心率与心血管疾病一个重要而被忽视的问题.pptx

单击此处编辑母版标题样式,单击此处编辑母版文本样式,第二级,第三级,第四级,第五级,#,心率与心血管疾病一个重要而被忽视的问题,心率与心血管疾病一个重要而被忽视的问题,第1页,序言,大家早已发觉心率较快小动物寿命较短，而心率较慢大动物，寿命较长。这一心率与寿命负相关现象除人类外，存在于全部哺乳动物。人类平均心率为70次/分左右，其预期寿命为80岁，有些人预测，将人类平均心率由70次/分降低到60次/分可使预期寿命增加到93.3岁。,心率与心血管疾病一个重要而被忽视的问题,第2页,心率主要性,心率（,HR,）,是心肌耗氧量最主要决定原因,HR,下降可增加缺血阈值，改进心肌做功,HR,是一个独立危险原因证据，既来自,Cohort,研究（有相同统计要素一组人）也来自前瞻性双盲临床试验,心率与心血管疾病一个重要而被忽视的问题,第3页,问题之一,普通人群中，,HR,对预后有何意义？,五大流行病学研究评定了心率与,CHD,与,CV,病关系,Framingham Heart Study,National Health Examination Survery,Multifactor Primary Prevention,Trial in Goteberg,Chicago Heart Association,心率与心血管疾病一个重要而被忽视的问题,第4页,结论,共入选,30000,表面健康人（大多为中年男性），随访,5年,36,年,结果：各种原因死亡与心血管病死亡危险随,HR,升高而递增，尤其是心率,84,次,/,分时，不论性别或种族怎样，死亡率均一致性地与,HR,升高相关,与,HR,60,次,/,分比较，,HR90,99,次,/,分者,死亡率要高,3,倍,!(,主要死于冠心病,),心率与心血管疾病一个重要而被忽视的问题,第5页,问题之二,心率是否是高血压病人主要预后原因,?,与血压正常对照组相比,高血压病人,静息时心率显著较快,4530,例高血压随访观察显示,心率,85,次,/,分者死亡率比,65,次,/,分者高,1,倍,且此与有没有传统冠心病危险原因无关,心率与心血管疾病一个重要而被忽视的问题,第6页,问题之三,心率对老年人,是否是预后原因,?,一项大型高危老年人群研究显示,在调整其它混杂原因后,心率每增加,5,次,/,分,其心梗与猝死危险性增加,14%,心率与心血管疾病一个重要而被忽视的问题,第7页,问题之四（1）,急性心梗病人,心率是否是一个主要预后原因,?,依据病人住院时心率快慢,并随访一年分析显示,如入院,2,小时内心率由小于,90,次,/,分增加到大于,100,次,/,分,则总死亡率增加,1,倍,.,深入分析死亡率与住院期间或出院前最高心率关系显示,与,7090,次,/,分相比,100,次,/,分者,死亡率增加达,4-6,倍,.,心率与心血管疾病一个重要而被忽视的问题,第8页,问题之四（2）,入院时心率,90,次,/,分,者比,90,次,/,分者严重心衰发生率要高,10,倍之多,.(1990,年,),将病人深入分为无心衰或轻,、,中,、,重度心衰组后,心率快慢仍是死亡率主要预报因子,。,比如,轻至中度心衰病人中,入院,90,次,/,分者死亡率要比,70,次,/,分者高,23,倍,.,心率与心血管疾病一个重要而被忽视的问题,第9页,问题之五,咱们从冠心病随机对照研究中对心率问题取得哪些信息,?,多项,-B,试验均一致地显示可降低心梗后病人心源性猝死率,心血管死亡率与再梗死率,对,16500,例,(11,个前瞻性研究,),心梗后病人研究显示,无内源性拟交感活性,-B,对心率与死亡率降低效益最大,;,死亡率降低与心率减慢之间有显著线性关系,即每降低,10,次,/,分心率可使死亡率降低,1520%,！,心率与心血管疾病一个重要而被忽视的问题,第10页,问题之六,心肌梗死存活者用,-B,后临床预后有何改观,?,11,个随机对照研究显示,心率与心梗面积,(,R=0.97.P0.001),死亡率,(,R=0.79,P0.005),与非致命性再梗率,(,R=0.59,P0.05),显著相关,总体来看,用,-B,后心率最少应降低,8-10,次,/,分,才能使心梗面积与死亡率显著下降,.,心率与心血管疾病一个重要而被忽视的问题,第11页,问题之七,用,-B治疗急性心肌梗死临床效益终究有多大,?,答案是剂量足够,心率下降到达一定幅度,治疗效益是很大,.,无内源性,-B,治疗,1000,例病人可挽救,2025,个生命,溶栓药为,4045,个生命,心率与心血管疾病一个重要而被忽视的问题,第12页,问题之八,（1）,心率是怎样影响心血管发病率与死亡率？,HR,下降降低,MVO,2,HR,下降增加冠脉血流,HR,下降缩小心梗面积,HR,下降增加室颤阈值,(,用,-B,预处理后再结扎冠状动脉,可预防试验犬发生,VF),心率与心血管疾病一个重要而被忽视的问题,第13页,问题之八（2）,HR,降低,有直接抗动脉粥样硬化作用。,灵长目动物试验,在相同血压,血脂与体重条件下,心率慢者粥样化病变仅为心率快者,1/3,左右,.,用饱和脂肪酸喂饲猴试验中显示,心率慢比心率快者,冠状动脉病变要轻,接收心得安治疗猴子,尽管血脂水平仍高,但比未治疗者粥样硬化病变要轻得多,.,Poor health and/or physical fitness,本类人群静息时心率常偏快,本类人群比体力活动锻炼多人易患冠心病,自主神经功效异常：心率快提醒交感神经亢奋,迷走神经张力降低，易发生室颤,.,心率与心血管疾病一个重要而被忽视的问题,第14页,70,60,50,40,30,20,10,0,25,30,35,45,40,55,50,60,HT per 1.000 men/YrTransient,tachycardia,Transient,Hypertension,-,+,-,+,-,-,+,+,Figure 1.Predictive value of transient tachycardia or transient blood pressure increase for the development of hypertension during a 5-year follow-up period.This study,performed in 22,741 American Army soldiers,was the first to document the predictive power of heart rate for the development of hypertension later in life,A transient heart rate increase showed the predictive power for the development of hypertension as did a transient blood pressure rise meant a significant increase inrisk.From Levy R.L.et al(1945).JAMA 129,585.,心率与心血管疾病一个重要而被忽视的问题,第15页,Q5,Q4,Q3,Q2,Q1,0.5,1.5,2.5,3,2,1,Heart rate(bpm),Relative risk,Figure 2.Risk of developing hypertension later in life on the basis of heart rate measured at the baseline visit in individuals enrolled in the Kaiser Permanente Study.Study participants,divided into heart rate quintiles(Q),showed a progressive increase in risk of hypertension with increasing baseline heart rate.Data had been adjusted for numerous confounding variables.Modified from Selby J.V.et al.(1990).Am J Epidemiol 131,1017.,心率与心血管疾病一个重要而被忽视的问题,第16页,80,70,60,50,40,30,61,90,100,HR intervals in bpm,AMI,incidenece,Figure 4.Incidence of acute myocardial infarction(AMI)adjusted for age during,a 5-year follow-up period,among,10,000 men,divided into baseline heart rate(HR)classes.Note the significant increase in AMI incidence with increasing HR.Reproduced from Medalie J.H.,Kahn H.A.Neufeld H.N.,Riss E,.,Goldbourt U.(1973).Five-year myocardial infarction incidence-II.Association of single variables to age and birthplace.J.Chronic Dis 26,329,reprinted with permission from Elsevier Science.,心率与心血管疾病一个重要而被忽视的问题,第17页,Nonfatal,0.5,3,4,2,1,Relative risk,Fatal,Total,Nonfatal,Fatal,Total,CV events,AMI,Figure 5.Relative risks of cardiovascular(CV)events and acute myocardial infarction(AMI)for a heart rate increase by 40 bpm in 5,209 individuals with hypertension enrolled in the Framingham Study and followed for,36,years,.Note that the heart rate-linked risk increase was particularly great for fatal events.Modified from Gillman M.W.et al.(1993).Am Heart J 125,1148.,心率与心血管疾病一个重要而被忽视的问题,第18页,Figure 6.Incidence of sudden death(SD)during a 26-year follow-up period in individuals enrolled in the Framingham Study,divided into baseline heart rate quintiles(Q1=heart rate 87 bpm).Among the men,risk increased progressively with increasing heart rate,while the trend among the women was much less clear and statistically insignificant.Modified from Kannel W.B.et al.(1985).Am Heart J 109,876.,6,4,2,0,Women,Men,p=NS,P0.001,Incidence of SD/1.000 cases,1,th,quintile,2,th,quintile,3,th,quintile,4,th,quintile,5,thquintile,心率与心血管疾病一个重要而被忽视的问题,第19页,Figure 8.Predictors of life expectance in the Framingham Study.In this analysis,performed on men ages 50 through 75,low heart rate(HR)was an important predictor of increased survival with a predictive value equal to that of nonsmoking and low systolic blood pressure(SBP).Modified from Goldberg R.J.et al(1996).Arch Int Med 156,505.,Nonsmoking,0.5,2,1.5,1,Relative risk,Low SBP,Low HR,心率与心血管疾病一个重要而被忽视的问题,第20页,Figure 12.Heart rate(HR)values above which there was a marked increase in the risk of cardiovascular events and death:results from 8 epidemiological studies.Note that the threshold heart rate for risk increase was between 80 and 90 bpm.Modified from Palatini P.(1999).Hypertension 33,622.,100,90,80,70,60,Medalie,et al.,1973,Dyer,et al.,1980,Dyer,et al.,1980,Dyer,et al.,1980,Kannel,et al.,1987,Gillum,et al.,1991,Gilman,et al.,1993,Palatini,et al.,1999,HR(bpm),Men,women,心率与心血管疾病一个重要而被忽视的问题,第21页,Figure 14.All-cause and cardiovascular mortality in a population of elderly men enrolled in the Castel Study.Participants were stratified into there groups by heart rate:,elevated(80 bpm),intermediate(64-80 bpm),and low(64 bpm),.Cardiovasculare and all-cause mortality was highest among individuals with tachycardia and lowest among those with bradycardia.Modified from Palatini P.et al.(1999).Arch Int Med 159(6),585.,1999 American Medical Association.All rights re-served.Reprinted with permission from the American Medical Association.,All-cause mortalityCardiovascular mortality,1.0,0.8,0.6,0.4,0,2,4,6,8,10,12,Follow-up(Yrs),1.0,0.8,0.6,0.4,0,2,4,6,8,10,12,Follow-up(Yrs),p,=0.011,p,=0.0007,心率与心血管疾病一个重要而被忽视的问题,第22页,84,Heart rate(bpm),Incidence/1,000 men/2 Yrs,60,50,40,30,20,10,0,CHD,CVD,All-cause,Figure 16.All-cause mortality,mortality from cadiovascular disease(CVD),and mortality from heart disease(CHD),in 5,209 men followed from 36 years in the Framingham Study.All types of increased progressively with increasing heart rate.Modified form Gillman M.W.et al.(1993).Heart J 125,1148.Reprinted with permission from Mosby Year Book.,心率与心血管疾病一个重要而被忽视的问题,第23页,1.00,0.95,0.90,0.85,0,1,2,3,4,5,6,7,8,9,10,11,12,Months,Survival,Heart rate(bpm),89,Figure 17.Survival cures for,1,044,AMI,patients stratified,by admission heart rate,.Mortality during the 12-month follow-up period was substantially higher in patients with heart rates 89 bpm than in those with lower heart rates,and lowest in patients whose heart rate was 70 bpm.From Disegni E.,Goldbourt U.,Reicher-Reiss H.et al.(1955).The predictive value of admission heart rate on mortality in patients with acute myocardial infarction.J.Clin.Epidemiol.48,1197.Reprinted with permission from Elsevier Science.,心率与心血管疾病一个重要而被忽视的问题,第24页,0,60,120,180,240,300,360,100%,80%,60%,40%,20%,0%,days,0,60,120,180,240,300,360,100%,80%,60%,40%,20%,0%,days,0,60,120,180,240,300,360,100%,80%,60%,40%,20%,0%,days,Survival,Day 1,Day 3,Day 7,*,*,*,*,p0.05*p0.01*p0.001,HR 80 bpm,HR,80 bpm,Figure 18.Predictive value of heart rate(HR)taken 1,3,and 7 days after admission for,acute myocardial infarction,for survival during a one-year follow-up period.Survival was greater among patients whose heart rate was less than 80 bpm than among those with higher heart rates.,Heart rate showed the greatest predictive power at 7 days after admission,.Data from Berton G.et al.(not published).,心率与心血管疾病一个重要而被忽视的问题,第25页,1,th,quintile,2,th,quintile,3,th,quintile,4,th,quintile,30,20,10,0,Death risk(%),Heart,rate,HR,variability,LVEF,Figure 19.Incidence of all-cause mortality among,579 AMI survivors,divided into mean heart rate(HR)HR variability,and left ventricular ejection fraction(LVEF)quartiles.For all three variables,there was an increase in mortality from the 1st to the 4th quartile.A clearer trend was observed for the HR quartiles.Modified from Copie X.et al.(1996).J Am Coll Cardiol 27,270.,心率与心血管疾病一个重要而被忽视的问题,第26页,Table 2.Predictors of progression of coronary atherosclerosis among 56 male MI survivors who unwent coronary angiography immediately post-Ml and after 4-7 years.Note that minimum heart rate 24-hour Holter monitoring was a significant predictor of progression of coronary artery disase and a predictor than dyslipidemia,hypertension,and smoking.Modified from Perski A.et al.(1992).Am H,J 123,609.,Predicators of Progression of Coronary,Atherosclerosis,VARIABLE P,Minimum heart rate on 24-hour HR recording,0.02,LDL/HDL ratio0.03,Fibrinogen0.12,Hypertension0.23,Beta-blocker therapy0.25,Lipoprotein A0.58Cigarette smoking0.62,Time elapsed between angiographies0.99,心率与心血管疾病一个重要而被忽视的问题,第27页,100,90,80,70,60,50,40,30,20,HR(bpm),Nor-Epi,MSNA,Controls,Hypertensives,Obese patients,Heart failure patients,bpm,pg/dl,burst/min,Figure 22.Markers of sympathetic activity in 4 different groups of subjects.Sympathetic tone show the greatest elevations in heart failure patients,followed in descending order by obese individuals,hyptensive patients,and controls.Heart rate was found to be a reliable marker of sympathetic activity,reflthing both circulating norepinephrine(Nor-Epi)and muscle sympathetic nerve activity(MSNA measured croneurographically at the posterior peroneal nerve).Modified from Grassi G.et al.(1998).J Hypertens 1635.Reprinted with permission from Lippincott Williams&Wilkins-A Wolters Kluwer Company.,心率与心血管疾病一个重要而被忽视的问题,第28页,Ischemic,heart disease,Platelet,activation,Dyslipidemia,Insulin resistance,Sympathetic hyperactivity,PV,LVH,Hematocrit,Vascular hypertrophy,Arrhythmia,Coronary spasm,Sudden death,Coronary thrombosis,Coronary reserve,Figure 23.Pathogenetic mechanisms by increased sympathetic tone may lead to coronary artery disease,coronary events and sudden death.,PV=plasma volume;LVH=left ventricular hypertrophy,心率与心血管疾病一个重要而被忽视的问题,第29页,Glucose,Blood,pressure,Insulin,Cholesterol,BMI,Hematocrit,Triglycerides,HDL,cholesterol,Heart,Rate,Figure 24.Association between heart rate and other risk factors for atherosclerosis.In this diagram,heart rate,being a marker of sympathetic activity,is the link between the other risk factors.The mechanism underlying the association between sympathetic tone and cardiovascular risk factors is explained in the text.From Palatini P.Julius S.(1997),J Hypertens 15,2.Modified with permission from Lippincott Williams&Wilkins A Wolters Kluwer Company.,心率与心血管疾病一个重要而被忽视的问题,第30页,结论,现有证据表明心率是高血压与心血管与非心血管性死亡,主要预报原因!,心率与死亡率关联存在于任何年纪人群，且男性强于女性,心动过速是交感神经兴奋性增高，副交感神经张力降低一个强力指标,心率与心血管疾病一个重要而被忽视的问题,第31页,60,50,40,30,20,10,0,0,0.1,0.2,0.3,0.4,0.5,High HR,Low HR,High HR,Low HR,p 0.02,p 0.05,%,with stenoses,mm,2,Figure 34.Percentage of coronary artery sections with 25%stenotic lesions and mean lesion area in a group of,monkeys,in which heart rate(HR)was reduced by,sinus node ablation,and which were fed an atherogenic diet fo six months and in a control group of monkeys that did not undergo sinus node ablation but were also fed an atherogenic diet for six months.The monkeys which had their heart rate reduced showed marked slowing of the formation of coronary lesions versus the group of monkety whose heart rate remained elevated.Reproduced from Beere P.A.et al.(1999).Am J Hypertens 12,1,part 3,with permission from Elsevier Science.,心率与心血管疾病一个重要而被忽视的问题,第32页,100,60,30,10,5,2,0,10,2,10,4,10,6,10,8,10,10,10,12,Total number of heart beats/lifetime,Life expectancy in yrs,Man,Elephant,Whale,Horse,Lion,Cat,Ciraffc,Tiger,Woodchuck,Rat,Mouse,Hamster,Monkey,Donkey,Dog,Figure 40.Relationship between life expect and total number of cardiac cycles during the time of mammals.Note that the total number of heart beats/lifetime are remarkably stable among all animal species.Modified from levine(1997).Rest heart rate and life expectancy.Coll Cardiol 30,4,1104-1106.Reprinted with mission from Elsevier Science.,心率与心血管疾病一个重要而被忽视的问题,第33页,1100,900,700,500,Male mice,Female mice,Survival(days),571,745,750,845,p 0.0001,p 0.02,Untreated,Treated,Figure 41.Survival in a group of mice with digoxin from their few days of life untreated group.Life span was significantly among treated mice,in which heart rate proximately half that in untreated mice.Benefit from digoxin was particularly great mice.Modified from Coburn A.F.(1971).Med J 128,168.,心率与心血管疾病一个重要而被忽视的问题,第34页,HR 90bpm,HR 90bpm,Heart failure,Sudden death,All-cause,Heart failure,Sudden death,All-cause,0,1,2,Relative risk,Figure 43.Relative risks of death from heart failure,sudden death and all-cause mortality among 519 patients with severe heart failure receiving,amiodarone,300 mg/day or placebo and followed,for two years,.In patients with a baseline heart rate(HR)greater than or equal to 90 bpm,amiodarone produced a marked reduction in risk of death from any cause.Patients whose baseline heart rate was less than 90 bpm derived no benefit from amiodarone therapy.Modified from Nul D.R.et al.(1997).J Am Coll Card 29,1199.,心率与心血管疾病一个重要而被忽视的问题,第35页,受体阻滞剂,减慢心率治疗效益,人类药品干预减低心率研究均属回顾性分析。研究使用药品大多为,受体阻滞剂，且多数研究对象为急性心肌梗死后存活者。对,29,个临床试验,Meta,分析显示，早期使用,受体阻滞剂作为二级预防性治疗使心肌梗死后存活者全因,死亡率降低,13%,（,p,0.02,）。,心率与心血管疾病一个重要而被忽视的问题,第36页,因为使用不一样,受体阻滞剂治疗，故心率减慢幅度亦不一样（,10.5%-22.8%,），但值得指出是，显著降低死亡率效果均出现在,用药后心率降低,14,次,/,min,人群中。,且降低再梗死率与死亡率程度与心率减慢幅度相关，,心率降低,8,次,/,min,患者死亡率并无任何降低。,心率与心血管疾病一个重要而被忽视的问题,第37页,对急性心梗发病后,12,小时进行药品干预研究深入显示心率减慢幅度与梗死面积缩小程度亲密相关；心率最少应减慢,15,次,/,分，方能使梗死面积降低,25%-30%,；心率降低,8,次,/,分者不能缩小梗死面积；,全部梗死后研究均显示，静息时心率减慢幅度与死亡率降低程度相关,（,r=0.68,，,p90,次,/,分,平板运动试验未能到达预期最大心率,85%,（死亡率独立预测原因）,最大运动量后第一分钟内心率减慢,12,次,/,分（,5,年死亡率增加,4,倍）,心率变异异常（迟缓深呼吸一分钟内，心率改变,10,次,/,分）,心率与心血管疾病一个重要而被忽视的问题,第42页,Horse,Rat,Hamster,Monkey,Woodchuck,Dog,Cat,Tiger,Giraffe,Whale,Lion,Elephant,Figure 39.An inverse relationship between heart rate and life expectance has been identified in the animal kingdom.The mouse has a heart rate greater than 500 bpm and lives little longer than two years,while the Galapagos tortoise has a heart rate of,6 bpm,and an average life span of,177 years,.Among mammals,heart rate decresase with increasing