HYPERTENSION – THE ABC
Brian Rayner,
Division of Nephrology and
Hypertension, Groote Schuur Hospital,
University of Cape Town
Global Mortality 2000: Impact of Hypertension
and Other Health Risk Factors
Developing region
Developed region
0
1
2
3
4
5
6
7
8
Attributable mortality in millions (total: 55,861,000)
Ezzati et al. Lancet 2002;360:1347–60
Cardiovascular Mortality Risk Doubles with Each
20/10 mmHg Increment in Systolic/Diastolic BP*
Cardiovascular mortality risk
8
8X
risk
The closer to target
the less reliable to office BP becomes
6
Benefit not established
4
Benefit
4X
risk
2
0
1X risk
2X
risk
115/75
135/85
155/95
175/105
Systolic BP/Diastolic BP (mmHg)
*Individuals aged 40–69 years
Lewington et al. Lancet 2002;360:1903–13
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
SA Demographic Survey
Group
Total men
Total women
Black men
Black women
White men
White women
Colored men
Colored women
Asian men
Asian women
Aware % Treated % Controlled %
26
51
20
47
47
63
24
57
37
75
21
36
14
29
43
64
19
48
46
71
10
18
7
15
17
19
7
14
28
5
Steyn K, 2003
CLINICAL PATHWAY
Office hpt
Evaluation of patient
Inadequate treatment
Appropriate Treatment
Non-adherence
BP not at goal
BP at goal 65%
Lifestyle
Patient, Funder
or MD failure
Secondary causes
Interfering drugs
Inappropriate
formularies
No fixed drug combinations
TRUE RESISTANCE ?
Side effects or contraindications to drugs
OUR PERCEPTION OF AVERAGE
HYPERTENSIVE
HYPERTENSION IN SA
• Malignant hypertension in young black men without
obvious risk factors, often complicated by ESRD
• 50% of black patients with ESRD have hypertensive
nephrosclerosis (?APOL1 gene)
• Higher stroke and hypertensive heart disease and less
coronary disease
• In the Heart of Soweto Study, cardiac heart failure
was the most common primary diagnosis, and 68% of
cases were attributable to dilated cardiomyopathy or
hypertensive heart disease, or both
Rayner et al, Nephron Clin Pract 2010
CASE STUDY
• 62 year old professional person (white)
• Slim, active exercise programme, excellent
diet
• Presented to neurologist with Bell’s palsy
• Received steroids and vangancylovir
• Offered to review diagnosis as atypical
features
Further history
• Told he has elevated BP – told to watch it
• Treated for hypertension after hospitalisation
for Bell’s
• Unable to walk for 1 week, recovering
slowly
• Examination:
•
•
•
•
subtle left 7th ? UMN
Subtle cerebellar signs
Pathological increased reflexes bilaterally, plantars ↓
Unable to walk heel to toe
Investigations
• ECG – LVH
• MRI – bilateral lacunar infarcts in internal
capsule, diffuse cerebral and cerebellar
atrophy due to microvascular changes
• BP 180/110, decreased K+
• REMEMBER A THIN HYPERTENSIVE
IS A DANGEROUS HYPERTENSIVE
CLASSIFICATION OF
HYPERTENSION (>18 years)
Blood pressure, mm Hg
Category
Systolic
Diastolic
Optimal
<120
Normal
<130
High-normal 130 - 139
and
and
or
<80
<85
85 - 89
Hypertension
Stage 1
140 - 159
Stage 2
160 - 179
Stage 3
 180
or
or
or
90 - 99
100 - 109
 110
DEFINITIONS OF BLOOD PRESSURE
•
•
•
•
•
Conventional office based measurments
Isolated systolic hypertension
White coat
Masked
Non-dipper, reverse dipper, or extreme
dipper
• Labile hypertension
• Central aortic BP
80
70
88
100
80
Wingfield D, et al QJM 2002
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
Superiority of ambulatory (nocturnal) BP
for predicting cardiovascular death
3.5
Nocturnal BP
3.0
Adjusted 5-Year Risk of
CV Death (%)
24-hour BP
2.5
Daytime BP
2.0
Conventional
office BP
1.5
1.0
N=5292
0.5
90
110
130
150
170
190
210
230
Systolic BP (mm Hg)
Dolan E, et al. Hypertension. 2005;46:156-161.
WHITE COAT OR OFFICE HYPERTENSION
24-h blood pressure profile in two patients
with hypertension (dipper and non-dipper)
Sleep
Blood pressure (mm Hg)
175
Non-dipper
155
135
Dipper
115
95
75
55
7:00
11:00
15:00
19:00
23:00
3:00
7:00
Time of day
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
Extreme Dipper
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)
Kario, K. et al. Hypertension 2001;38:852-857
Copyright ©2001 American Heart Association
Incidence of cardiovascular events in untreated NT, untreated ISH,
untreated WCH, treated NT, and treated ISH subjects with WCH
Franklin S S et al. Hypertension 2012;59:564-571
Copyright © American Heart Association
INDICATION FOR ABPM/SBPM
• Suspected white coat hpt
• Suspected masked hpt
• Refractory hypertension
• High risk hypertensives e.g. elderly, diabetics, IHD
• To improve compliance and assess adverse events(SBPM
only)
• All new hypertensives (NICE guidelines)
Seedat YK, Rayner BL, SA Hpt Guideline, SAMJ, 2011
DIFFERENT METHODS OF BP
MEASUREMENT
CLINIC
HOME
AMBULATORY
Predicts outcome
Yes
Yes
Strongly
Initial diagnosis
Yes
Yes
Yes
Cut-off BP levels
(in mm Hg)
140/90
135/85
120/70 (mean night)
135/85 (mean day)
Evaluation of treatment
Yes
Yes
Limited but valuable
Assess diurnal rhythm
No
No
Yes
N.B. Difference between ABPM and Office widens with increasing BP
Seedat YK, Rayner BL, SA Hpt Guideline, SAMJ, 2011
CAUSES OF ESSENTIAL
HYPERTENSION
• Genetic 40-50%
• environmental - stress, high salt, high
fat, increased refined carbohydrate,
lack of exercise, obesity, alcohol,
smoking
LEFT VENTRICULAR HYPERTROPHY
S4
Pressure overloaded
apex beat
ECG
Echo
Cornel – (S in V3 + R in aVL + 6 in females) x QRS duration > 2440
>=38 – Sokolow-Lyon)
Harbinger of death
MALIGNANT HYPERTENSION
BP > 120-130 diastolic
Renal failure
Dipsticks – protein and blood,
Improves with treatment
HYPERTENSIVE NEPHROSCLEROSIS
Raised creatinine, small kidneys on U/S,
dipsticks – trace to 1+ protein
MYOCARDIAL INFARCTION
STROKE
Classical stroke – lenticulostriate artery involving
internal capsule (ischaemic (lacunar)/haemorrhagic)
AORTIC ANEURYSM
ROUTINE INVESTIGATIONS
• Dipsticks (renal disease, TOD)
• Creatinine (renal disease, TOD)
• K + (primary aldosteronism, diuretics, secondary
aldosteronism, licorice)
• fasting glucose and lipogram (establish CVS risk, exclude
diabetes)
• (uric acid)
• ECG (LVH, IHD)
• (CXR)
• microalbuminuria (mandatory in diabetics to detect
incipient nephropathy)
PROBABILITY OF CHD EVENT IN MALES
WITH MILD HYPERTENSION
40
35
30
10 year %
25
probability of
event
20
Average risk
15
10
5
0
BP 150-160
TC 6.2-6.77
HDL 0.85-0.89
Diabetes
Smoker
ECH-LVH
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
MAJOR RISK FACTORS, AND
COMPLICATIONS
MAJOR RISK FACTORS
Smoking.
Dyslipidaemia:
ototal cholesterol > 5.1 mmol/L, OR
oLDL > 3 mmol/L, OR
oHDL men < 1 and women < 1.2
mmol/L.
Diabetes mellitus.
Men > 55 years.
Women > 65 years.
Family history of early onset of CVD:
oMen aged <55 years;
oWomen aged <65 years.
Waist circumference- abdominal obesity:
oMen ≥ 94 cm;
oWomen ≥ 80cm.
TOD
COMPLICATIONS
LVH: based on ECG
oSokolow-Lyons > 38
mm;
oCornel > 2440 mm.ms)
Microalbuminuria:
albumin creatine ratio
3-30 mg/mmol.
Slightly elevated creatinine:
omen 115-133 µmol/L;
owomen 107-124 µmol/L
Coronary heart disease.
Heart failure.
Chronic kidney disease:
oalbuminuria > 30mg/mmol OR
ocreatinine men > 133 µmol/L
ocreatinine women >124
µmol/L
Stroke or TIA.
Peripheral arterial disease.
Advanced retinopathy:
ohaemorrhages OR;
oexudates;
opapilloedema.
Seedat YK, Rayner BL, SA Hpt Guideline, SAMJ, 2011
RISK STRATIFICATION
Normal
High
normal
Grade 1
Grade 2
Grade 3
No risk factors
average
average
Low added
Moderate
added
High added
1-2 risk factors
Low
added
Low
added
Moderate
added
Moderate
added
Very high
added
≥3 risk factors
or TOD or
diabetes or MS
Moderate
added
High
added
High added
High added
Very high
added
Complications
High
added
Very
high
added
Very high
added
Very high
added
Very high
added
Seedat YK, Rayner BL, SA Hpt Guideline, SAMJ, 2011
STRATIFY ACCORDING TO ADDED RISK (as in risk chart Table II)
BP LEVEL + MAJOR RISK FACTORS + TOD + ACC
LOW
ADDED RISK
MODERATE
ADDED RISK
HIGH / VERY HIGH
ADDED RISK
LIFESTYLE MODIFICATION AS APPROPRIATE
Monitor BP & other risk factors
for 6 – 12 months
SBP ≥ 140
or DBP ≥ 90
SBP < 140
or DBP < 90
Monitor BP & other risk
factors for 3 – 6 months
SBP < 140
or DBP < 90
Continue to monitor
SBP ≥ 140
or DBP ≥ 90
BEGIN DRUG
TREATMENT
Seedat YK, Rayner BL, SA Hpt Guideline, SAMJ, 2011
SA HYPERTENSION GUIDELINE
ARB
Hydrochlorothiazide
12.5-25 mg,
ACE-I
indapamide 1.25mg –
2.5mg daily
Choose any first
line treatment or
combination if
>20/10 above
goal, CCBs
and/or diuretics
preferred in
blacks
Lifestyle
Calcium channel
blockers
Adapted, SA Hpt Guidelines, 2011
Reduction in mortality with
amlodipine/perindopril in ASCOT
Cardiovascular mortality
%
%
24%, P=0.001
3.5
11%, P=0.0247
10.0
atenolol/thiazide
(events=342)
3.0
All-cause mortality
atenolol/thiazide
(events=820)
8.0
2.5
6.0
2.0
4.0
1.5
amlodipine/perindopril
(events=263)
1.0
amlodipine/perindopril
(events=738)
2.0
0.5
0.0
0.0
0.0
1.0
3.0
2.0
Years
4.0
5.0
0.0
1.0
2.0
3.0
4.0
5.0
Years
Dahlof B, et al. Lancet. 2005;366:895-906.
“These practices overlooked 2 facts. First, such low
doses of HCTZ have never been shown to reduce
cardiovascular morbidity or mortality, although they
clearly increase the
antihypertensive efficacy of whatever other drug with
which they are combined.”
Hypertension 2009
Hypertension Treatment Significantly Reduced
Mortality and Morbidity
VA Cooperative Study Group – Estimated Cumulative Incidence of
All Morbid Events Over 5 Years
Estimated Cumulative
Incidence of All Morbid Events (%)
60
50
Control - Placebo
40
30
20
Active Treatment Groups Diuretic-based regimen
and hydralazine
10
0
0
1
2
3
Years
4
5
Hctz 50 -100mg
Veterans Administration Cooperative Study Group on antihypertensive agents JAMA 1970;213(7):1143-1152.
The Trial:
International, multi-centre, randomised double-blind placebo controlled
Exclusion Criteria:
Standing SBP < 140mmHg
Stroke in last 6 months
Dementia
Need daily nursing care
Inclusion Criteria:
Age 80 or more
Systolic BP; 160 – 199 mmHg
+ diastolic BP < 110mmHg
Informed consent
Ste p III + pe rindopril 4 mg
Ste p II + pe rindopril 2 mg
Step I i ndapami de SR 1.5 mg
n=
3845
Pla ce bo
Target BP 150/80
mmHg
Pla ce bo
+ Pla cebo
+ Pla cebo
M-2
M-1
M0
M3
M6
M9
M12
M18
M24
M60
Bulpitt C, et al. Drugs and Aging 2001;18(3):151-164
1
Primary outcomes
Major macro or microvascular event
Number of events
Per-Ind
Placebo
(n=5,569) (n=5,571)
Favours
Per-Ind
Favours
Placebo
Relative risk
reduction (95% CI)
861
938
9% (0 to 17) *
Macrovascular
480
520
8% (-4 to 19)
Microvascular
439
477
9% (-4 to 20)
Combined macro+micro
0.5
1.0
2.0
Hazard ratio
*2P=0.04
Goals of treatment
Systolic Diastolic
Uncomplicated
<140
<90
Diabetic
<130
<80
(or any high risk patient)
Seedat YK, Rayner BL, SA Hpt Guideline, SAMJ, 2011
Systolic Pressures (mean + 95% CI)
Mean # Meds
Intensive:
Standard:
3.2
1.9
3.4
2.1
3.5
2.2
3.4
2.3
Average after 1st year: 133.5 Standard vs. 119.3 Intensive, Delta = 14.2
Patients with Events (%)
20
Primary Outcome
Nonfatal MI, Nonfatal Stroke or
CVD Death
15
10
HR = 0.88
95% CI (0.73-1.06)
5
0
0
1
2
3
4
5
6
7
Years Post-Randomization
8
CONCLUSIONS
• Understanding the complexity of BP
measurement is becoming increasingly
important
• Very low targets in high risk patients are
not evidence based
• Good clinical practice remains essential to
evaluate hypertensives
• Basic investigations are essential
• Low dose Hctz is only acceptable as part of
combination therapy