A study of post exercise hypotension in normotensive offspring of hypertensives after acute exercise

The benefits of exercise in hypertension have been a focus of attention for clinicians for many years. Most of this interest has been on two issues: (i) the arterial blood pressure (BP) responses to exercise in hypertensives, and (ii) use of chronic exercise as a non-pharmacologic approach to lower arterial BP1. In recent years, however, the fall in BP after exercise - the post-exercise hypotension (PEH) has become an area of paramount interest to researchers.

Although there are no defined criteria for the magnitude of BP decrement or the duration of response, PEH is defined as sustained decrease in systolic and/or diastolic arterial BP below resting levels in the minutes and hours following a single bout of acute exercise2. The minimal magnitude of exertion for PEH, tested by Pescatello et al3,4 is compatible with a low-intensity walk, which is usually enjoyable and favours adherence. Furthermore, till date, it is not known whether a single session of high-intensity interval training (HIIE) maximizes PEH more than a bout of moderate-intensity continuous exercise (MICE). However, a recent meta-analysis found comparable reductions in BP in hypertensive adults following chronic HIIE training and MICE training5.

Hypertension clusters in families and a positive family history of hypertension represents a major risk factor for future hypertension in the non-hypertensive offspring6. Although PEH is a well known entity in hypertensive and borderline hypertensive patients, its occurrence in normotensive humans is inconsistent7-9. Hence, we hypothesized that the degree of PEH may be related to the genetic predisposition of humans to hypertension. To the best of our knowledge, no data has been reported yet to study PEH in the offspring of hypertensives and normotensives. Hence, the present study aims to compare the magnitude of PEH in normotensive offspring of hypertensives vs. normotensive offspring of normotensives, after an acute bout of MICE.

Material & Methods

Study design: This study was conducted in the Exercise Lab, department of Physiology, Maulana Azad Medical College, New Delhi, India, for a period of one year from September 2019-September 2020. The study was approved by the Institutional Ethics Committee. Prior written informed consent was obtained from all the participating individuals explaining the duration, type and objectives of the study.

Study design and participant enrolment: It was a non-randomized study, based on an interventional study design, with a convenience sampling strategy since only normotensive individuals were recruited from the general population based on their family history of hypertension. Following a single acute bout of moderate exercise on a treadmill, the studied outcome measures were the degree of PEH observed in both offspring of hypertensives and normotensives, in terms of changes in systolic blood pressure (SBP), diastolic blood pressure (DBP) and mean arterial blood pressure (MAP).

Sample size estimation: The sample size was calculated based on the following formula:

CV - coefficient of variation (CV=σ₂/µ₂)

PC - proportionate change in means (PC=µ₁-µ₂/µ₁).

Considering the existing data10, CV=30 per cent (0.3) and PC=20 per cent (0.2). After putting these values in the above formula, the sample size came out to be 29.52 ≈ 30. A total sample size of 60 (30 individuals in each group) was proposed.

Participant screening and analysis: Individuals were screened based on their detailed history, thorough clinical examination and inclusion and exclusion criteria. All the participants underwent thorough history taking, including family history. Data on their family history of hypertension were collected by using interviewer-administered questionnaire. The response options ‘yes’ or ‘no’ were considered for diagnosing parental history of hypertension. Presence of either or both parents having hypertension was considered as positive (cases).

Sixty normotensive participants (BP <120/80 mmHg according to JNC 8 criteria11 of hypertension) of both genders (M=F), aged 18-40 yr, untrained for exercise, with a normal body mass index (BMI: 19-22.9 kg/m²) were taken as the study population. Individuals with history of hypertension, diabetes or any other chronic illness, substance abuse and pregnant/lactating females were excluded from the study. All the females selected as cases or controls participated during their follicular phase of the menstrual cycle.

Participants were further divided into two groups based on their family history of hypertension. The cases (Group 1, n=30) consisted of the offspring of hypertensive parents, while the offspring of normotensive parents were taken as the controls (Group 2, n=30).

Experimental protocol: Participants were asked to abstain from caffeinated drinks 24 h prior to testing. All the recordings were performed at the same time of the day (in the morning) after an overnight fasting. The anthropometric measurements (weight and height) were recorded using a stadiometer and balance beam scale. BMI (kg/m²) was calculated by dividing the weight (in kg) by the height in metres squared.

Exercise test: This consisted of an acute bout of moderate isotonic exercise based on target heart rate (60-70% of MHR)12, on a treadmill according to the modified Bruce protocol. The resting SBP, DBP and MAP were measured using a mercury sphygmomanometer on the left arm in all the participants in a sitting position.

After a rest period of 5-10 min, each subject was first asked to walk on a treadmill to warm up (at 1.7 mph). The speed of the treadmill was gradually increased in stages till the subject achieved the target heart rate. The target heart rate was calculated individually for every subject using the Karvonen formula (heart rate reserve multiplied by 60-70% plus the subject’s resting heart rate). This is more accurate since it takes both age and resting heart rate into account. At this target heart rate, the exercise was continued for 10 min and then stopped. The BP parameters were recorded again immediately and after 10 min of cessation of exercise. All the requisite precautions in conducting an exercise protocol for a subject were followed.

Statistical analysis: Data were analysed using SPSS-25 software (IBM SPSS Inc., Chicago, IL, USA). and were presented as mean ± standard deviation. Continuous variables were analyzed using the Mann-Whitney test U or Student’s t test (independent group/unpaired data) and Wilcoxon signed-rank test or paired t test (for paired data) based on the normality of the data. A multiple linear regression model for BP-change as the dependent variable (output) was plotted, and beta-coefficients for independent predictors were assessed; P<0.05 was considered significant.

Results

The baseline parameters in both the groups (cases vs. controls) were comparable with respect to their age (27.23±7.14 vs. 27.67±6.7 yr, respectively), gender composition (males:females = 1:1) and BMI (21.88±2.05 vs. 21.35±3.63 kg/m², respectively).

As shown in Table I, it was observed that the pre-exercise resting SBP was similar in both the groups. However, after exercise, the mean SBP was reduced by 5 mmHg than the baseline SBP in cases (Group 1) as compared to the controls (Group 2; P=0.01). Although the fall in mean DBP and MAP was significant across both the groups (intragroup, paired t test; P<0.05), the intergroup variations were insignificant for the same.

The magnitude of PEH after exercise measured as delta change (BP change before and after exercise) in mean SBP (~5 mmHg) and delta MAP (~4 mmHg) was significantly higher (Table II) for the cases as compared to the controls (P=0.01). The delta DBP was insignificant for both the groups.

A multiple linear regression model (Table III) was plotted for the change in systolic BP as the dependent variable or output (y). The model consisted of age, gender (M=1, F=0) and BMI as independent explanatory variables (x); none of which achieved significance.

Discussion

The uniqueness of the current study rests with the fact that it revealed a greater degree of PEH in the offspring of hypertensives as compared to that in the offspring of normotensive parents. To the best of our knowledge, no comparative study has been reported yet on PEH in the offspring of hypertensives and normotensives. However, our findings are consistent with the results of various investigations, which reported a greater degree of PEH in hypertensives as compared to normotensives1,2. Wilcox et al13 suggested that the magnitude of pressure decrement increases with longer duration of exercise in hypertensive patients than in the normotensive population, though this could not be substantiated in our study since the duration of PEH remained the same (for 10 min) in both the study groups in our investigation. The post exercise measurements were monitored after 10 min based on the fact that PEH has been observed after as little as 10 min with an average decline of 8/9 mmHg in normotensives to 14/7 mmHg in hypertensives1,2. Interestingly, according to U.S. 2018 Physical Activity Guidelines Advisory Committee, it is now known that exercising for as little as 10 min is effective for positive health benefits, so exercise duration is no longer emphasized14.

Most of the ongoing research work currently focuses on adults already diagnosed with pre- or established hypertension, with PEH being targeted as the non-pharmacological tool to treat hypertension7-9. Apparently, exercise works best for those who are in greatest need of its BP-lowering capabilities. Hence, clinicians need to be cognizant and ensure that the patients or even the normal population who have been referred to specific exercise interventions can really derive benefit out of them. Offspring of the hypertensives and not the clinically diagnosed hypertensives were considered since the present study attempts to better characterize those who benefit most from exercise and hence identify PEH as an important primary preventive tool (apart from being a non-pharmacological method) to prevent or delay the development of hypertension. With respect to the aforementioned facts, the present study reveals that the offspring of hypertensives who are more susceptible to hypertension are likely to derive a greater benefit even after a single bout of MICE, quantified in terms of PEH, as compared to the offspring of normotensives.

Various mechanisms such as reduction in blood volume, the activation of the cardiac efferent and afferent sympathetic nervous system and of skeletal muscle ergoreceptors, as well as production of nitric oxide, adenosine, etc., reflecting the balance between sympathetic and parasympathetic influences have been postulated which regulate the cardiac output and peripheral resistance after exercise and hence explain the conflicting results in the degree and duration of PEH in normotensives vs. hypertensives7,13,15-18. However, no studies have been conducted on the offspring of hypertensives or normotensives, which may establish that the degree of PEH is determined by the genetic predisposition. Our study results may be explained by the fact that the complexity of BP regulation suggests that PEH has a multifactorial origin, also affected by genetic factors7. Cumulative data suggest that genetic polymorphism mapping may facilitate the identification of people that respond better in terms of PEH, particularly after moderate-intensity aerobic exercises3-4,19. The authors would recommend correlating PEH in the offspring of hypertensives and normotensives with gene polymorphism for candidate genes in future studies, so as to study the genetic predisposition to PEH in detail.

The main strength of our study was that in order to avoid the conflicting results as observed in previous investigations2,20 that revealed divergent relationship of PEH with gender and time of the day, the present study was conducted at the same time of the day and was designed to have an equal number of male and female participants. Our results are consistent with the studies which state that PEH occurs in both men and women21,22. Specifically, BP control post exercise in men seems to be centrally regulated through stroke volume, while females tend to regulate post exercise BP through peripheral vasodilation, although such regulation may be dependent on the mode and intensity of exercise21,22.

None of the predictors for PEH (age, gender or BMI) achieved significance in the present study and might be attributed to a smaller sample size as a limitation in our study. Gender based analysis can be carried out more accurately once larger number of participants are enrolled in future investigation. There were other limitations of our study as well. Firstly PEH had been documented under laboratory conditions in contrast to the ambulatory BP monitoring, and second, the duration for which PEH was observed was kept limited to only 10 min post exercise. The reason for choosing 10 min rather than 30-60 min or longer was that we were curious to explore the statement cited in the literature that PEH and positive effects of exercise could be observed as early as 10 min2,14. However, it would be worthwhile to study PEH in the offspring of both normotensives and hypertensives under normal day-to-day living conditions in future. Furthermore, we did not document a difference in the two groups either in terms of calculated METs from the treadmill at which 70 per cent HR max was reached or the duration of the exercise, which could be a potential confounder that might had affected the difference of magnitude of PEH in two groups. No resting BP screening or familiarization visits were performed that could have allowed greater rigour and reproducibility in the measure of PEH as recommended by de Brito et al23.

Post exercise hypotension may contribute to some of the long term adaptations associated with exercise training, such as amelioration of hypertension and plasma volume expansion24. Cumulative data support the notion that the reductions in BP experienced immediately following a single bout of aerobic exercise are similar to those experienced after aerobic exercise training; an observation that suggests BP-benefits attributed to chronic exercise is largely due to PEH1,2,16,24. PEH may thus serve a homeostatic purpose; henceforth, the development and understanding of non-pharmacological treatment modalities such as PEH for hypertension continue to deserve high priority.

From this investigation, it is concluded that the degree of PEH may be related to the genetic predisposition of humans to hypertension. PEH occurs in higher magnitude in normotensives who are genetically predisposed to hypertension, such as offspring of hypertensive parents. The present study supports the clinical implications of PEH as a crucial non-pharmacologic line of defence in treating hypertension and would justify participating in several periods of moderate physical activity interspersed throughout the day. The genetically predisposed normotensive offspring of hypertensives may find regular exercise-induced PEH as an important primary preventive tool to prevent or delay the development of hypertension, thus linking PEH to the long-term antihypertensive adaptations.