The influence of obesity duration on left ventricular mass, volume and function: A pilot study

Abstract

Introduction: Despite the bulk of evidence between obesity and cardiovascular complications, the effect of the duration of obesity (DOO) on cardiac function has so far received limited attention. The aim of the study is to study the relationship between a new, American Heart Association (AHA) and World Health Organization (WHO)-adapted formula for reporting DOO with echocardiographic findings and comorbidities in a large cohort of individuals whose BMI ranged from normal (<25 Kg·m2) to morbid obesity (>40 Kg·m2) and had been obese for varying lengths of time. Methods: 198 (M60/F138) asymptomatic patients were recruited. Patients were classified according to their reported DOO. The normal weight group (N = 92 (40/F52) was formed by those patients who did not recall maintaining a BMI > 30 Kg·m2 from age 18 while those recalling maintenance of a BMI > 30 Kg·m2 since age 18 and thereafter formed the obese group (N = 106 (M20/F86)). A detailed clinical, echo-cardiographic and analytical study was performed. Results: DOO in our series disclosed a significant correlation with left ventricular architecture and hemodynamics, left ventricular mass, cardiac output as well as the prevalence of diabetes mellitus, hypertension and insulin resistance. Stepwise multiple regression analysis revealed that almost 54% of the interventricular septum thickness’s variance can be independently predicted by a model including DOO, gender, hypertension and logtransformed HOMA. Conclusions: Our formula for estimating the duration of obesity provides a simple, user-friendly tool whose utilization in bariatric preoperative assessments and in advanced nursing practice deserves prospective studies.

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Ybarra, J. , Romeo, J. , Férnandez, S. and Sanchez-Hernandez, J. (2012) The influence of obesity duration on left ventricular mass, volume and function: A pilot study. Health, 4, 1420-1427. doi: 10.4236/health.2012.412A205.

1. BACKGROUND

Obesity is a worldwide epidemic; 66% of United States adults are overweight or obese [1], and a prevalence of obesity up to 31% has been reported in Europe [2]. If current trends continue, the number of obese individuals is expected to rise to over 1 billion worldwide by 2030 [3].

Obesity is associated with an increased risk of morbidity and mortality and is associated with reduced life expectancy [4,5]. There is a considerable body of data confirming obesity as a risk factor for severe cardiovascular complications, such as coronary heart disease, heart failure, stroke and venous thromboembolic disease [6-10]. Despite the bulk of evidence between obesity and cardiovascular complications [6-10], the permanent effects of obesity on cardiac function have so far received limited attention. Indeed, one publication reports longer duration of morbid obesity (estimated by subtracting the current age from the age at which the individual’s body weight equalled or exceeded twice their ideal body weight, the latter being derived from 1993 Metropolitan Life Insurance Tables) being associated with higher left ventricular (LV) mass, poorer LV systolic function, and greater impairment of LV diastolic filling [11].

Historically, the Metropolitan Life Insurance Company data that express body fat as percent ideal body weight have been used [12], but currently overweight and obesity are classified by body mass index (BMI). BMI (weight in kg/height2 in meters) is frequently used as a surrogate measure of fatness in children and adults. In adults, overweight is defined as a BMI of 25.0 to 29.9 Kg/m2; obesity is defined as a BMI ≥ 30.0 Kg/m2 [13,14]. Noteworthy, the correlation between self-reported duration of obesity (estimated by subtracting the current age from the age at which the individual’s BMI equalled or exceeded 30.0 Kg∙m−2), according with previous obesity definitions [13,14] and co-morbidities and echocardiographic findings has not, to the best of our knowledge, been correlated in large series of patients. Hence, we sought to study the relationship between this new American Heart Association (AHA) and World Health Organization (WHO)-adapted formula for reporting duration of obesity with echo-cardiographic findings (LV mass, internal dimensions in systole and diastole and diastolic dysfunction), co-morbidities and metabolic parameters (adiponectin and the HOMA-IR index) in a large cohort of individuals whose BMI ranged from normal (<25 Kg∙m−2) to morbid obesity (>40 Kg∙m−2) and who had been obese for varying lengths of time.

2. MATERIALS AND METHODS

2.1. Patient Population

One hundred and ninety eight (N = 198; M/F = 60/138) asymptomatic patients without underlying cardiac disease were included in the study. They were consecutively recruited from 1) the pool of individuals attending Centro Laparoscópico Ballesta (CLB) at Centro Médico Teknon and 2) from the pool of apparently healthy patients undergoing routine medical check-ups during that same time-period at the same medical facility (Medical Check-up Unit, Centro Médico Teknon) in Barcelona, Spain from January 1st until December 31st 2010.  

Exclusion criteria were: current coronary artery disease, current/prior angina, or myocardial infarction, current/prior history of arrhythmia, cardiovascular co-morbidity (prior cerebrovascular accidents and/or peripheral vascular disease), current therapy with vasoactive drugs, statins or fibrates, current/prior alcohol consumption averaging > 60 g/day, active smoking, creatinine > 2 mg/dl, presence of neoplasia and/or systemic disease, suboptimal echocardiographic window.   

From age 18 on, the time period (years) in which patients had sustained a body weight corresponding to a BMI ≥ 30 Kg∙m−2 was defined as duration of obesity (DOO years). Briefly, the body weight (Kg) corresponding to a BMI of 30 Kg∙m−2 was calculated as the squared height times 30, according to the AHA and WHO definition of obesity [13,14]. Thus, asking the patient how many years since age 18 had she/he maintained that body weight defined the duration of obesity. The duration of obesity information was obtained by the same trained observer (JY), using a systematic mode of in-person interview during the initial visit. Patients were further sub-classified into two groups, according to the reported DOO. Those patients who did not recall maintaining a body weight corresponding to a BMI ≥ 30 Kg∙m−2 from age 18 and thereafter formed the normal weight group (NW group) while those recalling maintaining a body weight corresponding to a BMI ≥ 30 Kg∙m−2 since age 18 and thereafter formed the obese group (Obese group). Anthropometrical measurements were performed by the same trained observer (JY) after participants had removed their shoes and heavy clothing. Weight (digital scales: Seca, Germany) and height (portable stadiometers: Holtain, Crymych, UK) were obtained and body mass index (BMI), defined as weight (Kg) divided by the height squared (in meters) was calculated. Excessive body weight (EBW) is reported according to Deitel et al. [15].

All patients underwent a detailed clinical, biochemical and echocardiography study. Patients were considered to be hypertensive according to Mancia’s criteria [16].

Written informed consent was obtained from each patient according to the standards established by the hospital’s ethics committee.

2.2. Echocardiography

A Standard two-dimensional M-mode color Doppler echocardiography was performed on all patients using a 2.5 MHz transducer (ALOKA ProSound SSD-4000) by the same experienced echocardiographist according to an established protocol. 

Telediastolic and telesystolic left ventricular (LV) diameters were measured whereas volume and cardiac output were calculated according to Teicholz’s formula [17]. LV mass was calculated by means of Devereux’s formula [18]. LV hypertrophy was defined according to Framingham’s criteria (LV mass/BSA > 110 g/m2 in females and LV mass/BSA > 134 g/m2 in males) [19]. LV, left atrium (LA) and inter-ventricle septum (IVS) measurements were determined according to the American Society of Echocardiography [20]. LA enlargement was defined as LA size > 40 mm. 

Intra-observer variability was estimated to be 0.0 - 1.0 mm and 5% for wall thickness assessment and LV diameters, respectively.   

2.3. Biochemical Measurements

Blood samples were drawn from each subject after an overnight fast (10 - 12 hours). Serum was spun at 4000 g for 10 min, immediately divided into aliquots, and frozen at –80˚C until analysis. Serum glucose concentrations were measured in duplicate by the glucose oxidase method with the use of a Beckman Glucose Analyser II (Beckman Instruments, Brea, CA). The coefficient of variation was 1.9%. 

Insulin was measured using an immunocheminoluminometric assay (IMMULITE Diagnostic Products Corporation, Los Angeles, CA). The intraand inter-assay coefficient of variation was 3% and 7%, respectively. Cross-reactivity with pro-insulin was less than 0.01%. Insulin Resistance was estimated using the HOMA-IR index [21].

Plasma adiponectin concentrations were measured using a commercial human adiponectin RIA kit (Linco, Labodia SA, Yens, Switzerland) whose detection limit and intraand inter-assay coefficient of variation were 2.0 ng/ml, 5.0 and 5.0%, respectively. Normal adiponectin results were considered above 10.0 µg/ml [22]. Cholesterol and triglycerides were measured by enzymatic methods; LDL-cholesterol was calculated by Friedwald’s formula and HDL-cholesterol after precipitation of apoB containing lipoproteins.  

2.4. Statistical Analysis

The sample size was calculated as follows: assuming an α risk of 0.05, a β risk of 0.10, and a unilateral test, 50 subjects were needed in each group to detect a statisticcally significant correlation, with r = 0.30. A greater number of patients were included to further decrease the α and β risks. Before statistical analysis, normal distribution and homogeneity of the variances were tested. Qualitative variables are expressed as sample size (number of cases) and percentage (%), and quantitative variables are expressed as mean and standard error of the mean (SEM). The relationship between two qualitative variables was assessed using Chi-squared test with a continuity correction whenever necessary. The relationship between two quantitative variables was assessed using Pearson’s correlation coefficient. Level of statisticcal significance was set at P < 0.05. Data were analysed and figures constructed using the SPSS 15.0 statistical package (SPSS Inc., Chicago, IL, USA).

3. RESULTS

Demographic and biochemical characteristics of the participants are illustrated in Table 1. The study population (including both groups) was 70% female, and included a wide spectrum of BMI ranging from 22 to 70 kg/m2. Age ranged from 20 to 65 in women and to 55 in men. There were no age differences between both groups.

As shown, BMI, body weight and obesity duration were higher in the obese group (P < 0.0005; for all three). Moreover, both heart rate, systolic and diastolic blood pressure values were also higher in the obese group (P < 0.0005). Hypertension and diabetes were more prevalent in the obese group while basal glucose, insulin and HOMA-IR were higher (P < 0.0005) and adiponectin lower in the obese group (P < 0.001). Lipid profiles were similar between both groups. The TG/HDL-C ratio was significantly higher in the obese group (P < 0.0005). Heart rate was lower while systolic and diastolic blood pressures were lower in the NW group (P < 0.005 for all). All patients displayed a regular sinus rhythm on twelve lead surface electrocardiograms (data not shown).

Table 1. Demographic and biochemical characteristics of the participants. NW: normal weight, BMI: Body Mass Index, SBP: systolic blood pressure, DLP: dyslipidemia, DBP: diastolic blood pressure, HR: heart rate, HOMA-IR: homeostasis model assessment. ***P < 0.0005, **P < 0.001, *P < 0.05.

Echocardiographic characteristics of the participants appear illustrated in Table 1. As depicted, ejection fraction (EF) was similar between both groups. On the contrary, left ventricle mass (LVM), inter-ventricular septum (IVS), Teicholz’s cardiac output (CO-Tei), left atrium size (LA) and diastolic and systolic cardiac volumes (DV, SV) and diameters (DD, SD) were significantly higher in the obese group (P < 0.0005).

Univariate correlation analysis of obesity duration vs. demographic, biochemical and echocardiographic parameters are depicted in Table 2. The first column stands for the entire population while the second and third columns show the results of male and female participants, respectively.

As shown, direct significant correlations appear between the DOO and diastolic and systolic cardiac vol-

Table 2. Univariate correlation analysis of duration of obesity vs demographic, biochemical and echocardiographic parameters. r: Univariate (Pearson’s) correlation coefficients; EF: ejection fraction, LVM: left ventricle mass, IVS: interventricle septum, CO-Teicholz: cardiac output by Teicholz method, DV: diastolic volume, SV: systolic volume, DD: diastolic diameter, SD: systolic diameter, HTN: hypertension prevalence, DM2: diabetes mellitus prevalence, LogHOMA: log-transformed homeostasis model assessment, LogAdp: log-transformed adiponectin, LogTG_HDL-C: log transformed [TG/HDL_C] ratio. ***: P < 0.001, **: P < 0.01, *: P < 0.05.

umes and diameters as well as cardiac output in the whole population and in the female group. Conversely, these correlations did not reach statistical significance in the male participants. The inter-ventricular septum and left atrium showed a more robust correlation with the DOO in the male group while the left ventricular mass correlation only reached significance in the female group. Conversely, ejection fraction indexes showed no correlation with the duration of obesity in either group.

Similar statistically significant correlations were found between BMI and/or excess body weight (EBW) with all the echocardiographic parameters described previously, gender bias included (data not shown). Noteworthy, all the echocardiography results provided by our apparel take into account height and weight.

Regarding co-morbidities and metabolic parameters for the whole group, the self-reported DOO disclosed direct significant correlations with hypertension and diabetes prevalence, log-transformed HOMA and log-transformed TG/HDL-C ratio. An inverse significant correlation appeared with log-transformed adiponectin. Male participants disclosed more robust correlations than their female counterparts. The correlation between diabetes mellitus and the duration of obesity did not reach statistical significance in female participants.

Table 3 illustrates a stepwise multiple regression analysis including variables related to inter-ventricular septum thickness (IVS; dependent variable). As shown, 53.9% of its variance can be independently predicted by the DOO, gender, hypertension and log-transformed HOMA. Excluded variables were age, systolic and diastolic blood pressure values, heart rate, diabetes and logtransformed adiponectin. Self-reported DOO accounts for as much as 30.0% of IVS’s variance by itself in this model whereas gender, hypertension and log transformed HOMA add (11%, 2.8% and 3.0%, respectively) of the variance (data not shown).

Conflicts of Interest

The authors declare no conflicts of interest.

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