Echocardiographic definition of left ventricular hypertrophy in the hypertensive: which method of indexation of left ventricular mass?

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1 Journal of Human Hypertension (1999) 13, Stockton Press. All rights reserved /99 $ ORIGINAL ARTICLE Echocardiographic definition of left ventricular hypertrophy in the hypertensive: which method of indexation of left ventricular mass? P Gosse, V Jullien, P Jarnier, P Lemetayer and J Clementy Hôpital Saint André, 1 rue Jean Burguet, Bordeaux cedex, France Objectives: It has been suggested that hypertensives at high risk of cardiovascular complications can be identified on the basis of their left ventricular mass as determined echographically. However, there is as yet a lack of consensus on the mode of indexation (body surface area, height, height 2.7 ) of left ventricular mass (LVM), and on the cut-off values for definition of left ventricular hypertrophy (LVH). The main objective of this study is to test the influence of the different modes of indexation for LVM on the prevalence of LVH in a population of never treated hypertensive patients on the basis of cut-offs for LVM based upon its relationship with ambulatory blood pressure (BP) measurement. Methods: A population of 363 untreated hypertensives was investigated using a standardised procedure. The men and women were analysed separately. We studied the relationship between mean daytime ambulatory sys- tolic BP and LVM and calculated the LVM cut-off for a BP of 135 mm Hg using three different methods of indexation. On the basis of these criteria, the population was divided into those with and those without LVH. Results: The prevalence of LVH was found to be higher when LVM was indexed to height 2.7 (50.4%) or height (50.1%). Prevalence was lowest when LVM was indexed to body surface area (48.2%), which tended to minimise the hypertrophy in obese individuals. Only indexation by height 2.7 fully compensates for relationships between height and ventricular mass in this population. Conclusions: Indexing LVM to height 2.7 thus appeared to give a more sensitive estimate of LVH by eliminating the influence of growth. Cut-offs of 47 g/m 2.7 in women and 53 g/m 2.7 in men corresponded to a cardiovascular risk indicated by a daytime systolic BP 135 mm Hg. Keywords: left ventricular hypertrophy; left ventricular mass; echocardiography Introduction An increase in left ventricular mass (LVM) is now recognised as an important risk factor for cardiovascular complications, 1 4 and it has been suggested that high risk patients could be identified by suitable definition of left ventricular hypertrophy (LVH) determined echographically. However, there are a number of methodological difficulties in the interpretation of routine echographic results in hypertensive patients. The M-mode tracings need to be done and measured under carefully controlled conditions by experienced echographists. 5 There are two main difficulties in the interpretation of the echographic results: (i) the mode of indexation of LVM. To assess the true increase in left ventricular mass related to risk, anthropometric factors which have an influence on it such as sex, height and level of physical activity need to be eliminated. Three modes of indexation have been used by different authors in an attempt to compensate for the influence of growth: indexing by height, height 2.7 and Correspondence: Dr Philippe Gosse, Hôpital Saint André, 1 rue Jean Burguet, Bordeaux cedex, France Received 20 November 1998; revised and accepted 18 May 1999 body surface area. However, no systematic study has been carried out to find out how the prevalence of LVH is affected by these different methods of indexation; (ii) the lack of consensus on the criteria for definition of LVH, which will also depend on the method of indexation used. In the present study, we examined the influence of three different methods of indexation of LVM on the prevalence of LVH in a population of untreated hypertensives. Subjects and methods Population We recruited all hypertensive patients referred since 1985 to our department for investigations prior to receiving antihypertensive therapy with suitable echocardiography and 24-h ambulatory blood pressure monitoring (ABPM). They had all been examined under the same conditions and benefited from a high quality echocardiographic evaluation of LVM. They all had a BP over 140/90 mm Hg measured on two separate occasions while seated. Patients with complications, secondary hypertension, clinical or ECG signs of coronary artery disease, myocardial involvement, heart valve conditions or renal insuf-

2 506 Definition of LVH ficiency (serum creatinine 150 micromoles/l), unsatisfactory echocardiography or ABPM were excluded from the study. Measurement of blood pressure Office BP was measured with a mercury sphygmomanometer in all patients after a 10-min period of rest by the same physician. BP was taken as the mean of three consecutive values (phase V for diastole). Ambulatory BP was recorded over a 24-h period using a Spacelabs 5200 (Redmond, WA, USA) between 1985 and 1989, and since 1989 with a Diasys 200 device (Novacor, Rueil, France). Both devices operated on the ausculatory principle, and were programmed to take four readings per hour during the day and two per hour (Spacelabs) or four per hour (Novacor) during the night. Only the recordings with at least 80% of valid reading were retained. The only editing criteria was pulse pressure 15 mm Hg. We calculated the mean BP over 24 h, mean BP during the day (between rising and going to bed) and that during the night (between going to bed and rising) as indicated from a diary. Echocardiographic determination of LVM All measurements were made by the same echographist (PG) using an identical procedure: twodimensional guided TM-mode tracings of the left ventricle from the left parasternal view were recorded on a Hewlett Packard instrument. Tracings over at least five consecutive cardiac cycles were made on a strip chart recorder (Kowa) running at 100 mm/sec. The tracings were then coded and read blind according to the Penn convention. LVM was calculated from Devereux s formula. 6 Data analysis The data were analysed using PCSM software (Deltasoft, Grenoble, France). To compare the different methods of indexations, we had to first define the cut-off values of LVM for each method. Numerous cut-offs have been proposed, although most are defined from a normal population with no reference to cardiovascular risk. We needed cut-offs for the same level of risk for the three methods of indexation. We assumed that in hypertension, the risk linked to LVH depends in part on the overall elevation in BP, which is best evaluated from ambulatory recordings. We therefore examined the relationship by linear regression between daytime BP and LVM for the different methods of indexation. We calculated the value of the indexed LVM corresponding to a daytime systolic BP of 135 mm Hg. This is the value recommended by JNC VI 7 and is generally recognised as the upper normal limit. The corresponding LVM was then employed to classify our population into those with and those without LVH. We then compared the influence of the method on the prevalence of LVH. The results, presented as means ± s.d., were subjected to analysis of variance followed by a Newman Keuls test if P Results We included 363 patients seen between 1985 and 1997 fulfilling the inclusion criteria. Their principle characteristics are summarised in Table 1. The relationship between mean daytime BP and LVM was examined. The results are listed in Table 2. The values of LVM corresponding to a daytime systolic BP of 135 mm Hg were calculated and the indexed LVM cut-offs were then used to define the existence (more than or equal to cut-off value) or not of LVH in the overall population. There was agreement between the three definitions of LVH for 315 patients: 159 (105 men and 54 women) had no LVH regardless of the method of indexation (LVM/H, LVM/H 2.7, LVM/BSA), while 156 (115 men and 41 women) had LVH with all three methods of indexation. In 48 cases, there were differences between the methods of indexation. The prevalence of LVH with LVM indexed to body surface area was 48.2%, 50.1% when indexed to height and 50.4% when indexed to height 2.7. These 48 cases could be split into six groups: three in which LVH was found with just one method of indexation, and three in which LVH was found with two of the methods of indexation. The details of these six groups and the two groups where the three methods of indexation were in agreement are listed in Table 3. Indexation to body surface area led to a non-recognition of LVH as recognised by indexation to height in the overweight patients (mean 89 kg for 167 cm), whereas it tended to over-include the lean patients (mean 60 kg for 167 cm) as having LVH. The distinction between the two methods of indexation to height was less clear-cut. Table 4 lists the patients allocated into four groups with or without LVH defined by the two methods of indexation by height. These results do not favour one or the other method. Indexation by height 2.7 underestimate the prevalence of LVH in tall patients as compared to indexation by height and to overestimate it in a small one. However we Table 1 Principal characteristics of the population m ± s.d. Range Sex (M/F) 247/116 Age (years) 47 ± Height (cm) 168 ± Height ± Weight (kg) 74 ± Body surface area (m 2 ) 1.83 ± Office SBP (mm Hg) 157 ± Office DBP (mm Hg) 97 ± Average daytime SBP (mm Hg) 137 ± Average daytime DBP (mm Hg) 91 ± Average night-time SBP 119 ± (mm Hg) Average night-time DBP 77 ± (mm Hg) Average 24-h SBP (mm Hg) 131 ± Average 24-h DBP (mm Hg) 86 ± LVM (g) 214 ± LVM/BSA (g/m 2 ) 116 ± LVM/H (g/m) 127 ± LVM/H 2.7 (g/m 2.7 ) 52.1 ± ±102.6 SBP, systolic blood pressure; DBP, diastolic blood pressure; LVM, left ventricular mass; H, height; BSA, body surface area.

3 Definition of LVH Table 2 Relationship between daytime SBP and LVM 507 Population LVM LVM/H LVM/H 2.7 LVM/BSA All r = 0.38, P r = 0.38, P r = 0.35, P r = 0.39, P (n = 363) = 1.62 SBP 7.7 = 0.90 SBP +3.1 = 0.32 SBP +8 = 0.76 SBP +12 Co = 211 g Co = 125 g/m Co = 51 g/m 2.7 Co = 115 g/m 2 Males r = 0.30, P r = 0.31, P r = 0.31, P r = 0.32, P (n = 247) = 1.29 SBP = 0.77 SBP = 0.31 SBP = 0.68 SBP Co = 231 g Co = 134 g/m Co = 53 g/m 2.7 Co = 121 g/m 2 Females r = 0.25, P 0.01 r = 0.26, P 0.01 r = 0.27, P 0.01 r = 0.32, P (n = 116) = 0.66 SBP +77 = 0.42 SBP = 0.20 SBP = 0.44 SBP Co = 166 g Co = 104 g/m Co = 47 g/m 2.7 Co = 101 g/m 2 r, coefficient of correlation; LVM, left ventricular mass; H, height; BSA, body surface area; SBP, average daytime systolic blood pressure; Co, cut-off value corresponding to a daytime SBP of 135 mm Hg. Table 3 Patients in overall population with or without LVH as defined by the three different methods of indexation No LVH LVH LVH LVH No LVH No LVH No LVH LVH g/m g/m 2.7 g/m 2 g/m g/m 2.7 g/m 2 n M/F 105/54 115/41 5/3 6/4 2/4 3/3 4/3 7/4 LVM (g) 165 ± ± ± ± ± ± ± ± 35 LVM/H (g/m) 97 ± ± ± ± ± ± ± ± 14 LVM/H ± 6 65± ± 3 53 ± 3 42± 9 53± 3 49± 4 55± 3 LVM/BSA (g/m 2 ) 91 ± ± ± ± ± ± ± ± 12 Age (years) 45 ± ± ± 9 48± ± ± ± ± 11 Height (m) 168 ± ± ± ± ± ± ± ± 9 Weight (kg) 70 ± ± ± ± ± ± 6 75 ± ± 10 Office SBP (mm Hg) 152 ± ± ± ± ± ± ± ± 12 Office DBP (mm Hg) 94 ± ± 9 95 ± 6 99 ± ± 9 96 ± ± ± 8 Day SBP (mm Hg) 133 ± ± ± ± ± ± ± ± 10 Day DBP (mm Hg) 89 ± ± ± ± ± ± ± ± 9 24-h SBP (mm Hg) 127 ± ± ± ± ± ± ± ± 8 24-h DBP (mm Hg) 84 ± ± ± ± ± ± ± ± 9 SBP, systolic blood pressure; DBP, diastolic blood pressure; LVM, left ventricular mass; H, height; BSA, body surface area; LVH, left ventricular hypertrophy. Table 4 Patients with or without LVH as defined according to an indexation to height or height : No LVH 2 : LVH g/m&g/m : LVH g/m 4 : LVH g/m 2.7 P n Age (years) 45 ± ± ± ± 12# M/F 107/58 122/45 9/6 9/7 NS Height (cm) 168 ± ± ± 8* 158 ± 7* # Weight (kg) 70 ± ± 13* 82 ± 16* 64 ± 11 # Office SBP (mm Hg) 152 ± ± 17* 151 ± ± 20* # Office DBP (mm Hg) 95 ± ± 9* 95 ± ± Day SBP (mm Hg) 133 ± ± ± ± Day DBP (mm Hg) 89 ± ± ± ± h SBP (mm Hg) 127 ± ± ± ± h DBP (mm Hg) 84 ± ± ± ± *P 0.05 vs 1; P 0.05 vs 2; #P 0.05 vs 3or4. SBP, systolic blood pressure; DBP, diastolic blood pressure; LVH, left ventricular hypertrophy. also noted that only indexation by height 2.7 fully compensated for the correlations of LVM with height (Table 5). Indexation by height 2.7 thus appeared to be the most sensitive method for detection of LVH as it included a further 2.2% of our population as having LVH who would have escaped detection using the indexation for BSA and to fully eliminate the influence of growth. Discussion An elevation in LVM confers an increased risk of cardiovascular complications independently of other risk factors in all populations studied to date. 1 4 Measurement of LVM can thus help identify a population at risk warranting more thorough follow-up. The most recent recommendations of the

4 Definition of LVH 508 Table 5 Correlations between physiological variables and LVM and indexed LVM Age Height Weight Day SBP Day DBP LVM *** 0.57*** 0.38*** 0.27*** LVM/height 0.11* 0.35*** 0.50*** 0.38*** 0.27*** LVM/height ** *** 0.35*** 0.26*** LVM/BSA 0.14* 0.24** 0.28*** 0.39*** 0.29*** *P 0.05; **P 0.01; ***P SBP, systolic blood pressure; DBP, diastolic blood pressure; LVM, left ventricular mass; H, height; BSA, body surface area. JNC VI 7 propose measurement of this parameter in stage 1 hypertensives without complications and with normal ECG. However, there are certain methodological difficulties in the evaluation of LVM by echocardiography. There are difficulties with feasibility, accuracy and reproducibility as the standard deviation of differences in LVM between examinations is around 30 g Notwithstanding the problems inherent with measurement, there are those of interpretation, as LVM is known to be affected by physiological factors such as age, sex, and physical activity. 12 The influence of growth can be compensated by indexing LVM to another parameter such as body surface area, which is widely used. However this method of indexation confers an overemphasis to body weight and tends to underestimate the prevalence of LVH in obese patients. 13 To circumvent this problem, indexation to height has been employed, in particular in the Framingham study. 13 De Simone has recently shown that the relationship between LVM and height is curvilinear rather than strictly linear during growth, and has proposed indexing LVM to height to the power of 2.7 to take this into account. 14 However, there have been few studies to date using this method of indexation. Furthermore, numerous cut-offs for LVH have been proposed, 15,16 most of which have been defined in normal populations. However, the marked variability in LVM in a normal population had led to the definition of cut-offs at the 95th percentile, which may be rather high and may underestimate the true prevalence of LVH in hypertensives. 17 Other cut-offs have been proposed with considerable differences between those used by different authors and even by the same authors in different studies. The value of cut-off used will clearly have an influence of the estimated prevalence of LVH, but as yet there is lack of agreement on a value of LVM corresponding to LVH. The main drawback of the current cut-offs is that they are not based on prognostic information, although they are designed to identify a population at high risk of cardiovascular complications. Risk may be better established from the correlation with ambulatory BP. One may argue that the risk associated with LVH is independent of BP, however this has been shown with office BP and not with ambulatory BP. LVM encompasses the influence of many different factors such as genetic, alcohol intake, blood viscosity and even cholesterol levels 18 but the relation to BP indicates a given level of risk. Thus LVH can be defined using the different methods of indexation for the same level of risk. However, the influence of previous antihypertensive treatment needs to be eliminated as most of the drugs used lead to a reduction in LVH over the long-term. Thus the present population was recruited from those patients who had never received antihypertensive medication. The relationship between LVM and daytime systolic BP may well vary in other populations. However our cut-off defined on the basis of a daytime systolic of 135 mm Hg is close to those proposed by other authors. Indexation to height 2.7 appeared to be the best choice as it increased the sensitivity of detection of LVH in a population of hypertensives. This is desirable as the main objective is to identify patients at high risk of cardiovascular complications. This method of indexation would appear to compensate best for the influence of normal growth on LVM. As pointed out by De Simone, 19 it also has the advantage of reducing the difference between men and women. In conclusion, indexation of LVM to height 2.7 gives rise to a more sensitive definition of LVH by compensating for the influence of growth. Cut-offs of 47 g/m 2.7 in women and 53 g/m 2.7 in men may thus correspond to a risk linked to a daytime systolic BP 135 mm Hg. References 1 Casale PN et al. Value of echocardiographic measurement of left ventricular mass in predicting cardiovascular morbid events in hypertensive men. Ann Intern Med 1986; 105: Levy D et al. Left ventricular mass and the incidence of coronary heart disease in an elderly cohort. The Framingham Heart Study. Ann Intern Med 1989; 110: Levy D et al. Prognostic implications of echocardiographically determined left ventricular mass in the Framingham Heart Study. N Engl J Med 1990; 322: Bikkina M et al. Left ventricular mass and risk of stroke in an elderly cohort. The Framingham Heart Study. JAMA 1994; 272: Devereux RB. Detection of left ventricular hypertrophy by M-mode echocardiography. Hypertension 1987; 9 (Suppl II): II19 II26. 6 Devereux RB, Reichek N. Echocardiographic determination of LVM in man: anatomic validation of the method. Circulation 1977; 5: The Sixth Report of the Joint National Committee on Prevention, Detection, Evaluation and Treatment of High Blood Pressure. Arch Intern Med 1997; 157: Gosse P, Roudaut R, Wicker P, Dallocchio M. Evaluation de la masse ventriculaire gauche par echocardiographie TM et bidimensionnelle. Arch Mal Coeur 1985; 78:

5 9 Gosse Ph, Roudaut R, Dallocchio M. Appréciation de la reproductibilité des échocardiographies TM et bidimensionnelles. J Echog Med Ultrason 1985; 6: Wallerson DC, Devereux RB. Reproducibility of echocardiographic left ventricular measurements. Hypertension 1987; 9 (suppl II): II6 II Gottdiener JS, Livengood SV, Meyer PS, Chase GA. Should echocardiography be performed to assess effects of antihypertensive therapy? Test-Retest reliability of echocardiography for measurement of left ventricular mass and function. J Am Coll Cardiol 1995; 25: Hammond IW, Devereux RB, Alderman MH, Laragh JH. Relation of blood pressure and body build to left ventricular mass in normotensive and hypertensive employed adults. J Am Coll Cardiol 1988; 12: Levy D et al. Echocardiographic criteria for left ventricular hypertrophy: The Framingham Heart Study. Am J Cardiol 1987; 59: Definition of LVH 14 De Simone G et al. Left ventricular mass and body size in normotensive children and adults: assessment of allometric relations and impact of overweight. JAm Coll Cardiol 1992; 20: Abergel E et al. Which definition for echocardiographic left ventricular hypertrophy? Am J Cardiol 1995; 75: Devereux RB et al. Left ventricular hypertrophy in hypertension. Prevalence and relationship to pathophysiologic variables. Hypertension 1987; 9 (Suppl II): II53 II Korner PI, Jennings GL. Assessment of prevalence of left ventricular hypertrophy in hypertension. J Hypertens 1998; 16: Jullien V et al. Relationship between left ventricular mass and serum cholesterol in the untreated hypertensive. J Hypertens 1998; 16: De Simone G, Devereux RB, Daniels SR, Meyer RA. Gender differences in left ventricular growth. Hypertension 1995; 26 (part 1):

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