Effect of Overweight and Obesity (Defined by Asian-Specific Cutoff Criteria) on Left Ventricular Diastolic Function and Structure in a General Korean Population

Abstract

Background: Although obesity is a well-known risk factor for cardiovascular disease, the cutoff of body mass index (BMI) for elevated cardiovascular risk is still controversial in Asian. Thus, this study was conducted to investigate the functional and structural changes of the left ventricle (LV) according to the degree of obesity in a general Korean population.

Methods and Results: A total of 31,334 apparently healthy Korean adults who underwent echocardiography were enrolled. The study population was stratified into 5 groups according to the degree of obesity classified by the Asian-Pacific obesity guideline. The odd ratios (ORs) with 95% confidence interval (CI) of impaired LV diastolic function, LV remodeling, and hypertrophy were compared among the 5 groups using multivariable logistic regression analysis. When the normal group was set as the reference, the adjusted ORs (95% CI) for impaired LV diastolic function showed a proportional relationship with BMI [OR; 0.86 (95% CI 0.59–1.22) in underweight, 1.81 (95% CI 1.63–2.00) in overweight, 2.75 (95% CI 2.49–3.03) in obese, and 4.34 (95% CI 3.65–5.16) in severe obese]. Adjusted ORs for LV remodeling and hypertrophy significantly increased proportional to BMI.

Conclusions: Even with strict classification of obesity by the Asian-Pacific guideline, BMI of more than overweight (≥23 kg/m²) was significantly associated with impaired LV diastolic function, remodeling, and hypertrophy. (Circ J 2016; 80: 2489–2495)

There is accumulating evidence for an incidental relationship between obesity and cardiovascular disease. It is currently recognized that obesity significantly contributes to cardiac morbidity and mortality independent of other cardiovascular risk factors.^1,2

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As a mechanism for these cardiovascular consequences of obesity, the adverse influence of obesity on cardiac function and structure has been suggested.^1,3,4 In particular, previous studies have demonstrated that obesity was significantly associated with the development of left ventricular diastolic dysfunction (LVDD) and remodeling.^5–8

LVDD and left ventricular (LV) remodeling are regarded as a preclinical form of heart failure that carries a substantial risk of subsequent heart failure and reduces survival even in the asymptomatic condition.^9,10 Thus, a high prevalence of obesity increases the concern for LVDD, cardiac remodeling and their clinical outcomes. Furthermore, Asia is an area with a rapidly growing incidence of obesity, which will undoubtedly contribute to the increasing burden of cardiovascular diseases related to functional and structural cardiac abnormalities in Asians. However, to date, there is little research that has evaluated the link between LV functional and structural abnormalities according to the degree of obesity in Asians. Although studies for Western populations demonstrate that a body mass index (BMI) more than overweight (≥25 kg/m²) is a major cutoff for increased risk of LVDD and remodeling,^6–8 the optimal BMI cutoff is still controversial for Asians. Additionally, considering that Asians have a higher risk for diabetes and cardiovascular disease at given BMI levels than Western populations,^11–13 it is important to estimate the BMI of Asians at which the risk of LV functional and structural abnormalities significantly increases.

Thus, this study aimed to assess the risk for LV functional and structural abnormalities according to the degree of obesity in a general Korean population.

Methods

Study Design and Population

This cross-sectional study was conducted to investigate the association between LV functional and structural abnormalities and the degree of obesity represented by BMI.

The study population comprised Korean men and women undergoing a medical health check-up at the Health Promotion Center of Kangbuk Samsung Hospital, Sungkyunkwan University, Seoul, Korea. Korea’s Industrial Safety and Health law regulates that all employees periodically receive a medical health check-up. The purpose of the medical health check-up program is to promote the health of employees by early detection of diseases. Most of the study population was employees of various companies and their family members. The cost of the medical examinations is largely paid by the employers.

A total of 33,254 men and women, aged from 18 to 84 years old, who had undergone echocardiography, including tissue Doppler echocardiography (TDI), as an item of the medical health check-up program between May 2011 and December 2012 were initially enrolled in this study. Of them, 1,716 were excluded for various reasons: 143 had an arrhythmia such as atrial fibrillation, AV block and tachycardia; 70 had systolic LV dysfunction (ejection fraction ≤50); 792 had a history of malignancy; 537 had a serious medical condition such as asthma, chronic obstructive pulmonary disease or endstage renal disease; 204 had a history of myocardial infarction or angina; 167 were excluded for incomplete TDI data and BMI; 7 were excluded for other reasons. The total number of eligible participants was 31,334. Ethics approval for the study protocol and analysis of the data was obtained from the Institutional Review Board of Kangbuk Samsung Hospital. The informed consent requirement was waived by the Board because researchers retrospectively accessed a de-identified database for analytical purposes.

Clinical and Laboratory Measurements

Study data included medical history, physical examination, information provided by a self-administered questionnaire, anthropometric measurements and laboratory measurements. The medical and drug prescription history was assessed by the examining physicians. All study participants were asked to respond to a health-related behavior questionnaire, which included the topics of alcohol consumption, smoking and exercise. The questions about alcohol intake included the frequency of alcohol consumption on a weekly basis and the typical amount that was consumed on a daily basis. We considered persons reporting that they smoked at the time of the questionnaire to be current smokers. Diabetes mellitus was defined as fasting serum glucose level ≥126 mg/dl, or serum hemoglobin A1c (HbA1c) level ≥6.5%, or the participant ever having been diagnosed with diabetes, or the current use of blood glucose-lowering agents. The BMI was calculated by dividing weight (kilograms) by the square of height (m²). Hypertension was defined as either the current use of antihypertensive medication or the participant ever having been diagnosed with hypertension or as having a measured blood pressure (BP) ≥140/90 mmHg at initial examination. Trained nurses measured participants’ seated BP 3 times using automated equipment (53000-E2, Welch Allyn, NY, USA) after a 5-min rest. Final BP was calculated as the average of the 2nd and 3rd BP measurements.

Blood samples from an antecubital vein were collected after more than 12 h of fasting. Insulin resistance was calculated using the following formula: homeostasis model assessment-insulin resistance (HOMA-IR)=fasting serum insulin (uU/ml)×fasting serum glucose (mg/dl)/405.

The fasting serum glucose was measured using the hexokinase method. Total cholesterol and triglyceride levels were measured using enzymatic colorimetric tests; low-density lipoprotein cholesterol was measured using the homogeneous enzymatic colorimetric test, and high-density lipoprotein cholesterol (HDL-C) was measured using the selective inhibition method (Advia 1650 Autoanalyzer, Bayer Diagnostics; Leverkusen, Germany).

Fasting insulin concentration was measured by immunoradiometric assay (Biosource, Nivelles, Belgium), and HbA1c was measured using an immunoturbidimetric assay with a Cobra Integra 800 automatic analyzer (Roche Diagnostics, Basel, Switzerland). Serum creatinine and uric acid levels were determined using the Jaffe reaction method (Advia 1650 kit, Bayer Corp, PA, USA) and the uricase EMST method, respectively.

Echocardiographic Measurements

Each participant underwent 2D transthoracic echocardiography with a 4-MHz, sector-type transducer probe (Vivid 7; GE, Milwaukee and E9; GE, Milwaukee, WI, USA). Transthoracic echocardiography was performed by a trained registered sonographer following a standardized protocol. Images from standard parasternal long- and short-axis views were digitally stored and reviewed. LV end-diastolic diameter (LVEDD), LV endsystolic diameter (LVESD), interventricular septum thickness (IVST) and posterior LV wall thickness (PWT) were routinely measured. LV mass was calculated with following formula: 0.8×{1.04[(LVEDD+IVST+PWT)³-(LVEDD)³]}+0.6 g,¹⁴ and indexed for body surface area. LV endsystolic volume (LVESV) and LV end-diastolic volume (LVEDV) were calculated by following formulae: LVESV=7.0/(2.4+LVESD)×LVESD³ and LVEDV=7.0/(2.4+LVEDD)×LVEDD³. Calculation of relative wall thickness (RWT) was by the formula, (2×PWT)/LVEDD, and increased RWT was defined as RWT >0.42. Those with LV hypertrophy were defined as LV mass index ≥115 in men or ≥95 in women.¹⁵

Deceleration time was measured by pulsed wave Doppler in the apical 4-chamber view. Peak velocities of the early (E) and late (A) phases of the mitral inflow were also measured and their ratio (E/A) was calculated. LV myocardial velocities were evaluated by TDI. The peak early diastolic (e′) and late diastolic (a′) velocities were measured at the level of the septal mitral valve annulus. The ratio of E/e′ was calculated as the index of LV filling pressure and diastolic performance. Subject with impaired LV diastolic function were defined by septal e’ velocity <8 cm/s.¹⁴

Statistical Analysis

Data are presented as mean±standard deviation within BMI groups for continuous variables and as proportions for categorical variables. The main clinical characteristics and echocardiographic parameters among the 5 BMI groups were compared using ANOVA for continuous variables and chi-square test for categorical variables. According to the International Obesity Task Force recommendation,¹⁶ the BMI categories were as follows: normal (between 18.5 and 23 kg/m²), underweight (<18.5 kg/m²), overweight (between 23 and 25 kg/m²), obese (between 25 and 30 kg/m²), severe obese (≥30 kg/m²).

The odd ratios (OR) of impaired LV diastolic function, increased RWT, and LVH with the presence of underweight, overweight, obese, and severe obese were analyzed using multivariable logistic regression analysis. After checking multicollinearity, selected variables were enrolled as adjusting covariates of multivariable logistic regression analysis: age, sex, smoking, average alcohol use (g/day), hypertension, diabetes, total cholesterol, HDL-C, and high-sensitivity C-reactive protein.

In order to test the mean differences between study groups after adjusting for covariates, we calculated the adjusted mean values and standard deviation of echocardiographic parameters including septal e’, E/e’ ratio, E/A ratio, LVEDV, LA diameter, RWT, and LVMI using the “lsmeans” package in R (“lsmeans” package version 2.23). The adjusted mean values in the present study were obtained by the least-squares means method. They are predicted marginal means that were estimated from fitted linear models after adjusting for major covariates. Statistically significance was considered as P<0.05. All statistical analyses were performed using R 3.2.1 (R Foundation for Statistical Computing, Vienna, Austria).

Results

Clinical Characteristics of the Study Population

Clinical and demographical characteristics of the study participants are presented in Table 1. The 31,334 study participants consisted of 22,718 men and 8,616 women. The mean age was 40.4±7.8 years, and only 2% of population (n=638) was older than 60 years. The more obese group had the more unfavorable clinical characteristics and metabolic profiles than the lesser obese groups. The groups with higher BMI values were more likely to have hypertension, diabetes, and higher values for weight, height, waist circumference, HbA1c, fasting insulin, triglyceride, total cholesterol, and HOMA-IR than the groups with lower BMI.

Table 1. Clinical Characteristics of a General Korean Population in a Study of BMI and Heart Health

	BMI category
	Underweight (n=1,131)	Normal (n=11,897)	Overweight (n=7,875)	Obese (n=9,288)	Severe obese (n=1,143)	P value
Sex
Female (n, (%))	869 (76.8)	5,240 (44.0)	1,257 (16.0)	1,092 (11.8)	158 (13.8)	<0.001
Male (n, (%))	262 (23.2)	6,657 (56.0)	6,618 (84.0)	8,196 (88.2)	985 (86.2)
Glucose (mg/dl)	90.2±8.3	94.2±12.2	97.8±13.8	101.3±18.2	106.5±23.2	<0.001
Total cholesterol (mg/dl)	179.2±30.4	190.0±32.5	199.7±34.2	205.3±35.0	209.4±36.6	<0.001
Triglyceride (mg/dl)	72.5±39.2	95.8±55.0	131.8±83.6	161.0±103.0	190.0±117.4	<0.001
HDL-C (mg/dl)	69.3±14.4	61.0±14.4	53.6±12.9	49.5±11.5	46.0±10.0	<0.001
LDL-C (mg/dl)	99.6±26.6	115.3±29.7	127.3±30.8	132.7±31.6	136.2±33.0	<0.001
HbA1c (%)	5.5±0.3	5.6±0.4	5.7±0.5	5.8±0.6	6.0±0.8	<0.001
Fasting insulin (uIU/ml)	3.5±1.9	4.5±2.7	5.8±4.5	7.8±4.6	12.6±7.0	<0.001
hsCRP (mg/L)	0.06±0.19	0.08±0.28	0.12±0.34	0.14±0.31	0.23±0.76	<0.001
Height (cm)	164.2±7.1	167.7±8.3	170.8±7.5	171.2±7.3	171.7±7.6	<0.001
Weight (kg)	47.6±4.6	59.8±7.4	70.1±6.3	78.7±7.7	94.4±10.2	<0.001
Waist circumference (cm)	67.0±3.9	76.9±5.3	84.6±4.0	91.3±5.0	102.9±6.3	<0.001
SBP (mmHg)	100.2±11.1	106.9±12.3	113.3±11.9	117.4±12.3	123.7±12.5	<0.001
DBP (mmHg)	64.8±8.5	68.8±9.6	73.2±9.7	76.2±10.2	79.5±10.6	<0.001
Heart rate (beats/min)	64.4±8.9	64.3±8.8	64.4±8.7	65.8±8.8	68.8±9.2	<0.001
Age (years)	37.0±6.6	39.5±7.7	41.2±7.9	41.3±7.7	39.8±7.3	<0.001
BMI (kg/m2)	17.6±0.8	21.2±1.2	24.0±0.6	26.8±1.3	32.0±2.0	<0.001
Average alcohol use (g/day)	6.9±13.1	12.3±18.7	18.7±23.5	21.8±26.3	23.3±29.0	<0.001
Smoking (n, (%))†
Never smoked	719 (63.6)	6,167 (51.8)	2,862 (36.3)	2,969 (32.0)	370 (32.4)	<0.001
Former smoker	58 (5.1)	1,776 (14.9)	1,905 (24.2)	2,333 (25.1)	238 (20.8)
Current smoker	112 (9.9)	2,081 (17.5)	2,085 (26.5)	2,899 (31.2)	395 (34.6)
HOMA-IR	0.8±0.4	1.1±0.7	1.4±1.4	2.0±1.4	3.4±2.2	<0.001
Hypertension (n, (%))	30 (2.7)	874 (7.3)	1,193 (15.1)	2,162 (23.3)	463 (40.5)	<0.001
Diabetes (n, (%))	13 (1.1)	286 (2.4)	372 (4.7)	775 (8.3)	189 (16.5)	<0.001

Data are mean (±SD). ^†There are some missing values in the smoking group (n=4,364). BMI categories: normal (between 18.5 and 23 kg/m²), underweight (<18.5 kg/m²), overweight (between 23 and 25 kg/m²), obese (between 25 and 30 kg/m²), severe obese (≥30 kg/m²). BMI, body mass index; DBP, diastolic blood pressure; HDL-C, high-density lipoprotein cholesterol; HOMA-IR, homeostasis model assessment of insulin resistance; LDL-C, low-density lipoprotein cholesterol; SBP, systolic blood pressure.

LV Diastolic Function and Structure

Table 2 compares the echocardiographic parameters of the study groups. The groups with higher BMI tended to have more unfavorable echocardiographic parameters than the groups with lower BMI. Although the overall prevalence of impaired LV diastolic function was 23.2% (n=7,271), BMI was proportionally associated with the prevalence of impaired LV diastolic function. The prevalence of impaired LV diastolic function was 5.0% (n=57) in the underweight group, 12.0% (n=1,428) in the normal-weight group, 25.1% (n=1,976) in the overweight group, 35.5% (n=3,297) in the obese group, and 44.9% (n=513) in the severe obese group. Increased RWT and LVH also had a dose–response relationship with BMI.

Table 2. Echocardiographic Characteristics of the Study Group According to BMI

	BMI category
	Underweight (n=1,131)	Normal (n=11,897)	Overweight (n=7,875)	Obese (n=9,288)	Severe obese (n=1,143)	P value
Deceleration time (ms)	190.4±39.9	190.2±39.8	192.0±41.0	191.2±40.3	193.1±40.2	0.006
E/e’	7.2±1.7	7.2±1.7	7.6±1.9	8.0±1.9	8.5±2.0	<0.001
E/A ratio	1.7±0.5	1.5±0.8	1.4±0.4	1.3±0.4	1.2±0.3	<0.001
Septal e’ (cm/s)	11.2±1.9	10.5±2.0	9.4±2.1	8.9±2.0	8.4±1.9	<0.001
Septal a’ (cm/s)	7.0±1.6	7.7±1.5	8.3±1.5	8.6±1.5	8.8±1.5	<0.001
E (cm/s)	78.8±15.7	73.5±15.4	69.1±14.9	68.5±14.8	69.7±15.2	<0.001
A (cm/s)	47.3±11.2	50.3±12.5	53.1±13.6	55.7±13.6	58.1±13.4	<0.001
Ejection fraction (%)	67.1±6.2	66.6±6.1	66.8±6.1	67.1±6.2	67.8±6.3	<0.001
IVST (mm)	7.1±1.0	7.8±1.1	8.5±1.1	8.9±1.2	9.4±1.3	<0.001
PWT (mm)	6.8±0.9	7.6±1.1	8.2±1.1	8.6±1.1	9.1±1.2	<0.001
LVEDD (mm)	44.5±3.4	47.6±3.7	49.5±3.7	50.2±3.9	51.0±4.0	<0.001
LVESD (mm)	27.9±3.3	30.0±3.5	31.0±3.6	31.4±3.7	31.5±3.9	<0.001
LVEDV (ml)	90.8±16.3	106.2±19.3	116.2±19.9	120.3±21.1	124.8±22.3	<0.001
LVESV (ml)	30.1±8.5	35.7±10.0	38.8±10.7	39.9±11.1	40.5±11.9	<0.001
RWT	0.31±0.05	0.32±0.05	0.33±0.05	0.35±0.05	0.36±0.06	<0.001
LA diameter (mm)	28.5±3.5	31.8±3.7	34.7±3.8	36.9±4.0	39.4±4.2	<0.001
LV mass (g)	93.8±19.9	120.1±27.4	141.9±28.2	154.6±31.4	170.4±34.0	<0.001
LVMI	63.6±12.0	71.8±13.9	77.8±14.3	79.9±15.2	80.3±15.0	<0.001
Impaired LV diastolic function [n, (%)]	57 (5.0)	1,428 (12.0)	1,976 (25.1)	3,297 (35.5)	513 (44.9)	<0.001
Increased RWT [n, (%)]	25 (2.2)	457 (3.8)	465 (5.9)	821 (8.8)	151 (13.2)	<0.001
LVH [n, (%)]	8 (0.7)	176 (1.5)	172 (2.2)	267 (2.9)	26 (2.3)	<0.001

Data are mean (±SD). BMI categories: normal (between 18.5 and 23 kg/m²), underweight (<18.5 kg/m²), overweight (between 23 and 25 kg/m²), obese (between 25 and 30 kg/m²), severe obese (≥30 kg/m²). A, maximum velocity of active mitral filling; BMI, body mass index; E, maximum velocity of passive mitral filling; IVST, interventricular septum thickness; LV, left ventricular; LVDD, LV diastolic dysfunction (septal e’ <8 cm/s); LVEDD, LV end-diastolic diameter; LVEDV, LV end-diastolic volume; LVESD, LV endsystolic diameter; LVESV, LV endsystolic volume; LVH, LV hypertrophy (LVMI >115 (male), LVMI >95 (female)); LVMI, LV mass index; PWT, posterior LV wall thickness; RWT, relative wall thickness: increased RWT, RWT >0.42.

The association between impaired LV diastolic function and the degree of obesity is shown in Table 3. The ORs for impaired LV diastolic function had a dose-response relationship with BMI even after adjusting covariates.

Table 3. OR of Impaired LV Diastolic Function (95% CI) in the Study Group According to BMI

	Unadjusted model	Model 1	Model 2
	OR (95% CI)	OR (95% CI)	OR (95% CI)
Underweight	0.39 (0.29–0.51)	0.62 (0.45–0.83)	0.86 (0.59–1.22)
Normal	Reference	Reference	Reference
Overweight	2.46 (2.28–2.65)	2.09 (1.92–2.28)	1.81 (1.63–2.00)
Obese	4.03 (3.76–4.33)	3.81 (3.51–4.13)	2.75 (2.49–3.03)
Severe obese	5.97 (5.25–6.79)	7.94 (6.87–9.19)	4.34 (3.65–5.16)

Model 1 covariates: age, sex; Model 2 covariates: age, sex, smoking, average alcohol use (g/day), hypertension, diabetes, total cholesterol, HDL-C, hs-CRP. CI, confidence interval; hs-CRP, high-sensitivity C-reactive protein; OR, odds ratio. Other abbreviations as in Tables 1.2.

We also evaluated the association between increased RWT, LV hypertrophy and the degree of obesity in order to investigate LV structural change according to BMI (Table 4). The ORs for increased RWT and hypertrophy were proportionally associated with BMI, but the patterns were subtly different. Whereas the OR for increased RWT was significant in the obese and severe obese groups, the OR for LVH was significant in the overweight and obese groups.

Table 4. OR of Increased RWT and LVH (95% CI) in the Study Group According to BMI

	Unadjusted model	Model 1	Model 2
	OR (95% CI)	OR (95% CI)	OR (95% CI)
Increased RWT
Underweight	0.57 (0.37–0.83)	0.85 (0.55–1.25)	1.01 (0.60–1.60)
Normal	Reference	Reference	Reference
Overweight	1.57 (1.38–1.79)	1.22 (1.06–1.40)	1.04 (0.89–1.22)
Obese	2.43 (2.16–2.73)	1.85 (1.64–2.09)	1.38 (1.19–1.60)
Severe obese	3.81 (3.13–4.62)	3.26 (2.67–3.97)	2.06 (1.62–2.60)
LVH
Underweight	0.47 (0.21–0.90)	0.45 (0.20–0.87)	0.47 (0.14–1.15)
Normal	Reference	Reference	Reference
Overweight	1.49 (1.20–1.84)	1.81 (1.45–2.27)	1.95 (1.43–2.66)
Obese	1.97 (1.63–2.39)	2.61 (2.12–3.23)	2.47 (1.84–3.34)
Severe obese	1.55 (1.00–2.31)	2.23 (1.41–3.40)	1.59 (0.85–2.81)

Model 1 covariates: age, sex; Model 2 covariates: age, sex, smoking, average alcohol use (g/day), hypertension, diabetes, total cholesterol, HDL-C, hs-CRP. Abbreviations as in Tables 1–3.

The adjusted mean values of parameters related with LV diastolic function and structure are presented in Table 5. In general, the overweight, obese, and severe obese groups had more unfavorable echocardiographic parameters such as elevated E/e’, decreased E/A ratio and decelerated septal e’ velocity than the underweight and normal groups. The adjusted mean of E/e’, for instance, showed no significant difference between the underweight and normal-weight groups. However, the normal, overweight, obese, and severe obese groups showed statistically significant results to each other, which indicated a positive dose-response relationship across groups (7.72 [95% confidence interval (CI) 7.59–7.84] in the underweight, 7.67 [95% CI 7.61–7.73] normal weight, 8.03 [95% CI 7.96–8.09] overweight, 8.38 (95% CI 8.32–8.44) obese, and 8.96 (95% CI 8.85–9.07) severe obese groups). The parameters representing LV geometry were also more unfavorably associated with the overweight, obese, and severe obese groups than the underweight and normal groups. In particular, parameters of RWT and LVMI showed a similar dose-dependent relationship with the BMI of the study groups.

Table 5. Adjusted Mean Values of LV Diastolic Function and Cardiac Dimension Parameters (95% CI) in the Study Group According to BMI

	BMI category
	Underweight (n=1,131)	Normal (n=11,897)	Overweight (n=7,875)	Obese (n=9,288)	Severe obese (n=1,143)
E/e’	7.72 (7.59–7.84)	7.67 (7.61–7.73)	8.03 (7.96–8.09)*	8.38 (8.32–8.44)*	8.96 (8.85–9.07)*
E/A ratio	1.53 (1.49–1.58)*	1.44 (1.42–1.47)	1.35 (1.33–1.38)*	1.31 (1.28–1.33)*	1.28 (1.24–1.32)*
Septal e’ (cm/s)	9.86 (9.73–9.99)	9.82 (9.75–9.89)	9.33 (9.26–9.40)*	8.96 (8.89–9.02)*	8.55 (8.43–8.67)
LVEDV (ml)	91.0 (89.5–92.5)	102.8 (102.1–103.6)	110.3 (109.6–111.1)	114.3 (113.5–115.0)*	119.8 (118.5–121.1)*
LA diameter (mm)	29.6 (29.3–29.8)*	32.3 (32.1–32.4)	34.6 (34.5–34.8)*	36.6 (36.5–36.8)*	39.3 (39.0–39.5)*
RWT	0.330 (0.326–0.334)	0.332 (0.330–0.334)	0.336 (0.334–0.338)	0.345 (0.343–0.347)*	0.356 (0.352–0.359)*
LVMI	67.6 (66.6–68.7)*	72.7 (72.2–73.3)	76.1 (75.5–76.6)*	77.7 (77.1–78.2)*	78.2 (77.3–79.1)*

*P<0.05 to normal value. Data are adjusted mean values for covariates: age, sex, smoking, average alcohol use (g/day), hypertension, diabetes, total cholesterol, HDL-C, hs-CRP. BMI categories: normal (between 18.5 and 23 kg/m²), underweight (<18.5 kg/m²), overweight (between 23 and 25 kg/m²), obese (between 25 and 30 kg/m²), severe obese (≥30 kg/m²). LA, left atrial. Other abbreviations as in Tables 1–3.

Discussion

In a cohort of apparently healthy general Korean population, we investigated the association between functional and structural LV abnormalities and the degree of obesity stratified by BMI. In this study, we found that increased BMI was closely associated with both functional and structural LV abnormalities. The ORs for impaired LV diastolic function, increased RWT and LVMI increased proportionally with the BMI of the study groups even after adjusting for multiple covariates. Additionally, the adjusted mean values of echocardiographic parameters reflecting diastolic dysfunction, remodeling and hypertrophy were significantly associated with increased BMI. These findings indicate the proportional relationship between functional and structural LV abnormalities and the degree of obesity, which is consistent with previous studies. Obesity is a potential risk factor for heart failure even with preserved systolic LV function,³ and BMI is proportionally associated with the risk of cardiovascular disease including heart failure.¹⁷ In particular, several studies report a close relationship between obesity and LVDD.^5,18,19 In a community-based cohort of subjects aged over 50 years, the risk of diastolic dysfunction was higher in overweight (BMI 25.0–29.9 kg/m²) and obese (BMI ≥30 kg/m²) subjects compared with normal subjects (BMI <25.0 kg/m²).⁵ A study of Turkish adults also showed the independent predictability of BMI for LVDD together with age, hypertension and diabetes.⁶ However, because these studies were based on data for Westerners with a conventional criterion of obesity, their findings cannot necessarily be extrapolated to Asians. Although there are several studies of Asians, they all have a limitation in establishing the correct association between structural and functional LV abnormalities and BMI. A study of Asian Indians demonstrated significant morphological and functional cardiac abnormalities in people with uncomplicated obesity, but its size of 239 study subjects was too small for the data to be generalized.²⁰ The Multi-Ethnic Study of Atherosclerosis (MESA) also showed a significant relationship of obesity with concentric LV remodeling in a multi-ethnic group including Chinese-Americans but could not clarify an ethnic-specific relationship.²¹ Furthermore, the appropriate cutoff of BMI for increased cardiovascular risk in Asians is still debatable. The commonly used guideline of obesity set by the World Health Organization (WHO) defines 25 kg/m² as the cutoff between normal and overweight and 30 kg/m² as the cutoff between overweight and obese.²² However, there is substantial evidence showing typical features of Asians in the relationship between BMI and cardiovascular risk. Asians have higher cardiovascular morbidity and mortality at given BMIs compared with Westerners, and some Asians have increased risk of diabetes and cardiovascular disease even within a “normal” BMI.^14,23–26 Therefore, such controversy confers the necessity of seeking the cutoff of BMI that increases the cardiovascular risk in Asians. The present study demonstrated a higher prevalence for LV diastolic dysfunction, remodeling, and hypertrophy in the obese and overweight groups than in a normal group defined by cutoff BMI values of 23 kg/m² and 25 kg/m², which could be evidence supporting the eligibility of an Asian-Pacific cutoff point.

Regarding underweight, we did not find a significant association between the underweight group and functional and structural LV abnormalities. However, previous studies have demonstrated the clinical significance of underweight as an obvious risk factor for cardiovascular events and death.^26–29 In particular, several studies show a U-shaped association between cardiovascular death and BMI, which implies an adverse influence of underweight on cardiovascular disease.^26–28 This discrepancy appears to be attributable to features of our study design and participants. Our study was cross-sectional in design, which has limitation in identifying a causative relationship between BMI and cardiovascular disease. Additionally, study participants were apparently healthy and comparatively young with an average age of 40.4±7.8 years. Thus, there is a possibility that the adverse outcome of underweight was yet to manifest at the time of our study, which suggests the necessity of subsequent study to investigate the long-term effect of BMI on functional and structural LV change.

A merit of this study is the robust sample size comprising a general Korean population receiving a medical health check-up with echocardiography, which enabled a large-scale study to estimate echocardiographically defined functional and structural LV deterioration according to BMI.

Nonetheless, several limitations should be considered. First, 98% of our study participants were comparatively young or middle-aged Koreans. Therefore, our study findings cannot be extrapolated to the elderly or to other ethnic groups. Second, we did not measure some echocardiographic parameters, such as lateral e’ velocity, isovolumic relaxation time and LA volume. These unmeasured parameters might have influenced our results. However, as mentioned, most of our study population was asymptomatic and young, undergoing echocardiography as an item of a health check-up program. Thus, it was not possible to measure all echocardiographic parameters.

In conclusion, our study demonstrated a proportional relationship between BMI and LVDD, LV remodeling, and hypertrophy. This result suggests that obese people are exposed to higher risk for heart failure than normal-weight people. Additionally, given that cutoffs of BMI for increased functional and structural LV abnormalities were 23, 25 and 30 kg/m², our study supports the validity of an Asian-Pacific obesity guideline. However, further prospective study with a longitudinal design is required to clarify the causal relationship between BMI and cardiovascular risk.

Conflict of Interest

Nothing to be declared. The authors report no relationships that could be construed as a conflict of interest.

Acknowledgments

This study was based on medical data collected and arranged by the Kangbuk Samsung Cohort Study (KSCS). Therefore, this study was possible by virtue of the work of all staff working in the KSCS and Total Healthcare Center, Kangbuk Samsung Hospital. Additionally, we especial appreciate Ms Jiin Ahn and Professor Yoosoo Chang of the Kangbuk Samsung Cohort team. We are also grateful to the staff working in the gastroenterology division of Kangbuk Samsung Total Healthcare Center (Hee Seon Kim, Na Rae Ha and Yun Young Lee). Their technical and statistical assistance contributed greatly to the making of our study.

Author Contributions

S.K.P. and J.-H.R. coordinated the study, analyzed the data and wrote the manuscript as co-first authors. C.-M.O. and J.Y.J. analyzed the data and edited the manuscript. J.G.K. and J.-M.C. contributed to writing the discussion and reviewing the manuscript. J.-H.L. and J.Y.C. participated in reviewing the manuscript. J.Y.J. is the guarantor of this work and, as such, had full access to all the data in the study and takes responsibility for the integrity of the data and the accuracy of the data analysis.

Financial Support / Disclosure Statement

The authors have nothing to disclose.

Authorship

All authors had access to the data used in this study and participated in writing the manuscript.

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