The association of left ventricular mass with blood pressure, cigarette smoking and alcohol consumption; data from the LARGE heart study

International Journal of Cardiology 120 (2007) 52 – 58 www.elsevier.com/locate/ijcard

The association of left ventricular mass with blood pressure, cigarette smoking and alcohol consumption; data from the LARGE heart study☆ John R. Payne a , Laurence E. James a , Kyriacos I. Eleftheriou a , Emma Hawe a , Jack Mann a , Alex Stronge b , Karen Banham c , Michael World d , Steve E. Humphries a , Dudley J. Pennell e , Hugh E. Montgomery a,⁎ a

Centre for Cardiovascular Genetics, BHF Laboratories, Royal Free and University College Medical School, 5 University Street, London, UK b Army Training Regiment Lichfield, Staffordshire, UK c Alliance Medical Limited, Oxfordshire, UK d Royal Centre for Defence Medicine, Selly Oak Hospital, Birmingham, UK e Cardiovascular Magnetic Resonance Unit, Royal Brompton Hospital, London, UK Received 22 July 2006; accepted 4 August 2006 Available online 31 October 2006

Abstract Background: Left ventricular mass is a risk factor for cardiovascular morbidity and mortality. Although factors associated with elevated left ventricular mass have been sought and studied extensively in elderly and in diseased subjects, few studies have examined the young and healthy. The aim of this study was to examine the possible influence of lifestyle on left ventricular mass in a large group of young men. Methods: Left ventricular mass was assessed using cardiovascular magnetic resonance in 541 healthy Caucasian male army recruits. Anthropometric, lifestyle and blood pressure data were collected. Results: Mean unadjusted left ventricular mass and left ventricular mass indexed to body surface area were 163.8 ± 24.9 g and 86.6 ± 10.2 g m− 2 respectively. In univariate analysis, age, height, weight, alcohol consumption, systolic blood pressure, diastolic blood pressure and indices of physical activity were positively associated with unadjusted left ventricular mass (all P b 0.02). By contrast, smoking was associated with lower mean left ventricular mass; never smoked 167.5 ± 25.8 g vs ex-smokers 159.1 ± 25.2 g vs current smokers 161.0 ± 23.1 g (P = 0.007). Multivariate analysis revealed weight, systolic blood pressure, smoking status and indices of physical activity to be independent predictors of left ventricular mass. Conclusions: Our data confirm an association of age, body weight, height, physical activity, diastolic and systolic blood pressure with left ventricular mass. In addition, unexpectedly, we have found smoking is associated with lower left ventricular mass in a large sample of young healthy men. Although the latter association may result from confounding effects, such an interesting observation deserves further investigation. © 2006 Elsevier Ireland Ltd. All rights reserved. Keywords: Smoking; Ventricular; Mass; Young; Cardiovascular magnetic resonance

☆

JRP (PG/02/021), EH and SEH (PG2000/015) are funded by the British Heart Foundation which also provide core funding for the Centre for Cardiovascular Genetics. LEJ and KIE are funded by Research into Ageing Fellowships. The Cardiovascular Magnetic Resonance Unit at Royal Brompton Hospital receives research support from CORDA, Siemens and the British Heart Foundation. HM is funded by the Portex Endowment at the Institute of Child Health, London. ⁎ Corresponding author. Institute for Human Health and Performance, University College London, Ground Floor, Charterhouse Building, Archway Campus, Highgate Hill, London N19 5LW, UK. Tel.: +44 20 7679 6965; fax: +44 20 7679 6212. E-mail address: [email protected] (H.E. Montgomery). 0167-5273/$ - see front matter © 2006 Elsevier Ireland Ltd. All rights reserved. doi:10.1016/j.ijcard.2006.08.043

1. Introduction Independently of cause or the pre-existence of coronary artery disease [1,2], increased left ventricular mass is associated with both excess prospective cardiac risk [1,2], and coronary-, peripheral-, and cerebro-vascular risk [2]. However, substantial variation exists in the left ventricular response to pathological trophic stimuli such as hypertension

J.R. Payne et al. / International Journal of Cardiology 120 (2007) 52–58

[3], whilst left ventricular mass also differs markedly even amongst otherwise ‘normal’ individuals [3,4]. Such variation is attributable to the interaction of genetic inheritance with other factors. In the search for such factors, the majority of studies have focused on elderly [5,6] or diseased subjects [7,8]. Studies of young healthy subjects are sparse, and the small sample size of many has led to limited statistical power [9,10]. Further, most have used echocardiography [11–14] rather than cardiac magnetic resonance, a more reproducible method for left ventricular mass measurement [15–17]. The Lichfield Study has been designed to explore the environmental and genetic determinants of a variety of cardiovascular and musculoskeletal responses to exercise training. As a component of this, the Lichfield Army Recruit Growth in Exercise Heart Study (LARGE Heart) represents the third in a series of studies which have examined the left ventricular growth response of young male Caucasian army recruits to a homogeneous physical training program. The first exclusively examined genetic determinants of physiological left ventricular growth [18], whilst the second was a pharmacogenomic study of left ventricular growth using cardiovascular magnetic resonance [19]. The ‘environmental’ component of the LARGE Heart study specifically sought to assess if any relationship existed between left ventricular mass and cigarette smoking. Additionally, we examined the role of known predictors of left ventricular mass in older populations such as age, height, weight, alcohol consumption and blood pressure in predicting left ventricular mass in young men. 2. Materials and methods This study complies with the Declaration of Helsinki and had appropriate ethics approval (Defence Medical Services Clinical Research Committee). Written informed consent was obtained from all subjects. 2.1. Study subjects Subjects were consecutive Caucasian males recruited to the Army Training Regiment, Lichfield, United Kingdom between July 2002 and April 2004. All subjects successfully completed an Army medical examination prior to training. 2.2. Anthropometric, lifestyle and blood pressure data Subject height and weight were recorded. At interview, cigarette smoking history and alcohol consumption were documented. A questionnaire was used to assess physical activity and to confirm smoking history documented earlier during interview. Smoking history included smoking status (current, ex- or never), consumption history in cigarettes per day, duration of smoking, and time since cessation. Alcohol consumption was recorded as the number of units consumed per week, estimated by the subject. Physical activity assessment listed the sports previously undertaken and

53

those currently undertaken; the period of participation (in years); the hours played per week; and the level of participation (leisure, or for school or county). For simplicity, a physical activity score was generated based on 3 factors: the number of sports participated in, whether the subject continued to play that sport, and the level the sport was played to; this score was used as the primary measure of physical activity. Systolic and diastolic blood pressure were measured after 20 min of supine rest using an automated unit (In Vivo Inc, Philadelphia, USA), the mean of two readings (2 min apart) being used in subsequent analysis. Body mass index was calculated using the formula: Weight (kg) / Height (m)2. Body surface area was estimated using the Dubois formula: 0.20247 × Height (m)0.725 × Weight (kg)0.425. 2.3. Assessment of left ventricular mass Recruit availability was limited to a twelve hour period, during which as many subjects as possible, randomly selected from those volunteering were imaged. A mobile 1.5 Tesla Siemens Sonata cardiovascular magnetic resonance scanner applied protocols as previously described [20]. In brief, the left ventricular short axis was identified by first piloting a vertical long axis plane from the transaxial plane. The horizontal long axis plane was imaged, and from this a stack of short axis images was obtained during breathholding, covering the length of the left ventricle. Electrocardiogram-gated cine images were used in order to measure the left ventricular mass at end-diastole. All cines were acquired using a ‘trueFISP’ sequence. Image analysis was performed by one investigator (JP) blind to other study data, using CMRtools (Cardiovascular Imaging Solutions, London, UK). The area of myocardium was calculated for each short axis slice and using Simpson's method, left ventricular myocardial volume calculated. This volume was then multiplied by myocardial tissue specific density (1.05 g/cm3) to calculate left ventricular mass. Both raw left ventricular mass and left ventricular mass indexed to body surface area were used in statistical analysis. Images of poor quality (such as those with respiratory/movement artefact) were prospectively excluded from analysis. 2.4. Statistical analysis Data were analysed using STATA (version 8, College Station, Texas). Left ventricular mass, weight, systolic blood pressure and physical activity score required natural log transformation to normalise their distribution; geometric means and approximate standard deviations are reported for these variables. Alcohol consumption was considered as a categorical variable because of its highly skewed distribution. Mean raw values (and standard deviations) were initially calculated for left ventricular mass by categorical variables (smoking status, alcohol consumption). Pearson correlation coefficients were determined individually for bivariate associations between left ventricular mass and age,

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J.R. Payne et al. / International Journal of Cardiology 120 (2007) 52–58

Table 1 Subject characteristics in those included in and those excluded from data analysis on the basis of either scanning time constraints or poor scan quality

Age (years) Height (m) Weight (kg) Alcohol consumption (units/week) Systolic blood pressure (mm Hg) Diastolic blood pressure (mm Hg) Body mass index (kg m− 2) Body surface area (m2) Smoking Never status smoked Exsmokers Current smokers Physical activity score

Subjects included

Subjects excluded

n

Mean ± SD

n

Mean ± SD

537 518 514 513

19.8 ± 2.2 1.78 ± 0.06 72.3 ± 9.6 a 6 (1–14) b

335 328 328 326

20.1 ± 2.3 1.77 ± 0.07 72.5 ± 9.5 a 8 (2–15) b

0.016 0.445 0.809 0.031

536

122.6 ± 12.0 a 211

121.2 ± 12.0 a

0.130

536

66.1 ± 8.3

211

65.9 ± 8.6

0.708

514

23.1 ± 2.5

328

23.2 ± 2.5

0.452

514

1.90 ± 0.14

328

1.90 ± 0.14 0.941

80 (42%) 23 (12%) 88 (46%) 191

–

201 – (49%) 47 (11%) – 165 (40%) 413

– 4.6 ± 3.6 a

Pvalue

0.285

Left ventricular mass (g) a

Age (years) Height (m) Weight (kg) a Systolic blood pressure (mm Hg) a Diastolic blood pressure (mm Hg) Physical activity score a a

R2 (%)

n

R

537 518 514 536

0.16 2.6 0.39 15.2 0.67 45.3 0.35 11.9

Left ventricular mass / body surface area (g m− 2)

P-value

n

R

R2 (%)

P-value

b0.0001 b0.0001 b0.0001 b0.0001

513 514 514 510

0.09 0.02 0.27 0.30

0.7 0.05 7.0 8.7

0.054 0.596 b0.0001 b0.0001

536 0.17

2.9

b0.0001 510 0.11 1.1

0.015

413 0.21

4.3

b0.0001 392 0.22 4.6

b0.0001

Log transformed.

c

– – 5.0 ± 3.5 a

Table 3 R2 from analysis of variance which represents the % variation in left ventricular mass and left ventricular mass indexed to body surface area which is explained fitting a univariate model with each variable

0.193

a

Geometric mean ± approximate standard deviations. Median (interquartile range) with P-value calculated using Kruskal– Wallis Test. c P-value calculated using chi-square. b

Of these, complete magnetic resonance imaging studies were obtained in 590 randomly selected individuals because of restrictions in available scanning time. Of these, scan quality was unacceptable in 49 and so left ventricular mass data were available in 541 subjects. Anthropometric and lifestyle data were generally similar for those studied and those excluded, although those excluded were slightly older and drank slightly more alcohol than those included (Table 1). 4. Univariate analysis

height, weight, heart rate, physical activity score and systolic and diastolic blood pressure. The independent association with left ventricular mass was determined for each of these potential covariates using stepwise regression modelling. Pvalues have been calculated from analysis of variance unless otherwise stated. 3. Results 3.1. Study subjects During the enrolment phase, 1430 subjects were invited to participate in the study of whom 897 subjects volunteered.

Mean left ventricular mass was 163.8 ± 24.9 g (range 104.6 to 241.9 g) and mean left ventricular mass indexed to body surface area was 86.6 ± 10.2 g m− 2 (range 57.9 to 128.6 g m− 2). Results of univariate analysis are shown in Tables 2 and 3. Age, height, weight, alcohol consumption, systolic and diastolic blood pressure, and physical activity score were all positively associated with left ventricular mass. With respect to physical activity, left ventricular mass was also positively correlated with number of sports ever undertaken (Table 2), with tertiles of number of hours spent playing sport per week (P = 0.018 and P = 0.007 for linear trend), and tertiles of number of years sport played for

Table 2 Left ventricular mass according to smoking status and alcohol consumption Left ventricular mass (g) ⁎

Smoking status

Alcohol consumption (units/week)

Never Ex-smoker Current smoker 0 1–10 ≥11

n

Geometric mean ± approx. SD

201 47 165 126 226 161

167.6 ± 25.8 159.1 ± 25.2 161.0 ± 23.1 160.6 ± 27.4 163.2 ± 23.3 168.3 ± 24.8

a P-value for linear trend. ⁎ Required log transformation to normalise distribution.

Left ventricular mass / body surface area (g m− 2) P-value 0.007 0.011 a 0.036 0.013 a

n

Geometric mean ± approx. SD

191 45 156 125 226 160

88.1 ± 10.4 83.9 ± 10.8 85.9 ± 9.5 86.0 ± 11.2 86.1 ± 9.5 87.9 ± 10.3

P-value 0.016 0.036 a 0.177 0.105 a

J.R. Payne et al. / International Journal of Cardiology 120 (2007) 52–58 Table 4 Output of stepwise regression modelling on log transformed left ventricular mass (final model shown, including only significant predictors of left ventricular mass) Variable

Incremental R2 (%) a

Standardised B-coefficient b

P-value

Weight (kg) c Systolic blood pressure (mm Hg) a Smoking Never status smoked Exsmoker Current smoker Physical activity score a

35.2 3.6

0.093 0.025

b0.0001 b0.0001

0.8

– −0.044

0.041

−0.004 1.3

0.017

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followed by systolic blood pressure (R2 = 3.6%). The significance of the association of left ventricular mass with smoking (P =0.041) was less than that seen in the univariate analysis (P =0.017); this may result from several confounders; Table 5 shows that smoking was negatively associated with weight and systolic blood pressure, whilst alcohol consumption is positively associated with smoking. Moreover, it is the presence of the relatively small ex-smoker group in the model which allows statistical significance to be reached with the standardised betacoefficient for current smokers (−0.004) differing little from the reference point of never smokers; consistent with this, the exclusion of ex-smokers from the model forces smoking status out of the model whilst not significantly changing the impact of other contributors to the model.

0.001

4.2. Effect of smoking history

a

The incremental R2 shows the additional variability in left ventricular mass explained by adding the variable to a model which contains all other variables listed above. b The beta-coefficient is for a one standard deviation increase in continuous variables (on the transformed scale where specified). c Required log transformation to normalise distribution.

(P = 0.05 and P = 0.006 for linear trend). Therefore, all indices of physical activity were positively associated with left ventricular mass; the calculated physical activity score was the best predictor of activity level of those indices considered in the multivariate model described below. In contrast to these positive associations, univariate analysis showed current smoking to be associated with lower mean left ventricular mass compared to those subjects who had never smoked (Table 2). 4.1. Multivariate analysis Multivariate analysis confirmed weight, systolic blood pressure, smoking status and physical activity score (Table 4) to be independent predictors of left ventricular mass. As expected, weight was the major contributing factor (R2 =35.2%)

Because of the paradoxical negative association of smoking with left ventricular mass on univariate analysis, we also examined the possible effect on left ventricular mass of cigarettes smoked per day and duration of smoking in current smokers; neither of these variables was associated with left ventricular mass. Ex-smokers were not examined in this fashion because of the small number of subjects in this group. 5. Discussion Our study attempted to document the possible associations between lifestyle factors and left ventricular mass amongst young healthy males using cardiovascular magnetic resonance. Univariate analysis revealed age, height, weight, alcohol consumption, physical activity level, systolic and diastolic blood pressure to be associated with increased left ventricular mass, whilst smoking was negatively associated. Of these variables weight, systolic blood pressure and physical activity score were convincing independent predictors on multivariate analysis.

Table 5 The relation of smoking with other variables and a summary of smoking history for current and ex-smokers Smoking status

Age (years) Height (m) Weight (kg) ⁎ Alcohol consumption (units/week) Systolic blood pressure (mm Hg) ⁎ Diastolic blood pressure (mm Hg) Physical activity score ⁎ Cigarettes per day Duration of smoking (years) Time since quitting smoking (years)

P-value

Never smoked

Exsmoker

Current smoker

ANOVA

Linearity

19.6 ± 2.2 1.78 ± 0.06 73.6 ± 9.7 5 (0–12) † 124.5 ± 12.3 66.1 ± 8.0 4.9 ± 3.9 – –

20.4 ± 2.3 1.77 ± 0.07 72.8 ± 9.4 8(2–16) † 121.8 ± 11.0 68.9 ± 6.8 5.1 ± 3.7 10 (5–10) † 2 (1–3) †

19.8 ± 2.4 1.78 ± 0.07 70.6 ± 9.7 10(3–16) † 120.7 ± 11.6 64.8 ± 8.8 4.2 ± 3.3 10 (6–12) † 3.5 (2–6) †

0.060 0.701 0.015 0.015 † 0.009 0.009 0.151 – –

0.300 0.654 0.004

–

0.8 (0.2–2.0) †

–

–

⁎ Required log transformation to normalise distribution. † Median (interquartile range). P-value where relevant by Kruskal–Wallis Test.

0.002 0.134 0.083

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5.1. Height, weight and physical activity Some of these data confirm the findings from other studies of young healthy individuals [21–23]. In particular, height and weight have consistently been demonstrated to bear such influence across a range of different healthy [11,24] and diseased [25,26] subjects, and across a variety of age ranges [27,28]. Our observation that measures of physical activity were consistently associated with greater left ventricular mass also support the observations of prospective training studies [18,19] and cross-sectional studies using athletes and sedentary controls [29,30]. 5.2. Blood pressure As well as being confirmatory, some of our data are novel and help clarify issues raised by past investigations. The association of blood pressure with left ventricular mass observed amongst older normotensive [31] and hypertensive [31] groups has been absent in some studies of younger subjects [32,33], whilst present in others [14,24]. Our finding of a positive association between systolic blood pressure and left ventricular mass in young healthy subjects is consistent with another large study by Gardin and colleagues, who used echocardiography to assess left ventricular mass in 3840 individuals aged 23 to 35 years [24]. 5.3. Alcohol consumption Univariate analysis showed alcohol consumption to be positively associated with left ventricular mass, although this may be linked to physical activity level. However, studies of alcoholics [34] and Framingham study subjects [35] have also suggested an association between alcohol consumption and left ventricular mass. Few studies have addressed this issue in young adults, in whom heavy drinking is most common [36]; in nearly 3500 young adults (mean age 29.9 years), Hoegerman et al. were unable to demonstrate an association between alcohol consumption and left ventricular mass assessed using echocardiography [37]. 5.4. Cigarette smoking This is the first large study using cardiovascular magnetic resonance to examine the role of smoking on left ventricular mass in a young healthy population. Our finding that smoking status was related to left ventricular mass in subjects as young as this might be unexpected. In addition, it might seem counterintuitive that this is an inverse relationship, with left ventricular mass being less in current smokers. It is tempting to suggest that such an association is mediated through blood pressure; systolic blood pressure is significantly lower in current smokers. However, such an observation is misleading. Although cross-sectional studies demonstrate that blood pressure is often lower amongst smokers [38], brachial artery systolic blood pressure measurement suffers from pulse

pressure amplification, a phenomenon which exaggerates the aortic pulse pressure when measured peripherally. Pulse pressure amplification is prominent in young subjects, and is known to be attenuated by smoking [39]. Thus, through reduced pulse pressure amplification, one might well expect brachial artery derived systolic blood pressure to be lower in smokers, especially in studies of the young. Furthermore, aortic systolic blood pressure (a determinant of LV workload) assessed using applanation tonometry appears to be greater in young smokers [39]. Thus, the argument that the association of lower left ventricular mass in smokers seen in our study is mediated by an effect of smoking to reduce systolic blood pressure has a poor foundation and an alternative explanation should be sought. In our study, smoking status is associated with weight and alcohol consumption (Table 5), and although on first inspection smoking status is independently associated with left ventricular mass, closer examination suggests this result is spurious and misleading. Finally, our findings are at variance with those in older age groups, where smoking and left ventricular mass seem to be positively related [40]. 5.5. Study limitations Our study does have some limitations. Although we assessed smoking history through two independent sources (interview and questionnaire), we had no biochemical confirmation of smoking status (e.g. cotinine measures). In addition, we were unable to determine the truthfulness of subject estimates of alcohol consumption and physical activity level. Acknowledgements The LARGE Heart study was primarily funded by a British Heart Foundation Project Grant (PG/02/021) and an unconditional educational grant from Aventis UK. Funding for the musculoskeletal component of this study was provided by Research into Ageing, National Osteoporosis Society, Wishbone Orthopaedic Trust, Dupuy and the Fares Haddad Research Fund. JRP (PG/02/021), EH and SEH (PG2000/015) are funded by the British Heart Foundation which also provide core funding for the Centre for Cardiovascular Genetics. LEJ and KIE are funded by Research into Ageing Fellowships. The Cardiovascular Magnetic Resonance Unit at Royal Brompton Hospital receives research support from CORDA, Siemens and the British Heart Foundation. HM is funded by the Portex Endowment at the Institute of Child Health, London. The authors would like to thank the army recruit volunteers at Lichfield, the hospitality and co-operation of the staff at the Army Training Regiment Lichfield particularly the staff of the Medical Reception Station, the staff of the Officer's Mess and the Commanding Officer. The authors would also like to thank Alliance Medical Limited, who provided the mobile scanner, and especially recognise the hard work of Maxine Whatley, Huub Van Loon and Karen Banham.

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Finally, help from Paul Kotwinsky, and Peter Wootton from the Centre for Cardiovascular Genetics, University College London has been much appreciated. Conflict of interest: This work was supported by an unconditional educational grant from Aventis UK, to whom we express our thanks. References [1] Wolfe LA, Cunningham DA, Rechnitzer PA, Nichol PM. Effects of endurance training on left ventricular dimensions in healthy men. J Appl Physiol 1979;47(1):207–12. [2] Levy D, Garrison RJ, Savage DD, Kannel WB, Castelli WP. Prognostic implications of echocardiographically determined left ventricular mass in the Framingham Heart Study. N Engl J Med 1990;322(22):1561–6. [3] Devereux RB. Left ventricular geometry, pathophysiology and prognosis. J Am Coll Cardiol 1995;25(4):885–7. [4] Post WS, Larson MG, Levy D. Impact of left ventricular structure on the incidence of hypertension. The Framingham Heart Study. Circulation 1994;90(1):179–85. [5] Ahmad A, Nawaz HM, Nevins L, Nawaz H. Longitudinal change in left ventricular hypertrophy in the elderly on antihypertensive therapy. Conn Med 2003;67(2):67–73. [6] Cicconetti P, Morelli S, Ottaviani L, et al. Blunted nocturnal fall in blood pressure and left ventricular mass in elderly individuals with recently diagnosed isolated systolic hypertension. Am J Hypertens 2003;16(11 Pt 1):900–5. [7] Bruno G, Giunti S, Bargero G, Ferrero S, Pagano G, Perin PC. Sexdifferences in prevalence of electrocardiographic left ventricular hypertrophy in Type 2 diabetes: the Casale Monferrato Study. Diabet Med 2004;21(8):823–8. [8] Pontiroli AE, Pizzocri P, Saibene A, Girola A, Koprivec D, Fragasso G. Left ventricular hypertrophy and QT interval in obesity and in hypertension: effects of weight loss and of normalisation of blood pressure. Int J Obes Relat Metab Disord 2004;28(9):1118–23. [9] Davis CL, Kapuku G, Snieder H, Kumar M, Treiber FA. Insulin resistance syndrome and left ventricular mass in healthy young people. Am J Med Sci 2002;324(2):72–5. [10] Marcus JT, DeWaal LK, Gotte MJ, van der Geest RJ, Heethaar RM, Van Rossum AC. MRI-derived left ventricular function parameters and mass in healthy young adults: relation with gender and body size. Int J Card Imaging 1999;15(5):411–9. [11] Burke GL, Arcilla RA, Culpepper WS, Webber LS, Chiang YK, Berenson GS. Blood pressure and echocardiographic measures in children: the Bogalusa Heart Study. Circulation 1987;75(1):106–14. [12] Chien KL, Sung FC, Hsu HC, Su TC, Lee YT. Left ventricular mass and correlated atherosclerotic risk factors in young adolescents: report from Chin-Shan community cardiovascular study in Taiwan. Atherosclerosis 2001;155(2):431–7. [13] Urbina EM, Gidding SS, Bao W, Elkasabany A, Berenson GS. Association of fasting blood sugar level, insulin level, and obesity with left ventricular mass in healthy children and adolescents: the Bogalusa Heart Study. Am Heart J 1999;138(1 Pt 1):122–7. [14] Daniels SR, Kimball TR, Morrison JA, Khoury P, Witt S, Meyer RA. Effect of lean body mass, fat mass, blood pressure, and sexual maturation on left ventricular mass in children and adolescents. Statistical, biological, and clinical significance. Circulation 1995;92 (11):3249–54. [15] Alfakih K, Reid S, Jones T, Sivananthan M. Assessment of ventricular function and mass by cardiac magnetic resonance imaging. Eur Radiol 2004;14(10):1813–22. [16] Myerson SG, Montgomery HE, World MJ, Pennell DJ. Left ventricular mass: reliability of M-mode and 2-dimensional echocardiographic formulas. Hypertension 2002;40(5):673–8.

57

[17] Myerson SG, Bellenger NG, Pennell DJ. Assessment of left ventricular mass by cardiovascular magnetic resonance. Hypertension 2002;39 (3):750–5. [18] Montgomery HE, Clarkson P, Dollery CM, et al. Association of angiotensin-converting enzyme gene I/D polymorphism with change in left ventricular mass in response to physical training. Circulation 1997;96(3):741–7. [19] Myerson SG, Montgomery HE, Whittingham M, et al. Left ventricular hypertrophy with exercise and ACE gene insertion/deletion polymorphism: a randomized controlled trial with losartan. Circulation 2001;103(2):226–30. [20] Bellenger NG, Davies LC, Francis JM, Coats AJ, Pennell DJ. Reduction in sample size for studies of remodeling in heart failure by the use of cardiovascular magnetic resonance. J Cardiovasc Magn Reson 2000;2(4):271–8. [21] Gosse P, Desrumeau GC, Roudaut R, Broustet JP, Dallocchio M. Left ventricular mass in normotensive subjects. Importance of blood pressure response to activity. Am J Hypertens 1989;2(2 Pt 1):78–80. [22] Watanabe K, Kishida K, Hayashi Y, et al. Relation between blood pressure, left ventricular mass and pulsed Doppler parameters in healthy school children. Acta Paediatr Jpn 1990;32(3):275–81. [23] Hinderliter AL, Light KC, Willis PWt. Left ventricular mass index and diastolic filling. Relation to blood pressure and demographic variables in a healthy biracial sample. Am J Hypertens 1991;4(7 Pt 1):579–85. [24] Gardin JM, Wagenknecht LE, Anton-Culver H, et al. Relationship of cardiovascular risk factors to echocardiographic left ventricular mass in healthy young black and white adult men and women. The CARDIA study. Coronary Artery Risk Development in Young Adults. Circulation 1995;92(3):380–7. [25] MacMahon SW, Wilcken DE, Macdonald GJ. The effect of weight reduction on left ventricular mass. A randomized controlled trial in young, overweight hypertensive patients. N Engl J Med 1986;314(6):334–9. [26] Schillaci G, Pasqualini L, Vaudo G, et al. Effect of body weight changes on 24-hour blood pressure and left ventricular mass in hypertension: a 4-year follow-up. Am J Hypertens 2003;16(8):634–9. [27] Henry WL, Gardin JM, Ware JH. Echocardiographic measurements in normal subjects from infancy to old age. Circulation 1980;62(5):1054–61. [28] Lauer MS, Anderson KM, Kannel WB, Levy D. The impact of obesity on left ventricular mass and geometry. The Framingham Heart Study. JAMA 1991;266(2):231–6. [29] Bekaert I, Pannier JL, Van de Weghe C, Van Durme JP, Clement DL, Pannier R. Non-invasive evaluation of cardiac function in professional cyclists. Br Heart J 1981;45(2):213–8. [30] Longhurst JC, Kelly AR, Gonyea WJ, Mitchell JH. Echocardiographic left ventricular masses in distance runners and weight lifters. J Appl Physiol 1980;48(1):154–62. [31] Fox E, Taylor H, Andrew M, et al. Body mass index and blood pressure influences on left ventricular mass and geometry in African Americans: the Atherosclerotic Risk In Communities (ARIC) Study. Hypertension 2004;44(1):55–60. [32] Georgiades A, Lemne C, de Faire U, Lindvall K, Fredrikson M. Stressinduced laboratory blood pressure in relation to ambulatory blood pressure and left ventricular mass among borderline hypertensive and normotensive individuals. Hypertension 1996;28(4):641–6. [33] Naumann D. Interrelations between blood pressure, age, body mass and echocardiographically determined left ventricular muscle mass of the heart in hypertensive and normotensive patients. Z Gesamte Inn Med 1991;46(7):229–33. [34] Urbano-Marquez A, Estruch R, Navarro-Lopez F, Grau JM, Mont L, Rubin E. The effects of alcoholism on skeletal and cardiac muscle. N Engl J Med 1989;320(7):409–15. [35] Manolio TA, Levy D, Garrison RJ, Castelli WP, Kannel WB. Relation of alcohol intake to left ventricular mass: the Framingham Study. J Am Coll Cardiol 1991;17(3):717–21. [36] Anda RF, Waller MN, Wooten KG, Mast EE, Escobedo LG, Sanderson LM. Behavioral risk factor surveillance, 1988. MMWR CDC Surveill Summ 1990;39(2):1–21.

58

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[37] Hoegerman GS, Lewis CE, Flack J, Raczynski JM, Caveny J, Gardin JM. Lack of association of recreational cocaine and alcohol use with left ventricular mass in young adults. The Coronary Artery Risk Development in Young Adults (CARDIA) study. J Am Coll Cardiol 1995;25(4):895–900. [38] Omvik P. How smoking affects blood pressure. Blood Press 1996;5 (2):71–7.

[39] Mahmud A, Feely J. Effect of smoking on arterial stiffness and pulse pressure amplification. Hypertension 2003;41(1):183–7. [40] Verdecchia P, Schillaci G, Borgioni C, et al. Cigarette smoking, ambulatory blood pressure and cardiac hypertrophy in essential hypertension. J Hypertens 1995;13(10):1209–15.