Epidemiology and treatment of hypertension

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Epidemiology and treatment of hypertension

• Note the first part of this presentation on
  risk-based assessment of BP treatment has been
  provided by Professor Rod Jackson, Head of
  Division of Community Health
• Faculty of Medical Health Sciences
• University of Auckland

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Part 1

• Defining hypertension and making decisions
  based on cardiovascular risk

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Argument

• 1. There is no clinically relevant entity that
  can be defined by a mildly raised blood pressure.
• 2. A mildly raised blood pressure level is not
  a major determinant of which patients benefit
  from blood pressure lowering

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• what is mild hypertension?

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Systolic blood pressure distribution Framingham
Study participants 35-64 years
top x??
74-119 120-139 140-159 160-179 180-300
SBP (mmHg)
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??
7
??
32
30
28
26
18
17
16
16
11
10
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(No Transcript)
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Definitions of mild hypertension prevalence
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Definitions of mild hypertension prevalence
?? 130/80
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• what is mild hypertension?
• its the wrong question

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• who benefits from blood pressure lowering?

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Meta-analysis of RCTs of BP lowering drugs
15,559 patients, SBP diff 17 mmHg, DBPdiff 9
mmHg, follow-up 4.1 years ( 60 years)
Endpoint Odds ratio (Relative risk red.)
Stroke mortality 36
Stroke morbidity 35
CHD mortality 25
CHD morbidity 15
0 0.5 1.0 1.5
Insua et al Ann Intern Med 1994121355-62
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Stroke and blood pressure loweringsubgroup
analysis from 17 RCTs
Trial Events
Relative risk red. group
control treatment
All entry 2.2 1.3
39 DBP lt 110
Some 110, 6.5 4.6 32
all 115
Some or all 8.2 4.7 45
115
0 0.5 1.0 1.5
MacMahon Rogers J Vasc Med Biol 19934265-71
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Stroke and blood pressure loweringsubgroup
analysis from 17 RCTs
Trial Events Odds
ratio (Relative risk red.) group
control treatment
Younger 2.3 1.3 43
patients
Older 7.0 4.6 34
patients
1º prev. 3.2 2.0 38
2º prev. 27.3 18.8 38

0 0.5 1.0 1.5
MacMahon Rogers J Vasc Med Biol 19934265-71
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Stroke and blood pressure loweringsubgroup
analysis from 17 RCTs
Trial Events Odds
ratio (Relative risk red.) group
control treatment
Younger 2.3 1.3 43
patients
1
Older 7.0 4.6 34
patients
2.4
1º prev. 3.2 2.0 38
1.2
2º prev. 27.3 18.8 38

8.5
0 0.5 1.0 1.5
MacMahon Rogers J Vasc Med Biol 19934265-71
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• which patients should be treated?
• individual treatment can only be justified if
  there is individual benefit
• only absolute benefits are relevant to patients

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(45 prospective studies 450,000 people 13,000
events)
PSC Lancet 19953461647-53
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PSC Lancet 19953461647-53
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Absolute risk of CVD risk in 40 year old men by
SBP and other risk factors, Framingham, USA
700
CVD risk per 1000 in 8 years
459
326
210
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SBP 105 ----189 105 ----189 105 ----189
105 ----189 105 ----189 high chol. -
gluc intol.
- -
cigarettes - - -
LVH - - -
-
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WOMEN
Diabet
es
No
D
iabet
es
Ratio of Total CholesterolHDL
Ratio of Total CholesterolHDL
AGE
70
AGE
60
AGE
50
AGE
40
Ratio of Total CholesterolHDL
Ratio of Total CholesterolHDL
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Diabetes
No
Diabetes
Ratio of Total CholesterolHDL
Ratio of Total CholesterolHDL
AGE
70
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CVD risk NNTs
5yr CVD risk 5 yr NNT gt 30 lt 10 . 5-10
40 2.5-5 85 lt 2.5 gt120 assumes 33
RRR
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is BP lowering therapy indicated ?
60 yr old man BP 148/ 88 mmHg smoker TC 240
mg/dl HDLC 38 mg/dl BMI 25 no Hx CVD
50 yr old woman BP 160/95 mmHg non smoker TC 240
mg/dl HDLC 62 mg/dl BMI 25 no Hx CVD
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is BP lowering therapy indicated ?
60 yr old man BP 148/ 88 mmHg smoker TC 240
mg/dl HDLC 38 mg/dl
50 yr old woman BP 160/95 mmHg non smoker TC 240
mg/dl HDLC 62 mg/dl
5 yr absolute CVD risk 24 5 yr NNT 12
5 yr absolute CVD risk 4 5 yr NNT 72
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50/60 yr old woman non smoker TC 240 mmol/L HDLC
60 mmol/L No diabetes
SBP mmHg 150 160 170 5 yr NNT 90 / 50 70 /
42 60 / 37
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To treat or not to treat mild hypertension

• treat risk not blood pressure
• only absolute risks and benefits are relevant to
  patients
• the payer should choose the threshold

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Part 2Pharmacological considerations in
hypertension management

• Sue Hill and David Henry
• Discipline of Clinical Pharmacology

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Factors that influence blood pressure

• sympathetic nervous system
• total peripheral resistance
• mainly arterioles
• intravascular volume (renin-angiotensin)
• renal excretion
• atheroma, thrombosis

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things that alter vascular resistance

• vascular smooth muscle
• mediators from sympathetic nerves and vascular
  endothelium
• calcium dependent
• contraction due to ? intracellular calcium
• relaxation due to ? calcium entry or ?cGMP, cAMP
• depends on intact endothelium
• complex, interdependent biochemical reactions

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drugs that will reduce vascular resistance

• nitric oxide, nitrates
• ?- antagonists
• ?- antagonists
• Calcium channel blockers
• angiotensin II antagonsists
• (lots more)

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other mechanisms to remember

• central control -
• methyldopa, ganglion blocking drugs
• renal excretion of sodium and water
• diuretics, spironolactone

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drugs we use for hypertension

• ?- blockers
• thiazide diuretics
• Calcium channel blockers
• angiotensin converting enzyme inhibitors
• ( others - alphamethyldopa, reserpine,
  hydralazine, prazosin )

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thiazide diuretics

• ACTION
• increase sodium and water excretion by decreasing
  reabsorption of sodium and chloride in the distal
  tubule (later effect on vessels)
• EFFECT
• lowers blood pressure- over several days
• decreases complications, morbidity and mortality
  ( good clinical trials)
• Side effects
• metabolic effects diabetes, gout, low Na, K,
  impotence

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?- adrenoceptor antagonists

• ACTION
• effects on heart (?1) and smooth muscle (?2 ) via
  noradrenaline
• lowers BP
• reduces cardiac output
• reduces renin release
• reduces central sympathetic activity
• effect on pre-synaptic noradrenaline release
• nonselective antagonist propranolol
• relatively selective ?1 metoprolol, atenolol
• mixed agonist/antagonist - oxprenolol

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?- adrenoceptor antagonists

• EFFECT
• lowers blood pressure - over several days
• decreases complications, mortality and morbidity
  (good clinical trials)
• SIDE EEFECTS
• bronchospasm, fatigue, bad dreams, cold
  extremities
• worsening cardiac failure, heart block
• hypoglyacaemia

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ACE-inhibitors

• ACTION
• inhibits conversion of angiotensin I to
  angiotensin II - effects on vasculature in kidney
  , brain, heart
• vasodilator
• eg captopril, enalapril, lisinopril, ramipril
• EFFECTS
• lower blood pressure- relatively rapidly
• effect on mortality, morbidity and
  complications??
• Reduces mortality in cardiac failure, post-AMI
  good clinical trials

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ACE-inhibitors

• SIDE EFFECTS
• cough, rash, taste disturbances
• renal failure, neutropenia, proteinuria
• COST
• relatively expensive

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Angiotensin II antagonists

• losarten, ibersarten, candesarten
• actions similar to ACE inhibitors
• effects
• lower blood pressure- relatively rapidly
• effects on clinical outcomes?
• Side effects
• rash, cough
• cost expensive

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calcium antagonists

• ACTION
• three classes verapamil, dihydropyridines,
  benzothiazepines
• block calcium entry into cells by preventing
  opening of voltage gated calcium channels
• act on heart and smooth muscle, depending on type
• vasodilator effect (mainly dihydropyridines)
• two forms - immediate and slow release
• EFFECTS
• lower blood pressure - can be rapid
• mortality, morbidity, complications??

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Calcium antagonists

• SIDE EFFECTS
• flushing, headache, ankle swelling, constipation
• heart block, worsening cardiac failure

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choices

• BENEFITS
• short-term
• long term

• RISKS
• side-effects
• lack of beneficial effect ( unnecessary
  medication)

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issues

• Preventive versus curative treatment
• need for joint decision making
• use of drugs with clinical effects versus elegant
  pharmacologically active molecules
• benefits versus risks!!

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terms

• agonist, partial agonist
• receptor
• antagonist, competitive antagonist
• ligand
• affinity
• mediators
• tolerance