Exercise as a treatment for hypertension: Literature review

Classification of hypertension

Blood pressure can be classified as normal blood pressure or non-elevated blood pressure, elevated blood pressure and hypertension. Elevated blood pressure is defined as having an office systolic blood pressure of 120–139 mmHg or a diastolic blood pressure of 70–89 mmHg. The effectiveness of blood pressure-lowering therapy within this range has been confirmed through meta-analyses of randomized controlled trials (RCTs).⁸ However, the average cardiovascular disease risk in individuals with elevated blood pressure is not high enough to warrant drug treatment for all patients.^9–11 Non-elevated blood pressure is defined as having a systolic blood pressure of less than 120 mmHg and a diastolic blood pressure of less than 70 mmHg. Individuals within this range have a lower risk of cardiovascular disease (CVD), and there is insufficient evidence to support the benefit of blood pressure-lowering pharmacological treatment, as relevant trials are lacking.¹⁰ Hypertension can in turn be classified as primary (essential) and secondary hypertension. While the cause of primary hypertension is poorly understood, secondary hypertension is usually due to uncommon and common medical conditions.¹

Risk factors

While the precise cause of primary hypertension is not fully understood, numerous risk factors are robustly and independently linked to its onset. As individuals age, they are more likely to experience increased blood pressure, especially systolic blood pressure, along with a higher incidence of hypertension. Obesity and weight gain are significant risk factors for hypertension and contribute to the increase in blood pressure often seen with advancing age.^12,13 Hypertension is roughly twice as prevalent in individuals with one or both hypertensive parents. Numerous epidemiological studies indicate that genetic factors contribute to about 30 percent of blood pressure variation across different populations.^14,15 Hypertension is more prevalent, severe, and tends to manifest earlier in life among Black individuals, leading to more significant target-organ damage.¹⁶ Having fewer nephrons in adulthood can increase the likelihood of developing hypertension. This condition can be influenced by genetic factors, disturbances during intrauterine development (such as hypoxia, drug exposure, and nutritional deficiencies), premature birth, and environmental conditions after birth (such as malnutrition and infections).¹⁷ High sodium intake in the diet, combined with low potassium intake, elevates the risk of developing hypertension.¹⁸ Excessive alcohol consumption: High alcohol intake is linked to the development of hypertension, and reducing alcohol intake can lower blood pressure in those who consume large amounts.¹⁹ Lack of physical activity raises the risk of developing hypertension, while various forms of exercise (aerobic, dynamic resistance, and isometric resistance) are effective in reducing blood pressure.^12,20,21 Insufficient sleep: Sleeping less than 7 hours per night is linked to a higher risk of hypertension.^22,23 Increasing sleep duration may help lower blood pressure.^24,25 History of gestational hypertension or preeclampsia: Women who experienced high blood pressure during pregnancy are at an increased risk of developing chronic hypertension later in life, even if their blood pressure returns to normal after giving birth.^26,27 Factors such as low socioeconomic status, lack of health insurance, food and housing insecurity, exposure to discrimination, and limited access to safe spaces for exercise can contribute to many of the previously mentioned risk factors for hypertension (like obesity, poor diet, and physical inactivity).^28,29 These social determinants are likely significant contributors to the racial disparities observed in hypertension rates. Exposure to noise and air pollution can elevate blood pressure and may play a significant role in the disparities seen in hypertension prevalence and management.³⁰

Conversely, risk factors for secondary hypertension can overlap with those for primary hypertension and pose significant challenges to maintaining proper blood pressure control. The major risk factors for the development of secondary hypertension include prescription or over the counter drugs like oral contraceptive pill, especially those containing higher doses of estrogen, nonsteroidal anti-inflammatory drugs when used chronically, acetaminophen when given at doses of 4 grams per day for several weeks or more,³¹ corticosteroids, decongestant like phenylephrine and pseudo phenylephrine, glycyrrhizin, sodium containing antacids, erythropoietin, cyclosporine or tacrolimus, stimulants like methylphenidate, amphetamines and some weight-loss medications, atypical antipsychotic drugs like clozapine and olanzapine, angiogenesis inhibitors such as bevacizumab, tyrosine kinase inhibitors like sunitinib and sorafenib.^11,32 Likewise, illicit drug use like methamphetamines and cocaine, primary kidney disease including acute and chronic kidney diseases, primary hyperaldosteronism, Reno vascular hypertension, obstructive sleep apnea, pheochromocytoma, Cushing syndrome, other endocrine disorders like hypothyroidism, hyperthyroidism and hyperparathyroidism and coarctation of the aorta.³³

Clinical manifestation of hypertension

Most persons with hypertension do not experience any symptoms. Extremely high blood pressure can induce headaches, impaired vision, chest pain, and other symptoms. The best technique to determine whether someone has high blood pressure is to take his or her blood pressure. If not addressed, hypertension can lead to other health problems such as renal disease, heart disease, and stroke. People with extremely high blood pressure (typically 180/120 or greater) may have symptoms such as: severe headaches, chest pain, dizziness, difficulty breathing, nausea, vomiting, blurred vision or other vision changes, anxiety, confusion, buzzing in the ears, nosebleeds, and abnormal heart rhythm.²

Exercise and hypertension

Research indicates that hypertensive patients tend to be less physically active compared to individuals with normal blood pressure.⁴³ Lifestyle changes, such as incorporating exercise, can help delay the onset of hypertension.⁴⁴ Numerous studies have demonstrated that physical activity reduces blood pressure independently of weight loss in both individuals with normal blood pressure and those with hypertension.^45,46 In a meta-analysis combining data from 72 trials involving hypertensive adults, it was found that aerobic exercise significantly reduced resting clinic systolic and diastolic blood pressure by 3.0/2.4 mmHg. Additionally, daytime ambulatory blood pressure was lowered by a similar amount, 3.3/3.5 mmHg.⁴⁷ Blood pressure reductions were more pronounced in trials with hypertensive patients compared to non-hypertensive individuals, showing reductions of 6.9/4.9 mmHg versus 1.9/1.6 mmHg. However, the overall magnitude of blood pressure reduction was not significantly influenced by factors such as exercise dose, training frequency, intensity, session duration, or specific exercise type. It is important to note that meta-analyses are not well-suited to explore these specific questions in detail.⁴⁷

Regular exercise is crucial for preventing hypertension and enhancing long-term survival.⁴⁸ The amount of oxygen consumed at rest is equal to 3.5 mL O₂ per kilogram of body weight, defined as one metabolic equivalent (MET). This concept is simple, practical, and easy to understand, expressing the energy expenditure during physical activity. For those not well conditioned in aerobic activities, the MET level corresponds to 40% of their maximum MET. In well-conditioned individuals, this level is 85% of their maximum MET. For healthy individuals, continuous aerobic exercise at 60-70% of the maximum MET, at the anaerobic threshold, is recommended.⁴⁹ Activities like sleeping, watching television, playing video games, or using a computer, which do not significantly raise energy expenditure above the resting level, are considered sedentary behaviors. These activities typically consume ≤1.5 MET.⁵⁰ Body movements are considered physical activity when they result in energy expenditure above the resting levels of skeletal muscles. Examples of physical activities include daily housework, gardening, shopping, and professional tasks. Planned, structured, and repetitive forms of physical activity aimed at improving and maintaining health are known as exercise. Physical fitness refers to the capacity of a person to engage in physical activities without experiencing excessive fatigue.⁵¹

Mechanism of exercise in decreasing hypertension

The precise molecular mechanisms underlying the positive impact of physical activity on blood pressure remain largely unclear, likely due to the intricate and multifaceted nature of blood pressure regulation, which involves neuro-hormonal, hemodynamic, and metabolic factors.⁵² One of the primary ways physical exercise influences blood pressure is through the regulation of endothelial function. Vascular homeostasis relies heavily on the endothelium, which is a crucial regulator of vasomotor responses and plays a significant role in maintaining the health and resilience of blood vessels. Nitric oxide (NO) acts as a key mediator in endothelial function, and both clinical and preclinical studies have demonstrated that exercise enhances NO-dependent endothelial vasodilation.^53–58 Physiologically, increased blood flow stimulates high nitric oxide (NO) production to counteract shear stress through vasodilation.^59–61 The SEFRET study (Study of endothelial function response to exercise training in hypertensive individuals) provides direct evidence that enhancing endothelial function is a key mechanism behind the antihypertensive benefits of physical exercise.⁶² The study highlights two essential findings: physical activity improves endothelium-dependent vasodilation in people with hypertension; and the extent of this improvement in endothelial function varies with the type of exercise training (aerobic, resistance, or concurrent). This evidence underscores the importance of prescribing specific exercise programs as part of the therapeutic strategy for patients with hypertension.

Hypertension is marked by microvascular rarefaction due to impaired angiogenesis.⁶³ Regular physical exercise has been shown to promote vessel adaptation, increasing blood flow reserves.⁶⁴ These structural changes in the vascular network are attributed to exercise-induced angiogenesis, which enhances both the size and number of blood vessels.⁶⁵ The creation of new micro vessels and the expansion of vessel networks are governed by vascular endothelial growth factor (VEGF) and other mediators. Released during exercise training, VEGF stimulates endothelial cell division, promotes endothelial cell migration, and encourages chemotaxis.⁶⁶ Additional factors that regulate angiogenesis are released in response to exercise, such as angiopoietins and metalloproteinase. These factors trigger the degradation of the extracellular matrix, a crucial process for forming vascular networks.⁶⁷

A groundbreaking study revealed that the hypertensive condition caused by a high-fructose diet was significantly mitigated by spontaneous physical activity in rodents, which was also associated with a notable reduction in insulin resistance.⁶⁸ This finding strongly indicates a pathophysiological connection between essential hypertension and hyperinsulinemia.⁶⁹ More recently, studies using an animal model of metabolic syndrome have demonstrated that moderate-intensity exercise training plays a preventive role by significantly impacting the regulation of blood pressure and insulin sensitivity.⁷⁰ The consistent link between exercise training and improved insulin sensitivity strongly bolsters the hypothesis that physical activity can prevent the onset and progression of hypertension by enhancing insulin responsiveness. Numerous studies provide direct evidence of this connection; for instance, Chisholm and colleagues showed that exercise training significantly boosts whole-body insulin sensitivity, particularly by increasing glucose uptake and oxidation in skeletal muscle.⁷¹

One of the pioneering clinical studies highlighting the antihypertensive benefits of physical activity was published in 1968. The research showed that men who reported engaging in over 5 hours of physical exercise per week experienced a significant reduction in the incidence of hypertension.⁷² Over the past five decades, this observation has been consistently validated by extensive prospective studies, reinforcing the inverse relationship between physical activity and hypertension.^12,21,73 Interventional studies have validated the direct impact of physical activity on blood pressure, identifying the populations that respond most favorably. A training regimen of two days per week has been shown to reduce blood pressure in both hypertensive and normotensive individuals.⁷⁴ Another study showed that the impact of physical exercise on blood pressure is more significant in hypertensive patients compared to normotensive individuals.⁷⁵ However, while exercise training primarily benefits those with hypertension, it also helps prevent the progression from normal blood pressure to pre-hypertension and from pre-hypertension to full hypertension.^74,76–79

Exercise recommendation

There is no single exercise plan that suits all adults. Exercise recommendations should be tailored to each individual’s abilities to prevent injuries and enhance motivation for sticking to a routine. It is often difficult to change patients’ behavior, and merely providing information and general advice is usually not enough. Therefore, clinicians should combine the exercise prescription with practical strategies, such as working out with friends, joining community groups, and keeping track of physical activity duration or counts.^80,81 Similar to various therapeutic approaches, both pharmacological and non-pharmacological, the exact mechanisms by which exercise reduces blood pressure and prevents hypertension remain unclear. This uncertainty is partly due to the complex and multifactorial nature of elevated blood pressure.⁷⁰

Engaging in regular aerobic exercise can support weight loss, lower blood pressure (BP), and reduce the overall risk of cardiovascular disease. With moderately intense activities, such as brisk walking for 30 minutes a day, five days a week, BP may be reduced by 4-9 mm Hg.⁸² Alternatively, more intense workouts lasting 20-30 minutes, three to four times a week, can also lower BP and offer additional health benefits.⁸²

World health organization recommends increasing physical activity by engaging in activities such as walking, running, swimming, dancing, or strength-building exercises like lifting weights. Aim for at least 150 minutes of moderate-intensity aerobic activity or 75 minutes of vigorous aerobic activity per week. Additionally, incorporate strength-building exercises at least twice a week. If he/she is overweight or obese, focus on losing weight as part of routine task. In addition, avoiding prolonged periods of sitting and making movement a regularly.⁸³ The Up-to-date online database suggests engaging in at least 150 minutes of moderate-intensity physical activity weekly, which equates to about 30 minutes per day for five or more days each week. Alternatively, they recommend at least 75 minutes of vigorous-intensity physical activity per week, translating to approximately 30 minutes per day for three or more days each week.⁸¹