This Article Abstract Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Permissions Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by de Simone, G. Articles by Laragh, J. H. Search for Related Content PubMed PubMed Citation Articles by de Simone, G. Articles by Laragh, J. H.

(Hypertension. 1996;28:276-283.)
© 1996 American Heart Association, Inc.

Articles

Influence of Obesity on Left Ventricular Midwall Mechanics in Arterial Hypertension

Giovanni de Simone; Richard B. Devereux; Gian Francesco Mureddu; Mary J. Roman; Antonello Ganau; Michael H. Alderman; Franco Contaldo; John H. Laragh

the Division of Cardiology, The New York Hospital–Cornell Medical Center, New York (G. de S., R.B.D., M.J.R., M.H.A., J.H.L.); Department of Clinical and Experimental Medicine, Federico II University Hospital, Naples, Italy (G. de S., G.F.M.); and Institute of Clinical Medicine, University of Sassari (Italy) (A.G.).

Correspondence to Dr Giovanni de Simone, Division of Cardiology, Box 222, The New York Hospital–Cornell Medical Center, 525 E 68th St, New York, NY 10021. E-mail mjograd@mail.med.cornell.edu (US); simogi@ds.unina.it (Italy).

	Abstract

Top Abstract Introduction Methods Results Discussion References

 
The evaluation of the effect of obesity on left ventricular systolic performance may differ in relation to the method used to measure left ventricular function and to the type of study population. Whether obesity worsens left ventricular midwall mechanics in arterial hypertension has never been investigated. Accordingly, we assessed echocardiographic left ventricular midwall shortening–circumferential end-systolic stress relations in 156 normotensive and normal-weight (reference) adults, 94 normotensive and overweight (1985 National Institutes of Health partition values) to obese (body mass index >30 kg/m²) adults, 263 hypertensive and normal-weight adults, and 224 hypertensive and overweight-to-obese adults. There was an inverse relation of midwall shortening to circumferential end-systolic stress in all groups (all P<.005). Left ventricular performance as a ratio of observed to predicted midwall shortening fell below the fifth percentile in 4 of 94 (4%) of overweight-to-obese normotensive individuals. Eighty-eight of 487 hypertensive subjects (18.1%) exhibited depressed midwall shortening as a percentage of the value predicted from wall stress, with no difference between normal-weight (50 of 263 [19%]) and overweight (38 of 224 [17%]) subjects. Sixty-one normotensive and 131 hypertensive subjects were frankly obese. After adjustment for sex and age, midwall shortening, as either absolute values or a percentage of predicted, was not statistically different among obese, overweight, and normal-weight subjects in both normotensive and hypertensive groups. For each quartile of observed-to-predicted midwall shortening ratio, obese subjects had greater left ventricular end-diastolic volume than normal-weight subjects among both normotensive and, more evidently, hypertensive subjects. A predicted midwall shortening was generated from both wall stress and left ventricular volume with the use of multiple regression analysis. High body mass index, mean blood pressure, aging, and male sex independently predicted low afterload and left ventricular volume–independent midwall left ventricular performance (multiple R=.31, P<.0001). Thus, (1) midwall left ventricular systolic performance in asymptomatic overweight or frankly obese individuals is comparable to that in normal-weight individuals in both the presence and absence of arterial hypertension; (2) however, maintenance of normal left ventricular performance in obese individuals is associated with the use of Starling reserve; and (3) this compensatory mechanism is especially evident when arterial hypertension and obesity coexist.

Key Words: obesity • ventricular function • hypertension, arterial • blood pressure • body mass index • echocardiography

	Introduction

Top Abstract Introduction Methods Results Discussion References

 
Similar to arterial hypertension, chronic obesity is associated with cardiac alterations that may lead to congestive heart failure.^{1 2} This association has been recognized since early in this century³ and has been attributed to the chronic increase in both pressure and volume overload that reduce the contractile reserve of the left ventricle in obese patients.⁴ The duration of obesity is reported to play an important role in the development of left ventricular (LV) pump dysfunction.⁵ When obesity is associated with hypertension, a very common combination,⁶ the overload on the myocardium is further increased,^{4 7 8} resulting in more severe cardiac hypertrophy,⁹ another potentially important contributor to the development of congestive heart failure.¹⁰ Systolic dysfunction may also develop because of excessive wall stress "if wall thickening fails to keep pace with dilatation."¹¹

The possibility that systolic dysfunction may be directly caused by obesity has been widely explored in the past, with conflicting results. There are studies showing reduction of different indexes of systolic function in preclinical conditions,^{12 13 14 15 16} studies failing to demonstrate early clinical signs of systolic dysfunction,^{7 17} and studies suggesting a protective effect of obesity against hypertensive cardiovascular disease.¹⁸ This inconsistency is due mainly to different population samples (from overweight to massive obesity), mostly from clinical settings, but also in part to the use of different approaches to the study of systolic function. Recently, we have refined a method to assess LV systolic function by relating minor axis shortening at the midwall, instead of at the endocardium, to end-systolic stress at the level of circumferential myocardial fibers,¹⁹ a method that revealed a prevalence of 16% of hypertensive patients with LV systolic dysfunction that could not be detected by assessment of LV chamber mechanics.

Accordingly, we designed this study to assess whether the presence of overweight to obesity increases the prevalence of asymptomatic LV systolic dysfunction using the relations between LV midwall shortening and end-systolic stress in a large population of uncomplicated normal-weight or overweight-to-obese hypertensive subjects and in normotensive control subjects in the same weight strata.

	Methods

Top Abstract Introduction Methods Results Discussion References

 
Subject Population Sample
Clinical, anthropometric, and echocardiographic measurements were available in 737 male and female subjects studied at the Hypertension Center of The New York Hospital–Cornell Medical Center (n=639) or at the Institute of Internal Medicine and Metabolic Diseases of Federico II University Hospital in Naples, Italy (n=98). Among the study participants, 156 (113 American and 43 Italian) were normotensive and of normal weight, 94 (52 American and 42 Italian) were normotensive and overweight to obese, 263 (all American) were hypertensive and of normal weight, and 224 (211 American and 13 Italian) were hypertensive and overweight to obese. Hypertensive subjects either were never treated with antihypertensive drugs or stopped taking them for at least 3 weeks before the echocardiographic study.

The American participants were part of a large employed cohort involved in a worksite hypertension screening and treatment program. Detailed characteristics of this population have been previously reported.^{9 20} The Italian participants were part of a screening program involving the staff of the Federico II University Hospital (normal-weight group) or were otherwise healthy obese subjects who came to the Nutrition Unit Outpatient Clinic of the Institute of Internal Medicine and Metabolic Diseases with the sole purpose of losing weight by dietary intervention. Thirteen of 55 (24%) obese Italians were found to be hypertensive at the outpatient clinic screening. All the Italian participants also underwent screening for coronary artery disease, including a bicycle or treadmill exercise test.

All participants gave informed consent under protocols approved by the Committee on Human Rights in Research of Cornell University Medical College and by the Institutional Ethics Committee of Federico II University of Naples.

Definition of Hypertension and Obesity
Blood pressure of hypertensive subjects was determined with an arm cuff of appropriate size and mercury sphygmomanometer and was above 140/90 mm Hg on each of several screening visits; blood pressure of normotensive subjects was consistently below this level. Seventy-eight subjects with isolated systolic hypertension (systolic pressure >140 mm Hg and diastolic pressure <90 mm Hg) were included in the group of hypertensive individuals.

Overweight was defined according to the National Institutes of Health Consensus Development Panel criteria as a body mass index greater than 27.8 kg/m² for men and 27.3 kg/m² for women.²¹ Frank obesity was defined as a body mass index greater than 30 kg/m² for both women and men.

Echocardiography
M-mode echocardiograms were made with commercially available machines (ESAOTE SIM7000/Challenge and Hewlett-Packard 770720), with the ultrasound beam at or just below the tips of the mitral valve leaflets, and were recorded on strip-chart paper with the subjects in the partial decubitus position. Measurements of septal and posterior wall thicknesses and LV chamber dimensions were made by two blinded observers according to the guidelines of both the American Society of Echocardiography²² and the Penn Convention.²³ Measurements of LV mass, relative wall thickness, and endocardial fractional shortening were computed by standard methods.²⁴ Systolic shortening of the LV minor axis at the midwall was calculated taking into account the epicardial migration of midwall during systole caused by thickening of the inner shell formed by longitudinal fibers.^{19 25} Midwall shortening (mFS) was computed as

where D is LV chamber diameter, H is the inner half of the posterior wall plus the inner half of the septum, and the subscripts d and s are diastole and systole, respectively. A method for calculation of the value of H_s, with the epicardial migration of the LV midwall during systole taken into account, has been previously reported.^{19 26}

Myocardial afterload has been represented as circumferential end-systolic wall stress (cESS), calculated at the midventricular level with a cylindrical model that does not require direct measurement of the LV long axis²⁷ :

where SBP is systolic pressure measured at the end of the echocardiogram, and P is posterior wall thickness. Brachial cuff systolic pressure has been previously reported to be closely related to central arterial end-systolic pressure in 72 normotensive and 92 hypertensive subjects with a wide range of body mass indexes studied at the Cornell Laboratory.²⁸ This analysis has been extended to 85 normotensive subjects (27 women) and 197 hypertensive subjects (75 women, 142 to 195 mm Hg brachial systolic pressure), including 82 obese individuals (25 women, body mass index up to 41.8 kg/m²). Central systolic pressure increased 8.8 mm Hg for every 10 mm Hg of brachial systolic pressure (r=.90, SEE=9 mm Hg, P<.0001). From the regression equation generated in this "learning series," central pressure was predicted in the present study population and was used for alternative calculation of end-systolic stress.

LV myocardial systolic performance was evaluated with the use of the ratio between the observed value of midwall fractional shortening and that predicted from circumferential end-systolic wall stress on the basis of the regression equation obtained in the subgroup of 156 normotensive normal-weight subjects. This value was also related to LV chamber volume in the pooled groups of normal-weight and overweight normotensive subjects to obtain an index of LV performance independently of both myocardial afterload and an indirect measure of preload.

Stroke volume was determined with the Teichholz formula for calculation of end-diastolic and end-systolic volumes from M-mode measurements.²⁹ This measurement has been validated by comparison with invasive and Doppler evaluations of LV chamber volumes and stroke volume in normotensive and hypertensive adults, as well as in individuals with a variety of other diseases.^{29 30 31 32} Cardiac output and peripheral resistance were thereafter calculated.

Normalization for Body Size
LV mass was normalized for height to the 2.7 power, an allometric signal that linearized the relation between LV mass and height in a large population of healthy individuals³³ and that has been recently shown to improve the prediction of cardiovascular risk in individuals with arterial hypertension.³⁴ Stroke volume and cardiac output have been traditionally normalized for body surface area.

Statistical Analysis
All variables are presented as mean±SD. Descriptive statistics were obtained by ² distribution and, when possible, computation of Fisher exact tests. Least-squares linear regression analysis was used for study of the relations between indexes of LV systolic function and wall stress or LV volume. The fifth percentile of the normal distribution of the observed-to-predicted midwall shortening ratio was used for identification of subjects with depressed LV performance. Two-factor ANOVA was used for comparison of the four subject groups, with the use of a hierarchical design in which the factor defining body habitus was entered first. The output of ANOVA was adjusted for age and sex by ANCOVA with priority entrance of these covariates into the model. One-way ANOVA and the Scheffe post hoc test were also used for comparison of normal-weight to overweight and frankly obese (body mass index >30 kg/m²) subjects, either without entering of covariates or after adjustment for age and sex, in separate groups of normotensive and hypertensive subjects. Because sex did not significantly affect any of the body habitus–LV function analyses, sex-specific analyses are not presented.

Forward stepwise multiple regression analysis was used for study of the independent effect of wall stress and LV end-diastolic volume on midwall shortening and for determination of independent predictors of measures of LV performance, identified by a simple univariate correlation matrix. Collinearity diagnostic was used for assessment of the stability of the models. A two-tailed value of P.05 was used for rejection of the null hypothesis.

	Results

Top Abstract Introduction Methods Results Discussion References

 
Characteristics of the Population Sample
The demographic characteristics of the study population are reported in Table 1. Hypertensive subjects were older than normotensive subjects (P<.0001). In the group of hypertensive overweight subjects, the proportion of women was lower than in the other groups (P<.005). Predicted central pressure was lower than brachial systolic pressure by 5±1 mm Hg in normotensive normal-weight men and women, 6±1 mm Hg in normotensive obese men, 5±2 mm Hg in normotensive obese women, and 9±2 mm Hg in hypertensive normal-weight men and women as well as in hypertensive obese men and women. Because the value of end-systolic stress calculated with predicted central pressure gave a nearly identical rank order of subjects and identified the same intergroup differences as stress calculated for brachial blood pressure, only results obtained with brachial systolic pressure used for calculation of end-systolic stress are reported below.

View this table: [in this window] [in a new window]   Table 1. Demographic Characteristics of Study Population

Stress-Shortening Relations in Normal-Weight and Overweight Subjects
The 156 normotensive normal-weight subjects comprised the reference group for this study. There were strong inverse relations of circumferential stress to endocardial shortening (eFS=110.6-36.2·log(cESS), r=-.78, SEE=3.1%, P<.0001) and midwall shortening (Fig 1, mFS=19.9-0.02·cESS, P<.002). These relations were also found in normotensive overweight subjects (eFS=111.6-36.2·log(cESS), r=-.79, P<.0001; mFS=21.3-0.03·cESS, P<.0003, Fig 1), hyperten-sive normal-weight subjects (eFS=113.4-36.3·log(cESS),ESS), r=-.79, P<.0001; mFS=18.6-0.02·cESS, P<.0001, Fig 2), and hypertensive overweight subjects (eFS=114.0-36.6·log(cESS), r=-.80, P<.0001; mFS=18.1-0.01·cESS, P<.005, Fig 2). In all subjects, a predicted value of midwall shortening was generated from the corresponding value of wall stress on the basis of the regression equation obtained in the normotensive normal-weight reference group.

View larger version (21K): [in this window] [in a new window]   Figure 1. Relation between midwall shortening and circumferential end-systolic stress in 156 normal-weight normotensive subjects (), the reference population for the present study, and in 94 overweight normotensive subjects (). Continuous lines are normal regression line with 95% confidence limits of the relation in the reference group.

View larger version (27K): [in this window] [in a new window]   Figure 2. Relation between midwall shortening and circumferential end-systolic stress in 263 normal-weight hypertensive subjects () and 224 overweight hypertensive subjects (). Continuous lines are regression line with 95% confidence interval of the relation in normal-weight normotensive reference group. For overweight subjects, r=-.37, SEE=2%; for normal-weight subjects, r=-.25, SEE=2%.

In the group of 250 normotensive subjects, 4 of 94 (4%) overweight people had ratios of observed to predicted midwall shortening below the fifth percentile of the normal distribution (0.796). In contrast, 88 of 487 (18.1%) subjects with arterial hypertension exhibited depressed midwall shortening as a percentage of the value predicted from wall stress, with no difference in prevalence between normal-weight (50 of 263 [19%]) and overweight (38 of 224 [17%]) subjects.

Even after adjustment for age and sex, the presence of overweight alone did not affect endocardial or midwall LV shortening either as absolute values or as observed-to-predicted ratios in either hypertensive or normotensive subjects. In contrast, hypertension was associated with enhanced endocardial shortening (36±7% in normal-weight and 36±6% in overweight individuals compared with 34±5% in either normotensive group, both P<.05) and reduced midwall LV function after the effect of overweight was taken into account (16±3% in both normal-weight and overweight subjects compared with 18±2% in both normotensive groups, P<.001).

Stress-Shortening Relations in Frankly Obese Individuals
Sixty-one normotensive subjects (35 women and 26 men, 37±12 years, 125±12/79±7 mm Hg) and 131 hypertensive subjects (64 women and 67 men, 51±10 years, 152±17/94±11 mm Hg) exhibited body mass indexes greater than 30 kg/m² and were considered frankly obese.

Normotensive Individuals
Table 2 shows that both endocardial and midwall shortening were normal in normotensive overweight and obese subjects compared with normal-weight individuals. LV chamber dimension and mass were greater in both normotensive overweight and obese subjects than in normal-weight subjects (.05<P<.004), whereas relative wall thickness was normal. Cardiac output and stroke volume were also higher in both overweight and obese normotensive subjects (.03<P<.0001), but these differences were offset by normalization for body surface area. Peripheral resistance was similar in all groups.

View this table: [in this window] [in a new window]   Table 2. Left Ventricular Function and Geometry in Relation to Presence of Overweight or Frank Obesity in Normotensive Subjects: One-Way ANOVA With Scheffe Post Hoc Test

Hypertensive Individuals
Table 3 shows that among the hypertensive groups, obese and overweight subjects also did not exhibit lower endocardial or midwall shortening, either as absolute values or as percentages of predicted values, than hypertensive normal-weight individuals. LV chamber dimension and mass were progressively higher in overweight and obese subjects than in normal-weight hypertensive subjects (.02<P<.0001), with a statistical difference also between overweight and obese individuals (.05<P<.005); relative wall thicknesses were similar in the three groups. Both overweight and frankly obese subjects had significantly higher cardiac output and stroke volume than the normal-weight group (.05<P<.0001), and obese subjects had higher cardiac output and stroke volume than overweight individuals (both P<.01). These differences were eliminated by normalization for body surface area. Peripheral resistance was comparable among the three groups.

View this table: [in this window] [in a new window]   Table 3. Left Ventricular Function and Geometry in Relation to Presence of Overweight or Frank Obesity in Hypertensive Subjects: One-Way ANOVA With Scheffe Post Hoc Test

Relation of Midwall Shortening as a Percentage of Predicted to LV Chamber Size
Tables 2 and 3 show that afterload-independent midwall LV performance was normal in overweight to obese normotensive and hypertensive individuals, but LV chamber dimension was progressively higher from normal-weight to obese subjects. This progression was most apparent in the presence of hypertension.

In the entire study population, as well as in separate normotensive and hypertensive groups, midwall LV shortening as a percentage of the value predicted for end-systolic stress was positively related to LV end-diastolic volume (.006<P<.0001, Fig 3). The top panel of Fig 4 shows that for each quartile of observed-to-predicted midwall shortening ratio, overweight-to-obese normotensive subjects had larger LV end-diastolic volumes than normal-weight subjects, a difference that attained statistical significance in the lowest, second, and highest quartiles of stress-adjusted midwall shortening (all P<.05). Among hypertensive subjects, a parallel progressive increase in LV end-diastolic volume in overweight subjects was also evident at every level of afterload-independent midwall shortening.

View larger version (27K): [in this window] [in a new window]   Figure 3. Relations between midwall shortening as a percentage of values predicted from end-systolic stress and LV end-diastolic volume calculated by the Teichholz approach in normal-weight normotensive subjects (, r=.26, P<.001), overweight-to-obese normotensive subjects (, r=.29, P<.006), normal-weight hypertensive subjects (, r=.34, P<.0001), and overweight-to-obese hypertensive subjects (, r=.34, P<.0001). Continuous lines represent regression line with 95% confidence interval in normal-weight normotensive individuals.

View larger version (26K): [in this window] [in a new window]   Figure 4. LV end-diastolic volume in normal-weight (open bars) and overweight-to-obese (solid bars) normotensive (top) and hypertensive (bottom) subjects in quartiles of midwall shortening (mFS) as percentage of predicted value from circumferential wall stress. At each level of afterload-independent midwall shortening, obese subjects exhibit higher LV end-diastolic volumes.

Because midwall LV shortening was related to both end-systolic wall stress and LV end-diastolic volume, an equation was generated relating circumferential wall stress (cESS) and end-diastolic volume (EDV) to midwall LV shortening in the entire normotensive group, including overweight-to-obese individuals:

(multiple R=.42, SEE=2.0%, P<.0001). Collinearity diagnostics confirmed good stability of the model.

Predictors of Depressed LV Performance
We generated a correlation matrix to examine the univariate correlates of midwall shortening as a percentage of predicted from both end-systolic stress and LV end-diastolic volume. Midwall shortening as a percentage of predicted from end-systolic stress and LV volume decreased with increasing age (r=-.15), systolic (r=-.18) and diastolic (r=-.29) arterial pressures, body mass index (r=-.13), body weight (r=-.23), LV mass index (r=-.53), and male sex (r=.26, all .005<P<.0001). In multivariate analyses, low values of LV midwall shortening as a percentage of predicted from both end-systolic stress and LV volume were independently related to high body mass index (ß=-0.11, slope=-0.29, P<.003), high mean arterial pressure (ß=-0.15, slope=-0.14, P<.0001), male sex (ß=-0.18, slope=-5.33, P<.0001), and older age (ß=-0.09, slope=-0.09, P<.04; intercept=115; multiple R=.31, SEE=13%, P<.0001).

	Discussion

Top Abstract Introduction Methods Results Discussion References

 
Both hypertension and obesity are predictors of congestive heart failure, and their effects may be potentiated when the two conditions coexist.¹ However, detection of early hemodynamic markers of the deterioration of cardiac function remains controversial. Technically, the greatest part of the controversy concerns the results obtained by using end-systolic indexes of LV chamber function or more direct measures of myocardial contractility. In the present study, we studied LV performance by taking into account the effects that LV geometric abnormalities, wall stress, and preload have on LV myocardial function, thereby approximating a measure of the true inotropic state of the myocardium. Because obesity is associated with LV geometric enlargement, we used the physiologically appropriate midwall shortening–circumferential end-systolic stress relation to assess ventricular function. With this method, we took into account elevated end-systolic stress, which has been invoked in previous studies as a potential cause of decline of LV function.¹¹ Therefore, the indexes of LV performance used in this study are likely to reflect myocardial contractility more directly than ejection phase indexes of LV chamber performance, which depend on loading conditions.

The present results show that the presence of overweight or frank obesity does not worsen LV myocardial efficiency in hypertensive individuals. Under the conditions of this study, clear-cut LV systolic dysfunction attributable to obesity could not be detected with either midwall LV shortening or the more traditional endocardial shortening in either normotensive or hypertensive subjects. Overweight and mild-to-moderate obesity, therefore, do not appear to be independent determinants of LV systolic dysfunction at rest. Previous pivotal studies showing depressed LV performance in obesity used indexes of LV function that could be influenced by the presence of LV hypertrophy and greater LV chamber stiffness¹³ or are not completely independent of load.¹⁶ In addition, ours is largely a population-based study, eliminating the potential selection bias that may affect clinical investigation of relatively small groups of subjects. Virtually all previous studies documenting "precocious" impairment of LV performance were based on clinical patients^{12 13 14 15 16} who might have been evaluated because of subtle symptoms.

The relative normality of midwall LV performance in overweight subjects in both normotensive and hypertensive groups was paralleled by evidence of increased stroke volume and cardiac output in obese subjects, which confirmed previous findings.^{2 4 8 13 16 35 36} This increase was directly related to body size differences, being unrecognizable when values of cardiac output and stroke volume were normalized for body surface area. However, on the basis of findings concerning relations between LV mass and body size and preliminary findings of allometric relations between stroke volume and body size,^{33 34 37} body surface area might be an inappropriate measure of body size for examination of the effect of obesity on cardiac output.

The high stroke volume in overweight normotensive or hypertensive subjects was a consequence of a greater chamber dimension that contributed substantially to the maintenance of efficient LV chamber function. Because obese subjects reach levels of afterload-independent LV performance comparable to those in normal-weight subjects at higher values of LV volume, recruitment of Starling reserve at rest may well occur. This possibility was also suggested by previous studies demonstrating that LV ejection fraction measured by radionuclide ventriculography, even when normal at rest, might not increase normally in response to peak exercise,^{14 38 39 40} a phenomenon that can be caused by the inability of the heart to recruit further Starling reserve during exercise.

Among hypertensive individuals, midwall shortening as a percentage of the value predicted from both end-systolic stress and an index of LV chamber size that would crudely parallel preload, a variable therefore heavily influenced by myocardial contractility, was indeed negatively influenced by obesity, high blood pressure, aging, and male sex. This suggests an independent additional negative effect of obesity in the setting of arterial hypertension but one that is largely offset by compensatory hemodynamic mechanisms, including the use of Starling reserve and compensatory LV hypertrophy.

In conclusion, midwall LV systolic performance as a measure of ventricular contractility independent of afterload and preload is comparable in asymptomatic overweight and normal-weight hypertensive subjects and in normotensive control subjects of similar weights. No precocious evidence of LV contractile dysfunction due to obesity could be detected in the resting conditions under which this study was conducted. In contrast, LV myocardial dysfunction was related to the presence of arterial hypertension and LV hypertrophy. Normal LV performance at rest was maintained in obese hypertensive and normotensive adults by LV chamber enlargement, thereby recruiting preload reserve, that might not be able to be augmented further when hemodynamic demand is increased during exercise or other stresses.

	Acknowledgments

 
This work was supported in part by grant HL-18323 from the National Heart, Lung, and Blood Institute, Bethesda, Md, and by grant 18/01/5495 MURST/60% of Ministry of University and Research, Italy. The authors wish to thank Virginia Burns for her assistance in the preparation of this manuscript.

Received November 27, 1995; first decision January 8, 1996; accepted March 25, 1996.

	References

Top Abstract Introduction Methods Results Discussion References

 
1. Hubert HB, Feinleib M, McNamara PM, Castelli WP. Obesity as an independent risk factor for cardiovascular disease: a 26-year follow-up of participants in the Framingham Heart Study. Circulation. 1983;67:968-975.[Abstract/Free Full Text]

2. Ventura HO, Johnson MR, Grusk B, Pifarre R, Costanzo-Nordin MR. Cardiac adaptation to obesity and hypertension after heart transplantation. J Am Coll Cardiol. 1992;19:55-59.[Abstract]

3. Smith HL, Willius RA. Adiposity of the heart: a clinical and pathological study of one hundred and thirty-six obese patients. Ann Intern Med. 1933;52:911-925.

4. Messerli FH, Christie B, DeCarvalho JGR, Aristimuno EE, Suarez DH, Dreslinski GR, Frohlich ED. Obesity and essential hypertension: hemodynamics, intravascular volume, sodium excretion and plasma renin activity. Arch Intern Med. 1981;141:81-85.[Abstract/Free Full Text]

5. Nakajima T, Fujioka S, Tokunaga K, Hirobe K, Matsukawa Y, Tarui S. Noninvasive study of left ventricular performance in obese patients: influence of duration of obesity. Circulation. 1985;71:481-490.[Abstract/Free Full Text]

6. Stamler R, Stamler J, Riedlinger WF, Algera G, Roberts RH. Weight and blood pressure: findings in hypertension screening of 1 million Americans. JAMA. 1978;240:1607-1610.[Abstract/Free Full Text]

7. Messerli FH, Sundgaard-Riise K, Reisin ED, Dreslinski GR, Dunn FG, Frohlich ED. Disparate cardiovascular effects of obesity and arterial hypertension. Am J Med. 1983;74:808-812.[Medline] [Order article via Infotrieve]

8. Messerli FH, Sundgaard-Riise K, Reisin ED, Dreslinski GR, Ventura HO, Oigman W, Frohlich ED, Dunn FG. Dimorphic cardiac adaptation to obesity and arterial hypertension. Ann Intern Med. 1983;99:757-761.

9. 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]

10. Devereux RB, de Simone G, Roman MJ. From `compensatory' hypertensive left ventricular hypertrophy to heart failure: is the transition so dramatic? Heart Failure. 1994;10:102-108.

11. Alpert MA, Hashimi MW. Obesity and the heart. Am J Med Sci. 1993;306:117-123.[Medline] [Order article via Infotrieve]

12. Alexander JK, Amad KH, Cole VW. Observation on some clinical features of extreme obesity, with particular reference to cardiorespiratory effects. Am J Med. 1962;32:512-524.

13. de Divitiis O, Fazio S, Petitto M, Maddalena G, Contaldo F, Mancini M. Obesity and cardiac function. Circulation. 1981;64:477-482.[Abstract/Free Full Text]

14. Licata G, Scaglione R, Barbagallo M, Parrinello G, Capuana G, Lipari R, Merlino G, Ganguzza A. Effect of obesity on left ventricular function studied by radionuclide angiocardiography. Int J Obes. 1991;15:295-302.[Medline] [Order article via Infotrieve]

15. Rockstroh JK, Schmieder RE, Schachinger H, Messerli FH. Stress response pattern in obesity and systemic hypertension. Am J Cardiol. 1992;70:1035-1039.[Medline] [Order article via Infotrieve]

16. Garavaglia GE, Messerli FH, Nunez BD, Schmieder RE, Grossman E. Myocardial contractility and LV function in obese patients with essential hypertension. Am J Cardiol. 1988;62:594-597.[Medline] [Order article via Infotrieve]

17. Schmieder RE, Messerli FH. Does obesity influence early target organ damage in hypertensive patients? Circulation. 1993;87:1482-1488.[Abstract/Free Full Text]

18. Bloom E, Reed D, Yano K, MacLean C. Does obesity protect hypertensives against cardiovascular diseases? JAMA. 1986;256:2972-2975.[Abstract/Free Full Text]

19. 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]

20. Hammond IW, Devereux RB, Alderman MH, Lutas EM, Spitzer MC, Crowley JS, Laragh JH. The prevalence and correlates of echocardiographic left ventricular hypertrophy among employed patients with uncomplicated hypertension. J Am Coll Cardiol. 1986;7:639-650.[Abstract]

21. National Institute of Health Consensus Development Panel on the Health Implication of Obesity. Health implication of obesity. Ann Intern Med. 1985;103:1073-1077.

22. Sahn DJ, DeMaria A, Kisslo J, Weyman A. The Committee on M-Mode Standardization of the American Society of Echocardiography: recommendations regarding quantitation in M-mode echocardiography. Results of a survey of echocardiographic measurements. Circulation. 1978;58:1072-1083.[Abstract/Free Full Text]

23. Devereux RB, Reichek N. Echocardiographic determination of left ventricular mass in man: anatomic validation of the method. Circulation. 1977;55:613-618.[Abstract/Free Full Text]

24. Devereux RB. Evaluation of cardiac structure and function by echocardiography and other noninvasive techniques. In: Laragh JH, Brenner BM, eds. Hypertension: Pathophysiology, Diagnosis, and Treatment. New York, NY: Raven Press Publishers; 1990:1479-1492.

25. Shimuzu G, Zile MR, Blaustein AS, Gaasch WH. Left ventricular chamber filling and midwall fiber lengthening in patients with left ventricular hypertrophy: overestimation of fiber velocities by conventional midwall measurements. Circulation. 1985;71:266-272.[Abstract/Free Full Text]

26. Shimuzu G, Hirota Y, Kita Y, Kawamura K, Saito T, Gaasch WH. Left ventricular midwall mechanics in systemic arterial hypertension: myocardial function is depressed in pressure-overload hypertrophy. Circulation. 1991;83:1676-1684.[Abstract/Free Full Text]

27. Gaasch WH, Zile MR, Hosino PK, Apstein CS, Blaustein AS. Stress-shortening relations and myocardial blood flow in compensated and failing canine hearts with pressure-overload hypertrophy. Circulation. 1989;79:872-873.[Abstract/Free Full Text]

28. Messina AG, Paranicas M, Yao FS, Illner P, Roman MJ, Saba PS, Devereux RB. The effect of midazolam on left ventricular pump performance and contractility in anesthetized patients with coronary artery disease: effect of preoperative ejection fraction. Anesth Analg. 1995;81:793-799.[Abstract]

29. Teichholz LE, Kreulen T, Herman MV, Gorlin R. Problems in echocardiographic volume determination: echocardiographic-angiographic correlations in the presence or absence of asynergy. Am J Cardiol. 1976;37:7-12.[Medline] [Order article via Infotrieve]

30. 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.

31. Kronik G, Slany J, Mosslacher H. Comparative value of eight M-mode echocardiographic formulas for determining left ventricular stroke volume: a correlative study with thermodilution and left ventricular single plane cineangiography. Circulation. 1979;60:1308-1316.[Abstract/Free Full Text]

32. Asanoi H, Sasayama S, Kameyama T. Ventriculoarterial coupling in normal and failing heart in humans. Circ Res. 1989;65:483-493.[Abstract/Free Full Text]

33. de Simone G, Daniels SR, Devereux RB, Meyer RA, Roman MJ, de Divitiis O, Alderman MH. Left ventricular mass and body size in normotensive children and adults: assessment of allometric relations and impact of overweight. J Am Coll Cardiol. 1992;20:1251-1260.[Abstract]

34. de Simone G, Devereux RB, Daniels SR, Koren MJ, Meyer RA, Laragh JH. Effects of growth on body size: left ventricular mass relations and impact on prediction of cardiovascular risk. J Am Coll Cardiol. 1995;25:1056-1062.[Abstract]

35. Dustan HP, Tarazi RC, Mujais S. A comparison of hemodynamic and volume characteristics of obese and non-obese hypertensive patients. Int J Obes. 1981;5:19-25.

36. Raison J, Achimastos A, Asmar R, Simon A, Safar M. Extracellular and interstitial fluid volume in obesity with and without associated systemic hypertension. Am J Cardiol. 1986;57:223-226.[Medline] [Order article via Infotrieve]

37. de Simone G, Daniels S, Roman MJ, Kimball TR, Witt S, Greco R, Mureddu GF, Contaldo F. Relation of stroke volume to body size in normotensive children and adults: assessment of allometric signals and effect of obesity. Circulation. 1995;92(suppl):I-278. Abstract.

38. Blake J, Devereux RB, Borer JS, Szulc M, Pappas TW, Laragh JH. Relation of obesity, high sodium intake and eccentric left ventricular hypertrophy to left ventricular exercise dysfunction in essential hypertension. Am J Med. 1990;88:477-485.[Medline] [Order article via Infotrieve]

39. Keteluth R, Losem CJ, Messerli FH. Is a decrease in arterial pressure during long-term aerobic exercise caused by a fall in cardiac pump function? Am Heart J. 1994;127:567-571.[Medline] [Order article via Infotrieve]

40. Alpert MA, Singh A, Terry BE, Kelly DL, Villarael D, Mukerji V. Effect of exercise on left ventricular systolic function and reserve in morbid obesity. Am J Cardiol. 1989;63:1478-1482.[Medline] [Order article via Infotrieve]

This article has been cited by other articles:

				M. Chinali, G. de Simone, M. J. Roman, E. T. Lee, L. G. Best, B. V. Howard, and R. B. Devereux Impact of Obesity on Cardiac Geometry and Function in a Population of Adolescents: The Strong Heart Study J. Am. Coll. Cardiol., June 6, 2006; 47(11): 2267 - 2273. [Abstract] [Full Text] [PDF]

				R S Vasan Cardiac function and obesity Heart, October 1, 2003; 89(10): 1127 - 1129. [Full Text] [PDF]

				B. M. Mitchell, B. Gutin, G. Kapuku, P. Barbeau, M. C. Humphries, S. Owens, S. Vemulapalli, and J. Allison Left Ventricular Structure and Function in Obese Adolescents: Relations to Cardiovascular Fitness, Percent Body Fat, and Visceral Adiposity, and Effects of Physical Training Pediatrics, May 1, 2002; 109(5): e73 - 73. [Abstract] [Full Text] [PDF]

				J. Mayet, B. Ariff, B. Wasan, N. Chapman, M. Shahi, N. R. Poulter, P. S. Sever, R. A. Foale, and S. A. McG. Thom Improvement in Midwall Myocardial Shortening With Regression of Left Ventricular Hypertrophy Hypertension, November 1, 2000; 36(5): 755 - 759. [Abstract] [Full Text] [PDF]

				J. P. Adams and P. G. Murphy Obesity in anaesthesia and intensive care Br. J. Anaesth., July 1, 2000; 85(1): 91 - 108. [Full Text] [PDF]

				A. Cittadini, C. S. Mantzoros, T. G. Hampton, K. E. Travers, S. E. Katz, J. P. Morgan, J. S. Flier, and P. S. Douglas Cardiovascular Abnormalities in Transgenic Mice With Reduced Brown Fat : An Animal Model of Human Obesity Circulation, November 23, 1999; 100(21): 2177 - 2183. [Abstract] [Full Text] [PDF]

				S. H. Dunlap, C. A. Sueta, L. Tomasko, and K. F. Adams Jr. Association of body mass, gender and race with heart failure primarily due to hypertension J. Am. Coll. Cardiol., November 1, 1999; 34(5): 1602 - 1608. [Abstract] [Full Text] [PDF]

				J. N. Bella, M. J. Roman, R. Pini, J. E. Schwartz, T. G. Pickering, and R. B. Devereux Assessment of Arterial Compliance by Carotid Midwall Strain-Stress Relation in Normotensive Adults Hypertension, March 1, 1999; 33(3): 787 - 792. [Abstract] [Full Text] [PDF]

				R. B. Devereux, G. de Simone, T. G. Pickering, J. E. Schwartz, and M. J. Roman Relation of Left Ventricular Midwall Function to Cardiovascular Risk Factors and Arterial Structure and Function Hypertension, April 1, 1998; 31(4): 929 - 936. [Abstract] [Full Text] [PDF]

This Article Abstract Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Permissions Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by de Simone, G. Articles by Laragh, J. H. Search for Related Content PubMed PubMed Citation Articles by de Simone, G. Articles by Laragh, J. H.