Pediatr Cardiol (2012) 33:245–251 DOI 10.1007/s00246-011-0123-5

ORIGINAL ARTICLE

Association Between Left Atrial Size and Measures of Adiposity Among Normal Adolescent Boys Valeria Hirschler • H. Laura Perez Acebo • Graciela B. Fernandez • Sandra Ferradas • Karin Oestreicher

Received: 17 June 2011 / Accepted: 12 September 2011 / Published online: 28 September 2011 Ó Springer Science+Business Media, LLC 2011

Abstract Obesity (OB) in adults is associated with insulin resistance, hypertension, and left atrial (LA) enlargement. This study aimed to determine the association between LA size and (1) different components of the metabolic syndrome (body mass index [BMI], waist circumference [WC], insulin levels, lipid levels, and blood pressure), and (2) left ventricular (LV) diameters and diastolic function. Data were collected cross-sectionally from 142 healthy adolescent boys age 16.8 ± 2.0 years in 2009. Measurements of BMI, WC, blood pressure, lipid profile, and insulin were performed. Mode M, two-dimensional Doppler echocardiography was performed. Measurements of LA area, LV end diastolic diameter (EDD), end systolic diameter (ESD), posterior wall, interventricular septum (IVS), and shortening fraction were performed. Tisular Doppler of the diastolic mitral annular E wave (DTE) and A wave (DTA) and the ratio of maximal early diastolic filling wave velocity to maximal early diastolic myocardial velocity (E/e0 ) were recorded. The study group included 38 OB boys (26.8%) and 32 overweight boys (22.5%). Significant univariate association was found between LA area and BMI (r = 0.61), WC (r = 0.56), systolic blood pressure (r = 0.21), insulinemia (r = 0.28), high-density lipoproteincholesterol (HDL-C) (r = –0.24), triglycerides (r = 0.20), EDD (r = 0.25), LV posterior wall (r = 0.25), IVS (r = 0.25), DTE (r = 0.27), DTA (r = 0.30), and E/e0 (r = –0.28). Multiple linear regression analysis showed that LA area was associated with BMI (B = 0.61; R2 = 0.47) adjusted for confounding variables. In adolescents, BMI

V. Hirschler (&)  H. L. P. Acebo  G. B. Fernandez  S. Ferradas  K. Oestreicher Durand Hospital, Maipu 812 5 M., 1006 Buenos Aires, Argentina e-mail: [email protected]

and WC were significantly associated with LA, suggesting that OB could be associated with LA enlargement as early as adolescence. Keywords Blood pressure  BMI  Left atrial size  Obesity  Waist circumference

The worldwide epidemic of obesity (OB) in recent decades [14] includes Argentina, which has experienced a marked increase in the prevalence of childhood overweight (OW) and OB [7]. Obesity [5] causes a variety of structural and functional cardiac changes that may affect left atrial (LA) size. The Framingham Heart Study [11] showed that heart failure had developed in 8.4% of their study population and that the risk of heart failure development increased approximately twofold for people with OB compared with the non-OB population. In adults, LA size is a key determinant of cardiovascular health, and LA enlargement is associated with a significantly increased risk of both atrial fibrillation [17] and stroke [4]. Several studies with adults have identified body mass index (BMI) as an independent predictor of LA size [2, 11]. Because OB in childhood tends to track into adult life, it is possible that the effects of excess adipose tissue on LA size may be present for many decades. The prevalence of such complications is lower and generally shorter in duration among children, and a recent study demonstrated a significant association between BMI and LA size [3]. We have described a significant association between waist circumference and LA size in children, adjusted for confounding variables including blood pressure [6]. To our knowledge, no large studies of apparently healthy adolescents in South America have shown the relationship of BMI and waist circumference to LA size. Therefore, this

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study aimed to determine the association in apparently healthy adolescent boys between the LA area and (1) different components of the metabolic syndrome (BMI, waist circumference, insulin levels, lipid profile, and blood pressure) and (2) left ventricular (LV) diameters and diastolic function.

Methods Data were collected from 142 adolescent boys age 16.8 ± 2.0 years from an amateur rugby club in Buenos Aires between April and May 2009. The exclusion criteria specified missing BMI and blood pressure information, not being in the fasting state, known diabetes, congenital heart disease, valve disease, primary myocardial disease, and other chronic diseases. Children also were excluded if they were receiving medication that could alter blood pressure or glucose or lipid metabolism and if informed consent had not been signed for them. Of the 189 adolescents recruited, 4 had missing BMI information, 4 had no blood pressure information, and 39 declined to participate. There was no significant difference in mean BMI, waist circumference, or blood pressure levels between the adolescents included in the study and those who did not participate. All the subjects were examined by the same physician. The study was approved by the Human Rights Committee of Durand Hospital in Buenos Aires. Each parent and subject gave written informed consent after an explanation of the study and before its initiation. Sociodemographic characteristics included age, level of parental education, and presence or absence of a refrigerator or a dirt floor. Questionnaires for socioeconomic status have been described in detail elsewhere [7]. The adolescents’ height, weight, and waist circumference were measured as previously described [7]. Because adolescent BMI varies according to age and gender, we standardized the values for age and sex by converting them to a z-score according to the growth charts of the Centers for Disease Control and Prevention (CDC) [13]. The adolescents were classified as normal weight (BMI \ 85 percentile) OW, (85 \ BMI \ 95 percentile) or OB (BMI [ 95 percentile) per CDC norms [13]. The physical examination also included determination of the puberty stage according to Tanner criteria [21]. Three separate blood pressure measurements were recorded by a trained technician using a random-zero sphygmomanometer after the participant had been seated at rest for 5 min. The averages of the last two systolic and diastolic blood pressure measurements were used [16]. We used the National Heart, Lung, and Blood Institute’s recommended cutoff point for hypertension [16].

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Echocardiographic measurements were performed using a General Electric Vivid 7 (GE Monogram, Zipf, Austria) with transducer frequencies appropriate for body size. Each subject underwent a two-dimensional, M-mode and Doppler echocardiogram as previously described [6]. The LA diameter and area were measured. The LA diameter indexed by height2 has the advantage of having a cutoff for abnormal, and LA area measurement is more accurate. We considered LA as enlarged when the LA diameter indexed by height2 was rated as third quartile or greater. The LV end diastolic diameter (EDD), end systolic diameter (ESD), posterior wall (PW), interventricular septum (IVS), shortening fraction, and LV mass were measured. From the apical four-chamber, with the sample volume positioned at the center of the mitral annulus near the tips of the leaflets, the early peak LV transmitral early peak filling velocity, late LV transmitral late peak filling velocity, and E deceleration time were registered. LA area was measured from apical four-chamber view at end-systole (ventricular). Transmitral Doppler imaging is another technique that enhances low-velocity, high-amplitude signals of myocardial motion and allows direct quantification of myocardial velocities as well as assessment of regional and myocardial systolic and diastolic functions [15]. Ttisular Doppler of diastolic mitral annular E wave (DTE) and A wave (DTA) and the ratio of maximal early diastolic filling wave velocity to maximal early diastolic myocardial velocity (E/e0 ) were registered. Blood specimens were obtained after a 12- to 14-h fast for determination of plasma glucose, insulin, and proinsulin concentrations. Plasma glucose was assayed by the glucose oxidase technique, and serum lipids were measured with an Abbot Bichromatic analyzer. Serum insulin levels were determined by radioimmunoassay (Diagnostic Products, Diagnostic Products corporation (Siemens), Los Angeles, CA, USA) and did not cross-react with proinsulin or C-peptide (%coefficient of variation, 5.2–6.8%). Statistical Analysis Data are presented as mean ± standard deviation or as median (quartile 1, 2, or 3). The nature of the quantitative variables distribution was assessed using the Shapiro– Wilks test. When more than three groups were compared and when the data were normally distributed, one-way analysis of variance was used (Student–Newman–Keuls post hoc test). When homogeneity of the variances could not be proved, the nonparametric Kruskal–Wallis test was used rather than analysis of variance. The chi-square test was used to compare proportions in RXC Crosstabs. When more than 20% of the cells had expected frequencies less than 5 and for 2 9 2 tables, Fisher’s exact test was used. Enlargement of LA was considered when LA diameter indexed by height2 was rated as quartile 3.

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The independent effects of several discrete variables on LA size were assessed, namely, age, gender, measures of obesity, blood pressure, and measures of LV function. To measure the strength of association between these variables and LA size, a Pearson correlation coefficient was used. To evaluate the influence of different cardiovascular risk factors on LA size, several linear regression analyses were performed. Furthermore, multiple logistic regression analysis was performed to examine the association between independent risk factors and LA enlargement (LA diameter indexed by height2 Cquartile 3) as a binary variable. In all cases, p values less than 0.05 were deemed statistically significant. Analyses were performed using the SPSS statistical software package, version 17.0 (SPSS, Chicago, IL, USA).

Results Clinical and Metabolic Characteristics The general characteristics of the participants are shown in Table 1. The subjects ranged in age from 14 to 21 years. All the subjects were at the pubertal or postpubertal stage. There was no significant difference in the level of physical activity between normal weight, overweight, and obese children because all of them practiced the same amount of sports per week. The prevalences of Tanner 3, 4, and 5 were 15, 37, and 48%, respectively. Among the participants, 38 (26.8%) were OB (BMI, [95th percentile) and 32 (22.5%) were OW (BMI, 85th–95th percentile). The subjects belonged to a middle-low socioeconomic class, as reflected in the educational backgrounds of the parents, with 47.9% of the mothers and 50.8% of the fathers having only an elementary school education or less. All the families had a refrigerator, and none had a dirt floor. The prevalence of hypertension was 8.5% overall, 18.4% among the obese children, and 4.8% among the nonobese children. Analysis of data classified according to the presence of OW and OB is presented in Table 1. The normal weight, OW, and OB boys did not differ significantly in terms of age. As expected from the criteria for classification, BMI and waist circumference differed significantly among the three groups. The mean values for diastolic and systolic blood pressure were higher in OB adolescents than in normal weight or OW subjects. Regarding metabolic parameters, the insulin concentration and the plasma levels of triglycerides, total cholesterol, and low-density lipoprotein-cholesterol (LDL-C) were significantly higher for the OB boys than for the normal weight and OW adolescent boys. On the other hand, the high-density lipoprotein-cholesterol (HDL-C) concentration was

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significantly lower for the OB boys than for the normal weight adolescents (Table 1). Left ventricular structure and function parameters according to the classification of normal weight, OW, or OB are depicted in Table 1. In the OB adolescent boys, EDD, LV mass, DTA, and LA size were significantly greater than in both the normal weight and OW subjects. As shown in Fig. 1, the mean values of LA area were significantly greater in the OB than in the OW boys, and also greater in the OW boys than in the normal weight children. Univariate Analysis Pearson analysis showed a significant association between LA area and BMI, waist circumference, systolic blood pressure, insulin levels, HDL-C, triglycerides, EDD, LV posterior wall (LVPW), IVS, DTE, DTA, and E/e0 . When LA area was replaced by LA diameter, the results did not change. In contrast, when LA diameter was replaced by LA diameter indexed by height2, the correlation with systolic blood pressure, DTE, E/e0 , EDD, LVPW, and IVS lost significance (Table 2). Multiple Regression Analysis To evaluate the influence of different cardiovascular risk factors on LA size, several linear regression analyses were performed. Strong associations with LA area were observed with the BMI z-score (z-BMI) (Table 3). Therefore, 47% of LA area total variance could be attributed to the selected model. Notably, when z-BMI was replaced by waist circumference, similar results were found (r2 = 0.47) (Table 4). No association of LA area with lipid levels, insulin levels, or blood pressure was observed. Multiple logistic regression analysis was used to examine the association between independent risk factors and LA enlargement as a binary variable. The results proved OB to be associated with LA size adjusted for age, blood pressures, triglycerides, insulin, and DTA (odds ratio, 5.8; 95% confidence interval, 1.8–18.5). Therefore, the OB children had six times the risk of experiencing LA enlargement.

Discussion In this cross-sectional analysis of healthy adolescent boys, the most important observation was that OW or OB, measured by BMI, and primarily OB measured by waist circumference, were significantly and independently associated with LA size, adjusted for confounding factors. The results of multivariate analysis showed that z-BMI could explain approximately half of LA area variance. Therefore, measures of adiposity such as z-BMI and waist

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Table 1 Physical, metabolic, and echocardiographic characteristics according to the presence of overweight (OW) or obesity (OB) Normal weight (n = 72)

OW (n = 32)

OB (n = 38)

Total (n = 142)

Age (years)

16.6 ± 1.9

16.9 ± 2.2

16.9 ± 2.0

16.8 ± 2.0

WC (cm)a**

75.1 ± 7.0

86.4 ± 6.6

99.7 ± 8.1

84.2 ± 12.6

BMI (kg/m2)a**

21.6 ± 2.3

26.1 ± 1.5

31.93 ± 2.9

25.4 ± 4.9

z-BMI **

0.1 ± 0.7

1.3 ± 0.1

2.0 ± 0.2

0.9 ± 0.9

Systolic BP (mmHg)b**

114 ± 10

113 ± 11

125 ± 12

117 ± 12

a

Diastolic BP (mmHg)b**

71 ± 8

68 ± 7

77 ± 8

72 ± 8

Hemoglobin (g/dl)

14.5 ± 0.9

14.7 ± 0.7

14.8 ± 0.7

14.0 ± 0.8

Triglycerides (mg/dl)b**

68 (54–93)

76 (54–89)

106 (78–141)

78 (57–101)

Cholesterol (mg/dl)d*

157 ± 37

147 ± 26

171 ± 34

158 ± 35

HDL-C (mg/dl)d**

46 ± 9

43 ± 9

39 ± 7

44 ± 9

Glucose (mg/dl)d Insulin (UI/ ml)b**

84 ± 11 4.6 (3.2–6.9)

80 ± 9 6.1 (4.7–8.1)

86 ± 10 10.2 (7.3–13.5)

83 ± 10 6.4 (4.1–9.0)

EDD (mm)c**

48.5 ± 4.8

51.1 ± 4.3

52.2 ± 3.8

50.1 ± 4.7

ESD (mm)e

30.3 ± 4.0

31.5 ± 3.1

31.9 ± 3.9

31.0 ± 3.8

SF (%)

e

37.4 ± 4.2

38.0 ± 4.2

38.6 ± 5.1

37.8 ± 4.5

IVS (mm)e

7.8 ± 1.7

7.9 ± 1.6

8.3 ± 1.4

7.9 ± 1.6

LVPW (mm)e

7.2 ± 1.4

7.4 ± 1.3

7.8 ± 1.4

7.4 ± 1.4

LVM (g)d**

153.5 ± 47.6

168.7 ± 50.9

186.8 ± 46.5

166.2 ± 49.8

LVM/height2 d**

37.3 ± 9.9

39.9 ± 10.8

44.4 ± 10.6

39.9 ± 10.7

e

0.9 ± 0.1

0.9 ± 0.1

0.9 ± 0.1

0.9 ± 0.1

MVA (m/s)e

0.4 ± 0.1

0.4 ± 0.1

0.4 ± 0.1

0.4 ± 0.1

EDT (ms)e

153.6 ± 34.9

162.3 ± 35.5

162.5 ± 35.1

157.9 ± 35.1

DTE (m/s)e

0.1 ± 0.0

0.2 ± 0.0

0.2 ± 0.1

0.2 ± 0.1

DTA (m/s)e

0.06 ± 0.01

0.07 ± 0.02

0.07 ± 0.02

0.07 ± 0.02

5.0 ± 1.2

5.1 ± 1.2

4.9 ± 1.3

5.0 ± 1.2

LA area (cm )**

14.6 ± 2.6

17.4 ± 3.0

19.5 ± 3.3

16.5 ± 3.5

LA diameter (mm)b** LA diameter/height2 b**

33.4 ± 3.8 11.9 ± 1.4

35.1 ± 2.8 12.1 ± 1.1

39.4 ± 3.9 13.7 ± 1.6

35.4 ± 4.4 12.4 ± 1.6

MVE (m/s)

E/e0 e 2a

WC waist circumference; BMI body mass index; z-BMI BMI z-score; BP blood pressure; HDL-C high-density lipoprotein-cholesterol; EDD end diastolic diameter; ESD end systolic diameter; SF shortening fraction; IVS interventricular septum; LV left ventricular; LVPW LV posterior wall; LVM LV mass; MVE early peak LV transmitral early peak filling velocity; MVA late LV transmitral late peak filling velocity; EDT E deceleration time; DTE diastolic mitral annular E wave; DTA diastolic mitral annular A wave; E/e0 ratio of maximal early diastolic filling wave velocity to maximal early diastolic myocardial velocity; LA left atrial a

The groups differ

b

OB differs from normal weight and OW

c

Normal weight differs from OW and OB

d

Normal weight differs from OB

e

Difference is not significant

Data are means ± standard deviation (SD) or median (quartile 1–3). OW/OB were classified using the CDC cut points. p Values compare means ± SD between normal weight, OW, and OB children * p \ 0.05; ** p \ 0.01

circumference remained a significant determinant of LA size even after adjustment for age, blood pressure, lipid levels, and LV diameters and diastolic functions. The LA area was significantly larger in the OB than in the OW boys, and also larger in the OW than in the normal weight adolescents. These findings suggest that BMI independently influences LA size in adolescence.

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Enlargement of LA has been proposed as a barometer of diastolic burden and a predictor of common cardiovascular outcomes such as atrial fibrillation, stroke, congestive heart failure, and cardiovascular death [1]. Several studies of adults have indicated that OB and OW are associated with an increased risk of heart failure [8, 12]. Evidence from epidemiologic studies has shown that OW or OB is a major

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Fig. 1 Mean adolescent left atrial (LA) area values and 95% confidence intervals (CI) according to the presence of overweight (OW) or obesity (OB)

risk factor for coronary heart disease and ischemic stroke [23]. Furthermore, in a large longitudinal study of adults, the risk of heart failure was increased during the follow-up period (mean, 14 years): 5% for men and 7% for women for each BMI increment of 1 after adjustment for established risk factors [11]. A recent study of children showed a significant association between BMI z-score and LA diameter in a large community-based sample of healthy children [3]. Consistent with these studies, we found a strong association between LA area and measures of adiposity such as BMI and waist circumference adjusted for confounding

variables. Furthermore, the logistic regression analysis showed that OB adolescent boys had six times the chance of having LA enlargement compared with non-OB boys. Additionally, in the Uppsala Longitudinal Study of Adult Men cohort, an increase of 1 standard deviation in waist circumference was associated with a 36% increased risk of heart failure [10]. A recent study, also found that an elevated waist circumference or waist-to-hip ratio was associated with a greater risk of heart failure in both men and women [8]. Consistent with these studies, we found that waist circumference also was significantly associated with LA area in the multiple regression analysis adjusted for confounding variables. Findings have shown OB to be associated with adverse levels of lipids, insulin, and blood pressure, all components of the metabolic syndrome among children and adolescents [18]. All these factors were associated with an increased risk of heart failure and considered to be mediating factors for the physiologic effects of adiposity on heart failure risk. However, a recent study found that OW and OB individuals, even without metabolic syndrome, had an increased risk for cardiovascular disease [20]. Consistent with this study, we showed that even if a univariate correlation existed between the lipid profile such as HDL-C and triglycerides and the LA area, this correlation was weak (r \ 0.25), and when these variables were introduced into the multivariate model, the associations lost significance. Wang et al. [22] found OB to be an important risk factor for new-onset atrial fibrillation. The increased risk for atrial fibrillation associated with OB appeared to be mediated by LA dilation. Interestingly, in their multivariate regression

Table 2 Univariate associations with left atrial (LA) size LA area (r)

LA diameter (R)

LA diameter/height2 (R)

BMI

0.61**

0.68**

0.46**

z-BMI

0.57**

0.63**

0.40**

Systolic BP

0.21*

0.29**

0.11

WC

0.56**

0.66**

0.38**

Insulin

0.28**

0.33**

0.33**

TG

0.20*

0.35**

0.21*

HDL-C

-0.24**

-0.22*

-0.13

DTE

0.27**

0.18*

0.15

DTA

0.30**

0.24**

E/e0

-0.28**

-0.18*

0.18* -0.07

EDD

0.25**

0.35**

0.05

LVPW

0.25**

0.20*

0.17

IVS

0.25**

0.20*

-0.01

BMI body mass index; z-BMI BMI z-score; BP blood pressure; TG triglycerides; HDL-C high-density lipoprotein-cholesterol; DTE diastolic mitral annular E wave; DTA diastolic mitral annular A wave; E/e0 ratio of maximal early diastolic filling wave velocity to maximal early diastolic myocardial velocity; EDD end diastolic diameter; LV left ventricular; LVPW LV posterior wall; IVS interventricular septum * p \ 0.05; ** p \ 0.01

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Table 3 Multiple linear regression analysis Model

Variable

1a

Age

0.14

0.021

b

Age

0.11

0.34

z-BMI

0. 56

2

3c

Age z-BMI

4d

5e

B

Table 4 Multiple linear regression analysis R

2

-0.14

p Value

Variable

0.09

1a

Age

0.14

0.15

2b

Age

-0.05

WC

0.57

\0.001 0.35

0. 59

R2

Model

0.08

3c

B

Age

-0.01

\0.001

WC

0.62

SBP

-0.06

0.57

SBP

-0.08

DBP

-0.04

0.69

DBP

-0.05

Age

0.13

Age

-0.01

z-BMI

0.58

\0.001

WC

0.63

0.38

0.13

4d

0.021 0.31

p Value 0.09 0.5 \0.001

0.32

0.88 \0.001 0.42 0.55

0.35

0.874 \0.001

SBP

-0.07

0.56

SBP

-0.08

0.44

DBP Insulin

-0.04 0.03

0.71 0.76

DBP Insulin

-0.07 -0.02

0.46 0.79

HDL-C

-0.06

Age

0.07

0.47 0.47

0.42

5e

HDL-C

-0.08

Age

-0.05

0.28 0.47

0.58

\0.001

WC

0.64

SBP

-0.01

0.99

SBP

-0.05

0.63

DBP

-0.07

0.50

DBP

-0.11

0.25

Insulin

-0.01

0.89

Insulin

-0.03

0.67

HDL-C

-0.07

0.56

HDL-C

-0.09

0.21

LVPW

-0.03

0.74

LVPW

-0.06

0.51

EDD

-0.08

0.38

EDD

-0.09

0.33

IVS

0.11

0.29

IVS

0.13

0.18

DTE

0.05

0.81

DTE

0.07

0.44

DTA

0.14

0.10

DTA

0.12

0.14

-0.12

0.17

E/e0

-0.16

0.06

z-BMI

E/e0

0.61

\0.001

B standardized coefficient; BMI body mass index; z-BMI BMI z-score; SBP systolic blood pressure; DBP diastolic blood pressure; HDL-C high-density lipoprotein-cholesterol; LV left ventricular; LVPW LV posterior wall; EDD end diastolic diameter; IVS interventricular septum; DTE diastolic mitral annular E wave; DTA diastolic mitral annular A wave; E/e0 ratio of maximal early diastolic filling wave velocity to maximal early diastolic myocardial velocity

B standardized coefficient; WC waist circumference; SBP systolic blood pressure; DBP diastolic blood pressure; HDL-C high-density lipoprotein-cholesterol; LV left ventricular; LVPW LV posterior wall; EDD end diastolic diameter; IVS interventricular septum; DTE diastolic mitral annular E wave; DTA diastolic mitral annular A wave; E/ e0 ratio of maximal early diastolic filling wave velocity to maximal early diastolic myocardial velocity

a

Model 1 data were adjusted for age

a

Model 1 data were adjusted for age

b

Model 2 data were adjusted for covariates in model 1 plus z-BMI

b

Model 2 data were adjusted for covariates in model 1 plus WC

c

Model 3 data were adjusted for covariates in model 2 plus blood pressures

c

d

Model 4 data were adjusted for covariates in model 3 plus insulin and HDL-C

d

e

Model 5 data were adjusted for covariates in model 4 plus LVPW, EDD, IVS, DTE, DTA, and E/e0

e

models, the association between BMI and risk of atrial fibrillation was not significantly influenced by systolic blood pressure [22]. A previous study performed by our group [6] with 40 obese, 28 overweight, and 16 healthy weight children showed that waist circumference was the only significant independent predictor of LA size adjusted for blood pressure, LV mass, and a measure of insulin resistance. This is in line with our observations that LA area was associated with measures of adiposity such as BMI and waist

circumference but not with blood pressure or insulin levels, suggesting that the LA enlargement is a result of volume overload and not pressure overload. Furthermore, recent studies also raise the possibility that adipose tissue has a direct effect on myocardial structure and function [9]. Whether one or both of these mechanisms are important in the pediatric population remains to be determined. As a result, the incidence of atrial fibrillation, with its subsequent risks of stroke and heart failure, could increase in OB individuals [19, 22].

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Model 3 data were adjusted for covariates in model 2 plus blood pressures

Model 4 data were adjusted for covariates in model 3 plus insulin and HDL-C Model 5 data were adjusted for covariates in model 4 plus LVPW, EDD, IVS, DTE, DTA, and E/e0

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Several limitations of this study are acknowledged. First, it was a cross-sectional analysis, so the directionality of the associations cannot be established. Second, the study was conducted with only male adolescents, although a previous study with children by our group [6] showed no differences between males and females. Third, LA size was determined by M-mode ultrasound measurement of LA area rather than by measurement of LA volume. Fourth, the lack of a comparable group that did not practice any sports limits the generalizability of our findings. Finally, 24-h ambulatory blood pressure recordings are more reliable than single blood pressure readings. However, ambulatory blood pressure monitoring was not feasible in our study of adolescents from the community. Nevertheless, the large sample size and the high level of significance of the results are more likely to confirm these findings. In conclusion, BMI and waist circumference, both measures of body fat, were significantly associated with LA size in adolescents. These associations remained significant after adjustment for the effects of age, blood pressure, and LV diastolic function parameters. Left atrial size showed a significant increase in OW and OB adolescents compared with normal weight adolescents. These results indicate that adolescents with the greatest body mass have the largest LA size, demonstrating that increased adiposity can influence LA size as early as adolescence. Furthermore, with regard to the increasing prevalence of severe OB, its importance in the development of atrial fibrillation will increase and may replace arterial hypertension as the main risk factor. Additional longitudinal studies should be conducted for further confirmation of these findings.

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