The Role of Beta-Blockers in the Treatment of Hypertension
The Role of Beta-Blockers in the Treatment of Hypertension
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DOI：
10.1007/5584_2016_36
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发表时间：
2017-01-01
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通讯作者：
Cruickshank, John M.
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作者：
Cruickshank, John M.
重要性两个主要的指南委员会（JNC-8和NICE UK）已经放弃了β受体阻滞剂作为治疗高血压的一线治疗。此外，最近的荟萃分析（不考虑年龄）得出结论，β受体阻滞剂是治疗高血压的不合适的一线药物。这篇综述旨在阐明这种行为和结论的“对与错”。ObjectivesBecause原发性/原发性高血压的病理生理学在老年人和年轻人中存在差异，后者与肥胖和交感神经活动增加密切相关，作者试图澄清β受体阻滞剂在年轻/中年组中降低死亡风险的疗效，证据采集利用PubMed进行了四次检索，截止日期为2015年12月31日。一个搜索是在“高血压和肥胖和交感神经活动”的条件下。第二个是“高血压和血浆去甲肾上腺素/去甲肾上腺素和生存”。第三个是“β受体阻滞剂或肾上腺素能β受体拮抗剂与高血压和年龄与中风或心肌梗死或死亡”。第四个是“β受体阻滞剂和高血压和年龄和死亡，中风，心肌梗死的荟萃分析“结果舒张期（有或没有收缩期）高血压，与孤立的收缩期高血压，主要发生在年轻的受试者，并与超重/肥胖和交感神经活动增加。在年轻/中年高血压受试者中，高血浆去甲肾上腺素水平与未来心血管事件和死亡风险增加相关（与血压无关）。高静息心率（高交感神经活动的替代物）同样预测年轻高血压受试者的过早全因死亡、冠心病和心血管事件。在该年轻/中年高血压组中，增加交感神经活动的降压药（利尿剂、二氢吡啶类钙拮抗剂和血管紧张素受体阻滞剂（ARB））不会降低（可能增加）心肌梗死的风险，因此不适合作为该年龄组的一线药物。相比之下，在年轻/中年高血压受试者（小于60岁）中，荟萃分析显示β受体阻滞剂在减少死亡/卒中/心肌梗死方面显著上级随机安慰剂，至少与随机对照药物一样有效。在这一年轻/中年高血压组中，β受体阻滞剂（与随机安慰剂或利尿剂相比）已被证明可使非吸烟男性的心肌梗死风险降低35- 50%，卒中风险降低50- 55%（与安慰剂相比）。阿替洛尔至少与ACE抑制剂一样有效（卡托普利）降低所有7个心血管终点（包括中风，减少了50%），与不严格控制血压相比，肥胖高血压合并2型糖尿病患者（UKPDS研究）;经过20年的随访，阿替洛尔在降低全因死亡风险方面显著上级ACE抑制剂（23（β-受体阻滞剂具有抗癌特性，这可能是相关的）.结论和相关性年轻/中年原发性/原发性高血压是由高交感神经活动支持的。在这个年龄组中，高静息心率和高血浆去甲肾上腺素水平（与血压无关）与过早心血管事件和死亡有关。因此，增加交感神经活动的降压药，即利尿剂、二氢吡啶类钙受体阻滞剂和ARB，不适合该年轻年龄组的一线选择。β受体阻滞剂与随机安慰剂和其他抗高血压药物相比，在降低年轻人死亡/卒中/心肌梗死风险方面表现良好（
ImportanceTwo major guide-line committees (JNC-8 and NICE UK) have dropped beta-blockers as first-line therapy in the treatment of hypertension. Also, recent meta-analyses (that do not take age into account) have concluded that beta-blockers are inappropriate first-line agents in the treatment of hypertension. This review seeks to shed some light on the "rights and wrongs" of such actions and conclusions.ObjectivesBecause the pathophysiology of primary/essential hypertension differs in elderly and younger subjects, the latter being closely linked to obesity and increased sympathetic nerve activity, the author sought to clarify the efficacy of beta-blockers in the younger/middle-aged group in reducing the risk of death, and cardiovascular end-points.Evidence acquisitionFour searches were undertaken, utilising PubMed up to 31st Dec 2015. One search was under the terms "hypertension AND obesity AND sympathetic nerve activity". A second was "hypertension AND plasma noradrenaline/norepinephrine AND survival". A third was "beta-blockers or adrenergic beta-antagonists AND hypertension AND age AND stroke or myocardial infarction or death". A fourth was "meta-analysis of betablockers AND hypertension AND age AND death, stroke, myocardial infarction"ResultsDiastolic (with or without systolic) hypertension, in contrast to isolated systolic hypertension, occurs primarily in younger subjects, and is linked to overweight/obesity and increased sympathetic nerve activity. In younger/middle-aged hypertensive subjects, high plasma norepinephrine levels are linked (independent of blood pressure) to an increased risk of future cardiovascular events and death. High resting heart rates (a surrogate for high sympathetic nerve activity) likewise predict premature all-cause death, coronary heart disease and cardiovascular events in younger hypertensive subjects. In this younger/middle-aged hypertensive group, antihypertensive agents that increase sympathetic nerve activity (diuretics, dihydropyridine calcium blockers, and angiotensin receptor blockers (ARBs)) do not decrease (and may increase) the risk of myocardial infarction, and are therefore inappropriate first-line agents in this age-group. By contrast, in younger/middle-aged hypertensive subjects (less than 60 years old), meta-analysis has shown that beta-blockers are significantly superior to randomised placebo, and at least as effective as randomised comparator agents, in reducing death/stroke/myocardial infarction. In this younger/middle-aged hypertensive group beta-blockers have been shown (vs randomised placebo or diuretics) to reduce the risk of myocardial infarction by 35-50 %, and stroke by 50-55 % (vs placebo), in non-smoker men. Atenolol was at least as effective as ACE-inhibition (captopril) in reducing all 7 cardiovascular endpoints (including stroke which was reduced by 50 %), vs less tight control of blood pressure, in obese hypertensive subjects with type-2 diabetes (UKPDS study); and after 20 years follow-up, atenolol was significantly (23 %) superior to the ACE-inhibitor in reducing the risk of all-cause death (beta-blockers have anti-cancer properties, which maybe relevant).Conclusions and RelevancePrimary/essential hypertension in younger/middle-age is underpinned by high sympathetic nerve activity. In this age-group high resting heart rates and high plasma norepinephrine levels (independent of blood pressure) are linked to premature cardiovascular events and death. Thus, antihypertensive agents that increase sympathetic nerve activity ie diuretics, dihydropyridine calcium blockers, and ARBs, are inappropriate first-line choices in this younger age-group. Beta-blockers perform well vs randomised placebo and other antihypertensive agents regarding reduced risk of death/stroke/myocardial infarction in younger (