高血压左室肥厚患者各种心电图改变的预后价值
作者：谢良地 陈达光 吴可贵 陈金水
单位：福建医科大学附属第一医院心内科 350005
关键词：高血压；左室肥厚；心电图；预后
高血压杂志990308
摘要 目的:研究高血压左室肥厚病人不同心电图改变的预后价值。方法:对126例高血压合并左室肥厚的20多项心电图改变进行预后追踪14年，以性别、年龄、职业、地区配对的正常高血压275人，无左室肥厚高血压患者163人做为非暴露组进行队列研究，观察各种心脑血管并发症的发生率，评价各项心电图改变的相对危险度(RR)。结果:高血压和高血压合并左室肥厚病人死亡的主要原因是心脑血管意外(56.8%)。单纯左室高电压不是高血压患者独立的危险因子。不对称倒置T波、左室劳损、V1 Ptf异常、QV5≥2 mm及多项心电图指标异常者发生心脑血管并发症的危险性明显升高，分别为正常人的30.67，14.75，14.73，12.48，和11.24倍。矫正血压和电压因素后这些心电图异常的危险性仍高，其RR分别为6.55，2.99，3.19，2.32，和2.26。结论:不对称倒置T波、左室劳损、V1 Ptf异常、QV5≥2 mm及多项心电图指标异常是既独立于血压因素又独立于电压因素之外的发生心脑血管并发症的危险因子
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要点：高血压合并左室肌厚有不对称倒置T波、左室劳损、V1 Ptf、QV5≥2 mm者，经14年观察其发生心脑血管并发症的危险性分别为正常人的11倍到30倍
中图分类号：R544.1;R541.3;R444 文献标识码：A
文章编号：1006-2866(1999)03-0213-06
The Prognostic Significance of Various Electrocardiographic Changes in Hypertensive Patients with Left Ventricular Hypertrophy
XIE Liangdi,CHEN Daguang,WU Kegui,CHEN Jinshui
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(Hypertension Division,The First Affiliated Hospital of Fujian Medical College,Fuzhou 350005 P.R.CHINA)
Objective:To investigate the prognostic significance of ECG changes in hypertensive patients with left ventricular hypertrophy.Methods:One hundred twenty six hypertensives with left ventricular hypertrophy (HT-LVH) were followed up for 14 years.A cohort of age,sex,region and occupation matched hypertensives without LVH (HT,n=163) and normotensives (NT,n= 275) served as controls.Correlation between 20 specific items of electrocardiographic abnormalities and cerebral-cardiovascular events were studied,and the relative risks (RR) were evaluated.Results:It was showed that the major causes of death in hypertensives with ECG LVH in this study was stroke (56.8%).LVH based on voltage criteria only was not risk factor,the higher incidence of cardiovascular events was ascribed to coexisting higher level of BP usually accompanying higher ECG voltage.Electrocardiographic manifestations of asymmetric inverted T wave,ST segment depression,V1 Ptf≤0.04 mm.sec,QV5≥2mm and comprehensive abnormalities in patients with hypertension increased the risk of cardiovascular events,with the RR of 30.67,14.75,14.73,12.48 and 11.24 respectively,as compared to the normotensives.After stratification of voltage and adjustment of coexisting hypertension,the risks of above abnormalities were still significant,with RR of 6.55,2.99,3.19,2.32 and 2.26 respectively.Conclusion:Asymmetric inverted T wave,ST segment depression,V1 Ptf≤0.04 mm.sec,QV5≥2 mm and comprehensive abnormalities are independent risk factors for hypertensives.
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Key Words:Hypertension;Left ventricular hypertrophy;Electrocardiography;Prognosis
It has long been recognised that left ventricular hypertrophy (LVH) is an independent risk factor for cardiovascular diseases[1-7].Currently,two dimensional echocardiography has been widely used in clinical practice,however,the standard 12-lead electrocardiogram (ECG) remains a practical,economic,uncomplicated and convenient method to detect LVH.Though the sensitivity of detection of left ventricular hypertrophy with echocardiography is much higher than that with ECG,while the specificity of ECG is much better[4,6,10～12].Therefore ,the 12-lead ECG remains the most widely used initial diagnostic test in the survey for left ventricular hypertrophy.In the most previous studies,the prognosis of left ventricular hypertrophy were carried out based on the different multiple criteria[1,4,12-16].However,studies on the prognosis of specific ECG changes regarding LVH were scanty.The present study was carried out in the southern part of Fujian province P.R.China,where 126 hypertensive patients with ECG-LVH diagnosed during a servey for hypertension.The patients were matched with a cohort of normotensives in age,sex,region,and occupation.The patients were followed up for 14 years,to investigate the prognostic importance of various specific ECG changes in hypertensives with LVH.
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SUBJECT AND METHODS
Study protocol
This study was initiated in 1974 in the southern part of Fujian province,including Yongchun,Anxi,Quanzhou and Chendi 4 mountain communities[17-19].A total of 26,642 people over 15 years old were survey for hypertension.Each subject underwent the same protocol described previously[17～19].Briefly,the determination of sitting blood pressure after 30 min rest with a mercury sphygmomanometer (Korotkoff phase I and V) was used as the mean of the two readings on three consecutive days.Measurement of body weight and height,physical examination,quantification of fasting plasma cholesterol ,triglyceride and serum glucose,routine tests of blood and urine samples,examination of ocular fundus were routinely performed.
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Electrocardiographic method
Standard 12-lead electrocardiograms were recorded in all subjects at 25 mm/s and 1 mV/cm calibration.Tracings were interpreted by 2 experienced investigators.Subjects with complete bundle branch block,previous myocardial infarction,Wolff-Parkinson-White syndrome,and atrial fibrillation were excluded from the analysis.No subject was being treated with digitalis.One hundred twenty six hypertensives with electrocardiographic left ventricular hypertrophy (HT-LVH) based on RV5+SV1≥40 mm ( for male,35 mm for female) were followed up for 14 years to investigate the prognostic value of various specific ECG changes in hypertensive patients with LVH.These ECG changes included :(1) R wave in lead Ⅰ (RⅠ)≥15 mm;(2) Sum of R wave in lead I+S wave in lead Ⅲ (RI+SⅢ) ≥25 mm;(3) ST segment depression in lead Ⅰ (STⅠ)≥ 1 mm and /or presence of inverted T wave in lead I;(4) R wave in lead aVL (RaVL)≥12 mm;(5) R wave in lead aVF (RaVF ) ≥20 mm;6)The sum of R wave in lead Ⅰ+ R wave in lead Ⅱ ( RⅠ+ RⅡ)≥40 mm ;(7) Deviation of QRS axis≤-30°;(8) P wave terminal force in lead V1 (V1 Ptf) ≤-0.04mm.s;(9) RV5 + SV1 ≥40 mm;(10) SV1 ≥22 mm;(11) SV3≥25 mm;(12) RV5 or V6≥25 mm;(13) Q wave in V5 (QV5) ≥2 mm;(14) STV5 or V6 depression ≥1 mm,or inverted T wave in V5 or V6 ;(15)QRS duration in lead V5 or V6 (TQRS) ≥0.09 s;(16)Presence of U wave;(17) Inverted U wave;(18) Asymmetrically inverted T wave;(19)T wave overshot in pericardial leads;(20) Ventricular activation time in V5 or V6 (VATV5 or V6)≥0.05 s.
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The abnormalities were classified into 3 categories :(1) voltage abnormality only:If any of about voltage abnormalities was present;(2) Left ventricular hypertrophy with strain:Abnormal ST segment depression or T wave inversion beside high voltage;(3) Multiple abnormalities:one or more non-voltage abnormalities in addition to voltage criteria.
Follow-up and end point evaluation
Information on annual stroke,cardiovascular disease deaths and deaths due to other causes was obtained by physicians responsible for local medical care in these communities.The data were collected annually.An interim and a final visits was carried out by our hypertension division in 1985 and 1991 and the data were accumulated.After reviewing the documents pertaining to deaths,the medical histories and courses,the death certification from local hospitals,and interviews with family members of the patients,the probable causes of death were established by a panel.The causes included stroke (cerebral haemorrhage,cerebral infarction),cardiac diseases (heart failure,myocardial infarction,and sudden death),and other causes (cancers,unexpected accidents,etc.).A cohort of sex,occupation and region matched normotensives (275) and 163 hypertensives without ECG LVH,randomly selected from the lists of local communities,served as controls.The acceptable difference of age between normotensives and hypertensives was within 5 years.
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Statistical methods
All data were fed into a Foxbase database and analysed using Systat software in 1991 when the study was ended.Mortality and morbidity owing to cardiac and cerebral-vascular complication of both groups were calculated.Correlation between above 20 specific ECG abnormalities and cerebral-cardiovascular events were performed,and relative risks (RR) were evaluated.Z test and Mantel-Haenszel X2 test were used to determine the significance of the relative risk of cardiac and cerebral events among these three groups.The difference in age,plasma cholesterol,blood pressure and body mass index were compared by ANOVA.
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RESULTS
1.Characteristics of the study population
Table 1 shows the general characteristics of the study groups .There was no difference in age,sex among these 3 groups.Of the 126 hypertensives with left ventricular hypertrophy,there was 57 male(44.5 %).Voltage abnormality only was seen in 39 hypertensives ,while multiple abnormalities were noted in 87 patients,of which 49 hypertensives were with ECG left ventricular strain.The blood pressure in hypertensives with and without LVH was significantly higher than that in normotensives (P<0.01 for both systolic and diastolic blood pressure),while both systolic and diastolic blood pressure in hypertensives with ECG-LVH was markedly higher than in hypertensives without ECG-LVH (P<0.01 respectively).The main causes of death for normotensives was non- cerebral cardiovascular events,accounting for 77% of the total,while stroke was the main cause of death for hypertensives without (51.4%) and with ECG-LVH (57.8%).In this study,the cardiovascular events constituted only a minor persentage in total cause of death(11.2%),and 14.0% for hypertensives with ECG-LVH.As a result,we combined the death caused both by cardiovascular events and stroke as cerebro-cardiovascular death.
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表1 各组研究对象随访开始时的一般情况比较
Tab 1 General characteristics of the study population at baseline
Normotensives
Hypertensives
HT-LVH
n
275
163
126
person years
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1728
1143
Sex(%)
male
48.4
40.0
44.5
female
51.6
60.0
55.5
years
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54.3±9.8
54.2±10.2
55.7±9
BP(mmHg)
SBP
117.2±12.4
160.7±20.2*
175.6±25.3*△
DBP
74.7±8.8
97.7±10.8*
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105.1±12.2*△
Cho(mmol/L)
4.27±0.90
4.81±1.04*
4.70±1.06*
*：P<0.01 vs NT;△：P<0.01 vs HT
2 The prognostic value of different specific ECG changes Table 2 shows the relative risk of cerebro-cardiovascular death for various specific ECG changes in hypertensives with left ventricular hypertrophy.It is clearly showed that the incidence of cerebro-cardiovascular death was significantly higher in hypertensives with different ECG changes as compared to normotensives.The most commonly used ECG criteria for diagnosis of LVH,the sum of R wave in V5+S wave in V1 ≥40 mm had highest specificity (92%).
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表2 高血压病并左心室肥厚各种心电图改变14年随访的相对危险性
Tab 2 Relative risk of various changes of ECG electrocardiographic left ventricular hypertrophy in hypertensives after 14 years follow up
n
Person
year
Mortality
Cerebral cardiovascular events
Total
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brain
heart
death
rate(%)
RR
Normotensivess
275
3113
60
10
4
14
4.4
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1.0
Inversion of U wave
2
10
2
2
0
2
200.0
44.47**
T wave overshot
4
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4
1
3
0
190.4
42.35**
Asymmetrically inverted T wave
5
29
5
3
1
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4
137.9
30.67**
STV5 or V6 depression ≥1 mm
or inverted T wave in V5 or V6
46
373
31
17
8
25
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67.0
14.9**
Left ventriculay hypertrophy with ischeamia
49
392
34
18
8
26
66.3
14.75**
V1 Ptf≤-0.04mm.s
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22
166
16
10
1
11
65.4
14.73**
RavL≥12 mm
5
33
3
2
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0
2
60.6
13.48**
STⅠdepression≥ 1 mm and/or inverted T wave in lead Ⅰ
16
120
8
3
4
7
58.3
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12.97**
QV5≥2 mm
24
196
15
9
2
11
56.1
12.48**
RV5+SV1 ≥50 mm
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254
19
8
5
13
51.1
11.38**
Multiple abnormalities
87
752
51
29
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9
38
50.5
11.24**
RV5≥30 mm
65
575
35
23
6
29
50.4
11.21**
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QRS axis≤-30°
8
67
4
3
0
3
44.8
9.96**
RⅠ+SⅢ≥25 mm
3
23
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1
1
0
1
43.4
9.67**
RV5+SV1≥40 mm
116
1044
61
36
9
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43.1
9.58**
RVV5 orV6≥25 mm
108
982
53
31
8
39
39.7
8.83**
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RⅠ+RⅡ≥40 mm
3
26
1
1
0
1
34.8
8.55*
SV1≥22 mm
15
157
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8
4
2
6
38.2
8.50**
SV3≥25 mm
16
151
10
2
3
5
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33.1
7.36**
U wave
32
303
15
9
1
10
33.0
7.34**
RⅠ≥15 mm
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4
33
1
1
0
1
30.3
6.74*
RavF≥20 mm
2
20
0
0
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0
0
0
TQRS≥0.09 s
12
106
4
3
0
3
28.3
6.29**
VATV5 or V6≥0.05 s
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3
28
1
0
0
0
0
0
Voltage abnormality only
39
398
13
8
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0
8
20.1
4.47**
*P<0.05 ,** P<0.01 vs Normotensives;Death rate was expressed as event per 1 000 person year
3 The risk of voltage abnormality alone Though the relative risk of cerebro-cardiovascular events was about 4.5 times higher in hypertensives with ECG voltage abnormality alone than in normotensives (Fig 1),the risk was as the same as in hypertensives without ECG abnormality,suggesting that the higher risk in hypertensives with ECG voltage abnormality alone may be ascribed to concomitant high blood pressure.The voltage abnormality alone could not predict the cerebral cardiovascular events in the future.
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图1 高血压病人合并心电图左心室高电压(n=39)和高血压无左心室高血压病人(n=163)的总死亡和心脑血管死亡危险性比较。NS：无差别。
Fig 1 Comparison of total and cerebral cardiovascular death between hypertensives without(HT n=163)and with LVH based on ECG voltage abnormal alone(n=39),NS:non significance.
4.The prognostic value of various specific ECG changes in hypertensives after stratification of BP
Figure 2 showed relative risk of cerebro-cardiovascular events in hypertensives with different ECG abnormalities.Of note,the cerebral cardiovascular risks were significantly higher in those with V1 Ptf abnormality,QV5≥2 mm,left ventricular strain,asymmetric T wave inversion and multiple ECG abnormalities than in hypertensives with voltage abnormality alone,with RR 6.85,3.30,3.32,2.79,2.45 respectively.However,the blood pressure was significantly higher in these hypertensives with different ECG abnormalities than in hypertensives with voltage abnormality alone.To verify the independent risk for these ECG changes,the RR of cerebral cardiovascular events was calculated in hypertensives with above five ECG abnormalities as compared to those hypertensives with voltage abnormality alone after stratification of blood pressure.It was showed that after adjustment of blood pressure,the risk of cerebral cardiovascular events was still markedly higher in those with V1 Ptf abnormality,QV5≥ 2 mm,left ventricular strain,asymmetric T wave inversion and multiple ECG abnormalities than in hypertensives with voltage abnormality only.The RR for these five ECG changes were 6.55,3.19,2.99,2.32,2.26 respectively after stratification of blood pressure (Fig 3),suggesting that V1 Ptf abnormality,QV5≥2 mm,left ventricular strain,asymmetric T wave inversion and multiple ECG abnormalities were independent risk factors for the prediction of cerebral cardiovascular events in the future.
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图2 高血压合并左心室肥厚病人各种不同心电图改变的总死亡和心脑血管死亡事件的危险度。*:P<0.05,**:P<0.01 与单纯电压指标异常相比。(n=39)
Fig 2 Relative risk of total and cerebral cardiovascular death for various specific ECG changes in hypertensives with left ventricular hypertrophy.
图3 纠正血压因素前后高血压病人各种心电图变化的相对危险度
Fig 3 Relative risk of various specific ECG changes in hypertensives before(□) and after(■) adjustiment of blood pressure.
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1.Asymmetric T wave;2.V1 Ptf abnormality;3.Repolarisation abnormality;4.QV5≥ 2mm;5.Multiple abnormalities
DISCUSSION
Hypertension has long been regarded as a main risk factor for both coronary heart disease and stroke[1-7].Hypertensive left ventricular hypertrophy based either echocardiography or electrocardiogram has also been demonstrated to be an independent risk factor for cerebral cardiovascular events.ECG-LVH has an especially strong association with development of stroke and cardiac failure.Left ventricular hypertrophy has many adverse impact on heart,such as decreased coronary reserve,insufficiency of myocardial perfusion,increased myocardial collagen content which may eventually impair diastolic function and cause electrophysiological instability,which may contribute to the higher incidence of arrhythmia in hypertensives with LVH[6].It has been repeatedly reported that hypertensives with LVH had increased morbidity and mortality of cardiovascular events.Framingham study showed that 5 year mortality was 35% for male and 20% for female hypertensives[6-7,20].In this 14 years long term follow up study,we demonstrated that (1) stroke was the main cause of death for Chinese hypertensives and hypertensives with left ventricular hypertrophy;(2) ECG voltage abnormality alone is not a risk factor independent of blood pressure;(3)V1 Ptf abnormality,QV5≥2 mm,left ventricular strain,asymmetric T wave inversion and multiple ECG abnormalities were independent risk factors and of prognostic value for prediction of cerebral cardiovascular events in hypertensives.
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Framingham study[12] has shown that ECG-LVH is independently associated with a marked increase in risk of all major clinical manifestations of coronary heart disease,suggesting it is more a sign of myocardial ischeamia than hypertrophy.A diagnosis of ECG-LVH is thought to chiefly reflect enlargement of the heart,particularly hypertensive hypertrophy,the ECG finding of so-called hypertrophy also reflects other phenomena.There is evidence to suggest that ECG-LVH,particularly when high amplitude R waves are accompanied by repolarisation abnormalities,probably indicates ischemic myocardial involvement as well as hypertensive hypertrophy,which is associated with increased risk of cardiovascular mortality.The accompanying repolarisation abnormalities signal the onset of a compromised coronary circulation and ischemic myocardial involvement.When manifested by repolarisation abnormalities,it carries a prognosis no better than that of ECG myocardial infarction.Within 10 years,20 per cent of men with ECG-LVH or ECG myocardial infarction developed cardiac failure,a rate five times that of the general Framingham sample of the same age[12].Stroke occurred in 17% of men with ECG-LVH in the Framingham study.In contrast,stroke constituted the major cause of death in this study population.It was suggested that any hypertensive patient with ECG-LVH should be treated as promptly and vigorously as a person recovering from a myocardial infarction[12].The voltage criteria appear to reflect only the severity and duration of the often-associated hypertension.In this study we found that ECG voltage abnormality alone is not a risk factor independent of blood pressure.The higher risk for those hypertensives with ECG-LVH based on the voltage criteria only may be ascribed to higher blood pressure per se,other than ECG voltage abnormality.
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Advances in echocardiographic methodology have enhanced the reliability of detection of LVH to a higher level than has been possible to achieve by conventional ECG criteria.The later was known to have a low sensitivity for LVH.Despite the advantages of echocardiograms,cost and operational considerations tend to limit their utility in large-scale population studies and clinical trials.Because of its low cost and broad availability,electrocardiogram is currently recommended as the routine test to detect LVH in all subjects with high blood pressure.Sensitivity of ECG criteria of LVH varied between 9% and 33% and specificity was generally≥ 90%.The performance of standard electrocardiogram for the diagnosis of LVH in essential hypertension can be improved using a modified sex-specific partition value of the Cornell voltage (2.4 mV in men and 2.0 in women).Siscovick DA et al[15]reported that continuous ECG indexes that reflect left ventricular hypertrophy,myocardial injury,and QT-interval prolongation are directly related to the risk of primary cardiac arrest among hypertensive patients without clinically recognized heart disease.Several multivariate statistical methods have recently been introduced for estimation of left ventricular mass from standard 12-lead electrocardiographic measurements[13,16,21] ,and many ECG criteria had been proposed to increase the sensitivity of detection of LVH[13,16].However,the sensitivity and specificity differ greatly.Of note,the Romhilt-Estes score which combines QRS voltage and voltage-independent signs such as QRS duration,retardation of the deflection of the highest point of the ECG wave,left atrial enlargement,left axis deviation and left ventricular strain,showed a specificity of 100% for LVH[13].The combination of 3 highly specific criteria ,Cornell voltage,Romhilt-Estes score,left ventricular strain,allows a further increase in sensitivity without compromising specificity in detecting LVH[13].
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V1 Ptf abnormality may be used as an non-invasive index for assessment of cardiac function and left atria overload[11,22].It was reported that patients with acute myocardial infarction exhibiting ECG V1 Ptf abnormality were at a higher risk of heart failure ,increased short term mortality and decreased long-term survival rates[23].ECG V1 Ptf abnormality may reflect pressure overload of left atria ,insufficiency of coronary blood flow,and increased left ventricular end diastolic pressure.Narrow and deep Q wave in V5 or V6 may represent diastolic overload of left ventricle.The association of an asymmetrically inverted T wave with left ventricular hypertrophy was recorded many years ago[24].Short et al[25] demonstrated a close relation between asymmetric T wave inversion and ventricular hypertrophy by using echocardiography.ECG ST depression is thought to be the hallmark of ischemia .T-wave abnormality is also considered as a risk indicator of coronary heart disease[8,26].Even non-specific electrocardiographic abnormalities was reported to carry a greater risk of CHD[27].In the Framingham study,the sensitivity of electrocardiography increased with increasing severity of LVH,and prevalence of left ventricular strain increased with the degree of LVH.It was reported that a strain pattern is a very specific marker of LVH (89%)[13],even in the absence of increased QRS voltages.Therefore,V1 Ptf abnormality,QV5≥2 mm,left ventricular strain,asymmetric T wave inversion appears to indicate the damage of left ventricle function and of prognostic value for prediction of cardiac and cerebro-vascular events in hypertensives.The mechanism that link LVH to cardiovascular mortality and morbidity are unclear.In essential hypertension,left ventricular mass may be considered a marker that reflects and integrates the long-term detrimental effects of high BP and other cardiovascular risk factors.Increased left ventricular mass is also associated with an increase risk for ventricular arrhythmia and sudden cardiac death[28-30].
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19 Wu KG,Xie LD,Chen DG,et al.The natural history of borderline hypertension in a Chinese population[J] J Hum Hypertens 1997;11:95-100
20 Kannel Wb,Castelli WP,McNamara PM.Role of blood pressure in the development of congestive heart failure;The Framingham study[J] N Engl J Med 1972;287:781
21 Rautaharju P M,Manolio T A,Siscovick D,et al.Utility of new electrocardiographic models for left ventricular mass in older adults[J] Hypertens 1996;28:8-15
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22 Zhang QG.progress in electrocardiographic diagnosis of ventricular hypertrophy[J] Chongqing Med 1988;17:34-35
23 Chen DG,Zhang ZH.Prognosis of electrocardiographic changes in acute myocardial infarction[J] Chin J Intern Med 1979;18:213
24 Katz L.Electrocardiography[M] 2nd ed.London:Henry Kimpton,1946:182
25 Short D,Weir J Significance of asymmetrically inverted T wave[J] Br Heart J 1983;49:564-567
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26 Harlan WR,Cowei CC,Oberman A,et al.Prediction of subsequent ischemic heart disease using serial resting electrocardiograms[J] Am J Epidemiol 1984;119:208-217
27 Kannel WB ,Anderson K,McGee DL et al.Non-specific electrocardiographic abnormalities as a predictor of coronary heart disease:The Framingham study[J] Am Heart J 1987;113(No 2,Pt1):370-376
28 Messerli FH,Ventura HO Elizardi DJ et al.Hypertension and sudden death:increased ventricular ectopic activity in left ventricular hypertrophy[J] Am J Med 1984;77:18-22
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29 McLenachan JM,Henderson E,Morris KI,et al.Ventricular arrhythmia in patients with hypertensive left ventricular hypertrophy[J] N Engl J Med 1987;317:787-792
30 Levy D,Garrison RJ,Savage DD,et al.Prognostic implication of echocardiographically determined left ventricular mass in the Framingham Heart Study[J] N Engl J Med 1990;322:1561-1566
Received：1999-02-15, http://www.100md.com
单位：福建医科大学附属第一医院心内科 350005
关键词：高血压；左室肥厚；心电图；预后
高血压杂志990308
摘要 目的:研究高血压左室肥厚病人不同心电图改变的预后价值。方法:对126例高血压合并左室肥厚的20多项心电图改变进行预后追踪14年，以性别、年龄、职业、地区配对的正常高血压275人，无左室肥厚高血压患者163人做为非暴露组进行队列研究，观察各种心脑血管并发症的发生率，评价各项心电图改变的相对危险度(RR)。结果:高血压和高血压合并左室肥厚病人死亡的主要原因是心脑血管意外(56.8%)。单纯左室高电压不是高血压患者独立的危险因子。不对称倒置T波、左室劳损、V1 Ptf异常、QV5≥2 mm及多项心电图指标异常者发生心脑血管并发症的危险性明显升高，分别为正常人的30.67，14.75，14.73，12.48，和11.24倍。矫正血压和电压因素后这些心电图异常的危险性仍高，其RR分别为6.55，2.99，3.19，2.32，和2.26。结论:不对称倒置T波、左室劳损、V1 Ptf异常、QV5≥2 mm及多项心电图指标异常是既独立于血压因素又独立于电压因素之外的发生心脑血管并发症的危险因子
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要点：高血压合并左室肌厚有不对称倒置T波、左室劳损、V1 Ptf、QV5≥2 mm者，经14年观察其发生心脑血管并发症的危险性分别为正常人的11倍到30倍
中图分类号：R544.1;R541.3;R444 文献标识码：A
文章编号：1006-2866(1999)03-0213-06
The Prognostic Significance of Various Electrocardiographic Changes in Hypertensive Patients with Left Ventricular Hypertrophy
XIE Liangdi,CHEN Daguang,WU Kegui,CHEN Jinshui
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(Hypertension Division,The First Affiliated Hospital of Fujian Medical College,Fuzhou 350005 P.R.CHINA)
Objective:To investigate the prognostic significance of ECG changes in hypertensive patients with left ventricular hypertrophy.Methods:One hundred twenty six hypertensives with left ventricular hypertrophy (HT-LVH) were followed up for 14 years.A cohort of age,sex,region and occupation matched hypertensives without LVH (HT,n=163) and normotensives (NT,n= 275) served as controls.Correlation between 20 specific items of electrocardiographic abnormalities and cerebral-cardiovascular events were studied,and the relative risks (RR) were evaluated.Results:It was showed that the major causes of death in hypertensives with ECG LVH in this study was stroke (56.8%).LVH based on voltage criteria only was not risk factor,the higher incidence of cardiovascular events was ascribed to coexisting higher level of BP usually accompanying higher ECG voltage.Electrocardiographic manifestations of asymmetric inverted T wave,ST segment depression,V1 Ptf≤0.04 mm.sec,QV5≥2mm and comprehensive abnormalities in patients with hypertension increased the risk of cardiovascular events,with the RR of 30.67,14.75,14.73,12.48 and 11.24 respectively,as compared to the normotensives.After stratification of voltage and adjustment of coexisting hypertension,the risks of above abnormalities were still significant,with RR of 6.55,2.99,3.19,2.32 and 2.26 respectively.Conclusion:Asymmetric inverted T wave,ST segment depression,V1 Ptf≤0.04 mm.sec,QV5≥2 mm and comprehensive abnormalities are independent risk factors for hypertensives.
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Key Words:Hypertension;Left ventricular hypertrophy;Electrocardiography;Prognosis
It has long been recognised that left ventricular hypertrophy (LVH) is an independent risk factor for cardiovascular diseases[1-7].Currently,two dimensional echocardiography has been widely used in clinical practice,however,the standard 12-lead electrocardiogram (ECG) remains a practical,economic,uncomplicated and convenient method to detect LVH.Though the sensitivity of detection of left ventricular hypertrophy with echocardiography is much higher than that with ECG,while the specificity of ECG is much better[4,6,10～12].Therefore ,the 12-lead ECG remains the most widely used initial diagnostic test in the survey for left ventricular hypertrophy.In the most previous studies,the prognosis of left ventricular hypertrophy were carried out based on the different multiple criteria[1,4,12-16].However,studies on the prognosis of specific ECG changes regarding LVH were scanty.The present study was carried out in the southern part of Fujian province P.R.China,where 126 hypertensive patients with ECG-LVH diagnosed during a servey for hypertension.The patients were matched with a cohort of normotensives in age,sex,region,and occupation.The patients were followed up for 14 years,to investigate the prognostic importance of various specific ECG changes in hypertensives with LVH.
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SUBJECT AND METHODS
Study protocol
This study was initiated in 1974 in the southern part of Fujian province,including Yongchun,Anxi,Quanzhou and Chendi 4 mountain communities[17-19].A total of 26,642 people over 15 years old were survey for hypertension.Each subject underwent the same protocol described previously[17～19].Briefly,the determination of sitting blood pressure after 30 min rest with a mercury sphygmomanometer (Korotkoff phase I and V) was used as the mean of the two readings on three consecutive days.Measurement of body weight and height,physical examination,quantification of fasting plasma cholesterol ,triglyceride and serum glucose,routine tests of blood and urine samples,examination of ocular fundus were routinely performed.
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Electrocardiographic method
Standard 12-lead electrocardiograms were recorded in all subjects at 25 mm/s and 1 mV/cm calibration.Tracings were interpreted by 2 experienced investigators.Subjects with complete bundle branch block,previous myocardial infarction,Wolff-Parkinson-White syndrome,and atrial fibrillation were excluded from the analysis.No subject was being treated with digitalis.One hundred twenty six hypertensives with electrocardiographic left ventricular hypertrophy (HT-LVH) based on RV5+SV1≥40 mm ( for male,35 mm for female) were followed up for 14 years to investigate the prognostic value of various specific ECG changes in hypertensive patients with LVH.These ECG changes included :(1) R wave in lead Ⅰ (RⅠ)≥15 mm;(2) Sum of R wave in lead I+S wave in lead Ⅲ (RI+SⅢ) ≥25 mm;(3) ST segment depression in lead Ⅰ (STⅠ)≥ 1 mm and /or presence of inverted T wave in lead I;(4) R wave in lead aVL (RaVL)≥12 mm;(5) R wave in lead aVF (RaVF ) ≥20 mm;6)The sum of R wave in lead Ⅰ+ R wave in lead Ⅱ ( RⅠ+ RⅡ)≥40 mm ;(7) Deviation of QRS axis≤-30°;(8) P wave terminal force in lead V1 (V1 Ptf) ≤-0.04mm.s;(9) RV5 + SV1 ≥40 mm;(10) SV1 ≥22 mm;(11) SV3≥25 mm;(12) RV5 or V6≥25 mm;(13) Q wave in V5 (QV5) ≥2 mm;(14) STV5 or V6 depression ≥1 mm,or inverted T wave in V5 or V6 ;(15)QRS duration in lead V5 or V6 (TQRS) ≥0.09 s;(16)Presence of U wave;(17) Inverted U wave;(18) Asymmetrically inverted T wave;(19)T wave overshot in pericardial leads;(20) Ventricular activation time in V5 or V6 (VATV5 or V6)≥0.05 s.
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The abnormalities were classified into 3 categories :(1) voltage abnormality only:If any of about voltage abnormalities was present;(2) Left ventricular hypertrophy with strain:Abnormal ST segment depression or T wave inversion beside high voltage;(3) Multiple abnormalities:one or more non-voltage abnormalities in addition to voltage criteria.
Follow-up and end point evaluation
Information on annual stroke,cardiovascular disease deaths and deaths due to other causes was obtained by physicians responsible for local medical care in these communities.The data were collected annually.An interim and a final visits was carried out by our hypertension division in 1985 and 1991 and the data were accumulated.After reviewing the documents pertaining to deaths,the medical histories and courses,the death certification from local hospitals,and interviews with family members of the patients,the probable causes of death were established by a panel.The causes included stroke (cerebral haemorrhage,cerebral infarction),cardiac diseases (heart failure,myocardial infarction,and sudden death),and other causes (cancers,unexpected accidents,etc.).A cohort of sex,occupation and region matched normotensives (275) and 163 hypertensives without ECG LVH,randomly selected from the lists of local communities,served as controls.The acceptable difference of age between normotensives and hypertensives was within 5 years.
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Statistical methods
All data were fed into a Foxbase database and analysed using Systat software in 1991 when the study was ended.Mortality and morbidity owing to cardiac and cerebral-vascular complication of both groups were calculated.Correlation between above 20 specific ECG abnormalities and cerebral-cardiovascular events were performed,and relative risks (RR) were evaluated.Z test and Mantel-Haenszel X2 test were used to determine the significance of the relative risk of cardiac and cerebral events among these three groups.The difference in age,plasma cholesterol,blood pressure and body mass index were compared by ANOVA.
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RESULTS
1.Characteristics of the study population
Table 1 shows the general characteristics of the study groups .There was no difference in age,sex among these 3 groups.Of the 126 hypertensives with left ventricular hypertrophy,there was 57 male(44.5 %).Voltage abnormality only was seen in 39 hypertensives ,while multiple abnormalities were noted in 87 patients,of which 49 hypertensives were with ECG left ventricular strain.The blood pressure in hypertensives with and without LVH was significantly higher than that in normotensives (P<0.01 for both systolic and diastolic blood pressure),while both systolic and diastolic blood pressure in hypertensives with ECG-LVH was markedly higher than in hypertensives without ECG-LVH (P<0.01 respectively).The main causes of death for normotensives was non- cerebral cardiovascular events,accounting for 77% of the total,while stroke was the main cause of death for hypertensives without (51.4%) and with ECG-LVH (57.8%).In this study,the cardiovascular events constituted only a minor persentage in total cause of death(11.2%),and 14.0% for hypertensives with ECG-LVH.As a result,we combined the death caused both by cardiovascular events and stroke as cerebro-cardiovascular death.
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表1 各组研究对象随访开始时的一般情况比较
Tab 1 General characteristics of the study population at baseline
Normotensives
Hypertensives
HT-LVH
n
275
163
126
person years
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1728
1143
Sex(%)
male
48.4
40.0
44.5
female
51.6
60.0
55.5
years
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54.3±9.8
54.2±10.2
55.7±9
BP(mmHg)
SBP
117.2±12.4
160.7±20.2*
175.6±25.3*△
DBP
74.7±8.8
97.7±10.8*
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105.1±12.2*△
Cho(mmol/L)
4.27±0.90
4.81±1.04*
4.70±1.06*
*：P<0.01 vs NT;△：P<0.01 vs HT
2 The prognostic value of different specific ECG changes Table 2 shows the relative risk of cerebro-cardiovascular death for various specific ECG changes in hypertensives with left ventricular hypertrophy.It is clearly showed that the incidence of cerebro-cardiovascular death was significantly higher in hypertensives with different ECG changes as compared to normotensives.The most commonly used ECG criteria for diagnosis of LVH,the sum of R wave in V5+S wave in V1 ≥40 mm had highest specificity (92%).
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表2 高血压病并左心室肥厚各种心电图改变14年随访的相对危险性
Tab 2 Relative risk of various changes of ECG electrocardiographic left ventricular hypertrophy in hypertensives after 14 years follow up
n
Person
year
Mortality
Cerebral cardiovascular events
Total
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brain
heart
death
rate(%)
RR
Normotensivess
275
3113
60
10
4
14
4.4
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1.0
Inversion of U wave
2
10
2
2
0
2
200.0
44.47**
T wave overshot
4
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4
1
3
0
190.4
42.35**
Asymmetrically inverted T wave
5
29
5
3
1
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4
137.9
30.67**
STV5 or V6 depression ≥1 mm
or inverted T wave in V5 or V6
46
373
31
17
8
25
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67.0
14.9**
Left ventriculay hypertrophy with ischeamia
49
392
34
18
8
26
66.3
14.75**
V1 Ptf≤-0.04mm.s
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22
166
16
10
1
11
65.4
14.73**
RavL≥12 mm
5
33
3
2
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0
2
60.6
13.48**
STⅠdepression≥ 1 mm and/or inverted T wave in lead Ⅰ
16
120
8
3
4
7
58.3
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12.97**
QV5≥2 mm
24
196
15
9
2
11
56.1
12.48**
RV5+SV1 ≥50 mm
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254
19
8
5
13
51.1
11.38**
Multiple abnormalities
87
752
51
29
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9
38
50.5
11.24**
RV5≥30 mm
65
575
35
23
6
29
50.4
11.21**
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QRS axis≤-30°
8
67
4
3
0
3
44.8
9.96**
RⅠ+SⅢ≥25 mm
3
23
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1
1
0
1
43.4
9.67**
RV5+SV1≥40 mm
116
1044
61
36
9
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43.1
9.58**
RVV5 orV6≥25 mm
108
982
53
31
8
39
39.7
8.83**
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RⅠ+RⅡ≥40 mm
3
26
1
1
0
1
34.8
8.55*
SV1≥22 mm
15
157
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8
4
2
6
38.2
8.50**
SV3≥25 mm
16
151
10
2
3
5
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33.1
7.36**
U wave
32
303
15
9
1
10
33.0
7.34**
RⅠ≥15 mm
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4
33
1
1
0
1
30.3
6.74*
RavF≥20 mm
2
20
0
0
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0
0
0
TQRS≥0.09 s
12
106
4
3
0
3
28.3
6.29**
VATV5 or V6≥0.05 s
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3
28
1
0
0
0
0
0
Voltage abnormality only
39
398
13
8
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0
8
20.1
4.47**
*P<0.05 ,** P<0.01 vs Normotensives;Death rate was expressed as event per 1 000 person year
3 The risk of voltage abnormality alone Though the relative risk of cerebro-cardiovascular events was about 4.5 times higher in hypertensives with ECG voltage abnormality alone than in normotensives (Fig 1),the risk was as the same as in hypertensives without ECG abnormality,suggesting that the higher risk in hypertensives with ECG voltage abnormality alone may be ascribed to concomitant high blood pressure.The voltage abnormality alone could not predict the cerebral cardiovascular events in the future.
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图1 高血压病人合并心电图左心室高电压(n=39)和高血压无左心室高血压病人(n=163)的总死亡和心脑血管死亡危险性比较。NS：无差别。
Fig 1 Comparison of total and cerebral cardiovascular death between hypertensives without(HT n=163)and with LVH based on ECG voltage abnormal alone(n=39),NS:non significance.
4.The prognostic value of various specific ECG changes in hypertensives after stratification of BP
Figure 2 showed relative risk of cerebro-cardiovascular events in hypertensives with different ECG abnormalities.Of note,the cerebral cardiovascular risks were significantly higher in those with V1 Ptf abnormality,QV5≥2 mm,left ventricular strain,asymmetric T wave inversion and multiple ECG abnormalities than in hypertensives with voltage abnormality alone,with RR 6.85,3.30,3.32,2.79,2.45 respectively.However,the blood pressure was significantly higher in these hypertensives with different ECG abnormalities than in hypertensives with voltage abnormality alone.To verify the independent risk for these ECG changes,the RR of cerebral cardiovascular events was calculated in hypertensives with above five ECG abnormalities as compared to those hypertensives with voltage abnormality alone after stratification of blood pressure.It was showed that after adjustment of blood pressure,the risk of cerebral cardiovascular events was still markedly higher in those with V1 Ptf abnormality,QV5≥ 2 mm,left ventricular strain,asymmetric T wave inversion and multiple ECG abnormalities than in hypertensives with voltage abnormality only.The RR for these five ECG changes were 6.55,3.19,2.99,2.32,2.26 respectively after stratification of blood pressure (Fig 3),suggesting that V1 Ptf abnormality,QV5≥2 mm,left ventricular strain,asymmetric T wave inversion and multiple ECG abnormalities were independent risk factors for the prediction of cerebral cardiovascular events in the future.
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图2 高血压合并左心室肥厚病人各种不同心电图改变的总死亡和心脑血管死亡事件的危险度。*:P<0.05,**:P<0.01 与单纯电压指标异常相比。(n=39)
Fig 2 Relative risk of total and cerebral cardiovascular death for various specific ECG changes in hypertensives with left ventricular hypertrophy.
图3 纠正血压因素前后高血压病人各种心电图变化的相对危险度
Fig 3 Relative risk of various specific ECG changes in hypertensives before(□) and after(■) adjustiment of blood pressure.
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1.Asymmetric T wave;2.V1 Ptf abnormality;3.Repolarisation abnormality;4.QV5≥ 2mm;5.Multiple abnormalities
DISCUSSION
Hypertension has long been regarded as a main risk factor for both coronary heart disease and stroke[1-7].Hypertensive left ventricular hypertrophy based either echocardiography or electrocardiogram has also been demonstrated to be an independent risk factor for cerebral cardiovascular events.ECG-LVH has an especially strong association with development of stroke and cardiac failure.Left ventricular hypertrophy has many adverse impact on heart,such as decreased coronary reserve,insufficiency of myocardial perfusion,increased myocardial collagen content which may eventually impair diastolic function and cause electrophysiological instability,which may contribute to the higher incidence of arrhythmia in hypertensives with LVH[6].It has been repeatedly reported that hypertensives with LVH had increased morbidity and mortality of cardiovascular events.Framingham study showed that 5 year mortality was 35% for male and 20% for female hypertensives[6-7,20].In this 14 years long term follow up study,we demonstrated that (1) stroke was the main cause of death for Chinese hypertensives and hypertensives with left ventricular hypertrophy;(2) ECG voltage abnormality alone is not a risk factor independent of blood pressure;(3)V1 Ptf abnormality,QV5≥2 mm,left ventricular strain,asymmetric T wave inversion and multiple ECG abnormalities were independent risk factors and of prognostic value for prediction of cerebral cardiovascular events in hypertensives.
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Framingham study[12] has shown that ECG-LVH is independently associated with a marked increase in risk of all major clinical manifestations of coronary heart disease,suggesting it is more a sign of myocardial ischeamia than hypertrophy.A diagnosis of ECG-LVH is thought to chiefly reflect enlargement of the heart,particularly hypertensive hypertrophy,the ECG finding of so-called hypertrophy also reflects other phenomena.There is evidence to suggest that ECG-LVH,particularly when high amplitude R waves are accompanied by repolarisation abnormalities,probably indicates ischemic myocardial involvement as well as hypertensive hypertrophy,which is associated with increased risk of cardiovascular mortality.The accompanying repolarisation abnormalities signal the onset of a compromised coronary circulation and ischemic myocardial involvement.When manifested by repolarisation abnormalities,it carries a prognosis no better than that of ECG myocardial infarction.Within 10 years,20 per cent of men with ECG-LVH or ECG myocardial infarction developed cardiac failure,a rate five times that of the general Framingham sample of the same age[12].Stroke occurred in 17% of men with ECG-LVH in the Framingham study.In contrast,stroke constituted the major cause of death in this study population.It was suggested that any hypertensive patient with ECG-LVH should be treated as promptly and vigorously as a person recovering from a myocardial infarction[12].The voltage criteria appear to reflect only the severity and duration of the often-associated hypertension.In this study we found that ECG voltage abnormality alone is not a risk factor independent of blood pressure.The higher risk for those hypertensives with ECG-LVH based on the voltage criteria only may be ascribed to higher blood pressure per se,other than ECG voltage abnormality.
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Advances in echocardiographic methodology have enhanced the reliability of detection of LVH to a higher level than has been possible to achieve by conventional ECG criteria.The later was known to have a low sensitivity for LVH.Despite the advantages of echocardiograms,cost and operational considerations tend to limit their utility in large-scale population studies and clinical trials.Because of its low cost and broad availability,electrocardiogram is currently recommended as the routine test to detect LVH in all subjects with high blood pressure.Sensitivity of ECG criteria of LVH varied between 9% and 33% and specificity was generally≥ 90%.The performance of standard electrocardiogram for the diagnosis of LVH in essential hypertension can be improved using a modified sex-specific partition value of the Cornell voltage (2.4 mV in men and 2.0 in women).Siscovick DA et al[15]reported that continuous ECG indexes that reflect left ventricular hypertrophy,myocardial injury,and QT-interval prolongation are directly related to the risk of primary cardiac arrest among hypertensive patients without clinically recognized heart disease.Several multivariate statistical methods have recently been introduced for estimation of left ventricular mass from standard 12-lead electrocardiographic measurements[13,16,21] ,and many ECG criteria had been proposed to increase the sensitivity of detection of LVH[13,16].However,the sensitivity and specificity differ greatly.Of note,the Romhilt-Estes score which combines QRS voltage and voltage-independent signs such as QRS duration,retardation of the deflection of the highest point of the ECG wave,left atrial enlargement,left axis deviation and left ventricular strain,showed a specificity of 100% for LVH[13].The combination of 3 highly specific criteria ,Cornell voltage,Romhilt-Estes score,left ventricular strain,allows a further increase in sensitivity without compromising specificity in detecting LVH[13].
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V1 Ptf abnormality may be used as an non-invasive index for assessment of cardiac function and left atria overload[11,22].It was reported that patients with acute myocardial infarction exhibiting ECG V1 Ptf abnormality were at a higher risk of heart failure ,increased short term mortality and decreased long-term survival rates[23].ECG V1 Ptf abnormality may reflect pressure overload of left atria ,insufficiency of coronary blood flow,and increased left ventricular end diastolic pressure.Narrow and deep Q wave in V5 or V6 may represent diastolic overload of left ventricle.The association of an asymmetrically inverted T wave with left ventricular hypertrophy was recorded many years ago[24].Short et al[25] demonstrated a close relation between asymmetric T wave inversion and ventricular hypertrophy by using echocardiography.ECG ST depression is thought to be the hallmark of ischemia .T-wave abnormality is also considered as a risk indicator of coronary heart disease[8,26].Even non-specific electrocardiographic abnormalities was reported to carry a greater risk of CHD[27].In the Framingham study,the sensitivity of electrocardiography increased with increasing severity of LVH,and prevalence of left ventricular strain increased with the degree of LVH.It was reported that a strain pattern is a very specific marker of LVH (89%)[13],even in the absence of increased QRS voltages.Therefore,V1 Ptf abnormality,QV5≥2 mm,left ventricular strain,asymmetric T wave inversion appears to indicate the damage of left ventricle function and of prognostic value for prediction of cardiac and cerebro-vascular events in hypertensives.The mechanism that link LVH to cardiovascular mortality and morbidity are unclear.In essential hypertension,left ventricular mass may be considered a marker that reflects and integrates the long-term detrimental effects of high BP and other cardiovascular risk factors.Increased left ventricular mass is also associated with an increase risk for ventricular arrhythmia and sudden cardiac death[28-30].
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REFERENCES
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3 Weber JR.Left ventricular hypertrophy;Its prime importance as controllable risk factor[J] Am Heart J 1988;116:272-279
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4 Kannel WB.Prevalence and natural history of electrocardiographic left ventricular hypertrophy.Proceedings of symposium:left ventricular hypertrophy in essential hypertension,mechanism and therapy[J] Am J Med 1983;75:4
5 Abisamra F,Fouad FM,Tarazi RC.Determinants of left ventricular hypertrophy and function in hypertensive patients[J] Am J Med 1983;75(suppl 10):26
6 Hachamovitch R,Sonnenblick EH,Strom JA.Left ventricular hypertrophy and effect of antihypertensive drug therapy[J] Curr Prob Cardiol 1988;13:375
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7 Kannel WB,Gordon T,Castelli WP,et al.Electrocardiographic left ventricular hypertrophy and risk of coronary heart disease:The Framingham study[J] Ann Intern Med 1970;72:813
8 Rose G,Baxter PJ,Reid DD,et al.Prevalence and prognosis of electrocardiographic findings in middle- aged men[J] Br Heart J 1978;40:636-643
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Received：1999-02-15, http://www.100md.com