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Abstract

  1. Top of page
  2. Abstract
  3. Introduction
  4. Methods and Procedures
  5. Results
  6. Discussion
  7. REFERENCES

Alterations in left ventricular mass and geometry vary along with the degree of obesity, but mechanisms underlying such covariation are not clear. In a case–control study, we examined how body composition and fat distribution relate to left ventricular structure and examine how sustained weight loss affects left ventricular mass and geometry. At the 10-year follow-up of the Swedish obese subjects (SOS) study cohort, we identified 44 patients with sustained weight losses after bariatric surgery (surgery group) and 44 matched obese control patients who remained weight stable (obese group). We also recruited 44 matched normal weight subjects (lean group). Dual-energy X-ray absorptiometry, computed tomography, and echocardiography were performed to evaluate body composition, fat distribution, and left ventricular structure. BMI was 42.5 kg/m2, 31.5 kg/m2, and 24.4 kg/m2 for the obese, surgery, and lean groups, respectively. Corresponding values for left ventricular mass were 201.4 g, 157.7 g, and 133.9 g (P < 0.001). In multivariate analyses, left ventricular diastolic dimension was predicted by lean body mass (β = 0.03, P < 0.001); left ventricular wall thickness by visceral adipose tissue (β = 0.11, P < 0.001) and systolic blood pressure (β = 0.02, P = 0.019); left ventricular mass by lean body mass (β = 1.23, P < 0.001), total body fat (β = 1.15, P < 0.001) and systolic blood pressure (β = 2.72, P = 0.047); and relative wall thickness by visceral adipose tissue (β = 0.02, P < 0.001). Left ventricular adjustment to body size is dependent on body composition and fat distribution, regardless of blood pressure levels. Obesity is associated with concentric left ventricular remodeling and sustained 10-year weight loss results in lower cavity size, wall thickness and mass.


Introduction

  1. Top of page
  2. Abstract
  3. Introduction
  4. Methods and Procedures
  5. Results
  6. Discussion
  7. REFERENCES

Obesity is frequently associated with disturbances in cardiac structure (1). Left ventricular changes include increments in both chamber size and wall thickness (2) and lead to left ventricular hypertrophy (3), a powerful risk factor for cardiovascular morbidity and mortality. Altered left ventricular structure in obese people is considered to be a result of increased hemodynamic load (4) and metabolic aberrations (5) occurring along with body fat accumulation. Also, sleep disordered breathing with recurrent hypoxia, which frequently occurs in obese subjects, may contribute to left ventricular structural aberrations via various hormonal and hemodynamic mechanisms (6).

Some of the cardiovascular variation found in obese people is related to the hemodynamic changes that occur with an accumulation of excess body fat (7). As weight increases, total blood volume and cardiac output rise and cause volume overload leading to eccentric hypertrophy. Moreover, obesity is frequently associated with the development of arterial hypertension, a state of pressure overload that results in concentric hypertrophy. With time obesity may thus lead to various degrees of eccentric and/or concentric left ventricular hypertrophy.

Stimuli other than hemodynamic factors are also likely to be of importance in the development of cardiovascular disturbances in obese people (8). Obesity is associated with a cluster of metabolic and hormonal disturbances and it has been suggested that some of them could be involved in the modulation of left ventricular structure. Indeed, some investigators have reported a correlation between measurements of insulin resistance and left ventricular mass (9).

Both lean body mass and adipose tissue increase as obesity develops, but the hemodynamic and metabolic effects of these body compartments differ widely. Furthermore, the distribution body fat is of importance, since metabolic disturbances are associated with abdominal obesity in particular (10). In this respect, the separate effects of different body compartments and fat distribution on cardiac structure are of interest.

Short-term weight reduction has been reported to be associated with regression of left ventricular mass (11,12), but the effects of long-term sustained weight loss on cardiac geometry have not been described. Further, little is known about the influence of different body compartments and fat distribution on left ventricular structure. The aim of this study was to investigate the long-term effects of sustained weight loss on cardiac structure and study how body composition and adipose tissue distribution relate to left ventricular mass and geometry.

Methods and Procedures

  1. Top of page
  2. Abstract
  3. Introduction
  4. Methods and Procedures
  5. Results
  6. Discussion
  7. REFERENCES

The Swedish obese subjects (SOS) study is a prospective, controlled, surgical interventional trial, which enrolled 4,047 obese subjects at 25 surgical departments and 480 primary health care centers in Sweden (13). The study protocol is described in detail elsewhere (13,14). Briefly, the surgery group comprised 2,010 eligible subjects desiring surgery and, at the same time, a matched control group of 2,037 obese subjects. Inclusion criteria were age ranging from 37 to 60 years and BMI of ≥34 for men and of ≥38 or more for women. The exclusion criteria, aiming to obtain operable patients, were the same for both study groups.

Patients included in the present case–control study were recruited among participants of the SOS study that had been monitored for at least 10 years. We identified 44 surgery patients who, after 10 years, displayed a weight loss of >15% and 44 obese control patients, in which the weight had changed <5%. To ensure that the surgery group, prior to intervention, was comparable with the obese group, the two groups were carefully matched with respect to baseline data from the SOS study. Matching variables included age, gender, BMI, hypertension, hyperlipidemia, diabetes, and smoking status (Table 1).

Table 1.  Clinical characteristics of the obese and surgery groups (s.d. or %) at baseline in the SOS study
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In addition, we included 44 healthy normal weight patients, recruited from a randomly selected sample of adults living in the municipality of Mölndal (15), who matched the surgery and obese groups at the 10-year follow-up with respect to age, height, and smoking status. In total, 132 subjects were included in the study, comprising 69 women and 63 men with ages ranging from 44 to 71 years. The three study groups were examined cross-sectionally with respect to body composition and left ventricular structure. In addition, 10-year prospective follow-up data on anthropometry and metabolic parameters were available for the obese and surgery groups from the SOS study, but not for the lean group. The study protocol was approved by the ethics committee at the University of Gothenburg, and all study subjects gave their informed consent to participate.

Measurements of weight and height were obtained and BMI was calculated as follows: body weight divided by height squared. Blood pressure was measured in the supine position after 10-min rest and the mean of the two recordings was registered. Blood samples were obtained in the morning after a fast of 12 h and analyzed at the Central Laboratory of Sahlgrenska University Hospital (accredited according to European norm 45001). An estimate of insulin resistance was calculated according to the Homeostasis Model Assessment (16).

Lean body mass and total body fat was measured with a whole-body dual-energy X-ray absorptiometry scanner (DPXL; Lunar Radiation, Madison, WI) using software version 1.35. Repeated daily examinations in 10 females showed a coefficient of variance for lean body mass and total body fat of 0.7% and 1.7%, respectively.

Intra-abdominal and subcutaneous adipose tissue areas were measured at the level of the fourth lumbar vertebra using a single slice Computed Tomography scan (HSA, version RP2; GE Medical Systems, Milwaukee, WI). Adipose tissue areas were evaluated in accordance with the method described by Chowdhury et al. (17). Precision errors, calculated from double determinations, were for intra-abdominal and subcutaneous adipose tissue 1.2% and 0.5%, respectively. A reduction protocol for radiation dose was used resulting in an effective radiation dose equivalent to <0.8 msv per examination (18).

Echocardiographic examinations were performed by use of an Acuson Sequoia 512 ultrasound system with 2.5-3.5 MHz transducers (Siemens, Mountain View, CA). Data were acquired with the subject in the left lateral decubitus position at end-expiration. All measurements were averages deriving from three consecutive cardiac cycles. Left ventricular dimension along with interventricular septal and posterior wall thickness were determined at end-diastole by means of two-dimensionally guided m-mode examinations obtained from the parasternal short axis view. Measurements were performed with the leading-edge to leading-edge principle at the onset of the QRS wave according to the recommendations of the American Society of Echocardiography (19). The mean wall thickness, derived by averaging septal and posterior wall dimensions, was used in data analyses. Relative wall thickness was defined as the ratio of mean wall thickness to left ventricular end-diastolic dimension. Left ventricular mass was determined from two-dimensional echocardiograms using the truncated ellipsoid model according to Byrd et al. (20).

Recordings were performed by two dedicated research sonographers and analyzed by a single observer blinded with respect to the subjects using customized dedicated research software (Echopac; GE Vingmed Sound, Horten, Norway). For evaluation of left ventricular mass, only good-quality readings were accepted, which for technical reasons can be difficult to achieve, especially in obesity. Despite this, satisfactory recordings were obtained in 70%, 86%, and 100% of patients in the obese, surgery, and lean groups, respectively. Within obese and surgery groups there were no clinical differences between subjects for whom adequate recordings were available and those for whom they were not. In our laboratory, the intraobserver and interobserver coefficient of variation for determination of left ventricular mass have been found to be 11.4% and 17.9%, respectively.

Statistical analyses were performed using the SPSS for Windows version 15 (SPSS, Chicago, IL). Descriptive statistical results are given as the mean (s.d.) or proportions (%). ANOVA was used to assess linear trend of parameters in the three groups, and Bonferroni post hoc testing was undertaken for comparisons between groups, obese vs. surgery and surgery vs. lean. χ2 analysis was used for categorical variables. After pooling 10-year data from the obese and surgery groups and data from the lean group, correlation coefficients were calculated in order to estimate associations between clinical variables and measurements of left ventricular mass and geometry. Forward stepwise multiple regression analyses, with age and sex forced into the model, were then used to determine which of the clinical variables were independently associated with the indices of left ventricular structure. A P value of <0.05 was considered significant.

Results

  1. Top of page
  2. Abstract
  3. Introduction
  4. Methods and Procedures
  5. Results
  6. Discussion
  7. REFERENCES

Clinical characteristics

Table 1 shows data from the SOS study by means of which the obese and surgery groups were matched at baseline. The two groups were quite comparable with respect to clinical parameters apart from diastolic blood pressure which was slightly higher in the surgery group.

Table 2 shows clinical characteristics of the obese and surgery groups after 10 years of follow-up in the SOS study and for the matched lean group. The lean group was somewhat younger than the obese and surgery group but of comparable height. As compared with the obese group, the surgery group showed lower body weight, BMI and diastolic blood pressure. The surgery group also had lower triglycerides, glucose and insulin and higher high-density lipoprotein than the obese group. Surgery patients smoked more often but had less diabetes and hypertensive treatment than the obese patients. As compared with the surgery group, the lean group showed lower body weight, BMI, glucose and insulin. None of the lean patients had diabetes or were treated with antihypertensive medication.

Table 2.  Clinical characteristics and body composition assessed by DXA and CT at the 4th lumbar vertebra of obese, surgery, and lean groups (s.d. or %)
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Body composition

Dual-energy X-ray absorptiometry measurements of lean body mass and total body fat and CT measurements of intra-abdominal and subcutaneous adipose tissue area at L4 are shown in Table 2. All body composition parameters decreased significantly across the groups in the order from obese to surgery to lean groups.

Echocardiography

Results from the echocardiography investigations can be seen in Figure 1. The surgery group showed significantly lower left ventricular dimension, mean wall thickness and mass as compared to the obese group and higher left ventricular wall thickness and mass as compared with the lean group. The obese group displayed significantly higher relative wall thickness as compared with the lean group. When analyzed separately for males and females, trends in left ventricular structure across study groups remained similar for both genders (data not shown).

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Figure 1. Bar diagrams displaying means and standard deviation for echocardiographic measures of left ventricular structure by study group. Results from overall comparisons with ANOVA (upper right corner) and post hoc analyses according to Bonferroni are shown.

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Univariate and multivariate analysis

Correlation coefficients for associations between clinical variables and left ventricular measurements can be seen in Table 3. Left ventricular end-diastolic diameter correlated positively with lean body mass and showed a weak negative correlation with cholesterol. Left ventricular wall thickness, left ventricular mass and relative wall thickness displayed significant positive correlations with measurements of body composition, fat distribution, systolic blood pressure, glucose, insulin and Homeostasis Model Assessment index.

Table 3.  Univariate correlation coefficients (r) of body compartments, fat distribution and blood pressure on LVED, WT, LVM, and RWT
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Stepwise multiple regression analyses for lean body mass, total body fat, visceral adipose tissue and systolic blood pressure on left ventricular measurements are shown in Table 4. Age and sex were also forced into the models, but this did not affect the relationships between body composition and left ventricular structure. Left ventricular end-diastolic diameter was related to lean body mass only, whereas left ventricular wall thickness was independently associated with intra-abdominal adipose tissue area and systolic blood pressure. Left ventricular mass was positively and independently related to lean body mass, total adipose tissue and systolic blood pressure, whereas relative wall thickness was solely associated with visceral adipose tissue area. Other exploratory multivariate models including metabolic variables showed no independent relationships between these measures and left ventricular structure, when body composition was accounted for (data not shown).

Table 4.  Forward stepwise regression analyses of left ventricular measures on body composition, fat distribution, and systolic blood pressure with age and sex forced into the model
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Discussion

  1. Top of page
  2. Abstract
  3. Introduction
  4. Methods and Procedures
  5. Results
  6. Discussion
  7. REFERENCES

In the present study, we have shown that the left ventricle in obese subjects adapts to long-term sustained weight loss with a smaller cavity, thinner walls and lower left ventricular mass. The adjustment of left ventricular structure to body size appears to be dependent on body composition and distribution of body fat. Also, systolic blood pressure was found to be of importance with respect to left ventricular mass and geometry, but none of the metabolic variables measured in this study were independently related to cardiac structure.

Weight loss and cardiac structure

The high prevalence of left ventricular hypertrophy in obese people is of great importance as it may increase their risk of premature morbidity and mortality. Previous studies have shown that short-term weight reduction with a maximum follow-up of 1 year is associated with regression of left ventricular hypertrophy (11,12,21). In the present study, we have shown that long-term weight loss maintained over 10 years is associated with a significant and sustained reduction in cavity size, wall thickness, and left ventricular mass.

To some extent, the regression of myocardial muscle mass following weight loss could be considered to be a simple adjustment to a change in body size. However, reversibility of cardiac structure associated with weight reduction should probably be regarded as favorable since left ventricular hypertrophy in obesity is, at least in part, a maladaptive process related to abnormal hemodynamic and metabolic stimuli and a marker of increased risk.

Determinants of left ventricular dimension

Obesity is associated with increased blood volume and cardiac output and such hemodynamic changes have been assumed to be secondary to metabolic demands of excess adipose tissue (7). In the present study, however, left ventricular dimension was predicted solely by lean body mass, suggesting that volume overload and chamber enlargement is more dependent on the obesity-associated increase in lean body mass than on the actual body fat accumulation. The mechanisms underlying the rise of lean body mass in obesity are poorly understood, but increased workload on ambulation has been suggested to be a contributing factor.

Our findings indicate that the metabolic requirements of increased muscle mass are a more important regulator of blood flow than the needs of expanded adipose tissue. Supportive of this are observations from the Strong heart study, in which fat free mass was a stronger determinant of stroke volume and cardiac output than adipose mass (22). Resting blood flow has been shown to be higher in skeletal muscle than that in adipose tissue (23) and the perfusion per unit of adipose tissue actually decreases with increasing obesity (24). Also, during exercise, blood flow to skeletal muscle increases far more than that to adipose tissue, which may further add to the impact of lean body mass on left ventricular chamber size.

Determinants of left ventricular wall thickness

The previous belief that obesity gives rise to eccentric left ventricular hypertrophy (25) has been contradicted by more recent studies showing that obese subjects, irrespective of their blood pressure levels, have increased wall thickness to cavity size, consistent with concentric remodeling (6,26,27). This is in accordance with the observations of the present study, which adds to the growing bulk of evidence supporting that obesity, in contrast to conventional views, promotes concentric left ventricular remodeling. Our finding that intra-abdominal fat was the main predictor of left ventricular wall thickness sheds further light on the issue by suggesting that accumulation of visceral adipose tissue, may be involved in the pathogenesis of concentric left ventricular hypertrophy.

The association between visceral fat and wall thickness was independent of blood pressure and in line with the findings of Morricone and co-workers, who reported an independent relationship between visceral fat and septum thickness in an obese population with normal blood pressure (28). In this context, the cluster of metabolic and hormonal aberration associated with visceral adiposity is of great importance, as it may modulate left ventricular structure. Insulin resistance with secondary hyperinsulinemia has been suggested to mediate the effects of visceral adipose tissue on left ventricular structure (29,30) but neither insulin nor any other metabolic variable measured in this study were independently related to wall thickness. Sleep disordered breathing, which frequently occurs in abdominal obesity, could also contribute to left ventricular structural aberrations through repetitive hypoxia and sympathetic nervous system activation (6). Others have suggested that the renin–angiotensin–aldosterone system may be a link between visceral adiposity and cardiovascular abnormalities (31).

Determinants of left ventricular mass

Left ventricular mass is determined not only by the size of the ventricle but also by the thickness of its walls and both components are frequently increased in obesity. Increased chamber size appears mainly related to increased lean body mass, which probably should be regarded to be a normal cardiac adaptation, matching the augmented perfusion needs of expanded fat free tissue. Support for this is found in a study by Hense et al., in which adjustments for fat- free mass eliminated gender differences in left ventricular mass (32). Consequently, lean body mass has been proposed as the optimal normalization of left ventricular mass to body size (33).

A rise in wall thickness is, on the contrary, linked to accumulation of body fat and visceral adipose tissue, in particular. This is most likely a maladaptive process related to abnormal hemodynamic, metabolic, and hormonal stimuli. In conformity, concentric geometry has been shown to carry a higher risk than eccentric hypertrophy. Therefore, it seems reasonable to avoid correcting left ventricular mass for measures that are strongly affected by the existing amount of adipose tissue, such as BMI and body surface area. Still, prospective will be needed to clarify the prognostic significance of various indexations of left ventricular mass, not least in subgroups like the obese population.

Limitations

The main limitation of the present study was that echocardiographic examinations for the obese and surgery groups were not performed prior to inclusion in the SOS study. This weakens our conclusions with respect to the effect of weight loss on left ventricular structure. On the other hand, these two groups were carefully matched with respect to important SOS baseline characteristics, resulting in two almost identical groups prior to inclusion. It is therefore reasonable to assume that left ventricular mass and geometry did not differ between obese and surgery groups at baseline in the SOS study. Further, our study is unique with respect to the long-term follow-up of obese subjects with large and sustained weight losses. Such patient populations have rarely been studied previously due to the difficulties in attaining reliable long-term weight reductions with conventional therapy.

Conclusion

Left ventricular adjustment to body size is dependent on body composition and fat distribution. Different body compartments have disparate effects on left ventricular structure, regardless of blood pressure levels. Whereas lean body mass determines cavity size, visceral adipose tissue is the main contributor to absolute and relative wall thickness. In contrast to previous beliefs, obesity was found to be associated concentric left ventricular remodeling, possibly mediated by intra-abdominal adiposity. Ten years of maintained weight loss is associated with favorable reductions in left ventricular cavity size, wall thickness, and mass.

REFERENCES

  1. Top of page
  2. Abstract
  3. Introduction
  4. Methods and Procedures
  5. Results
  6. Discussion
  7. REFERENCES