Ht12 - GP education seminar

 147
 The number of different anti-
hypertensives in Mims
 3
 The number of guidelines applicable to
Hypertension with largely dissimilar
recommendations

Australian Guidelines
Evidence Base
 1
 The number of studies it took for the
Australian guidelines to recommend a
treatment pathway based on a drug
which is not available in
 AUSTRALIA

 10
 The number of promotional mail-outs
received per week by GPs in 2008
 Choice, August 2008

 Measurement
 Lifestyle factors
 When to investigate for secondary
causes, and when not to
 Postural hypertension
 New drugs on the horizon
 New procedures

Targets
 What to do if you don’t hit targets
 Should there be targets?
 Are the targets correct

Hypertension
Exciting new horizons and updates
Sunday 1st
April 2012

Dr Alistair Begg
 Consultant cardiologist
 Ashford Heart Centre
 Conflicts of interest…presentations for
various pharmaceutical companies on
hypertension

HYPERTENSION IS ASSOCIATED
WITH NUMEROUS COMORBIDITIES
Comorbidity Hypertension involvement
Coronary artery disease 50% of patients with coronary artery disease have hypertension1
Left ventricular
hypertrophy
15 to 20% of hypertensive adults have an increased left ventricular
mass2
Ischaemic stroke
77% of patients who have a first stroke have a blood pressure
>140/90 mmHg3
Chronic kidney disease
8 to 15% of hypertensive adults have decreased renal function4
30 to 40% of patients with microalbuminuria have hypertension5
Diabetes
75% of added cardiovascular risk in diabetic patients is attributable to
hypertension6
Peripheral artery disease 74% of patients with peripheral artery disease have hypertension7
Reference: 1.Pepine CJ. Am J Cardiol 1998;82(3A):21H-24H; 2. Diamond JA, Phillips RA. Hypertens Res 2005;28:191-202; 3.
Rosamond W, et al. Circulation 2008; Reference: 1. National Heart Foundation of Australia (National
Blood Pressure and Vascular Disease Advisory Committee). Guide to management of

National Heart Survey 2004-
2005
Prevalence of hypertension (%)*
*Weighted estimates
Self-reported hypertension Australian Bureau of Statistics 2006
45.0
40.0
35.0
30.0
25.0
20.0
15.0
10.0
5.0
0.0
Children 0-14
years
Children 15-17
years
18-64 years 65-75 years 75 years and
over
0.1 0.1
9.1
38.0
41.0
PrevalenceofHypertension(%)*

Classification of BP in Australian
National Heart Foundation
Guidelines
Diagnostic category Systolic
(mmHg)
Diastolic (mmHg)
Normal <120 <80
High-normal 120-139 80-89
Grade 1 (mild) hypertension 140-159 90-99
Grade 2 (moderate) hypertension 160-179 100-109
Grade 3 (severe) hypertension ≥ 180 ≥ 110
Isolated systolic hypertension ≥ 140 <90
Isolated systolic hypertension with
widened pulse pressure
≥ 160 ≤ 70
National Heart Foundation of Australia. Guide to management of Hypertension, 2008.

Cardiovascular Mortality Risk Doubles with
each 20/10 mmHg Increase in Usual
Systolic/Diastolic BP*
Systolic BP/Diastolic BP (mmHg)
RiskofdeathfromIHDandother
vascularcauses(excludingstroke)*
8
6
4
2
0
115/75 135/85 175/105
1X risk 2X risk
4X risk
8X risk
155/95
*Individuals aged 40–69 years Adapted from Lewington et al. Lancet 2002;360:1903–13

National Heart Foundation Guidelines:
Target BP Goals in Adults
Patient Group Target (mmHg)
People with proteinuria >1 g/day
(with or without diabetes)
<125/75
People with associated condition/s or end organ
damage:
coronary heart disease, diabetes, chronic kidney
disease, proteinuria (> 300 mg/day), or Stroke/TIA*
< 130/80
People with none of the following:
coronary heart disease, diabetes, chronic kidney
disease, proteinuria (> 300 mg/day), or Stroke/TIA*
< 140/90
*TIA: transient ischaemic attack

Consequences of doctors
failing to meet hypertension
targets

Title and artist
 1 the downfall of man Raffaella
Sazio da Urbino
 2 expulsion of adam and eve
Michaelangelo di Lodoviro Buonarotti
3 The wrath of God
Leonardo da Vinci
4 the moment of mortal Sin
Peter Paul Rubens

Across the Ditch
 In New Zealand, there is no numerical
BP target.
 They recommend you reduce the
overall CV risk by a certain amount

Figure 5
Source: American Journal of Medicine, The 2010; 123:719-726 (DOI:10.1016/j.amjmed.2010.02.014 )
Copyright © 2010 Terms and Conditions

Targets
 The J curve is real
 Nadirs are probably age depndent
 Nadirs are very important in Ischaemic
heart disease patients
 Treatment should be lightenned
at110/60, and maybe at higher levels in
the elderly
 These nadirs hold in the diabetic,”lower
the better” is not strictly true

MEASURING BLOOD PRESSURE
ACCURATELY IN THE CLINIC1
 Practice tips
• Service mercury sphygmomanometers annually
• Calibrate non-mercury sphygmomanometers every 6 months
• In new patients, measure BP on both arms
• In patients with suspected orthostatic hypotension, measure BP
both sitting and standing
• Ensure patient has not had caffeine/caffeinated soft drink/coffee
before having BP reading
Reference: 1. National Heart Foundation of Australia (National Blood Pressure and Vascular Disease Advisory Committee). Guide to
management of hypertension 2008; Available at: www.heartfoundation.org.au. Accessed: January 2009.

PTCA/stent to sublavian
stenosis

BP measurement outside the
clinic
 15% have isolated clinic or white coat HT
 Similar proportion have normal clinic BP but
high ambulatory BP (often referred to as
‘masked’,or’reverse white coat’,or isolated
ambulatory HT
 Normal ambulatory BP values lower than
clinic readings ie
 Daytime less than 135>85 mm Hg
 Nocturnal <120/70 mm Hg
 Over 24 hrs <130/80

 Stuff about 5 measurements here

Medications that may increase
blood pressure
 Clozapine
 Corticosteroids
 Haemopoietic agents (darbopoetin,epoetin)
 Immunomodifiers (cyclosporin,tacrolimus)
 Leflunomide (Arava)
 Monoamine oxidase inhibitors : reversible
(moclobemide),irreversible (phenelzine,tranylcypromine)
 Oral contraceptives
 Oral decongestants (eg pseudoephedrine)
 Stimulants(dexamphetamine sulfate,methylphenidate
hcl=Ritalin)
 Sympathomimetic agents
 Venflaxine (=Efexor,dose related)
 Rebound hypertension may be seen after abrupt withdrawl of
Bromocriptine or clonidine

Complementary medicines
and hypertension

Complementary medicines that
may increase blood pressure
 American mistletoe
 Angel’s trumpet
 Butcher’s broom
 Caffeine containing products eg guarana,black and
green tea,yerba mate
 Ephedra (ma huang)
 Gentian
 Ginger preparations
 Liquorice
 Melatonin
 St John’s wart

Examination pointers
Identify all CV risk factors
Detect end organ damage eg
CCF,CAD,PVD
Detect related or comorbid clinical
conditions eg CKD,neurological
disease,obesity (waist <94 cm
males,<80cm females,BMI<25
Identify secondary causes eg Cushingoid

Initial investigations
 Urinary micoalbuminuria on spot urine,if
confirmed obtain a 24 hour urine for
accurate assessment
 Blood analysis for
Na/K/Ur/Cr/Urate,Hb,fasting BSL,Lipid
profile,LFTs
 ECG for conduction
disease,arrhythmias,CHD,LVH (incr CV
risk)

Further investigations
 Renin:aldosterone ratio if treatment
resistant,moderate to severe,or hypokalemia
(morning sample)
 24 hr urine catecholamines,cortisol
 Renal artery stenosis assessment eg renal
US,CTA,nuclear scan if suspect renal artery
stenosis

Renal artery stenosis
assessment
 Renal CTCA most precise anatomical test
but lacks functionality
 Nuclear scan-functional test,limitations
 Renal ultrasound-low sensitivity
 MRI

NHF: When to Initiate Treatment
of Hypertension
Are any of the following present?
• Grade 3 hypertension (SBP ≥ 180 mmHg and/or DBP ≥ 110 mmHg)
• Isolated systolic hypertension with widened pulse pressure
(SBP ≥ 160 mmHg and DBP ≤ 70 mmHg)
• Associated conditions or target-organ damage (Table 3)
Start drug treatment immediately
(See Figure 3: Initiating drug treatment)
• Lifestyle modification
• Manage associated conditions†
• Confirmed hypertension grades 1–2
(SBP 140–179 mmHg or DBP 90–109 mmHg)
• All other adults
Assess 5-year absolute cardiovascular risk (Figure 1)*
SBP < 140 mmHg
DBP < 90 mmHg
Continue monitoring‡
• Monitor BP
Reassess 5-year absolute
cardiovascular risk in 3–6 months
• Monitor BP
Reassess 5-year absolute
cardiovascular risk in 6–12 months
SBP 140–150 mmHg
DBP < 90 mmHg
Continue monitoring‡
SBP ≥ 140 mmHg
DBP ≥ 90 mmHg
SBP ≥ 150 mmHg
DBP ≥ 90 mmHg
NoYes
High (>15%) Low (<10%)Moderate (10–15%)
Moderate
(10–15%)
Low
(<10%)
National Heart Foundation of Australia. Guide to Management of Hypertension, 2008.

Lifestyle modification
 Advise patients to aim for healthy targets:
 • At least 30 minutes of moderate-intensity physical activity on most, if not all, days of the
 week (daily total can be accumulated e.g. three 10-minute sessions). Advise patients of all
 ages to become more active.
 • Smoking cessation. Refer patients to Quitline. Consider recommending nicotine
replacement
 therapy and/or prescribing oral therapy (bupropion or varenicline) in patients who smoke
 more than 10 cigarettes per day and have no contraindications.
 • Waist measurement < 94 cm for men and < 80 cm for women, body mass index
 (BMI) < 25 kg/m2. When recommending weight loss, advise patients on reducing kilojoule
 intake as well as increasing physical activity.
 • Dietary salt restriction: ≤ 4 g/day (65 mmol/day sodium). Recommend low-salt and
reducedsalt
 foods as part of a healthy eating pattern.
 • Limited alcohol intake: ≤ two standard drinks per day for men or ≤ one standard drink per
 day for women.

Benefits of lifestyle
modification
 Smoking cessation….may not reduce
BP but 2-6 fold increase risk MI and 3
fold increase risk of CVA
 Regular physical activity…regular
aerobic exercise 4/2.5 mm Hg…..30/60
a day
 Salt restriction .avge reduction 4.5/2mm
Hg while increased dietary potassium
can reduce BP by 6 mm in HT and 2
mm Hg in normotensives (unless renal
impairment)

How many patients have you
had that have a good
therapeutic response to a low
salt diet
 0
 1
 2-4
 >5

DASH DIET
 A few guidelines of the DASH diet menu:
 the diet includes a minimum of 4-5 servings of fruits and
vegetables a day
 three servings of low-fat dairy product
 7-8 servings of grains
 2 servings of non-vegetarian food
 fat/oils should be around 2-3 servings
 on a weekly basis one needs to consume 4-5 serves of nuts,
seeds and legumes
 the sweet consumption should not exceed 5 serves a week
(foods with little or no sugar as best, although sugar from fruits
is considered natural and benefiting)
 avoid or at least use moderation on alcohol consumption

Additional lifestyle factors
 Weight reduction…every 1% reduction
in body weight lowers SBP by average
of 1%
 Alchohol limited to max 2 standard
drinks for males and one for
females,advise at least 2 alchohol free
days a week

National Heart Foundation of Australia. Guide to Management of Hypertension, 2008.
If target BP not reached
ACE inhibitor or angiotensin II receptor antagonist + calcium channel blocker
OR
ACE inhibitor or angiotensin II receptor antagonist + low-dose thiazide diuretic
ACE inhibitor or angiotensin II receptor antagonist
+ calcium channel blocker + low-dose thiazide diuretic
Consider seeking specialist advice
NHF: Initiating Antihypertensive Therapy
First Choice
ACE inhibitor or angiotensin II receptor antagonist
OR
Calcium channel blocker
OR
Low-dose thiazide diuretic (consider for people aged ≥65 years only)

Factors determining drug
choices
 Patient age
 Presence of associated conditions or
end organ damage
 Potential interactions with other drugs
 Adherence implications
 cost

Summary of Recommendations for
Multiple-mechanism Therapy: What the NHF
Hypertension Management Guidelines Say
 Start with lowest recommended dose of selected first line agent;
If not well tolerated, change to a drug of a different class
 If BP target is not reached or there is no significant BP reduction
with initial monotherapy, add another agent from a different drug
class at low dose, rather than increasing dose of the first agent
 If BP still above target and both agents well tolerated, increase
dose of one of the agents (other than thiazide diuretic)
incrementally to maximal recommended dose before increasing the
dose of the other agent
 Once a combination is established as long-term therapy, it may be
more convenient for the patient to use a combined preparation

*Lower doses generally used in fixed-dose combinations
+ = potential advantage
Advantages of Fixed Dose versus Free
Dose Combinations of Two Antihypertensive
Drugs
Fixed Free
Simplicity of treatment + –
Persistence + –
Efficacy + +
Tolerability +* –
Price + –
Flexibility – +
Burnier M. Am J Hypertens 2006;19:1190–6.

Inadequacy of Agents with a Single
Mechanism of Action (MoA)
 Materson et al. observed that antihypertensive agents
with a single MoA were inadequate to achieve a
diastolic BP <95 mmHg in 41−58%
of hypertensive patients1
 In patients with hypertension and diabetes, more than
65% will require two or more antihypertensive agents
to achieve a BP of 130/80 mmHg2
 Because hypertension is a multifactorial disease, in
most cases at least two antihypertensive agents are
needed for patients to achieve BP goal3
1. Materson et al. N Engl J Med 1993;328:91421
2. Bakris et al. Am J Kidney Dis 2000;36:64661
3. Milani. Am J Manag Care 2005;11:S2207

Advantages of Multiple-
mechanism Therapy: Efficacy
 Components with a different mechanism of action interact on
complementary pathways of BP control1
 Each component can potentially neutralise counter-regulatory
mechanisms, e.g.
 Diuretics reduce plasma volume, which in turn stimulates the
renin angiotensin system (RAS) and thus increases BP; addition
of a RAS blocker attenuates this effect1,2
 Multiple-mechanism therapy may result in BP reductions that
are additive2
Multiple-mechanism therapy results in a greater BP reduction
than seen with its single-mechanism components alone1,2
1. Sica. Drugs 2002;62:443−62
2. Quan et al. Am J Cardiovasc Drugs 2006;6:103−13

Multiple Antihypertensive Agents are
Needed to Reach BP Goal
Bakris et al. Am J Med 2004;116(5A):30S–8
Dahlöf et al. Lancet 2005;366:895–906; Jamerson et al. Blood Press 2007;16:80–6
Average no. of antihypertensive medications*Interim 6-month data
ACCOMPLISH* (132 mmHg)
Initial 2-drug combination
therapy
1 2 3 4
ASCOT-BPLA (136.9 mmHg)
ALLHAT (138 mmHg)
IDNT (138 mmHg)
RENAAL (141 mmHg)
UKPDS (144 mmHg)
ABCD (132 mmHg)
MDRD (132 mmHg)
HOT (138 mmHg)
AASK (128 mmHg)
Trial (SBP
achieved)

1. Pitt et al. Circulation 2000;102:1503–10; 2. Nissen et al. JAMA 2004;292:2217–26; 3. Dahlof et al. Lancet
2005;366:895–906; 4. Williams et al. Circulation 2006;113:1213–25; 5. Leenen et al. Hypertension 2006;48:374–84
Amlodipine: Wealth of CV Outcomes Data
PREVENT1
825 CAD patients (≥30%): Multicentre, randomised,
placebo controlled
Primary outcome: No difference in mean 3 yr coronary angiographic changes
vs. placebo
35%  hospitalisation for heart failure + angina
43%  coronary revascularisation procedures
CAMELOT2
1,991 CAD patients (>20% stenosis by coronary
angiography): Double-blind, randomised study vs.
placebo and enalapril 20 mg
Primary outcome: 31%  in CV events vs. placebo
(P = 0.003)
42%  hospitalisation for angina (P = 0.002)
27%  coronary revascularisation (P = 0.03)
ASCOT-BPLA/CAFE3,4
19,257 HTN patients: Multicentre, randomised,
prospective study vs. atenolol
Primary outcome: 10%  in non-fatal MI & fatal CHD (NS*)
16%  total CV events and procedures (P< 0·0001)
30%  new-onset diabetes (P< 0·0001)
23%  fatal & non-fatal stroke (P= 0·0003)
11%  all-cause mortality (P= 0·0247)
 central aortic systolic blood pressure by
4.3 mmHg (P< 0.0001)
ALLHAT5
18,102 HTN patients: Randomized, prospective study vs.
lisinopril
Primary outcome: No difference in composite of fatal CHD
+ non-fatal MI vs. lisinopril
6%  combined CVD (P = 0.047)
23%  stroke (P = 0.003)
*NS: NOT SIGNIFICANT

Accomplish is the name of the
trial which saw the australian
guidelines recommend
 Therapy when the drug used in the trial
is not available in Australia
 ARB use with CCB, when no ARBs
where used in the trial
 All of the above
 other

Combination therapies….50-75%
will need 2+ agents for control
 ACE/ARB + CCB……..diabetes/lipid abnormalities
 ACE/ARB + diuretic…..congestive cardiac
failure/cerebrovascular disease
 ACE/ARB + betablocker…post myocardial infarction/congestive
cardiac failure
 Betablocker + dihydropyridine CCB…coronary heart disease
 Thiazide plus dihydropyridine CCB…..isolated systolic
hypertension

Specific side effect patterns
 Constipation…….CCB especially Verapamil
 Cough……….ACE inhibitors
 Dyspnoea……Betablockers
 Hyperglycaemia..thiazides
 Hyperkalemia…..ACE inhibitor/ARB
 Erectile dysfunction…thiazides/beta blockers
 Oedema……..CCB
 Postural hypotension..all except b.blockers

Hypertension in preganacy
 Women planning pregnancy. Consider using either
betablockers in particular labetalol/oxprenolol, or
methyldopa,or clonidine
 Hydrallazine second line agent
 ACE/ARB/diuretics contraindicated
 CCB contraindicated in first half pregnancy

Managing other CV risk
factors
 Consider antiplatelet therapy with aspirin if stable
 Evidence for lipid lowering in HT shown to reduce CV
events and stroke

Nonresponsive hypertension
 If BP remains elevated despite maximal doses of at least two
appropriate agents, reassess for:
 • non-adherence
 • undiagnosed secondary hypertension
 • hypertensive effects of other drugs
 • treatment resistance due to sleep apnoea
 • undisclosed use of alcohol or recreational drugs
 • unrecognised high salt intake (particularly in patients taking ACE
inhibitors or angiotensin II
 receptor antagonists)
 • ‘white coat’ hypertension
 • technical factors affecting measurement
 • volume overload, especially with chronic kidney disease (CKD).

SYMPLICITY TRIAL
 Renal sympathetic denervation in patients with treatment-resistant hypertension (The Symplicity HTN-2
Trial): a randomised controlled trial
 Symplicity HTN-2 Investigators‡
 Summary
 Background
 Activation of renal sympathetic nerves is key to pathogenesis of essential hypertension. We aimed to assess effectiveness and
safety of catheter-based renal denervation for reduction of blood pressure in patients with treatment-resistant hypertension.
 Methods
 In this multicentre, prospective, randomised trial, patients who had a baseline systolic blood pressure of 160 mm Hg or more
(≥150 mm Hg for patients with type 2 diabetes), despite taking three or more antihypertensive drugs, were randomly allocated in
a one-to-one ratio to undergo renal denervation with previous treatment or to maintain previous treatment alone (control group) at
24 participating centres. Randomisation was done with sealed envelopes. Data analysers were not masked to treatment
assignment. The primary effectiveness endpoint was change in seated office-based measurement of systolic blood pressure at 6
months. Primary analysis included all patients remaining in follow-up at 6 months. This trial is registered with ClinicalTrials.gov,
number NCT00888433.
 Findings
 106 (56%) of 190 patients screened for eligibility were randomly allocated to renal denervation (n=52) or control (n=54) groups
between June 9, 2009, and Jan 15, 2010. 49 (94%) of 52 patients who underwent renal denervation and 51 (94%) of 54 controls
were assessed for the primary endpoint at 6 months. Office-based blood pressure measurements in the renal denervation group
reduced by 32/12 mm Hg (SD 23/11, baseline of 178/96 mm Hg, p<0·0001), whereas they did not differ from baseline in the
control group (change of 1/0 mm Hg [21/10], baseline of 178/97 mm Hg, p=0·77 systolic and p=0·83 diastolic). Between-group
differences in blood pressure at 6 months were 33/11 mm Hg (p<0·0001). At 6 months, 41 (84%) of 49 patients who
underwent renal denervation had a reduction in systolic blood pressure of 10 mm Hg or more, compared with 18 (35%) of 51
controls (p<0·0001). We noted no serious procedure-related or device-related complications and occurrence of adverse events
did not differ between groups; one patient who had renal denervation had possible progression of an underlying atherosclerotic
lesion, but required no treatment.
 Interpretation
 Catheter-based renal denervation can safely be used to substantially reduce blood pressure in treatment-resistant hypertensive
patients.
Lancet Published Online: 17 November 2010

CAROTID BARORECEPTOR
STIMULATION

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