Antihypertensive Treatment and Central Arterial Hemodynamics: A Meta-Analysis of Randomized Controlled Trials

Abstract

Background: Antihypertensive treatment may have different effects on central arterial hemodynamics. The extent of the difference in effects between various antihypertensive drugs remains undefined.Methods: We conducted a systematic review and meta-analysis of randomized controlled trials that explored the effects of antihypertensive agents on both central and peripheral systolic blood pressure (SBP) and pulse pressure (PP) or central augmentation index, with a special focus on the comparison between newer [renin-angiotensin-aldosterone system (RAS) inhibitors and calcium-channel blockers (CCBs)] and older antihypertensive agents (diuretics and β- and α-blockers).Results: In total, 20 studies (n = 2,498) were included. Compared with diuretics (10 studies), β-blockers (16 studies), or an α-blocker (1 study), RAS inhibitors (21 studies), and CCBs (6 studies) more efficaciously (P < 0.001) reduced both central and peripheral SBP by a weighted mean difference of −5.63 (−6.50 to −4.76 mmHg) and −1.97 mmHg (−2.99 to −0.95 mmHg), respectively. Compared with older agents, the newer agents also more efficaciously (P < 0.001) reduced central PP (−3.27 mmHg; −4.95 to −1.59 mmHg), augmentation index (−6.11%; −7.94 to −4.29) and augmentation (−3.35 mmHg; −5.28 to –1.42 mmHg) but not peripheral PP (p ≥ 0.09). Accordingly, the newer agents reduced central-to-peripheral PP amplification significantly less than the older agents (0.11 mmHg; 0.05 to 0.17 mmHg; P < 0.001).Conclusion: Newer agents, such as RAS inhibitors and CCBs, were significantly more efficacious than older agents in their effects on central hemodynamics.

Central hypertension is a non‐negligible cardiovascular risk factor

“…Since central BP elevation is related to adverse outcomes, and various classes of antihypertensive agents have different treatment effects on central BPs, there is growing interest in the treatment of central hypertension. 2,5,6 Recently, we performed a meta-analysis of 20 published randomized controlled trials to compare newer (reninangiotensin-aldosterone system [RAS] inhibitors and calcium-channel blockers [CCBs]) with older antihypertensive agents (diuretics and βand α-blockers) regarding their effects on central hemodynamics. 6 The analyses showed that compared with older drugs, RAS inhibitors and that an even newer antihypertensive drug class, that is, angiotensin receptor neprilysin inhibitor (ARNI), was more effective in reducing central systolic and pulse pressures by about 4 mmHg compared with olmesartan.…”

“… 1 , 9 Although BP is routinely measured at the brachial artery in clinical settings, discrepancies between brachial and central BPs have been noticed in their absolute values, 2 associations with target organ damage 3 and adverse outcomes, 4 and effects of BP lowering agents. 5 , 6 The anatomic proximity of the aorta to heart, brain, and kidney gives rise to the hypothesis that central BP might be a better reflection of pulsatile pressure load of the target organs and a better predictor of outcomes than peripheral BP. However, up to now the evidence supporting the hypothesis remains inconsistent.…”

“…Since central BP elevation is related to adverse outcomes, and various classes of antihypertensive agents have different treatment effects on central BPs, there is growing interest in the treatment of central hypertension. 2 , 5 , 6 Recently, we performed a meta‐analysis of 20 published randomized controlled trials to compare newer (renin–angiotensin–aldosterone system [RAS] inhibitors and calcium‐channel blockers [CCBs]) with older antihypertensive agents (diuretics and β‐ and α‐blockers) regarding their effects on central hemodynamics. 6 The analyses showed that compared with older drugs, RAS inhibitors and CCBs more efficaciously ( P < .001) reduced central and brachial systolic BPs by a weighted mean difference of −5.63 mmHg (−6.50 to −4.76 mmHg) and −1.97 mmHg (−2.99 to −.95 mmHg), respectively, and central PP −3.27 mmHg (−4.95 to −1.59 mmHg), augmentation index −6.11% (−7.94% to−4.29%), and augmentation pressure −3.35 mmHg (−5.28 to –1.42 mmHg).…”

“… 2 , 5 , 6 Recently, we performed a meta‐analysis of 20 published randomized controlled trials to compare newer (renin–angiotensin–aldosterone system [RAS] inhibitors and calcium‐channel blockers [CCBs]) with older antihypertensive agents (diuretics and β‐ and α‐blockers) regarding their effects on central hemodynamics. 6 The analyses showed that compared with older drugs, RAS inhibitors and CCBs more efficaciously ( P < .001) reduced central and brachial systolic BPs by a weighted mean difference of −5.63 mmHg (−6.50 to −4.76 mmHg) and −1.97 mmHg (−2.99 to −.95 mmHg), respectively, and central PP −3.27 mmHg (−4.95 to −1.59 mmHg), augmentation index −6.11% (−7.94% to−4.29%), and augmentation pressure −3.35 mmHg (−5.28 to –1.42 mmHg). 6 The difference in the effects of agents on heart rate and vasodilatation, which are 2 important regulators of central hemodynamics, might explain the observations at least in part.…”

Use of antihypertensive medications and the risk of glaucoma onset: Findings from the 45 and Up Study

“…In contrast, several cross‐sectional studies suggest that vascular dysregulation and retinal ischaemia secondary to excessive hypotension also contribute to the onset of glaucoma 10,11 . The potential bimodal effect of BP on glaucoma risk 12 has raised concerns regarding the association between glaucoma and antihypertensive medications, which regulate the BP level and affect systemic hemodynamics 13 . Further exploration of this association will greatly improve a mechanistic understanding of BP in glaucoma development, and may yield novel insights into glaucoma prevention and treatment.…”