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Hipertensie Die verlede en hede

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Duiretika gee die mees indrukwekkende resultate. Laat 70's tot mid 90's ... 24-h blood pressure profile in two patients with hypertension (dipper and non-dipper) ... – PowerPoint PPT presentation

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Title: Hipertensie Die verlede en hede


1
Hipertensie Die verlede en hede
  • FCJ Bester
  • Fichmed GF06
  • Sell 082 554 2799

2
Classification of BP JNC VI WHO/ISH
3
Hantering - JNC VI
4
Vyftigs
  • Ganglion blokkers
  • Baie newe effekte
  • Slegs in lewensbedreigde hts

5
1960S
  • Reserpien
  • Reserpien kombinasie met hidralasien
  • Reserpien in kombinasie met chlorotiasied
  • Eerste grootskaalse effektiwiteits analise
  • Duiretika gee die mees indrukwekkende resultate

6
Laat 70s tot mid 90s
  • HTS Rx very significant in the elderly
  • 1977 JNC I - High dose diuretics
  • 1980 JNC II - High dose diuretics
  • 1984 JNC III - Lower dose diuretics or beta
    blocker
  • 1988 JNC IV - Diuretics or beta blocker or Ca
    antagonist or AECI

7
Laat 70s verder
  • 1993 - JNC V - Diuretic or beta blocker or AECI
    or CCB or alpha blocker (prefer singel agent)
  • 1997 - JNC VI
  • Individualise
  • Still single agent therapy
  • Low dose combination an option

8
2002 - JNC VII
  • Big focus on systolic control
  • HOT - 70 persons need combination.
  • Emphasis move to combination therapy.

9
1990s nuwe klasse en baie navorsing
  • Kort en lang termyn studies
  • Langtermyn studies
  • AASK, ALLHAT, ANHP2, ASCOT, CONVINCE, CSGTEI,
  • Diab-Hycar, ELSA, HYVET, INSIGHT, LIFE
  • NORDIL, PROGRESS, SCOPE, SHELL, VALUE
  • Meer as 150 000 pasiente in totaal

10
Results of randomised trials of antihypertensive
drug therapy
STROKE
Randomised trials
Epidemiological data
CHD
Randomised trials
Epidemiological data
0 10 20 30
40 50
reduction / 6 mm Hg fall in diastolic blood
pressure
Collins and Peto, 1994
11
Blood pressure and target organ damage
Current evidence suggests that
  • Measures of 24-h blood pressure more closely
    predict target organ damage than do clinic or
    casual measurements
  • There is a higher incidence of cardiovascular
    complications when night-time blood pressure
    remains elevated
  • Blood pressure variability is an additional
    and independent determinant of target organ
    damage
  • The highest incidence of cardiovascular events
    occurs in the morning at (approximately) 24 h
    post dose

Sokolow et al, 1966 Devereux et al, 1983
Devereux et al, 1987 Parati et al,1987 Mancia,
1990
12
24-h blood pressure profile in two patients with
hypertension (dipper and non-dipper)
Sleep
Blood pressure (mm Hg)
175
Non-dipper
155
135
Dipper
115
95
75
55
700 1100 1500 1900
2300 300 700
Time of day
Redman et al, 1976 Mancia et al, 1983 Kobrin et
al, 1984 Baumgart et al, 1989 Imai et al, 1990
Portaluppi et al, 1991
13
Cardiovascular events that are coincident with
the morning blood pressure surge
  • Myocardial ischaemia
  • Myocardial infarction
  • Sudden cardiac death
  • Cerebrovascular accident
  • thrombotic
  • haemorrhagic

Muller et al, 1985 Rocco et al, 1987 Marler et
al, 1989 Willich et al, 1992
14
Circadian incidence of cardiovascular events
myocardial ischaemia
Ischaemia (min)
300
n24
250
200
150
100
50
0
0100 0500 0900 1300
1700 2100


Time of day
Rocco et al, 1987
15
Blood pressure variability and target organ
damage a longitudinal analysis
n73
30 minute S.D. of MAP (mm Hg)
plt0.01
17
15
13
11
9
7
10 8 11 8
11 9 8
8
5
95108
109120
lt95
gt120
Initial 24-h MAP (mm Hg)
Frattola et al, 1993
16
Correlation between left ventricular mass index
(LVMI) and elevated systolic blood pressure
measurement
Correlation coefficient (r)
n15
0.8



0.6
0.4
0.2
0.0
Conventional or casual BP
Elevated daytime average SBP
Elevated night-time average SBP
Elevated 24-h average SBP
White et al, 1993
plt0.05
17
Circadian incidence of cardiovascular events
myocardial infarction
Infarctions/h
50
n703
40
30
20
10
0
0100 0500 0900 1300
1700 2100

Time of day
Muller et al, 1985
18
Circadian incidence of cardiovascular events
cerebrovascular accident
No. of events
n1167
160
120
80
40
0
0000 0400 0800 1200
1600 2000

Time of day
Marler et al, 1989
19
Relevance of troughpeak ratios to 24h blood
pressure control
Blood pressure (mmHg)
180
Placebo
160
Trough
Drug A (TP ratio 75)
Peak
140
120
Drug B (TP ratio 45)
100
Dose
0700 1100 1500 1900
2300 0300 0700 Time of day
Elliott and Meredith, 1995
20
Bloeddruk metings
  • Spreekkamer of kliniek - Kwik sphygmomanometer
  • Self monitering
  • elektroniese meters
  • anaeroiede meters
  • AMBULATORIESE BLOEDDRUK MONITERING

21
Bloeddruk meting
  • Kwik meters die betroubaarste
  • Geen kaffeien bevattende drankies, rook of eet 30
    minute voor meting nie.
  • Band grootte (2/3 of 30 cm omtrek)
  • Die gemiddeld van 2 agtereenvolgende metings wat
    minder as 5 mmHg verskil.
  • 24 hour ABDM is nie deel van roetine bloeddruk
    evaluasie nie.

22
Voordele van tuismonitering
  • Onderskei tussen volgehoue en wit jas
    hipertensie.
  • Respons op antihipertensiewe terapie.
  • Verbeter pasiënt samewerking.
  • Verminder koste.

JNC VI
23
Afsnywaardes
  • Tuis bloeddruk
  • lt 135/85 mmHg
  • AMBULANTE BLOEDDRUK
  • Wakker lt 135 / 85 mmHg
  • Slaaplt 120 / 75 mmHg
  • 24 uur gemiddeld lt125 / 80 mmHg

24
Situasies waar 24 uur monitering oorweeg moet
word.
  • Groot variasie in bloeddrukwaardes tydens
    dieselfde of verskillende besoeke.
  • Hipertensiewe metings by pasiënte met lae
    Kardiovaskulêre risiko.
  • Moontlike hipotensie.
  • Weerstandige hipertensie.

WHO/ISH
25
SPESIALE ONDERSOEKEEssensiele Hipertensie
  • Urine analise
  • Volbloedtelling
  • Ureum en elektroliete.
  • Vastende glukose.
  • Totale cholesterol en HDL
  • EKG

(JNC VI)
26
Opsionele ondersoeke bepaal deur bevindinge
tydens geskiedenis, ondersoek en roetine
ondersoeke
  • CXR
  • Vastende TG
  • LDL Cholesterol
  • Mikroalbuminurie
  • 24 uur urine proteien
  • Bloed kalsium
  • Uraat
  • Glikosileerde hemoglobien
  • TSH
  • Hartsonar
  • Plasma renien aktiwiteit
  • Plasma aldosteroon
  • urine Katekolamiene
  • Ultraklank
  • Niergroottes
  • Renale arteries

(JNC VI WHO/ISH
27
TREATMENT
  • Life Style modification
  • Drugs

28
Lewensstyl veranderinge
  • Massaverlies
  • Beperkte Etanol inname (maksimum 30 ml)
  • Aerobiese oefeninge (30-45 min meeste dae)
  • Maksimum 6 g NaCl/dag
  • Genoegsame kaluim inname
  • Genoegsame Ca en Mg
  • Staak rook, verminderde diere vette

29
Recommendations for follow-up based on initial
blood pressure measurements for adults
30
MAJOR RISK FACTORS
  • Smoking
  • Dyslipidemia (WHO/ISH Total cholesterol
    gt6,5mmol/l)
  • Diabetes mellitus
  • Age gt 60 years (WHO/ISH men gt55 yrs women gt65
    yrs)
  • Sex (men and postmenopausal women)
  • Family history of cardiovascular disease (Women lt
    65 or men lt 55)

JNC VI WHO / ISH
31
TARGET ORGAN DAMAGE / CLINICAL CARDIOVASCULAR
DISEASE
  • HEART DISEASE
  • Left ventricular hypertrophy
  • Angina or prior myocardial infarction
  • Prior coronary revascularization
  • Heart failure
  • Stroke or transient ischemic attack
  • Nephropathy
  • Vascular Disease
  • Symptomatic arterial disease
  • Dissecting anneurysm
  • Retinopathy
  • Haemorrhages or exudates
  • Papilloedema

(JNC VI WHO /ISH)
32
ASSOCIATED CLINICAL CONDITIONS
These diseases influence not only the threshold
for intervention but also the antihypertensive
agent to be used
  • DIABETES
  • GOUT
  • ASTHMA
  • PERIPHERAL VASCULAR DISEASE
  • PROSTATIC HYPERTROPHY

33
INITIATION OF TREATMENT
(WHO/ISH)
34
ORAL ANTI-HYPERTENSIVE DRUGS
  • Diuretics
  • Adrenergic inhibitors
  • Peripheral agents
  • Central ? agonists
  • ? blockers
  • ? blockers
  • Calcium antagonists
  • ACE inhibitors
  • Angiotensin II receptor blockers

35
COMPELLING INDICATIONS JNC VI
36
Die RAS
Angiotensinogeen
Angiotensien I
Angiotensien II
Angiotensien III
Angiotensien IV
Angiotensien (1-7)
37
Die RAS
Angiotensinogeen
Renien
Serien proteases
AOE
Angiotensien II
Angiotensien I
Serien proteases 40
AII reseptor Blokker
AT1 Reseptor
38
Die RAS
Angiotensien II
ATII RESEPTOR BLOKKER
AT 1 reseptor
AT 2 (en x) reseptor

Vasokonstriksie Stimuleer selgroei Na
retensie Verhoogde simpatiese akt.
Vasodilatasie Antiproliferatief Seldifferensiasie
Induseer apoptose Bradikinien vrystelling NO
vrystelling Beta 2 stimulasie
39
Class limitations how do the AIIRAs rate?
  • Adverse effect Thiazide ?- Calcium channel ACE
    AIIRAs diuretics blockers blockers
    inhibitors
  • Cardiovascular
  • Heart failure ?? ??
  • Bradyarrhythmias ?? ??
  • Peripheral ischaemia ??
  • Postural hypotension ??
  • First-dose hypotension ??
  • Excessive vasodilatation ???
  • Angioedema ?
  • Rebound phenomena ?? ??
  • Respiratory
  • Asthma exacerbation ???
  • Chronic obstructive ??? airways disease
    exacerbation
  • Cough ??
  • Metabolic
  • Electrolyte disturbances ??? ? ?
  • Effects in diabetes ??? ??
  • Dyslipidaemia ?? ??
  • Central nervous system ? ?

Hypokalaemia reported for losartan
Kostis (1996) Ellis Patterson (1996) Goa
Wagstaff (1996) Gradman et al (1995) Belcher et
al (1997) Oparil et al (1986) Goldberg et al
(1995)
40
Class limitations how do the AIIRAs rate?
  • Adverse effect Thiazide ?- Calcium channel ACE
    AIIRAs diuretics blockers blockers
    inhibitors
  • Cardiovascular
  • Heart failure ?? ??
  • Bradyarrhythmias ?? ??
  • Peripheral ischaemia ??
  • Postural hypotension ??
  • First-dose hypotension ??
  • Excessive vasodilatation ???
  • Angioedema ?
  • Rebound phenomena ?? ??
  • Respiratory
  • Asthma exacerbation ???
  • Chronic obstructive ??? airways disease
    exacerbation
  • Cough ??
  • Metabolic
  • Electrolyte disturbances ??? ? ?
  • Effects in diabetes ??? ??
  • Dyslipidaemia ?? ??
  • Central nervous system ? ?

Hypokalaemia reported for losartan
Kostis (1996) Ellis Patterson (1996) Goa
Wagstaff (1996) Gradman et al (1995) Belcher et
al (1997) Oparil et al (1986) Goldberg et al
(1995)
41
The ideal antihypertensive agent
  • Effectively reduces BP
  • Maintains BP control over 24 hours with
    once-a-day dosing
  • Effective in all hypertensive patients
  • No adverse effects
  • No negative metabolic side effects
  • Affordable

42
Die ideale antihipertensiewe middel
  • Effektiewe bloeddrukkontrole
  • Lang werkingsduur
  • Minimale newe effekte
  • Metabolies neutraal
  • Vermindering in eindorgaanskade
  • Vermindering in morbiditeit
  • Vermindering in mortaliteit

43
Ideale antihipertensiewe middel
  • n Goeie afrodiasiac
  • Verklein die gat in die osoonlaag
  • Beskerm die reënwoude
  • beskerming teen die Sydney virus

44
The AIIRAs a unique class profile
  • Specific blockade of AII effects through
    selective AT1 receptor antagonism
  • Excellent troughpeak DBP ratio (gt0.6) allowing
    once-daily dosing
  • Tolerability profile comparable to placebo
  • No drug interactions
  • Metabolically neutral
  • No restrictions for use in patients with
    concomitant conditions, eg diabetes, asthma,
    dyslipidaemia and heart failure
  • Potentially greater beneficial effects on
    hypertensive end-organ damage (eg heart, kidney)
    than other antihypertensive agents

Gradman et al (1995) Oparil et al (1986) Heuer
et al (1997) Belcher et al (1997)
45
Use of AIIRAs current and future prospects
  • Current prospects
  • All patients with primary hypertension
  • All age groups
  • Patients with concomitant disease (diabetes,
    hyperlipidaemia etc)
  • Patients with renal or hepatic dysfunction
  • Future prospects
  • Potential end-organ protective effect(kidney,
    heart, blood vessels, brain)

Goa Wagstaff (1996) Trenkwalder et al (1997)
Csajka et al (1997)Pitt et al (1997) Kostis
(1996) Nishikawa et al (1997)
46
GUIDELINES FOR SELECTING DRUG TREATMENT OF
HYPERTENSION
  • Class of drug DIURETICS
  • Compelling indications
  • Heart failure,Elderly patients, Systolic
    hypertension
  • Possible indications Diabetes
  • Compelling contraindications Gout
  • Possible contraindications
  • Dyslipidaemia, Sexually active male

WHO / ISH
47
GUIDELINES FOR SELECTING DRUG TREATMENT OF
HYPERTENSION
  • Class of drug ? - BLOCKERS
  • Compelling indications Angina,Tachyarrhythmias
    After myocardial infarct
  • Possible indications
  • Heart failure Pregnancy, Diabetes
  • Compelling contraindications
  • Asthma and COPD Heart block
  • Possible contraindications
  • Dyslipidaemia, Athletes physically active
    patients Peripheral vascular disease

WHO /ISH
48
GUIDELINES FOR SELECTING DRUG TREATMENT OF
HYPERTENSION
  • Class of drug ?-BLOCKERS
  • Compelling indications
  • Prostatic hypertrophy
  • Possible indications
  • Glucose intolerance, Dyslipidaemia
  • Possible contraindications
  • Orthostatic hypotension

WHO / ISH
49
GUIDELINES FOR SELECTING DRUG TREATMENT OF
HYPERTENSION
  • Class of drug CALCIUM ANTAGONISTS
  • Compelling indications
  • Angina, Elderly patients, Systolic hypertension
  • Possible indications
  • Peripheral vascular disease
  • Compelling contraindications Heart block
  • Possible contraindications Congestive heart
    failure

WHO / ISH
50
GUIDELINES FOR SELECTING DRUG TREATMENT OF
HYPERTENSION
  • Class of drug ACE INHIBITORS
  • Compelling indications
  • Heart failure, Left ventricular dysfunction,
    After myocardial infarct, Diabetic nephropathy
  • Compelling contraindications Pregnancy,
    Hyperkalaemia, Bilateral renal artery stenosis

WHO / ISH
51
GUIDELINES FOR SELECTING DRUG TREATMENT OF
HYPERTENSION
  • Class of drug ANGIOTENSIN II ANTAGONIST
  • Compelling indications
  • ACE inhibitor cough
  • Possible indications
  • Heart failure
  • Compelling contraindications Pregnancy,
    Bilateral renal artery stenosis, Hyperkalaemia

WHO / ISH
52
Effective Drug Combinations
Combination of drugs produce blood pressure
reductions that are greater than those produced
by individual agents used alone
  • Diuretic and ?-Blocker
  • Diuretic and ACE-I or AIIA
  • Calcium antagonist and ?-Blocker
  • Calcium antagonist and ACE-I
  • ?-Blocker and ?-Blocker
  • Diuretic and Reserpine

WHO / ISH
53
HOW FAR SHOULD BLOOD PRESSURE BE LOWERED ?
54
Stabilization, maintenance and follow-up after
initiation of drug therapy
Antihypertensive Drug Treatment Initiated
Not at Goal Blood Pressure After 3 months
  • If no response, substitute a drug or low dose
    combination from other classes
  • If partial response, increase dose, add a drug
    form another class, or change to low dose
    combination
  • Intensify lifestyle measures
  • Hypertension difficulty to manage Refer to
    specialist physician or clinic

WHO / ISH
55
Antihypertensive treatment for the future
  • Duration of action which is appropriate for
    once-daily administration
  • High troughpeak ratio which is consistent over
    the recommended dosage range
  • Maintenance of control of blood pressure fully
    and consistently throughout 24 h
  • Maintenance of control of blood pressure beyond
    24 h despite poor compliance with treatment
  • No increases in blood pressure variability

Meredith et al, 1995
56
JNC-VI Hypertension Management Guidelines
Long-acting formulations that provide 24-h
efficacy are preferred over short-acting agents
for many reasons - adherence is better with
once-daily dosing - for some agents fewer
tablets incur lower costs - control of
hypertension is persistent and smooth rather
than intermittent - protection is provided
against whatever risk for sudden death, heart
attack and stroke that is due to the abrupt
increase of blood pressure after arising from
over night sleep
JNC-VI, 1997
57
JNC-VI Hypertension Management Guidelines
The optimal formulation should provide 24-hour
efficacy with a once-daily dose with at least 50
of the peak effect remaining at the end of the
24 hours
Agents with a duration of action beyond 24
hours are attractive because many patients
inadvertently miss at least 1 dose of
medication each week
JNC-VI, 1997
58
Antihypertensive treatment for the future
  • Additional benefit may be offered by a profile of
    pharmacological activity which can augment the
    benefits of blood pressure reduction
  • interference with the early stages of the
    atherosclerotic process
  • protection against renal damage

59
Hantering van hipertensie
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