HIPERTENSI PADA PASIEN USIA LANJUT

Trends in the Awareness , Treatment and Control of High Blood Pressure in Adults :

United States, 1976-94*

NHANES IINHANES II NHANES IIINHANES III NHANES IVNHANES IV (1976-80) (Phase 1) (Phase 2)

1988-91 1991-94

Awareness 51%51% 73% 73% 68.4% 68.4%Treatment 31%31% 55% 55% 53.6% 53.6%Control** 10%10% 29% 27.4% 29% 27.4%

* Data are for adults age 18 to 74 years with SBP of 140 mmHg or greater, DBP of 90 mmHg or greater , or taking antihypertensive medication.

** SBP below 140 mmHg and DBP below 90 mmHg.Source : Burt V et al and unpublished NHANES III, phase 2, data provided by Centers for Disease Control and Prevention, National Center for Health Statistics

Risk of Cardiovascular events by hypertensive status

0

10

20

30

40

50Cardiac Failure

PeripheralArtery

disease

Stroke

Coronary disease

M W M W M W M W

Risk ratio 2.0 2.2 3.8 2.6 2.0 3.7 4.0 3.0

Excess risk 23 12 9 4 5 5 10 4

Normal Hypertension M=men, W=woman

Data are from subjects of 35-64 years of age, after 36 years of the Framingham study

Bie

nnia

l age

-adj

uste

d ra

te p

er 1

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Systolic and diastolik pressure and age

60708090100110120130140150160170180

25 35 45 55 65 75 25 35 45 55 65 75

SBPSBP

DBP DBP

MEN WOMEN

Age (years)

Arte

rial p

ress

ure

(mm

Hg)

Data from a group in London

Causes of secondary hypertension in the elderlyDrugs Corticosteroid

Estrogen replacementNon-steroidal anti-inflammatoryAlcoholErgotamineAntihistamine/sympathomimetic decongestantsLiguorice

Renal Renal artery stenosisPyelonephritisGlomerulonephritisObstructive neuropathyAnalgesic nephropathyPolycystic kidney diseaseConnective tissue disease

Endocrine Conn's syndromeCushing's syndromePheochromocytomaAcromegalyHyperparathyroidism

Neurological Spinal cord diseaseRaised intracranial pressure

Other Coarction of the aortaPsedohypertension

Profil tekanan darah&

akibatnya

Blood Pressure in a Resting Subject

Mechanisms Responsible for Blood Pressure Variability

Increased Variability is Associated with Greater End-Organ Damage

Association of End-Organ Damage with Blood Pressure

Hasil Terapi Hipertensi pada

Usia Lanjut

EWPHE* Summary

• Number of patients 840 (70% woman)• Age >60 years• Entry BP SBP 160-239 mmHg

DBP 90-119 mmHg• Treatment HCT/triamterene,

adding methyldopa• Result 32% fewer stoke deaths

38% fewer cardiac deaths

*EWPHE = European Working Party on High Blood Pressure in the elderly

STOP*-Hypertension Summary

• Number of patients 1627 men and woman• Age 70-84 years• Entry BP SBP 180-230 mmHg

DBP 90-120 mmHg• Treatment Beta blockers or HCT,

adding amiloride• Result 40% fewer cardiovascular events

47% fewer strokes, 42% lower mortalityBenefit up to 84 years of age

*STOP = Swedish Trial in Old Patients with Hypertension

MRC* Trial Summary

• Number of patients 4396 men and woman• Age 65-74 years• Entry BP SBP 160-209 mmHg

DBP < 115 mmHg• Treatment Amiloride, atenolol or placebo• Result 17% fewer cardiovascular events

(but only with diuretic)25% fewer strokes19% fewer coronary events

*MRC = Medical Research Council

Events/1000 patients in the MRC* Trial

*MRC = Medical Research Council

Diuretic Atenolol PlaceboTotal Stroke 7.3 9.0 10.8Total Coronary 7.7 12.8** 12.7All deaths 21.3 26.4* 24.7

Group

Klasifikasi, stratifikasi hipertensi dan

jenis obat anti hipertensi

CLASSIFICATION OF BLOOD PRESSURE FOR ADULTS AGE 18 CLASSIFICATION OF BLOOD PRESSURE FOR ADULTS AGE 18

AND OLDER*AND OLDER*

Category Systolic Diastolic(mmHg) (mm Hg)

Optimal** < 120 and < 80Normal < 130 and < 85High-normal 130-139 or 85-89Hypertension***

Stage 1 140-159 or 90-99Stage 2 160-179 or 100-109Stage 3 > 180 or > 110

* Not taking antihypertensive drugs and not acutely ill. When systolic and diastolic blood pressures fall into different categories , the higher category should be selected to classify the individual’s blood pressure status

** Optimal Blood Pressure with respect to cardiovascular risk is below 120/80 mm Hg, However , unusually low readings should be evaluated for clinical significance

*** Based on the average of two or more readings taken at each of two or more visits after an initial screening

COMPONENTS OF CARDIOVASCULAR RISK STRATIFICATION IN PATIENTS WITH HYPERTENSION *

Major Risk Factors- Smoking - Dyslipidemia- Diabetes mellitus - Age older than 60 years- Sex (men and postmenopausal women)- Family history of cardiovascular disease :- Women under age 65 or men under age 55

Target Organ Damage/Clinical Cardiovascular Disease• Heart diseases

- Left ventricular hypertrophy- Angina/prior myocardial infarction- Prior coronary revascularization- Heart failure

• Stroke or transient ischemic attack• Nephropathy• Peripheral arterial disease• Retinopathy

RISK STRATIFICATION AND TREATMENT *Risk Group B Risk Group C

(At Least 1 Risk (TOD/CCD and/or Risk Group A Factor, Not including Diabetes, With or

Blood Pressure (No Risk Factors Diabetes, No Without Other RiskStages (mmHg) No TOD/CCD)** TOD/CCD) Factors)

High - normal Lifestyle Lifestyle Drug therapy ~(130-139/85-89) modification modification

Stage I Lifestyle Lifestyle Drug therapy(140-159/90-99) modification modification ^

(up to 12 months) (up to 6 months)

Stages 2 and 3 Drug therapy Drug therapy Drug therapy(> 160/> 100)

For example, a patient with diabetes and a blood pressure of 142/94 mmHg plus left ventricular hypertrophy should be classified as having stage I hypertension with target organ disease (left ventricular hypertrophy) and with another major risk factor (diabetes). This patient would be categorized as Stage I, Risk Group C, and recommended for immediate initiation of pharmacologic treatment.

* Lifestyle modification should be adjunctive therapy for all patients recommended for pharmacologic therapy** TOD/CCD indicates target organ disease/clinical cardiovascular disease (see table Components of Cardiovascular Risk Stratification in Patients with Hypertension)^ For patients with multiple risk factors, clinicians should consider drugs as initial therapy plus lifestyle modifications~ For those with heart failure, renal insufficiency, or diabetes

LIFESTYLE MODIFICATIONS FOR HYPERTENSION PREVENTION AND MANAGEMENT

• Lose weight if overweight• Limit alcohol intake to no more than 1 oz (30 mL) ethanol {e.g., 24

oz (720 mL) beer, 10 oz (300 mL) wine, or 2 oz (60 mL) 100-proof whiskey} per day or 0.5 oz (15 mL) ethanol per day for women and lighter weight people.

• Increase aerobic physical activity (30 to 45 minutes most days of the week).

• Reduce sodium intake to no more than 100 mmol per day (2.4 g sodium or 6 g sodium chloride).

• Maintain adequate intake of dietary potassium (approximately 90 mmol per day).

• Maintain adequate intake of dietary calcium and magnesium for general health.

• Stop smoking and reduce intake of dietary saturated fat and cholesterol for overall cardiovascular health.

ALGORITHM FOR THE TREATMENT OF HYPERTENSIONBegin or Continue Lifestyle Modifications

Initial Drug Choices *Uncomplicated hypertension Compelling Indications **Diuretics Diabetes mellitus (type 1) with proteinuriaBeta-blockers - ACE inhibitors

Heart failureSpecific Indications for the - ACE inhibitorsFollowing Drugs (see table Consi- - Diuretics derations for Individualizing Antihypertensive Drug Therapy)ACE inhibitors Isolated systolic hypertension (older persons)Angiotenson II receptors blockers - Diuretics preferredAlpha-blockers - Long-acting dihydropyridineAlpha-beta-blockers calcium antagonistsBeta-blockers Myocardial infarctionCalcium antagonists - Beta-blockers (non-ISA)Diuretics - ACE inhibitors (with systolic dysfunction)

- Start with a low dose of a long-acting once-daily drug, and titrate dose- Low-dose combinations may be appropriate

Not at Goal Blood Pressure (<140/ 90 mmHg)Lower goals for patients with diabetes or renal disease

Not at Goal Blood Pressure

Substitute another drug from a different class

Add a second agent from a different class (diuretic if not already used)

No response or troublesome side effects Inadequate response but well tolerated

Not at Goal Blood Pressure

Continue adding agents from other classes. Consider referral to a hypertension specialist

* Unless contraindicated. ACE : angiotensin-converting enzyme; ISA : intrinsic sympathomimetic activity** Based on randomized controlled trials

Target Systolic DiastolicIdeal 130 70Realistic 140 80-85

Blood Pressure (mmHg)

Target pressures in otherwise healthy elderly patients with hypertension

NB : Take sitting and standing blood pressures to prevent orthostatic hypotension. Ambulatory targets can be lower

Australian EWPHE Coope & SHEP STOP- MRC Syst-[27] [28] Warrender [33] Hypertension [32] Eur

[29] [30] [34]Nonfatal eventsStroke -37 -35 -27 -37* -38* -30 -44*Myocardial Infaction +18 nr +11 -33* -16 nr -20All cardiac -10 -9 -26 -40* nr -13 -33*All cardiovascular -26 -36* -26 -36* nr -25* nrFatal EventsStroke -1 -32 -70* -29 -73* -12 -27Cardiac -75* -38* +1 120a -25b -22a -27All cardiovascular -61 -27 -22 -20 nr -89 -27All noncardiovascular +13 +21 nr +5 nr +5 -1Total deaths -23 -9 -3 -13 -43* -3 -14All events (Fatal & nonfatal)Stroke -34 -36* -42* -36* -47* -25* -42*Cardiac -19 -20 -15 -27* -13b -19 -26*All cardiovascular -24 -34* -23* -32* -40* -17* -31*

Percentage change in the end point of the seven larger trials on hypertension in the elderly

*p<0.05, a = ishemic hear disease, b=MI

Low Dose Beta ACE AT2 Alpha Dihydro BenzDiuretic Blockers Inhibitors Antagonist Blockers CCB CCB

Asthma or COPD ++ CI + ++ + + +Heart failure + C ++ + + C C/CI*Angina + + + + C ++ ++Past MI + ++ ++ + C C CSick sinus syndrome + CI + + + + CIPeripheral vascular disease + C + + ++ ++ ++Aortic stenosis + + CI C + CI +Renal failure, + RAS + + CI C + + +Renal failure, no RAS + + C C + + +Prostatic hypertrophy + + + + ++ + +Diabetes Mellitus + C ++ + + + +Dyslipidemia + C + + + + +Impotence C C + + + + +Gout C + + + + + +Constipation + + + + + + +Glaucoma + ++ + + + + +

Coexisting Pathology

Antihypertensive treatment according to concomintant diseases in elderly patients

C=Use with caution; CI=Contraindicated C/CL* = Benz CCB = C, Ver = CI, ++ = First line drug, + can be added

Recommended drugs by JNC VI

• Diuretic thiazide• Beta-blocker + thizide• Long-acting dihydropyridine Calcium

Antagonist (such as amlodipine)

24 Hour BP Control: Long Acting Vs. Short Acting Drug

IDEAL ANTI HYPERTENSIVE DRUG

• ONCE DAILY DOSEONCE DAILY DOSE

• BP THROUGHOUT DAYBP THROUGHOUT DAY

• SUPPRESION NEUROHUMORAL SUPPRESION NEUROHUMORAL MECHANISMSMECHANISMS

• SAFESAFE

• TOLERABLETOLERABLE

• PREVENTION & REVERSAL OF PREVENTION & REVERSAL OF PATHOLOGIC AREASPATHOLOGIC AREAS

LACK OF ADVERSE LACK OF ADVERSE EFFECTSEFFECTS

Memilih obat anti hipertensi

24 Hour BP Control: Long Acting Vs. Short Acting Drug

The Concept of T:P ratioThe Concept of T:P ratio

The concept of T:P ratio was developed to assess the ‘smoothness’ of the antihypertensive effect of an agent : it assumes that a ‘peak’ effect is readily apparent and can be used to measure how much of this maximum effect is left when a new dose is administered.

- Concept developed for ‘clinic’ blood pressure measurements

- Correction for blood pressure changes in placebo-treated group is necessary (placebo effect often considerable with ‘clinic’ blood pressure)

Source : Zanchetti et al, 1994

Calculation of T:P Ratio

Effect of T:P Ratio on BP Variability

Optimal Antihypertensive Treatment

Blood Pressure and Target Organ Damage

USE OF CALCIUM ANTAGONIST AS ANTIHYPERTENSIVE AGENTS

Vasodilatation

PVR

BP

SNS activity

Renin-angiotensin

aldosterone activity

Renal perfusion

Natriuretic hormones

PVR

Heart Rate

Contractility

Venoconstriction

Na+,Fluid retention

PVR

Na+,Fluid retention??

COCO

CACA : : Block Ca influx into cardiac & smooth muscle cells ---> modification of excitation - contraction coupling vasodilatation

Effectivity of CA : Effectivity of CA :

• AntiatherogenicAntiatherogenic

• Regression of LV hypertrophyRegression of LV hypertrophy Inhibition of proliferation of SMC Inhibition of platelet aggregation Inhibition of impaired endothelium dependent vasodilatation Inhibition of development of early coronary lesion

Tissue protection against oxyradical induced injury

MECHANISMS

MECHANISMS

Calcium ChannelBlocker

Half-life(h)

Tmax (h) Vd(l/ kg)

PhenylalkylaminesØ VerapamilØ Gallopamil

3-73-4

1-2 1.6-6.8

1,4-DihydropyridinesØ NifedipineØ NitrendipineØ NimodipineØ NisoldipineØ NicardipineØ I sradipineØ FelodipineØ NilvadipineØ Amlodipine

4-581-26-191-4920-2515-2035-50

20-40min1.5-2

1-21-21-22-86-12

0.6-1.413.4

2.7-5.9

410

21Benzothiazepines

Ø Diltiazem 2-7 1-2 5.3

Elimination half-lives, time to maximal plasma concentration after oral administration (tmax), and volume of distribution (Vd)

of first and second-generation CCBs

Calcium Channel Blocker Vascular/ cardiacratio

PhenylalkylaminesØ VerapamilØ Gallopamil

33

1,4-DihydropyridinesØ NifedipineØ NitrendipineØ NimodipineØ NisoldipineØ NicardipineØ I sradipineØ FelodipineØ NilvadipineØ Amlodipine

10100

1000100100100

100Benzothiazepines

Ø Diltiazem 3

Vascular / cardiac ratios of first and second generation Calcium Antagonist

Potential Advantages of Long Acting Dihydropyridine Calcium Antagonists

Amlodipine Shows Efficacy in Controlling Systolic BP

• Study 1: Mildly elevated systolic BP (SBP 140-159 mmHg)

• Study 2: Moderately to severely elevated systolic BP (Baseline BP 178/87 mmHg)

* p=0.05, ** p<0.001 vs. baseline, †;<0.005 vs. placebo

‡p=0.001 between active treatment groups

*†*†

**

**

**

‡**

‡**

Recommended drugs by JNC VI

• Diuretic thiazide• Beta-blocker + thizide• Long-acting dihydropyridine Calcium

Antagonist (such as amlodipine)

Summary• Pengontrolan tekanan darah hingga mencapai

sasaran sesuai dengan WHO/ISH tidak terkecuali pasien usia lanjut

• Pemilihan terapi hipertensi pada usia lanjut yang direkomendasikan oleh JNC VI adalah– Diuretic thiazide– Beta-blocker + thizide– Long-acting dihydropyridine Calcium Antagonist

(contohnya : amlodipine)