update on htn and abpm raj padwal division of general internal medicine university of alberta
TRANSCRIPT
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Update on HTN and ABPM
Raj PadwalDivision of General Internal Medicine
University of Alberta
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Disclosures
Funding: CIHR, AIHS, HSF, UHF
Research Collaboration: Novo Nordisk, CVRx
Consulting: Vivus, Medtronic
Speaking and other Honoraria: Abbott
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Outline
1. Understand how to interpret ABPM.
2. Review the pros and cons of different methods to diagnose hypertension.
3. Discuss some current controversies in HTN management.
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Epidemiology and Significance
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European Society of Hypertension Classification of Blood Pressure
Category Systolic Diastolic
Optimal <120 and / or <80
Normal <130 and / or <85
High-Normal 130-139 and / or 85-89
Grade 1 (mild hypertension ) 140-159 and / or 90-99
Grade 2 (moderate hypertension) 160-179 and / or 100-109
Grade 3 (severe hypertension) 180 and / or 110
Isolated Systolic Hypertension (ISH) 140 and <90
The category pertains to the highest risk blood pressure
*ISH=Isolated Systolic Hypertension.
J Hypertens 2007;25:1105-87.
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Hypertension in Canada: Prevalence and Control
McAlister et al. CMAJ 2011
Overall prevalence is 21%
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Life time risk of Hypertension in Normotensive Women and Men aged 65 years
Risk of Hypertension %
0 2 4 6 8 10 12 14 16 18 20
Years to Follow-up
Women
Risk of Hypertension %
Years to Follow-up
0 2 4 6 8 10 12 14 16 18 20
Men
JAMA 2002: Framingham data.
100
80
60
40
20
0
100
80
60
40
20
0
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Diagnosing Hypertension
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Blood Pressure Assessment:Patient preparation and posture
Standardized Preparation:
Patient1. No acute anxiety, stress or pain.2. No caffeine, smoking or nicotine in the preceding
30 minutes.3. No use of substances containing adrenergic
stimulants such as phenylephrine or pseudoephedrine (may be present in nasal decongestants or ophthalmic drops).
4. Bladder and bowel comfortable.5. No tight clothing on arm or forearm.6. Quiet room with comfortable temperature 7. Rest for at least 5 minutes before measurement8. Patient should stay silent prior and during the
procedure.
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II. Criteria for the diagnosis of hypertension and recommendations for follow-up
BP: 140-179 / 90-109
ABPM (If available)
Diagnosisof HTN
Awake BP>135 SBP or>85 DBP or
24-hour>130 SBP or
>80 DBP
Awake BP<135/85
and24-hour<130/80
Continue to follow-up
Clinic BP
Diagnosisof HTN
Hypertension visit 3
>160 SBP or >100 DBP
>140 SBP or>90 DBP
< 140 / 90
Diagnosisof HTN
Continue to follow-up
<160 / 100
Hypertension visit 4-5
ABPM or HBPMor
Home BPM
>135/85 < 135/85
Diagnosisof HTN
Continue to follow-up
Patients with high normal blood pressure (clinic SBP 130-139 and/or DBP 85-89) should be followed annually.
Confirm with repeat Home BPM or ABPM
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Clinic, Home, Ambulatory (ABP) Blood Pressure Measurement Equivalence Numbers
Description Blood Pressure mmHg
Home pressure average 135 / 85
Daytime average ABP 135 / 85
24-hour average ABP 130 / 80
A clinic blood pressure of 140/90 mmHg has a similar risk of a:
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ABPM Indications
Chughtai and Peixoto. Hosp Phys 2003
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Contraindications to ABPM
1. Not cooperative
2. Severe PVD or thrombocytopenia
3. Afib (relative): not accurate
4. Arm too big
5. Severe office HTN (≈220/120)
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ABPM 1
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ABPM 1
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Information Provided by ABPM
1. Estimate of true overall 24 hour BP
2. Diurnal variation in BP
3. Variability in BP
4. Duration of action of drug
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ABPM Normal Parameters
Chughtai and Peixoto. Hosp Phys 2003
BP should dip by 10-20% during sleep
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ABPM 2
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ABPM 2
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ABPM 3
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ABPM 3
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ABPM 4
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ABPM: Number of Readings
• Recommendation is at least 14 readings in the daytime (NICE Guidance).
• Minimum number is 2 per hour.
• We usually do a reading an hour at night.
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ABPM 5
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ABPM 5
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ABPM 5
Ziemmsen. J Neurol Sci 2010
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White Coat and Masked Hypertension
Derived from Pickering et al. Hypertension 2002: 40: 795-796
Office SBP mmHg
Ho
me/
Am
bu
lato
ry S
BP
mm
Hg
Hypertension
Normotension White CoatHypertension
MaskedHypertension
200
180
160
140
120
100
100 120 140 160 180 200
135
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Prognosis of Masked Hypertension
J Hypertension 2007;25:2193-98
Prevalence of masked hypertension is approximately 10% in the general population but is higher in patients with diabetes
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Prognostic Significance of Clinic vs. ABPM
Dawes. BP Monit 2006
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Prognostic Significance of Clinic vs. ABPM
Dawes. BP Monit 2006
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Diagnostic Utility of BP Measures
NICE 2011 Guidance Document
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Diagnostic Utility of BP Measures
Hodgkinson. BMJ 2011
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Cost-Effectiveness of ABPM
Lovibond. Lancet 2011
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Diagnosis of Hypertension: Key Points
• Non-automated office BP measurements are not accurate.
• This results in inappropriate management.
• Out-of-office measurement – particularly ABPM – should be used to confirm the diagnosis of HTN.
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Bedtime Dosing of Antihypertensive Drugs
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Predictive Role of Nighttime BP
Hansen. Hypertension 2012
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The MAPEC Trial
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MAPECHypothesis: Bedtime chronotherapy leads to better
BP control and reduces CV endpoints.Design: PROBE RCTCountry: SpainSample Size: 2156; mean age 56 Endpoints: 1. All-cause mortality and CVD events (huge
composite endpoint)2. 48-hour ABPM
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MAPEC: Results
Baseline awake systolic ABPM was 134 mm Hg. Baseline asleep systolic ABPM was 123 mm Hg.
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MAPEC: Results
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MAPEC Study: Issues
• Inconsistent numbers presented across trial publications. Is this truly an RCT with a predefined start and end? Original sample size in the protocol was 3344. Subsequent publication mentions 734 normotensive subjects – uncertain if they are included in the main paper.
• Most of the literature in the field comes from a single centre and one group of investigators.
• Huge effect size from such a small, simple change.
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Bottom Line: Bedtime Dosing
• Practical point: relatively simple ‘intervention’
• Conversely, I don’t view the data as definitive yet.
• I don’t routinely do it; however, I will in refractory hypertension. Also, in this group, I often use drugs that need bedtime dosing (alpha blockers and some CCBs).
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Choice of ‘Thiazide’ Diuretic for HTN
Chlorthalidone vs. HCTZ
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Pharmacologic Structure
• Chlorthalidone is often mislabeled as ‘thiazide-like’.
• It is a non-thiazide with a distinct pharmacological structure….
• ….that has similar pharmacological action (DCT NaCl symporter blockade)
Kurtz. Hypertension 2012.
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Thiazides and Non-thiazides
ThiazidesHydrochlorothiazideChlorothiazideMethychlothiazidePolythiazideBendroflumethiazide
Non-thiazidesChlorthalidoneIndapamideMetolazone
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Pharmacokinetics
Carter BL. Hypertension 2004;43:4-9
DRUG ONSET (h)
PEAK T1/2 (h) Duration (h)
HCTZ 2 4-6 6-9 (single)8-15 (long term)
12 (single)16-24 (long term)
Chlorthalidone 2-3 2-6 40 (single)45-60 (long term)
24-48 (single)48-72 (long term)
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BP Control
• Meta-analysis of 108 HCTZ and 20 chlorthalidone studies (n=10443)
• Comparisons are indirect, not head-to-head
• Chlorthalidone is a more potent drugDose
Ernst, ME. Am J Hypertens. 2010
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MRFIT Trial Results
MRFIT. JAMA 1986
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Trial ResultsTrial Drug Result
MRFIT Both +
HDFP Chlorthalidone +
ALLHAT Chlorthalidone +
SHEP Chlorthalidone +
Oslo BP HCTZ -
MAPHY HCTZ -
MRC HCTZ -
Wing HCTZ -
Amery HCTZ +
MIDAS HCTZ +
ANBP HCTZ +
INSIGHT HCTZ +
ACCOMPLISH HCTZ -
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Diuretic Choice: Summary
• Thiazides and non-thiazides are similar and dissimilar properties.
• Chlorthalidone (non-thiazide) is more potent and can reduce BP more than HCTZ at equal doses.
• Non-definitive ‘hard outcome’ indirect comparisons: ?chlorthalidone better
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Diuretic Choice: Practical Considerations
• Chlorthalidone: smallest dose available in Canada is 50 mg.
• Chlorthalidone: not commonly available in combos (atenolol only). HCTZ: many combos
• If BP controlled on HCTZ, I don’t change. If I need to choose a fixed dose combo with a diuretic, I use perindopril indapamide or a HCTZ combo ($$ and coverage considered)
• In uncontrolled refractory hypertension, I will usually use chlorthalidone
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Treatment Target in Mild HTN
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Treatment of Mild Hypertension
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Treatment of Mild Hypertension
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Treatment of Mild Hypertension
Diao et al. Cochrane Collaboration 2013
Total events 77 vs 90: Nearly all from one study
Primary Prevention Subjects with Mild HTN
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Comments on This Review
1. Essentially reflects one study (that used BB in half the active treatment group)
2. Underpowered – study not designed to specifically look at this subgroup. Randomization not stratified for this subgroup.
3. The authors excluded relevant studies:a) Non-placebo controlled studies (e.g., HDFP).b) Didn’t have data for some studies (VA, Oslo, others)
but number of events for these would have been small
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Major Trials Including Patients with Mild Hypertension
Trial (n) AgeBP
Results for Primary Endpoint(intervention vs. control)
MRC173545y
35-64
90-109
Stroke events: 60 vs 1090.14 vs. 0.26 per 100 pt*y p<0.01 ARD 0.12% over 5 y
ANBP34274y
30-70
95-109
Nonfatal and fatal CV events:138 vs 1682.0 vs. 2.5 per 100 pt*yP<0.05ARD 0.5% over 4 y
HDFP109405y
30-69
≥ 90
Total mortality: 349 vs. 4196.4% vs. 7.7%P<0.01; ARD 1.3% over 5 y
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Major Trials Including Patients with Mild Hypertension
Trial (n) AgeBP
Results for Primary Endpoint(intervention vs. control)
HDFP7825
30-69
90-104 stratum
Total mortality: 231 vs. 2915.9% vs. 7.4%P<0.01; ARD 1.5%
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HDFP Mortality RRR
HDFP. JAMA 1971
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Canadian Hypertension Education Program Recommendations For Initiating Drug Therapy
1. Prescribe for DBP ≥ 100 or SBP ≥ 160 (Grade A).
2. Strongly consider for DBP ≥ 90 and TOD or other CV risk factors (Grade A).
3. Strongly consider for SBP ≥ 140 and TOD (Grade C for mild HTN).
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Major Trials Including Patients with Mild Hypertension
Trial (n) AgeBP
Results for Primary Endpoint(intervention vs. control)
NNT over 1 year NNT over 10 y
MRC173545y
35-64
90-109
Stroke events: 60 vs 1090.14 vs. 0.26 per 100 pt*y p<0.01 ARD 0.12% over 5 y
4167 416
ANBP34274y
30-70
95-109
Nonfatal and fatal CV events:138 vs 1682.0 vs. 2.5 per 100 pt*yP<0.05ARD 0.5% over 4 y
800 80
HDFP109405y
30-69
≥ 90
Total mortality: 349 vs. 4196.4% vs. 7.7%P<0.01; ARD 1.3% over 5 y
385 39
NNT over 10y for statins for CV event in high-risk patient is 11 and in mod risk pt. is 23.
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Major Trials Including Patients with Mild Hypertension
Trial (n) AgeBP
Results for Primary Endpoint(intervention vs. control)
NNT over 1 year
NNT over 10 y
HDFPsubgroup7825
30-69
90-104 stratum
Total mortality: 231 vs. 2915.9% vs. 7.4%P<0.01; ARD 1.5%
333 33
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HDFP Trial
Alderman. Hypertension 1983
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II. Indications for Pharmacotherapyafter diagnosis of hypertension (1)
• Patients at low risk with stage 1 hypertension (140-159/90-99 mmHg)– lifestyle modification can be the sole therapy.
• Patients with target organ damage (e.g. left ventricular hypertrophy) (140-159/90-99 mmHg)– Treat with pharmacotherapy
• Patients with chronic kidney disease should be considered for pharmacotherapy if the blood pressure is equal or over 140/90 mmHg
• Patients with diabetes should be considered for pharmacotherapy if the blood pressure is equal or over 140/90 mmHg
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II. Indications for Pharmacotherapyafter diagnosis of hypertension (2)
• Patients with other risk factors (over 90% of Canadians with hypertension have other risk factors) (140-159/90-99 mmHg despite lifestyle modification) – Treat with pharmacotherapy
• Treatment Gap Alert: Many younger hypertensive Canadians with multiple cardiovascular risks are currently not treated with pharmacotherapy. Health care professionals need to be aware of this important care gap and recommend pharmacotherapy.
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Treatment of Mild Hypertension: Key Points
1. All patients should be treated with lifestyle modification.
2. Decision to institute drug treatment should take into account global risk.
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Renal Denervation
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Resistant Hypertension
• Failure to achieve BP target despite treatment with three antihypertensive drugs (including a diuretic) at optimal doses.
• Prevalence is not well studied. Appears to be about 10-20% of hypertensive patients.
Sarafidis. J Clin Hypertens 2011
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Sympathectomy for Severe Hypertension
Bilateral T8-L3 Sympathectomy
Ray BS. Ann Surg 1949
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Renal Sympathetic Denervation
Papademetriou et al. Int J Hypertens 2011
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Renal Sympathetic Denervation for Resistant Hypertension
Source: Medtronic
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Renal Sympathetic Denervation for Resistant Hypertension: SYMPLICITY HTN-2 RCT
Esler et al. Lancet 2010
6 month BP difference of 33/11P<0.0001 (n=106)
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Renal Sympathetic Denervation: Safety
• Well tolerated – one femoral pseudoaneurysm was the only adverse effect. Renal function similar at end of six months.
• Only half had ABPM measured; ABPM difference was 16/8 mm Hg between groups.
• Irreversible nature of the procedure• Renal adverse effects?
– Stenosis, dilation– Proteinuria– Renal function
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Renal Sympathetic Denervation: Key Point
• An emerging procedure
• Potential to be used in a large number of patients
• Long-term efficacy and safety data required.
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Outline
1. Understand how to interpret ABPM.
2. Review the pros and cons of different methods to diagnose hypertension.
3. Discuss some current controversies in HTN management.