10 year follow-up of central pulse pressure
components and effect of nitrovasodilating therapy in
women
Marina Cecelja,
Jiang B, K McNeill, Spector T, Chowienczyk P.
Department of Twin
Research & Genetic
Epidemiology
Department of Clinical Pharmacology
St Thomas’ Hospital
King’s College London
Pulse pressure
pSBP
cSBP
cPP
pPP
DBP
Peripheral Pressure
Aortic Pressure
CAFE study
Amlodipine +perindopril
Atenolol + bendroflumethiazide
Brachial
SBP
Central
SBP
The CAFÉ Investigators. Differential impact of blood-lowering drugs on central aortic pressure and clinical
outcomes: Principle Results of the Conduit Artery Function Evaluation (CAFÉ) Study.
Circulation 2006; 113: 1213-1225
P1 and AP differentially associated
with aortic stiffness
Inflection
Point
(P1)
Arterial dimensions
Augmentation
(AP)
Forward Pressure
Wave P1:
Aortic Stiffness
(↓ distension)
Cecelja et al. J Am Coll Cardiol. 2009; 18: 54: 695-703.
Augmentation (AP)
Aims
Pulse
Pressure
Forward Pressure
Wave (P1)
10-year prospective follow-up

Examine the contribution of P1 and AP to age related
increase in cPP

Degree to which age-related increase can be reversed
by pharmacological vasodilation (Glyceryl Trinitrate)
411 Female Twins
TWINS UK Registry
Department of Twin
Research & Genetic
Epidemiology
Visit 1
(1996 – 2001)
Central BP
n = 411
Visit 2
(2006 – 2010)
Visit 2
400 μg GTN
Central BP
Carotid BP
Central BP
Arterial stiffness
Arterial diameter
Arterial stiffness
Arterial diameter
n = 40
Aortic Pressure Waveforms:
Baseline and Follow-up




Applanation tonometry
High fidelity pressure transducer (Millar
Instruments, Texas)
SphygmoCor System
Calibrated to brachial BP
Carotid pressure waveforms
• Quality control – variation in recorded waveform
• n = 477
• Inconclusive - excluded
Pulse wave velocity (PWV)
Carotid
SphygmoCor
t1
d
t2
Femoral
PWV = distance
transit time
Ultrasonography

Arterial dimensions
Arterial diameter change expressed as a ratio:
femoral/abdominal diameter
Abdominal
aortic
diameter
•Carotid and brachial diameters
Femoral
artery
diameter
Subject characteristics
Visit 1
(n = 411)
Visit 2
(n = 411)
P
Age (years)
Height (cm)
Weight (kg)
HR (bpm)
Peripheral SBP (mm Hg)
47.6 ± 9.4
161.8 ± 6.0
66.0 ± 11.5
72.6 ± 11.1
118.9 ± 15.8
58.2 ± 9.0
161.4 ± 6.0
69.8 ± 12.5
63.6 ± 9.5
125.0 ± 15.9
< 0.0001
< 0.0001
< 0.0001
< 0.0001
< 0.0001
Peripheral DBP (mm Hg)
MAP (mm Hg)
Central SBP(mm Hg)
Central DBP (mm Hg)
Total cholesterol (mmol/L)
HDL (mmol/L)
Glucose (mmol/L)
76.1 ± 11.1
92.4 ± 13.1
110.3 ± 16.0
73.0 ± 8.3
92.3 ± 10.6
117.1 ± 15.7
< 0.0001
NS
< 0.0001
77.4 ± 11.3
5.5 ± 1.1
1.5 ± 0.4
4.6 (4.27 - 4.97)
73.9 ± 8.3
5.6 ± 1.0
1.8 ± 0.5
5 (4.7 - 5.3)
< 0.0001
< 0.05
< 0.0001
< 0.0001
TG (mmol/L)
1.0 (0.75 - 1.37)
0.98 (0.72 - 1.31)
NS
Greater increase in cPP compared to pPP
in younger subjects
P = NS
∆ Pressure (mm Hg)
14
P<0.0001
12
10
8
6
4
2
0
pPP
cPP
<50 years
at baseline
pPP
cPP
≥50 years
at baseline
AP contributed more than P1 to age-related
increase in cPP
Pressure (mm Hg)
50
AP
P1
16.8
40
12.7
30
10.1
6.3
20
10
23.7
27.0
26.0
31.5
0
Baseline Followup
Baseline Followup
<50 years
at baseline
≥50 years
at baseline
Carotid pressure waveform: P1 and AP
60
APTF
Pressure (mm Hg)
50
20.3
16.9
40
APCA
13.4
30
8.6
9.3
P1CA
4.9
20
10
P1TF
23.1
26.8
27.3
31.5
32.7
36.0
0
< 40
40 - 50
> 50
Carotid Pulse Pressure
(mm Hg)
Multivariate regression analysis
Variable
beta
R2
P
Age
MAP
HR
PWV
0.15
0.46
-0.17
0.29
0.01
0.36
0.03
0.07
<0.0001
<0.0001
<0.0001
<0.0001
Age
MAP
HR
TG
Abd Diameter
Fem/Abd diameter
0.33
0.6
-0.45
0.07
-0.16
-0.22
0.09
0.32
0.18
0.01
0.12
0.18
<0.0001
<0.0001
<0.0001
<0.05
<0.0001
<0.0001
Carotid P1
Carotid AP
% Diameter Change
Glyceryl Trinitrate (400 μg)
Diameter Change
All P<0.0001
18
16
14
12
10
8
6
4
2
0
Brachial
Carotid
Femoral
Abdominal
Aorta
Glyceryl Trinitrate: P1 and AugP
50
AugP
P1
∆ 9.3 mm Hg ≈ 10 years ageing
Pressure (mm Hg)
40
15.2
5.9
30
20
27.9
27.4
Baseline
post GTN
10
0
Glyceryl trinitrate:
PWV and heart rate
NS
P<0.05
70
Heart Rate (bpm)
PWV (m/sec)
12
10
8
6
4
60
50
40
30
20
2
10
0
Baseline
GTN
0
Baseline
GTN
Errors bars = 1 SD
Conclusion
 Augmentation pressure is an important determinant
of the progression in central pulse pressure
AugP is not associated with PWV but is associated
with attenuation of arterial diameter
 AugP can be effectively reduced by vasodilation,
independently of an effect on PWV
Discussion
 Our findings challenge the conventional view that
cPP is influenced predominantly by irreversible
stiffening of the proximal aorta.
 Suggest that drugs that dilate muscular arteries may
be effective in reducing age-related widening in cPP.
Acknowledgements



Department of Twin Research
& Genetic Epidemiology
British Heart Foundation
British Research Council
Twins UK
Age –related change in P1 and AP
AIx = AP/AP+P1
P1 and AP differentially associated
with aortic stiffness
Inflection
Point
(P1)
Arterial dimensions
Augmentation
(AP):
Forward Pressure
Wave P1:
Aortic Stiffness
(↓ distension)
Augmentation Index (AIx) = AP/cPP * 100
Cecelja et al. J Am Coll Cardiol. 2009; 18: 54: 695-703.
P1 and AP differentially associate with
age?
Augmentation
Index
AP/AP+P1
Augmentation
Pressure
McEniery, et al. J Am Coll Cardiol 2005;46:1753-1760
Measurement of ascending aortic (top) and brachial (bottom) pressure waves at diagnostic
cardiac catheterization in an older patient, by Millar micromanometer before (control) and
after administration of 0.3 mg nitroglycerin (GTN) sublingually.
O'Rourke M F , Seward J B Mayo Clin Proc. 2006;81:10571068
© 2006 Mayo Foundation for Medical Education and Research
Tracings from all four group B patients illustrate simultaneously recorded invasively
Tracings
from all four
B patients(tonometer)
illustrate simultaneously
recorded
invasively as
(micromanometer)
andgroup
noninvasively
obtained carotid
artery waveforms
(micromanometer)
and (AIm)
noninvasively
(tonometer)
carotidindexes
artery waveforms
well as the invasive
and noninvasive
(AIt)obtained
augmentation
(expressed as
as
well as the invasive (AIm) and noninvasive
(AIt)
augmentation
indexes
(expressed
as
percent)
percent)
Chen, C.-H. et al. Hypertension 1996;27:168-175
Copyright ©1996 American Heart Association
Pressure (mm Hg)
50
P1
AP
40
14.4
30
15.2
5.9
7.9
20
10
24.7
28.8
27.9
27.4
Follow-up
Control
post NTG
0
Baseline
Prospective Follow-up
n=411
NTG Sub-study
n=42
Carotid pressure waveform: P1 and AP
Pressure (mm Hg)
70
60
AP
P1
18.8
50
40
30
10.4
5.7
20
10
27.9
33.8
40.9
0
< 40
40 - 50
> 50
Carotid pulse pressure
(mm Hg)