blood pressure variability: the good and the bad sola aoun bahous lau medical center – rizk...
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Blood Pressure Variability: The Good And The Bad
Sola Aoun Bahous
LAU Medical Center – Rizk Hospital
Master Course in HypertensionMarch 2015
Blood Pressure Variability: Mechanisms and Clinical Relevance
1. BPV: a physiological characteristic of the cardiovascular system
2. Assessment of BPV
3. Prognostic importance of BPV
4. BPV reduction: CV risk lowering independent of BP reduction?
Blood Pressure Variability: Mechanisms and Clinical Relevance
1. BPV is a physiological characteristic of the cardiovascular system
2. Assessment of BPV
3. Prognostic importance of BPV
4. 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
19 22 1 4 7 10 13 16 19
0
100
200mm Hg
Mancia G, Parati G, J Hypertens 1990;8(suppl. 7):S1-S13
Within-individual BPV over time varies from one patient to another
Rothwell PM. Lancet. 2010;375:938-948.
Patient 1 with lower BPV Patient 2 with higher BPV
Weeks
40
60
80
100
120
140
160
180
200
220
Bloo
d pr
essu
re
(mm
Hg)
1 2 3
SBP
DBP
40
60
80
100
120
140
160
180
200
220
Bloo
d pr
essu
re
(mm
Hg)
1 2 3Weeks
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: MechanismLong-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
24h Intra-Arterial BP
19 22 1 4 7 10 13 19
Hours
0
100
200
mmHg
Protective Damaging
Different Prognostic Impact of Nocturnal BP Fall and Short Term BPV
Mancia G, Parati G 1983
Blood Pressure Variability: Mechanisms and Clinical Relevance
1. BPV is a physiological characteristic of the cardiovascular system
2. Assessment of BPV3. Prognostic importance of BPV4. 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-to-
peak, 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. BPV is a physiological characteristic of the cardiovascular system
2. Assessment of BPV
3. Prognostic importance of BPV
4. 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
Study
Parati, 1987Palatini, 1992Mancia, Parati, 2001Liu, 2003Frattola, Parati, 1993Sander, 2000Dawson, 2000Kikuya, 2000Pringle, Parati, 2003Mena, 2005Mancia, 2007 Tatasciore, Parati, 2007Parati, 2009Hansen, 2010
Design
Cross-sectionalCross-sectionalCross-sectionalLongitudinal (rats)LongitudinalLongitudinalLongitudinalLongitudinalLongitudinalLongitudinalLongitudinalCross-sectionalLongitudinalLongitudinal
Endpoint
TOD scoreTOD scoreCarotid IMTCardiac /renal damageLV mass (echo)Carotid IMT / CV eventsDead / dependency (after acute stroke)CV mortalityStrokeCV eventsCV mortalityCarotid IMT, LVMICV eventsOnly DBP for CV events / stroke
Clinical Relevance of 24h BP Variability
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
Metoki et al. Hypertension.2006
Stroke total Ischaemic Haemorrhagic0
1
2
3
4
5
I I
I
II II IIIII
III
III
IVIV
IV
V
V
V
Quintiles of morning BP surge
RR
p = 0.12 p = 0.94 p = 0.03
N = 1430
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
Nocturnal BP Dipping
CV Fatal Events in Relation with DBP Variability
Mancia G, Short-Terma and Long-Term Blood Pressure Variability, In Special Issues in Hypertension, 2012, A. Berbari and G. Mancia
CV Events CV Events
10
9
8
7
6
5
4
3
2
10
9
8
7
6
5
4
3
2
7 9 11 13 15 17 5 7 9 11 13
150
133
123
114
105
np=8938 ne=1049
Parv=0.03 Pbp<0.001
89
79
73
67
60
np=8938 ne=1049
Parv=0.04 Pbp<0.001
10-year risk of combined
CV events, %
Average real variability (mmHg)
10-year risk associated with ARV24 at different levels of 24-h BP
10-year risk associated with ARV24 at different levels of 24-h BP
Systolic BP Diastolic BP
Hansen TW et al, Hypertension 2010; 55: 1049-57
Prognostic Importance of BPV
Clinical Relevance of Long Term BPV
17164 M
SD of SBPSD of SBP SD of DBPSD of DBP
CV
mor
tali
ty (
%)
Follow-up (years)
15
10
5
0
0 3 6 9 12 0 3 6 9 12
Q4
Q3
Q2Q1
Q4
Q3
Q2Q1
Home measurements once a day for 4 weeks
Follow-up (years)
CV
mor
tali
ty (
%)
15
10
5
0
Max
Min
Max
Min
Kikuya et al. Hypertension. 2008
OHASAMA STUDY - Kaplan-Meier Survival Estimates for CV Mortality across Quartiles of Day-by-Day BP Variability (HBPM)
(n= 2455)
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
BPV: Types and Prognostic Significance
Parati G et al. Nature Reviews Cardiology. 2013.10:143-155
Blood Pressure Variability: Mechanisms and Clinical Relevance
1. BPV: a physiological characteristic of the cardiovascular system
2. Assessment of BPV
3. Prognostic importance of BPV
4. BPV reduction: CV risk lowering independent of BP reduction?
DRUG A
DRUG B
BP
(m
m H
g)
DrugAdministration
Peak Trough
Peak Trough
24 h SD of BP
BP
(m
m H
g)
Target for Research
WHICH ANTIHYPERTENSIVE DRUG DO REDUCE BP VARIABILITY BEST?
PM Rothwell et al., www.thelancet.com/neurology Published online March 12, 20106083 P
Within-visit variability of systolic blood pressure in ASCOT-BPLA
Placebo L50 R10 V80 V160 T40 T80 A50.0
0.2
0.4
0.6
0.8
1.0
1.2SBP
DBP
Sm
ooth
ness
inde
x
§ §
††
§
§
†
‡
*
*
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
(n = 160) (n = 50) (n = 712) (n = 197) (n = 430) (n = 140) (n = 2033) (n = 206)
Parati G et al J.Hypertens 2010; 28: 2177-2183
Comparison of Monotherapies
P=0.04
P=0.01P=0.03
P=0.08
*
*
*
*
SB
P v
aria
bilit
y (m
mH
g)
**
Amlodipine significantly reduces short-term BPV
Yi Zhang, et al. Hypertension. 2011;58:155-160.
Placebo
Candesartan
Indapamide
Amlodipine
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?
• 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?
BothMainly short
SD
Some correlations exist?
Conclusions
• 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?
?
Probably CCBs and long-acting ARBs?
?
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