Racial Differences in Left Ventricular Filling Pressure Following Acute Aerobic Exercise Between Chinese and Caucasians

Left ventricular filling pressure (LVFP) is an important early indicator of heart failure that is more prevalent in Caucasians than Chinese. Exercise-induced change in LVFP may provide more incremental information to assess diastolic function. But it was unknown whether there was difference in LVFP following acute exercise between Caucasians and Chinese. The purpose of this study was to investigate the change of LVFP following an acute 45-min aerobic exercise in healthy Caucasian and Chinese individuals. Sixty participants (30 Caucasians and 30 Chinese, half was male, respectively) performed an acute bout of aerobic exercise at 70% of heart rate reserve. Hemodynamics, Left ventricle (LV) morphology and function parameters were measured at baseline, then at 30-min and 60-min post-exercise. There was a similar LV ejection fraction, LV fraction shorten, lateral E/eʹ and lateral eʹ between Chinese and Caucasians at baseline. There was a significant race-by-time interaction in lateral E/eʹ and lateral eʹ between Chinese and Caucasians from pre-exercise to 30 min and 60 min after acute aerobic exercise. The ΔE/eʹ was significant correlated with baseline systolic blood pressure. The change of LVFP was different between Chinese and Caucasians following acute aerobic exercise. The racial differences may be primarily caused by the changes of LV relaxation following exercise, baseline systolic blood pressure may also contribute to the differences.


Introduction
Cardiovascular disease (CVD) is the main contributor to morbidity and mortality worldwide but there are interracial differences [18]. Caucasian (CA) population have significantly higher prevalence of CVD compared with their Chinese (CH) counterparts [46,48,49]. Previous studies have reported that the prevalence of coronary heart disease was 2.4% in CA and 0.9% in CH [16]. Left ventricle (LV) diastolic function, which often precedes systolic dysfunction [14], is an independent predictor of prognosis and adverse cardiac events [15], particularly in heart failure (HF), and HF is more prevalent in CA than in CH populations [4].
LV diastolic dysfunction (LVDD) is characterized by impaired diastolic relaxation and elevated LV filling pressure (LVFP) [9]. High baseline LVFP is also associated with a significantly increased all-cause mortality [1], and small 1 3 changes in LVFP have been associated with significant clinical events and mortality [50]. Although most patients with HF had normal resting LVFP, during exercise, LVFP may rise rapidly [6]. Hence, the changes of LVFP caused by exercise may provide more incremental information to assess diastolic function. However, reported changes of LVFP following exercise have been variable and may influenced by exercise intensity, duration, and mode and recovery period after exercise [12]. To date, it is unknown if exercise at a pre-set duration, intensity and mode, produces different responses between CH and CA individuals.
The ratio of the early diastolic velocity on trans-mitral Doppler (E) and the early diastolic velocity of mitral valve annulus obtained from tissue Doppler (eʹ) has been suggested as a reliable estimate of LVFP regardless of the cardiac rhythm and LV systolic function at rest [30], during or after exercise [22]. Elevated E/eʹ indicates a higher LVFP [26]. Most previous studies of exercise-induced changes of LVFP have focused on patients with LVDD, and found these patients had a significantly higher E/eʹ immediately post exercise compared to baseline [32]. In contrast, in healthy adults, E/eʹ does not change, or decreases slightly, immediately post exercise compared to baseline [31,32]. Most studies have focused only on the immediately post-exercise period; however, the effect of exercise on LVFP may persist longer into recovery [12]. It is unclear whether evaluating changes of E/eʹ during a longer recovery period following exercise will provide additional useful information.
Therefore, the present investigation was conducted to investigate the change of LVFP at 30 and 60 min after an acute bout of aerobic exercise in healthy CA and CH men and women. In addition, we aimed to identify contributors to the changes of LVFP following exercise. The research hypothesis is that an acute bout of aerobic exercise can cause the change of LVFP, and the E/eʹ in the recovery period after exercise is higher in CA than in CH.

Subjects
Healthy young CA and CH between the ages of 18 and 40 years were recruited in this study. Physical activity was assessed by the Lipid Research Clinics Questionnaire [2]. All subjects had normotensive blood pressure (SBP < 140 mmHg, DBP < 90 mmHg), the BP guidelines for hypertension were based on the guideline at the time of data collection. To minimize the influence of hormones, the female subjects were tested during the early follicular phase of menstrual cycle [34]. This study was approved by the Institutional Review Board at the University of Illinois at Urbana-Champaign.

Study Design
All subjects were tested on two separate occasions with 48 h-2 weeks between each visit. Following the health history questionnaire, a peak aerobic capacity test was performed during the first visit. Hemodynamics and LV morphology and function parameters were measured while subjects were in the supine position pre-exercise. And then, an acute bout of aerobic exercise was performed using a treadmill. After completion of the treadmill exercise, the hemodynamics and LV morphology and function parameters were measured again 30 min and 60 min post exercise. All subjects were tested during the same time period (15:00-20:00) [23].

Assessment of Peak Aerobic Capacity and Maximal Heart Rate
The Bruce treadmill protocol was used to determine the peak aerobic capacity (VO 2peak ) [7]. Real-time heart rate (HR) was monitored with a Polar HR Monitor (Polar Electro, Woodbury, NY, USA). The Quark b 2 breath-by-breath metabolic system (Cosmed, Rome, Italy) was used to analyze expired gas [41]. The HR max was obtained to calculate the target HR during the exercise session [25].

Aerobic Exercise Protocol
After completion of 5-min warm-up exercise, a supervised treadmill exercise was performed at 70% of heart rate reserve (HRR). The Polar HR Monitor (Polar Electro, Woodbury, NY) was used to monitor Real-time HR.

Measurement of Anthropometrics
Height was measured using a stadiometer while weight was measured using an electronic scale. The ultrasonography (SSD-α10, Aloka, Tokyo, Japan) was used to measure the right common carotid artery intima-media thickness (IMT).

Measurement of Hemodynamics
The automated oscillometric cuff (HEM-907 XL; Omron, Shimane, Japan) was used to measure the right brachial artery blood pressure with the subjects in supine position. All brachial artery blood pressure measurements were recorded twice with a 1-min interval at rest. The average of two measurements was used for subsequent analysis.

Measurement of LV Morphology and Functions
The ultrasonography (SSD-α10, Aloka, Tokyo, Japan) was used to obtained the echocardiographic measurements before and after exercise according to guidelines suggested by American Society of Echocardiography (ASE) and the European Association of Cardiovascular Imaging (EACVI) [30]. Left ventricular end-systolic and enddiastolic diameters and wall thickness were used to determined left ventricular dimensions. The diastolic wall strain (DWS) = (PWTs − PWTd)/PWTs, where PWTs is the left ventricular posterior wall thickness at end-systole and PWTd is that at end-diastole. Left ventricular end-systolic volume (LVESV), left ventricular end-diastolic volume (LVEDV), left ventricular ejection fraction (EF) and fraction shorten (FS) were determined using a biplane Simpson method. The pulse-wave Doppler echography was used to determine early trans-mitral inflow velocity (E) and deceleration time (DT). The tissue Doppler imaging was used to measure myocardial tissue lengthening velocity during early (eʹ) diastole. The E/eʹ ratio, which represents the LVFP, was also calculated [40]. Left ventricular mass index (LVMI) was calculated as follows: LVMI = left ventricular mass/body surface area.

Statistical Analysis
All data are presented as mean ± SE. An independent samples T test was used to analyze possible racial differences between Chinese and Caucasian subjects. A 2 × 3 ANCOVA was used to determine the effects of aerobic exercise on left ventricular systolic and diastolic function parameters between CH and CA subjects, controlling for age and brachial SBP and DBP. When a significant group-by-time interaction was detected, Bonferroni post hoc tests were used to analyze where the difference occurred. The strength of the linear relationship between the variables of interest was analyzed using Pearson correlation coefficient analysis. Statistical analyses were completed using SPSS 20.0 (SPSS Inc., Chicago, IL), and the significance level was P < 0.05.

Results
Participant characteristics at baseline are presented in Table 1. Overall, CH participants were slightly older than their CA counterparts (P < 0.05). Furthermore, CH participants exhibited lower height, weight, SV, CO and BP than CH (P < 0.05). There were no differences in BMI, VO 2peak , HR rest , HR max , HR target , LVMI, or IMT between CH and CA groups. Table 2 shows the data comparing the hemodynamic variables following exercise between CH and CA. Significant race-by-time interactions were found for brachial SBP and DBP, HR and CO (P < 0.05), but there was no race-by-time interaction for SV. Table 3 shows the LV morphology and function parameters between CH and CA at baseline. The baseline IVSs, LVDs and LVESV, were slightly lower in the CH compared to the CA group (P < 0.05). The baseline LV systolic function parameters, such as LVEF, LVFS and diastolic function parameters, such as E, DT, lateral eʹ, and lateral E/eʹ, were not significantly different between the CH and CA groups. LV function is reportedly associated with age, HR, BP, and our data showed that age and resting BP were different between the CA and CH. Hence, age and brachial SBP and DBP were used as the covariates to analyze the changes in LV function parameters following acute aerobic exercise in CH and CA (Fig. 1A-F). There were no race-by-time interactions for systolic function parameters, such as LVEF and LVFE (Fig. 1A, B). But there was a significant race-by-time interaction for lateral E/eʹ (F = 12.03; P < 0.05; Fig. 1F), showing that the change in E/eʹ from pre-exercise to 30and 60-min post-exercise was different between the groups. The lateral E/eʹ was sharply reduced in CH and increased in CA after exercise. These changes led to higher postexercise lateral E/eʹ for CA than for CH. Furthermore, our data showed there also was a significant race-by-time interaction for lateral mitral annular eʹ velocity between groups following exercise (F = 23.55; P < 0.05; Fig. 1E). Moreover, our data showed that lateral E/eʹ decreased sharply in CH subjects 30 min after exercise, but increased in CA. The change of mitral E velocity or DT was similar between groups (Fig. 1C, D).
A Pearson correlation coefficient analysis was performed between the change values of lateral E/eʹ (ΔE/eʹ) from preexercise to 30-min post-exercise and baseline HR, SBP, DBP, VO 2peak , DWS and BMI. Our data showed that there was a significant correlation between lateral ΔE/eʹ and baseline SBP (R = 0.297, P = 0.020; Fig. 2B), but there was no significant correlation between lateral ΔE/eʹ and baseline HR (R = − 0.021, P = 0.875; Fig. 2A

Discussion
To our knowledge, this is the first study to focus on LVFP following an acute bout of aerobic exercise between CH and CA individuals. In the present study, we examined the changes in LV morphological and functional parameters from pre-exercise to 30 min and 60 min after exercise. Our primary findings were that (1) baseline lateral E/eʹ, was similar between CH and CA individuals; (2) the change in lateral E/eʹ and lateral mitral annular eʹ velocity was different between CH and CA individuals from pre-exercise to 30and 60-min post-exercise. Particularly, at the 30th min of the recovery period, lateral E/eʹ decreased sharply in CH subjects, while the CA group increased compared to baseline; and (3) there was a significant correlation between lateral ΔE/eʹ and baseline SBP.
Cardiovascular loading conditions, which is induced by the fluid shifts caused by exercise, directly influence cardiac function, which may affect the contractile properties of the myocardium [11]. However, the effect of exercise on LV systolic function is still controversial. LVEF is a valuable indicator of LV systolic function [20]. Several studies have found increased LVEF immediately after exercise compared to rest [19,37], while another study showed that there was no change in LVEF at 15 min post exercise [36]. Middleton and colleagues [27] observed that increased exercise duration resulted in greater reductions in post-exercise LVEF. Our data showed that there was no significant change in either LVEF or LVFS at either 30 min or 60 min after 45-min aerobic exercise, suggesting CH and CA subjects exhibited similar LV systolic function following acute aerobic exercise.
LV diastolic function is an important early indicator of myocardial dysfunction often present in various heart conditions, and often precedes alterations in systolic function [14,40]. Elevated LVFP is thought to be the direct causes of impairment of LV diastolic function [21]. Exercise-induced change in LVFP may provide more incremental information to assess diastolic function [6,8,13] at rest [30] and after exercise [3,8]. Noninvasive echocardiographic tissue Doppler assessment (E/eʹ) in response to exercise has been proposed as a useful parameter to assess LVFP and LV diastolic function [10,38]. The effects of exercise on LVFP are controversial. Previous investigations have shown that the E/eʹ ratio, an accurate   estimator of LVFP, significantly increased immediately after exercise [36,42,44], while other studies found there was no any change [19,37]. Shave et al. suggested, unlike systolic function, temporary reductions in diastolic function were more readily triggered by short and high-intensity exercise [39]. Our data showed that the change in lateral E/eʹ was significantly different between CH and CA subjects from pre-exercise to 30 min and 60 min after 45-min aerobic exercise. Of note is the fact that CH had a sharp decrease at 30 min post exercise, while CA subjects increased when compared to the baseline values. These changes led to higher post-exercise LVFP for CA than for CH, which may be associated with a higher incidence of CVD in CA. The reduction of E/eʹ exhibits the ability of the heart to fill at lower pressures during the recovery period after exercise. Exercise-induced LVFP changes are likely to be caused by alteration in myocardial relaxation [5,12]. Consistent with this, our data showed that the changes of lateral mitral annular eʹ velocity, which reflect LV relaxation, were also different between CH and CA following exercise, while the changes of mitral E velocity were similar between the races. This suggests the different change of LVFP between races may be caused by disproportionate changes in mitral annular eʹ velocity and mitral E velocity between CH and CA subjects following exercise. As previously reported, LV diastolic function and LVFP were associated with HR [39], hemodynamics [5,28,29], exercise capacity [17,24], LV deformation [33,43,45] and BMI [35,47]. We also investigated whether baseline HR, BP, aerobic capacity, DWS, and BMI might produce different influences on ΔE/eʹ between races. Our data showed that there was no significant correlation between ΔE/eʹ and baseline HR, DBP, VO 2peak , DWS and BMI, respectively, following exercise. The ΔE/eʹ was significantly correlated with baseline SBP, suggesting SBP may contribute to the change of lateral E/eʹ following exercise. The lower baseline SBP can produce a greater exercise-induced drop in E/eʹ, but the exact mechanism is unclear.

Limitations
The study was conducted in a population of healthy adults and would be more valuable in a population with cardiovascular disease. Furthermore, we measured the LV morphological and functional parameters only at pre-exercise,

Conclusion
In our study, we demonstrated racial differences in the changes of lateral E/eʹ ratio, an estimate of LVFP, following acute aerobic exercise. In addition, we suggested that this racial difference might be primarily caused by the changes of lateral mitral annular eʹ velocity, reflecting LV relaxation, following exercise, and baseline SBP might contribute to the differences, lower baseline SBP could produce a greater exercise-induced drop in E/eʹ. Moreover, although the exact potential mechanism for the racial differences on CVD is not known, our findings suggest that exercise-induced changes in myocardial function may yield future insight regarding racial differences in the development of CVD.
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