HYPERTENSION: WHEN TO TREAT
& WHEN TO REFER
Dr Charles Knight, Consultant Cardiologist
BMI The London Independent Hospital
Barts and the London NHS Trust
Why is hypertension important?
 Diagnosis- ABPM, screening tests for primary
causes / essential BP / secondary
 Lifestyle modification
 Medical therapy
v
 Renal Denervation
Untreated hypertension
51 yrs- 136/78
54 yrs- 162/98
59 yrs- 188/105
v
62 yrs- 226/118 short of breath at rest and LV strain
BP at death aged 63 - 300/190
Roosevelt’s blood pressure (Breunn)
Messerli NEJM 1945
v
Hypertension
• Major risk factor for stroke, myocardial
infarction, heart failure, chronic kidney disease,
cognitive decline and premature death.
• Untreated hypertension can cause vascular
and renal damage leading
to a treatmentv
resistant state.
v
Normal Wall thickness
Thickened heart muscle
LVH
Hypertension
 One billion hypertensives worldwide
 BP important in 50% of 17.5m deaths
 4.5% of global disease burden
 In the U.K. ~25% of all adults are hypertensive;
v
 Hypertension is 12% of consultations
in primary care
 2 mm Hg increase in BP = 7% increase in CHD risk
and 10% increase in stroke
 Treatment ~£1billion P/A in drug costs alone.
UK Epidemiology
 Hypertension is common in the UK population.
 Prevalence influenced by age and lifestyle
factors.
 At least 25% of the adult population in the UK
have hypertension.
v
 50% of those over 60 years have hypertension.
 With an ageing population, the prevalence of
hypertension and requirement for treatment will
continue to increase.
CV Mortality Risk
Cardiovascular Mortality Risk Doubles With
Each 20/10 mm Hg Increase in BP*
CV = cardiovascular
SBP – systolic blood pressure
DBP = diastolic blood pressure
* In individuals aged 40 to 69 years (10-year study period
starting at BP 115/75 mm Hg.
SOURCE: Lewington S, et al. Lancet. 2002;360:1903-1913.
v
SBP/DBP,mm Hg
CVD death rate
(per 10,000 person-year)
‘Double jeopardy’: type 2 diabetes and hypertension
and cardiovascular risk
SOURCE: Afbeelding 3 van 32, PACE
v
Systolic blood pressure
(mmHg)
Blood Pressure, mmHg
Other CVRF,
TOL, of
established
disease
Normal SBP
120-129 or DBP
80-84
Normal – High
SBP 130-139 or
DBP 85-89
Grade 1 HT SBP
140-159 or DBP
90-99
Grade 2 HT SBP
160-179 or DBP
100-109
Grade 2 HT
SBP≥180 or
DBP≥110
No Other CVRF
Medium Risk
Medium Risk
Low Added Risk
Moderate Added
Risk
High Added Risk
1-2 CVRF
Low Added Risk
Low Added Risk
Moderate Added
Risk
Moderate Added
Risk
Very High Added
Risk
High Added Risk
High Added Risk
Very High Added
Risk
Very High Added
Risk
Very High Added
Risk
Very High Added
Risk
3 or More CVRF,
TOL, Diabetes
or Metabolic
Syndrome
Moderate Added
Risk
High Added Risk
Established
Cardiovascular
or Renal Disease
Very High Added
Risk
Very High Added
Risk
v
Why is hypertension important?
 Diagnosis- ABPM, screening tests for primary causes
/ essential BP / secondary
 Lifestyle modification
 Medical therapy
v
 Renal Denervation
v
v
v
Secondary hypertension
• Consider particularly if:
–
–
–
–
Young
No FH hypertension
Severe HT
Unresponsive to treatment
• Tests
–
–
–
–
Renal ultrasound
v
Echo
24 hour urinary catecholamines
MR imaging
v
v
Diagnosis (1)
If clinic BP is 140/90 mmHg or higher, offer
ambulatory blood pressure monitoring (ABPM)
to confirm the diagnosis of hypertension.
v
Diagnosis (2)
When using the following to confirm diagnosis, ensure:
ABPM:
– at least two measurements per hour during the person’s
usual waking hours (usually 14/day).
HBPM:
– two consecutive seated measurements,
1 minute apart
v
– BP is recorded twice a day for at least 4 days and
preferably for 7 days
– measurements on the first day are discarded –
average value of all remaining is used.
Definitions
Stage 1 hypertension:
• Clinic blood pressure (BP) is 140/90 mmHg or
higher and
• ABPM or HBPM average is 135/85 mmHg or higher.
Stage 2 hypertension:
• Clinic BP 160/100 mmHg is or higher and
• ABPM or HBPM daytime average
is 150/95 mmHg
v
or higher.
Severe hypertension:
• Clinic BP is 180 mmHg or higher or
• Clinic diastolic BP is 110 mmHg or higher.
Assessing cardiovascular risk and target organ
damage
Updated recommendations:
– Estimation of CV risk to discuss prognosis and healthcare
options with people with hypertension.
– For all with hypertension offer to:
– test urine for presence ofv protein
– take blood to measure glucose, electrolytes, creatinine,
estimated glomerular filtration rate and cholesterol
– examine fundi for hypertensive retinopathy
– arrange a 12-lead ECG.
Why is hypertension important?
 Diagnosis- ABPM, screening tests for primary causes
/ essential BP / secondary
 Lifestyle modification
 Medical therapy
v
 Renal Denervation
v
SOURCE: Analysis by London Health Observatory using Office for National Statistics data. Diagram produced by Department of
Health. Parliamentary copyright images are reproduced with the permission of Parliament.
Lifestyle and adherence
Lifestyle interventions
– Offer guidance and advice about:
– diet (reduce sodium and caffeine intake), weight reduction and
exercise
– alcohol consumption
– smoking.
v
Patient education and adherence
– Provide:
– information about benefits of drugs and side effects
– details of patient organisations
– an annual review of care.
CBPM ≥140/90 mmHg
& ABPM/HBPM
≥ 135/85 mmHg
CBPM ≥160/100 mmHg
& ABPM/HBPM
≥ 150/95 mmHg
Stage 1 hypertension
Stage 2 hypertension
If target organ damage present or
10-year cardiovascular risk > 20%
If younger than 40 years
Offer antihypertensive
drug treatment
Consider specialist
referral
v
Offer lifestyle interventions
Offer patient education and interventions to support adherence to treatment
Offer annual review of care to monitor blood pressure, provide support and
discuss lifestyle, symptoms and medication
Why is hypertension important?
 Diagnosis- ABPM, screening tests for primary causes
/ essential BP / secondary
 Lifestyle modification
 Medical therapy
v
 Renal Denervation
Treatment of hypertension
19 million with hypertension in UK (2.6 million with CAD)
500 per GP surgery (70 with CAD)
v
Aged under
55 years
Aged over 55 years
or black person of
African or Caribbean
family origin of any
age
C*
A
Step 1
A + C*
Step 2
A+C+D
v
Step 3
Resistant hypertension
Step 4
A + C + D + consider further diuretic
or alpha- or beta-blocker
Consider seeking expert advice
Summary of
antihypertensive
drug treatment
Key
A – ACE inhibitor or low-cost
angiotensin II receptor
blocker (ARB)1
C – Calcium-channel
blocker (CCB)
*D – Thiazide-like diuretic
First Line Antihypertensives
ARB’s
Thiazide diuretics
Calcium antagonists
ACE Inhibitors
v
Second Line Antihypertensives
Alpha blockers
Beta blockers
v
Monitoring drug treatment (1)
Use clinic blood pressure measurements to
monitor response to treatment.
Aim for target blood pressure below:
– 140/90 mmHg in people
aged under 80
v
– 150/90 mmHg in people aged 80 and over
Monitoring drug treatment (2)
For people with a ‘white-coat effect’ consider ABPM or
HBPM as an adjunct to clinic BP to monitor response to
treatment.
Aim for ABPM/HBPM target average of:
 below 135/85 mmHg in people aged under 80
v
 below 145/85 mmHg in people
aged 80 and over.
White-coat effect: a discrepancy of more than 20/10 mmHg between
clinic and average daytime ABPM or average HBPM blood pressure
measurements at the time of diagnosis.
BP still high…





Measurement correct?
Compliance?
Weight loss/salt reduction
Untreated secondary cause?
Stop drugs that raise BP
 NSAI
 Cocaine
 Alcohol
v
Step 4: - Resistant Hypertension
 Step 4 is patients >140/90 on at least 3
medicines (steps 1-3) and still hypertensive
 Spironolactone 25 mg can be considered for
patients with K less than 4.5 mMol/L and eGFR
>45
v
 Or more thiazide diuretics
 alpha blockers and betablockers
Consider Specialist Referral…
Why is hypertension important?
 Diagnosis- ABPM, screening tests for primary causes
/ essential BP / secondary
 Lifestyle modification
 Medical therapy
v
 Renal Denervation
Percutaneous Renal Denervation
SOURCE: Frontiers in Physiology and Professor Markus Schlaich MD, Nephrologist & Hypertension Specialist Adjunct Professor, Central Clinical SchoolFaculty of Medicine, Nursing & Health
Sciences, Monash University. Reproduced with permission.
v
• Standard interventional technique
• 4-6 two-minute treatments per artery
• Proprietary RF Generator
− Automated
− Low-power
− Built-in safety algorithms
37
Symplicity HTN-1
Initial Cohort – Reported in the Lancet, 2009:
-First-in-man, non-randomized
-Cohort of 45 patients with resistant HTN (SBP ≥160 mmHg on ≥3 antiHTN drugs, including a diuretic; eGFR ≥ 45 mL/min)
- 12-month data
\
Expanded Cohort – This Report (Symplicity HTN-1):
-Expanded cohort of patients (n=153)
v
-24 and 36 -month follow-up
Symplicity HTN-1 Investigators. Hypertension. 2011;57:911-917.
Sobotka P, ACC 2012
Change in Office BP Through 36 Months
0
-5
-10
-9
-10
-10
BP change
(mmHg)
-12
-13
-15
-15
-20
-14
-19
-19
-21
-25
v
-22
-26
Systolic BP
-26
Diastolic BP
-30
P<0.01 for ∆ from BL
for all time points
-35
1M
(n=143)
3M
(n=148)
6M
(n=144)
-33
12 M
(n=130)
Sobotka P, ACC 2012
18 M
(n=107)
24 M
(n=59)
-33
30 M
(n=24)
-33
36 M
(n=24)
Chronic Safety Out to 3 Years





One progression of a pre-existing stenosis unrelated to
RF treatment (stented without further sequelae)
One new moderate stenosis which was not
hemodynamically relevant and no treatment
3 deaths within the follow-up period; all unrelated to the
device or therapy
v required hospitalization
No hypotensive events that
There were no observed changes in mean electrolytes
or mean eGFR to 18 months
Symplicity HTN-1 Investigators. Hypertension. 2011;57:911-917.
Sobotka P, ACC 2012
Symplicity HTN-2
Lancet. 2010;376:1903-1909.
• Purpose: To demonstrate the effectiveness of catheter-based renal
denervation for reducing blood pressure in patients with uncontrolled
v
hypertension in a prospective, randomized,
controlled, clinical trial
• Patients: 106 patients randomized 1:1 to treatment with renal
denervation vs. control
• Clinical Sites: 24 centers in Europe, Australia, & New Zealand
(67% were designated hypertension centers of excellence)
Symplicity HTN-2 Investigators. Lancet. 2010;376:1903-1909.
Symplicity HTN-2 Trial
• Treatment-resistant
HTN population
• BL OBP 178/97 mmHg
• 49 RDN, 51 Control
• Age 58 years
• BMI 31 kg/m²
• 40% with Diabetes
• eGFR 77*
• Mean no of drugs 5.2
• RDN and Control groups
generally well-matched
*MDRD, ml/min/1.73m2
Symplicity HTN-2 Investigators. Lancet. 2010;376:1903-1909.
Inclusion Criteria:
– Office SBP ≥ 160 mmHg (≥ 150 mmHg with
type II diabetes mellitus)
– Stable drug regimen of 3+ more anti-HTN
medications
– Age 18-85 years
Exclusion Criteria:
– Hemodynamically or anatomically
significant renal artery abnormalities or prior
v renal artery intervention
– eGFR < 45 mL/min/1.73m2 (MDRD
formula)
– Type 1 diabetes mellitus
– Contraindication to MRI
– Stenotic valvular heart disease for which
reduction of BP would be hazardous
– MI, unstable angina, or CVA in the prior 6
months
Procedural Safety
RDN Group (n=52)
• No serious device or procedure related adverse events
• Minor adverse events (n-5)
• 6-month renal imaging (n=43)
• No vascular abnormality at any RF treatment site
• 1 MRA indicates possible progression of a pre-existing stenosis unrelated
to RF treatment (no further therapy warranted)
v
One renal artery dissection following injection of contrast through the guide
catheter during angiography. The lesion was stented without further
consequence
One hospitalization prolonged in a crossover patient due to hypotension
following the RDN procedure. IV fluids administered, anti-hypertensive
medications decreased and patient discharge without further incident
Cross Over Group (n-35)
•
•
Esler M, ACC 2012
Symplicity HTN-2: Primary Endpoint
and Latest Follow-up
Primary Endpoint
(6M post Randomisation)
Latest Follow-up
(12M post Randomisation)
10
RDN (n= 47)
0
∆ from
Baseline
to
6 Months
(mmHg)
Systolic Diastolic
Diastolic
Systolic
p <0.01 for
difference
between RDN
and Control
v
Primary Endpoint:
•84% of RDN patients had ≥10 mmHg
reduction in SBP
•10% of RDN patients had no reduction in SBP
-10
∆ from
Baseline
-20
to
12 Months
-30
(mmHg)
-10
-28 Diastolic
-40
-50
Systolic
p <0.01 for 
from baseline
Latest Follow-up:
•Control crossover (n = 35): -24/-8 mmHg
(Analysis on patients with SBP ≥ 160
mmHg at 6 M)
Expanded results presented at the American College of Cardiology Annual Meeting 2012 (Esler, M.)
SYMPLICITY HTN-3
 Larger trial against sham procedure in US
 535 patients
 Did not meet primary endpoint
 Fall in office BP at 6/12
 Met safety endpoints
 Details not yet available
v
Scott’s parabola – the rise and fall of a surgical
technique
Standard treatment
Strong media pressure
for universal acceptance
Promising Idea
Encouraging
reports
“Of possible value but
only as a research tool”
General
introduction
Doubts
creep in
Damaging survey reported
Condemned by several authorities
Widespread
enthusiasm
v
Widely publicised
medicolegal case
Used only in highly
specialised circumstances
SOURCE: J W Scott consultant gynaecologist, Poole Hospital NHS Trust, Poole, Dorset.
Falls into disuse
Very old surgeons amaze
their juniors with rollicking
stories of the old days
Operating theatre staff ponder
possible uses for large quantities
of expensive, obsolete equipment
Pre - FLO2w Procedure
Post - FLO2w Procedure
v
ROX Preliminary results
v
Conclusions (1)




Hypertension a huge global health problem
Mostly primary hypertension
ABPM key in diagnosis
Lifestyle measures very important
 Treat all the patient’s Cv risks
 Medication usually controls
without significant
v
side effects
 But many patients not treated/undertreated
 New technologies becoming available for
resistant hypertension
Conclusions (2)
 Vast majority of hypertensives treated easily in
primary care
 Referral for






BP not controlled on 2/3 drugs
Multiple drug intolerance/poor
compliance
v
Concern about white coat
Concern re secondary causes
Young patients
Consideration of BP interventions (research at present)