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”
To the Editor:
The aims of this letter are to congratulate the authors for the results of Conduit Artery Function Evaluation (CAFE) study1 and to challenge the difference in heart rate as a preponderant explanation for the differences in central systolic blood pressure (SBP) between amlodipine- and atenolol-based treatment. On the basis of the Regression of Arterial Stiffness in a Controlled Double-Blind Study (REASON), in which perindopril plus indapamide (Per/Ind) was compared with atenolol alone for 12 months in hypertensive subjects,2 we would like to contribute to this question.
In the REASON Study, Per/Ind reduced SBP more than atenolol did for the same diastolic blood pressure reduction. The differences were more pronounced when using carotid measurements than with brachial measurements, to the same extent as in the CAFE study. Cardiac hypertrophy, used as a surrogate of cardiac outcomes, was reduced more with Per/Ind. All results were adjusted for previous antihypertensive therapy and to per-trial drug dosage. Changes in ventricular ejection and vascular resistance were identical in the 2 arms. Differences in brachial SBP occurred at month 1 but became significant only at month 12. During this period, the arm difference in augmentation index (AI) was also significant, but the difference was considerably attenuated after adjustment to left ventricular ejection time (LVET). However, results from month 0 to month 12 clearly showed the progressive reduction of AI with Per/Ind but not atenolol. Moreover, we did a multivariate analysis in which brachial or central SBP reduction (%) in each arm was defined as the dependent variable and mean arterial pressure, LVET, AI, and pulse wave velocity were defined as independent variables. LVET had no significant contribution to SBP reduction. Mean arterial pressure was correlated with brachial but not central SBP reduction in either arm. With Per/Ind but not atenolol, the central SBP reduction was independently correlated with AI (only between month 0 and month 6) and with pulse wave velocity (throughout the 12 months). We suggested that the reversibility of arteriolar structural changes, already described for perindopril,3 was responsible for the difference in central SBP between drug regimens, causing differences in reflection sites under perindopril but not atenolol.1,4 The SBP reduction was significantly more pronounced in the presence of increased C-reactive protein, a result that favors the role of Per/Ind.5 Finally, the diuretic indapamide was probably a key point of treatment because comparison between atenolol and converting enzyme inhibition alone usually shows differences in wave reflections but never in SBP.2,4
Williams B, Lacy PS, Thom SM, Cruickshank K, Stanton A, Collier D, Hughes AD, Thurston H, O’Rourke M. 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. 2006; 113: 1213–1225.
London GM, Asmar RG, O’Rourke MF, Safar ME, on behalf of the REASON Project Investigators. Mechanism(s) of selective systolic blood pressure reduction after a low-dose combination of perindopril/indapamide in hypertensive subjects: comparison with atenolol. J Am Coll Cardiol. 2004; 43: 92–99.
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Amar J, Ruidavets JB, Peyrieux JC, Mallion JM, Ferrieres J, Safar ME, Chamontin. C-reactive protein elevation predicts pulse pressure reduction in hypertensive subjects. Hypertension. 2005; 46: 151–155.