Impact of Heart Rate on Central Aortic Pressures and Hemodynamics: Analysis From the CAFE (Conduit Artery Function Evaluation) Study: CAFE-Heart Rate

Abstract

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. 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. 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. 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. 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.