Blood Pressure Variability:

Target of Hypertension Management

Bimanesh Sutarjo
 Blood Pressure Variability:
Target of Hypertension Management

AGENDA

1. BPV is a physiological characteristic of the

cardiovascular system
2. Assessment of BPV
3. Prognostic importance of BPV
4. Target of Hypertension Management
 Blood Pressure Variability:
Target of Hypertension Management

AGENDA

1. BPV is a physiological characteristic of the

cardiovascular system
2. Assessment of BPV
3. Prognostic importance of BPV
4. Target of Hypertension Management
Normal 24 – Hour Variation in BP
 What is the True Blood Pressure?

Daytime BP? Dipping Night time BP?

Pattern?
Morning
Surge?

Clinic 24 Hr Average
BP? BP?

Variability of
BP?
Home BP?
 What is BP Variability?

• BP normally fluctuates during day, can vary from day-to-day1

• Pronounced fluctuations in BP can occur over short / long-term

• Episodic Hypertension is common:2

o In TIA patients, 12% had stable HT, 69% had episodic HT
(some SBP readings ≤140 mmHg, some >140 mmHg)
• Self BP monitoring widely encouraged (ESC / JSH) 3

• BPV is difficult to measure in routine clinical practice: no

clearly defined or widely adopted diagnostic definitions or
treatment goals

1. Schillaci et al. Hypertension 2011;58:133-135

2. Rothwell. Lancet 2010;375:938-948.
3. Mancia et al. J Hypertension 2013;31:1281-1357
 Blood Pressure Variability

Blood pressure variability (BPV) has been defined

as an average BP variation throughout the day,
which is measured as the standard deviation of
ambulatory BP readings

BPV is of particular importance in patients with HT.

The amplitude of BPV in patients increases
progressively with increasing levels of HT
 Ambulatory BP Differences for Normotensives, and Mild
and Established HTN Patients

120-
110-
Diastolic 100- Established
Blood 90-
hypertensives
Pressure 80-
Mild
(mm Hg) 70-
hypertensives
60-
Normotensives

0-
Clinic Work Home Sleep
 Circadian Variability of BP

• Beat-to-beat variability

• Day-to-night variability
– Dippers
– Non-dippers
– Reverse dippers/risers
– Excessive dippers

• Night-to-day variability: morning surge

 Within-individual BPV over time varies
from one patient to another

220 220
200 200
180 180 SBP
160

Blood pressure
160
Blood pressure

(mmHg)
140
(mmHg)

140
120 120
100 100 DBP
80 80
60 60
40 40
1 2 3 1 2 3
Weeks Weeks

Patient 1 with lower BPV Patient 2 with higher BPV

Rothwell PM. Lancet. 2010;375:938-948.

Clinical Situations in which The Normal Diurnal Rhythm of BP
may be lost

Autonomic Dysfunction Syndromes

Diabetes Mellitus
Renal Failure
Secondary forms of hypertension e.g. Cushing’s
disease
Drugs, e.g. cyclosporine
African-American ethnicity
 BP Variability : Subtypes

• Short-term BPV (within 24 hrs) :

– Very short: beat-to-beat
– Short : within a 24-h period (minute-to-minute,
hour-to-hour, and day-to-night)

• Long-term BPV :
– Day-to-day
– Visit-to-visit
– Seasonal
Factors involved in development of
blood pressure (BP) variability
 Blood Pressure Variability:
Target of Hypertension Management

AGENDA

1. BPV is a physiological characteristic of the

cardiovascular system
2. Assessment of BPV
3. Prognostic importance of BPV
4. Target of Hypertension Management
 Blood Pressure Variability:
Target of Hypertension Management

AGENDA

1. BPV is a physiological characteristic of the

cardiovascular system
2. Assessment of BPV
3. Prognostic importance of BPV
4. Target of Hypertension Management
 BPV : Types and Prognostic Significance

Parati G et al. Nature Reviews Cardiology. 2013.10:143-155

Reproducibility of morning blood pressure surge and
cardiovascular risk
 Morning Hypertension and Diurnal BPV

Kario K. Time for focus on morning hypertension: Am J Hypertens. 2005;18:149-151

 Morning Surge

• No consensus on the definition and threshold value of

pathological MBPS
• Usually assessed using the ABPM
• Exaggerated surge is associated with TOD and leads to
increased risk of CV events or death
• Weekly and seasonal variations in MBPS: augmented on
Mondays and in winter
• MBPS increases with age, HTN, glucose intolerance,
inflammation, alcohol, smoking, stress, etc

(Kario, Pickering et al, Circ 2003; 107:1401)

 Definition of Morning BP Surge

A. Berbari and G. Mancia, Kazuomi

, Kario, In Special Issues in Hypertension, 2012
Analysis of The Influence of the Morning Surge of BP
on Stroke Incidence

Cox regression analysis for clinical stroke events

Covariates RR P value
Age ( 10 yrs) 1.80 (1.21-2.69) 0.004
Male gender 1.42 (0.76-2.67) 0.266
BMI 0.98 (0.90-1.07) 0.663
24 hr SBP 1.37 (1.16-1.63) 0.003
SCI 4.40 (1.95-10.1) 0.001
Morning BP surge* 1.29 (1.10-1.51) 0.001
Nocturnal BP fall* 0.88 (0.73-1.06) 0.167
Lowest sleep BP 1.05 (0.65-1.71) 0.837
* per 10 mmHg

(Kario, Pickering et al, Circ 2003; 107:1401)

 Nocturnal Hypertension
Nighttime BP ≥120/70 mmHg (ABPM)

• Normally BP ↓ by 10-20% at night (Dipping)

Range of BP Dipping Class

<0% Reverse Dipping
≥0%, <10% Non-Dipping
≥10%, <20% Dipping (Normal pattern)
≥20% Extreme Dipping

• Non-dipping / Reverse Dipping :

✓ ↑ risk of organ damage (brain, heart, kidney)
✓ ↑ CV events and mortality

JSH. Hypertension Research. 2009;32:70-7.

 Nocturnal Hypertension
Nighttime BP ≥120/70 mmHg (ABPM)
Nocturnal BP Changes and CV Mortality: Ohasama Study

4
3,69
3,5
3
2,56
2,5

Risk of CV 2
Mortality 1,5
0,96 1
1

0,5
0
Extreme Dippers Non- Risers
dippers dippers

(Ohkubo et al; AJH 1997; 10: 1201)

 CV Fatal Events in Relation with
DBP Variability

CV Events CV Events

Mancia G, A. Berbari and G. Mancia. Short-Term and Long-Term Blood Pressure Variability,
In Special Issues in Hypertension, 2012
Risk of Cardiovascular Mortality for a 1-SD increase in Various Measures
of 24-hours Diastolic Blood Pressure (BP) Variability.

Giuseppe Mancia Hypertension. 2012;60:512-517

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

Visit-to-visit Variability and Risk of Stroke and Coronary
Events in UK-TIA and ASCOT-BPLA

Rothwell PM et al., Lancet 2010; 375: 895-905

 Blood Pressure Variability:
Target of Hypertension Management

AGENDA

1. BPV is a physiological characteristic of the

cardiovascular system
2. Assessment of BPV
3. Prognostic importance of BPV
4. Target of Hypertension Management
 Goals of Treatment

• In hypertensive patients, the primary goal of treatment is to

achieve maximum reduction in the long-term total risk of
cardiovascular disease.
• This requires treatment of the raised BP per se as well as of
all associated reversible risk factors.
• BP should be reduced to at least below 140/90 mmHg
(systolic / diastolic) and to lower values, if tolerated, in all
hypertensive patients.

Kazuomi Kario, In Special Issues in Hypertension, 2012

 Strategies to Reduce BPV
in Hypertensive Patients

 Buffering the enhanced BPV commonly found in hypertensive

patients is an equally important target of antihypertensive treatment

 Optimal BP control requires strategies that lower BP consistently

and fully throughout a 24-hour period

 Maintain the normal circadian pattern of BP

 Do not increase BPV
 Optimize the patient’s compliance

1. Rothwell. Lancet 2010;375:938-948.

2. Mancia et al. J Hypertension 2013;31:1281-1357
JNC 8-2014
Evidence-Based
Guidelines for
the Management
of High Blood
Pressure in
Adults
 Guidelines on BPV

The Target of Management of Hypertension

should be BPV Control
 Preferred AHT action in controlling BPV

DRUG A
BP (mm Hg)

Peak Trough
DRUG B
BP (mm Hg)

Peak Trough
Drug
Administration 24 h SD of BP
 Effects of Time of Administration of CCBs
on Diurnal Changes of BP
(Lemmer BPM 1996: 1;169)

Drug Dose Effect on BP

Time Day Night 24 hr Pattern
Amlodipine (1) AM Unchanged
PM Unchanged
Isradipine (2) AM Unchanged
PM Unchanged
Nifedipine GITS (3) AM Unchanged
PM Unchanged
Nitrendipine (4) AM Unchanged
PM Unchanged
1. Mengden J Hypertens 1992:10 (supp 4); S136
2. Fogari Br J Clin Pharm 1993: 35:51
3. Lemmer Naunyn- Schmiederberg Arch Pharm 1994; 349(supp); R141
4. Meilhac Therapie 1992: 47: 205
 Effects of Time of Administration of ACEi’s
on Diurnal Changes of BP
(Lemmer BPM 1996: 1;169)

Drug Dose Effect on BP

Time Day Night 24 hr Pattern

Benazepril (1) AM Nearly Unchanged
PM Changed
Enalapril (2) AM Nearly
Unchanged PM
Changed
Quinapril (3) AM Nearly Unchanged
PM Changed
1. Palatini Int J Clin Pharm Ther Toxicol 1993:31:295
2. Witte Clin Pharm Ther 1993: 54:177
3. Paltini Clin Pharm Ther 1992; 52: 378
Within-Visit Variability of Systolic Blood Pressure
in ASCOT-BPLA

PM Rothwell et al., www.thelancet.com/neurology Published online March 12, 2010

 Amlodipine significantly reduces short-term BPV

14 P= 0.03 P=0.01
* *
* AJH 2006; 19:113-121
12 * P=0.08
SBP variability (mmHg)

*
10
*
P=0.04
8
Placebo
安慰剂
6 Candesartan
坎地沙坦
Indapamide
吲达帕胺缓释剂
4 Amlodipine
氨氯地平

0
Daytime SD Nightime SD Daily SD ARV

Yi Zhang, et al. Hypertension. 2011;58:155-160.

 Conclusions
 24 h BPV values are more closely related to TOD and future
CV events, than office readings

 Higher 24 h BP Variability = Higher CV risk

 Long lasting CCBs are the antihypertensive class of choice

for BPV control (short and long term)

 Among CCBs, Amlodipine as initial monotherapy has

proven efficacy in reducing BPV and MBP surge

 Prospective outcome studies needed to confirm that

treatment-induced reduction in BPV improves outcome
THANKS FOR YOUR KIND ATTENTION