广州市第一人民医院 李广镰

? 动脉粥样硬化 - 多种危险因素的汇聚 心肌梗塞 脑卒中 CVD 死亡 经典的危险因素 动脉血栓病史 肥胖、 CVD家族史、 稳定型心绞痛 糖尿病 生活方式因素 房颤 高半胱氨酸血症 高血脂 高血压 高凝状态 性别 年龄 动脉血栓病史 稳定型心绞痛 不稳定型心绞痛 MI史 脑卒中史 TIA PAD 心肌梗塞 脑卒中 CVD 死亡 6 ? 新发现的危险因素 前凝血酶因子升高: 纤维蛋白原, CRP, PAI-1, 颈动脉内膜增厚 遗传特质 BP: ≤ 140/90 / 130/80 mmHg LDL-C: ≤ 120 / 100 / 70 mg/dl HbA1C: ≤6.0% / ≤ 6.5%

提 要 心率与正常人 心率与高血压 心率与冠心病 心率的控制

心率是哺乳动物的物种特征之一 心率（次 / 分） 虎 驴 1000 小鼠 500 仓鼠 300 老鼠 猴 土拨鼠 猫 狗 100 200万年，猎人 / 采集。20岁 2万年，农夫 / 牧人， 30岁 200年，工人 / 白领，70岁 1000 小鼠 500 仓鼠 450bpm / 1.5ys 心率（次 / 分） 300 老鼠 猴 30kg / 200bpm / 15ys 土拨鼠 猫 狗 100 猩猩 200kg / 120bpm/ 30ys 长颈鹿 虎 马 动物体型越小、 心率越快、寿命越短； 从仓鼠到鲸鱼体重相差50万倍， 心率相差35倍，寿限相差20倍。 50 驴 狮 象 人 60kg / 70bpm / 80ys 20 鲸 18 bpm / 30ys 寿限（年） 5 10 20 30 40 80 100 M. Bohm et al. Euro Heart J. (2003) 5:114

冥冥之中有定数 Heart rate and life expectancy 上帝给每个人的活期存款 尽管哺乳动物的寿限相差可达40倍，但其一生总的心跳次数是相对恒定的，约 7 亿次 老鼠心率240次/分，寿命5年，一生心跳 6.3 亿次 Galapagos龟6次/分，寿命177年，一生心跳 5.6 亿次 人类平均心率70次/分， 平均每天10万次，运送10吨血液 一生约 25 – 30 亿次。 如能将心率从70次/分减至60次/分， 寿限将从 80 年增至 93.3年。 心率慢 3 bpm，寿命多3年 交感神经张力、体温、代谢水平、细胞能量需求都与心率呈负相关，都受心率控制；

正常人中心率与心血管事件的关系 Framingham 研究 5070 例 35~94岁无心血管疾病男性 36 年追踪的结果 2 4 倍 年内每千人发生事件数 4 倍 心率( 次/分 ) heart rate elevated by 40 beats/min was accompanied by a 70% increase in the age- and systolic blood pressure–adjusted relative risk for cardiovascular mortality. Gillman M et al. Am Heart J. 1983;125:1148-1154.

正常人群中静息心率加快的后果 小结： 正常人静息心率加快 是高血压 、冠心病发生的重要危险因素 是全因死亡率升高的独立危险因素 研究 发表 时间 研究对象 观察 时期 主要结果 日本研究 2007 4 331 3 年 高血压发病率：HR <58 vs >72 bpm RR 1.61 (1.10 – 2.37） HARVEST Study 2006 1 103 6.4 年 持续性高血压：心率加快 ：心率正常， RR 2.0 ( 1.4 - 2.9) 以色列男性公务员研究 1973 10 000 (男) 5 年 急性心梗发生率：HR<61 vs >100 bpm, 发生率升高 2 倍 Paris Prospective Study 2005 5 713 (男) 23 年 心梗猝死发生率：HR <60 vs >75 bpm；RR 3.92 ( 1.91 - 8.00) National FINRISK Study 2010 11 334 (女) 6- 27 年 CHD事件： HR 增加 15 bpm, RR 1.20 (1.03 - 1.40) French Cohort Study 1999 19 389 18 年 全因死亡率：HR< 60 vs >80 bpm RR 1.44 (1.04 - 2.00), 21 853 12 年 全因死亡率: HR 增加 15 bpm, RR 1.21 (1.10 - 1.34) 小结： 正常人静息心率加快 是高血压 、冠心病发生的重要危险因素 是全因死亡率升高的独立危险因素 反映了交感神经张力升高的重要影响

提 要 心率与正常人 心率与高血压 心率与冠心病 心率的控制

高血压患者的静息心率更快 293例高血压患者，平均年龄59.2岁，男156例，女性137例，测定其静息心率、血糖、血脂及进行冠脉造影，并与正常血压人群作对比 结果：高血压患者静息心率显著高于正常血压者 1175例35-64岁高血压患者，将心率分为四个等级，建立logistic回归模型，校正多种心率相关因素，分析静息心率与高血压之间的关系 结果：与血压得到控制者相比较，未治疗的高血压患者更可能处于较高的静息心率级别 心率 次/分 魏玲，杨丽霞，郭传明. 原发性高血压患者静息心率增加的临床意义. 高血压杂志. 2003;11(3):211-214. Ferrieres J, Ruidavets,Am J Hypertens. 1999 Jun;12(6):628-631.

未治疗的高血压静息心率与死亡率间的关系 Framingham Heart Study (n=4530) 36 Year follow-up OR 2.18(95%CI 1.68-2.83) n=2037, Hypertating males N=2493, Hypertating females 年龄校正2年死亡率/每千人 Influence of heart rate on mortality among persons with hypertension: the Framingham Study. Gillman MW, Kannel WB, Belanger A, D'Agostino RB. Source Evans Section of Preventive Medicine and Epidemiology, Boston University School of Medicine, MA 02118. Abstract Previous studies have shown positive associations between heart rate and both all-cause and cardiovascular mortality. These relationships, however, have not been investigated in persons with hypertension. Using 36-year follow-up data from the Framingham Study, we evaluated from 4530 subjects, aged 35 to 74, whose blood pressures were > or = 140 mm Hg systolic or > or = 90 mm Hg diastolic and who were not treated with antihypertensive medication. We used pooled logistic regression to calculate biennial mortality rates. Odds ratios and 95% confidence intervals for each increment in heart rate of 40 beats/min, adjusted for age and systolic blood pressure level, were: for all-cause mortality, 2.18 (1.68, 2.83) for men and 2.14 (1.59, 2.88) for women; and for cardiovascular mortality, 1.68 (1.19, 2.37) for men and 1.70 (1.08, 2.67) for women. Exclusion of outcomes in the first 2 or 4 years after measurement of heart rate did not materially change the results, which suggests that rapid heart is not merely an indicator of preexisting illness. Therefore heart rate may be an independent risk factor for cardiovascular death in persons with hypertension. 静息心率（次/分） 心率＞85次/分组，与心率＜65次/分组比较，有显著统计学差异 Gillman M et al. Am Heart J. 1993;125:1148-1154

静息心率加快对老年收缩期高血压患者的影响 Systolic Hypertension in Europe Trial 纳入了4682 名基线SBP 160-219 / DBP＜95mmHg 的老年患者。 诊所心率均值为3次随访 测量6次血压的均值 结果：在未经治疗的老年收缩期高血压患者中，诊所心率>79 bpm者的死亡率显著增加。与≤79bpm者相比全，相对风险为 1.89 倍(95% CI, 1.33-2.68 ) Abstract OBJECTIVE: To examine the association of clinic and ambulatory heart rate with total, cardiovascular, and noncardiovascular death in a cohort of elderly subjects with isolated systolic hypertension from the Systolic Hypertension in Europe Trial. METHODS: A total of 4682 patients participated, whose untreated blood pressure on conventional measurement at baseline was 160 to 219 mm Hg systolic and lower than 95 mm Hg diastolic. Clinic heart rate was the mean of 6 readings during 3 visits. Ambulatory heart rate was recorded with a portable intermittent technique in 807 subjects. RESULTS: Raised baseline clinic heart rate was positively associated with a worse prognosis for total, cardiovascular, and noncardiovascular mortality among the 2293 men and women taking placebo. Subjects with heart rates higher than 79 beats/min (bpm) (top quintile) had a 1.89 times greater risk of mortality than subjects with heart rate lower than or equal to 79 bpm (95% confidence interval, 1.33-2.68 bpm). In a Cox regression analysis, predictors of time to death were heart rate (P<.001), age (P<.001), serum creatinine level (P =.001), presence of diabetes (P =.002), previous cardiovascular disease (P =.01), triglyceride readings (P =.02), smoking (P =.04), and elevated systolic blood pressure (P =.05), while total cholesterol level was found to be nonsignificant in the model. In the ambulatory monitoring subgroup, clinic and ambulatory heart rates predicted noncardiovascular but not cardiovascular mortality. However, in a Cox regression analysis in which clinic and ambulatory heart rates were included, a significant association with noncardiovascular mortality was found only for clinic heart rate (P =.004). In the active treatment group, the weak predictive power of clinic heart rate for mortality disappeared after adjustment for confounders. CONCLUSIONS: In untreated older patients with isolated systolic hypertension, a clinic heart rate greater than 79 bpm was a significant predictor of all-cause, cardiovascular, and noncardiovascular mortality. Ambulatory heart rate did not add prognostic information to that provided by clinic heart rate. Palatini P,et al. Predictive value of clinic and ambulatory heart rate for mortality in elderly subjects with systolic hypertension. Arch Intern Med. 2002 Nov 11;162(20):2313-21.

静息心率增加导致高血压前期患者的心血管事件升高 ARIC研究包括 3275名45-64岁高血压前期患者，平均随访10.1年 结果 ：静息心率增高的患者较心率较低的患者，全因死亡率高 50%（HR 1.50 95%CI：1.0-2.15）；CHD 死亡率高 49% (HR 1.49, 95%CI 1.03–2.14)。 随访结果显示，心率每增加1次/分，患者死亡率上升1%， elevated heart rate is a risk factor of cardiovascular morbidity and mortility King DE,et al. Long-term prognostic value of resting heart rate in subjects with prehypertension. Am J Hypertens. 2006 Aug;19(8):796-800.

提 要 心率与正常人 心率与高血压 心率与冠心病 心率的控制

(1 years)

Heart rate at admission and 6 months mortality in MI survivors：GISSI-3 Heart rate at admission and in-hospital mortality in MI survivors：GISSI-3 Mortality at 6 months of follow-up in patients with AMI Heart rate at admission and 6 months mortality in MI survivors：GISSI-3 Zuanetti. G. et al. Eur Heart J. 1999;1(suppl. H):H52-H57

European Heart Journal .2010. 31;3040–3045. 欧洲糖尿病和心脏病调查研究纳入了4961名稳定型冠心病管着，随访至少1年， 分析在治疗条件下不同心率组患者的心血管事件（全因死亡率、心梗和卒中）发生率。 Q2 (≤70 bpm) Q1 (≤62 bpm) Q4 (> 78 bpm) Q3 (≤78 bpm) 欧洲糖尿病和心脏病调查研究纳入了4961名稳定型冠心病患者，随访至少1年。根据静息心率将患者分层，(Q1 ≤62次/分, 62次/分<Q2 ≤70次/分, 70次/分<Q3≤78次/分,Q4>78次/分），结果发现坚持治疗的条件下，Q3，Q4的患者心血管事件累积发生率显著高于Q1和Q2，说明静息心率加快导致稳定型冠心病患者的心血管事件发生率增加。 European Heart Journal .2010. 31;3040–3045.

小结：心率增快是健康人群发生冠心病的重要危险因子 也是冠心病患者发生冠心病事件的独立预测因素

提 要 心率与正常人 心率与高血压 心率与冠心病 心率的控制

是否仅仅控制心率就能获益？ 是否将心率降低得越低越好？ 心率加快 与心血管事件的发生 及其所导致的死亡 / 病残率 密切相关 是否仅仅控制心率就能获益？ 是否将心率降低得越低越好？

f-通道 乙酰胆碱 去甲肾上腺素 M 型胆碱受体 -受体 Ca 通道 T-型 f-通道 Ca 通道 L-型 K 通道 伊伐布雷定是首个高度特异性超极化激活通道(If)阻滞剂,以剂量依赖性方式抑制If电流降低窦房结节律,由此减慢心率,而对心内传导、心肌收缩力或心室复极化无影响。 If电流是心脏动作电位4期内向电流,内流离子主要是Na+,也有K+参与,是窦房结的主要起搏电流,它决定舒 张期去极化曲线趋向于阈电位的斜率,因此,它控制着连续动作电位的间隔。抑制剂选择性作用于窦房结自律性P细胞的活性,不仅抑制其自律性,还能降低交感神经兴奋后的心率,增加舒张期充盈,保持各种运动程度时冠状大动脉及小动脉的血管舒张,保证在运动时心内膜有足够的血流灌注。 If电流是心脏动作电位4期内向电流,是窦房结的主要起搏电流；内流离子主要是Na+,也有K+参与, If电流决定舒张期去极化曲线趋向于阈电位的斜率, 控制着连续动作电位的间隔 伊伐布雷定选择性作用于窦房结自律性 P 细胞的活性,由此减慢心率 伊伐布雷定对心内传导、心肌收缩力或心室复极化无影响。 Liu Yanxia,Wang Zulu. Chin J Cardiovasc Rehabil Med,Oct 2010;19 (5): 562-5 Mulder P et al. Circulation. 2004;109:1674-9 21

仅仅减慢心率不能使所有冠心病/心衰患者获益 87%的患者联用β受体阻滞剂的可能影响了研究的结果 BEAUTIFUL研究：冠心病患者 减慢心率对心血管保护有益 仅仅减慢心率不能使所有冠心病/心衰患者获益 87%的患者联用β受体阻滞剂的可能影响了研究的结果 33个国家781个中心的10,917名患有冠脉疾病且左室射血分数<40%的患者。其中5,479名患者接受伊伐布雷定5 -7.5mg bid. 治疗，另外 5,438名患者接受相匹配的安慰剂治疗 主要终点:包括心血管死亡、因急性心肌梗死住院、因心力衰竭新发或恶化而住院的复合终点。 伊伐布雷定平均剂量： 6.18 mg 心率 (bpm) 50 60 70 80 随访时间(天) 15 30 90 180 360 540 720 安慰剂（n=5438） 伊伐布雷定（n=5479） 69 61 64 72 主要复合终点事件的发生率（%） 伊伐布雷定（n=5479） 安慰剂（n=5438） P = 0.94 *HR= 1.00（95%CI: 0.91 – 1.10) 5 10 15 20 25 时间（年） 0.5 1 1.5 2 一项随机、双盲、安慰剂对照、平行组研究，纳入了33个国家781个中心的10,917名患有冠脉疾病且左室射血分数<40%的患者。其中5,479名患者初始接受伊伐布雷定5 mg bid治疗，并逐渐提高至7.5 mg bid，另外5,438名患者接受相匹配的安慰剂治疗。观察降低心率是否可以降低患有冠脉疾病和左心室功能障碍的心血管死亡 主要终点定义为包括心血管死亡、因急性心肌梗死住院、因心力衰竭新发或恶化而住院的复合终点。 Fox K et al. Lancet Online August 31, 2008.

SHIFT trial, at 677 centers in 37 countries, >6500 pats with NYHA II-IV; LVEF <35%, resting heart rate >70 bpm, and a heart-failure hospitalization within the previous year Receive either placebo or ivabradine, a starting dose of 5 mg twice daily, with adjustments to achieve a resting heart rate of 50 to 60 bpm. Systolic Heart Failure Treatment with the If Inhibitor Ivabradine Trial (SHIFT), The SHIFT trial, conducted at 677 centers in 37 countries, randomized >6500 patients with NYHA class 2-4 heart failure, an LVEF <35%, a resting heart rate >70 bpm, and a heart-failure hospitalization within the previous year to receive either placebo or ivabradine at a starting dose of 5 mg twice daily, with adjustments to achieve a resting heart rate of 50 to 60 bpm. All patients were on standard heart-failure medications according to guidelines, including include ACE inhibitors or angiotensin-receptor blockers, beta blockers, aldosterone antagonists, and diuretics. Over a mean follow-up of 23 months, patients taking ivabradine showed a highly significant 18% reduction in the hazard ratio for cardiovascular death or hospitalization for worsening heart failure, compared with the control group, driven by significant 26% reductions in hazard ratios for the individual secondary end points of death from heart failure and hospitalization for worsening heart failure. signal a new potential direction for the treatment of heart failure characterized by an elevated heart rate as a therapeutic target. Ivabradine is a selective inhibitor of a sodium-potassium channel highly expressed in the sinoatrial node, it has a mild dampening effect. The drug has few other, if any, known cardiac effects. All patients were on standard heart-failure medications according to guidelines, including include ACE inhibitors or angiotensin-receptor blockers, beta blockers, aldosterone antagonists, and diuretics. The benefit of ivabradine appeared to go up with increasing heart rate. The hazard ratio for the primary end point was 0.93 (95% CI 0.80-1.08) for patients starting out with a rate <77 bpm but was 0.75 (95% CI 0.67-0.85) among those with rates of >77 bpm; the difference between the subgroups was significant at p=0.029. Dr Inder Anand (University of Minnesota, Minneapolis) "SHIFT confirms the importance of heart rate in the pathophysiology of heart failure and supports the concept that reduction of heart rate contributes significantly to beneficial outcomes in patients with heart failure. It appears therefore likely that heart rate is not only a risk factor but may well be a mediator of the progression of heart failure," "In patients with systolic heart failure who are in sinus rhythm, with heart rates over 70 bpm, receiving the usual clinical care, who are unable to tolerate higher doses of beta blockers," he said, "ivabradine is likely to improve their outcomes." The authors describe ivabradine as being "well tolerated" despite a 10% rate of bradycardia, which prompted withdrawal from the study by 1% of patients receiving the drug. that only one patient in the trial needed implantation of a pacemaker, "which tells you about the safety of this drug in terms of bradycardia. One of the messages of SHIFT is that there is very good tolerance of ivabradine on top of beta blockers." Swedberg et al point out that about 90% of patients in both groups were on beta blockers at randomization, 91% were on either ACE inhibitors or ARB, and about 60% were on aldosterone antagonists. But they also note that only 49% of patients in the trial were at >50% of beta-blocker target dosage and only 26% were at target dosages. "The average doses of the beta blockers were lower than doses used in clinical trials of beta blockers but are actually higher than doses reported in surveys and more closely mirror clinical practice than do doses used in trials testing these drugs," according to the authors. "Would these benefits have occurred if the dose of beta blocker had been more consistently closer to the recommended doses in the patients studied? Achieving recommended doses of evidence-based beta-blocker use in this study at only a 25% threshold despite urgings from well-recognized experts in heart failure highlights an opportunity to improve the quality of care of patients with heart failure." But Anand contends that further beta blockade probably wouldn't have made much difference. In a meta-analysis of 23 beta-blocker heart-failure trials involving over 19 000 patients, he observed, "McAcalister and his colleagues found that the mortality benefit was related more to the magnitude of heart-rate reduction and not to the dose of beta blocker."

SHIFT: 对心衰患者进一步减慢心率对心血管保护有益 可使住院率降低，但不能降低死亡率 Hazard ratio for cardiovascular death or heart-failure hospitalization by quintiles of increasing baseline heart rate, relative to lowest quintile Baseline heart rate quintiles, bpm HR (95% CI) p 70 to <72 1.00 — 72 to <75 1.15 (0.88-1.48) 0.308 75 to <80 1.33 (1.03-1.70) 0.027 80 to <87 1.80 (1.40-2.31) <0.0001 >87 2.34 (1.84-2.98) 对心衰患者进一步减慢心率对心血管保护有益 可使住院率降低，但不能降低死亡率 ESC guidelines for the management of heart failure（2012） ivabradine：充分使用ACEI/β-B/MRA仍不能控制，NYHA II-IV, EF< 35%, HR≥70 bpm 的慢性心力衰竭患者，降低心衰住院率（IIa, B）

β阻滞剂降低高血压患者的冠心病事件发生率 降压药物预防CVD的荟萃分析 荟萃分析纳入147项随机对照研究， 共46.4万患者： 对既往有CHD病史的高血压患者， β阻滞剂具有超越通过降压预防CHD 事件复发的特殊作用 与其他降压药物比较，β阻滞剂能更 多降低CHD事件发生风险 （ 29% vs 15%，P<0.001）。 但无心脏选择性的β阻滞剂缺乏预防 心衰的作用。 Results In the blood pressure difference trials β blockershad a special effect over and above that due to blood pressure reduction in preventing recurrent CHD events in people with a history of CHD: risk reduction 29% (95% CI 22% to 34%) compared with 15%(11% to 19%) in trials of other drugs. MR Law, JK Morris, NJ Wald, BMJ 2009;338:1245-1259.

冠心病是心脏性猝死的最主要原因 83% 快速性 室性心律失常 在美国，冠心病占心脏性猝死的潜在病因的比例高达62％ 17% 缓慢性 83% 快速性 室性心律失常 我国每年有近50余万人死于心脏性猝死，在心脏性猝死患者中， 80%的原因是冠心病 1. Zheng ZJ, Croft JB, Giles WH, Circulation 2001;104:2158-63. 2.我国每年5O余万人死于心脏性猝死。综述与进展. 2007; 36(1): 98. .

Prediction of mode of derth in heart failure Circulation 10 538例心力衰竭病人 ，NYHA II~IV，追踪1.5年；期间 2014 例死亡； 用西雅图心衰评分模式（SHFM）进行评分，比较不同原因的死亡率和构成比 SHFM 计分 0(n=4043) 1(n=4356) 2(n=1729) 3(n=361) 4(n=49) 猝死 死亡例数 265 407 242 90 10 年死亡率(%) 3.8 5.8 10.3 25.1 24.9 相对风险 1.0 1.5 2.7 6.5 6.5 泵衰竭死亡 死亡例数 56 227 273 102 26 年死亡率(%) 0.8 3.2 11.7 28.4 64.7 相对风险 1.0 4.1 15.0 38.4 87.6 在所有的心力衰竭病人中，猝死是最常见/最重要的死亡原因， 在低危（0~1分）的心衰患者中，绝大多数的死亡是由猝死引起的 在中—高危（2~3分）的患者中，猝死和泵衰竭同等重要 泵衰竭所致的死亡在极高危患者中为主，但此时的病人总数和死亡例数已很少

心率是代表交感激活的“窗口”，治疗的标靶 BBs是唯一被一致证明能够降低猝死的AAD 心率是代表交感激活的“窗口”，治疗的标靶 高血压、冠心病、心衰 交感神经过度激活 心率 加快 心肌 收缩 加强 自律性 增加 血管 收缩 交感 神经 刺激 肾素 分泌 增加 心律 失常 心肌 耗氧 增加 心律 失常 猝死 血压升 高、内 皮受损 儿茶酚 胺毒性 增加 RASS 活性 增加

Analysis from TNT study: 9580 stable CAD patients , Median follow-up of 4.9 years 静息心率≥70 bpm与<70 bpm比较 全因死亡、主要心血管事件明显增加 稳定性冠心病患者静息心率每增加10次导致主要心血管事件增加8％，尤其在静息心率≥70 bpm患者全因死亡率增加40％、心衰住院增加1 倍 冠心病患者的最佳心率—52.4次/分 "Heart rate in patients with coronary artery disease - the lower the better? An analysis from the Treating to New Targets (TNT) trial" [Meeting Abstract] Background: In patients post myocardial infarction and in those with established coronary artery disease (CAD), lower heart rate has been shown to improve long term cardiovascular prognosis. However, how low is low enough and the existence of J-curve relationship has not been proven. Methods: We evaluated 9602 patients, with CAD and a LDL cholesterol level <130 mg/dL, randomized to atorvastatin 80 mg vs. 10 mg, enrolled in the TNT trial. The post-baseline, time-dependent heart rate were categorized into 10 mm Hg increments. The primary outcome was a composite of death from coronary disease, nonfatal myocardial infarction, resuscitated cardiac arrest, and fatal or nonfatal stroke. Results: Among the 9602 patients, 886 (9.23%) experienced a primary outcome at 4.9 years (median) of follow-up. The relationship between heart rate and primary outcome followed a J-curve with increased event rates above and below the reference heart rate range, both unadjusted and adjusted (for baseline covariates, treatment effect and LDL levels). A time-dependent, non-linear, multivariate Cox proportional hazard (PH) model identified a nadir of 52.4 bpm where the event rate was lowest (Figure). Similar, non-linear relationship, with higher risk of events at lower heart rate was found for most of the secondary outcomes of all-cause mortality, CV mortality, nonfatal MI, or stroke. (Figure presented) Conclusions: In patients with CAD, a very low heart rate portends an increased risk of future cardiovascular events. Ho.JE. Et al. Am J Cardiol . 2010;105:905-911 European Heart Journal ( 2011 ) 32:339

对于心衰的病人……

The mortality benefit was related more to the magnitude of heart-rate reduction and not to the dose of beta blocker.

Admission heart rate and in-hospital cardiovascular events in patients with non-ST-ACS: results from 135 164 patients in the CRUSADE 一级终点 全因死亡 再次心梗 脑猝中

静息心率与心血管事件的关系：INVES 研究 22576例老年冠心病合并高血压患者中， 静息心率与心血管事件的关系：INVES 研究 22576例老年冠心病合并高血压患者，应用阿替洛尔与维拉帕米对照治疗，观察静息心率变化 静息心率每增加5 bpm心血管事件风险提高6％，静息心率>75 bpm与心血管事件增加直接相关；静息心率<59 bpm，心血管事件发生率有所增加。提示在该类患者中应关注心率j型曲线问题。

心率减慢 – 有效的指标 可将心率作为观察疗效的一项指标 作为治疗心衰/冠心病 /高血压 病人的目标之一 应将心率尽量减慢至病人可耐受的程度 病人不因心率慢而出现体位性低血压、眩晕、过度疲乏 综合近年的高血压 / ACS / 心衰的指南意见 β-blockers 推荐用于所有无禁忌症的心衰 /冠心病/高血压 病人 β-blockers 通常能够很好耐受 良好的β-blockers 治疗的判定指标： 静息心率 60次/分左右 ( 心衰 / 老年病人60-70次 / 分) 中等运动量如爬一层楼梯后心率增加不超过20次/分

结 论 心率是人类长期进化的结果 / 个人身体代谢水平的综合体现 结 论 心率是人类长期进化的结果 / 个人身体代谢水平的综合体现 心率加快是健康人群以后发生高血压/冠心病/心血管死亡的重要预测因素，它代表了交感神经活性对人群的影响 静息心率增加 / 心率变异性降低是高血压和冠心病患者发生心血管事件的危险因素，独立于其他心血管危险因素 应该将心率作为治疗高血压、冠心病、和心衰患者的重要指标 将心率尽量减慢至病人可耐受的程度