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 Clinical Pharmacology

St Thomas’ Hospital

King’s College LondonDepartment of Twin Research & Genetic Epidemiology

pPPcPP

DBP

pSBP

cSBP

Aortic PressurePeripheral Pressure

Pulse pressure

CAFE study

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

Amlodipine +perindopril

Atenolol + bendroflumethiazide

CentralSBP

BrachialSBP

P1 and AP differentially associated with aortic stiffness

Arterial dimensionsAugmentation

(AP)

Forward Pressure Wave P1: Aortic Stiffness

(↓ distension)

Cecelja et al. J Am Coll Cardiol. 2009; 18: 54: 695-703.

Inflection

Point(P1)

Aims

10-year prospective follow-up 10-year prospective follow-up

Examine the contribution of P1 and AP to age related Examine the contribution of P1 and AP to age related increase in cPP increase in cPP

Degree to which age-related increase can be reversed Degree to which age-related increase can be reversed by pharmacological vasodilation (Glyceryl Trinitrate)by pharmacological vasodilation (Glyceryl Trinitrate)

Pulse Pressure

Augmentation (AP)

Forward Pressure Wave (P1)

411 Female TwinsTWINS UK RegistryTWINS UK Registry

Department of Twin Research & Genetic Epidemiology

Visit 1 (1996 – 2001)

Visit 2 (2006 – 2010)

n = 411

Central BP Central BPCarotid BP

Arterial stiffnessArterial diameter

Visit 2

Central BP

Arterial stiffnessArterial diameter

n = 40

400 μg GTN

Aortic Pressure Waveforms:Baseline and Follow-up

Applanation tonometryApplanation tonometry High fidelity pressure transducer (Millar High fidelity pressure transducer (Millar

Instruments, Texas)Instruments, Texas) SphygmoCor System SphygmoCor System Calibrated to brachial BPCalibrated to brachial BP

Carotid pressure waveforms

• Quality control – variation in recorded waveform• n = 477

• Inconclusive - excluded

d

t1

t2

Pulse wave velocity (PWV)

Femoral

Carotid

PWV = distance transit time

SphygmoCor

Ultrasonography Arterial dimensionsArterial dimensions

Abdominal aortic

diameter

Femoral artery

diameter

Arterial diameter change expressed as a ratio: femoral/abdominal diameter

•Carotid and brachial diameters

  Visit 1(n = 411)

Visit 2(n = 411)

P

Age (years) 47.6 ± 9.4 58.2 ± 9.0 < 0.0001Height (cm) 161.8 ± 6.0 161.4 ± 6.0 < 0.0001Weight (kg) 66.0 ± 11.5 69.8 ± 12.5 < 0.0001HR (bpm) 72.6 ± 11.1 63.6 ± 9.5 < 0.0001Peripheral SBP (mm Hg) 118.9 ± 15.8 125.0 ± 15.9 < 0.0001

Peripheral DBP (mm Hg) 76.1 ± 11.1 73.0 ± 8.3 < 0.0001MAP (mm Hg) 92.4 ± 13.1 92.3 ± 10.6 NS

Central SBP(mm Hg) 110.3 ± 16.0 117.1 ± 15.7 < 0.0001

Central DBP (mm Hg) 77.4 ± 11.3 73.9 ± 8.3 < 0.0001Total cholesterol (mmol/L) 5.5 ± 1.1 5.6 ± 1.0 < 0.05HDL (mmol/L) 1.5 ± 0.4 1.8 ± 0.5 < 0.0001Glucose (mmol/L) 4.6 (4.27 - 4.97) 5 (4.7 - 5.3) < 0.0001

TG (mmol/L) 1.0 (0.75 - 1.37) 0.98 (0.72 - 1.31) NS

Subject characteristics

∆ P

ress

ure

(mm

Hg) P<0.0001

P = NS

Greater increase in cPP compared to pPPin younger subjects

<50 years at baseline

≥50 years at baseline

AP contributed more than P1 to age-related increase in cPP

≥50 years at baseline

<50 years at baseline

Carotid pressure waveform: P1 and AP

  Variable   beta R2 P

Carotid P1Age 0.15 0.01 <0.0001MAP 0.46 0.36 <0.0001HR -0.17 0.03 <0.0001

  PWV   0.29 0.07 <0.0001

Carotid APAge 0.33 0.09 <0.0001MAP 0.6 0.32 <0.0001HR -0.45 0.18 <0.0001TG 0.07 0.01 <0.05Abd Diameter -0.16 0.12 <0.0001Fem/Abd diameter -0.22 0.18 <0.0001

Multivariate regression analysis

Glyceryl Trinitrate (400 μg)Diameter Change

All P<0.0001

% D

iam

eter

Cha

nge

Glyceryl Trinitrate: P1 and AugP

∆ 9.3 mm Hg ≈ 10 years ageing

Glyceryl trinitrate: PWV and heart rate

PW

V (

m/s

ec)

NS

Errors bars = 1 SD

P<0.05

Heart

Rate

(b

pm

)

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

British Heart Foundation British Research Council Twins UK

Department of Twin Research & Genetic Epidemiology

Age –related change in P1 and AP

AIx = AP/AP+P1

P1 and AP differentially associated with aortic stiffness

Arterial dimensionsAugmentation

(AP):

Forward Pressure Wave P1: Aortic Stiffness

(↓ distension)

Cecelja et al. J Am Coll Cardiol. 2009; 18: 54: 695-703.

Augmentation Index (AIx) = AP/cPP * 100

Inflection

Point(P1)

P1 and AP differentially associate with age?

McEniery, et al. J Am Coll Cardiol 2005;46:1753-1760

Augmentation Pressure

Augmentation Index

AP/AP+P1

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;81:1057-1068

© 2006 Mayo Foundation for Medical Education and Research

Copyright ©1996 American Heart Association

Chen, C.-H. et al. Hypertension 1996;27:168-175

Tracings from all four group B patients illustrate simultaneously recorded invasively (micromanometer) and noninvasively (tonometer) obtained

carotid artery waveforms as well as the invasive (AIm) and noninvasive (AIt) augmentation indexes (expressed as percent)

Tracings from all four group B patients illustrate simultaneously recorded invasively (micromanometer) and noninvasively (tonometer) obtained

carotid artery waveforms as well as the invasive (AIm) and noninvasive (AIt) augmentation indexes (expressed as percent)

Carotid pressure waveform: P1 and AP