147 The number of different anti-

hypertensives in Mims

3 The number of guidelines applicable

to Hypertension with largely dissimilar recommendations

Australian GuidelinesEvidence 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 ASSOCIATEDWITH 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 disease8 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 hypertension 2008; Available at: www.heartfoundation.org.au. Accessed: January 2009.117:e25-146; 4.Segura J, et al. Curr Opin Nephrol Hypertens 2004;13:495-500; 5. Volpe M. Int J Clin Pract 2008;62:97-108; 6. El-Atat F, et al. Curr Hypertens Rep 2004;6:215-23; 7.Selvin E, Erlinger TP. Circulation. 2004;110:738-43.

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

0.0Children 0-14

yearsChildren 15-17

years18-64 years 65-75 years 75 years and

over

0.1 0.1

9.1

38.041.0

Pre

vale

nce

of H

yper

tens

ion

(%)*

Classification of BP in Australian National Heart Foundation GuidelinesDiagnostic 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.

Cerebrovascular disease

Cardiovascular Mortality Risk Doubles with each 20/10 mmHg Increase in Usual Systolic/Diastolic BP*

Systolic BP/Diastolic BP (mmHg)

Ris

k of

dea

th f

rom

IH

D a

nd o

ther

va

scu

lar

caus

es (

excl

udin

g st

roke

)*

8

6

4

2

0115/75 135/85 175/105

1X risk 2X risk4X risk

8X risk

155/95

*Individuals aged 40–69 years Adapted from Lewington et al. Lancet 2002;360:1903–13

TREATMENT TARGETS

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 National Heart Foundation of Australia. Guide to management of Hypertension, 2008.

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 Buonarotti3 The wrath of God Leonardo da Vinci4 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 PRESSUREACCURATELY 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.

Left subclavian stenosis

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

PANADOL RAISES BP

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 factorsDetect end organ damage eg

CCF,CAD,PVDDetect 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)

Echocardiography

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

Renal artery stenosis

Renal artery stenting

Sleep apnoea testing

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 adultsAssess 5-year absolute cardiovascular risk (Figure 1)*

SBP < 140 mmHgDBP < 90 mmHgContinue monitoring‡

Start drug treatment immediately(See Figure 3: Initiating drug treatment)• Lifestyle modification• Manage associated conditions†

• Lifestyle modification• Monitor BP

Reassess 5-year absolute cardiovascular risk in 3–6 months

• Lifestyle modification• Monitor BP

Reassess 5-year absolute cardiovascular risk in 6–12 months

Start drug treatment immediately(See Figure 3: Initiating drug treatment)• Lifestyle modification• Manage associated conditions†

SBP 140–150 mmHgDBP < 90 mmHgContinue monitoring‡

SBP ≥ 140 mmHgDBP ≥ 90 mmHg

SBP ≥ 150 mmHgDBP ≥ 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)

SALT RESTRICTION

How many patients have you had that have a good therapeutic response to a low salt diet

0 1 2-4 >5

DASH DIET

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

DASH PYRAMID

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

Treatment decision making

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

If target BP not reachedACE inhibitor or angiotensin II receptor antagonist

+ calcium channel blocker + low-dose thiazide diuretic

If target BP not reachedConsider seeking specialist advice

NHF: Initiating Antihypertensive Therapy

First ChoiceACE inhibitor or angiotensin II receptor antagonist

ORCalcium channel blocker

ORLow-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

National Heart Foundation of Australia. Guide to management of Hypertension, 2008.

*Lower doses generally used in fixed-dose combinations+ = potential advantage*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 4158%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;328:914212. Bakris et al. Am J Kidney Dis 2000;36:646613. Milani. Am J Manag Care 2005;11:S2207

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 thatare additive2

Multiple-mechanism therapy results in a greater BP reduction than seen with its single-mechanism components alone1,2

1. Sica. Drugs 2002;62:443622. Quan et al. Am J Cardiovasc Drugs 2006;6:10313

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

therapy1 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)

Dynamic duos

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 + angina43% 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. lisinopril6% 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

Side effects

Side effects

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

Pregnancy and hypertension

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).

Renal denervation

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

BARORECEPTOR STIMULATION

You be the judge!