(Hypertension. 2000;36:766.)
© 2000 American Heart Association, Inc.
Scientific Contribution |
From the Department of Medicine, Division of Cardiology, Weill Medical College of Cornell University (P.M.O., R.B.D.), New York, NY; Sahlgrenska University Hospital/Östra (S.J., B.D.), Göteborg, Sweden; Ullevål University Hospital (S.E.K.), Oslo, Norway; and University of Michigan Medical Center (S.J.), Ann Arbor, Mich.
Correspondence to Peter M. Okin, MD, Weill Medical College of Cornell University, 525 E 68th St, New York, NY 10021. E-mail pokin{at}mail.med.cornell.edu
| Abstract |
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Key Words: blood pressure electrocardiography hypertension hypertrophy
| Introduction |
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Hypertensive patients with ECG LVH were selected for participation in LIFE on the basis of gender-specific Cornell voltage-duration product21 22 and/or nongender-specific Sokolow-Lyon voltage criteria.23 However, these criteria have demonstrated varying performance characteristics for the identification of LVH, particularly in relation to obesity24 25 and race,26 which suggests that each might identify different patient subsets with potentially different baseline risks for adverse cardiovascular outcomes. This article examines baseline characteristics of the LIFE study participants in relation to the presence or absence of ECG LVH by these criteria.
| Methods |
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Electrocardiography
Presence of LVH on screening ECG read at a central core
laboratory was required for entry into LIFE as a cost-effective means
to identify patients at high risk of morbid events due to the important
target organ manifestations of LVH. Patients enrolled into LIFE also
underwent baseline ECG at randomization. On the basis of previous
evidence that the product of QRS voltage and duration, as an
approximation of the time-voltage area of the QRS complex, had a high
level of sensitivity with maintained specificity in relation to
anatomic and echocardiographic reference standards of
LV mass,21 22 the product of QRS duration times the
Cornell voltage combination (RaVL +
SV3, plus 8 mm in
women21 22 ) was used with a threshold value of
2440 mm · ms to identify LVH. After results of 2 studies
published in late 1995 suggested that a smaller gender adjustment was
more appropriate28 29 and feedback from field
investigators indicated that a number of otherwise eligible
hypertensive patients had ECG LVH by the insensitive but highly
specific Sokolow-Lyon voltage but not by the Cornell product
criteria, 2 changes were made in ECG entry criteria that affected
patients enrolled in LIFE after April 30, 1996: the gender adjustment
of Cornell voltage criteria was reduced from 8 to 6 mm and
Sokolow-Lyon voltage (SV1 +
RV5/6) >38 mm was accepted as an
alternative ECG eligibility criterion.2
All ECGs were interpreted at the Core Laboratory at Sahlgrenska University Hospital/Östra in Göteborg, Sweden, by experienced investigators blinded to clinical information. QRS duration was measured to the nearest 4 ms, and the R-wave amplitudes in leads aVL, V5, and V6 and S wave amplitudes in leads V1 and V3 were measured to the nearest 0.5 mm (0.05 mV) by use of calipers. Cornell and Sokolow-Lyon voltages were calculated as defined above,21 22 23 and the Cornell voltage-duration product was calculated as the product of Cornell voltage and QRS duration, as previously reported.21 22 Presence of ECG LVH by Sokolow-Lyon voltage criteria was defined according to the preselected partition value of 38 mm used to determine LIFE study eligibility as defined above.1 2 ECG LVH according to Cornell product criteria was defined according the partition value of 2440 mm · ms for this study, with a 6-mm gender adjustment in women; use of an 8-mm gender adjustment did not appreciably alter the results.
Statistics
Data are presented as mean±SD for continuous
variables and proportions for categorical variables, with
patients grouped according to the presence or absence of Cornell
voltage-duration product or Sokolow-Lyon voltage criteria for LVH
on baseline LIFE study ECG. Data management and analysis were
performed with SPSS version 9 software. Differences in prevalences
between groups were compared by use of
2
analyses. Mean values of demographic, clinical, and biochemical
variables were compared with 2-way ANOVA to take into account the
potential effect of gender on these variables. Independent
associations of variables with the presence of ECG LVH by Cornell
product and by Sokolow-Lyon voltage criteria were determined with
logistic regression analyses. For all tests, a 2-tailed
P<0.05 was required for statistical significance.
| Results |
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Demographic data according to the presence or absence of ECG by Cornell product and Sokolow-Lyon voltage criteria are shown in Table 1. Although ECG LVH by each method was associated with slightly older age, significant differences existed in gender, race, and tobacco use according to each method. Compared with patients without ECG LVH by Cornell voltage-duration product criteria, patients with ECG LVH by this method were more likely to be female, white, and to have never smoked. In contrast, patients with ECG LVH by Sokolow-Lyon voltage criteria were more likely to be male, black, and to be current smokers than patients without ECG LVH by this approach.
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Clinical variables according to the presence or absence of ECG LVH by each method are shown in Table 2. Body habitus characteristics of patients with ECG LVH differed significantly according to the definition of LVH. Patients with ECG LVH according to the Cornell model were heavier but of similar heights; thus, they had higher BMIs and a greater prevalence of obesity than patients without ECG LVH by this method. In comparison, ECG LVH by Sokolow-Lyon voltage criteria was associated with lower body weight, greater height, and, consequently, much lower BMIs and lower prevalence of obesity than in the absence of ECG LVH by Sokolow-Lyon voltage criteria. Systolic blood pressure was higher in both ECG LVH groups, but diastolic blood pressure was higher in patients with LVH by the Cornell product and lower in patients with Sokolow-Lyon voltage criteria for LVH, such that pulse pressure was significantly higher in patients with Sokolow-Lyon LVH but only marginally elevated in patients with Cornell product LVH. Consequently, only Sokolow-Lyon LVH was associated with a higher prevalence of isolated systolic hypertension. Diabetes was more common in patients with Cornell product LVH but less common in patients with ECG LVH by Sokolow-Lyon criteria. Both criteria sets for LVH were associated with higher rates of preexisting angina, but only Cornell product criteria were associated with a higher rate of diabetes, whereas LVH by Sokolow-Lyon voltage criteria was associated with a higher prevalence of stroke or transient ischemic attack. Previous myocardial infarction and preexisting peripheral vascular disease prevalence was similar in patients with and without ECG LVH by each approach.
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Biochemical characteristics according to the presence or absence of ECG LVH by Sokolow-Lyon voltage and Cornell voltage-duration product criteria are shown in Table 3. Compared with patients without ECG LVH by this method, patients with Cornell product criteria for LVH had marginally but significantly higher hemoglobin and uric acid levels and marginally lower serum potassium levels but similar serum sodium and serum and urine creatinine levels. In contrast, compared with patients without ECG LVH, patients with ECG LVH by Sokolow-Lyon voltage criteria had lower hemoglobin and higher serum uric acid and creatinine levels but had similar serum sodium, potassium, and urine creatinine levels.. The relation of cholesterol levels to the presence or absence of ECG LVH also differed between the methods. ECG LVH by Cornell product criteria was associated with higher total cholesterol and lower HDL cholesterol levels and consequently with higher total/HDL cholesterol ratios. In comparison, patients with ECG LVH by Sokolow-Lyon voltage criteria had lower total cholesterol and higher HDL cholesterol levels, with resultant lower total/HDL cholesterol ratios. The relation of biochemical manifestations of diabetes to ECG LVH also differed according to the definition of LVH. Patients with Cornell product LVH had higher serum glucose levels and greater urinary microalbuminuria, whereas patients with Sokolow-Lyon LVH had lower serum glucose levels and only marginally elevated levels of urine microalbumin.
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Because of the potential for interrelation between some of these variables, the independent associations of demographic, clinical, and biochemical characteristics to the presence of ECG LVH by Cornell product and Sokolow-Lyon voltage criteria was assessed by multivariate logistic regression analyses (Tables 4 and 5). After these interrelations are taken into account, the presence of ECG LVH by Cornell voltage-duration product criteria was predominantly associated with higher BMI, increased age, and female gender; was less strongly related to increased hemoglobin, white race, and elevated serum glucose level; and was additionally related to increased diastolic blood pressure, decreased serum potassium, absence of any tobacco use, and history of angina. In contrast, presence of ECG LVH by Sokolow-Lyon voltage criteria was predominantly related to lower body mass index, male gender, and black race; was less strongly related to an elevated pulse blood pressure, decreased hemoglobin, lower age, and higher HDL cholesterol levels; and was additionally related to the absence of diabetes, to current smoking, and to higher systolic blood pressure, serum creatinine, and serum uric acid levels.
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The frequently opposite relations of demographic and clinical variables to the risk of Cornell product LVH as opposed to ECG LVH by Sokolow-Lyon voltage criteria can be further appreciated by examining odds ratios for LVH by each method (Tables 4 and 5). For example, each SD of the mean increase in BMI could be related to a 136% greater likelihood of ECG LVH by Cornell product criteria but was associated with only half the chance of having LVH by Sokolow-Lyon voltage. Similarly, male gender was associated with a 30% lower likelihood of LVH by Cornell product criteria but was associated with a 231% higher likelihood of Sokolow-Lyon LVH.
Because some of the patients met both Cornell product and Sokolow-Lyon voltage criteria for ECG LVH, which could potentially affect the above analyses, the relation of select clinical and demographic variables to the presence and/or absence of ECG LVH by these 2 criteria was further examined to allow assessment of patient groups with either Cornell product or Sokolow-Lyon voltage ECG LVH in relation to patients meeting neither of these criteria (Table 6). Analyzing data in this fashion did not change the associations when patients with both forms of ECG LVH were included in analyses (Tables 1 to 3). Both Sokolow-Lyon and Cornell product LVH remained associated with increased age, systolic blood pressure, and pulse blood pressure. Similarly, the presence of only Sokolow-Lyon LVH was associated with increased prevalence of male gender and black race, decreased body mass index, and slightly decreased diastolic blood pressure, whereas Cornell product LVH was associated with female gender, white race, increased body mass index, and similar diastolic blood pressure compared with patients without ECG LVH by either set of criteria. Of note, patients with both Sokolow-Lyon and Cornell product ECG LVH showed a mixed pattern with respect to these risk factors, which demonstrates summated effects for variables that tracked in common, such as age and systolic and pulse blood pressure, and shows intermediate relationships with gender, race, and body mass index, variables that have opposite associations with the 2 ECG criteria sets. When additional logistic regression analyses were performed to examine the independent relations of clinical variables to the presence of ECG LVH by either Sokolow-Lyon or Cornell product LVH after first excluding patients with both Sokolow-Lyon and Cornell product ECG LVH, no substantive differences were found compared with the results in Tables 4 and 5.
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Because the partition values selected to identify LVH by each ECG method are somewhat arbitrary in nature and were used to select the patient population for inclusion in the LIFE study, select demographic and clinical variables were further examined in relation to quartiles of Cornell voltage-duration product and Sokolow-Lyon voltage in the study population (Tables 7 and 8). Increased levels of Cornell product (Table 7) were associated with older age, female gender, and white race predominance, and increased levels of BMI and systolic, diastolic, and pulse blood pressures. In contrast, increased quartiles of Sokolow-Lyon voltage were related only weakly to age, associated with increased prevalence of male gender and black race, and strongly associated with decreased levels of BMI but had similar associations with increased levels of blood pressure (Table 8).
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| Discussion |
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Cornell product criteria for LVH were strongly and independently associated with increased BMI, consistent with the known relation of anatomic LVH to obesity.30 31 32 In contrast, Sokolow-Lyon voltage were independently associated with decreased BMI, which suggests that these criteria identify patients with anatomic LVH in which obesity does not play a significant role in the genesis of hypertrophy and, in addition, reflects the negative effect of obesity on precordial voltage amplitudes and subsequent lower sensitivity of Sokolow-Lyon voltage criteria for LVH in obese patients.23 24 33 In addition, after we controlled for interactions between variables, patients with Cornell product LVH had higher hemoglobin levels, consistent with greater blood viscosity levels, whereas patients with Sokolow-Lyon LVH had lower hemoglobin levels, consistent with lower blood viscosity levels (Tables 4 and 5). However, actual differences in hemoglobin levels were small (Table 3), which suggests that differences in blood viscosity between patients with and without ECG LVH are minimal.
LIFE patients with Cornell product LVH were more likely to be female but LVH by Sokolow-Lyon voltage was associated with a male preponderance, even after adjusting for other baseline differences (Tables 4 and 5). This gender difference in part reflects use of gender adjustment in implementation of the Cornell product, whereas a single, nongender-specific partition value of 38 mm was used for Sokolow-Lyon voltage.21 22 Use of a single partition value in both men and women is expected to produce lower sensitivity for LVH in women as a result of lower voltage values in women that persist even after taking into account gender differences in height, weight, and LV mass.34 In addition, female predominance among patients with Cornell product LVH may in part reflect use of an initially higher gender adjustment and consequent initial over-recruitment of women into LIFE that was subsequently corrected for by a decrease in the gender adjustment for the Cornell product.2 In this context, note that use of the initial gender adjustment to determine the presence of LVH by Cornell product criteria did not affect the current findings. The different proportions of men and women with LVH identified by Sokolow-Lyon voltage and Cornell product criteria are unlikely to reflect attenuation of precordial voltages by breast tissue in women, given that this effect previously has been demonstrated to account for <1% of ECG amplitude variations.35
Although not directly examined in the present study because of the designed absence of echocardiographic data in the vast majority of LIFE patients,2 differences in the ability of Sokolow-Lyon voltage and Cornell product criteria to detect increases in LV mass could also contribute to differences in baseline risk according to ECG LVH definition.7 8 9 10 11 12 Among LIFE patients enrolled in the echocardiographic substudy, those who met Cornell product criteria for LVH had higher LV mass indexes and were more likely to meet echocardiographic criteria for LVH than patients with Sokolow-Lyon voltage LVH.36 Moreover, these criteria appear to identify groups with different admixtures of concentric versus eccentric geometric patterns of hypertrophy.36 Because risk reduction with the different antihypertensive therapies used could potentially vary according to the severity and geometric pattern of hypertrophy, these differences further enrich the LIFE study population.
Thus, in summary, hypertensive patients enrolled in LIFE meeting Cornell product criteria for LVH differ significantly in several important ways from patients who met Sokolow-Lyon voltage criteria for LVH. Cornell product LVH was strongly associated with increased BMI, increased age, female gender, and potentially with greater severity of hypertrophy, whereas Sokolow-Lyon voltage LVH was strongly associated with male gender, leaner body builds, black race, and higher pulse blood pressures. The varying risk factor profiles associated with Cornell product and Sokolow-Lyon criteria for LVH suggest that patients who meet these criteria differ in their baseline risk of cardiovascular mortality and morbidity and thus may potentially derive varying prognostic benefit from the 2 LIFE therapeutic approaches to antihypertensive therapy aimed at reducing LV mass. Further assessment of this issue will be possible after completion of follow-up and unblinding of data in the LIFE study.
| Acknowledgments |
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Received May 8, 2000; first decision May 23, 2000; accepted June 1, 2000.
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