CLINICAL RESEARCH: HYPERTENSION
Mechanism(s) of selective systolic blood pressure reduction after a low-dose combination of perindopril/Indapamide in hypertensive subjects: comparison with atenolol
Gérard M. London, MD*,
Roland G. Asmar, MD ,
Michaël F. O'Rourke, MD ,
Michel E. Safar, MD ,* REASON Project Investigators
* Hôpital Manhès, Fleury-Mèrogis, France
L'Institut Cardiovasculaire, Paris, France
St. Vincent Hospital, Darlinghurst, Australia
Hôtel-Dieu, Paris, France
Manuscript received February 4, 2003;
revised manuscript received July 28, 2003,
accepted July 28, 2003.
* Reprint requests and correspondence: Dr. Michel E. Safar, Centre de Diagnostic, Hôtel-Dieu, 1 Place du Paris Notre Dame, Paris, 75004 France.
michel.safar{at}brs.ap-hop-paris.fr
OBJECTIVES: The goal of this study was to determine if a low-dose combination of the angiotensin-converting enzyme inhibitor perindopril (Per) and the diuretic indapamide (Ind) reduces central (thoracic aorta, carotid artery) as well as brachial systolic blood pressure (SBP) more than the beta-blocker atenolol and to determine the hemodynamic factors influencing independently brachial and central SBP: pulse wave velocity (PWV) and pattern of wave reflections.
BACKGROUND: In high cardiovascular risk populations, angiotensin blockade improves survival without affecting brachial SBP and diastolic blood pressure (DBP). Whether central SBP, which is physiologically lower than brachial SBP, is significantly reduced has never been investigated.
METHODS: This study was a double-blind randomized trial for one year in patients with essential hypertension.
RESULTS: For a similar DBP reduction, Per/Ind decreased SBP significantly more than atenolol, with a more pronounced reduction for central than for brachial SBP. After one year, the difference between brachial and central SBP was maintained by Per/Ind (8.28 ± 1.53 mm Hg) and significantly attenuated by atenolol (0.29 ± 1.61 mm Hg). Under atenolol, the principal factor modulating SBP reduction was mean blood pressure. Under Per/Ind, this parameter played a minor role, and the central SBP reduction implied a major role for disturbed PWV and wave reflections.
CONCLUSIONS: Under Per/Ind, but not atenolol, normalization of brachial SBP is achieved with a significantly greater reduction of central SBP. This hemodynamic profile reflects changes of wave reflections issued from distal arterial and arteriolar territory, where Per/Ind, but not atenolol, is known to improve vessel wall structure.
|
Abbreviations and Acronyms
| | ACEI | = angiotensin-converting enzyme inhibitor | | AIa | = augmentation index (aortic) | | AIc | = augmentation index (carotid) | | CV | = cardiovascular | | DBP | = diastolic blood pressure | | Ind | = indapamide | | ITT | = intention-to-treat | | LVET | = left ventricular ejection time | | MBP | = mean blood pressure | | M0, M6, M12 | = month 0, month 6, month 12 | | Per | = perindopril | | PP | = pulse pressure | | PWV | = pulse wave velocity | | SBP | = systolic blood pressure |
|
This article has been cited by other articles:
|
|
|
|
 
P. Lacolley, M. E. Safar, V. Regnault, and E. D. Frohlich
Angiotensin II, mechanotransduction, and pulsatile arterial hemodynamics in hypertension
Am J Physiol Heart Circ Physiol,
November 1, 2009;
297(5):
H1567 - H1575.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
C. Manisty, J. Mayet, R. J. Tapp, P. S. Sever, N. Poulter, S. A. McG. Thom, A. D. Hughes, and on behalf of the ASCOT Investigators
Atorvastatin Treatment Is Associated With Less Augmentation of the Carotid Pressure Waveform in Hypertension: A Substudy of the Anglo-Scandinavian Cardiac Outcome Trial (ASCOT)
Hypertension,
November 1, 2009;
54(5):
1009 - 1013.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
Y. Matsui, K. Eguchi, M. F. O'Rourke, J. Ishikawa, H. Miyashita, K. Shimada, and K. Kario
Differential Effects Between a Calcium Channel Blocker and a Diuretic When Used in Combination With Angiotensin II Receptor Blocker on Central Aortic Pressure in Hypertensive Patients
Hypertension,
October 1, 2009;
54(4):
716 - 723.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
M. E. Safar, A. Protogerou, and J. Blacher
Central Blood Pressure Under Angiotensin and Calcium Channel Blockade
Hypertension,
October 1, 2009;
54(4):
704 - 706.
[Full Text]
[PDF]
|
|
|
|
|
|
|
C. H. Manisty, A. Zambanini, K. H. Parker, J. E. Davies, D. P. Francis, J. Mayet, S. A. McG Thom, A. D. Hughes, and on behalf of the Anglo-Scandinavian Cardiac Outcom
Differences in the Magnitude of Wave Reflection Account for Differential Effects of Amlodipine- Versus Atenolol-Based Regimens on Central Blood Pressure: An Anglo-Scandinavian Cardiac Outcome Trial Substudy
Hypertension,
October 1, 2009;
54(4):
724 - 730.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
B. Williams, P. S. Lacy, and for the CAFE and the ASCOT (Anglo-Scandinavian Car
Impact of heart rate on central aortic pressures and hemodynamics: analysis from the CAFE (Conduit Artery Function Evaluation) Study: CAFE-Heart Rate.
J. Am. Coll. Cardiol.,
August 18, 2009;
54(8):
705 - 713.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
A. P. Avolio, L. M. Van Bortel, P. Boutouyrie, J. R. Cockcroft, C. M. McEniery, A. D. Protogerou, M. J. Roman, M. E. Safar, P. Segers, and H. Smulyan
Role of Pulse Pressure Amplification in Arterial Hypertension: Experts' Opinion and Review of the Data
Hypertension,
August 1, 2009;
54(2):
375 - 383.
[Full Text]
[PDF]
|
|
|
|
|
|
|
A. Protogerou, J. Blacher, G. S. Stergiou, A. Achimastos, and M. E. Safar
Blood Pressure Response Under Chronic Antihypertensive Drug Therapy The Role of Aortic Stiffness in the REASON (Preterax in Regression of Arterial Stiffness in a Controlled Double-Blind) Study.
J. Am. Coll. Cardiol.,
February 3, 2009;
53(5):
445 - 451.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
M. E. Safar, A. D. Protogerou, and J. Blacher
Statins, Central Blood Pressure, and Blood Pressure Amplification
Circulation,
January 6, 2009;
119(1):
9 - 12.
[Full Text]
[PDF]
|
|
|
|
|
|
|
O. Cseprekal, E. Kis, P. Schaffer, T. E. H. Othmane, B. Cs. Fekete, A. Vannay, A. J. Szabo, A. Remport, A. Szabo, T. Tulassay, et al.
Pulse wave velocity in children following renal transplantation
Nephrol. Dial. Transplant.,
January 1, 2009;
24(1):
309 - 315.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
R. D. Smith and P. J. Levy
Review: New techniques for assessment of vascular function
Therapeutic Advances in Cardiovascular Disease,
October 1, 2008;
2(5):
373 - 385.
[Abstract]
[PDF]
|
|
|
|
|
|
|
A Williams, S Davies, A G Stuart, D G Wilson, and A G Fraser
Medical treatment of Marfan syndrome: a time for change
Heart,
April 1, 2008;
94(4):
414 - 421.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
P. Jankowski, K. Kawecka-Jaszcz, D. Czarnecka, M. Brzozowska-Kiszka, K. Styczkiewicz, M. Loster, M. Kloch-Badelek, J. Wilinski, A. M. Curylo, D. Dudek, et al.
Pulsatile but Not Steady Component of Blood Pressure Predicts Cardiovascular Events in Coronary Patients
Hypertension,
April 1, 2008;
51(4):
848 - 855.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
M. E. Safar and H. Smulyan
Central Blood Pressure and Hypertension
Hypertension,
April 1, 2008;
51(4):
819 - 820.
[Full Text]
[PDF]
|
|
|
|
|
|
|
M. P Schneider, C. Delles, A. U Klingbeil, M. Ludwig, R. E Kolloch, M. Krekler, K. O Stumpe, and R. E Schmieder
Effect of angiotensin receptor blockade on central haemodynamics in essential hypertension: results of a randomised trial
Journal of Renin-Angiotensin-Aldosterone System,
March 1, 2008;
9(1):
49 - 56.
[Abstract]
[PDF]
|
|
|
|
|
|
|
M. E. Safar
Review: Pulse pressure, arterial stiffness and wave reflections (augmentation index) as cardiovascular risk factors in hypertension
Therapeutic Advances in Cardiovascular Disease,
February 1, 2008;
2(1):
13 - 24.
[Abstract]
[PDF]
|
|
|
|
|
|
|
M. Frimodt-Moller, A. H. Nielsen, A.-L. Kamper, and S. Strandgaard
Reproducibility of pulse-wave analysis and pulse-wave velocity determination in chronic kidney disease
Nephrol. Dial. Transplant.,
February 1, 2008;
23(2):
594 - 600.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
M. Osranek, J. H. Eisenach, B. K. Khandheria, K. Chandrasekaran, J. B. Seward, and M. Belohlavek
Arterioventricular Coupling and Ventricular Efficiency After Antihypertensive Therapy: A Noninvasive Prospective Study
Hypertension,
February 1, 2008;
51(2):
275 - 281.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
M. F. O'Rourke
Arterial aging: pathophysiological principles
Vascular Medicine,
November 1, 2007;
12(4):
329 - 341.
[Abstract]
[PDF]
|
|
|
|
|
|
|
M. E. Safar
Mechanism(s) of Systolic Blood Pressure Reduction and Drug Therapy in Hypertension
Hypertension,
July 1, 2007;
50(1):
167 - 171.
[Full Text]
[PDF]
|
|
|
|
|
|
|
E. Agabiti-Rosei, G. Mancia, M. F. O'Rourke, M. J. Roman, M. E. Safar, H. Smulyan, J.-G. Wang, I. B. Wilkinson, B. Williams, and C. Vlachopoulos
Central Blood Pressure Measurements and Antihypertensive Therapy: A Consensus Document
Hypertension,
July 1, 2007;
50(1):
154 - 160.
[Full Text]
[PDF]
|
|
|
|
|
|
|
M. E. Safar and A. Fournier
Letter by Safar and Fournier Regarding Article, "Differential Impact of Blood Pressure-Lowering Drugs on Central Aortic Pressure and Clinical Outcomes: Principal Results of the Conduit Artery Function Evaluation (CAFE) Study"
Circulation,
October 10, 2006;
114(15):
e539 - e539.
[Full Text]
[PDF]
|
|
|
|
|
|
|
K. Hirata, T. Yaginuma, M. F. O'Rourke, and M. Kawakami
Age-Related Changes in Carotid Artery Flow and Pressure Pulses: Possible Implications for Cerebral Microvascular Disease
Stroke,
October 1, 2006;
37(10):
2552 - 2556.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
M. F. O'Rourke and J. B. Seward
Central Arterial Pressure and Arterial Pressure Pulse: New Views Entering the Second Century After Korotkov
Mayo Clin. Proc.,
August 1, 2006;
81(8):
1057 - 1068.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
P. S. Sever, N. R. Poulter, W. J. Elliott, M. C. Jonsson, H. R. Black, P. S. Sever, N. R. Poulter, W. J. Elliott, M. C. Jonsson, and H. R. Black
Blood Pressure Reduction Is Not the Only Determinant of Outcome
Circulation,
June 13, 2006;
113(23):
2754 - 2774.
[Full Text]
[PDF]
|
|
|
|
|
|
|
P. S.M., M. T., S. A., Y. H.T., C. D., K. S.A., S. V.P., W. B., L. P.S., T. S.M., et al.
Leaking Capillaries and White Lung in Sepsis--Is Angiopoietin 2 the Culprit?: Excess Circulating Angiopoietin-2 May Contribute to Pulmonary Vascular Leak in Sepsis in Humans. PLoS Medicine 3: e46, 2006
J. Am. Soc. Nephrol.,
May 1, 2006;
17(5):
1207 - 1217.
[Full Text]
[PDF]
|
|
|
|
|
|
|
The CAFE Investigators, for the Anglo-Scandinavian Cardiac Outcomes Trial, CAFE Steering Committee and Writing Committee, B. Williams, P. S. Lacy, S. M. Thom, K. Cruickshank, A. Stanton, D. Collier, A. D. Hughes, et al.
Differential Impact of Blood Pressure-Lowering Drugs on Central Aortic Pressure and Clinical Outcomes: Principal Results of the Conduit Artery Function Evaluation (CAFE) Study
Circulation,
March 7, 2006;
113(9):
1213 - 1225.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
T. Weber, J. Auer, M. F. O'Rourke, E. Kvas, E. Lassnig, G. Lamm, N. Stark, M. Rammer, and B. Eber
Increased arterial wave reflections predict severe cardiovascular events in patients undergoing percutaneous coronary interventions
Eur. Heart J.,
December 2, 2005;
26(24):
2657 - 2663.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
M. E. Safar
Wave reflections and cardiovascular epidemiology and therapeutics
Eur. Heart J.,
December 2, 2005;
26(24):
2609 - 2610.
[Full Text]
[PDF]
|
|
|
|
|
|
|
M. E. Safar
New problems raised by increased pulse pressure
Eur. Heart J.,
October 2, 2005;
26(20):
2081 - 2082.
[Full Text]
[PDF]
|
|
|
|
|
|
|
M. F. O'Rourke, W. W. Nichols, E. O'Brien, B. A. Kingwell, and P. A. Blombery
Effects of Ramipril on Arterial Stiffness
Hypertension,
October 1, 2005;
46(4):
e14 - e15.
[Full Text]
[PDF]
|
|
|
|
|
|
|
M. F. O'Rourke and M. E. Safar
Relationship Between Aortic Stiffening and Microvascular Disease in Brain and Kidney: Cause and Logic of Therapy
Hypertension,
July 1, 2005;
46(1):
200 - 204.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
J. Amar, J.-B. Ruidavets, J.-C. Peyrieux, J.-M. Mallion, J. Ferrieres, M. E. Safar, and B. Chamontin
C-Reactive Protein Elevation Predicts Pulse Pressure Reduction in Hypertensive Subjects
Hypertension,
July 1, 2005;
46(1):
151 - 155.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
H. H. Dao, R. Essalihi, C. Bouvet, and P. Moreau
Evolution and modulation of age-related medial elastocalcinosis: Impact on large artery stiffness and isolated systolic hypertension
Cardiovasc Res,
May 1, 2005;
66(2):
307 - 317.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
M. F. O'Rourke and W. W. Nichols
Aortic Diameter, Aortic Stiffness, and Wave Reflection Increase With Age and Isolated Systolic Hypertension
Hypertension,
April 1, 2005;
45(4):
652 - 658.
[Full Text]
[PDF]
|
|
|
|
|
|
|
C. Vlachopoulos, F. Kosmopoulou, D. Panagiotakos, N. Ioakeimidis, N. Alexopoulos, C. Pitsavos, and C. Stefanadis
Smoking and caffeine have a synergistic detrimental effect on aortic stiffness and wave reflections
J. Am. Coll. Cardiol.,
November 2, 2004;
44(9):
1911 - 1917.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
M. E. Safar
Peripheral Pulse Pressure, Large Arteries, and Microvessels
Hypertension,
August 1, 2004;
44(2):
121 - 122.
[Full Text]
[PDF]
|
|
|
|
|
|
|
G. F. Mitchell, H. Parise, E. J. Benjamin, M. G. Larson, M. J. Keyes, J. A. Vita, R. S. Vasan, and D. Levy
Changes in Arterial Stiffness and Wave Reflection With Advancing Age in Healthy Men and Women: The Framingham Heart Study
Hypertension,
June 1, 2004;
43(6):
1239 - 1245.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
