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CLINICAL RESEARCH: ARTERIAL REFLECTIONS AND STIFFNESS

Impact of Heart Rate on Central Aortic Pressures and Hemodynamics

Analysis From the CAFE (Conduit Artery Function Evaluation) Study: CAFE-Heart Rate

Department of Cardiovascular Sciences, University of Leicester School of Medicine, and the Leicester NIHR Cardiovascular Biomedical Research Unit, Leicester, United Kingdom

Manuscript received November 19, 2008; revised manuscript received February 11, 2009, accepted February 23, 2009.

^_* Reprint requests and correspondence: Dr. Bryan Williams, Department of Cardiovascular Sciences, University of Leicester, Clinical Sciences Building, Leicester Royal Infirmary, P.O. Box 65, Leicester, LE2 7LX, United Kingdom (Email: bw17{at}le.ac.uk).

Objectives: The CAFE (Conduit Artery Function Evaluation) study showed less effective central aortic pressure lowering with atenolol-based therapy versus amlodipine-based therapy in people with hypertension. The present study examined the importance of heart rate (HR) as a determinant of this effect.

Background: Recent analyses have suggested that beta-blockers are less effective at reducing cardiovascular events than alternative blood pressure (BP)-lowering therapies. There has been much debate about the mechanism for this shortfall in benefit and specifically the role of HR lowering by beta-blockers.

Methods: Central pressures were derived from brachial pressure and radial pulse wave analysis in 2,073 patients, and 7,146 measurements were recorded and analyzed over follow-up for up to 4 years.

Results: There was no impact of HR on brachial systolic or pulse pressures; however, there was a highly significant inverse relationship between HR and central aortic systolic and pulse pressures (p < 0.001). This was dependent on a strong inverse relationship between HR and augmentation index, indicative of increased wave reflection at lower HRs. Multiple regression, adjusted for brachial BP, showed HR to be the major determinant of central pressures. Moreover, HR and brachial BP accounted for 92% of the variability in central systolic and pulse pressures. Consequently, drug-related differences in central aortic pressures were markedly attenuated after adjustment for HR.

Conclusions: When comparing beta-blocker–based treatments with other BP-lowering strategies, HR reduction with beta-blockers is a major mechanism accounting for less effective central aortic pressure reduction per unit change in brachial pressure.

Key Words: beta-blocker • heart rate • central aortic pressure • hypertension

Abbreviations and Acronyms   AIx = augmentation index   BP = blood pressure   HR = heart rate   PP = pulse pressure

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