An evidence-based guide to the efficacy and safety of isometric resistance training in hypertension and clinical implications

An isometric muscle contraction is one where there is no change in muscle length, but a force is applied, and muscle tension may increase (Fig. 1A). This may occur because the force produced by the muscle(s) is the same as the external resistance (e.g., holding a dumbbell) or because the opposing load is greater than the force generated (e.g., trying to push over a large, stable tree trunk). As there is no observable change in joint angle and muscle length during the contraction, it is often referred to as a “static” contraction. Simply, dynamic or isotonic contractions (concentric and eccentric) move loads, while isometric contractions create force and/or tension without movement.

During isometric work the contraction is static and sustained and therefore the intramuscular pressure generated is often enough to partially or fully inhibit vascular blood flow in the vessels that serve that particular muscle or muscle group [36]. For example, handgrip squeezing exercise requires a static forearm contraction and therefore the flow in the brachial artery may be partially or fully occluded. The extent of the disruption to blood flow is dependent on the relative intensity of the contraction [39, 44]. After the isometric contraction ceases reactive hyperemia occurs; this is transient blood flow, at a raised rate, that occurs in healthy blood vessels following an ischemic episode, such as IRT at a sufficient proportion or percentage of maximal voluntary contraction (MVC; the maximal force-generating capacity of a muscle or group of muscles in humans), usually this is 15% to 30% of MVC [14, 45]. This reactive hyperemia is facilitated by vasodilation, and this results in a sustained blood pressure reduction that lasts for an undefined period of time but commonly several hours [46]. As with other types of exercise training, repeated exposure to cycles of ischemia-hyperemia-reperfusion can lead to stable blood pressure changes (lowering) which are sustained if one continues to train. This training status dependent lowering of blood pressure has been shown to be a result of anatomical increases in blood vessel diameter with aerobic exercise [47], but similar data is not available for IRT. However, IRT causes an acute stimulation of the metaboreflex in an attempt to restore muscle blood flow. This and other long-term physiological responses (occurring from approximately 4 weeks onwards) may reduce tissue oxidative stress, and improve vascular endothelial function, baroreflex sensitivity, and autonomic balance [48].

To put this into context, a healthy man aged 20 to 50 years would be expected to generate a maximal isometric handgrip contraction of about 40 to 50 N. It is thought that at about 20% to 30% of one’s handgrip MVC, there is a measurable disruption to blood flow. For lower limb isometric contractions (e.g., squatting with one’s back resting against a wall with knees at a 90° angle), it is believed that the disruption to blood flow occurs at a slightly lower relative intensity of 15% to 25% MVC; this is probably due to the greater force generated and specific fiber arrangement [49] in the muscles of the lower limb. The relative exercise intensity (equivalent to %MVC) generated in isometric wall squats can be adjusted by changing the knee joint angle [50, 51].

A rapidly growing body of evidence continues to highlight the benefits of IRT in lowering blood pressure (BP). However, to date, the exact mechanisms responsible for the BP lowering effects of IRT have not been fully elucidated. The effects of IRT most likely involve interactions of a number of pathways and mechanisms, including endothelial function, structural vascular adaptations, oxidative stress, and autonomic nervous system activity [13, 52].

An intensity-dependent rise in HR and BP occurs with all types of physical exercise. Central command, muscle reflexes, and the arterial baroreflex are important regulators of the cardiovascular system during exercise [58, 59]. An exaggerated BP response to exercise is a predictor of future chronic hypertension which may lead to risk of organ damage, cardiac events, and mortality [60‐62]. Somewhat paradoxically regular exercise, at an appropriate intensity and volume, has been shown to reduce BP and reduce the risk of organ damage and cardiovascular disease. As with many novel medical treatment approaches there is often an inherent concern that new ideas may cause harm. In hypertensive individuals compared to normotensive individuals, it is this “possible” exaggerated pressor (hypertensive) response, resulting in an increase in pressure load on the heart, that appears to raise the most concern among professionals in relation to the safety of IRT. However, as outlined below, evidence indicates that the acute increase in BP during IRT is no larger, and in fact in some studies smaller [36, 63, 64], than that observed with AET.

We acknowledge that the threshold for an extreme or exaggerated hypertensive response does vary with different datasets [65]. The threshold for a hypertensive response to physical stress is as low as 190/90 mmHg and as high as 250/120 mmHg in different settings [65]. The physiological basis of why isometric contractions at or above 50% MVC may cause extreme hypertensive responses was outlined in the early 1970s. In 1970, Lind [41] described that at 10% to 15% MVC, isometric contractions can be maintained for 30 min or more. At these low tensions, the HR increases by only a few beats per minute (bpm) and BP by only 5 to 15 mmHg, for as long as the tension is maintained. Muscle blood flow also increases to a steady state, which corresponds with the indefinite period contractions can be held for. At 20% MVC and higher, fatigue occurs rapidly. At 20% MVC, contractions can be held for around 10 min. At 30% MVC, the duration is about 5 min, while at 50% MVC, it is 1 to 2 min. When working to a constant force above 20% MVC, the blood flow in the muscle does not reach a steady state, nor does the HR or BP. Instead, all these factors continue to increase until fatigue, as a function of duration intervenes. At the point of fatigue, it is uncommon for HR to be over 120 bpm. However, both SBP and DBP increase dramatically and almost in parallel, and MAP at fatigue is commonly 140 mmHg or more. By contrast, in fatiguing rhythmic exercise (a treadmill test of progressive severity), the HR characteristically reaches near maximum values, while the MAP shows only slight changes. In isometric exercise, widespread peripheral vasoconstriction occurs, so increased cardiac output then elicits a BP rise, but stroke volume does not increase and at higher tensions (for example, 50% MVC) it decreases, so that increased HR is the sole contributor to the increase in cardiac output [41].

For the reasons outlined in the previous paragraph, there was a historical reluctance to use IRT in people with even mild hypertension, but recent trials have used low to moderate training intensities (10%–30% MVC) [2, 9] normally performed for a short 2-min duration; these are associated with, relatively modest [64] rises in BP during IRT. In summary, during both isotonic and isometric muscular contractions there is a notable pressor (BP raising) response at intensities of 50% MVC or above, but this is mitigated by the lower (10%–30% MVC) training intensities and shorter durations that have become common practice. Finally, one should not forget that there is also evidence of blood flow impairment with repeated concentric contractions [66].

As mentioned previously, from a historical perspective IRT was contraindicated for people with hypertension [67, 68]. In some of the early studies, IRT was employed at a relatively high proportion (> 50%) of MVC, with some studies asking research subjects to contract at maximal capacity (100% MVC) resulting in an exaggerated pressor response [69, 70]. Contractions 50% MVC, or above, are likely to generate a notable pressor (hypertensive) response > 200/100 mmHg and should be avoided in all but young, healthy people clinically free of cardiovascular disease.

One should point out that once IRT ceases, BP will return very close to baseline levels in a matter of seconds [71, 72], whereas the normal time course of recovery to prolonged aerobic exercise is of longer duration, usually several minutes, but can be several hours [73]. Previous work has identified that people are at a raised risk of adverse exertional-related health events during aerobic exercise and the 30 to 60 min post exercise recovery period [74]. Three key points are evident from our observations of BP responses to IRT. First, one can see from Fig. 3 that RPP exhibits a positive linear correlation with %MVC during IRT activity. Second, despite a slight cumulative upward drift, the RPP values still remain less that the RPP values for moderate aerobic intensity in hypertensive individuals at equivalent %MVC (Fig. 3, Table 1). Third, individuals with hypertension exhibit slightly higher RPP values than people with normal BP, at the same %MVC intensity (Table 1).

A recently published meta-analysis [19] of RCTs of IRT showed long-term BP lowering effects are achieved with isometric contractions at 15% to 30% MVC. While contractions at this intensity do raise BP, the increase is much smaller (20–30 mmHg) than would be seen with moderate intensity aerobic exercise. IRT also results in much smaller (10–30 bpm) increases in HR. The net RPP is much lower with IRT versus aerobic exercise (Table 1). Available data suggests that this difference is greatest when participants use small muscle mass isometric handgrip training, compared to a RPP value of 18,000 bpm × mmHg (based upon BP and HR average over the last 30 s of the final/fourth wall squat bout) for participants (with high-normal BP) performing double-leg IRT [64]. RPP is used primarily by cardiologists to estimate oxygen utilization in the myocardial tissues. Often people with symptoms of angina pectoris become symptomatic at a reproducible threshold [75]. In people with exertional angina symptoms, or cardiac arrhythmia, an RPP threshold can be set in order to minimize symptom exacerbation and lower the risk of serious cardiovascular events.

IRT produces an ischemic preconditioning response that is cardio protective [3, 76]. This effect is also seen with aerobic and possibly dynamic resistance exercise, but a much higher RPP is generated during these latter two forms of exercise. IRT produces a reactive hyperemic response immediately post exercise that improves endothelial function long-term [73]. IRT elicits greater uptake of blood into the coronary collateral circulation in people with coronary artery disease [35]. Similarly, in people with peripheral arterial disease, IRT was reported to reduce brachial DBP, and increase flow mediated dilatation [4], a measure of endothelial function. IRT also elicits rises in vascular endothelial growth factor (stimulant for new blood vessel growth) in heart failure patients [5]. The available evidence therefore suggests that the “default” position that IRT is unsafe is perhaps unsupported, and indeed contradicted somewhat, by the published literature. Benefits can also be seen in other patient populations, as shown in Table 2, which provides a summary of analyses and studies across different populations indicating any safety concerns or possible contraindications to the use of IRT.

While the benefits of IRT can be seen in a range of patient populations, concerns about safety of this type of exercise may be further alleviated if one recalls IRT is only sustained for 1 to 2 min, which is below the 3-min threshold scientists believe is necessary to develop reperfusion injury [77]. With 2 to 3 min rest periods for IRT the minimal increase in HR and mild/moderate hypertensive responses are brief. IRT protocols allow for adequate (complete) recovery periods, which are achieved in seconds with IRT and not minutes as with aerobic exercise. We have reported the findings from IRT training and studies below. A detailed summary of analyses and recent RCTs can be found in Table 2.

Current evidence indicates IRT lowers BP, but one may ask if these changes are clinically meaningful and hence supportive of the transition of IRT into “real world” clinical practice. In order to provide a “clinical” meaning, we conducted secondary analyses from our earlier IPD and categorized participants as responders versus nonresponders [17]. We defined “responders” as any participant who showed a 5 mmHg or greater reduction in SBP, a 3 mmHg or greater reduction in DBP, and/or a 3 mmHg or greater reduction in MAP [78].

For each of SBP, DBP, and MAP, we calculated responder rate, absolute risk reduction (ARR) and number needed to treat (NNT). The 28.1% ARR is the difference between the proportion of responders in the IRT (55.5%) minus control (27.4%). The NNT is the inverse of the ARR. Approximately three times as many people who undertake IRT experience a favorable BP lowering response compared to controls who do not undertake IRT. This means that about one-quarter (27.4%) of people will lower their BP independent of IRT, probably due to any of the following approaches, or combination thereof—medication changes, weight loss, or improved diet. Moreover, if someone with hypertension undertakes a program of IRT then their likelihood of reducing their BP increases to about 55% (Table 3).

A landmark meta-analysis by Xie et al. [79] demonstrated that if one were able to reduce a participant’s SBP by 7 mmHg this would equate to a 13% risk reduction for myocardial infarction and a 22% risk reduction for stroke. Moreover, our 2019 IPD meta-analysis [17] demonstrates that this magnitude of BP reduction is possible to detect in a sample of > 320 participants, as demonstrated in our two-step model of our IPD data. Additionally, the recent Delphi study of experts’ consensus fully supports IRT as it produces clinically meaningful BP reductions [57].

Time, accessibility, and cost are commonly reported barriers to exercise participation and adherence [85‐87]. The evidence for the benefits of IRT in improving general health including chronic conditions is unequivocal. Given the low rate of participation and the problem of long-term adherence, where possible, exercise specialists need to consider interventions that can reduce barriers, promote adherence and in turn have patients reap the benefits. IRT has the potential to do this. It is accessible to most people, takes as little as 17 min per session three times weekly, and the cost is negligible, especially when appropriately transitioned to a home exercise program.