Effect of isometric resistance exercise on blood pressure in normotensive adults: a systematic review of randomized clinical trials

Introduction

Arterial hypertension (AH) is one of the leading causes of morbidity and mortality globally, representing a significant burden on public health and substantially impacting the economy due to the costs associated with treatment and cardiovascular complications (1,2). According to the World Health Organization (WHO), it is estimated that more than 1.13 billion people worldwide suffer from hypertension, which is responsible for approximately 7.5 million deaths annually (1,2). AH is strongly associated with an increased risk of serious cardiovascular events such as myocardial infarction, stroke and heart failure, as well as contributing to the development of other chronic conditions such as chronic kidney disease and retinopathy (2,3).

Given this scenario, the search for effective strategies to prevent and control hypertension has intensified. Non-drug interventions, especially physical exercise, have gained prominence due to their proven effectiveness in reducing blood pressure (BP) and promoting cardiovascular health (4-6). Among the various types of exercise, isometric resistance exercise (IRE) has emerged as a promising intervention. IRE is characterized by static muscle contractions maintained for a prolonged period without changing the length of the muscle, differing from dynamic modalities which involve continuous movements (5,6).

A systematic review with meta-analysis that included normotensive, pre-hypertensive and hypertensive individuals revealed that IRE promoted average reductions of 6 mmHg in systolic blood pressure (SBP), 3 mmHg in diastolic blood pressure (DBP) and 3 mmHg in mean arterial pressure (MAP), respectively (7). These results indicate that IRE can offer significant and clinically relevant improvements in BP, suggesting its potential as a preventive intervention.

Although there is robust evidence of the beneficial effects of IRE in hypertensive and pre-hypertensive populations (8,9), there is a gap in the literature regarding the effects of this form of exercise in normotensive adults. Research into the impact of IRE in normotensive individuals is crucial, as it can offer an accessible and low-cost preventive strategy to avoid the development of hypertension, especially in populations with moderate risk factors.

Physiologically, IRE seems to promote changes that induce the release of vasodilator substances by the vascular endothelium (10). Studies suggest that IRE improves autonomic balance (11,12), decreases the sensitivity of baroreceptors (13) and attenuates oxidative stress derivatives (14). In addition, there is evidence that IRE promotes adaptations in the arterial vasculature, such as increased collateral circulation and expansion of the arterial tree (15), which can result in a reduction in BP in normotensive adults.

Therefore, the main objective of this systematic review is to describe the effect of IRE on BP in normotensive adults. The relevance of this study lies in the possibility of offering an additional alternative to traditional hypertension prevention strategies, contributing to the diversification and optimization of physical exercise protocols aimed at maintaining cardiovascular health. We present this article in accordance with the PRISMA reporting checklist (16) (available at https://atm.amegroups.com/article/view/10.21037/atm-24-124/rc).

Methods

Type of study

This is a systematic review composed of randomized clinical trials, following the acronym PICO to answer the following clinical question: What is the chronic effect of IRE on BP in normotensive individuals?

• P = normotensive adults;
• I = isometric resistance exercise;
• C = other neuromuscular interventions and/or placebo;
• O = systolic, diastolic and mean blood pressure.

The study was prospectively registered with PROSPERO under opinion: CRD42024496749.

Eligibility criteria

We included randomized clinical trials that tested IRE intervention in normotensive adult individuals, evaluating the outcomes of SBP, DBP and/or MAP. There were no restrictions on how long the studies had been published. On the other hand, the following were excluded: randomized clinical trials that tested the intervention of IRE combined with other modalities (blood flow restriction training and aerobic training), randomized clinical trials with a crossover design and clinical trials involving individuals with pre-existing pathologies, such as diabetes mellitus, metabolic syndrome and cardiovascular diseases.

Outcome of interest

The outcomes adopted for the study were: SBP, DBP and MAP.

To classify individuals as normotensive, we took into account BP measurements based on the WHO reference values (17). BP is considered normotensive if:

• Optimal: SBP less than 120 mmHg and DBP less than 80 mmHg.
• Normal: SBP between 120–129 mmHg and/or DBP between 80–84 mmHg.
• High normal: SBP between 130–139 mmHg and/or DBP between 85–89 mmHg.

Search strategy

Randomized clinical trials aimed at evaluating the effect of IRE on BP in normotensive individuals were selected. The searches were carried out in the following databases: PubMed, Virtual Health Library (VHL), Web of Science, Scopus, and Physiotherapy Evidence Database (PEDro). The search was conducted by two independent authors (R.M.B. and A.C.N.S.) between January 2023 and November 2024. The descriptors were selected using the “Medical Subject Headings” (MeSH) and “Health Sciences Descriptors” (DeCS), using the terms: “Resistance Training”, ‘Isometric Exercise’ and ‘Blood Pressure’. The Boolean operators [AND], [OR] and [NOT] were used for the respective crossings, as described in Table S1.

Searching other resources

In addition to searching the electronic databases, we consulted the gray literature using Google Scholar to identify other published, unpublished or ongoing studies. We screened direct citations of all included studies and other relevant studies using Google Scholar (scholar.google.co.uk/) for additional references.

Study selection

The selection of studies was carried out by two independent authors (R.M.B. and A.C.N.S.). In the event of disagreements, a third reviewer was requested (J.P.). First, titles and abstracts were thoroughly read. Those that met the aforementioned eligibility criteria were selected for the final stage. As described in Table 1, the eligible studies were selected for full-text reading, a new assessment of the selection criteria and data retrieval. The references reviewed and included in this review were analyzed by the second reviewer (A.C.N.S.) in order to check for potential studies not identified in the electronic database searches. Figure 1 summarizes the strategies for selecting the studies that make up the scope of this systematic review.

Figure 1 Flowchart illustrating the selection of studies included in this review.

Data extraction

The data extracted were: (I) author and year of publication of the study; (II) characteristics of the population; (III) intervention protocol (weekly frequency, intensity and duration); (IV) control (form of control); (V) main results obtained by the studies; (VI) conclusion of the study.

Risk of bias

The quality of the studies was assessed using the PEDro (Physiotherapy Evidence Database) scale, based on the Delphi list. The PEDro scale consists of 11 items, with each item contributing 1 (one) point, with the exception of item 1, which is not scored. The total score ranges from 0 (zero) to 10 (ten). This scale assesses the methodological quality of randomized controlled clinical trials, looking at two main aspects: internal validity (credibility of scientific observations and results with the reality of what is being studied) and sufficient statistical information to make them interpretable. The scale does not assess the external validity, significance or size of the treatment effect (18).

The articles were rated independently by two assessors familiar with the PEDro scale. Differences in classification were discussed by the evaluators and, by consensus, the score of the studies was defined (Table 2). The kappa value for each of the 11 items ranged from 0.36 to 0.80 for individual raters and from 0.50 to 0.79 for consensus ratings generated by groups of 2 or 3 raters. The interval confidence (IC) for the total score was 0.56 (95% confidence interval: 0.47–0.65) for ratings by individuals, and the ICC for consensus ratings was 0.68 (95% confidence interval: 0.57–0.76). The cut-off point established to separate studies of low, moderate and high methodological quality was: 0–3 low quality; 4–5 moderate quality; 6–10 high quality (19).

Results

The search strategies developed and the references analyzed by manual search returned a total of 3,195 articles. However, after analysis by the reviewers (R.M.B. and A.C.N.S.), 32 were excluded due to duplication, leaving 2,983 studies. After removal based on title and abstract, 12 studies were screened. In another step, after screening based on eligibility criteria, another 7 studies were excluded. The main reasons for exclusion were: clinical trials that included pre-hypertensive patients in the sample, clinical trials of IRE combined with blood flow restriction training, crossover studies and clinical trials with a cross-over design. Finally, five [5] studies met the established selection criteria and are summarized in Figure 1 (15,18-21).

According to the data presented in Table 1, the studies included were published between 2000 and 2022, and 100% of them were randomized clinical trials with a parallel design. Regarding the characteristics of the population, the individuals were normotensive and sedentary or regularly active, aged between 19 and 34 years. The number of participants varied between 17 and 35 individuals of both sexes, totaling 142 volunteers, 84 of whom were in the experimental groups and 57 in the control groups. In addition, all the studies aimed to describe the effect of IRE on BP in normotensive adult individuals.

Table 1 also shows that, in all the studies, the participants in the intervention group underwent IRE for the upper and/or lower limbs, using handgrip and leg extension. The exercise protocols for the experimental group were prescribed at an intensity of 20% to 34% of maximum voluntary contraction, 4 sets of 2 to 3 minutes, with rest intervals of between 2 and 3 minutes, frequency of 2 to 5 times a week, and duration of 3 to 8 weeks. On the other hand, the control group underwent simulated exercise (18), no intervention (19) or recommendations to maintain a normal lifestyle (15,20,21). As for the outcomes, the variables analyzed were SBP, DBP and MAP, assessed by methods such as automated BP measurements and brachial oscillometry. The main results of the studies included in this review indicate that IRE promoted a significant reduction in SBP, DBP and MAP.

With regard to methodological quality (Table 2), the average score of the studies was 6.4 on the PEDro scale. Among the criteria for analyzing methodological quality, all the studies presented limitations related to the blinding of participants, therapists and evaluators (15,18-21). In addition, two studies presented limitations regarding the allocation of participants, suggesting that both the sham group and the therapy group ended up receiving psychological effects related to the intervention (18,19).

Discussion

In response to the objective of this systematic review, we identified that IRE is effective in reducing SBP, DBP and MAP, even in normotensive adults. The main mechanisms proposed for this reduction include the release of vasodilator substances (10), a reduction in oxidative stress (14), an improvement in autonomic balance (11,12) and the adaptation of baroreceptors (13). In addition, a functional endothelial adaptation was observed (20). These findings are supported by the moderate to high methodological quality of the studies analyzed.

Based on the literature reviewed, the reduction in BP seems to be influenced by the training protocols used. It was observed that IRE applied to the lower limbs (15,18,20) produced similar effects in reducing BP when compared to training aimed at the muscles of the upper limbs (19,21). This effect can be explained by the fact that, although training the lower limbs involves larger muscle groups, the load applied to these exercises was, in some studies, lower than that used for the muscles of the upper limbs. In addition, the recovery time between sets was longer in the studies focusing on the lower limbs. This factor may also have contributed to the reduction in BP.

When comparing unilateral protocols for the dominant and non-dominant upper limbs, an eight-week study involving thirty-two normotensive women (20) found that IRE performed on the non-dominant hand was only able to reduce SBP. However, in a study carried out with seventeen untrained individuals (18), IRE on the dominant hand, lasting five weeks, reduced SBP, DBP and MAP. The differences between the two studies can be explained by the smaller sample size and greater volume of training in the study by Ray et al. (18). It is also worth mentioning that the participants in the study in question (18) were untrained, while in the study by Bradov et al. (20) it was recommended that no vigorous activity be practiced in the 24 hours prior to the experimental protocol. This fact raises doubts about the level of training of the population, since, according to the literature, trained and untrained individuals show different responses in reducing BP (22,23).

Another important justification for BP reduction is mediation by vasodilator substances. The studies included in this review suggest that IRE mainly promotes the release of nitric oxide (NO) and endothelium-derived vasodilator substances (EDVS) (15,19). According to the authors, this is because sustained muscle contraction causes mechanical vasoconstriction of the arterial vessels, followed by the rapid release of blood flow after the contraction ends. The sudden and substantial increase in blood flow and velocity increases the shear force on the arterial vessel wall, inducing the production of the enzyme nitric oxide synthase (NOS). This enzyme is a precursor of NO, a potent arterial vasodilator that substantially reduces peripheral vascular resistance (24).

In line with this mechanism, IRE has also been shown to reduce the production of pro-oxidative molecules (14,20). The increase in basal production of NO and SVDE seems to be modulated by the reduction of pro-oxidative molecules. Reactive oxygen species (ROS) react vigorously with NO and SVDE, reducing their subsequent bioavailability. Therefore, regular isometric exercise can increase the body’s antioxidant defenses, reducing the concentration of ROS and preserving NO levels. This reduction in oxidative stress favors the maintenance of healthy BP (25).

In addition NO production, an additional mechanism suggested for the vasoprotective effects of exercise is functional endothelial adaptation (20). This adaptation occurs in response to increased shear stress caused by increased blood flow. To restore hemodynamic balance, the endothelium undergoes functional remodeling, increasing its capacity to release vasodilatory substances and improving its response to mechanical stimuli. Studies indicate that isometric training can induce improvements in vascular function, resulting in reduced resting blood pressure and reduced arterial stiffness (20,26). These adaptations can emerge rapidly with the initiation of training and regress with the interruption of the stimulus (27).

Although these studies discuss the reduction in cardiac output and peripheral vascular resistance as events that potentiate the reduction in BP, in a study carried out with normotensive individuals (19), no changes were found in these variables after IRE. In line with this data, there are no studies carried out with normotensive individuals that have directly measured the levels of NO or the enzyme NOS after performing IRE. This raises doubts about the potential effect of these substances in reducing BP in healthy populations.

Another hypothesis related to the reduction in BP induced by IRE derives from autonomic imbalance (7,15). During IRE, there is an increase in arterial blood flow, which leads to an increase in sympathetic autonomic activity due to an increase in plasma levels of norepinephrine. After exercise, there is a rebound effect with a reduction in plasma norepinephrine levels and, consequently, an autonomic imbalance which leads to a reduction in sympathetic activity and an increase in parasympathetic activity through vagal modulation (18). This increase in vagal modulation, added to the reduction in sympathetic activity, reduces electrical activity in the tunica media of the vessels and consequently promotes greater muscle relaxation, leading to arterial vasodilation (28).

In line with this, it has also been suggested that autonomic imbalance may involve adaptations in the functions of baroreceptors (19). These structures control the baroreflex activity of resting BP, modulated by the autonomic system, which supplies the heart and the sympathetic innervation of the peripheral vasculature (29). Thus, there is a hypothesis that repeated exposure to IRE may promote an increase in MAP and serve as a stimulus to reset the baroreceptors. However, in the study by Wiles and colleagues, no changes were observed in the low/high frequency ratio of heart rate variability (HRV) at rest after 8 weeks of exercise (19). This suggests that changes in HRV, either autonomic or in baroreceptor activity, are unlikely to have a significant effect on cardiovascular function.

These data are extremely important. When compared to other modalities, such as dynamic resistance exercise and aerobic exercise, IRE has shown comparable and, in some cases, superior results in reducing BP (30). Studies suggest (31-33) that aerobic exercise is still the most widely recommended and studied modality for reducing BP, being effective in reducing both SBP and DBP consistently in hypertensive and normotensive patients. However, IRE, such as handgrip training or isometric wall squats, can promote significant reductions in BP with smaller training volumes. This may favor adherence, especially in patients with limitations in aerobic activities. Dynamic resistance exercise, on the other hand, although it also has cardiovascular benefits and can help reduce BP, tends to have less significant effects on this parameter when compared to other modalities (6).

Thus, although aerobic exercise is still the first line of BP control, IRE has been shown to be a viable and efficient alternative, with the potential to complement and diversify exercise protocols (30). In line with the literature, an IRE protocol consisting of 4 sets of 2–3 minutes, with a 2–3 minutes interval between repetitions and an intensity of 10–40% of maximum voluntary contraction (MVC) has been shown to promote such systemic effects (6,30,33). This suggests that this intervention is effective in reducing the likelihood of developing cardiovascular disease and increasing life expectancy.

Finally, this study has some limitations that need to be discussed. The first is that the recommendations for classifying individuals as normotensive were not clear in some studies, as they suggest that in some studies the effect may have been substantially greater because baseline levels were higher. This suggests that the higher the BP, the greater the pressure reduction. Secondly, the included studies included normotensive young adults, limiting the extrapolation of these data to other clinical subpopulations. In addition, there were methodological limitations related to the blinding of therapists and evaluators, and in two studies regarding the allocation of participants. This suggests that both the sham group and the therapy group ended up receiving psychological effects related to the intervention. Another important point is that BP is a multifactorial variable; therefore, factors such as circadian cycle, nutrition and consumption of psychostimulants can affect it and were not included in the analysis of the studies, which may limit the exploration of the findings in some respects.

Conclusions

We conclude that IRE promotes a reduction in SBP, DBP and MAP in normotensive individuals. The main mechanisms identified to explain this reduction were the release of vasodilator substances, a reduction in oxidative stress, an improvement in autonomic balance and the adaptation of baroreceptors. Functional endothelial adaptation was also observed. These results are supported by the moderate to high methodological quality of the included studies.

Acknowledgments

None.

Footnote

Reporting Checklist: The authors have completed the PRISMA reporting checklist. Available at https://atm.amegroups.com/article/view/10.21037/atm-24-124/rc

Peer Review File: Available at https://atm.amegroups.com/article/view/10.21037/atm-24-124/prf

Funding: This work was carried out with the support of the Coordination for the Improvement of Higher Education Personnel - Brazil (CAPES) - Financing Code 001.

Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://atm.amegroups.com/article/view/10.21037/atm-24-124/coif). The authors have no conflicts of interest to declare.

Ethical Statement: The authors are accountable for all aspects of the work in ensuring that questions related to the accuracy or integrity of any part of the work are appropriately investigated and resolved.

Open Access Statement: This is an Open Access article distributed in accordance with the Creative Commons Attribution-NonCommercial-NoDerivs 4.0 International License (CC BY-NC-ND 4.0), which permits the non-commercial replication and distribution of the article with the strict proviso that no changes or edits are made and the original work is properly cited (including links to both the formal publication through the relevant DOI and the license). See: https://creativecommons.org/licenses/by-nc-nd/4.0/.

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