6. Metabolic acidosisAcetazolamides

AmiloridesTriamterene

Kussmaul respirationsMuscle weakness

Neurological symptomsLethargy

ComaSeizureStupor


7. Hypercalcemia Thiazides

GoutTissue calcification

FatigueDepressionConfusionAnorexiaNauseaVomiting

ConstipationPancreatitis

Increased urination

8. HyperuricemiaThiazides

Loop diureticsGout

β-blockers

• Preferenced are selective before nonselective agents• Don´t differ very much in antihypertensive effect, selection

according to adverse effect profile• Suitable for:

– Younger patients with ↑ sympathicoadrenal activity

– Hyperkinetic circulation

– Patients under psychological stress

– Patients with existent ischaemic heart disease and mainly after myocardial infarction

• Agents:• Atenolol• Metoprolol • Bisoprolol• Carvedilol• Nebivolol

β-blockers – Mechanism of Action

β-blockers – Side Effects

1. Tendency to bronchoconstriction– Use with caution in patients with asthma and reactive

airway disease

2. Negative chronotropic effects– Slowing of the resting heart rate and the development of

sinus bradycardia - relatively contraindicated in patients with symptomatic bradycardia

3. Heart Block– By blocking AV node resulting in serious bradyarrhythmia

complete or partial AV conduction defect (i.e., second or third degree AV block)

β-blockers – Side Effects

4. Metabolic Effects– Worsening of lipid profile– Mask symptoms of hypoglycemia and can impair glucose

tollerance – more at non-selective agents– Sleep disturbances, bad dreams → Depression– At very high doses can worsen heart failure; if indicated at

chronic heart failure, dose should be increased step by step

β-blockers

!Selectivity of action is only relative!

• At higher doses selectivity is dissapearing - even among β1-selective agents appear β2-lytic effects

• Should not be combined with verapamil or a diltiazem

• Treatment can´t be stopped abruptly – rebound effect!

Calcium Channel Blockers (CCB)

CCB – Mechanism of Action

• Block influx of calcium to cell through slow L-type channels, lower its intracellular concentration what causes relaxation of smooth muscle in vessel wall, decrease of contractility, decrease of electrical irritability and conductivity

CCB in Hypertension

• Most commonly used Calcium channel blockers in treatment of hypertension are:

– Dihydropyridines – especially Amlodipine (Norvasc)– Non dihydropyridines – Verapamil and Diltiazem only in

presence of tachycardia– Prototype short-acting DHP nifedipine is contraindicated!

• It reduces BP too rapidly, so induces reflex activation of sympathatic stimulation with subsequent increase of BP and such a repeated BP fluctuation causes worse vessel damage as untreated hypertension → instead of mortality decrease its increase!

CCB in Hypertension

• Ca++ blockers are suitable for– Patients with DM– Metabolic syndrome– Peripheral vascular disease

• It has of particularly advantageous in treatment of isolated systolic hypertension

• Nimodipine (1st generation) affinity to brain vasculature → effectively relieves spasms of cerebral arteries → used in subarachnoid bleeding

CCB – Side Effects

• Side effects of CCB are:– Dizziness– Headache– Redness in the face– Fluid buildup in the legs and ankle – dependent

edema– Rapid heart rate– Slow heart rate– Constipation– Gingival overgrowth

Renin Angiotensin Aldosterone system

ACE Inhibitors

• It block the conversion of angiotensin I to angiotensin II and at the same time block inactivation of bradykinin– Vasodilation in both resistant and capacitance vessels

• Indication:– Hypertensive patients with heart failure

– In acute myocardial infarction

– In diabetes and diabetic nephropathy with or without microalbuminuria

Main Benefits

ACE Inhibitors

• Hydrophilic ACEI: – Captopril– Ramipril– Enalapril– Lisinopril

• Lipophilic ACEI:– Perindopril– Trandolapril– Quinapril

ACE Inhibitors – Side Effects

• Hypotension• Cough• Hyperkalemia• Angioedema• Renal impairment• Headache• Dizziness• Fatigue• Nausea• Rash and taste disturbances- with captopril

ACE Inhibitors – Side Effects

• A persistent dry cough is a relatively common adverse effect believed to be associated with the increases in bradykinin levels produced by ACE inhibitors

• Patients who experience this cough are often switched to angiotensin II receptor antagonists

ACE Inhibitors - Contraindications

• Previous angioedema associated with ACE inhibitor therapy• Renal artery stenosis (bilateral or unilateral with a solitary functioning

kidney)• Hypersensitivity to ACE inhibitors• Hyperkalemia (>5.5mmole/L)• Creatinine >2.5mg/dl• ACE inhibitors should be used with caution in patients with:

– Impaired renal function– Aortic valve stenosis or cardiac outflow obstruction

– Hypovolemia or dehydration

ACE Inhibitors - Contraindications

• In pregnancy - category D– Should be avoided in women who are likely to become

pregnant– Taken during the first trimester have been reported to cause

major congenital malformations, stillbirths, and neonatal deaths

– Commonly reported fetal abnormalities include hypotension, renal dysplasia, anuria/oliguria, oligohydramnios, intrauterine growth retardation, pulmonary hypoplasia, patent ductus arteriosus, and incomplete ossification of the skull

– Overall, about half of newborns exposed to ACE inhibitors are adversely affected

Angiotensin Receptor Blockers

• Most often replacement of ACEI in case of cough– Losartan– Valsartan– Candesartan– Irbesartan

• Sometimes prescribed as 1st choice, even before ACEI clinical studies indicate that they have among patients with HT and DM 2 slightly better protective effects than ACEI

• Side effect profile (except cough) and contraindications are same as that of ACEI

α1- Blockers

• Along with BP reduction they reduce the size of prostate

→ Indicated mainly in older man with simultaneous benign prostate hyperplasia (BPH)

• Other indications:– In combination for severe resistant hypertension– strong 1st dose phenomenon! → postural

hypotension, syncopes

α1- Blockers

• Prazosin• Doxazosin• Terazosin

Side effects– Hypotension– Orthostatic hypotension (postural hypotension) –

thus alpha blockers should be taken at bedtime– First dose phenomenon may be reduced by starting

at a low dose and titrating upwards as needed

α2 - Agonists

• Centraly acting – stimulation of central α2 receptors

• Through negative feedback inhibit release of norepinephrine on periphery → reflex BP reduction– α-metyldopa– Clonidine

• S/E:– Central depression – sleepiness, bad dreams– Clonidine has significant rebound phenomenon

Direct vasodilators

• Hydralazines– Specific mechanism of action is unknown

• S/E: tachycardia, palpitations, lupus erythematodes

What Medicine to Choose First?

Relative Efficacy of Each group

N Engl J Med. 1993;328(13):914-21.

These observations are secondary to the plasma Renin activity, older and

blacks have less activity than younger and white population

Meta Analysis

0

2

4

6

8

10

12

14

SBP Reduction (mmHg)

Thiazides BB ACEI ARB CCB

1/2 Standard

Standard

2x Standard

• All five drug categories produced similar BP reductions

• Blood pressure reduction achieved with half standard dose was only 20% lower than standard dose

Law MR et al. BMJ. 2009;338:b1665.

• The ASCOT trial found a lower rate of cardiovascular disease and death with a calcium channel blocker (Amlodipine) compared to a beta blocker (Atenolol)– Patients in the Amlodipine arm had a

significantly lower mean blood pressure at the end of the study (3/2 mmHg)

Anglo-Scandinavian Cardiac Outcomes Trial-Blood Pressure Lowering Arm (ASCOT-BPLA): Lancet. 2005;366(9489):895-906.

Ramipril1 and Perindopril2 produced better outcomes than placebo in the HOPE and EUROPA trials of patients at increased cardiovascular risk, but the blood pressure was significantly lower in the treated patients: 3.3/1.4 mmHg (with a greater difference overnight) in HOPE and 5/2 mmHg in EUROPA

1. The Heart Outcomes Prevention Evaluation Study Investigators. N Engl J Med. 2000;342(3):145-53.2. EURopean trial On reduction of cardiac events with Perindopril in stable coronary Artery disease Investigators.

Lancet. 2003;362(9386):782-8.

When differences in outcomes have

been noted in trials comparing different

antihypertensive drugs, the drug

producing better outcomes had better

blood pressure control

AHA statement on the treatment of blood pressure in

ischemic heart disease, and European Society of

Hypertension/ESC guidelines on the management of

hypertension all concluded that the amount of blood

pressure reduction is the major determinant of reduction

in cardiovascular risk in both younger and older patients

with hypertension, NOT the choice of antihypertensive

drug

Is it appropriate to start multiple anti-hypertensive?

Administering two drugs as initial therapy should be

considered when the blood pressure is more than

20/10 mmHg above goal

Fixed dose combinations can be used as it increased

patient compliance

The JNC 7 report. JAMA. 2003;289(19):2560-72.

Is it appropriate to start 2 agents?

• In ALLHAT, 60% of patients achieved SBP control• The mean number of drugs to achieve BP control

was 1.6• Inadequate titration of drug regimens is a primary

reason patients do not reach BP goal• Patients and providers should be educated that

more than one antihypertensive is the norm not the exception

Low Dose Combinations

• Meta-analysis of 354 randomized trials of antihypertensives: BB, ACEI, ARB, & CCB

• Dose of each agent expressed as a multiple of a standard dose

• n=56,000 patients • Placebo adjusted

reductions in SBP and DBP

• Prevalence in adverse effects based on dose

Law MR et al. BMJ. 2009;338:b1665.


BP lowering effects from different drug categories were additive

Law MR et al. BMJ. 2009;338:b1665.

6.7

13.3

0

10

20

SBP Reduction (mmHg)

1 Drug 2 Drug 3 Drugs

19.9


• Adverse effects in all drug categories, except ACEI, were dose related

• Prevalence of adverse effects in combination was less than additive

Conclusion:

Utilization of low dose combination therapy can effectively reduce blood pressure while limiting the incidence of side effects

Law MR et al. BMJ. 2009;338:b1665.

Compelling Indications for Individual Drug Classes

Compelling Indication

Initial Therapy Options

Clinical Trial Basis

Heart failure THIAZ, BB, ACEI, ARB, ARA

ACC/AHA Heart Failure Guideline, MERIT-HF, COPERNICUS, CIBIS, SOLVD, AIRE, TRACE, ValHEFT, RALES

Postmyocardialinfarction

BB, ACEI ACC/AHA Post-MI Guideline, BHAT, SAVE, Capricorn, EPHESUS

High CAD risk THIAZ, BB, ACEI, CCB

ALLHAT, HOPE, ANBP2, LIFE, CONVINCE

Compelling Indications for Individual Drug Classes

Compelling Indication

Initial Therapy Options

Clinical Trial Basis

Diabetes ACEI, ARB, CCB,

THIAZ, BB,

NKF-ADA Guideline, UKPDS, ALLHAT

Chronic kidney disease

ACEI, ARB NKF Guideline, Captopril Trial, RENAAL, IDNT, REIN, AASK

Recurrent stroke prevention

THIAZ, ACEI PROGRESS

"The Goal is to Get to Goal!”

Hypertension-PLUS-

Diabetes or Renal Disease

< 140/90 mmHg < 130/80 mmHg

Patients should return for follow-up and adjustment of medications every 1-2 months until the BP goal is reached

When a Patient is Still Not at Goal?

Optimize dosages or add additional

drugs until goal blood pressure is

achieved

When a Patient is Still Not at Goal?

What do you do when you are using

several effective medications?

Consider causes of resistant hypertension

Causes of Resistant Hypertension Improper BP measurement Dietary and medicine non compliance Inadequate diuretic therapy Medication

• Inadequate doses

•Drug actions and interactions:

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


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


Other Medications

(1)Aspirin:

• Use 75mg daily if patient is aged 50 years with blood pressure controlled to <150/90 mm Hg and either; target organ damage, diabetes mellitus, or 10 year risk of cardiovascular disease of 20%

(2) Statin:

• Use when 10 year risk of cardiovascular disease of 20% and with total cholesterol concentration 200mg/dl

(3) Vitamins—no benefit shown, do not prescribe

Rational Combination Therapy:

Chinese Menu Approach

Pharmacologic Sites of Action

Thiazides

Loops

Aldosterone Ant.

Nitrates

ACEI

ARB

Beta Blockers

Diltiazem

Verapamil

Via Central Mechanism:

Clonidine

Dihydropyridine CCBs

Hydralazine

Minoxidil

Alpha1 Blockers

ACEI

ARB

HeartArteries

Veins

Chinese Menu Approach

Thiazides

Loops

Aldosterone Ant.

Nitrates

ACEI

ARB

Beta Blockers

Diltiazem

Verapamil

Via Central Mechanism:

Clonidine

Dihydropyridines

Hydralazine

Minoxidil

Alpha1 Blockers

ACEI

ARB

HeartArteries

Veins

Choose one agent from each category

Algorithm for Treatment of Hypertension

Not at Goal Blood Pressure (<140/90 mmHg) (<130/80 mmHg for those with diabetes or chronic kidney disease)

Initial Drug Choices

Drug(s) for the compelling indications

Other antihypertensive drugs (diuretics, ACEI, ARB, BB, CCB)

as needed.

With Compelling Indications

Lifestyle Modifications

Stage 2 HTN (SBP >160 or DBP >100 mmHg)

2-drug combination for most (usually thiazide-type diuretic

and ACEI, or ARB, or BB, or CCB)

Stage 1 HTN (SBP 140–159 or DBP 90–99 mmHg)

Thiazide-type diuretics for most. May consider ACEI, ARB, BB,

CCB, or combination.

Without Compelling Indications


Not at Goal Blood Pressure

Optimize dosages or add additional drugs until goal blood pressure is achieved.

Consider consultation with hypertension specialist.

Follow-up and Monitoring

Patients should return for follow-up and adjustment of medications every 1-2 months until the BP goal is reached

After BP at goal and stable, follow-up visits at 3- to 6-month intervals More frequent visits for stage 2 HTN or with

complicating comorbid conditions Continue to encourage self BP monitoring

Serum potassium and creatinine monitored 1–2 times per year


Malignant Hypertension (HTN Emergency)

• Hypertensive emergencies encompass a spectrum of clinical presentations in which uncontrolled blood pressures lead to progressive or impending end-organ dysfunction

• BP should be lowered aggressively over minutes to hours

• Neurologic manifestations:– Hypertensive encephalopathy– Cerebral vascular accident/cerebral infarction– Subarachnoid hemorrhage– Intracranial hemorrhage

• Cardiovascular manifestations:– Myocardial ischemia/infarction– Acute left ventricular dysfunction– Acute pulmonary edema– Aortic dissection

• Other organ systems:– Acute renal failure/insufficiency– Retinopathy– Eclampsia– Microangiopathic hemolytic anemia


• The history and the physical examination determine the nature, severity, and management of the hypertensive event

• The history should focus on the presence of end-organ dysfunction, the circumstances surrounding the hypertension, and any identifiable etiology

• The duration and severity of the patient’s preexisting hypertension


• Patients may complain of specific symptoms that suggest end-organ dysfunction– Chest pain may indicate myocardial ischemia or

infarction– Back pain may denote aortic dissection– Dyspnea may suggest pulmonary edema or

congestive heart failure– Presence of neurologic symptoms may include

seizures, visual disturbances, and altered level of consciousness and may be indicative of hypertensive encephalopathy


• Physical examination should assess whether end-organ dysfunction is present

• BP should be measured in both the supine and standing position as well as in both arms

• The presence of new retinal hemorrhages, exudates, or papilledema suggests a hypertensive emergency

• Evaluate for the presence of heart failure– Indicated jugular venous distention– Crackles on auscultation– Peripheral edema

• CNS findings may include changes in the patient's level of consciousness and visual fields, and/or the presence of focal neurologic signs

• Abdominal masses or bruits may be noted


• Immediate admission• Close monitoring• Parentral antihypertensive• Selection of antihypertensive agent depends

upon target organ at risk• Goal is to rapidly lower BP in minutes to

hours


Hypertensive Urgency

• Severe hypertension (as defined by a Systolic BP >200mmHg &/or diastolic blood pressure above 120 mmHg) in asymptomatic patients without any evidence of target organ damage

• Don't require immediate reduction in BP

• Don't require admission in monitored setup

• Treat with oral medications

• BP should be lower in hour to days

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

Take Home Message

Take Home Message

• Start with one of CCB/ACEI/ARB/HCTZ– All have equal efficacy in lowering BP

– Unless compelling indication

• Use two or more drugs or in combination if needed – have additive effect

• And the goal is TO GET THE GOAL

hypertension

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