Palatini Paolo, Benetos Athanase, Julius Stevo
Department of Clinical and Experimental Medicine, University of Padova, Padova, Italy.
Drugs. 2006;66(2):133-44. doi: 10.2165/00003495-200666020-00001.
Thirty-eight studies have been published to date on the association between elevated heart rate and mortality. After adjustment for other risk factors, only two studies for all-cause mortality and four studies for cardiovascular mortality reported an absence of association between heart rate and mortality in male populations. This relationship has been found to be generally weaker among females. Most of these studies investigated samples of general populations. The four studies performed in hypertensive men found a positive association between heart rate and all-cause mortality (hazard ratios ranging from 1.9 to 2.0) or cardiovascular mortality (hazard ratios ranging from 1.3 to 1.7). In spite of this evidence, elevated heart rate remains a neglected cardiovascular risk factor in both genders. The pathogenetic mechanisms connecting high heart rate, hypertension, atherosclerosis and cardiovascular events have also been explicated in many studies. Elevated heart rate is due to an increased sympathetic and decreased parasympathetic tone. This altered balance of the autonomic nervous system tone could explain the increase in events with the increased heart rate. However, it has also been proved that blood flow changes associated with high heart rate favour both the formation of the atherosclerotic lesion and the occurrence of the cardiovascular event. Reduction of heart rate in hypertensive patients with increased heart rate could be an additional goal of antihypertensive therapy. Several trials retrospectively showed the beneficial effect of cardiac-slowing drugs, such as beta-adrenoceptor antagonists (beta-blockers) and non-dihydropyridine calcium channel antagonists, on mortality, notably in patients with coronary heart disease, but no published data are available in patients with hypertension free of coronary heart disease. Other antihypertensive drugs that have been shown to reduce the heart rate are centrally acting drugs and angiotensin II receptor antagonists, but their bradycardic effect is rather weak. The f-channel antagonist ivabradine is a selective heart rate-lowering agent with no effect on blood pressure. Although it has not been proven in existing trials, it would seem reasonable to recommend antihypertensive agents that decrease the heart rate in hypertensive patients with a heart rate higher than 80-85 beats per minute. Since the fast heart rate per se causes cardiovascular damage, all drugs that lower the heart rate have the potential of further reducing cardiovascular events in patients with elevated heart rate. Unfortunately, lowering of the heart rate is not a clinically recognised goal. Prospective trials investigating whether treatment of high heart rate can prevent cardiovascular events, notably in hypertensive patients, are warranted.
迄今为止，已发表了38项关于心率升高与死亡率之间关联的研究。在对其他风险因素进行调整后，仅有两项关于全因死亡率的研究以及四项关于心血管死亡率的研究报告称，在男性人群中，心率与死亡率之间不存在关联。而在女性中，这种关系通常较弱。这些研究大多调查的是普通人群样本。在高血压男性中进行的四项研究发现，心率与全因死亡率（风险比在1.9至2.0之间）或心血管死亡率（风险比在1.3至1.7之间）呈正相关。尽管有这些证据，但心率升高在男女两性中仍然是一个被忽视的心血管风险因素。许多研究也阐述了将高心率、高血压、动脉粥样硬化和心血管事件联系起来的发病机制。心率升高是由于交感神经张力增加和副交感神经张力降低所致。自主神经系统张力的这种改变平衡可以解释随着心率增加事件的增多。然而，也已证明与高心率相关的血流变化有利于动脉粥样硬化病变的形成和心血管事件的发生。对于心率升高的高血压患者，降低心率可能是抗高血压治疗的一个额外目标。几项试验回顾性地显示了心脏减慢药物，如β肾上腺素能受体拮抗剂（β阻滞剂）和非二氢吡啶类钙通道拮抗剂，对死亡率的有益影响，尤其是在冠心病患者中，但在无冠心病的高血压患者中尚无已发表的数据。其他已被证明可降低心率且具有心脏减慢作用的抗高血压药物是中枢作用药物和血管紧张素II受体拮抗剂，但其减慢心率的作用相当微弱。If通道拮抗剂伊伐布雷定是一种选择性降低心率的药物，对血压无影响。尽管在现有试验中尚未得到证实，但对于心率高于每分钟80 - 85次的高血压患者，推荐使用能降低心率的抗高血压药物似乎是合理的。由于快速心率本身会导致心血管损害，所有降低心率的药物都有可能进一步减少心率升高患者的心血管事件。不幸的是，降低心率并非临床上公认的目标。有必要进行前瞻性试验，以研究治疗高心率是否能预防心血管事件，尤其是在高血压患者中。
