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Original Article
Prevalence of left-ventricular hypertrophy by multiple electrocardiographic criteria in general population: Hermex study Francisco J. Fe´lix-Redondo a, Daniel Ferna´ndez-Berge´s b, Alberto Caldero´n c, Luciano Consuegra-Sa´nchez d, Luı´s Lozano e, and Vivencio Barrios f
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Objectives: To determine the prevalence of left-ventricular hypertrophy (LVH) in the general population by means of multiple electrocardiographic criteria and the variables which are independently associated. Methods: Random-sample cross-sectional study of the general population aged between 25 and 79 years, representative of a health area, was conducted. An electrocardiogram was recorded ‘on line’ in the Electropres project website; 17 LVH criteria together with 2 combined criteria were used. By multivariate analysis we examined those variables independently associated with the presence of electrocardiographic LVH. Results: We recruited 2564 individuals, mean age 50.9 [standard deviation (SD) 14.7] years, 45.7% men. The criteria more prevalent were: Dalfo´ 19.4%, RV6/V5 14.5%, Perugia 10.9%, any combination with at least three positive criteria (Combined 3) 9.4%, Romhilt 7.5%, Lewis 6.2% and the recommended criteria of European Society of Hypertension 4%. The best prevalence ratio between hypertensive and normotensive individuals was achieved with Lewis, Dalfo´ and Perugia criteria. The least prevalence was Sokolow 0.7%. The variables that were independently associated with the presence of LVH by Combined 3 criterion were pulse pressure at least 50 [odds ratio (OR) 2.13, 95% confidence interval (CI) 1.47–3.09], arterial hypertension (OR 1.75, 95% CI 1.21–2.53) and smoking (OR 0.69, 95% CI 0.50–0.95). Conclusions: The detection ability of the electrocardiogram with regard to the LVH may improve with the use of other criteria than those currently recommended by the guidelines. The presence of LVH is positively associated with hypertension and elevated pulse pressure and negatively with a history of smoking. Keywords: diagnosis, electrocardiography, epidemiology, high blood pressure, left-ventricular hypertrophy, pulse pressure Abbreviations: CVD, cardiovascular disease; HTN, arterial hypertension; LVH, left-ventricular hypertrophy; PP, pulse pressure; SD, standard deviation; VDP, voltage-duration product
INTRODUCTION
L
eft-ventricular hypertrophy (LVH) is considered to be a cardiac condition secondary to hemodynamic stress, which causes hypertension (HTN), and is also related to genetic, metabolic and environmental factors [1]. The value of detection and monitoring of LVH is twofolds: it is a strong predictor of cardiovascular disease (CVD) and death [2], and regression with antihypertensive therapy reduces the risk of an adverse outcome [3]. Different methods of diagnosis exist, but the one that is mostly used in clinical practice is ECG. ECG has been shown to have prognostic values in different studies of the general [4,5], hypertensive [2,6] and even nonhypertensive populations [7], although it is variable for the different criteria used in each study [8,9]. The studies have also AQ3 reported the benefit of LVH regression [10], independent of blood pressure control. The ECG, however, shows limited sensitivity for the detection of LVH and thus it is not being recommended for this purpose [11], although some authors continue to develop new criteria [5,9] to improve it. In this context, a national online electronic reading project has been developed for the assessment of multiple electrocardiographic criteria [12] on the basis that sensitivity could be improved with a manageable loss of specificity [13–16]. In Spain, there is little information on the prevalence of LVH in the general population or in a representative sample of all hypertensive patients, in spite of the importance that its identification could have for this latter group [17]. The aim of this study was to determine the electrocardiographic prevalence of LVH in the general population
Journal of Hypertension 2012, 30:000–000 a Centro de Salud Villanueva Norte, bCardiovascular Diseases Program. Research Unit Health Area Don Benito-Villanueva de la Serena, Villanueva de la Serena, Badajoz, c Centro de Salud Rosa Luxemburgo, San Sebastia´n de los Reyes, Madrid, d Departament of Cardiology, Hospital Universitario de Santa Lucı´a, Cartagena, Murcia, eCentro de Salud Urbano I, Me´rida, Badajoz and fDepartament of Cardiology, Hospital Ramo´n y Cajal, Madrid, Spain
Correspondence to Francisco Javier Fe´lix Redondo, Plaza de Salamanca n8 9, Villanueva de la Serena (Badajoz), Spain. E-mail:
[email protected] Received 29 October 2011 Revised 12 March 2012 Accepted 3 April 2012 J Hypertens 30:000–000 ! 2012 Wolters Kluwer Health | Lippincott Williams & Wilkins. DOI:10.1097/HJH.0b013e3283546719
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by means of 17 criteria described in the literature. A secondary aim involved determining the variables independently related to its presence.
METHODS A cross-sectional descriptive study was conducted to determine the prevalence of risk factors and atherosclerotic-related subclinical organ damage in the general population of Extremadura (Spain). The methodology of the present study, response rate and demographic variables have previously been published [18]. Briefly, a representative sample of the population, between the age of 25 and 79 years, living in the health area of Don Benito-Villanueva de la Serena in the Spanish region of Badajoz, was randomly selected from Extremadura’s health service database of health card holders with universal coverage at the time of selection. The sample size was calculated to determine the prevalence of different cardiovascular risk factors with the highest degree of indeterminacy, accuracy of 2% and an a error of 5%, resulting in 2400 participants. The data collection period occurred between 2007 and 2009. Medical notes were taken for risk factors and previous CVD, as well as height, weight, waist circumference and blood pressure measurements. Fasting venous blood samples were also taken for blood glucose, creatinine and
total cholesterol and a first-morning urine sample for albumin and creatinine. A 12-lead electrocardiogram was performed with a MAC 1200 ST V1 device (General Electric). The digitized electrocardiograms were sent online to the website of the ELECTROPRES web platform [12], which can identify 17 LVH criteria. The definition of the criteria and cut-off points for LVH diagnosis are presented in Table 1. The supporting bibliography of each criterion is available on the same website [12]. The validation of the software and main diagnostic criteria have been recently published [15,16]. They have reported that most of the study criteria show specificity that exceeds 90%. Further, Dalfo´, Lewis and Perugia criteria showed a good sensitivity (37.1, 19– 20 and 13.3–16%, respectively). Finally they have also documented that the use of a combination of criteria increases sensitivity at expense of a loss of specificity [15,16].
Study variables Hypertension, hypercholesterolemia and diabetes mellitus were considered present if the patient had been previously diagnosed by a doctor or showed an average blood pressure (from the second and third measurements) of at least 140/90 mmHg, total cholesterol at least 240 mg/dl and fasting glucose at least 126 mg/dl. Smoking was defined
TABLE 1. LVH criteria (definitions) Criteria Voltage Sokolow Cornell QRS 12-lead sum Gubner-Ungerleider Lewis R V6/V5 R aVL Dalfo´ Voltage-duration QRS product Sokolow Cornell QRS 12-lead sum Gubner-Ungerleider R aVL Composite criteria Romhilt-Estes
Perugia
Hannover ECG System Combined criteria European Guidelines criteria Combined criterion 1 Combined criterion 3
2
Equations
LVH diagnostic value
S (V1) þ max (R(V5, V6) R (aVL) þ S (V3) Sum R and S or Q (according to most)In the 12-lead R (I) þ S (III) (R (I) þ S (III)) - (R (III) þ S(I)) R (V6)/R(V5) R (aVL) R (aVL) þ S (V3)
"3.5 mV M: "2.8 mV; F: "2.0 mV M: >19 530 mV; F: >18 499 mV
Sokolow voltaje x QRS duration M: R(aVL) þ S(V3) x QRS duration; F: (R(aVL) þ S(V3) þ 0,6)x Dur QRS QRS voltage sum x QRS duration Gubner voltage x QRS duration R aVL voltage x QRS duration
M: >367.4 mV.ms; F: >322.4 mV.ms >244 mV
R or S en I, II, III, aVR, aVL or aVF S in V1, V2 R in V5, V6 ST polarity opposite max V5 o V6 (without digital) ST polarity opposite max V5 o V6 (with digital) Left deviation axis "30o QRS Duration "90 ms Intrinsicoid deflection V5, V6 "50 ms S V3 þ R aVL >2.4 (M), >2.0 (F) S-T Alteration Romhilt-Estes "5 Logistic regression equation
3 points 3 points 3 points 3 points 1 point 2 points 1 point 1 point At least 1 positive criterion
Sokolow voltage "3.8 mV Cornell voltage x Duration product All criteria All criteria
At least 1 positive criterion
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>2.5 mV >1.7 mV >1 mV >1.1 mV M: >16 mV; F: >14 mV
M: >1957.9 mV.ms; F: >1683.8 mV.ms >207 mV.ms >103 mV.ms 5 or more points
At least 1 positive criterion At least 3 positive criteria
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Left-ventricular hypertrophy electrocardiographic AQ1
if the patient was a current smoker or had regularly smoked in the past, and previous CVD was considered if the patient had previously experienced an ischemic heart event or a stroke. Other relevant variables were defined as follows: BMI of at least 30; waist circumference greater than 102 cm (men) and 88 cm (women); elevated pulse pressure (PP), calculated as the difference between SBP and DBP of at least 50 mmHg; estimated creatinine clearance using the Cockroft-Gault equation, less than 60 ml/min/1.73 m2 and an albumin/creatinine ratio higher than 22 and 31 mg/g for men and women, respectively [17]. Left-ventricular hypertrophy was considered present if, after excluding those with complete bundle branch blocks (according to QRS duration of equal to or greater than 120 ms with compatible image) or ventricular activation by pacemaker, they fulfilled certain electrocardiographic criteria in isolation and by means of various combinations according to three definitions: Overall combined 1: at least one positive ECG criterion. Overall combined 3: at least three positive ECG criteria. European combined guideline: one of the two ECG criteria recommended by the European Cardiology and Hypertension Societies [16]. The combined criterion 3 was selected a priori as a joint LVH criterion with the aim of increasing diagnostic accuracy and due to the fact that repeated criteria existed in the combined state.
Analysis Quantitative variables are represented by the mean and standard deviation (SD). Qualitative variables are expressed as frequencies with a confidence interval (CI) of 95% for population estimates. Differences between quantitative variables were assessed with a Student’s t-test and the qualitative variables with a chi-square test. To analyze the evolution of the prevalence with age, linear by linear chi-square test (P for trend) was determined. Binary logistic regression models were used to assess the association of clinically relevant variables (cardiovascular risk factors, asymptomatic renal disease and CVD) with LVH (Dalfo´, Lewis, Perugia and Combined 3 criteria). These criteria were selected because of their high
prevalence or their known prognostic value. Independent variables were considered to be all of those that were significantly associated (P < 0.05) with LVH (diabetes, hypercholesterolemia, smoking, CVD, BMI obesity, abdominal obesity, PP "50, estimated renal failure and pathological urinary albumin excretion) in addition to age and sex in the univariate analysis. The ‘enter’ method was used as a covariate selection method. The discrimination of the resulting model was calculated by the assessment of the area under the receiver-operating characteristic curve and the calibration of the final model was estimated with the Hosmer–Lemeshow test.
RESULTS Baseline characteristics Two thousand eight hundred and thirty-three patients participated, which is 80.5% of the selected sample, of which 2648 (93.5%) obtained a report from the Electropres platform. The lack of obtaining of an ECG report from Electropres was due to logistical difficulties in the storage and despatch of ECGs at the beginning of the study. Eightyfour cases were excluded as a result of the detection of complete bundle branch blocks or pacemakers, leaving 2564 for analysis. The mean age was 50.9 years (SD 14.7) with no differences between sexes. Forty-five percentage of patients were men, who showed a worse risk profile than women, who only had higher prevalence of abdominal obesity as compared to men. Patients with hypertension were older and showed more cardiovascular risk factors than nonhypertensive patients, with the exception of smoking (Table 2).
Simple electrocardiographic left-ventricular hypertrophy criteria Table 3 presents the LVH prevalence [voltage criteria, voltage-duration product (VDP) and combined criteria] according to sex, age, obesity, smoker, diabetes and HTN condition. Overall the prevalence of each criterion was not substantially different across these groups of comparison. With regard to the voltage criteria, the highest prevalence occurred in Dalfo´ with 19.4%, R V6/V5 with
TABLE 2. Baseline demographics, anthropometrics and cardiovascular risk factors
N (%) Age m (SD) BMI m (SD) SBP m (SD) DBP m (SD) PP m (SD) Obesity (%) Visceral Ob (%) HTN (%) DM (%) HCHOL (%) Smoker (%) CVD (%)
Total
Male
Female
HTN
Non-HTN
2564 (100) 51 (15) 28.6 (5.3) 126.4 (21.8) 76.4 (10.9) 50.0 (16.8) 34.8 52.4 38.6 13.8 38.7 53.2 4.3
1173 (45.7) 51 (14) 29.2 (4.7)$ 132.1 (18.5)$ 78.8 (10.1)$ 53.3 (15.1)$ 37.9$ 39.2$ 42.5$ 15.3$ 40.0 70.6$ 5.6$
1391 (54.3) 51 (15) 28.1 (5.8)$ 121.5 (23.2)$ 74.4 (11.1)$ 47.2 (17.7)$ 32.2$ 63.5$ 35.4$ 12.5$ 37.6 38.5$ 3.2$
990 (38.6) 62 (12)$ 31.2 (5.3)$ 146.1 (18.2)$ 83.5 (10.4)$ 62.6 (18.4)$ 55.3$ 72.9$ – 27.0$ 54.4$ 43.8$ 9.8$
1574 (61.4) 44 (12)$ 26.9 (4.7)$ 114.0 (13.1)$ 71.9 (8.5)$ 42.1 (9.3)$ 21.9$ 39.5$ – 5.5$ 28.8$ 59.0$ 0.8$
CVD, cardiovascular disease history (ischemic heart disease or stroke); DM, diabetes mellitus; HCHOL, hypercholesterolemia; HTN, arterial hypertension; m, mean; obesity, BMI at least 30; PP, pulse pressure; SD, standard deviation; smoker, current or former smoker; visceral Ob, visceral obesity (waist circumference >102 cm in men and >88 cm in women). $ P < 0.05 (for the difference between sexes and hypertensive status).
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4 TABLE 3. Prevalence of left-ventricular hypertrophy on cardiovascular risk conditions by different electrocardiogram criteria [N (%)] Female (N1391)
Male (N 1173)
Sokolow Cornell QRS sum Gubner Lewis R V6/V5 R aVL Dalfo´ Sokolow VDP Cornell VDP QRS sum VDP Gubner VDP RaVL VDP Romhilt-Estes Perugia Hannover ESH-ESC Combined 1 Combined 3
2 61 7 22 91 278 40 281 3 61 13 37 38 73 134 25 62 542 129
15 6 14 14 69 93 27 216 15 31 24 39 37 120 145 35 40 387 111
(0.1) (4.4) (0.5) (1.6) (6.5) (20.0) (2.9) (20.2) (0.2) (4.4) (0.9) (2.7) (2.7) (5.2) (9.6) (1.8) (4.5) (39.0) (9.3)
(1.3)$ (0.5)$ (1.2) (1.2) (5.9) (7.9)$ (2.3) (18.4) (1.3)y (2.6)z (2.0)z (3.3) (3.2) (10.2)$ (12.4)z (3.0)z (3.4) (33.0)y (9.5)
