Transcript Blood Pressure Variability: Mechanisms and Clinical Relevance

Blood Pressure Variability: The
Good And The Bad
Sola Aoun Bahous
LAU Medical Center – Rizk Hospital
Master Course in Hypertension
March 2015
Blood Pressure Variability:
Mechanisms and Clinical Relevance
1.
2.
3.
4.
BPV: a physiological characteristic of the
cardiovascular system
Assessment of BPV
Prognostic importance of BPV
BPV reduction: CV risk lowering
independent of BP reduction?
Blood Pressure Variability:
Mechanisms and Clinical Relevance
1.
2.
3.
4.
BPV is a physiological characteristic of
the cardiovascular system
Assessment of BPV
Prognostic importance of BPV
BPV reduction: CV risk lowering
independent of BP reduction?
Blood Pressure Variability:
Mechanisms and Clinical Relevance
Weber M, J Hypertens 2006
A. Zanchetti, Residual Risk in Treated Hypertension In Special Issues in Hypertension,
2012, A. Berbari and G. Mancia
A. Zanchetti, Residual Risk in Treated Hypertension In Special Issues in Hypertension,
2012, A. Berbari and G. Mancia
A. Zanchetti, Residual Risk in Treated Hypertension In Special Issues in Hypertension,
2012, A. Berbari and G. Mancia
Blood Pressure Parameters
• What BP parameter to use?
• What anatomical site?
• What time to consider?
BP Variability
• Site variability
• Time variability
BP is a highly variable parameter
Intra-arterial BP recording in a subject lying supine, at rest
Time Variability of Arterial BP
mm Hg
200
100
0
19
22
1
4
7
10
13
16
19
Mancia G, Parati G, J Hypertens 1990;8(suppl. 7):S1-S13
220
220
200
200
180
180
Blood pressure
(mmHg)
Blood pressure
(mmHg)
Within-individual BPV over time varies
from one patient to another
160
140
120
100
160
140
120
100
80
80
60
60
40
1
2
3
Weeks
Patient 1 with lower BPV
Rothwell PM. Lancet. 2010;375:938-948.
SBP
DBP
40
1
2
Weeks
Patient 2 with higher BPV
3
BP Variability
• “Rather than representing a “background
noise” or a phenomenon occurring at random,
these variations are known to be the result of
complex interactions between extrinsic
environmental and behavioral factors and
intrinsic cardiovascular regulatory mechanisms
(neural central, neural reflex, and humoral
influences) that are not yet completely
understood”. (Parati G. et al, Nat. Rev. Cardiol.
2013; 10:143)
BP Variability Subtypes
• Short-term BPV (within 24hrs):
– 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
BP Variability: Mechanism
Short-time Variability:
• Beat-to-beat
• Baroreceptors
• Respiration
• Sleep
• Chemoreceptors
Mechanisms: central and reflex autonomic modulation, reduced
arterial compliance, humoral effects, rheological factors,
emotional factors, behavioral influences/physical activity, sleep,
postural changes.
BP Contour
BP Variability: Mechanism
Long-time Variability:
• Day-to-day (behavioral changes)
• Visit-to-visit
• Seasonal: SBP and DBP have been reported to
be lower during summer and higher during
winter. Inappropriate down dosing of drugs
leads to increase in night-time BP with hot
weather reported in some studies.
Mechanisms: less well studied. Behavioral factors, increased
arterial stiffness, poor BP control, or inconsistent office readings.
Blood Pressure Variability
• BPV is a known and natural characteristic of
blood pressure
• BPV is secondary to mechanisms of varied
nature
• Divided into short-term and long-term
Different Prognostic Impact of Nocturnal BP Fall and
Short Term BPV
24h Intra-Arterial BP
Protective
Damaging
mmHg
200
100
0
19
22
1
4
7
10
13
Hours
Mancia G, Parati G 1983
19
Blood Pressure Variability:
Mechanisms and Clinical Relevance
1.
2.
3.
4.
BPV is a physiological characteristic of the
cardiovascular system
Assessment of BPV
Prognostic importance of BPV
BPV reduction: CV risk lowering
independent of BP reduction?
Assessment of BPV
• Indices: SD, CV, day-to-night BP changes, ARV, residual BPV,
trough-to-peak, night-to-day
• Setting:
– Continuous beat-to-beat BP recordings: SD
– Repeated OBPM: SD, CV, ARV
– 24h ABPM: SD, CV, residual BPV, ARV, day-to-night, trough-topeak, night-to-day
– HBPM: SD and CV
– Visit-to-visit: SD and CV
• Smoothness Index: used to assess the amplitude and
distribution over time of BP reduction by treatment. 24-hourly
BP changes/SD
Assessment of BPV
• CV: (SD/BP)100
• Residual BPV: fast fluctuations that remain
after exclusion of the slower components of
the 24h profile through spectral analysis
• ARV: (BP2-BP1) + (BP3-BP2) + (BP4-BP3) + etc.
/N
• Day-to-night: Dipping status
• Night-to-day: Morning surge
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
Nocturnal Dipping Status
1. The correct time period of sleep and
awakening should be considered
2. Poor reproducibility of the classification of
hypertensives into dippers and nondippers
based on 1 ABPM
Nocturnal Dipping Status
Mechanisms underlying nondipping status:
• Persistence of sympathetic drive at night
• Reduced sensibility of baroreceptors at night
• Volume overload in specific conditions
• Autonomic dysfunction
Nocturnal Dipping Status
• Nondipping status is associated with CV risk
• Nocturnal BP independently predicts outcome
• Extreme dipping is associated with higher risk
for cerebral and retinal ischemia
• Chronotherapy?
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…
Kazuomi Kario, In Special Issues in Hypertension, 2012, A. Berbari and G. Mancia
Blood Pressure Variability:
Mechanisms and Clinical Relevance
1.
2.
3.
4.
BPV is a physiological characteristic of the
cardiovascular system
Assessment of BPV
Prognostic importance of BPV
Reduction of BPV on top of BP reduction
may represent a new target for treatment to
further reduce cardiovascular risk (?)
Prognostic Importance of BPV
Clinical Relevance of Short-Term
BPV
Clinical Relevance of 24h BP Variability
Study
Parati, 1987
Palatini, 1992
Mancia, Parati, 2001
Liu, 2003
Frattola, Parati, 1993
Sander, 2000
Dawson, 2000
Kikuya, 2000
Pringle, Parati, 2003
Mena, 2005
Mancia, 2007
Tatasciore, Parati, 2007
Parati, 2009
Hansen, 2010
Design
Endpoint
Cross-sectional
Cross-sectional
Cross-sectional
Longitudinal (rats)
Longitudinal
Longitudinal
Longitudinal
Longitudinal
Longitudinal
Longitudinal
Longitudinal
Cross-sectional
Longitudinal
Longitudinal
TOD score
TOD score
Carotid IMT
Cardiac /renal damage
LV mass (echo)
Carotid IMT / CV events
Dead / dependency (after acute stroke)
CV mortality
Stroke
CV events
CV mortality
Carotid IMT, LVMI
CV events
Only DBP for CV events / stroke
Mancia G, Short-Term and Long-Term Blood Pressure Variability, In Special Issues in
Hypertension, 2012, A. Berbari and G. Mancia
Relation Between Risk of Stroke and Morning
BP Surge In The Ohasama Study
5
V
4
p = 0.12
p = 0.03
p = 0.94
RR
3
IV
III
2
V
I
III
II
IV
I
I
II
III
IV
V
II
1
0
Stroke total
Ischaemic
Haemorrhagic
Quintiles of morning BP surge
N = 1430
Metoki et al. Hypertension.2006
Nocturnal BP Dipping
Incidence of CV events,
24 h BP and Night/day
SBP ratio in Syst Eur
study
Staessen JA, Parati G et al. for
the Systolic Hypertension in
Europe (Syst-Eur) Trial
Investigators.
JAMA 1999; 282: 539-546
CV Fatal Events in Relation with
DBP Variability
CV Events
CV Events
Mancia G, Short-Terma and Long-Term Blood Pressure Variability, In Special Issues in
Hypertension, 2012, A. Berbari and G. Mancia
10-year risk associated with ARV24 at
different levels of 24-h BP
10-year risk of combined
CV events, %
10
Systolic BP
150
10
9
9
8
8
Diastolic BP
89
7
7
133
6
6
5
4
123
5
114
4
67
3
60
105
3
79
73
np=8938 ne=1049
2
Parv=0.03 Pbp<0.001
7
9
11
13
15
np=8938 ne=1049
2
17
Parv=0.04 Pbp<0.001
5
7
9
11
13
Average real variability (mmHg)
Hansen TW et al, Hypertension 2010; 55: 1049-57
Prognostic Importance of BPV
Clinical Relevance of Long Term
BPV
OHASAMA STUDY - Kaplan-Meier Survival Estimates for CV
Mortality across Quartiles of Day-by-Day BP Variability (HBPM)
(n= 2455)
SD of SBP
SD of DBP
15
15
Max
10
Q3
5
Q2
Q1
CV mortality (%)
CV mortality (%)
Q4
Max
10
Q4
5
Q3
Q1
Q2
Min
0
0
0
3
6
9
Follow-up (years)
12
0
3
6
9
Follow-up (years)
Home measurements once a day for 4 weeks
17164 M
Kikuya et al. Hypertension. 2008
12
Min
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-
BPV: Types and Prognostic
Significance
Parati G et al. Nature Reviews Cardiology. 2013.10:143-155
Blood Pressure Variability:
Mechanisms and Clinical Relevance
1.
2.
3.
4.
BPV: a physiological characteristic of the
cardiovascular system
Assessment of BPV
Prognostic importance of BPV
BPV reduction: CV risk lowering
independent of BP reduction?
BP (mm Hg)
DRUG A
Peak
Trough
BP (mm Hg)
DRUG B
Drug
Administration
Peak
Trough
24 h SD of BP
Target for Research
WHICH ANTIHYPERTENSIVE DRUG
DO REDUCE BP VARIABILITY BEST?
Within-visit variability of systolic blood
pressure in ASCOT-BPLA
6083 P
PM Rothwell et al., www.thelancet.com/neurology Published online March 12, 2010
Comparison of Monotherapies
1.2
SBP
Smoothness index
1.0
*
DBP
†
§
0.8
†
0.6
†
§
*
‡
0.4
0.2
§ §
0.0
Placebo
(n = 160)
L50
R10
V80
V160
T40
T80
A5
(n = 50) (n = 712) (n = 197) (n = 430) (n = 140) (n = 2033) (n = 206)
L50, losartan 50 mg; R10, ramipril 10 mg; V80–160, valsartan 80–160 mg;
T40–80, telmisartan 40–80 mg; A5, amlodipine 5 mg
*p < 0.05; †p < 0.01; ‡p < 0.001; §p < 0.0001 vs telmisartan 80 mg
Parati G et al J.Hypertens 2010; 28: 2177-2183
Amlodipine significantly
reduces short-term BPV
P=0.04
SBP variability (mmHg)
* *
P=0.01
*
P=0.03
* *
P=0.08
*
Placebo
Candesartan
Indapamide
Amlodipine
Yi Zhang, et al. Hypertension. 2011;58:155-160.
Does Treatment-Induced Reduction in BPV
Improve Outcome?
Target for Research
• Studies in rats showed improvement outcome
related to TOD
• Conclusive clinical studies are pending
BPV – Need of additional studies
•
•
•
•
Average BP levels and/or BPV?
Short or Long Term BPV?
Which measure of BPV to choose?
Relationships with physiological variables
(e.g. endothelial function, SpO2, arterial
stiffness)?
• BPV in Risk Stratification?
BPV – Need of additional studies
• Is a drug-induced reduction in BPV
accompanied by a reduction in event rate?
• Do different drug classes have a different
effect on BPV and on outcome?
• Is there enough evidence to consider BPV as a
new target for treatment?
Conclusions
•
•
•
•
Average BP levels and/or BPV? Both
Short or Long Term BPV? Mainly short
Which measure of BPV to choose? SD
Relationships with physiological variables
(e.g. endothelial function, SpO2, arterial
stiffness)? Some correlations exist
• BPV in Risk Stratification? ?
Conclusions
• Is a drug-induced reduction in BPV
accompanied by a reduction in event rate? ?
• Do different drug classes have a different
Probably
CCBs
effect on BPV and on outcome?
and long-acting
ARBs?
• Is there enough evidence to consider BPV as a
new target for treatment? ?
Conclusions
• 24 h BP values more closely related to TOD and
future events than office readings
• Higher 24 h BP Variability = Higher CV risk
• Long lasting CCBs seem to score best in reducing
short term and long term BPV
• Prospective outcome studies needed to confirm that
treatment-induced reduction in BPV improves
outcome
Lebanese Variability
Thank You