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J Am Coll Cardiol, 2006; 47:2267-2273, doi:10.1016/j.jacc.2006.03.004 © 2006 by the American College of Cardiology Foundation |

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* Department of Medicine, New York Presbyterian Hospital-Weill Medical College of Cornell University, New York, New York
Department of Clinical and Experimental Medicine, "Federico II" University Hospital School of Medicine, Naples, Italy
University of Oklahoma School of Public Health Science, Oklahoma City, Oklahoma
Missouri Breaks Industries Research, Inc., Timber Lake, South Dakota
|| MedStar Research Institute, Washington, DC
Manuscript received October 18, 2005; revised manuscript received December 5, 2005, accepted December 13, 2005.
* Reprint requests and correspondence: Dr. Giovanni de Simone, Echocardiography Laboratory, Department of Clinical and Experimental Medicine, "Federico II" University School of Medicine, Via S. Pansini 5, 80131 Napoli, Italy (Email: simogi{at}unina.it).
| Abstract |
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BACKGROUND: There is little information on how much the excess of body weight impacts LV geometry and function in populations of adolescents.
METHODS: Anthropometric, laboratory, and Doppler echocardiographic parameters of cardiac geometry and function were obtained in 460 adolescent participants (age 14 to 20 years, 245 female participants, 27 hypertensive, 10 with diabetes) from the Strong Heart Study. Body build was classified based on 85th and 95th percentiles of body mass index (BMI)-for-age charts.
RESULTS: Range of BMI was 16.3 to 56.5 kg/m2 (28.8 ± 8.3 kg/m2); 114 participants (24.9%) fell within the 85th percentile of BMI distribution (normal weight [NW]), 113 (24.6%) fell between 85th and 95th percentile (overweight [OW]), and 223 (48.5%) fell above the 95th percentile (obese [OB]). Obese participants were older than OW and NW subjects (p < 0.01), without differences in heart rate. Both OW and OB had greater LV diameter and mass than NW (all p < 0.05). Left ventricular hypertrophy was more prevalent in the OB (33.5%) and OW (12.4%), as compared with NW participants (3.5%; p < 0.001), largely compensating increased cardiac workload. However, OB subjects had four-fold higher probability of carrying an LV mass exceeding values compensatory for their cardiac workload (p < 0.001), a feature associated with lower ejection fraction, myocardial contractility, and greater force developed by left atrium to complete LV filling (all p < 0.05).
CONCLUSIONS: While in OW adolescents increased levels of LV mass are appropriate to compensate their higher hemodynamic load, in OB increase in LV mass exceeds this need and is associated with mildly reduced LV myocardial performance and increased left atrial force to contribute to LV filling.
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Increased left ventricular mass (LVM) in overweight children and adolescents has been described to be strongly associated with increased values of systolic blood pressure and lean body mass, suggesting that left ventricular hypertrophy (LVH) often reported in obese children and adolescents might represent a compensatory response to increased cardiac workload (11). This would be consistent with the notion that up to 82% to 86% of variability of LVM can be explained by phenotypic variations in body size and cardiac workload (12). There are conditions, however, in which LVM exceeds the amount that would be needed to compensate cardiac workload, and in adults this excess is associated with high-risk cardiovascular phenotype and adverse outcome, independently of clear-cut LVH (13). To date, no unselected population-based study has examined the impact of increasingly severe abnormalities of body build on cardiac geometry and function in adolescents, and resolved the question of whether the increase in LVM reported in clinical settings represents a compensatory response for increased cardiac workload. Thus, we examined LV geometry and function in a large unselected population of adolescents with different degrees of abnormal body size.
| Methods |
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Physical examination and laboratory testing. The examination included medical history, computerized electrocardiogram, measurement of brachial blood pressure, fasting glucose and insulin, glycosylated hemoglobin, lipid and lipoprotein levels, and a 2-h, 75-g glucose tolerance test. Blood pressure was measured after recommendations of the Fifth Report of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure (15). Laboratory tests and anthropometric measures (weight, height, and waist circumferences) were taken as previously reported (15). Fat-free mass and adipose body mass were estimated by the use of an RJL impedance meter (model B14101, RJL Equipment Co., Clinton Township, Missouri) and equations based on total body water validated in the American Indian population (16).
Evaluation of abnormal body weight, blood pressure, and metabolic syndrome. Body mass index (BMI)-for-age charts developed by the National Center for Health Statistics (NCHS) (17) were used to classify body weight groups. The 85th and 95th percentiles of the normal distribution were used to identify risk of overweight and clear-cut overweight, respectively, according to the NCHS charts. For convenience, we will use the term overweight to label the NCHS "risk of overweight" class and the terms obese for the NCHS "overweight" class. Guidelines correction was applied (18) so that the limit separating overweight and obesity did not exceed a BMI of 30 kg/m2.
For adolescents up to 18 years of age, normal blood pressure was assessed by using age-, gender-, and height-specific partition values according to the Fourth Report on the Diagnosis, Evaluation, and Treatment of High Blood Pressure in Children and Adolescents (19). For adolescents over 18 years of age, recommendations from the Seventh Report of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure were used (20). Because single blood pressure measurements were available, we did not use the terms hypertension and pre-hypertension for children and adolescents. Deviations from normal values will be called high or high-normal casual blood pressure (21). Prevalence of metabolic syndrome was assessed according to Adult Treatment Panel III criteria (22) modified for adolescent population (23).
Echocardiography. Echocardiograms were performed by expert sonographers, according to standardized methods and reviewed off-line using computerized review station with digitizing tablet and monitor screen overlay for calibration and performance of needed measurements (24).
Left ventricular internal dimension, septal and posterior wall thickness were measured at end-diastole and end-systole using American Society of Echocardiography recommendations on up to three cycles (25,26). As previously described (27), left atrial anteroposterior diameter was measured from the parasternal long-axis view in end-systole, and aortic root diameter was measured at level of the sinus of Valsalva in end-diastole.
Standard formula was used to calculate LVM (28,29), which was normalized for body height in meters to the allometric power of 2.7, which linearizes the relations between LVM and height and identifies the impact of obesity (30).
To evaluate the concentricity of LV geometry, myocardial thickness (wall + septum) was divided by LV minor axis (diameter) to generate a relative wall thickness (RWT). Because normal RWT increases with age (31), its raw value was normalized to age 10 years or 46 years (RWTa) by the following equations (31):
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To establish whether the possible increase in LVM was consistent with the increase in cardiac workload in groups with body builds abnormalities, we calculated the individual theoretical ideal value of LVM (LVMp), using age-stratum specific equations generated by stroke work (systolic blood pressure times stroke volume times 0.014, in grammeters/beat), gender (male gender = 1; female gender = 2) and height in meters to the 2.7 power. Equations were (13):
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%LVM), as a measure of compensation for cardiac workload. Thus, a high value of
%LVM represented an excess of LVM relative to the value that would compensate and sustain the individual cardiac workload. For convenience, values of
%LVM were categorized using 5th and the 95th percentile of the distribution in the reference subgroup of 92 normal participants. Inadequately low LVM was defined as
%LVM <66%, while inappropriately high LVM was defined as
%LVM >109%. We measured LV systolic function using a traditional assessment of LV chamber function with the shortening of LV minor axis measured at the endocardial level (endocardial shortening), and with a more complex measure of shortening at the mid-wall level (mid-wall shortening), which reflects more accurately myocardial contractile force, independent of LV concentric geometry (32), which has been demonstrated to preserve LV chamber function, when myocardial contractility is depressed (33).
Stroke volume was determined by an invasively validated Doppler method (34) and used to calculate cardiac output.
Left ventricular diastolic properties were assessed by Doppler interrogation of transmitral peak velocity at early (E) and late (A) LV filling and their ratio. Isovolumic relaxation time was measured between mitral valve closure and aortic opening. We also measured the force that left atrium develops to complete LV filling (left atrial systolic force), according to previously reported methods (35).
Statistical analysis. Statistical analyses were performed using SPSS 12.00 (SPSS Inc., Chicago, Illinois) software. Data are presented as mean ± SD for continuous variables and as proportions for categorical variables. Chi-square statistics were used to determine differences for categorical variables (with Monte Carlo method to compute exact two-tailed alpha value, when appropriate). One-way analysis of variance and analysis of covariance were used to compare continuous variables. When needed, Ryan-Einot-Gabriel-Welsch F post-hoc test was used, or main effects were compared by Sidaks adjustment of p value (36). The p values were shown for post-hoc tests. Two-tailed p < 0.05 was considered statistically significant.
| Results |
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Obese adolescents were slightly older and more frequently female patients than normal weight and overweight adolescents (Table 1). Both overweight and obese participants had greater adipose mass, fat-free mass, and waist circumference, and similarly higher blood pressure than normal weight adolescents (all p < 0.05). No differences between groups were found in smoking habit or alcohol drinking. High-normal and high casual blood pressure and diabetes as well were more frequent in both strata of abnormal BMI (all p < 0.005).
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Appropriateness of increased LV mass
No overweight or obese participant had values of LVM inadequately low for their cardiac workload. In contrast, while LVM index was progressively higher in overweight and obese adolescents, only obese participants exhibited excess of LVM relatively to their cardiac workload. The prevalence of clear-cut LVH was 12% in overweight and 34% in obese individuals (both p < 0.001 vs. normal weight control subjects), whereas a clear-cut excess of LVM was not statistically different in normal weight and overweight participants (6% and 10%, respectively), whereas it was more than four-fold higher in obese (27%) than in normal weight adolescents (p < 0.001).
| Discussion |
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During the past two decades, we are registering an increasing incidence of overweight and obesity in adolescents (2). This increase represents a major public concern because overweight in adolescence has been associated with increased incidence of arterial hypertension, unfavorable lipid profile, diabetes, as well as increased risks of adult obesity (4). Recent studies have also reported increased prevalence of LVH in selected samples of children with or without arterial hypertension associated with increased BMI (39,40).
The present study has been carried out in a cohort of unselected adolescents from a specific ethnic group (American Indians). Even in this population-based study, the highest level of abnormality of body build (we have named conventionally obesity) was associated with worse lipid profile, glucose metabolism, and increased prevalence of metabolic syndrome.
Our findings demonstrate that, even among adolescents at a mean age under 18, severity of abnormality in body build also parallels early cardiac changes, including high prevalence of LVH and increased hemodynamic load, paralleling previous findings (30,38,39) and suggesting that increased LVM occurs to sustain the increased cardiac workload. This was apparently the case in the adolescent group with mild elevation of body weight (classified as "risk of overweight" and called for convenience "overweight" in the present study). In contrast, in the adolescent group with more severe elevation of body weight (classified as "overweight" and called for convenience "obese" in the present study), the level of increased LVM substantially exceeded the need to compensate for cardiac workload, resulting in a markedly higher prevalence of inappropriate LVM. As already demonstrated in adults, the phenotype of excess LVM was also associated with reduced LV systolic function and myocardial performance. In contrast with adults, however, traditional indexes of LV filling were normal and only studying left atrial performance could reveal a slight abnormality in the late phase of LV filling.
The demonstration that at higher stages of abnormal body weight increase in LVM is not depending on hemodynamic load in a cohort of adolescents, which has not been yet exposed for a long time to overload, reinforces the view that development of LVH also depends on non-hemodynamic factors. This is particularly interesting in the present population, not only for the young age, but also because of the relatively low prevalence of abnormal casual blood pressure, indicating that non-hemodynamic factors play a significant role in determining the inappropriate increase in LVM found in the obese subgroup. This observation, paired with the high prevalence of metabolic syndrome, exceeding 50%, in the obese adolescents, suggests that, in frankly obese participants, the increase in LVM is a response not only to substantially increased hemodynamic load but also to possible neurohormonal effects of clustered metabolic factors influencing LV growth.
Study limitations.
There are limitations in this study that need to be highlighted. The analysis was performed in an American Indian population and whether these results can be generalized to other ethnic groups needs to be demonstrated. However, similar analyses previously performed in other ethnic groups, as Caucasians and African Americans, have suggested similar association between LVM and adiposity, independently of other cardiovascular risk factors (4042). Also, determination of Tanner stage was not performed, and the relation between body maturation and cardiac geometry/function could not be investigated; however, all participants were
14 years of age and, therefore, most probably all post-pubertal.
Blood pressure was measured by standardized methods during a single clinical visit, instead of three distinct measurements as suggested by current guidelines, causing participants with seldom increase in blood pressure to be included in the high blood pressure group. For this reason, we decided to avoid the definition of hypertension, while using the definition of "high casual blood pressure." We have previously shown that high casual blood pressure in children is associated with LV geometric abnormalities similar to those found in the presence of sustained hypertension (21). Eventually, the prevalence of high blood pressure/hypertension in this population is low, and any possible misclassification is unlikely to have substantially influenced the results.
Conclusions. In an unselected cohort of adolescents, participants with high values of BMI have increased values of LVM and a dramatically higher prevalence of LVH. While in overweight participants the increased levels of LVM are appropriate for their higher hemodynamic load, in obese adolescents this increase is disproportionately high and is associated with mildly reduced LV chamber and mid-wall function, and increased left atrial contribution to LV filling. Early intervention during childhood and adolescence to reduce the prevalence of obesity and prevent the transition from overweight to overt obesity might represent a crucial step in averting unfavorable cardiac phenotype present in the obese adolescents.
| Acknowledgments |
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| Footnotes |
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| References |
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