Relation of Positive T Wave in Lead aVR to Risk of Cardiovascular Mortality




We examined the prevalence and prognostic impact of a positive T wave in lead aVR (aVRT+) on a standard electrocardiogram in the general population. Data were collected from a large nationally representative (random sample) health examination survey conducted in Finland from 2000 through 2001. The survey consisted of 6,354 subjects (2,876 men and 3,478 women) ≥30 years who participated in the field health examination including standard electrocardiographic (ECG) recording at rest. The prevalence of aVRT+ (defined as positive or isoelectric T wave in lead aVR) was 2.2%. During the median follow-up of 98.5 months (interquartile range 96.6 to 99.6), there were 214 (3.5%) cardiovascular (CV) deaths. In Cox regression analysis after adjustment for age and gender, relative risks for CV and total mortalities associated with aVRT+ were 3.24 (95% confidence interval [CI] 2.32 to 4.54, p <0.001) and 1.91 (95% CI 1.47 to 2.49, p <0.001), respectively. In the fully adjusted model controlling for other risk factors, CV morbidity, and ECG findings, the relative risk for CV mortality for aVRT+ was 2.94 (95% CI 2.07 to 4.18, p <0.001). In conclusion, aVRT+, an easily recognized ECG finding, predicts risk for CV mortality in the general population. This finding could aid in screening for risk of total and CV mortalities.


T-wave abnormalities are among the most frequently encountered pathologic electrocardiographic (ECG) findings in apparently healthy population. Even minor ST-T abnormalities are associated with increased long-term cardiovascular (CV) and total mortalities. Prevalence of a positive T wave in lead aVR (aVRT+) in the general population is not known. Neither is it known whether there are differences in prevalence between women and men. There is no population-based data on the impact of aVRT+ on mortality. Therefore, the aim of the present study was to determine the prevalence and prognostic impact of aVRT+ on standard electrocardiogram at rest in a population-based cohort.


Methods


This study is based on the Health 2000 Study, which is a major Finnish health examination survey. It was carried out from 2000 through 2001, and a representative stratified random cluster sample of the Finnish population was examined. For the population ≥80 years of age, the sampling probability was 2 times as high as in those <80 years. Implementation of the survey is described in detail elsewhere. One of the goals of the Health 2000 Survey was to obtain contemporary information about major diseases in Finland.


The Health 2000 Survey sample consisted of 8,028 subjects (3,637 men and 4,391 women) ≥30 years old, of whom 79% (6,354 subjects, 2,876 men and 3,478 women) participated in the health examination. The national hospital discharge register and the national register on rights to reimbursements for medication costs were linked to the Health 2000 Survey data. The study protocol of the Health 2000 Survey was approved by the epidemiology ethics committee of the Helsinki and Uusimaa hospital district. Participants in the survey signed an informed consent before the health interview and at the beginning of the health examination.


Examining physicians followed detailed written instructions and applied uniform diagnostic criteria in accordance with good clinical practice. Information on rights for drug reimbursements was obtained from the national register. Study participants were asked whether they used any medications and the names and doses of these medications were recorded. Subjects with typical angina pectoris symptoms were identified by the World Health Organization chest pain questionnaire. Also, a history of coronary bypass surgery or percutaneous coronary intervention was checked during the interview.


Information on previous hospitalization for myocardial infarction (MI) or coronary heart disease was obtained from hospital discharge summaries that study participants brought along or from the national hospital discharge register. The Finnish hospital discharge register has been shown to be valid in identifying major coronary heart disease events.


Classification of coronary heart disease required ≥1 of the following: diagnosis of MI and/or angina pectoris during the field health examination by a physician, large Q waves on electrocardiogram at rest, hospitalization for coronary heart disease ( International Classification of Diseases, Eighth Revision [ICD-8] or Ninth Revision [ICD-9] codes 410 to 414 or Tenth Revision [ICD-10] codes I20 to I25), history of a coronary revascularization procedure, right to drug reimbursements for coronary heart disease, or use of nitroglycerin combined with an anticoagulant, acetyl salicylic acid, or β blocker.


Classification for MI required a clinical diagnosis of old MI by the examining physician, large Q waves on electrocardiogram at rest, or previous discharge diagnosis of MI (ICD-8 or ICD-9 code 410 or ICD-10 codes I21 to I22). MI was defined as a positive history of the condition in medical records or old MI on electrocardiogram or typical self-reported history of MI treated in a hospital. Large Q waves indicating probable previous MI included Minnesota Codes 1.1 to 1.3.


Heart failure classification required a clinical diagnosis by the examining physician and a previous discharge diagnosis of heart failure (ICD-8 code 4270, ICD-9 code 428, or ICD-10 code I50) or right to drug reimbursements for heart failure. Almost without exception the classification for stroke required ≥1 discharge diagnosis of stroke (ICD-8 codes 430 to 431, 433 to 434, ICD-9 codes 430 to 434, or ICD-10 codes I60, I61, I63). Classification for peripheral arterial disease required a clinical diagnosis by the examining physician or previous hospitalization for peripheral arterial disease. Chronic obstructive pulmonary disease classification required a clinical diagnosis by the examining physician including bronchial obstruction in lung function tests (forced expiratory volume <70%) or previous hospitalization for chronic obstructive pulmonary disease (ICD-8 or ICD-9 codes 490 to 492 or ICD-10 code J44).


Height and weight were measured and body mass index calculated. Waist circumference was measured in the standing position using standards created for population health studies. Blood pressure was measured with a mercury sphygmomanometer (Mercuro 300, Speidel and Keller, Juningen, Germany) from the right arm. The first measurement was carried out after ≥5 minutes of rest in the sitting position. Korotkoff first phase was used as the sign of systolic blood pressure and the fifth phase as the sign of diastolic pressure. Measurement was repeated 2 minutes after the first measurement. The average of the 2 measurements was used in the analysis. Clinic hypertension was defined as a clinic blood pressure ≥140/90 mm Hg. Diabetes mellitus was defined as a serum glucose level ≥7.0 mmol/L or a history of use of oral hypoglycemic agents or insulin therapy. Smoking was defined as daily use of tobacco products.


Venous blood samples were drawn from the antecubital vein. High-density lipoprotein cholesterol, total cholesterol, triglyceride, and serum glucose concentrations were determined enzymatically (high-density lipoprotein: Roche Diagnostics, GmbH, Mannheim, Germany; total cholesterol, triglycerides, and glucose: Olympus System Reagent, Olympus, Hamburg, Germany) with a clinical chemistry analyzer (AU400, Olympus). Low-density lipoprotein cholesterol was calculated with the Friedewald formula. Serum uric acid concentration was determined enzymatically (Urikaasi PAP, Konelab, Thermo Electron Oy, Vantaa, Finland). High-sensitivity C-reactive protein concentrations were determined using a chemiluminescent immunometric assay (Immulite, Diagnostic Products Corporation, Los Angeles, California). Gamma-glutamyltransferase activity concentration was determined enzymatically according to the International Federation of Clinical Chemistry (Gamma-GT, Konelab, Thermo Electron Oy, Vantaa, Finland).


Standard 12-lead electrocardiograms were recorded at rest in the supine position using recommended standardized procedures and MAC 5000 recorders (Marquette Hellige, Freiburg, Germany/Milwaukee, Wisconsin). Electrocardiogram was recorded and printed using a paper speed of 50 mm/s. The maximal filter setting of the system (150 Hz) was used. ECG analyses were performed by a Health 2000 Survey investigator blinded to patients’ clinical data. Minnesota coding was performed at the Institute of Cardiology, Kaunas Medical Academy, Kaunas, Lithuania by 2 investigators who were also blinded to patients’ clinical data. Electrocardiograms were obtained successfully in 6,318 subjects (99%) who attended the health examination. Abnormalities identified visually on the ECG strips were coded in accordance with the Minnesota coding scheme. Electrical recordings were analyzed using Magellan software (Marquette Electronics, Inc., Milwaukee, Wisconsin). Nineteen electrocardiograms were rejected owing to data lost in further processes, leaving 6,299 electrocardiograms for analysis.


Mortality information until January 2009 was gathered by linking the personal identity code from the Health 2000 Survey database to the causes of death register, maintained by Statistic Finland, which records 100% of deaths of Finnish citizens at home and nearly 100% abroad.


Subjects with atrial fibrillation (n = 94), cardiac pacemaker (n = 4), preexcitation (n = 1), and right or left bundle branch block (n = 143) were excluded (Minnesota Codes 6.4, 6.8, 7.1 to 7.2, 7.8, 8.3). Final analysis was performed with 6,063 subjects (3,330 women and 2,733 men).


We defined aVRT+ as aVRT ≥0 mm (isoelectric or positive deflection). Negative aVRT (aVRT−) was defined as aVRT <0 mm.


Prevalence of aVRT+ was defined for the total study population and by gender and 3 age groups. Chi-square test was applied to confirm the significance of differences between groups. Data were categorized into 2 groups according to aVRT: “aVRT− group” (aVRT <0 mm) and “aVRT+ group” (aVRT ≥0.00 m). To evaluate prevalence, cross tabs with aVRT+, gender, and age groups were used.


Comparisons between groups were calculated with t test for independent samples or with chi-square test as applicable ( Table 1 ).



Table 1

Baseline characteristics of the Health 2000 Survey participants






















































































































































Variable Women Men
aVRT− aVRT+ p Value aVRT− aVRT+ p Value
(n = 3,246) (n = 84) (n = 2,669) (n = 69)
Age (years) 52.6 ± 73.7 <0.001 50.3 ± 66.8 <0.001
Height (cm) 162.4 ± 156.8 <0.001 176.0 ± 171 <0.001
Weight (kg) 70.2 ± 73.1 0.054 83.9 ± 83.2 0.692
Body mass index (kg/m 2 ) 26.7 ± 2.7 <0.001 27.0 ± 28.4 0.006
Waist circumference (cm) 88.1 ± 93.0 <0.001 97.5 ± 102.1 0.001
Glucose (mg/dl) 97 ± 114 <0.001 103 ± 112 <0.001
Total cholesterol 0.001 0.56
mg/dl 228 ± 243 232 ± 228
mmol/L 5.9 ± 6.3 6.0 ± 5.9
High-density lipoprotein cholesterol <0.001 0.002
mg/dl 54 ± 46 46 ± 42
mmol/L 1.4 ± 1.2 1.2 ± 1.1
Low-density lipoprotein cholesterol 0.314 0.328
mg/dl 147 ± 151 147 ± 143
mmol/L 3.8 ± 3.9 3.8 ± 3.7
Triglycerides <0.001 0.031
mg/dl 124 ± 177 159 ± 186
mmol/L 1.4 ± 2.0 1.8 ± 2.1
C-reactive protein (mg/L) 2.1 ± 3.0 0.126 2.2 ± 4.3 0.017
γ-Glutamyltransferase (U/L) 26.7 ± 30.7 0.234 46.1 ± 53.3 0.284
Uric acid (mg/dl) 4.5 ± 5.7 <0.001 5.7 ± 6.3 <0.001

Values are presented as mean ± SD.


Receiver operating characteristic curve analysis was used to determine the ability of aVRT+ to distinguish between subjects with and without CV mortality during follow-up.


In Cox proportional hazards models the aVRT+ was used. The proportionality assumption was checked for the main analyses based on correlations of survival rankings with Schoenfeld residuals; all covariates fulfilled this criterion. The end point was CV death and models used the following covariates: age, gender, left or right ventricular hypertrophy, Q waves, ST-segment depression in lead V 5 , heart rate, angina pectoris, diabetes mellitus, hypertension, smoking, total cholesterol, high-density lipoprotein cholesterol, low-density lipoprotein cholesterol, and body mass index.


Age group analyses (30 to 44, 45 to 54, and ≥55 years) were performed. The complex sampling design was taken into account by correcting for the oversampling of subjects ≥80 years of age. All analyses were performed with SPSS 17.0 for Windows (SPSS, Inc., Chicago, Illinois). Statistical significance was based on a p value <0.05.




Results


Prevalence of aVRT+ was 2.2% (n = 138, 69 women and 69 men) with no difference between men and women. Subjects with aVRT+ were older and more often had a history of CV disease and risk factors than subjects with aVRT− ( Tables 1 and 2 ). Prevalence of aVRT+ was 5.2% in subjects ≥55 years of age and 0.4% in subjects <55 years of age.



Table 2

Clinical characteristics and mortality of the study population according to presence of T-wave amplitude ≥0 mm in lead aVR







































































































































































































Men Women
aVRT− aVRT+ p Value aVRT− aVRT+ p Value
Regular smoking 740 (27.8%) 14 (20.3%) 0.169 556 (17.1%) 9 (10.7%) 0.122
Heart failure 60 (2.3%) 10 (14.5%) <0.001 106 (3.3%) 16 (13.1%) <0.001
Chronic obstructive pulmonary disease 39 (1.5%) 1 (1.4%) 0.988 35 (1.1%) 3 (3.6%) 0.034
Hypertension 792 (29.8%) 27 (39.1%) 0.097 950 (29.1%) 49 (59.0%) <0.001
Stroke 57 (2.1%) 10 (14.5%) <0.001 58 (1.8%) 5 (6.1%) 0.005
Peripheral artery disease 48 (1.8%) 2 (2.9%) 0.506 38 (1.2%) 4 (4.9%) 0.003
Diabetes mellitus 133 (5.0%) 10 (14.5%) <0.001 158 (4.9%) 14 (16.9%) <0.001
Left ventricular hypertrophy/right ventricular hypertrophy 342 (12.8%) 6 (8.7%) 0.308 407 (12.5%) 13 (15.5%) 0.423
Coronary heart disease
No 2,437 (91.5%) 62 (89.9%) 0.634 2,922 (90.0%) 74 (88.1%) 0.562
Yes 227 (8.5%) 7 (10.1%) 327 (10.0%) 10 (11.9%)
Myocardial infarction
No 2,556 (95.9%) 69 (100%) 0.088 3,087 (95.1%) 78 (92.9%) 0.349
Yes 108 (4.1%) 0 (0%) 159 (4.9%) 6 (7.1%)
Death
All-cause 231 (8.7%) 31 (44.9%) <0.001 232 (7.1%) 35 (41.7%) <0.001
Cardiovascular 90 (3.4%) 25 (36.2%) <0.001 78 (2.4%) 21 (25.0%) <0.001
Medication
β Blockers 310 (11.6%) 10 (14.5%) 0.466 459 (14.1%) 10 (11.9%) 0.561
Calcium channel blockers 128 (4.8%) 6 (8.7%) 0.139 182 (5.6%) 2 (2.4%) 0.201
Angiotensin-converting enzyme inhibitors/angiotensin receptor antagonists 203 (7.6%) 7 (10.1%) 0.437 255 (7.9%) 7 (8.3%) 0.872
Statins 136 (5.1%) 6 (8.7%) 0.185 157 (4.8%) 2 (2.4%) 0.565
Aspirin 179 (6.7%) 3 (4.3%) 0.435 237 (7.3%) 5 (6.0%) 0.860

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Dec 16, 2016 | Posted by in CARDIOLOGY | Comments Off on Relation of Positive T Wave in Lead aVR to Risk of Cardiovascular Mortality

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