316 β -Blockers are recognized by most clinical guidelines 1,2 as valuable blood pressure (BP)-lowering drugs. 3–5 However, despite the fact that reduction in cardiovascular morbidity and mortality in hypertension is largely driven by treatment-induced BP changes, 6,7 cardiovascular protection offered by β-blockers is weaker than that predicted from BP reduction. In fact, when compared with other antihypertensive classes, despite comparable BP reductions, β-blockers afford a lower protection from stroke, 8 cardiovascular events, 9 and death. 3 Moreover, in some prospec- tive trials, β-blockers were less effective renin–angiotensin system blockers in inducing regression of left ventricular hypertrophy. 10,11 One of the reasons why β-blockers may provide a lesser cardiovascular protection involves their effects on central BP. In a prospective trial in which an atenolol-based combina- tion therapy was compared with a perindopril-based regimen, subjects randomized to atenolol showed significantly higher values of central systolic BP (cSBP) despite similar peripheral SBP (pSBP) reduction. 12 Because the pressure waveform undergoes a progres- sive amplification ongoing from the heart to the peripheral sites, SBP and pulse pressure (PP) measured at the brachial level are generally higher than the corresponding aortic (cen- tral) values. At the individual level, pressure amplification is determined by the timing and amplitude of the reflected wave from peripheral sites, as well as by height, sex, heart rate, posture, arterial tapering, and the degree of peripheral vasoconstriction. 13 Thus, drugs with different effects on the physiological determinants of SBP amplification may result in different SBP-lowering effects at the aortic and brachial level. β-blocking agents, such as atenolol and metoprolol, negatively affect SBP amplification through a reduction in heart rate and a contemporary increase in peripheral vasoconstriction, which Abstract—β-Blockers are less effective than other antihypertensive drug classes in reducing central systolic blood pressure (cSBP) as compared with peripheral SBP (pSBP). Whether this effect is less pronounced with vasodilating β-blockers (VBB) when compared with nonvasodilating β-blockers (NVBB) remains unsettled. We conducted a systematic review and meta-analysis of randomized trials exploring the effects of β-blockers on both pSBP and cSBP in hypertension. We selected 20 studies, for a total of 32 treatment arms (n=21 for NVBB, n=11 for VBB) and 1263 participants (n=962 for NVBB, n=301 for VBB). pSBP decreased from 150 to 133 mm Hg for NVBB and from 145 to 134 mm Hg for VBB. cSBP decreased from 137 to 126 mm Hg for NVBB and from 132 to 123 mm Hg for VBB. SBP amplification (pSBP– cSBP) decreased significantly under VBB (-5.6 mm Hg; 95% confidence interval, -7.8, -3.4 mm Hg), but not under NVBB (-1.1 mm Hg; 95% confidence interval, -3.4, +1.2 mm Hg; P<0.01 versus NVBB). There was high heterogeneity both within and between β-blockers subclasses. In a meta-regression model, the weighted difference in treatment-induced changes in SBP amplification between NVBB and VBB lost its significance after adjustment for mean age and baseline pSBP and heart rate (-2.9±2.3 mm Hg; P=0.22) and was almost abolished after adjustment for treatment-induced heart rate changes (-0.1±0.5 mm Hg; P=0.78). In conclusion, NVBBs, but not VBBs, determine a lower reduction in cSBP than in pSBP. However, the difference in treatment-induced SBP amplification changes between NVBB and VBB is nearly abolished after accounting for differences in heart rate changes. (Hypertension. 2016;67:316-324. DOI: 10.1161/HYPERTENSIONAHA.115.06467.) • Online Data Supplement Key Words: antihypertensive agents ■ aortic blood pressure ■ beta-adrenergic blockers ■ blood pressure ■ confidence intervals ■ heart rate ■ hypertension Received September 11, 2015; first decision October 7, 2015; revision accepted November 5, 2015. From the Dipartimento di Medicina (G.P., F.B., G.S.) and Dipartimento di Scienze Politiche (M.G.R.), Università di Perugia, Perugia, Italy; and Struttura Complessa di Medicina Interna, Azienda Ospedaliero-Universitaria di Terni, Terni, Italy (G.P., F.B., G.S.). The online-only Data Supplement is available with this article at http://hyper.ahajournals.org/lookup/suppl/doi:10.1161/HYPERTENSIONAHA. 115.06467/-/DC1. Correspondence to Giuseppe Schillaci, Dipartimento di Medicina, Università degli Studi di Perugia, Struttura Complessa di Medicina Interna, Azienda Ospedaliero-Universitaria di Terni, Piazzale Tristano di Joannuccio, 1, IT-05100 Terni, Italy. E-mail giuseppe.schillaci@unipg.it Effects of β-Blockers With and Without Vasodilating Properties on Central Blood Pressure Systematic Review and Meta-Analysis of Randomized Trials in Hypertension Giacomo Pucci, Maria Giovanna Ranalli, Francesca Battista, Giuseppe Schillaci © 2015 American Heart Association, Inc. Hypertension is available at http://hyper.ahajournals.org DOI: 10.1161/HYPERTENSIONAHA.115.06467 β-Blockers and Central Blood Pressure Downloaded from http://ahajournals.org by on June 12, 2020