brian rayner, division of nephrology and hypertension, groote schuur hospital, university of cape...
TRANSCRIPT
Brian Rayner,Division of Nephrology and
Hypertension, Groote Schuur Hospital, University of Cape Town
HYPERTENSION – THE ABC
Global Mortality 2000: Impact of Hypertension and Other Health Risk Factors
Attributable mortality in millions (total: 55,861,000)
Developing region
Developed region
0 87654321
High BP
Tobacco
High cholesterol
Unsafe sex
High BMI
Physical inactivity
Alcohol
Underweight
Ezzati et al. Lancet 2002;360:1347–60
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
BenefitBenefit not established
The closer to targetthe less reliable to office BP becomes
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 Aware % Treated % Controlled %
Total men 26 21 10Total women 51 36 18
Black men 20 14 7Black women 47 29 15White men 47 43 17
White women 63 64 19Colored men 24 19 7
Colored women 57 48 14Asian men 37 46 28
Asian women 75 71 5
Steyn K, 2003
CLINICAL PATHWAY
Evaluation of patient
Appropriate Treatment
BP at goal 65%
BP not at goal
Office hpt
Inadequate treatment
Non-adherence
TRUE RESISTANCE ?
Patient, Funderor MD failure
Lifestyle
Interfering drugs
Secondary causes Inappropriate formularies
No fixed drug combinations
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 and <80Normal <130 and <85High-normal 130 - 139 or 85 - 89
Hypertension Stage 1 140 - 159 or 90 - 99Stage 2 160 - 179 or 100 - 109Stage 3 180 or 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
Wingfield D, et al QJM 2002
70
80
80
88100
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
Conventional office BP
Daytime BP
24-hour BP
Nocturnal BP
Systolic BP (mm Hg)
Adj
uste
d 5-
Yea
r R
isk
of
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.
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 a l, 1983; Kobrin et al, 1984; Baumgart et al, 1989; Imai et al, 1990; Portaluppi et al, 1991
Reverse Dipper
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 >=2 SCIs per person)
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
CLINIC HOME AMBULATORY
Predicts outcome Yes Yes Strongly
Initial diagnosis Yes Yes Yes
Cut-off BP levels (in mm Hg)
140/90 135/85120/70 (mean night)135/85 (mean day)
Evaluation of treatment Yes Yes Limited but valuable
Assess diurnal rhythm No No Yes
DIFFERENT METHODS OF BP MEASUREMENT
Seedat YK, Rayner BL, SA Hpt Guideline, SAMJ, 2011
N.B. Difference between ABPM and Office widens with increasing BP
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
S4Pressure overloadedapex beat ECGEcho
>=38 – Sokolow-Lyon)
Cornel – (S in V3 + R in aVL + 6 in females) x QRS duration > 2440
Harbinger of death
MALIGNANT HYPERTENSION
BP > 120-130 diastolicRenal failureDipsticks – 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 INVESTIGATIONSROUTINE 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)
0
5
10
15
20
25
30
35
40
10 year %probability ofevent
PROBABILITY OF CHD EVENT IN MALES WITH MILD HYPERTENSION
BP 150-160 + + + + + +
TC 6.2-6.77 + + + + +
HDL 0.85-0.89 + + + +
Diabetes + + +
Smoker + +
ECH-LVH +
Average risk
MAJOR RISK FACTORS, AND COMPLICATIONS
MAJOR RISK FACTORS TOD COMPLICATIONS
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.
LVH: based on ECGoSokolow-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 ORocreatinine 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
Monitor BP & other risk factors for 6 – 12 months
SBP ≥ 140or DBP ≥ 90
SBP < 140or DBP < 90
SBP < 140or DBP < 90
SBP ≥ 140or DBP ≥ 90
Continue to monitor BEGIN DRUGTREATMENT
LIFESTYLE MODIFICATION AS APPROPRIATE
Monitor BP & other risk factors for 3 – 6 months
Seedat YK, Rayner BL, SA Hpt Guideline, SAMJ, 2011
SA HYPERTENSION GUIDELINE
ACE-I
Lifestyle
Hydrochlorothiazide 12.5-25 mg,
Calcium channel blockers
ARB
Adapted, SA Hpt Guidelines, 2011
Choose any first line treatment or combination if >20/10 above goal, CCBs and/or diuretics preferred in blacks
indapamide 1.25mg – 2.5mg daily
Reduction in mortality with amlodipine/perindopril in ASCOT
Cardiovascular mortality
amlodipine/perindopril(events=263)
atenolol/thiazide(events=342)
24%, P=0.001
0.0 1.0 2.0 3.0 4.0 5.0Years
0.0
0.5
1.0
1.5
2.0
2.5
3.0
3.5
%
All-cause mortality
0.0 1.0 2.0 3.0 4.0 5.0Years
0.0
2.0
4.0
6.0
8.0
10.0
%
atenolol/thiazide(events=820)
amlodipine/perindopril(events=738)
11%, P=0.0247
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
VA Cooperative Study Group – Estimated Cumulative Incidence of All Morbid Events Over 5 Years
Veterans Administration Cooperative Study Group on antihypertensive agents JAMA 1970;213(7):1143-1152.
0
10
20
30
40
50
60
0 1 2 3 4 5Years
Estim
ated
Cum
ulat
ive
Inci
denc
e of
All
Mor
bid
Even
ts (%
)
Control - Placebo
Active Treatment Groups - Diuretic-based regimen and hydralazine
Hypertension Treatment Significantly Reduced Mortality and Morbidity
Hctz 50 -100mg
Inclusion Criteria:Age 80 or more
Systolic BP; 160 – 199 mmHg+ diastolic BP < 110mmHg
Informed consent
Exclusion Criteria:Standing SBP < 140mmHg
Stroke in last 6 monthsDementia
Need daily nursing care
Target BP 150/80 mmHg
The Trial:International, multi-centre, randomised double-blind placebo controlled
n = 3845
Bulpitt C, et al. Drugs and Aging 2001;18(3):151-164
1
Macrovascular 480 520 8% (-4 to 19)
Microvascular 439 477 9% (-4 to 20)
Combined macro+micro 861 938 9% (0 to 17)
Number of events
Per-Ind Placebo(n=5,569) (n=5,571)
Relative riskreduction (95% CI)
FavoursPer-Ind
FavoursPlacebo
Hazard ratio
0.5 1.0 2.0
*
*2P=0.04
Primary outcomesMajor macro or microvascular event
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)
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
Pat
ien
ts w
ith
Eve
nts
(%
)
0
5
10
15
20
Years Post-Randomization0 1 2 3 4 5 6 7 8
Primary Outcome Nonfatal MI, Nonfatal Stroke or CVD Death
HR = 0.8895% CI (0.73-1.06)
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