Abstract
Background:
Cardiac enlargement is an important predictor of adverse cardiovascular (CV) events. Left ventricular (LV) dilatation is a precursor both of LV dysfunction and clinical heart failure. The present study examines risk factors for LV dilatation among 832 young adults (341 male, 491 female) who participated in the Bogalusa Heart Study.
Hypothesis:
A unique set of risk factors predicts LV dilatation among young adults.
Methods:
Standard ventricular dimensions were determined by M‐mode echocardiography and indexed to height using a standard method. LV dilatation was considered as the top 20th percentile of LV end‐diastolic dimension indexed to height. Logistic regression models were used, stratified by race and sex, to assess the relationship of CV risk factors with quintile of LV end‐diastolic dimension indexed to height.
Results:
The mean age (standard deviation) of men and women in the population was 36.4 years (3.9 years) and 35.9 years (4.6 years), respectively. In sex‐specific models adjusted for age, race, systolic and diastolic blood pressure, high‐density lipoprotein cholesterol, low‐density lipoprotein cholesterol, triglycerides, and glycosylated hemoglobin, body mass index (BMI) was a significant predictor of LV dilatation in both men and women. The odds ratio (95% confidence interval) for a 1‐unit change in BMI was 1.12 (1.02–1.19) in men and 1.09 (1.05–1.13) in women. Among men, triglyceride level was also significantly associated with LV dilatation (P = 0.03), whereas among women there was no such association.
Conclusions:
Our findings indicate that obesity is the most consistent predictor of LV dilatation in both men and women, whereas triglyceride level was a significant predictor among men only. © 2011 Wiley Periodicals, Inc.
The Bogalusa Heart Study is supported by a grant from the National Institute of Aging (5R01AG016592). Dr. Bazzano was supported by grant no. K08HL091108 from the National Heart Lung and Blood Institute (NHLBI). The authors have no other funding, financial relationships, or conflicts of interest to disclose.
Introduction
Cardiovascular disease (CVD) is the leading cause of death in the United States and world‐wide, accounting for 30.9% of global mortality and 10.3% of the global burden of disease.1 Of all deaths in the United States, 34.3% or 831272 deaths (1 in every 2.9 deaths) are due to CVD.2 According to the latest estimates, approximately 81.1 million Americans (more than 1 in 3) have 1 or more forms of CVD, and the estimated annual direct and indirect cost of caring for Americans with CVD is $503.2 billion dollars.2 Therefore, CVD is the most important public health challenge in the United States and world‐wide.
Cardiac enlargement is an important predictor of adverse cardiovascular (CV) events among healthy middle‐aged and elderly people.3, 4, 5 Among persons with coronary heart disease, cardiac enlargement, and specifically left ventricular (LV) end‐diastolic diameter, is suggested to be a precursor of heart failure.6, 7, 8, 9 Yet, among young individuals without symptomatic ischemic heart disease or heart failure the prevalence and risk factors for early LV dilatation have not been well studied. It is now established that significant coronary atherosclerosis and hypertensive CV disease occur in asymptomatic individuals prior to clinical cardiac events. Therefore, to examine the relationship between CV risk factors and LV end‐diastolic diameter (LVEDD) in younger age groups, we took advantage of the large population of young adults with detailed echocardiographic measures in the Bogalusa Heart Study.
Methods
The Bogalusa Heart Study is a long‐term epidemiological study of the natural history of CV disease beginning in childhood from the semirural, biracial (65% white, 35% black) community of Bogalusa, Louisiana. The population and study design of the Bogalusa Heart Study have been previously described.8, 9 Some 246 white males, 95 black males, 324 white females, and 167 black females underwent M‐mode echocardiography as part of a continuing risk factor study. Informed consent was obtained from all participants and the protocols were reviewed by the institutional review board of the Tulane University Health Science Center.
General Examination
All examinations followed previously described protocols.9, 10 Height and weight were measured twice to the nearest 0.1 cm and to the nearest 0.1 kg, respectively, and the average values were used to calculate body mass index (BMI) as a measure of overall adiposity. Replicate blood pressure measurements were obtained by trained observers on the right arm of the subjects in a relaxed, sitting position. Arm measurements, length and circumference, were made during the examination to ensure proper cuff size. Systolic and diastolic blood pressure levels were recorded as the 1st, 4th, and 5th Korotkoff phases using mercury sphygmomanometers. Blood pressure levels were reported as the mean of six 5th phase replicate readings, taken by each of 2 randomly assigned observers.
Subjects were instructed to fast for 12 hours before screening, with compliance ascertained by interview on the morning of the examination. Venipuncture was performed after confirmation of a 12‐hour fast. Serum total cholesterol and triglyceride levels were assayed using an enzymatic procedure on the Abbott VP instrument (Abbott Laboratories, Chicago, IL). Serum lipoprotein cholesterol levels were analyzed by a combination of heparin‐calcium precipitation and agar‐agarose gel electrophoresis procedures.10 The laboratory was monitored by the Lipid Standardization and Surveillance Program of the Centers for Disease Control and Prevention in Atlanta, Georgia. A commercial radioimmunoassay kit was used for measuring plasma immunoreactive insulin levels (Phadebas insulin kit; Pharmacia Diagnostics, Piscataway, NJ). Plasma glucose levels were measured as part of a multiple chemistry profile (SMA20; Laboratory Corporation of America, Burlington, NC) by a glucose oxidase method. The homeostasis model of insulin resistance (HOMA‐IR) was used as a measure of insulin resistance.11 An index of insulin resistance was calculated according to the homeostasis model formula: HOMA‐IR=fasting insulin (μU/mL) × fasting glucose (mmol/L)/22.5. This model is considered useful to assess insulin resistance in epidemiologic studies.12
Aorta‐femoral pulse wave velocity (PWV) measurements were performed using the Toshiba Power Vision SSH‐380 (Toshiba America Medical Systems, Tustin, CA). A transcutaneous Doppler flow probe (2.5 MHz) was positioned at the suprasternal notch and another probe (7.5 MHz) was positioned at the left femoral artery in a supine position. After collection of waveform data, the distance between the aorta and femoral arteries was measured. Aorta‐femoral PWV was calculated by dividing the distance traveled by the time differential between 2 waveforms. A mean of 3 replicate measurements was used.
Echocardiography
LV dimensions were assessed by 2‐dimensional M‐mode echocardiography with 2.25‐ and 3.5‐MHz transducers according to the American Society of Echocardiography recommendations.13 Images were recorded on standard VHS videocassette tapes by trained technicians, and repeated observations were obtained on a random 6% sample of subjects selected for repeat measurements 10 to 12 days apart. The measurement errors were consistent with other epidemiological studies. The coefficient of variation for inter‐reader and intrareader variability for all measures of cardiac anatomy was less than 10%. All echocardiograms were digitized and measured on Tomtec/Freeland Cardiology Workstation digitizing systems (Tomtec/Freeland Systems, Broomfield, CO).
Parasternal long and short axis views were used for measuring LV end‐diastolic and LV end‐systolic measurements in duplicate and then averaged. LVEDD (indexed to height, lean body mass, and/or body surface area) was then categorized into quintiles to avoid assumptions about the dose‐response shape of any association identified. LV mass was calculated based on the formula recommended by Devereux.14 Fractional shortening was calculated. Mitral inflow velocity patterns were available only as velocity time integrals. We calculated the ratio of E‐wave mitral velocity time integral to A‐wave mitral velocity time integral.
Statistical Analysis
Independent variables were compared across quintiles of LVEDD. LV dilatation was considered as the top 20th percentile of LVEDD indexed to height, lean body mass, and/or body surface area. Tests for linear trend were performed using orthogonal trend coefficients. Sex‐specific means and standard deviations (SD) for continuous variables or percentages for categorical variables are presented.
We used multiple logistic regression analysis based on maximum‐likelihood methods to calculate multivariable‐adjusted odds ratios and 95% confidence intervals (CIs) for LV dilatation defined as having an LVEDD in the top 20th percentile adjusted for age (in 5‐year increments), race (black vs white), BMI (kg/m2), systolic blood pressure (mm Hg), diastolic blood pressure (mm Hg), total serum cholesterol (mg/dL), low‐density lipoprotein (LDL) cholesterol (mg/dL), high‐density lipoprotein (HDL) cholesterol (mg/dL), triglycerides (mg/dL), glycosylated hemoglobin (%), and aorta‐femoral PWV (cm/msec). Independent variables were modeled both in continuous and categorical form. For example, BMI was modeled both as a continuous predictor (1 kg/m2 increment) as well as categorically in the form of standard definitions of overweight (BMI ≥25 and <30 kg/m2 and obesity (BMI ≥30 kg/m2). Additionally, blood pressures were modeled both continuously as systolic and diastolic pressures and as the presence or absence of hypertension.
In sensitivity analyses, we used separate models where LVEDD was indexed to height2.7, lean body mass, or body surface area to ensure that our results were robust to the effect of different methods of indexing to account for body size in young adults.15, 16, 17 All data analyses were performed using SAS version 9.0 for Windows (SAS Institute Inc., Cary, NC).
Results
Of the 1357 participants who had echocardiographic measures, 405 were excluded due to missing measures of LVEDD, 119 were excluded due to missing data on race and sex. A total of 832 participants, ranging in age from 23 years to 43 years, were included in this analysis. We examined the available demographic and risk factor data for those participants who were excluded and found no significant differences in age, race, or current smoking habit as compared to participants who were included in the current analysis. However, participants who were missing data were more likely to be men and less likely to have completed high school than those participants who were not missing data.
The mean age (SD) of men and women in the population was 36.4 (3.9) and 35.9 (4.6), respectively. Table 1 shows mean and standard deviation or percent of participants with risk factors and echocardiographic parameters by quintiles of LVEDD indexed by height for males, and Table 2 for females. Among both men and women, a higher proportion of blacks had LVEDD in the uppermost quintiles; however, this trend did not reach statistical significance. Of black women, 23.9% were in the top quintile of LVEDD indexed to height, whereas only 18.0% of white women were in the top quintile of LV end‐diastolic diameter indexed to height. Similarly, among black men, 25.7% were in the top quintile of LVEDD indexed to height, whereas only 17.9% of white men were in the top quintile of LVEDD indexed to height. BMI was strongly and significantly associated with LVEDD indexed to height in both men and women. Among women, hypertension, diabetes, LDL cholesterol levels, triglycerides, insulin levels, HOMA‐IR and, glycosylated hemoglobin increased across quintiles of LVEDD indexed to height. In contrast, HDL cholesterol levels decreased across quintiles. Among men, total serum cholesterol and insulin levels, and HOMA‐IR increased across quintiles of LVEDD indexed to height. Among both men and women, LV mass and mass index increased across quintiles, whereas interventricular septal thickness in diastole decreased in men and decreased marginally in women. Among men, LV diastolic posterior wall thickness also decreased significantly across quintiles.
Table 1.
Risk Factors and Echocardiographic Parameters by Quintiles of Left Ventricular End‐Diastolic Diameter Indexed by Height Among Men
| Left Ventricular End Diastolic Diameter Indexed by Height | |||||
|---|---|---|---|---|---|
| Men Only, N = 341 | Quintile 1 | Quintile 2 | Quintile 3 | Quintile 4 | Quintile 5 |
| No. | 67 | 69 | 68 | 69 | 68 |
| Age, y | 37.2 ± 4.5 | 36.4 ± 4.3 | 36.4 ± 3.9 | 35.7 ± 4.5 | 36.4 ± 4.1 |
| Race | |||||
| Black | 19.4 | 30.4 | 29.4 | 24.6 | 35.3 |
| White | 80.6 | 69.6 | 70.6 | 75.4 | 64.7 |
| Current smokers | 37.3 | 37.7 | 33.3 | 21.7 | 34.3 |
| BMI (kg/m2) | 26.1 ± 5.0 | 27.1 ± 4.5 | 27.5 ± 4.8 | 29.3 ± 5.6 | 31.0 ± 5.6 |
| Hypertensive | 14.9 | 18.8 | 14.7 | 10.1 | 16.1 |
| Diabetes | 3.0 | 2.9 | 2.9 | 2.9 | 1.5 |
| Systolic blood pressure (mm Hg) | 119.1 ± 10.4 | 120.1 ± 12.7 | 119.1 ± 13.6 | 118.4 ± 11.0 | 122.5 ± 14.8 |
| Diastolic Blood pressure (mm Hg) | 80.9 ± 7.8 | 81.0 ± 8.6 | 80.4 ± 8.8 | 80.4 ± 8.2 | 82.6 ± 10.2 |
| Total serum cholesterol (mg/dL) | 183.1 ± 38.2 | 193.9 ± 38.4 | 197.0 ± 49.6 | 195.2 ± 36.6 | 199.2 ± 44.2 |
| HDL cholesterol (mg/dL) | 46.4 ± 13.8 | 46.8 ± 15.0 | 48.5 ± 18.2 | 45.5 ± 15.6 | 43.8 ± 12.8 |
| LDL cholesterol (mg/dL) | 109.1 ± 33.0 | 117.7 ± 35.5 | 118.9 ± 38.5 | 123.0 ± 33.3 | 118.3 ± 37.5 |
| Triglycerides (mg/dL) | 145.3 ± 138.9 | 154.8 ± 128.3 | 146.5 ± 140.0 | 142.7 ± 117.7 | 188.2 ± 144.8 |
| Insulin | 10.6 ± 7.6 | 10.9 ± 6.6 | 12.0 ± 11.0 | 10.8 ± 6.2 | 14.6 ± 10.7 |
| HOMA‐IR | 2.3 ± 2.1 | 2.4 ± 1.6 | 3.1 ± 3.5 | 2.4 ± 1.6 | 3.3 ± 2.7 |
| HbA1C (%) | 5.7 ± 0.4 | 5.9 ± 1.3 | 6.0 ± 1.3 | 5.7 ± 0.5 | 5.8 ± 0.5 |
| Fibrinogen | 248.6 ± 25.8 | 255.6 ± 37.2 | 255.9 ± 32.8 | 249.9 ± 27.4 | 252.2 ± 50.7 |
| LV end diastolic diameter (cm) | 4.8 ± 0.5 | 5.2 ± 0.4 | 5.3 ± 0.4 | 5.5 ± 0.4 | 6.0 ± 0.6 |
| LV mass (g) | 186.1 ± 49.3 | 195.7 ± 45.2 | 205.3 ± 50.8 | 211.5 ± 51.4 | 238.0 ± 55.9 |
| LV mass index (g/m2.7) | 28.8 ± 6.8 | 32.1 ± 7.2 | 34.9 ± 8.2 | 36.8 ± 7.9 | 42.1 ± 8.3 |
| LV diastolic posterior wall (cm) | 0.87 ± 0.16 | 0.82 ± 0.15 | 0.84 ± 0.16 | 0.82 ± 0.14 | 0.79 ± 0.14 |
| IVS diastolic thickness (cm) | 0.90 ± 0.16 | 0.88 ± 0.17 | 0.85 ± 0.17 | 0.83 ± 0.14 | 0.81 ± 0.13 |
| Fractional shortening (%) | 32.9 ± 7.1 | 34.1 ± 7.2 | 35.7 ± 6.4 | 34.1 ± 7.1 | 30.7 ± 7.7 |
| Mitral VTI E/A ratio | 2.5 ± 1.1 | 2.7 ± 1.0 | 2.9 ± 1.5 | 2.6 ± 1.2 | 2.5 ± 1.2 |
| Aorta femoral PWV (cm/msec) | 0.54 ± 0.07 | 0.53 ± 0.09 | 0.52 ± 0.07 | 0.52 ± 0.08 | 0.54 ± 0.10 |
Abbreviations: PWV, pulse wave velocity; BMI, body mass index; HbA1C, glycosylated hemoglobin; HDL, high density lipoprotein; HOMA‐IR, insulin resistance index; IVS; interventricular; LDL, low‐density lipoprotein; LV; left ventricular; VTI E/A; mitral valve velocity time integral E to A ratio.
Table 2.
Risk Factors and Echocardiographic Parameters by Quintiles of Left Ventricular End‐Diastolic Diameter Indexed to Height Among Women
| Left Ventricular End‐Diastolic Diameter Indexed to Height | |||||
|---|---|---|---|---|---|
| Women Only, N = 491 | Quintile 1 | Quintile 2 | Quintile 3 | Quintile 4 | Quintile 5 |
| No | 98 | 98 | 97 | 100 | 98 |
| Age, y | 36.3 ± 4.6 | 35.9 ± 4.6 | 35.9 ± 4.6 | 36.3 ± 4.3 | 35.9 ± 4.6 |
| Race | |||||
| Black | 34.7 | 22.4 | 36.1 | 36.0 | 40.8 |
| White | 65.3 | 77.6 | 63.9 | 64.0 | 59.2 |
| Current smokers | 26.8 | 32.7 | 29.9 | 29.0 | 26.5 |
| BMI (kg/m2) | 25.1 ± 5.4 | 27.3 ± 7.2 | 28.5 ± 7.2 | 29.9 ± 7.3 | 32.2 ± 8.0 |
| Hypertensive | 8.2 | 10.2 | 13.4 | 26.0 | 15.5 |
| Diabetes | 0.0 | 3.1 | 4.1 | 4.0 | 4.1 |
| Systolic blood pressure (mm Hg) | 111.9 ± 13.1 | 111.1 ± 12.6 | 111.7 ± 12.1 | 115.7 ± 15.7 | 113.9 ± 13.0 |
| Diastolic blood pressure (mm Hg) | 75.2 ± 8.7 | 74.4 ± 8.7 | 75.6 ± 9.8 | 77.5 ± 10.8 | 77.4 ± 9.5 |
| Total serum cholesterol (mg/dL) | 185.9 ± 35.4 | 186.8 ± 33.7 | 190.7 ± 34.6 | 190.5 ± 34.5 | 192.1 ± 41.4 |
| HDL cholesterol (mg/dL) | 58.3 ± 17.8 | 55.2 ± 12.9 | 53.4 ± 14.1 | 51.6 ± 13.3 | 52.8 ± 12.2 |
| LDL cholesterol (mg/dL) | 107.8 ± 33.5 | 107.9 ± 30.6 | 114.3 ± 32.0 | 114.5 ± 29.2 | 115.4 ± 37.8 |
| Triglycerides (mg/dL) | 96.6 ± 52.1 | 117.5 ± 73.6 | 116.2 ± 78.2 | 119.5 ± 66.7 | 117.0 ± 65.1 |
| Insulin | 10.1 ± 6.9 | 11.7 ± 10.3 | 11.9 ± 8.0 | 12.4 ± 7.2 | 13.6 ± 12.5 |
| HOMA‐IR | 2.1 ± 1.5 | 2.5 ± 2.8 | 3.1 ± 4.6 | 3.0 ± 2.5 | 3.2 ± 3.8 |
| HbA1C (%) | 5.8 ± 0.4 | 5.8 ± 0.6 | 6.0 ± 0.7 | 6.0 ± 0.6 | 6.0 ± 0.8 |
| Fibrinogen | 253.5 ± 29.7 | 257.0 ± 37.0 | 263.8 ± 36.0 | 256.5 ± 34.2 | 262.6 ± 30.6 |
| LV end diastolic diameter (cm) | 4.5 ± 0.4 | 4.8 ± 0.4 | 4.9 ± 0.4 | 4.9 ± 0.4 | 5.2 ± 0.5 |
| LV mass (g) | 137.8 ± 45.4 | 146.5 ± 46.9 | 151.4 ± 49.3 | 159.8 ± 50.8 | 166.7 ± 50.2 |
| LV mass index (g/m2.7) | 26.5 ± 8.5 | 29.3 ± 8.1 | 31.6 ± 9.5 | 35.2 ± 10.2 | 38.6 ± 10.2 |
| LV diastolic posterior wall (cm) | 0.75 ± 0.19 | 0.74 ± 0.15 | 0.74 ± 0.17 | 0.75 ± 0.17 | 0.72 ± 0.14 |
| IVS diastolic thickness (cm) | 0.79 ± 0.19 | 0.75 ± 0.16 | 0.75 ± 0.17 | 0.77 ± 0.17 | 0.73 ± 0.14 |
| Fractional shortening (%) | 35.3 ± 7.1 | 34.8 ± 6.6 | 35.6 ± 7.3 | 34.3 ± 6.2 | 34.1 ± 6.0 |
| Mitral VTI E/A ratio | 2.5 ± 1.1 | 2.6 ± 1.4 | 2.4 ± 1.2 | 2.3 ± 1.2 | 2.5 ± 1.5 |
| Aorta femoral PWV (cm/msec) | 0.52 ± 0.09 | 0.50 ± 0.09 | 0.53 ± 0.15 | 0.53 ± 0.09 | 0.53 ± 0.11 |
Abbreviations: PWV, pulse wave velocity; BMI, body mass index; HbA1C, glycosylated hemoglobin; HDL, high‐density lipoprotein; HOMA‐IR, insulin resistance index; IVS; interventricular; LDL, low‐density lipoprotein; LV; left ventricular; VTI E/A; mitral valve velocity time integral E to A ratio.
Multivariable‐adjusted odds ratios and 95% CIs for risk factors related to LVEDD are presented by sex in Table 3. After adjustment for age, race, body mass index, systolic and diastolic blood pressure, LDL cholesterol, HDL cholesterol, triglycerides, and glycosylated hemoglobin level among both men and women, BMI was the strongest risk factor for LV end‐diastolic dilatation (OR, 1.12; 95% CI, 1.02–1.19 in men; OR, 1.09; 95% CI, 1.05–1.13 in women). Among men, triglyceride level was also significantly positively associated with LV end‐diastolic dilatation, whereas among women, this was not the case.
Table 3.
Multivariate‐Adjusted Odds Ratios and 95% Confidence Intervals of Risk Factors for Left Ventricular End‐Diastolic Diameter Indexed to Height in Top Quintile by Gender.
| Risk Factora | Odds Ratio | 95% Confidence Interval | P Value |
|---|---|---|---|
| Men | |||
| Age (y) | 0.989 | (0.918–1.065) | 0.76 |
| Raceb | 1.371 | (0.652–2.881) | 0.40 |
| BMI (kg/m2) | 1.119 | (1.015–1.193) | 0.0006 |
| Systolic blood pressure (mm Hg) | 1.005 | (0.963–1.048) | 0.83 |
| Diastolic blood pressure (mm Hg) | 0.979 | (0.923–1.038) | 0.48 |
| HDL cholesterol (mg/dL) | 1.004 | (0.979–1.030) | 0.77 |
| LDL cholesterol (mg/dL) | 0.999 | (0.990–1.007) | 0.73 |
| Triglycerides (mg/dL) | 1.005 | (1.001–1.009) | 0.02 |
| HbA1C (%) | 0.863 | (0.578–1.289) | 0.47 |
| Women | |||
| Age (yr) | 1.004 | (0.949–1.061) | 0.90 |
| Race | 1.460 | (0.820–2.601) | 0.20 |
| BMI (kg/m2) | 1.087 | (1.049–1.129) | <0.0001 |
| Systolic blood pressure (mm Hg) | 0.956 | (0.918–0.995) | 0.03 |
| Diastolic blood pressure (mm Hg) | 1.037 | (0.984–1.023) | 0.17 |
| HDL cholesterol (mg/dL) | 1.004 | (0.984–1.023) | 0.72 |
| LDL cholesterol (mg/dL) | 1.000 | (0.992–1.007) | 0.92 |
| Triglycerides (mg/dL) | 1.001 | (0.996–1.005) | 0.72 |
| HbA1C (%) | 1.133 | (0.780–1.644) | 0.51 |
Abbreviations: BMI, body mass index; HbA1C, glycosylated hemoglobin; HDL, high‐density lipoprotein; LDL, low‐density lipoprotein.
All odds ratios are simultaneously adjusted for age, race, body mass index, systolic and diastolic blood pressure, LDL cholesterol, HDL cholesterol, triglycerides and glycosylated hemoglobin level, and expressed in relation to a 1 unit change in the risk factor, for example, a 1‐year change in age or 1‐mm Hg change in blood pressure.
Race signifies black as compared to white.
To clarify the role of obesity in LV end‐diastolic dilatation, we compared echocardiographic parameters among men and women who were obese and those who were not. Table 4 presents these comparisons. Both men and women who were obese had significantly greater values for LVEDD, LV mass, posterior and septal wall thickness, and lower values of mitral velocity time integral E:A ratio. The Figure 1 illustrates the relationship between LVEDD and BMI category: normal (<25 kg/m2), overweight (>25 and <30 kg/m2), and obese (>30 kg/m2) for each race‐sex group. Indexing LVEDD to fat free body mass or body surface area to account for body size did not affect the results (data not shown). Across all race‐sex groups, BMI was significantly positively associated with LVEDD regardless of method of indexing for body size.
Table 4.
Echocardiographic Parameters by Level of Body Mass Index
| Men | Women | |||||
|---|---|---|---|---|---|---|
| BMI | >30 | <30 | P Value | >30 | <30 | P Value |
| No. | 103 | 238 | 181 | 310 | ||
| LV end diastolic diameter | 5.7 ± 0.6 | 5.2 ± 0.5 | <0.0001 | 5.1 ± 0.5 | 4.7 ± 0.5 | <0.0001 |
| LV mass (g) | 246.4 ± 52.9 | 190.5 ± 43.8 | <0.0001 | 187.4 ± 47.2 | 132.1 ± 38.0 | <0.0001 |
| LV mass index (g/m2.7) | 41.1 ± 8.8 | 32.3 ± 7.5 | <0.0001 | 39.5 ± 10.1 | 28.0 ± 7.6 | <0.0001 |
| LV diastolic posterior wall | 0.88 ± 0.18 | 0.81 ± 0.18 | 0.0001 | 0.82 ± 0.18 | 0.69 ± 0.14 | <0.0001 |
| IVS diastolic thickness | 0.90 ± 0.16 | 0.83 ± 0.15 | 0.0001 | 0.84 ± 0.17 | 0.71 ± 0.15 | <0.0001 |
| Fractional shortening (%) | 32.4 ± 7.6 | 34.0 ± 7.1 | 0.07 | 35.5 ± 6.5 | 34.4 ± 6.7 | 0.08 |
| Mitral VTI E/A ratio | 2.4 ± 1.0 | 2.7 ± 1.3 | 0.05 | 2.2 ± 0.9 | 2.6 ± 1.44 | <0.0001 |
| Aorta femoral PWV (cm/msec) | 0.54 ± 0.08 | 0.52 ± 0.09 | 0.08 | 0.53 ± 0.11 | 0.51 ± 0.11 | 0.01 |
BMW, body mass index, IVS, interventricular septum; LV, left ventricular; PWV, pulse wave velocity; VTI E/A, mitral valve velocity time integral E to A ratio.
Figure 1.
Mean left ventricular end‐diastolic diameter indexed to height presented by sex, race, and body mass index categories. P value for trend <0.001 for body mass index categories.
Discussion
In the present study, obesity was the strongest and most consistent determinant of LVEDD among both men and women. Among men, a significant positive relationship was observed between triglyceride level and LVEDD. Earlier studies in this cohort have shown that obesity even precedes hyperinsulinemia in development of the metabolic syndrome and is the major predictor of increased LV mass as an adult.18, 19 These observations emphasize the importance of obesity as a risk factor for LV end‐diastolic dilatation and potentially subsequent CV events, specifically heart failure.
The prevalence of obesity in the United States has doubled in adults and children and tripled in adolescents over the past 2 decades. More than two‐thirds of Americans are overweight or obese.20, 21 In the United States, between 300 000 and 400 000 deaths annually are attributable to obesity, and $75 billion dollars were spent in 2003 on healthcare and related costs.22, 23 With its important relationship to dyslipidemia, hypertension, and diabetes mellitus, increasing obesity may be a major contributor to the pathogenesis of LV enlargement and mediator of heart failure as indicated by LV dilatation.
The contribution of obesity to heart disease, and particularly heart failure, has gained recognition in recent years.24 After over 14 years of follow‐up, Framingham investigators found a 5% to 7% increase in relative risk of developing heart failure for each increase of 1 unit in BMI.25 Obesity can lead to LV dilatation by multiple mechanisms including excessive vascularity of adipose tissue, increasing total blood volume, and cardiac output.26 Obesity can also cause an accumulation of lipids around myocytes with resulting lipotoxicity. Adipocytes generate cytokines and inflammatory factors that enhance cardiac remodeling. Further, the presence of relatively large numbers of stem cells in adipose tissue may influence apoptosis and angiogenesis important to remodeling of the heart.27, 28 Cardiac dilatation also produces increased stress and a compensatory hypertrophy with increased collagen formation. The loss of compliance with such structural change results in echocardiographic detection of diastolic dysfunction. The comparison of obese to nonobese individuals in this cohort showed that mitral velocity time integral E:A ratio was lower among obese individuals, whereas LV posterior wall and interventricular septal thickness in diastole was higher among obese individuals as compared to those with normal BMI. LV mass and mass index were also significantly higher among the obese individuals. Yet, with increasing LV dilatation, wall thickness tended to decrease, which may be consistent with a pattern of eccentric enlargement. The current study reflects various LV myocardial structural changes occurring in a young adult population. Specific aspects of LV structure must be resolved in individuals by the etiology and specific pattern of remodeling that may be present.
This study is a cross‐sectional examination of risk factors for LV end‐diastolic dilatation among asymptomatic young adults. Because risk factor data were collected at the same time as echocardiographic data, temporality cannot be inferred from this cross‐sectional examination. Nevertheless, data from this cohort and others have strongly suggested that obesity precedes LV remodeling and likely other cardiac changes.29, 30 Subsequent development of heart failure becomes predictable by such changes.7, 25 Additional evidence indicates that obesity has a direct effect on the myocardium through cardiac steatosis and lipoapoptosis.31
Conclusion
In the current study, an increase in LV mass and abnormal diastolic function was observed particularly when BMI was greater than 30 kg/m2. In addition, fractional shortening was altered with marginal statistical significance. Long‐term follow‐up of obese children will aid in determining the natural course of LV dilatation leading to clinical heart failure. There is substantial evidence that even modest weight reduction in severely obese individuals has the potential to beneficially affect LV hypertrophy and improve cardiac function in both systole and diastole.32 Current findings clearly show that obesity among young and middle‐aged adults is a determinant of cardiac dilatation and likely predictive of heart failure in a susceptible population. These observations stress the importance of preventive strategies for obesity directed to young adults and beginning in childhood.
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