Brian Rayner, Division of Nephrology and Hypertension, University of Cape Town

THE ART OF TREATING HYPERTENSION

www.strokeandhypertension2014.co.za

Lewington et al. Lancet 2002;360:1903–13

Cardiovascular Mortality Risk Doubles with Each

20/10 mmHg Increment in Systolic/Diastolic BP*

Cardiovascular mortality risk

0

2

4

8

115/75 135/85 155/95 175/105

6

Systolic BP/Diastolic BP (mmHg)

*Individuals aged 40–69 years

2X

risk

4X

risk

8X

risk

1X risk

BENEFITS OF LOWERING BP

(12/6 mmHg)

• Stroke ↓ 35-40%

• MI ↓ 20-25%

• CCF ↓ 50%

• Stage 1 with 1 risk factor, SBP ↓ 12 mmHg

for 10 years prevents 1 death for 11 treated

• Stage 1 plus TOD – only 9 patients

Treatment status of hypertensive South African women (BP≥140/90mmHg) in 1998

SADHS

Steyn et al 2001, Chronic Diseases of

Lifestyle Unit, MRC

Deaths attributable to high blood pressure in males, South Africa 2000

0

1000

2000

3000

4000

5000

6000

7000

30 - 44 45 - 49 60 - 69 70 - 79 80+

Stroke Hypertensive disease Ischaemic heart disease other cardiovascular

Norman et al. 2007 BOD at the MRC

CLINICAL PATHWAY

Evaluation of patient

Appropriate Treatment

BP at goal 65%

BP not at goal

Office hpt

Inadequate treatment

Non-adherence

TRUE RESISTANCE ?

Patient, Funder

or MD failure

Lifestyle

Interfering drugs

Secondary causes Inappropriate

formularies

No fixed drug combinations

Side effects or contraindications to drugs

EXPERIENCE/MADNESS

• Experience is doing the same things over

and over again with increasing confidence

• Madness is doing the same things over and

over again anticipating a different outcome

• Everything should be made as simple as

possible, but not simpler. Einstein

Wendy Hoy

NEW DEFINITION AND

CLASSIFICATION OF HYPERTENSION

• “Hypertension is a progressive cardiovascular syndrome arising from complex and interrelated aetiologies. Early markers of the syndrome are often present before blood pressure elevation is observed; therefore, hypertension cannot be classified solely by discrete blood pressure thresholds. Progression is strongly associated with functional and structural cardiac and vascular abnormalities that damage the heart, kidneys, brain, vasculature, and other organs, and lead to premature morbidity and death”

Giles et al, Hypertension Writing Group, J Clin Hypertens, 2005

DEFINITION OF HYPERTENSION

• Abolish term hypertension, treat overall

CVS risk (Jackson 2005)

• There is no division between normal and

high BP (Pickering, 1972)

• Operational definition – the level (of BP) at

which benefits of action exceed inaction

(Rose 1980)

Kaplan’s Clinical Hypertension 2006

DEFINITION OF

HYPERTENSION (>18 years)

Blood pressure, mm Hg

Category Systolic Diastolic

Optimal <120 and <80

Normal <130 and <85

High-normal 130 - 139 or 85 - 89

Hypertension

Stage 1 140 - 159 or 90 - 99

Stage 2 160 - 179 or 100 - 109

Stage 3 180 or 110

DEFINITIONS OF BLOOD PRESSURE

• Conventional office based measurements

(incorrect measurement, bias, faulty equipment,

variability around mean)

• White coating

• Masking

• Self or home

• 24 Hour ABPM - non-dipping, reverse dipping,

variability or extreme dipping

• Central aortic BP

Arterial Pulse WaveformWhat is it?

Arterial Pulse WaveformWhat is it?

Superiority of ambulatory (nocturnal) BP

for predicting cardiovascular death

Conventional

office BP

Daytime BP

24-hour BP

Nocturnal BP

Systolic BP (mm Hg)

Adju

sted

5-Y

ear

Ris

k o

f

CV

Dea

th (

%)

3.5

3.0

2.5

2.0

1.5

1.0

0.5

90 110 130 150 170 190 210 230

N=5292

Dolan E, et al. Hypertension. 2005;46:156-161.

Mx of Diabetes

Patient 1 2 3

0 month 10.5 27 8.5

1 month 6.8 28 3.1

3 months 12.8 12.5

6 months 7.5 6.8

12 months 15.5 14.5

1. Fasting, pre or post prandial

2. HBA1C

3. 8 or 4 point profiles

WHITE COAT OR OFFICE HYPERTENSION

24-h blood pressure profile in two patientswith hypertension (dipper and non-dipper)

Blood pressure (mm Hg)

7:00 11:00 15:00 19:00 23:00 3:00 7:00

Sleep

Dipper

Non-dipper

Time of day

175

135

115

95

75

55

155

Redman et al, 1976; Mancia et al, 1983; Kobrin et al, 1984; Baumgart et al, 1989; Imai et al, 1990; Portaluppi et al, 1991

Reverse Dipper

Think of sleep apnoea

Extreme Dipper

Copyright ©2001 American Heart Association

Kario, K. et al. Hypertension 2001;38:852-857

Prevalence of SCIs: shaded area indicates 1 SCI detected by brain MRI per person; solid area, multiple SCIs (defined as &gt;=2 SCIs per person)

Odds ratios (95% confidence intervals [CI]) for cognitive decline associated with the

combination of home systolic blood pressure (BP) value and the SD of the home systolic BP,

after adjusting for sex, age, history of cardiovascular disease, low level of education, baseline

Mini-Mental State Examination (MMSE) score <27, and follow-up duration.

Matsumoto A et al. Hypertension. 2014;63:1333-1338

Copyright © American Heart Association, Inc. All rights reserved.

Mechanistic relationship between increased blood pressure variability and cognitive decline.

Palatini P Hypertension. 2014;63:1163-1165

Copyright © American Heart Association, Inc. All rights reserved.

STROKE

Classical stroke – lenticulostriate artery involving

internal capsule (ischaemic (lacunar)/haemorrhagic)

SCI, cerebral WML, atrophy

MRI of a Practicing Dentist

Presenting with a Facial Palsy

• MRI – bilateral lacunar infarcts in internal

capsule, diffuse cerebral and cerebellar

atrophy due to microvascular changes

• REMEMBER A THIN HYPERTENSIVE

IS A DANGEROUS HYPERTENSIVE

Alzheimer’s and Risk

• ApoEe4 polymorphism

• Hypercholesterolaemia

• Hypertension

• Hyperhomocystinaemia

• Diabetes

• Metabolic S

• Smoking

• Inflammation

• Fat intake and obesity

Casserly I, et al, Lancet 2004

WHITE COAT AND MASKED

HYPERTENSION

White coat or office Masked

↑ BP in office Normal BP in office

Normal BP at home ↑ BP at home

?Regression to mean ?progression to mean

? Pre-hypertensive state ?BP bias, method of

measurement

Incidence of cardiovascular events according to the cross-classification of subjects by

conventional and daytime ambulatory blood pressure in normotensives and in persons with

solated systolic hypertension (ISH) presenting with white-coat hypertension, mask...

Franklin S S et al. Hypertension 2012;59:564-571

Copyright © American Heart Association

RECOGNITION OF MASKING

• Normal office BP but patient has significant

TOD or TOD that is not resolving

• Higher out of office BP readings

• Treatment must be based on self, automated

or ambulatory BP monitoring

Office Self Ambulatory

Predicts outcome + ++ +++

Initial diagnosis Yes Yes Yes

Cut-off BP

(mmHg)

140/90 135/85 Mean day135/85

Mean night 120/70

Evaluation of

treatment

+ ++ +++

Assess diurnal

variation

No No Yes

Limitations No of

readings

Patient bias Expense, inconvenience

Office Automated

office

Self Ambulatory

Predicts

outcome

+ ++ ++ +++

Initial

diagnosis

Yes Yes Yes Yes

Cut-off BP

(mmHg)

140/90 Mean 135/85 135/85 Mean day135/85

Mean night

120/70

Evaluation of

treatment

+ ++ ++ +++

Assess diurnal

variation

No No No Yes

Limitation No of

readings

Does not

completely

eliminate WC

Bias Expense,

inconvenience

Figure 1

FIGURE 1. Proposal for incorporating

automated office blood pressure (mmHg)

into an algorithm for diagnosis of

hypertension using automated

sphygmomanometers.

Copyright © 2012 Journal of Hypertension. Published by Lippincott Williams & Wilkins. 34

The great myth of office blood pressure

measurement

Myers, Martin G.

Journal of Hypertension. 30(10):1894-1898,

October 2012.

doi: 10.1097/HJH.0b013e3283577b05

Systolic Pressures (mean + 95% CI)

Average after 1st year: 133.5 Standard vs. 119.3 Intensive, Delta = 14.2

Mean # Meds

Intensive: 3.2 3.4 3.5 3.4

Standard: 1.9 2.1 2.2 2.3

Figure 4. Incidence of primary outcome (bar graphs) and HR (line graphs; adjusted for

baseline conditions, without propensity score analysis) as a function of SBP and DBP in

patients with and without previous revascularization.

Denardo S J et al. Hypertension 2009;53:624-630

Copyright © American Heart Association

HYPERTENSIVE SMALL VESSEL

DISEASE (kidney, brain, eye)

Sites of auto-regulation

Also eye and brain

Causes • Severe HT

• DM

• Stiff arteries

HYPERTENSIVE EMERGENCY

• Elevation of BP associated with acute and on going organ

damage to kidneys, brain, heart, eyes or vascular system.

•Requires rapid (within minutes to a few hours) lowering of

BP to safe levels.

•Treatment: Hospitalisation in an intensive care unit.

Intravenous antihypertensive therapy – labetalol,

nitroglycerin, nitroprusside

•25% lowering immediately, avoid excessive drops, target

160/100 in first 24 hours, no SL adalat

•Avoid ACEi initially especially if Na < 130

SA Hpt Guidelines, SAMJ 2006

BP > 120-130 diastolic

Renal failure

Dipsticks – protein and blood,

Improves with treatment

LOSS OF AUTOREGULATION

• Endothelial injury

• Increased vascular permeability

• Cell proliferation

• Activation of platelets and coagulation

• Vascular damage, volume depletion and tissue ischaemia

• Activation of RAAS – low K+ often hallmark of malignant hypertension

• Vicious cycle

STROKE

Classical stroke – lenticulostriate artery involving

internal capsule (ischaemic (lacunar)/haemorrhagic)

SCI, cerebral WML, atrophy

HYPERTENSIVE NEPHROSCLEROSIS

Raised creatinine, normal/small echogenic kidneys on U/S,

dipsticks – trace to 1+ protein

Remember NSAIDs

LEFT VENTRICULAR HYPERTROPHY

S4

Pressure overloaded

apex beat

ECG

Echo

>35 – Sokolow-Lyon)

Cornell – (S in V3 + R in aVL + 6 in females) x QRS duration > 2440

Harbinger of death

R in AvL > 11

ECG criteria for LVH

– Sokolow-Lyons >35mm (V1 = V5 or V6)

– R in aVL > 11 mm

– Cornel > 2440 (mm.ms) (S in V3 + R in AvL + 6 in

females) x QRS duration

– LA enlargement = diastolic dysfunction

ESC 2013

MYOCARDIAL INFARCTION

AORTIC ANEURYSM

1. Silver wiring

2. Av nipping

3. Hx and exudates

4. Papilloedema

LIFESTYLE MODIFICATION

Modification Recommendation Approx ↓ BP

Weight ↓ BMI 18.5 – 24.9 5-20 per 10 kg

Dash diet ↓ saturated fat and total fat, ↑

fruit and vegetables

8-14

Dietary Na+ <100 mmols or 6 gm

NaCl/day

2-8

Physical activity Brisk walking for 30 minutes

per day most days

4-9

Moderation of

alcohol

No more than 2 drinks per

day, 1 for female and small

male

2-4

Hypertension Guideline 2011

NO SMOKING!

SALT INTAKE

100 mmols = 6 gm NaCl, measure 24 hour urine

60-70% is non-discretionary

CONCLUSIONS

• Hypertension is a complex disorder

requiring a rigorous approach to treatment

• Out of office BP measurement is changing

the landscape of treatment

• Hypertension is also a small vessel disease

and auto-regulation is critically important

• Large vessel stiffening is very important in

the elderly and complicates treatment