Relationship between left ventricular mass and blood pressure in ...

Journal of Human Hypertension (2002) 16, 61–66  2002 Nature Publishing Group All rights reserved 0950-9240/02 $25.00 www.nature.com/jhh

ORIGINAL ARTICLE

Relationship between left ventricular mass and blood pressure in treated hypertension LH Missault, ML De Buyzere, DD De Bacquer, DD Duprez and DL Clement Department of Cardiology, Hypertension Unit, University Hospital Ghent, Belgium

This study evaluated prospectively whether there is still a relationship between left ventricular mass and blood pressure once hypertension is treated and determined the relative importance of daytime vs night-time blood pressure, systolic vs diastolic blood pressure and office vs ambulatory blood pressure. A total of 649 patients (305 or 47% female) with essential hypertension, treated with antihypertensive drugs for at least 3 months, underwent office blood pressure measurement and both daytime and night-time ambulatory blood pressure measurement, electrocardiography and echocardiography. Correlations were made between blood pressure values and parameters of left ventricular mass. Electrocardiographic voltage criteria and even more so echocardiographic parameters correlate significantly albeit weakly (r ⭐ 0.28) with blood pressure in treated hypertension. Correlations are consistently higher when systolic blood pressure is considered. Overall, the best cor-

relations are found between 24-h ambulatory systolic or night-time blood pressure and the Sokolow–Lyon voltage as well as the echocardiographic age and body mass index adjusted left ventricular mass. In conclusion, once hypertension is treated, the relationship between blood pressure and left ventricular mass is low. Nevertheless, in this the largest single centre study of its kind, echocardiographic parameters of left ventricular mass in treated hypertensive subjects correlate better with blood pressure than electrocardiographic parameters. Parameters of hypertrophy are more closely related to systolic blood pressure than to diastolic blood pressure. In accordance with the finding that dippers have a better prognosis than non-dippers, nighttime blood pressure consistently correlates better with left ventricular mass than daytime blood pressure. Journal of Human Hypertension (2002) 16, 61–66. DOI: 10.1038/sj/jhh/1001295

Keywords: essential hypertension; left ventricular hypertrophy; ambulatory blood pressure; electrocardiography; echocardiography

Introduction Hypertensive left ventricular hypertrophy is established as an independent risk factor triplicating cardiovascular morbidity and mortality.1,2 Its prevalence depends on the assessment technique with the most useful routine methods being electrocardiography and echocardiography. Although blood pressure is considered the most important haemodynamic factor in the development and extent of left ventricular hypertrophy, left ventricular mass is determined by a multitude of both haemodynamic and non-haemodynamic influences.3 According to two meta-analyses, only few studies that have examined associations between left ventricular mass and blood pressure included large Correspondence: Dr L Missault, Department of Cardiology, University Hospital, De Pintelaan 185, B-9000 Ghent, Belgium E-mail: luc.missault얀azbrugge.be Received 18 May 2000; revised 24 July 2001; accepted 2 August 2001

numbers of subjects.4,5 Furthermore, antihypertensive medication was usually discontinued a few weeks before blood pressure measurement and target organ assessment, thereby blurring both the potentially beneficial effect of treatment on left ventricular mass and vice versa the actual influence of blood pressure per se on left ventricular mass. Since different types of treatment have different short term effects on left ventricular mass,5–8 correlations between blood pressure and left ventricular mass in a heterogeneously treated population (both in duration and type of treatment) may be different from those in untreated patients. In most studies, single office blood pressure measurement shows a weaker correlation with left ventricular mass than ambulatory or average 24-h blood pressure.9–15 In addition, single office blood pressure only weakly predicts coronary events.9–15 However some of these studies have been criticised in terms of trial design.16,17 Furthermore with regards to the development of target organ damage, controversy exists regarding the relative importance

Left ventricular mass in treated hypertension LH Missault et al

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of daytime vs night-time blood pressure, and of diastolic vs systolic blood pressure.4,18,19 The aim of this prospective study was to evaluate the relationship, if any, between left ventricular mass and different measures of blood pressure such as day- vs night-time blood pressure, office vs 24-h ambulatory blood pressure and systolic vs diastolic blood pressure in treated hypertension.

Materials and methods Patients Patients aged ⭓18 years were eligible for inclusion provided that the diagnosis of essential hypertension was based on at least two previously performed separate measurements during which office diastolic blood pressure in the sitting subject had to be at least 90 mm Hg. In addition they could only be included if they had been treated for at least 3 months after the diagnosis of hypertension was made. Patients were excluded in the presence of valvular heart disease, electrocardiographic bundle branch block or Q-wave infarction, clearly visible infarction on the echocardiogram, technically inadequate echocardiography such as poor visibility due to obesity or when the M-mode measurements could not be done perpendicular to the interventricular septum. At the time of entry in the study, patients had been treated with antihypertensive drugs for at least 3 months before measurement of office blood pressure, 24-h ambulatory blood pressure, electrocardiographic and echocardiographic parameters. Treatment consisted of one or more of the following drug classes: diuretics, beta-blocking agents, angiotensin converting enzyme inhibitors, angiotensin II antagonists, calcium antagonists, alpha-blockers, centrally acting antihypertensives. Treatment choice was at the treating physicians’ discretion. Current guidelines were followed as close as possible and target office blood pressure was 140/90 mm Hg. However, patients did not have to reach target blood pressure for inclusion but instead were suitable if they had been under treatment for at least 3 months. A total of 649 ambulatory or outpatients (305 or 47% female) were included in the present analysis. Mean age was 54.9 ± 12.4 years, weight 79.4 ± 15.6 kg, body mass index 27.9 ± 4.7 kg/m2. Median plasma cholesterol levels was 233 mg/dl, creatinine 1.0 mg/dl, uric acid 5.5 mg/dl and glucose 97 mg/dl. All patients agreed to participate in the study. Blood pressure Diastolic and systolic office blood pressure were expressed as the mean value of three consecutive readings separated by 2-min intervals and measured using the auscultatory technique with a mercury sphygmomanometer (appearance and disappearance of Korotkoff sounds) with the patient resting comfortably in a sitting position for 5 minutes. Mean Journal of Human Hypertension

arterial pressure was defined as diastolic blood pressure + 1/3 (systolic − diastolic blood pressure) and expressed in mm Hg. All patients underwent 24-h ambulatory blood pressure recordings during normal daily activities, on at least 30-min intervals, both during daytime (fixed-time definitions of 08.00 to 20.00) and nighttime (defined as 20.00 to 08.00). For ambulatory blood pressure monitoring, either a SpaceLabs 90205 model or 90207 (Redmond, WA, USA) was used. The 24-h ambulatory blood pressure measurement started on the same day as the office blood pressure measurement. From these recordings, 24-h, day- and night-time mean systolic and diastolic blood pressure and heart rate were calculated. Analysis by clock time was performed using the ‘wide method’, ie morning and evening transition periods were included in the analysis. For quality purposes, ambulatory blood pressure data were included only if they were technically acceptable: at least 80% of readings were present and no 2-h period was present without any measurement. In addition, readings that had not successfully been completed by the monitor or fell outside the preset boundaries for blood pressure or heart rate (systolic blood pressure ⬍70 or ⬎260 mm Hg, diastolic blood pressure ⬍40 or ⬎150 mm Hg, pulse pressure ⬍20 or ⬎150 mm Hg, heart rate ⬍20 or ⬎200 beats per minute (bpm)) were omitted. Data of each ambulatory blood pressure reading were visually inspected by one of the investigators to identify and eliminate artefact readings. Electrocardiography Standard 12-lead electrocardiography was performed on the same day as the office blood pressure measurement. The following electrocardiographic voltage indices for left ventricular mass were measured and expressed in mm: single lead voltages RaVL; RI; SIII; SV1 and RV5; combined lead voltages RI + SIII = Gubner-Ungerleider voltage20 and SV1 + RV5 = Sokolow–Lyon voltage.21 Voltages were measured to the nearest 0.1 mV. Although the Cornell voltage-duration product (gender-specific Cornell voltage times QRS duration) provides the best combination of overall accuracy with regards to left ventricular hypertrophy,22 the method is complex as compared to the simple voltage criteria which are much easier to use in clinical practice and also have high specificity. Therefore simple voltage criteria were used in this study. Only validated data were introduced into the statistical analysis. Correlations between electrocardiographic parameters of left ventricular mass and both office and ambulatory blood pressures were calculated. Echocardiography For inclusion, echocardiographic images had to consist of a two-dimensionally guided M-mode


evaluation of the left ventricle using the recommendations of the American Society of Echocardiography.23 From these end-diastolic M-mode measurements of septum (SD), posterior wall (PWD) and left ventricle (LVD), LVM was calculated using the Devereux formula: LVM (in grams) = 0.84 (SD + LVD + PWD)3 − LVD3).24 All patients underwent echocardiography on the same day as the office blood pressure measurement. Correlations between echocardiographic parameters of left ventricular mass and both office and ambulatory blood pressures were calculated. Statistical analysis Descriptive statistics of measured and calculated parameters are expressed as mean ± standard deviation. Data of office vs 24-h ambulatory blood pressure and daytime vs night-time were compared by Mann–Whitney tests. Correlations were calculated using Pearson correlation tests.

Results Table 1 illustrates that systolic, diastolic and mean ambulatory blood pressures and heart rate are respectively 19 mm Hg, 8 mm Hg, 12 mm Hg and 2 bpm lower than the corresponding office blood pressures and heart rate (P ⬍ 0.01). In addition, night-time blood pressure values are lower than daytime values: 10 mm Hg, 9 mm Hg, 10 mm Hg, 7 bpm (P ⬍ 0.01). Blood pressure values during treatment at the time of entry ranged over the study population as follows: with regard to office systolic blood pressure 25th percentile was at 140 mm Hg, 50th percentile at 151 mm Hg and 75th percentile was at 167 mm Hg; with regard to office diastolic blood pressure 25th percentile was at 86 mm Hg, 50th percentile at 93 mm Hg and 75th percentile was at 100 mm Hg. Electrocardiographic and echocardiographic results are shown in Table 2. The septal wall is 0.8 mm thicker than the posterior wall (P ⬍ 0.01). Significant correlations were found between electrocardiographic and echocardiographic parameters

Table 2 Electrocardiographic and echocardiographic parameters Parameter RaVL RI SIII SV1 RV5 RI + SIII SV1 + RV5 SD LVD PWD LVM

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Result 6 ± 4 mm 9 ± 4 mm 3 ± 4 mm 9 ± 4 mm 13 ± 6 mm 12 ± 7 mm (Gubner–Ungerleider voltage) 22 ± 8 mm (Sokolow–Lyon voltage) 11.1 ± 2.3 mm 49.8 ± 6.0 mm 10.3 ± 2.1 mm 240 ± 82 gram

R, amplitude of R wave; S, amplitude of S wave; SD, septum thickness at end-diastole; PWD, posterior wall thickness at enddiastole; LVD, left ventricular internal diameter at end-diastole; LVM, calculated left ventricular mass.

of left ventricular mass and blood pressure (Tables 3 and 4). Although electrocardiographic voltage criteria correlate significantly with blood pressure, the correlations are weak. Standard lead criteria (RaVL and RI + SIII) correlate better with office blood pressure than with ambulatory blood pressure while the Sokolow–Lyon voltage (SV1 + RV5) has a better correlation with ambulatory blood pressure. Correlations are consistently higher when systolic blood pressure is considered. Night-time blood pressure consistently correlates better with voltage criteria than daytime blood pressure. In addition, correlations between night-time blood pressure and voltage criteria are the same or even better than correlations between 24-h ambulatory blood pressure and voltage criteria. The best electrocardiographic correlation is found between the Sokolow–Lyon voltage and either 24-h ambulatory systolic blood pressure or night-time systolic blood pressure. Echocardiographic parameters of left ventricular mass correlate better with blood pressure than electrocardiographic. There are better correlations with systolic than with diastolic blood pressure. Nighttime blood pressure tends to correlate better with left ventricular mass than daytime blood pressure. Unadjusted calculated left ventricular mass has a Table 3 Correlations between blood pressure and simple and combined electrocardiographic voltages

Table 1 Blood pressure and heart rate measurements SBP (mm Hg) OBP 24-h ABP Daytime ABP Night-time ABP

152 ± 21 133 ± 16* 138 ± 17 128 ± 18*

DBP (mm Hg)

MAP (mm Hg)

93 ± 11 113 ± 13 85 ± 11* 101 ± 12* 89 ± 12 106 ± 12 80 ± 12* 96 ± 13*

HR (bpm) 74 ± 12 72 ± 10* 75 ± 11 68 ± 10*

ABP, ambulatory blood pressure; OBP, office blood pressure; SBP, systolic blood pressure; DBP, diastolic blood pressure; MAP, mean arterial pressure; HR, heart rate; bpm, beats per minute. *P ⬍ 0.01 (24-h ABP vs OBP; daytime vs night-time).

Office SBP Office DBP 24-h ambulatory SBP 24-h ambulatory DBP Daytime SBP Daytime DBP Night-time SBP Night-time DBP

SV1 + RV5

RaVL

RI + SIII

0.09** 0.07* 0.22*** 0.15*** 0.20*** 0.13*** 0.22*** 0.15***

0.15*** 0.11*** 0.05 −0.03 0.03 −0.04 0.08* −0.01

0.18*** 0.12*** 0.11*** −0.01 0.08* −0.04 0.14*** 0.02

SBP, systolic blood pressure; DBP diastolic blood pressure. *P ⬍ 0.05; **P ⬍ 0.01; ***P ⬍ 0.001. Journal of Human Hypertension


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Table 4 Correlations between blood pressure and echocardiographic indices of LVH

Office SBP Office DBP 24-h ambulatory SBP 24-h ambulatory DBP Daytime SBP Daytime DBP Night-time SBP Night-time DBP

SD

LVD

PWD

LVM

LVMI

LVMIage

0.12** 0.07 0.23*** 0.16*** 0.21*** 0.14*** 0.22*** 0.16***

0.10* 0.04 0.05 −0.01 0.05 −0.01 0.05 0.01

0.07 0.04 0.16*** 0.10** 0.15*** 0.07 0.15*** 0.11**

0.14*** 0.07 0.19*** 0.11* 0.17*** 0.08* 0.19*** 0.13***

0.15*** 0.04 0.22*** 0.14*** 0.19*** 0.09** 0.23*** 0.17***

0.14*** 0.02 0.28*** 0.19*** 0.24*** 0.14*** 0.28*** 0.22**

SBP, systolic blood pressure; DBP, diastolic blood pressure; SD, septum thickness at end-diastole; PWD, posterior wall thickness at end-diastole; LVD, left ventricular internal diameter at end-diastole; LVM, calculated left ventricular mass; LVMI, left ventricular mass indexed for body mass index; LVMIage, left ventricular mass adjusted for body mass index and for age. *P ⬍ 0.05; **P ⬍ 0.01; ***P ⬍ 0.001.

weaker correlation with blood pressure than measured parameters. Adjustment of left ventricular mass for body mass index does not substantially change the results. However, adjustment of left ventricular mass for both body mass and age leads to much better correlations, especially for systolic 24-h and night-time blood pressure. Thus, the best echocardiographic correlation exists between (age and body mass adjusted) left ventricular mass and both 24-h ambulatory and night-time systolic blood pressure.

Discussion The present study on the relationship of blood pressure with echocardiographic and electrocardiographic criteria of left ventricular mass, in a large well defined cohort of treated hypertensive patients without interruption of treatment prior to the study measurements, shows that almost all parameters of left ventricular mass, a so-called surrogate end point for blood pressure related target-organ damage, are more closely associated with ambulatory than with office blood pressure. Although this has previously been demonstrated in 1966 by Sokolow et al9 and has been confirmed by other studies assessing targetorgan disease in the heart, kidneys, brain and blood vessels,11–15 according to the data presented here, the relationship between criteria of left ventricular mass and blood pressure in a selection of treated hypertensive patients is weak (at most 0.28). This is in contrast with the relationship found in studies including subjects with a wide spectrum of blood pressure values, including normotensive and untreated hypertensive subjects (correlation coefficients up to 0.56).25–27 However, contrary to what was done in this study, in most of the previously published data antihypertensive treatment was interrupted for several weeks before measurements were done.4 Strikingly, our results are very similar to the results of untreated mildly hypertensive subjects.28 In the latter study the range of blood pressure was also very limited, potentially leading to similar weak correlations between left ventricular mass and blood pressure of only 0.15 to 0.30. This study compares ambulatory blood pressure Journal of Human Hypertension

measurement with single office blood pressure measurement defined as the mean value of three consecutive readings. Other authors have stated that clinic blood pressures may predict left ventricular mass as well as ambulatory monitoring provided that multiple readings are performed in well-standardised conditions in the clinic, for instance five readings on two different occasions.29 Previous studies suggest that left ventricular mass is more closely related to systolic blood pressure, whereas left ventricular wall thickness correlates better with diastolic blood pressure.18 A constant finding in our study is that all parameters of hypertrophy are more closely related to systolic blood pressure than to diastolic or mean blood pressure. This finding is in line with a recent metaanalysis,4 adding further evidence to the hypothesis that wall stress, which is mostly related to systolic blood pressure is a key factor influencing left ventricular hypertrophy development.26 Although our data are consistent with the finding that daytime and night-time blood pressures both correlate with target organ damage,30 an important conclusion from our study is that night-time pressure consistently correlates better with left ventricular mass than daytime pressure. This has previously been described both in treated severe hypertension19 and untreated mild hypertension.28 This finding is in line with the observation that dippers and nondippers have a different prognosis.26 Previous investigations have also found that high average nighttime blood pressure is a powerful marker of left atrial enlargement in arterial hypertension.31 However, our findings are in disagreement with a recent metaanalysis suggesting that night-time blood pressure is not a significantly better predictor of left ventricular mass than daytime blood pressure.4 These differences may be due to differences in time schedules and selection of patients. The present data illustrates that echocardiographic parameters of left ventricular mass correlate better with blood pressure than electrocardiographic parameters. In addition, our results confirm that adjusting echographic parameters of left ventricular


mass for age or body mass index improve their performance.32 This study also has its particular limitations. The range of blood pressure of the included patients is rather small with absence of normotensive patients and absence of patients with the higher stages of blood pressure. We also combined data for men and women regardless of the fact that the associations between left ventricular mass and the day–night blood pressure difference may differ between men and women.33 Furthermore, in this study, the antihypertensive treatment was not interrupted several weeks prior to the study measurements, contrary to what is done in most studies.4 These differences in study design could explain the low correlation coefficients. Finally, the use of antihypertensive medication has been associated with reductions in the prevalence of both severe hypertension and electrocardiographic findings of left ventricular hypertrophy.34 The study was not designed to evaluate the specific role of treatment as to the extent of hypertrophy regression nor the time duration before regression of hypertrophy occurs. The latter is of particular importance in the study presented here since our patients needed to be treated for at least 3 months but there was no upper limit of the duration of the treatment. Another possible limitation could be that although strict adherence to quality criteria was followed for reading the echocardiographic tracings, M-mode measurements and calculations may not reflect global hypertrophy patterns.35 The current study confirms that increased afterload recorded during the night is a powerful predictor of left ventricular mass. It also suggests that in treatment of hypertension systolic blood pressure is more important than diastolic blood pressure adding further evidence to the hypothesis that wall stress is a key factor influencing left ventricular hypertrophy development.26 Therefore treatment should aim at 24-h control of both systolic and diastolic hypertension, including night-time pressures. To the best of our knowledge, this is the largest single study on the relationship between left ventricular mass and blood pressure in treated essential hypertension. The major findings are that a significant relationship continues to exists between left ventricular mass and blood pressure under treatment and that left ventricular mass remains more related to systolic than to diastolic blood pressure and more to night-time than to daytime blood pressure.

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