Background
Echocardiographic measures of left ventricular (LV) mass and relative wall thickness and left atrial (LA) size predict future cardiovascular morbidity and mortality. The aim of this study was to compare young adults with low cardiovascular risk (body mass index, 18.5–24.9 kg/m 2 ; blood pressure < 120/80 mmHg; no tobacco use, no diabetes, and physical fitness) with those without these characteristics with regard to LV mass and relative wall thickness and LA size, to determine the protective effect of a healthy lifestyle on the development of these characteristics.
Methods
Cross-sectional assessment of 4059 black and white men and women aged 23 to 35 years in the Coronary Artery Risk Development in Young Adults (CARDIA) study at the year 5-examination, when risk factors were measured, and echocardiography to assess LV mass and relative wall thickness were performed. Physical fitness was measured at baseline using a symptom-limited maximal treadmill test. All other covariates were measured concurrently with echocardiography.
Results
Gender, body mass index, and systolic blood pressure were associated with LV mass and relative wall thickness and LA size in multivariate models. Additional correlates of LV mass/height 2.7 ratio were tobacco use, resting heart rate (inverse), self-reported physical activity, gender (male higher), and age. Age was associated with LV relative wall thickness but not other measures of LV size. Additional correlates of LA diameter/height ratio were tobacco use, resting heart rate (inverse), serum glucose, and self-reported physical activity. Seven hundred ninety of 4059 subjects (19%) were classified as having low risk; black race was less likely in the low-risk group. Those with low risk had lower LV mass/height 2.7 ratios (32.0 vs 34.6 g/m 2.7 , P < .0001), better LV relative wall thickness (0.33 vs 0.35, P < .0001), and lower LA diameter/height ratios (2.02 vs 2.08 cm/m, P < .01).
Conclusions
A low cardiovascular risk profile in young adulthood is associated with more favorable LV mass, LV relative wall thickness, and LA size. This may be one mechanism of lifestyle protection against cardiovascular morbidity and mortality.
Echocardiographic measures of left ventricular (LV) mass and relative wall thickness (the ratio of LV wall thickness to LV diameter) and left atrial (LA) size are important independent predictors of cardiovascular morbidity and mortality, particularly congestive heart failure, coronary artery disease, stroke, and atrial fibrillation. Abnormalities of LV mass and relative wall thickness and LA size in individuals with other cardiovascular risk factors, most importantly obesity and hypertension, can be detected in children and young adults, long before cardiovascular morbidity occurs. Increases in body weight and blood pressure are important predictors of increasing LV mass and suboptimal LV relative wall thickness. Conversely, some factors associated with cardiovascular health, low resting heart rate and high levels of physical fitness, are also associated with higher LV mass.
Studies of individuals with healthy lifestyles and low cardiovascular risk have shown very low rates of cardiovascular disease. Part of this health benefit may be from the prevention of chronic strain on the heart caused by excess body weight, elevated blood pressure, and tobacco use. Prior work in this field has not investigated the association of a low cardiovascular risk factor profile on LV mass and relative wall thickness and LA size. No prior studies have investigated the association of physical fitness with LV mass and relative wall thickness and LA size in a population-based cohort, as opposed to studies of trained athletes.
The Coronary Artery Risk Development in Young Adults (CARDIA) study is a prospective study of cardiovascular risk development in young white and black men and women. At baseline, individuals were aged 18 to 30 years, and echocardiography was performed in year 5. Prior analyses of LV structure and function in the CARDIA cohort have shown that in young adults, the most important determinants of LV mass and relative wall thickness are body size and blood pressure; additional determinants are tobacco use, physical activity, male gender, and possibly race. The importance of physical fitness on these measures and the determinants of LA diameter have not previously been studied in CARDIA. The purpose of this study was to determine the health benefit of normal body mass index (BMI), normal blood pressure, absence of tobacco use, and relative physical fitness on LV mass and relative wall thickness and LA diameter in young adults.
Methods
Details regarding the overall design, recruitment, and overall methods of the CARDIA study have been previously published. The CARDIA study is a longitudinal study of acquisition of cardiovascular risk factors in young adults recruited at age 18 to 30 years. The cohort was selected from the general population to include black and white men and women, about half of whom had more than a high school education and half had less. The year 25 examination will occur in 2010 and 2011. In year 5, of the CARDIA study, echocardiography was performed at 4 sites: Chicago, Illinois; Minneapolis, Minnesota; Birmingham, Alabama; and Oakland, California. The protocol has been previously described. Briefly, 2-dimensionally guided M-mode echocardiography was performed. and measurements of the left ventricle and left atrium were made according to American Society of Echocardiography guidelines using a parasternal window and long-axis and short-axis views. Tracings were not analyzed if the eccentricity index on comparison of views was > 1.3. First the desired interface was identified using the thinnest continuous echo lines, and then the leading edge of the anterior and posterior interfaces was identified for diameter measurement. LV mass was derived from the Devereux formula and indexed for body size by dividing by height 2.7 . LV relative wall thickness or geometry ratio was calculated as the ratio of the sum of ventricular septum and posterior wall thicknesses divided by LV internal diameter in diastole. LA diameter was indexed to height. Studies were interpreted at a central reading center within 1 to 3 weeks of their performance. Echocardiograms were classified according to quality measures as fair, good, or excellent.
All measurements were collected using standardized protocols across all field centers. In brief, height and weight were measured in light clothing, and BMI was calculated as weight in kilograms divided by the square of height in meters. Cigarette smoking was determined by self-report. Physical activity was determined by questionnaire. After 5 minutes of rest, blood pressure was measured 3 times by random-zero sphygmomanometer, and the last 2 values were averaged; resting heart rate was also measured. Diabetes mellitus was defined by 1997 American Diabetes Association fasting glucose criteria at year 0 (glucose > 126 mg/dL) and by self-report of medication use at year 5. At the baseline examination, a graded symptom-limited treadmill exercise test was performed using the modified Balke protocol. This test uses a series of 2-minute stages, with treadmill speed (baseline, 3.0 mi/h; peak, 5.6 mi/h) and grade (baseline, 2%; peak, 25%) increased at each stage. Total treadmill time was used as the measure of fitness; energy expenditure for the lowest stage is 4.1 metabolic equivalents, increasing to 19.6 metabolic equivalents at peak. The correlation of fitness measured at year 0 with fitness measured at year 7 was 0.77, suggesting reasonable stability of the measure at examinations bracketing the year 5 examination. Blood lipid levels were not used in risk determination, because they are unrelated to measures of cardiac size and function.
Low cardiovascular risk was defined as the simultaneous presence of blood pressure < 120/80 mm Hg, BMI of 18.5 to 24.9 kg/m 2 , not diabetic, no current cigarette smoking, and treadmill time > 60th percentile for gender.
Data Analysis
From the 4111 participants with available echocardiograms at the year 5 examinations, we excluded 45 participants who did not have fitness data at baseline and 7 more who were missing height measurements at baseline. A total of 4059 participants were included in this cross-sectional analysis.
Descriptive statistics were calculated for all covariates of interest. Next, we standardized the continuous covariates (predictor variables of interest) to a mean of 0 and a standard deviation of 1. We then conducted a linear regression analysis to calculate β coefficients and standard errors of the association of these standardized covariates of interest with LV mass and LA diameter. Next, we ran a series of multivariate linear regression models that included race, gender, age, blood pressure, BMI, heart rate, physical activity score, treadmill time, cigarette smoking status, and fasting glucose as predictors of LV mass, LV mass indexed for height 2.7 , LV relative wall thickness, and LA diameter indexed for height. We tested for interaction by race in the association of health status with echocardiographic parameters separately by gender using a multiplicative interaction term between race and health status in linear regression models that also included lower order terms. After identifying interaction (multiplicative interaction term P < .05) between health status and race among women, we conducted further analyses stratified by both sex and race. We calculated means and 95% confidence intervals of the association between low risk factor status and each of the echocardiographic variables separately by race-sex groups. Finally, the cohort was stratified into 4 groups according to the presence of LV hypertrophy (LV mass > 46.7 g/m 2.7 in women and > 49.2 g/m 2.7 in men) and the presence of eccentric or concentric LV geometry (a ratio > 0.43 implies eccentric geometry). Comparisons between low-risk and non-low-risk groups were made using t tests. Statistical significance was determined at P < .05. All analyses were conducted using SAS version 9.1 (SAS Institute Inc, Cary, NC).
Results
The distribution of echocardiographic parameters in the total sample and stratified by sex is reported in Table 1 . All of the echocardiographic parameters were smaller in women compared with men.
| Variable | Total sample (n = 4059) | Women (n = 2228) | Men (n = 1831) |
|---|---|---|---|
| LV mass (g) | 149.6 ± 44.7 | 130.5 ± 36.7 | 172.8 ± 42.5 |
| LV relative wall thickness | 0.348 ± 0.058 | 0.343 ± 0.058 | 0.354 ± 0.058 |
| LA diameter (cm) | 3.53 ± 0.47 | 3.42 ± 0.45 | 3.66 ± 0.46 |
| LV mass/ height 2.7 (g/m 2.7 ) | 35.2 ± 9.3 | 34.1 ± 9.5 | 36.6 ± 8.8 |
| LA diameter/height (cm/m) | 2.07 ± 0.27 | 2.08 ± 0.28 | 2.06 ± 0.26 |
Blacks were less likely to have low optimal health status. For the entire group with nonoptimal health status, blood pressure was 5.3/3.9 mm Hg higher, BMI was 3.4 kg/m 2 higher, treadmill duration was 3 minutes less, and self-reported physical activity was 75 exercise units less.
Univariate correlates of LV mass and LA diameter are shown in Table 2 . With the exception of former smoking, all variables were significantly associated with LV mass. All variables were significantly associated with LA diameter, except for treadmill duration. LV mass was larger with increasing BMI, activity level, treadmill duration, and systolic and diastolic blood pressure and lower with increasing heart rate. Black participants, men, and current smokers had larger LV mass than white participants, women, and nonsmokers, respectively. The direction of association with LA diameter was similar.
| LV mass ∗ | LA diameter † | |||
|---|---|---|---|---|
| Variable | β | SE | β | SE |
| Age (per 3.6 y) | 2.18 | 0.70 | 0.031 | 0.007 |
| Race (black vs white) | 7.28 | 1.40 | 0.039 | 0.015 |
| Gender (male vs female) | 42.30 | 1.24 | 0.239 | 0.014 |
| Smoking status | ||||
| Current vs never | 6.29 | 1.61 | 0.043 | 0.022 |
| Former vs never | −1.55 | 2.08 | 0.048 | 0.017 |
| Glucose (per 14.1 mg/dL) | 5.02 | 0.70 | 0.049 | 0.007 |
| BMI (per 5.8 kg/m 2 ) | 15.87 | 0.66 | 0.201 | 0.007 |
| Physical activity (per 293 exercise units) | 7.15 | 0.70 | 0.048 | 0.007 |
| Baseline treadmill duration (per 3.09 min) | 6.56 | 0.69 | 0.010 | 0.007 |
| Heart rate (per 4.9 beats/min) | −7.02 | 0.69 | −0.065 | 0.007 |
| SBP (per 11.4 mm Hg) | 15.72 | 0.66 | 0.107 | 0.007 |
| DBP (per 9.9 mm Hg) | 10.71 | 0.68 | 0.063 | 0.007 |
∗ All P values < .01 except for former smoking ( P = .46).
† All P values < .01 except for treadmill duration ( P = .16).
In both women and men, BMI, current smoking and systolic blood pressure were positively associated with LV mass/height 2.7 , and heart rate was inversely associated with LV mass/height 2.7 ( Table 3 ) independent of other cardiovascular disease risk factors. Among men, age was also positively associated with LV mass/height 2.7 , whereas among women, black race was positively associated with LV mass/height 2.7 . In a multivariate model describing the association with LV relative wall thickness, black race, BMI, and systolic blood pressure were positively associated with LV relative wall thickness in women and men. Multivariate correlates of LA diameter/height among women were BMI, current and former smoking (compared with never smoking), heart rate (inverse), and systolic blood pressure. By contrast, multivariate correlates of LA diameter/height among men were age, BMI, current smoking, heart rate (inverse), systolic blood pressure, and physical activity.
| Women | Men | |||||
|---|---|---|---|---|---|---|
| Risk characteristic | β | SE | P | β | SE | P |
| LV mass | ||||||
| Age (per years) | 1.68 | 0.69 | .02 | 1.31 | 0.93 | .16 |
| Race (black vs white) | 0.44 | 1.58 | .78 | 1.42 | 1.92 | .46 |
| BMI (per 5.8 kg/m 2 ) | 13.23 | 0.72 | <.01 | 21.04 | 1.25 | <.01 |
| Treadmill duration (per 3.09 min) | 0.97 | 1.06 | .36 | 1.66 | 1.20 | .17 |
| Smoking status | ||||||
| Current vs never | 6.38 | 1.64 | <.01 | 7.86 | 2.11 | <.01 |
| Former vs never | 3.87 | 2.01 | .05 | −2.53 | 2.85 | .37 |
| Heart rate (per 4.9 beats/min) | −2.28 | 0.71 | <.01 | −6.47 | 1.00 | <.01 |
| SBP (per 11.4 mm Hg) | 6.56 | 0.79 | <.01 | 6.00 | 0.97 | <.01 |
| Glucose (per 14.1 mg/dL) | 1.19 | 0.71 | .09 | 1.04 | 0.89 | .24 |
| Physical activity (per 293 exercise units) | 1.68 | 0.85 | .05 | 2.63 | 0.85 | <.01 |
| LV mass/height 2.7 (g/m 2.7 ) | ||||||
| Age (per years) | 0.35 | 0.18 | .05 | 0.22 | 0.19 | .26 |
| Race (black vs white) | 0.54 | 0.41 | .18 | 0.94 | 0.40 | .02 |
| BMI (per 5.8 kg/m 2 ) | 3.50 | 0.18 | <.01 | 4.40 | 0.26 | <.01 |
| Treadmill duration (per 3.09 min) | −0.16 | 0.27 | .55 | 0.20 | 0.25 | .43 |
| Smoking status | ||||||
| Current vs never | 1.52 | 0.42 | <.01 | 1.98 | 0.44 | <.01 |
| Former vs never | 0.77 | 0.52 | .13 | −0.41 | 0.59 | .49 |
| Heart rate (per 4.9 beats/min) | −0.56 | 0.18 | <.01 | −1.38 | 0.21 | <.01 |
| SBP (per 11.4 mm Hg) | 1.41 | 0.20 | <.01 | 0.98 | 0.20 | <.01 |
| Glucose (per 14.1 mg/dL) | 0.21 | 0.18 | .25 | 0.08 | 0.19 | .66 |
| Physical activity (per 293 exercise units) | 0.19 | 0.22 | .38 | 0.28 | 0.18 | .11 |
| LV relative wall thickness | ||||||
| Age (per years) | 0.002 | 0.001 | .06 | 0.002 | 0.001 | .08 |
| Race (black vs white) | 0.013 | 0.003 | <.01 | 0.018 | 0.003 | <.01 |
| BMI (per 5.8 kg/m 2 ) | 0.003 | 0.001 | .04 | 0.006 | 0.002 | <.01 |
| Treadmill duration (per 3.09 min) | −0.001 | 0.002 | .51 | −0.002 | 0.002 | .22 |
| Smoking status | ||||||
| Current vs never | 0.004 | 0.003 | .16 | 0.006 | 0.003 | .08 |
| Former vs never | 0.0001 | 0.004 | .98 | −0.002 | 0.004 | .64 |
| Heart rate (per 4.9 beats/min) | 0.001 | 0.001 | .41 | 0.0004 | 0.002 | .76 |
| SBP (per 11.4 mm Hg) | 0.006 | 0.001 | <.01 | 0.003 | 0.001 | .02 |
| Glucose (per 14.1 mg/dL) | 0.002 | 0.001 | .16 | 0.001 | 0.001 | .45 |
| Physical activity (per 293 exercise units) | 0.001 | 0.002 | .38 | 0.0004 | 0.001 | .77 |
| Left atrial diameter/height (cm/m) | ||||||
| Age (per years) | −0.002 | 0.005 | .69 | 0.017 | 0.006 | <.01 |
| Race (black vs white) | 0.002 | 0.012 | .87 | −0.021 | 0.012 | .07 |
| BMI (per 5.8 kg/m 2 ) | 0.121 | 0.005 | <.01 | 0.133 | 0.008 | <.01 |
| Treadmill duration (per 3.09 min) | 0.006 | 0.008 | .44 | −0.003 | 0.007 | .70 |
| Smoking status | ||||||
| Current vs never | 0.049 | 0.012 | <.01 | 0.044 | 0.013 | <.01 |
| Former vs never | 0.040 | 0.015 | .01 | 0.013 | 0.018 | .47 |
| Heart rate (per 4.9 beats/min) | −0.028 | 0.005 | .04 | −0.041 | 0.006 | <.01 |
| SBP (per 11.4 mm Hg) | 0.012 | 0.006 | .04 | 0.014 | 0.006 | .02 |
| Glucose (per 14.1 mg/dL) | 0.008 | 0.005 | .12 | 0.010 | 0.006 | .08 |
| Physical activity (per 293 exercise units) | 0.006 | 0.006 | .34 | 0.011 | 0.005 | .03 |
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