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Effect of Baseline Status on Cardiovascular Responses Post-isometric Handgrip Exercise


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Introduction

The isometric handgrip (IHG) exercise is a relatively simple test that measures the hemodynamic response to a “pressor” stimulus. However, the response is a function of multiple factors, including sympathetic and parasympathetic output, negative feedback baroreceptor loop, local factors, cardiac function, and feedforward central commands [1]. Isometric handgrip exercise increases cardiac output due to increased metabolic demands on the body. Multiple hemodynamic parameters govern cardiac output. Abnormal changes in hemodynamic parameters during IHG may reflect the early stages of cardiovascular disease [2]. In addition, the role of IHG in the management of hypertension has been envisaged; training for more than six weeks could reduce blood pressure and cause modulation of cardiac autonomic function [2, 4,5,6]. Further, the isometric handgrip (IHG) test might be an approach to the early detection of individuals prone to developing hypertension [7, 8]. The isometric handgrip exercise causes changes in hemodynamic parameters and heart rate variability, with individual differences. Heart rate variability is an effective procedure to evaluate cardiovascular autonomic dysfunction [9]. The present study aimed to delineate the effects of baseline measurements on post-exercise hemodynamic responses. Nowadays, machine learning models have been developed to predict various diseases [10, 11]. The baseline measurements, along with post-exercise hemodynamic responses, could be used as features in predicting cardiovascular disease.

Material and Methods

In this hospital-based cross-sectional study, 45 male students aged between 17 to 22 years enrolled from SMS Medical College, Jaipur (Rajasthan, India) after approval from the Institutional Ethical Committee. The study evaluated the effect of baseline measurements on hemodynamic responses and heart rate variability after doing the IHG exercise.

To evaluate the effect of baseline status, measurement of absolute responses was followed by calculation of relative responses (see Data Analysis). The relationships between absolute and relative responses were evaluated using correlation.

Protocol

The participants avoided tea, coffee, and food for at least 2 hours before data collection. Researchers did the recording between 09:00 AM and 12:00 PM to prevent the effect of diurnal variation. They clinically examined participants to rule out any morbidity. If the participant was found healthy, researchers collected hemodynamic and heart rate variability data in three phases as follows:

Baseline: 5 minutes duration before performing IHG exercise,

Phase 1: 5 minutes duration after completion of the IHG exercise, and

Phase 2: Duration between 5 and 10 minutes after completing the IHG exercise.

Isometric handgrip exercise

The participants were instructed to hold the hand dynamometer to provide a maximal voluntary contraction as a baseline. The tension was called maximal isometric tension (Tmax). After a rest of one minute, the participants compressed the dynamometer to 30% of the maximal effort (Tmax) for 5 minutes. Researchers measured the blood pressure, pulse rate, and ECG signals before, during, and after IHG exercise.

Recording of hemodynamic parameters

Researchers measured systolic and diastolic blood pressure and pulse rate (PR) in the participant's non-tested arm in all the phases. An automated digital device was used to avoid a manual error. Further, researchers calculated pulse pressure (PP), mean arterial pressure (MAP), and rate pressure product (RPP).

Acquisition of heart rate variability

The ECG signals for heart rate variability (HRV) were recorded using RMS Polyrite D (version 1.0) after a supine rest for 15 minutes. The resting ECG was recorded at a sampling frequency of 256 Hz. The tachogram (RR-interval series) was constructed from ECG signals. Researchers calculated time and frequency domain measures using Kubois software. The time-domain measures include the standard deviation of all RR intervals (SDNN), the square root of the mean of the sum of the squares of differences between adjacent RR intervals (RMSSD), and pNN50, which is the percentage of consecutive RR intervals that differ by more than 50 milliseconds. The frequency-domain measures include total power, power in the high frequency (HF) band (0.15–0.40Hz), power in the low frequency (LF) band (0.04–0.15 Hz), and LF/HF ratio [12,13,14].

Data analysis

The absolute readings were further processed to find out the relative readings. Let the baseline, phase 1, and phase 2 values of parameter X be represented by bX, X1, and X2, respectively. Then, the relative value of X1 is given by ΔX1=X1-bX.

Similarly, the relative value of X2 is given by ΔX2=X2-bX.

Statistical analysis

Based on normality, the quantitative variables were expressed as mean (SD) or median (IQR). The comparison of absolute values of parameters during baseline (bX), phase1 (X1), and phase 2 (X2) were performed using the Friedman test. The relative values of parameters during phase 1(ΔX1) and phase 2 (ΔX2) were compared using the Wilcoxon signed-rank test. Further, Pearson's coefficient measured the relationship between absolute and relative changes. The level of significance was considered at 5%. The JASP version 0.16.1.0 was used for statistical analysis (JASP Team) and MATLAB [15, 16].

Results

The study showed significant increase in the absolute SBP [W = 5.75 ; p < 0.001], DBP [W = 8.62; p < 0.001], HR [W = 8.52; p < 0.001], MAP [W = 8.90; p < 0.001] and RPP [W = 8.64; p < 0.001] during phase 1 as compared to the baseline values. However, absolute PP [W = 3.33; p = 0.004] showed significant decrease as compared to the baseline. Similarly, significant increase was observed in absolute SBP [W = 4.06; p < 0.001], DBP [W = 4.061; p < 0.001], HR [W = 5.39; p < 0.001], MAP [W = 4.77; p < 0.001] and RPP [W = 5.44; p < 0.001] during phase 2 as compared to the baseline. During phase 2, absolute DBP [W = 4.56; p < 0.001], HR [W = 3.13; p = 0.007], MAP [W = 4.13; p < 0.001] and RPP [W = 3.20; p = 0.006] were significantly lowered as compared to phase 1. However, absolute PP2 showed significant increase as compared to phase 1 PP [W = 2.63; p = 0.03] (Table 1). The comparison of absolute values of heart rate variability parameters showed no significant differences in SDNN, RMSSD, TP, and HF during phase 1 and phase 2 compared to the baseline. However, LF/HF ratio showed a significant increase in phase 1 and pN50 and LF/HF ratio showed significant increase in phase 2 compared to baseline. As compared to phase 1, RMSSD and pN50 showed a significant increase, while LF/HF ratio was decreased in phase 2 (Table 2).

One-way repeated-measures ANOVA to compare various absolute hemodynamic parameters before (baseline), during (phase 1), and after 5 minutes (phase 2) of handgrip exercise

Repeated measures ANOVA using Friedman Test Conover's post hoc comparisons
Hemodynamic Variable Levels Median IQR Test statistic p Level 1 Level 2 T-Stat pbonf
SBP bSBP 114 10 34.785 < .001 bSBP SBP1 5.747 < .001
SBP1 120 12 bSBP SBP2 4.057 < .001
SBP2 120 12 SBP1 SBP2 1.69 0.284
DBP bDBP 78 10 74.235 < .001 bDBP DBP1 8.622 < .001
DBP1 90 14 bDBP DBP2 4.061 < .001
DBP2 80 10 DBP1 DBP2 4.561 < .001
HR bHR 80 19 74.279 < .001 bHR HR1 8.523 < .001
HR1 86 20 bHR HR2 5.394 < .001
HR2 86 18 HR1 HR2 3.129 0.007
PP bPP 38 12 12.358 0.002 bPP PP1 3.335 0.004
PP1 31 12 bPP PP2 0.699 1
PP2 37 12 PP1 PP2 2.635 0.03
MAP bMAP 89.333 10 79.416 < .001 bMAP MAP1 8.905 < .001
MAP1 99.333 13.333 bMAP MAP2 4.771 < .001
MAP2 94 10.667 MAP1 MAP2 4.135 < .001
RPP bRPP 92.4 17.84 76.227 < .001 bRPP RPP1 8.637 < .001
RPP1 107.1 24.84 bRPP RPP2 5.438 < .001
RPP2 101.48 18.63 RPP1 RPP2 3.199 0.006

One-way repeated-measures ANOVA to compare various absolute heart rate variability measures before (baseline), during (phase 1), and after 5 minutes (phase 2) of handgrip exercise

Repeated measures ANOVA using Friedman Test Conover's post hoc comparisons
Levels Median IQR Test statistic p Level 1 Level 2 T-Stat pbonf
SDNN bSDNN 0.059 0.04 7.112 0.029 bSDNN SDNN1 0.159 1
SDNN1 0.064 0.039 bSDNN SDNN2 2.385 0.058
SDNN2 0.073 0.059 SDNN1 SDNN2 2.226 0.086
RMSSD bRMSSD 0.067 0.058 9.911 0.007 bRMSSD RMSSD1 0.527 1
RMSSD1 0.061 0.066 bRMSSD RMSSD2 2.424 0.052
RMSSD2 0.068 0.071 RMSSD1 RMSSD2 2.951 0.012
pN50 bpN50 0.211 0.374 11.227 0.004 bpN50 pN501 0.427 1
pN501 0.26 0.268 bpN51 pN502 2.666 0.027
pN502 0.378 0.46 pN501 pN502 3.092 0.008
TP bTP 1087 2077.8 4.844 0.089 bTP TP1 0.211 1
TP1 1204 2390.5 bTP TP2 2.003 0.145
TP2 1427 3198 TP1 TP2 1.792 0.23
HF bHF 322.08 826.42 5.404 0.067 bHF HF1 0.742 1
HF1 356.4 832.54 bHF HF2 1.537 0.384
HF2 534.79 967.96 HF1 HF2 2.279 0.075
LF/HF bLF/HF 0.66 0.46 70.136 < .001 bLF/HF LF/HF1 8.21 < .001
LF/HF1 1.1 1.05 bLF/HF LF/HF2 5.545 < .001
LF/HF2 0.9 0.78 LF/HF1 LF/HF2 2.666 0.027

Further, researchers compared relative cardiovascular responses and found a significant decrease in phase 2 compared to phase 1 (Table 3). Similarly, the relative change in all heart rate variability parameters, except LF/HF ratio, were higher during phase 2 as compared with phase 1 (Table 4).

Comparison of relative hemodynamic parameters during (phase 1) and after 5 minutes (phase 2) of IHG exercise

Variable PhaseΔX=X-baselineX Mean/Median SD/IQR Statistic p
SBP ΔSBP1 6 12 413 0.018
ΔSBP2 4 7
DBP ΔDBP1 12 10 736 < .001
ΔDBP1 6 8
HR ΔHR1 7 6 694.5 < .001
ΔHR2 4 4
PP ΔPP1 −5.333 9.677 −3.964 < .001
ΔPP2 −1.378 7.779
MAP ΔMAP1 9.667 7.667 916 < .001
ΔMAP2 4.667 7.333
RPP ΔRPP1 13.057 7.909 3.769 < .001
ΔRPP2 9.647 6.083

Mean and SD were calculated for PP and RPP, and paired Student t test was used for comparison. For others median and IQR were calculated, and Wilcoxon signed-rank test was used for comparison

Comparison of various relative heart rate variability parameters during (phase 1) and after 5 minutes (phase 2) of IHG exercise

Variable PhaseΔX=X-baselineX Median IQR Statistic# p
RMSSD ΔRMSSD1 −0.001 0.032 314 0.022
ΔRMSSD2 0.01 0.046
pN50 ΔpN501 0 0.11 213 0.002
ΔpN502 0.049 0.129
SDNN ΔSDNN1 0 0.021 269 0.005
ΔSDNN2 0.006 0.032
TP ΔTP1 −2.7 1067.8 334 0.038
ΔTP2 557.5 2461
HF ΔHF1 −34.32 433.16 309 0.03
ΔHF2 101.9 572.9
LF/HF ΔLF/HF1 0.47 0.57 715 < .001
ΔLF/HF2 0.24 0.27

Wilcoxon signed-rank test was used for comparison

To find the effect of baseline values on post-exercise responses, the authors calculated Pearson's correlation between absolute and relative responses. The study showed a significant effect of baseline values on the relative DBP, PP, and MAP in phases 1 and 2. However, baseline values had no significant impact on relative changes in SBP, HR, and RPP in phases 1 and 2 (Table 5). The relative values of all heart rate variability parameters in phase 1 were significantly correlated with baseline values. However, baseline values had no significant association with relative changes in phase 2 heart rate variability measures (Table 6).

Relationship between absolute and relative changes in hemodynamic parameters before (baseline), during (phase 1), and after 5 minutes (phase 2) of isometric handgrip exercise

Variable Parameter 1 Parameter 2 Pearson's correlation coefficient p
SBP bSBP ΔSBP1 −0.17 0.264
bSBP ΔSBP2 −0.158 0.299
SBP1 ΔSBP1 0.594 < .001
SBP2 ΔSBP2 0.497 < .001
DBP bDBP ΔDBP1 −0.41 0.005
bDBP ΔDBP2 −0.367 0.013
DBP1 ΔDBP1 0.397 0.007
DBP2 ΔDBP2 0.362 0.015
HR bHR ΔHR1 −0.197 0.195
bHR ΔHR2 −0.274 0.069
HR1 ΔHR1 0.09 0.557
HR2 ΔHR2 −0.054 0.724
PP bPP ΔPP1 −0.408 0.005
bPP ΔPP2 −0.339 0.023
PP1 ΔPP1 0.594 < .001
PP2 ΔPP2 0.492 < .001
MAP bMAP ΔMAP1 −0.317 0.034
bMAP ΔMAP2 −0.304 0.042
MAP1 ΔMAP1 0.401 0.006
MAP2 ΔMAP2 0.363 0.014
RPP bRPP ΔRPP1 −0.077 0.615
bRPP ΔRPP2 −0.147 0.336
RPP1 ΔRPP1 0.401 0.006
RPP2 ΔRPP2 0.244 0.107

Relationship between absolute and relative changes in heart rate variability parameters before (baseline), during (phase 1), and after 5 minutes (phase 2) of isometric handgrip exercise

Variable Parameter 1 Parameter 2 Pearson's correlation coefficient p
TP bTP ΔTP1 −0.819 < .001
bTP ΔTP2 −0.163 0.286
TP1 ΔTP1 0.206 0.174
TP2 ΔTP2 0.59 < .001
HF bHF ΔHF1 −0.763 < .001
bHF ΔHF2 −0.116 0.447
HF1 ΔHF1 0.224 0.139
HF2 ΔHF2 0.544 < .001
LF/HF bLF/HF ΔLF/HF1 0.335 0.025
bLF/HF ΔLF/HF2 0.188 0.215
LF/HF1 ΔLF/HF1 0.832 < .001
LF/HF2 ΔLF/HF2 0.737 < .001
RMSSD bRMSSD ΔRMSSD1 −0.581 < .001
bRMSSD ΔRMSSD2 −0.078 0.611
RMSSD1 ΔRMSSD1 0.347 0.02
RMSSD2 ΔRMSSD2 0.605 < .001
pN50 bpN50 ΔSpN501 −0.524 < .001
bpN50 ΔSpN502 −0.027 0.86
pN501 ΔSpN501 0.193 0.203
pN502 ΔSpN502 0.438 0.003
SDNN bSDNN ΔSDNN1 −0.634 < .001
bSDNN ΔSDNN2 −0.023 0.882
SDNN1 ΔSDNN1 0.151 0.323
SDNN2 ΔSDNN2 0.585 < .001
Discussion

Isometric exercise is defined as a sustained muscular contraction with no joint movements. Conventionally, no work was done during the exercise. The oxygen consumption is moderate compared to isotonic exercise. The cardiovascular effects of static or isometric exercise primarily reflect the response to increased afterload or blood pressure. In contrast, the response to isotonic exercise is due to volume overload on the heart [12]. The high muscle tension and reduced blood flow produce a unique “pressor” reflex increase in systemic arterial pressure [17]. The reflex increases sympathetic activity in the heart and vessels and decreases parasympathetic activity, increasing BP, heart rate, and total peripheral resistance through arteriolar constriction. The sympathetic output varies in contracting and non-contracting skeletal muscle and is differentially controlled by a central command and the metaboreflex in healthy conditions. Further, studies on animals and humans showed the effect of cardiovascular diseases, such as diabetes, hypertension, and heart failure, on altered “pressor” reflex function [18]. The hemodynamic response to isometric handgrip exercise results from a complex interaction of multiple factors, including sympathetic and parasympathetic output, norepinephrine uptake, baroreceptor loop, cardiac function, central commands, and age [1, 19]. Most studies showed the effect of IHG exercise on cardiovascular responses. The present study evaluated changes in absolute and relative responses compared to baseline measurements.

Similar to the present study, Laird et al. showed the effect of submaximal (25% maximal) IHG in 32 normal adolescents. They found significant increases in mean heart rate, systolic, diastolic, and mean blood pressures [20]. Aminoff et al. reported increased heart rate and blood pressure during sustained IHG were partly due to central command and partly due to activation of the afferent limb reflex arc from contraction of muscles. At least a 15 mmHg increase in diastolic pressure was considered normal [21]. The present study enrolled only males within a narrow range of age to eliminate the effects of age on post-exercise responses. Cauwenberghs et al. observed a positive correlation of age with blood pressure and pulse pressure changes in 3 minutes of 40% maximal IHG. They showed significantly higher heart rate and diastolic BP after exercise in males compared to females [2]. In addition, Goulopoulou et al. showed greater mean arterial pressure responses in adults compared to children (p < 0. 0 5) after doing IHG. However, heart rate variability measures were not significantly different in adults and children (p > 0.05) [22]. The causes of post-exercise response might be multifactorial. In a study by Watanabe et al., 39 healthy subjects performed a 1-minute IHG exercise at 50% of maximal voluntary contraction followed by a 4-minute post-exercise muscle ischemia period to selectively maintain activation of the muscle metaboreflex. Researchers hypothesized an inverse correlation between changes in cardiac output (CO) and total peripheral vascular resistance (TPR) during IHG [r = - 0.751; p = 0.01] but showed CO and TPR were positively correlated with corresponding responses during post-exercise muscle ischemia [r = 0.568 and 0.512, respectively, p =0.01][23]. Clark et al. evaluated the effect of omega-3 polyunsaturated fatty acid consumption on cardiovascular responses at the onset of IHG exercise. Fourteen young and fifteen old subjects ingested 4 g of fish oil daily for 12 weeks. Participants performed 15-second bouts of IHG at 10%, 30%, 50%, and 70% maximal voluntary contraction. The systolic and diastolic blood pressure and heart rate were recorded before and after the intervention. Researchers found that fish oil supplementation attenuates MAP and DBP increases at the onset of IHG exercise in young and older subjects [change from baseline during 70% MVC handgrip pre- and post-intervention: young ΔMAP =14 ± 2mmHg versus 10 ± 2mmHg, older ΔMAP =14 ± 3mmHg versus 11 ± 2mmHg; young ΔDBP =12 ± 1mmHg versus 7 ± 2mmHg, older ΔDBP = 12 ± 1mmHg versus 7 ± 1mmHg; p < 0.05] [24]. Chaney et al. calculated the predictor variables for systolic BP response [age, gender, resting systolic BP, and maximal treadmill systolic BP, yielded 70% predictability] and diastolic BP response [handgrip strength, resting diastolic BP, treadmill HR, systolic BP, and diastolic PB allowed 66% prediction] [25].

The present study evaluated the effects of IHG exercise on heart rate variability parameters. Kluess et al., in a study on 34 participants (age, 20 ± 1 year), compared heart rate variability parameters during spontaneous breathing, venous-occluded exercise (60% maximal voluntary contraction, 0.5 Hz), and immediate postexercise arterial occlusion. Similar to the present study, researchers found increased LFnu (+9.39 ± 16.83%) and MAP (+25.40 ± 17.55 mm Hg) after exercise. On the contrary, mean R-R interval (−230.73 ± 125.79 msec) and SDNN (−38.54 ± 36.02 msec) showed decrease (P < 0.05). During forearm arterial occlusion, SDNN (−17.89 ± 64.41 msec) and LFnu (9.89 ± 21.01%) showed recovery (P < 0.05) [26]. Farah et al. did a systematic review and meta-analysis of seven randomized controlled trials with 86 participants. Mean difference (MD) and 95% confidence interval (95% CI) were calculated using an inverse variance method with a random-effects model. The results showed no significant effects of IHG exercise on heart rate variability parameters [4 trials to SDNN: MD = −1.44 ms and 95% CI = −8.02, 5.14 ms; RMSSD: MD = −1.48 ms and 95% CI = −9.41, 6.45 ms; pNN50: MD = 0.85% and 95% CI = −1.10, 2.81%; 7 trials to LF: −0.17 nu. and 95% CI = −6.32, 5.98 nu.; HF: MD = 0.17 nu. and 95% CI = −5.97, 6.30 nu.; and LF/HF: MD = 0.13 and 95% CI = −0.34, 0.59] [27]. Kurita et al. studied the effect of IHG on frequency domain heart rate variability in healthy and coronary artery disease patients. The authors found no significant differences in low-frequency (LF) spectra and LF/HF ratios during handgrip exercise, but HF spectra significantly increased from 10.1 ± 4.5 to 12.2 ± 7.0 ms (P < 0.05) in normal subjects. However, LF and LF/HF spectra showed significant (P < 0.05 and 0.01, respectively) increase in the CAD subjects, while HF spectra were not significantly changed by handgrip exercise [28].

The present study found that initial baseline status affects cardiovascular responses after IHG exercise. In a meta-analysis of seven randomized controlled trials, Yin et al. found the effect of isometric handgrip (IHG) training on resting BP and heart rate. They analyzed the association between IHG training and participants with different initial BP status. The participants in training groups showed significantly decrease in SBP [MD= −8.33, 95% CI: −11.19 to −5.46; P <0.01) and DBP (MD=−3.93, 95% CI: −6.14 to −1.72; P <0.01] compared to control group. In subgroup analysis, SBP, DBP, and HR significantly decreased in prehypertensive subjects (P < 0.01). However, medicated hypertensive subgroup showed a significant reduction in SBP and DBP (P < 0.01) [29]. Although researchers compared post-exercise outcomes in various studies, the intensities (that is, percentage of maximum voluntary contraction) used in different studies had not shown standardized protocols. The effect of exercise intensity was evaluated by Kluess et al. using repeated measures ANOVAs and found the effect of intensity of IHG on blood pressure and heart rate variability measures. Researchers found that the mean R-R interval responded to exercise in an intensity-dependent manner. However, SDNN decreased with IHG but did not correlate with exercise intensity [30].

The present study evaluated the acute effects of IHG exercise on cardiovascular responses. Many studies suggested IHG training as an intervention for hypertension. On the contrary, Moldoven et al. found that IHG training for 8–10 weeks had an impact on resting arterial blood pressure and heart rate variability in an investigation. However, blood pressure and heart rate variability parameters had no significant effects [p > 0.05] [27]. In a few instances, post-exercise dizziness and hypotension were observed. In a meta-analysis of 30 trials, Farinatti et al. proposed no role of autonomic dysfunction during post–resistance exercise hypotension [31], considering multiple factors in post–IHG exercise cardiovascular responses. The present study outlines the importance of initial baseline status in the development of post-exercise cardiodynamics.

Conclusion

The present study concludes that initial baseline status should be considered while evaluating the post–IHG exercise responses. The study showed a significant effect of baseline measurements on post–IHG exercise diastolic blood pressure, pulse pressure, and mean arterial pressure, and the heart rate variability parameters.

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