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(Hypertension. 1999;34:1032-1040.)
© 1999 American Heart Association, Inc.

Scientific Contributions

Ambulatory Blood Pressure and M;etabolic Abnormalities in Hypertensive Subjects With Inappropriately High Left Ventricular Mass

Vittorio Palmieri; Giovanni de Simone; Mary J. Roman; Joseph E. Schwartz; Thomas G. Pickering; Richard B. Devereux

From the Division of Cardiology and Hypertension Center, Department of Medicine, New York Presbyterian Hospital, Joan and Sanford I. Well Medical College of Cornell University, New York, NY.

Correspondence to Richard B. Devereux, MD, Division of Cardiology, Box 222, New York Presbyterian Hospital–Weill Medical College of Cornell University, 525 E 68th St, New York, NY 10021. E-mail rbdevere{at}mail.med.cornell.edu

	Abstract

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Abstract—Appropriateness of left ventricular (LV) mass to cardiac workload can be evaluated by the ratio of observed LV mass to the value predicted for an individual’s gender, height^2.7, and stroke work at rest (%PLVM). It is unclear which pathophysiological factors are associated with inappropriately high LV mass in hypertensive subjects. Adequate LV mass was defined by the 90% confidence interval (73% to 128%) of the distribution of %PLVM in 393 normal-weight normotensive subjects. In 185 hypertensive subjects (aged 56±11 years; 60% male, 29% black), according to %PLVM, 164 (88%) had adequate LV mass, 16 (9%) had inappropriately high LV mass (%PLVM >128%), and 5 (3%) had %PLVM <73% (low LV mass). Age, gender, smoking habit, proportion of never-treated subjects, total cholesterol, triglycerides, and creatinine levels did not differ significantly between subjects with adequate and inappropriately high LV mass. Body mass index, fasting glucose, and proportion of black subjects were higher (all P<0.05), while HDL cholesterol was lower (P<0.05) in subjects with inappropriately high LV mass. Blood pressure at the echocardiogram was comparable between subjects with adequate and inappropriately high LV mass, but the latter group had higher ambulatory blood pressure (P<0.01). Subjects with inappropriately high LV mass also had higher aortic root dimension and LV relative wall thickness and relatively lower LV systolic performance than those with adequate LV mass (all P<0.001). Larger aortic root diameter and lower systolic function were also found in hypertensive subjects with inappropriate LV hypertrophy compared with those with adequate LV hypertrophy. In an exploratory case-control study that compared subjects with low %PLVM with age-matched counterparts with adequate LV mass, low %PLVM was associated with lower body mass index, more favorable metabolic profile, and higher LV myocardial contractility. Higher body mass index, larger aortic root, and black race were independent correlates of increased %PLVM. Thus, in arterial hypertension, levels of LV mass inappropriately high for gender, cardiac workload, and height^2.7 are associated with higher body mass index, higher ambulatory blood pressure, larger aortic root diameters, and relatively low myocardial contractility.

Key Words: hypertrophy, left ventricular • hypertension, white coat • obesity • metabolism • echocardiography

	Introduction

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Although left ventricular (LV) hypertrophy is an adaptation that preserves cardiac pump function in arterial hypertension, it also represents a preclinical disease strongly predictive of cardiovascular morbidity and mortality.^{1 2} LV mass growth is related to hemodynamic factors, such as systolic blood pressure (BP), stroke volume, and body size. The ideal amount of lean body mass genetically programmed has been estimated to be proportional to height^2.7 in adults. Therefore, height^2.7, cardiac workload, and gender have been identified as major physiological determinants of LV growth,³ and, in a reference sample of normal-weight normotensive subjects, they may be used to estimate ideal amount of cardiac muscle. The observed/predicted LV mass ratio may be used to evaluate correlates of the deviation of measured LV mass from predicted LV mass. In a preliminary study, hypertensive subjects with LV mass exceeding values predicted by major physiological correlates (termed "inappropriately high LV mass") had a higher rate of subsequent cardiovascular death.⁴

Evaluation of the 24-hour ambulatory BP profile explains the variability of LV mass better than clinic BP^{5 6} and can assess day-night BP variability,^{7 8} which is of interest because lack of a nocturnal BP fall has been associated with increased LV mass.^{8 9} Moreover, "white coat" hypertension can be detected by ambulatory monitoring.¹⁰ Furthermore, lower LV contractility,^{11 12} larger arterial size,^{13 14} and metabolic abnormalities^{15 16 17} have all been associated with higher LV mass. However, whether 24-hour ambulatory BP profile, metabolic abnormalities, and myocardial contractility may contribute to explain levels of LV mass inappropriately high for hemodynamic stimuli, height^2.7, and gender in hypertensive subjects is unclear. Accordingly, this study was designed to investigate ambulatory BP and cardiovascular features in hypertensive subjects with adequate or inappropriate LV mass. In addition, metabolic status (fasting glucose, total and HDL cholesterol, and triglyceride levels), LV geometry, and systolic function were also evaluated.

	Methods

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Study Population
A total of 185 hypertensive individuals were studied, of whom 76 were referred from the Hypertension Center of The New York Hospital from January 1990 to July 1995, 104 were referred from a worksite-based study,^{18 19} and 5 were identified in a population survey of elderly volunteers from the community. Criteria for diagnosis of hypertension were clinic systolic BP 140 (or 160 mm Hg for subjects older than 65 years) or diastolic BP 90 mm Hg. Subjects underwent 24-hour ambulatory BP monitoring, echocardiogram, and metabolic screening; 41% of the subjects had not been previously treated, while the others had stopped antihypertensive treatment 3 weeks to 6 years before the study protocol. All subjects were free of clinical, echocardiographic, or laboratory evidence of coronary or valvular heart disease, diabetes mellitus, cerebrovascular disease, or secondary hypertension. Subjects with awake ambulatory BP <134/90 mm Hg were considered to have white coat hypertension.¹⁰ Informed consent was obtained from all subjects included.

BP Determination
Clinic BP was estimated by a mercury sphygmomanometer as the average of at least 3 measurements by a physician or qualified nurse. Echo BP is BP measured at the end of the echocardiogram, after 30 minutes of supine rest in a dark room. Ambulatory BP monitoring was recorded during a routine day by a SpaceLabs 90207 device.¹⁰ Briefly, the monitor was placed on the nondominant arm and set to take BP readings every 15 minutes during the working day and every 30 or 60 minutes during sleep. Subjects were instructed to record their activity and location after each awake in a diary to permit identification of the awake and sleep time. The sleep-awake BP fall was assessed as the absolute and relative changes between sleep and awake systolic and diastolic BP.

Echocardiography
All subjects underwent standard M-mode and 2-dimensional echocardiography by a skilled research technician using commercially available echocardiography equipped with 2.5- to 3.5-MHz transducers. LV dimensions were assessed from 2-dimensionally guided M-mode tracings (American Society of Echocardiography)²⁰ or, if M-mode recordings were not technically adequate, by 2-dimensional measurements.²¹ M-mode measurements of blinded tracings were performed on up to 6 cycles with the use of a digitizing tablet and were averaged. LV end-systolic, end-diastolic, and stroke volumes were calculated with the use of Teichholz’s method.^{22 23} Aortic root diameter was measured at end-diastole by the leading-edge-to-leading-edge technique at the maximal diameter of the sinuses of Valsalva.²⁴ Observed LV mass was calculated by the adjusted American Society of Echocardiography method²⁵ and indexed for height^2.7 or body surface area. LV hypertrophy was defined with the use of gender-specific cut points (LV mass/height^2.7 >47 g/m^2.7 in women; LV mass/height^2.7 >50 g/m^2.7 in men).²⁶ Predicted values of LV mass were derived by an equation previously developed in a reference population of 393 normal-weight, normotensive adults, aged 18 to 85 years, which includes an indicator variable for gender (men=2; women=1), height^2.7, and stroke work as a measure of cardiac workload [echo systolic BPxDoppler stroke volumex0.0144³ ]: predicted LV mass=18.1xgender+0.64xstroke work+6.63xheight^2.7+55.7; (R²=0.60, SEE=23.2 g, P<0.001).³ This equation provides estimates of LV mass expected for cardiac workload, height^2.7 (used as surrogate for genetically programmed lean body mass for that specific height^{27 28 29} ), and gender. The observed/predicted LV mass ratiox100 (%PLVM) was estimated in the reference population to identify the 5th and 95th percentiles of its distribution (73% to 128%). With the use of the aforementioned equation, the %PLVM was then computed in hypertensive subjects. Subjects with %PLVM >128% (16 of 185 subjects [9%]) were classified as having inappropriately high LV mass, whereas LV mass was considered adequate if %PLVM was between 73% and 128% (164 of 185 subjects [88%]). Subjects with %PLVM <73% (5 of 185 subjects [3%]) were classified as having inadequate LV mass but were not considered in primary analyses because of the likelihood of unstable results with such small cell size. Relative wall thickness was calculated as twice posterior wall in diastole divided by internal diameter¹ and was used as an estimate of LV geometry. Midwall circumferential end-systolic stress (ESS) was assessed as previously reported.²⁶ Endocardial fractional shortening (FS), midwall fractional shortening (MWS), as well as 2 estimates of afterload-independent LV systolic function, the percentage of predicted midwall shortening for a given circumferential ESS (termed stress-corrected MWS), a measure of myocardial contractility, and the ratio ESS/LV end-systolic volume index (ESS/ESVi), a measure of LV systolic chamber function, were derived as previously described.^{11 26}

Statistical Analysis
Data were stored and analyzed with SPSS 8.0 (SPSS Inc). Continuous variables, expressed as mean±SD, were log-transformed when necessary to better satisfy distributional assumptions before parametric tests were used. Student’s t test for independent groups was used to compare subjects with inappropriately high or adequate LV mass. ANCOVA was used to adjust the results for age, body mass index (BMI), gender, and race (blacks versus nonblacks), and adjusted means and SDs are provided in parentheses in the tables. Two-tailed Fisher’s exact tests were used to test the null hypothesis for categorical variables. Pearson correlations were used to investigate relationships between LV mass, %PLVM, and demographic, metabolic, and echocardiographic data. The relationships of %PLVM to aortic root diameter and LV systolic performance, controlling for age, BMI, and diastolic ambulatory BP, were investigated with partial correlation. In an exploratory analysis, the small group classified as having inadequate LV mass was matched by age ±1 year with subjects having adequate LV mass. Gender was not considered because it was included in the equation to predict LV mass. To maximize statistical power, we matched on average 7 subjects with adequate LV mass to each subject having relatively low LV mass. ANOVA, weighted to simulate an equal number of control subjects per case, was used to test differences between these 2 groups. A 2-tailed P<0.05 was considered statistically significant.

	Results

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Comparisons Between Hypertensive Subjects With Adequate Versus Inappropriately High LV Mass
Demographic and Metabolic Characteristics
The sample for the primary analyses comprised 180 clinically hypertensive subjects (mean age, 56±11 years; range, 30 to 81 years; 111 men [62%]; 54 blacks [30%]), of whom 164 had adequate and 16 inappropriately high LV mass (Table 1). No significant differences were found in age, gender, height^2.7, proportion of never-treated subjects, or smoking habit. BMI and the proportion of blacks were higher in subjects with inappropriately high LV mass. Total cholesterol, triglyceride, and creatinine levels were comparable between the 2 groups, while fasting glucose was higher and HDL cholesterol was lower in subjects with inappropriately high LV mass. Adjustment for covariates eliminated differences in fasting glucose and HDL cholesterol.

View this table: [in this window] [in a new window]   Table 1. Demographic and Metabolic Characteristics of Hypertensive Subjects With Adequate vs Inappropriately High LV Mass

Blood Pressure
Subjects with inappropriately high or adequate LV mass had comparable systolic BP at the end of the echocardiogram, whereas diastolic BP tended to be higher (P=0.1) in those with inappropriately high LV mass (Table 2). In contrast, 24-hour, awake, and sleep systolic and diastolic ambulatory BPs were consistently higher in subjects with inappropriately high than in those with adequate LV mass. After adjustment for covariates (age, gender, race, and BMI), differences in ambulatory systolic BP did not reach statistical significance (24 hour, P=0.08; awake, P=0.07; and sleep, P=0.09), while differences in diastolic BP remained statistically significant. The day-night difference in BP was similar in the 2 groups, even when genders were analyzed separately (data not shown; all P>0.1). Pulse pressure was also comparable in subjects with adequate versus inappropriately high LV mass (clinic pulse pressure, 60±16 versus 58±12 mm Hg; awake pulse pressure, 55±11 versus 56±11 mm Hg; all P>0.1).

View this table: [in this window] [in a new window]   Table 2. Rest and Ambulatory BP in Patients With Adequate or Inappropriately High LV Mass

All 23 subjects (13% of 180) with white coat hypertension, according to previously defined criteria,¹⁰ exhibited adequate LV mass; none had clear-cut LV hypertrophy.

Echocardiographic Findings
As partially expected from the study design, LV mass/height^2.7 as well as LV mass/body surface area, used to minimize the influence of obesity, were higher in subjects with inappropriately high LV mass than in those with adequate LV mass (Table 3). LV systolic and diastolic dimensions and relative wall thickness were also higher in subjects with inappropriately high LV mass. ESS was similar between the 2 groups. LV endocardial FS, MWS, stress-corrected MWS, and ESS/ESVi ratio were lower in subjects with inappropriately high LV mass, even when we controlled for covariates.

View this table: [in this window] [in a new window]   Table 3. Echocardiographic Findings in Patients With Adequate or Inappropriately High LV Mass

The aortic root diameter was also significantly larger in subjects with inappropriately high LV mass even with adjustment for covariates. In subjects with adequate LV mass, aortic root diameter did not differ between those with or without LV hypertrophy (3.29 versus 3.25 cm; P>0.1).

Adequate and Inappropriate LV Hypertrophy
A separate analysis was performed among subjects with LV hypertrophy, comparing those with inappropriately high LV mass (inappropriate LV hypertrophy, n=12) with those with adequate LV mass (adequate LV hypertrophy, n=19) (Table 4). Subjects with inappropriate LV hypertrophy tended to be younger and have higher BMI than those with adequate LV hypertrophy, but those differences did not reach statistical significance. Women predominated among subjects with adequate LV hypertrophy, whereas no difference was found in race prevalence. Echo BPs (not shown) were similar between groups. However, ambulatory BP tended to be higher in subjects with inappropriate LV hypertrophy. LV mass/height^2.7 or LV mass/body surface area to account for the impact of obesity, relative wall thickness, and aortic root diameter were higher in subjects with inappropriate than adequate LV hypertrophy. Endocardial FS, MWS, stress-corrected MWS, and ESS/ESVi were lower, while creatinine level was higher, in subjects with inappropriate LV hypertrophy. Fasting glucose level tended to be higher and HDL cholesterol lower in subjects with inappropriate LV hypertrophy (P=NS).

View this table: [in this window] [in a new window]   Table 4. Comparison Between Patients With Adequate vs Inappropriately High LV Mass Among Hypertensive Subjects With LV Hypertrophy

Comparisons Between Hypertensive Subjects With Inappropriately Low LV Mass and Age-Matched Hypertensive Subjects With Adequate LV Mass
An age-matched pilot case-control study was designed to compare the 5 subjects with relatively low LV mass (%PLVM <73%) with age-matched hypertensive subjects with adequate LV mass (n=36) (Table 5). After weighting, subjects with low LV mass and those with adequate LV mass had similar mean age (68 years) by design. BMI and the proportion of women were similar between the 2 groups. There were no black hypertensive subjects in the group with low LV mass, although there were 7 (19%) among those with adequate LV mass (P=NS). Echo systolic and diastolic BP tended to be higher in subjects with low LV mass (185/94 versus 159/89 mm Hg; all P>0.05), while 24-hour, awake, and sleep BPs were similar between groups. None of the subjects with low LV mass had white coat hypertension. LV mass, indexed for either height^2.7 or body surface area, and relative wall thickness were statistically indistinguishable between groups. Aortic root diameter tended to be lower and FS higher in subjects with inappropriately low LV mass, without reaching statistical significance (P0.06). Of note, MWS, stress-corrected MWS, and ESS/ESVi were significantly higher and fasting glucose and triglyceride (P<0.05) levels were lower in subjects with inappropriately low LV mass. The difference in HDL cholesterol was not statistically significant.

View this table: [in this window] [in a new window]   Table 5. Comparison Between Age-Matched Patients With Inappropriately Low vs Adequate LV Mass

Relationships of Observed/Predicted LV Mass Ratio to Aortic Root and LV Function
LV mass was not significantly related to age, but %PLVM showed a negative relationship to age, probably reflecting the positive relationships between age and stroke work (r=0.27, P<0.01) that may tend to reduce the increment of observed/predicted LV mass ratio with increasing age (Table 6). BMI was more strongly related to LV mass than to %PLVM. Ambulatory (awake or sleep) and echo diastolic BP were positively related to LV mass, whereas %PLVM showed a positive relationship to ambulatory diastolic BPs (both awake or sleep) but not to echo diastolic BP. After adjustment for age and BMI, awake diastolic BP showed a significant positive relationship to LV mass (partial r=0.36, P<0.001) and %PLVM (partial r=0.20, P<0.005). No significant associations were found between LV mass or %PLVM with systolic or diastolic day-night BP differences. A positive relationship was found between ESS and LV mass but not with %PLVM. Of interest, parameters of LV systolic function (endocardial FS, MWS, stress-corrected MWS, and ESS/ESVi ratio) had moderate negative correlations to LV mass but were even more strongly negatively related to %PLVM. After adjustment for age, BMI and awake diastolic BP, high values of LV mass, and %PLVM were associated with higher aortic root diameters and lower LV systolic function.

View this table: [in this window] [in a new window]   Table 6. Correlates of LV Mass and Observed/Predicted LV Mass Ratio

	Discussion

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In the present study we investigated cardiovascular features associated with values of LV mass that are higher than those predicted by gender, height^2.7, and cardiac workload,³ a condition we termed inappropriately high LV mass.⁴ This study provides initial evidence that inappropriately high LV mass is associated with high BMI even though the formula to predict LV mass accounts for ideal lean body mass for given height (that is, height^2.7) and hemodynamic factors (stroke volume and systolic BP) that mediate obesity-associated increases of LV mass.³⁰ Within this clinically hypertensive sample, diastolic ambulatory BP slightly discriminated those with inappropriately high LV mass, even after controlling for obesity and systolic BP (included in stroke work). Inappropriately high LV mass was also associated, independently of age, diastolic awake BP, and BMI, with relatively depressed LV systolic performance, which is documented to have adverse prognostic significance. The association of metabolic abnormalities (high fasting glucose levels and worse lipid profile) with inappropriately high LV mass could be explained by the confounding effect of obesity. The fact that a similar pattern was found in the subset of subjects with LV hypertrophy suggests that inappropriateness of LV mass may represent a marker of a transition from a compensatory to a pathological phenotype of severe LV hypertrophy.

In continuity with our main results, an additional case-control study performed to explore differences between subjects with inappropriately low LV mass and age-matched hypertensive subjects with adequate LV mass provided initial evidence of associations of relatively low LV mass with lower BMI, higher LV systolic performance, and a favorable metabolic profile, characterized by lower fasting glucose and triglyceride levels and higher HDL cholesterol.

Inappropriately High LV Mass, Obesity, and Metabolic Findings
Subjects with inappropriately high LV mass had higher BMI, higher fasting glucose levels, and lower mean HDL cholesterol than subjects with adequate LV mass. The strong association of overweight with the observed/predicted LV mass ratio in hypertensive subjects might not be purely an extension of an association between relative body weight and LV mass in apparently normal adults but may reflect, at least in part, the importance of overweight/obesity in the pathophysiology of hypertension. The equation used to predict LV mass was derived in normal-weight subjects and includes body height to the power of 2.7 but not weight. Height^2.7 is a marker of the individual’s "ideal" lean body mass programmed for the size of skeleton^{27 28 29} for which the cardiac muscle might be also genetically programmed and is linearly related to LV mass. However, height^2.7 does not account for the additional increase in lean body mass that usually occurs in obese subjects. Thus, the ratio of observed/predicted LV mass may be particularly sensitive to the effect of overweight-related metabolic abnormalities and hemodynamic impact of increased lean body mass. However, the equation to predict adequacy of LV mass includes both systolic BP and stroke volume, which we have previously shown to increase in parallel with body size in overweight and obese individuals.³⁰ Therefore, the equation to predict LV mass accounts for hemodynamic stimulus for LV growth in obesity. Obesity-related insulin resistance (as suggested by metabolic findings) and/or elevated blood viscosity³¹ might contribute to increase the ratio of observed/predicted LV mass. Obesity has been repeatedly associated with increased LV mass^{32 33 34} as well as with hyperinsulinemia and insulin resistance.^{15 35}

In contrast, subjects with relatively low LV mass tended to be lean and to have low fasting glucose, total cholesterol, and triglyceride levels as well as high HDL cholesterol, which are hallmarks of potentially optimal glucose tolerance. Furthermore, differences in BMI and other metabolic findings between subjects with adequate versus inappropriately high LV mass approached statistical significance among the small subgroup (n=31) of subjects with LV hypertrophy, which suggested associations of a magnitude that could be pathophysiologically important.¹⁷

Contribution of Ambulatory Blood Pressure to Inappropriately High LV Mass
LV mass is more closely correlated with ambulatory BP than conventional clinic BP measurements.^{5 6 8 9 10} Although BP evaluated at the end of the echocardiogram under standardized resting conditions may be more reliable than usual measures of clinic BP, in our study only ambulatory BP statistically differentiated the 2 groups, independently of age, gender, race, and BMI. In the analysis of subjects with LV hypertrophy, ambulatory BPs tended to be higher (10 mm Hg) in subjects with inappropriate LV mass than adequate LV mass, with a loss of statistical significance that may have been due to the small cell size. Thus, our study provides evidence of a better definition of cardiac hemodynamic load by ambulatory than clinical BP. On the other hand, subjects with inappropriately high LV mass did not exhibit a different day-night BP profile than subjects with adequate LV mass, either in the entire sample or in analyses performed separately in women and men. However, men predominated in our sample, reducing power to detect abnormalities in the smaller subset of hypertensive women. Relations of day-night BP difference to absolute or indexed LV mass are debated,^{6 7 8 9 36 37 38 39 40 41 42 43} and further investigation is required to address relationships of inappropriate levels of LV mass to day-night BP profile in hypertensive as well as in population-based samples.

Blood Pressure and Relatively Low LV Mass
Hypertensive subjects with low %PLVM exhibited high echo BPs, and none of them had white coat hypertension, while the levels of 24-hour and awake BPs were similar to those in age-matched subjects with adequate LV mass, leading to a greater difference between clinical BP and ambulatory BP. In this small group, therefore, resting stroke work may overestimate the average daily stroke work, leading to low observed/predicted LV mass ratio. The small cell size represents a major limitation for conclusive physiological inference, and further studies are needed.

Echocardiographic Findings
The larger aortic root diameters in subjects with inappropriate as opposed to adequate LV mass suggest morphological and functional relationships between the proximal arterial tree and appropriateness of LV mass. The difference in aortic root diameter remained significant (P<0.01, data not shown) after adjustment for age, gender, race, and BMI as potential covariates of aortic root diameter, as well as in alternative analyses that considered systolic, diastolic, or pulse pressure alternatively as covariates. Thus, the between-group difference in aortic root diameter is independent of BP differences between subjects with inappropriate or adequate LV mass. It is also notable that this difference was still present in the subset of subjects with LV hypertrophy. Mean aortic root diameter showed a significant positive trend (from 3.0 to 3.3 to 3.8 cm) from subjects with relatively low %PLVM, to subjects with adequate LV mass, and to those with inappropriate LV hypertrophy. Parallel changes in cardiac and large-artery structure have been previously documented for smaller-capacitance arteries,⁴⁴ and a positive relationship between BP and aortic root size has also been reported.^{45 46} A relationship between aortic root diameters and LV mass has been recently reported in a population-based study.¹⁴ Although pulse pressure was comparable in the 2 groups, the association between larger aortic root size and inappropriately high LV mass may depend on increased proximal aortic stiffness, by enhancing LV wall stress in early systole as a result of loss of aortic elastic reserve.⁴⁷ Changes in the arterial pressure waveform because of vascular stiffening⁴⁸ may mediate the stronger relation of LV mass with aortic root dimension than with BP, with possible additional contributions of a nonhemodynamic nature.^{13 49}

Additionally, inappropriately high LV mass was associated with lower myocardial function as well as lower afterload-independent LV systolic chamber function, which are strong independent predictors of cardiovascular events.^{50 51} Those differences remained highly significant even when we compared inappropriate LV hypertrophy with adequate LV hypertrophy, while subjects with relatively low observed/predicted LV mass had high LV systolic performance. Our findings support previous observations of a potentially bidirectional relationship between myocardial contractility and adaptation of LV muscle to growth stimuli.^{11 14 26}

Conclusions
In hypertensive adults, values of LV mass that exceeded the ones predicted by individual gender, height^2.7, and stroke work were associated with higher BMI, metabolic abnormalities, black race, higher ambulatory BP (but not with different day-night BP profile), larger aortic root diameter, concentric LV geometry, and lower LV systolic performance. These characteristics were also confirmed in the subgroup of subjects with LV hypertrophy. Our findings also extend previous observations in which lower myocardial contractility was associated with less favorable metabolic profile, impaired arterial compliance, and higher arterial wall thickness.⁵² Genetic factors may have an additional role in LV adaptation to workload and body size.⁵³

	Acknowledgments

 
This work was supported in part by grants HL-18323 and HL-47540 from the National Heart, Lung, and Blood Institute, Bethesda, Md. We would like to thank Mariane Spitzer, RDMS, for performing echocardiograms and Virginia Burns for assistance in preparation of the manuscript.

Received May 11, 1999; first decision May 31, 1999; accepted July 6, 1999.

	References

Top Abstract Introduction Methods Results Discussion References

 

1. Koren MJ, Devereux RB, Casale PN, Savage DD, Laragh JH. Relation of left ventricular mass and geometry to morbidity and mortality in uncomplicated essential hypertension. Ann Intern Med. 1991;114:345–352.
2. Levy D, Garrison RT, Savage DD, Kannel WB, Castelli WP. Prognostic implications of echocardiographically determined left ventricular mass in the Framingham Heart Study. N Engl J Med. 1990;332:1561–1566.
3. de Simone G, Devereux RB, Kimball TR, Mureddu GF, Roman MJ, Contaldo F, Daniels SR. Interaction between body size and cardiac workload: influence on left ventricular mass during body growth and adulthood. Hypertension. 1998;31:1077–1082.[Abstract/Free Full Text]
4. de Simone G, Devereux RB, Roman MJ, Koren JM, Mensah GA, Alderman MH. Inadequate, adequate and inappropriate left ventricular hypertrophy in arterial hypertension. Circulation. 1997;96(suppl I):I-89. Abstract.
5. Devereux RB, Pickering TG, Harshfield GA, Kleinert HD, Denby L, Clark L, Pregibon D, Jason M, Kleiner B, Borer JS, Laragh JH. Left ventricular hypertrophy in patients with hypertension: importance of blood pressure response to regularly recurring stress. Circulation. 1983;68:470–476.[Free Full Text]
6. Verdecchia P, Porcellati C, Schillaci G, Borgini C, Ciucci A, Battistelli M, Guerrieri M, Gatteschi C, Zampi I, Santucci A, Santucci C, Reboldi G. Ambulatory blood pressure: an independent predictor of prognosis in arterial hypertension. Hypertension. 1994;24:793–801.[Abstract/Free Full Text]
7. Littler WA, Honour AJ, Carter RD, Sleight P. Sleep and blood pressure. Br Med J. 1975;3:346–348.
8. Verdecchia P, Schillaci G, Guerrieri M, Gatteschi C, Benemio G, Boldrini F, Porcellati C. Circadian blood pressure changes and left ventricular hypertrophy in hypertension. Circulation. 1990;81:528–536.[Abstract/Free Full Text]
9. Rizzoni D, Muiesan ML, Montani G, Zulli R, Celebich S, Agabiti-Rosei E. Relationship between initial cardiovascular structural changes and day-time and night time blood pressure monitoring. Am J Hypertens. 1992;5:180–186.[Medline] [Order article via Infotrieve]
10. Pickering TG, James GD, Boddie C, Harshfield GA, Blank S, Laragh JH. How common is white coat hypertension? JAMA.. 1988;259:225–228.[Abstract]
11. Ganau A, Devereux RB, Pickering TG, Roman MJ, Schnall PL, Santucci S, Spitzer MC, Laragh JH. Relation of left ventricular hemodynamic load and contractile performance to left ventricular mass in hypertension. Circulation. 1990;81:25–36.[Abstract/Free Full Text]
12. Devereux RB, Roman MJ, de Simone G, O’Grady MJ, Paranicas M, Yeh JL, Fabsitz RR, Howard BV. Relations of left ventricular mass to demographic and hemodynamic variables in American Indians: the Strong Heart Study. Circulation. 1997;96:1416–1423.[Abstract/Free Full Text]
13. Roman MJ, Saba PS, Pini R, Spitzer M, Pickering TG, Rosen S, Alderman MH, Devereux RB. Parallel cardiac and vascular adaptation in hypertension. Circulation. 1992;86:1909–1918.[Abstract/Free Full Text]
14. Chen CH, Ting CT, Lin SJ, Hsu TL, Ho SJ, Chou P, Chang MS, O’Connor F, Spurgeon H, Lakatta E, Yin FCF. Which arterial and cardiac parameters best predict left ventricular mass? Circulation.. 1998;98:422–428.[Abstract/Free Full Text]
15. Sasson Z, Rasooly Y, Bhesania T, Rasooly I. Insulin resistance is an important determinant of left ventricular mass in the obese. Circulation. 1993;88:1431–1436.[Abstract/Free Full Text]
16. Lind L, Anderson P-E, Andren B, Hanni A, Lithell HO. Left ventricular hypertrophy in hypertension is associated with the insulin resistance metabolic syndrome. J Hypertens. 1995;13:433–438.[Medline] [Order article via Infotrieve]
17. de Simone G, Celentano A, Devereux RB. Metabolic risk factors and left ventricular hypertrophy. Nutr Metab Cardiovasc. 1998;8(suppl 1):40–45.
18. Schnall PL, Schwartz JE, Landsbergis PA, Warren K, Pickering TG. Relation between job strain, alcohol and ambulatory blood pressure. Hypertension. 1992;19:488–494.[Abstract/Free Full Text]
19. Roman MJ, Alderman MH, Pickering TG, Pini R, Keating JO, Sealey JE, Devereux RB. Differential effects of angiotensin converting enzyme inhibition and diuretic therapy on reductions in ambulatory blood pressure, left ventricular mass, and vascular hypertrophy. Am J Hypertens. 1998;11:387–396.[Medline] [Order article via Infotrieve]
20. Sahn DJ, De Maria A, Kislo J, Weyman A. Recommendations regarding quantitation in M-mode echocardiography: results of a survey of echocardiographic measurements. Circulation. 1978;58:1072–1083.[Abstract/Free Full Text]
21. Schiller NB, Shah PM, Crawford M, DeMaria A, Devereux RB, Feigenbaum H, Gutgesell H, Reichek N, Sahn D, Schnittger I, Silverman NH, Tajik AJ. Recommendations for quantitation of the left ventricle by two dimensional echocardiography. J Am Soc Echocardiogr. 1989;2:358–367.[Medline] [Order article via Infotrieve]
22. Teichholz LE, Kreulen T, Herman MV, Gorlin R. Problems in echocardiographic volume determination: echocardiographic-angiographic correlation in the presence or absence of asynergy. Am J Cardiol. 1976;37:7–12.[Medline] [Order article via Infotrieve]
23. Wallerson DC, Ganau A, Roman MJ, Devereux RB. Measurement of cardiac output by M-mode and two-dimensional echocardiography: application to patients with hypertension. Eur Heart J. 1990;11(suppl 1):67–78.
24. Roman MJ, Devereux RB, Kramer-Fox R, O’Loughlin J. Two-dimensional echocardiographic aortic root dimensions in normal children and adults. Am J Cardiol. 1989;17:422–430.
25. Devereux RB, Alonso DR, Lutas EM, Gottlieb GJ, Campo E, Sachs I, Reichek N. Echocardiographic assessment of left ventricular hypertrophy: comparison to necropsy findings. Am J Cardiol. 1986;57:450–458.[Medline] [Order article via Infotrieve]
26. de Simone G, Devereux RB, Roman MJ, Ganau A, Saba PS, Alderman MH, Laragh JH. Assessment of left ventricular function by the midwall fractional shortening/end-systolic stress relation in human hypertension. J Am Coll Cardiol. 1994;23:1444–1451.[Abstract]
27. de Simone G, Devereux RB, Daniels SR, Koren M, Meyer RA, Laragh JH. Effect of growth on variability of left ventricular mass: assessment of allometric signals in adults and children and their capacity to predict cardiovascular risk. J Am Coll Cardiol. 1995;25:1056–1062.[Abstract]
28. Prange HD, Anderson LF, Rahn H. Scaling of skeletal mass to body mass in birds and mammals. Am Nat. 1979;113:103–122.
29. Barlett HL, Puhl SM, Hodgson JL, Buskirk ER. Fat-free mass in relation to stature: ratios of fat-free mass to height in children, adults and elderly subjects. Am J Clin Nutr. 1991;53:1112–1116.[Abstract/Free Full Text]
30. de Simone G, Devereux RB, Daniels SR, Mureddu G, Roman MJ, Kimball TR, Greco R, Witt S, Contaldo F. Stroke volume and cardiac output in normotensive children and adults: assessment of relations with body size and impact of overweight. Circulation. 1997;95:1837–1843.[Abstract/Free Full Text]
31. de Simone G, Devereux RB, Chien S, Alderman MH, Atlas SA, Laragh JH. Relation of blood viscosity to demographic and physiologic variables and to cardiovascular risk factors in apparently normal adults. Circulation. 1990;81:107–117.[Abstract/Free Full Text]
32. de Simone G, Devereux RB, Roman MJ, Alderman MH, Laragh JH. Relation of obesity and gender to left ventricular hypertrophy in normotensive and hypertensive adults. Hypertension. 1994;23:600–606.[Abstract/Free Full Text]
33. Lauer MS, Anderson KM, Kannel WB, Levy D. The impact of obesity on left ventricular mass and geometry. JAMA. 1991;266:231–236.[Abstract]
34. 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;12:996–1004.[Abstract]
35. Kolterman OG, Insel J, Saekow M, Olefsky JM. Mechanisms of insulin resistance in human obesity. J Clin Invest. 1980;65:1272–1284.
36. Schillaci G, Verdecchia P, Borgioni C, Ciucci A, Zampi I, Battistelli M, Gattobigio R, Sacchi N, Porcellati C. Association between persistent pressure overload and ventricular arrhythmias in essential hypertension. Hypertension. 1996;28:284–289.[Abstract/Free Full Text]
37. Verdecchia P, Schillaci G, Gatteschi C, Zampi I, Battistelli M, Bartoccini C, Porcellati C. Blunted nocturnal fall in blood pressure in hypertensive women with future cardiovascular morbid events. Circulation. 1993;88:986–992.[Abstract/Free Full Text]
38. Schmieder RE, Rockstroh JK, Aepfelbacher F, Schulze B, Messerli FH. Gender-specific cardiovascular adaptation due to circadian blood pressure variation in essential hypertension. Am J Hypertens. 1995;8:1160–1166.[Medline] [Order article via Infotrieve]
39. Verdecchia P, Schillaci G, Boldrini F, Guerrieri M, Porcellati C. Sex, cardiac hypertrophy and diurnal blood pressure variation in essential hypertension. J Hypertens. 1992;10:683–692.[Medline] [Order article via Infotrieve]
40. Roman MJ, Pickering TG, Schwartz EJ, Cavallini MC, Pini R, Devereux RB. Is the absence of a normal nocturnal fall in blood pressure (nondipping) associated with cardiovascular target organ damage? J Hypertens.. 1997;15:969–978.[Medline] [Order article via Infotrieve]
41. Schulte K-L, Lienderwald K, Meyer-Sabellek W, van Gemmeren D, Lens T, Gotzen R. Relationships between ambulatory blood pressure, forearm vascular resistance and left ventricular mass in hypertensive and normotensive subjects. Am J Hypertens. 1993;6:786–793.[Medline] [Order article via Infotrieve]
42. Boley E, Pickering TG, James GD, de Simone G, Roman MJ, Devereux RB. Relations of ambulatory blood pressure level and variability to left ventricular and arterial function and left ventricular mass in normotensive and hypertensive adults. Blood Press Monit. 1997;2:323–331.[Medline] [Order article via Infotrieve]
43. Fagard R, Staessen JA, Thijs L. The relationships between left ventricular mass and daytime and night-time blood pressure: a meta-analysis of comparative studies. J Hypertens. 1995;13:823–829.[Medline] [Order article via Infotrieve]
44. Roman MJ, Pickering TG, Pini R, Schwartz JE, Devereux RB. Prevalence and determinants of cardiac and vascular hypertrophy in hypertension. Hypertension. 1995;26:369–373.[Abstract/Free Full Text]
45. Vasan RS, Larson MG, Levy D. Determinants of echocardiographic aortic root size: the Framingham Heart Study. Circulation. 1995;91:734–740.[Abstract/Free Full Text]
46. Kim M, Roman MJ, Cavallini C, Schwartz JE, Pickering TG, Devereux RB. Effect of hypertension on aortic root size and prevalence of aortic regurgitation. Hypertension. 1996;28:47–52.[Abstract/Free Full Text]
47. O’Rourke M. Arterial stiffness, systolic blood pressure, and logical treatment of arterial hypertension. Hypertension. 1990;15:339–347.[Abstract/Free Full Text]
48. Saba PS, Roman MJ, Pini R, Spitzer M, Ganau A, Devereux RB. Relation of arterial pressure waveform to left ventricular and carotid anatomy in normotensive subjects. J Am Coll Cardiol. 1993;22:1873–1880.[Abstract]
49. Ferrara LA, Mancini M, Celentano A, Galderisi M, Iannuzzi R, Marotta T, Gaeta I. Early changes of the arterial carotid wall in uncomplicated primary hypertensive patients: study by ultrasound high resolution B-mode imaging. Arterioscler Thromb. 1994;14:1290–1296.[Abstract/Free Full Text]
50. Mock MB, Ringqvist I, Fisher LD, Davis KB, Chaitman BR, Kouchoukos NT, Kaiser GC, Alderman E, Ryan TJ, Russel RO Jr, Mullin S, Fray D, Killip T III, and Participants in the Coronary Artery Surgery Study. Survival of medically treated patients in the Coronary Artery Surgery Study (CASS) Registry. Circulation. 1982;66:562–571.[Abstract/Free Full Text]
51. de Simone G, Devereux RB, Koren MJ, Mensah GA, Casale PN, Laragh JH. Midwall left ventricular mechanics: an independent predictor of cardiovascular risk in arterial hypertension. Circulation. 1996;93:259–265.[Abstract/Free Full Text]
52. Devereux RB, de Simone G, Pickering TG, Schwartz JE, Roman MJ. Relation of left ventricular midwall function to cardiovascular risk factors and arterial structure and function in normotensive and hypertensive adults. Hypertension. 1998;31:929–936.[Abstract/Free Full Text]
53. Post WS, Larson MG, Myers RH, Galderisi M, Levy D. Heritability of left ventricular mass: the Framingham Heart Study. Hypertension. 1997;30:1025–1028.[Abstract/Free Full Text]

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