The current public health crisis of coronavirus (COVID-19) has redirected the world's focus. Patients with hypertension have been identified as one of the high-risk groups for severe illness. The rapid spread of this infectious disease led to global shutdown and extreme quarantine measures to an unprecedented extent, having social, economic and primary healthcare implications. As all public health efforts are directed to controlling this pandemic, management of chronic illnesses such as hypertension may be forsaken.⁵

The purpose of this article is threefold, to provide an overview of the current trends in hypertension, highlight the recently updated global hypertension management guidelines and to discuss hypertension in the time of a global pandemic.

Current trends in hypertension

Hypertension: a growing global epidemic

Hypertension is a complex disease defined as having a systolic blood pressure ≥ 140 millimetres of mercury (mmHg) and/ or diastolic blood pressure ≥ 90 mmHg.^6,7 In 2019, the World Health Organization estimated that 1.13 billion people around the world are hypertensive, compared to the 972 million people at the dawn of the millennium. A large burden of this illness occurs in low- and middle-income countries, accounting for up to two-thirds of all hypertensives.^7,8 The growing number of newly diagnosed hypertensive cases is not the only concern, since uncontrolled blood pressure among existing hypertensive patients represents a further global health challenge especially in developed countries.⁷ Lack of awareness, treatment and control rates are the key factors contributing to the imbalance in incidence in low- and middle-income countries compared to high-income countries.⁶ These factors also drive the higher burden of uncontrolled hypertension in low- and middle-income countries.⁷ In an effort to control the prevalence of hypertension, the WHO has aimed to reduce the global prevalence of hypertension by 2025.⁸ However, the global shift in focus on the COVID-19 pandemic may affect this goal.⁵ It stands to reason that failure to slow down a rapidly growing hypertension epidemic may increase the disease burden over the next decade.⁷

Hypertension in South Africa: factors driving increased prevalence

South Africa (SA) ranks the highest in Sub-Saharan Africa in terms of hypertension prevalence. With 42% to 54% of South Africans suffering from hypertension, the incidence is expected to increase exponentially if action is not taken.⁹

Ethnicity and race

The prevalence, treatment and control rates of hypertension vary significantly according to ethnicity.⁶ This is particularly relevant given that South Africa ranks as the ninth most ethnically diverse country in the world.¹⁰ Although genetic variation contribute the most to these differences, lifestyle and socioeconomic status affect the health behaviours of South Africans.⁶ Regardless of geographic location, black populations develop hypertension and the associated organ damage at a younger age.⁶ The frequency of resistant and nighttime hypertension, kidney disease, stroke, heart failure and mortality are also higher compared to other ethnic groups.⁶ In addition, differences in physiological processes such as suppressed renin-angiotensin-aldosterone system (RAAS), altered renal sodium control, increased cardiovascular reactivity and early vascular aging (large artery stiffness) are possible causes of this increased cardiovascular risk.⁶ In South Africa, black Africans account for over 80% of the entire 58.8 million population. Therefore, patient ethnicity is a critical consideration in managing hypertension.^6,11,12

Age

During the first decade of the millennium, the prevalence of hypertension among South Africans between 15 and 24 years of age doubled, bringing the incidence of hypertension in this age group to approximately 10%. A local and global increase in hypertension in the younger age groups, particularly in those under 40 years of age, has been reported. Of great concern is the implication of this epidemiologic trend, which may be a harbinger of a future “cardiovascular epidemic”.¹³ Lifestyle factors contributing to this increased prevalence in adolescents and young adults include urbanisation, change in diet and lack of exercise. As a result, more people are becoming overweight and obese.¹³ Over 90% of young hypertensives have essential hypertension, associated with family history, obesity or metabolic syndrome.¹³ The guidance for managing young hypertensives relies on expert opinion, usually extrapolating from adult guidelines. The mainstay of therapy should be the institution of lifestyle changes and only when strict adherence to these lifestyle interventions has failed to normalise blood pressure, should antihypertensive medication be considered.¹³ Furthermore, the use of diuretics should be reserved for severe hypertension or where there is a compelling indication, such as fluid overload, to avoid the long-term metabolic consequences of diuretics, especially the predisposition to diabetes.¹³ Other indications for the antihypertensive treatment in this younger age group would include failure of lifestyle therapy, the presence of target organ damage, secondary causes, and severely high blood pressure levels.¹³

The HIV/AIDS crisis

With 7.7 million people living with human immunodeficiency virus (HIV), South Africa is a country crippled by the highest prevalence of HIV in the world.¹⁴ In a cohort of 77,696 HIV-positive people, more than 20% of these were hypertensive at the time of antiretroviral (ARV) therapy initiation.¹⁵ Studies have also indicated a consistently higher prevalence of hypertension in HIV positive people compared to non-HIV infected individuals. Thus, the coexistence of HIV and hypertension is a public health burden of increasing concern.¹⁶

2020 International Hypertension Guidelines: a global fit

The increasing incidence of hypertension and the implication thereof on mortality emphasizes the importance of interventions that target prevention and management of the disease.^3,4,6 The mission of the International Society of Hypertension (ISH) is to reduce the global burden of hypertension is represented by the global practice guidelines in managing hypertension in adults, aged 18 years and older.⁶ Low-and middle-income countries often rely on guidelines

from high-income countries. However, adopting guidelines from high-income regions poses many challenges and may not be easy to implement due to the lack of resources and basic needs that many, if not most, low-and middle-income regions face. Thus, guidelines from high-income countries may not fulfil a global purpose.⁶

The 2020 ISH Global Hypertension Guidelines was developed to be used globally advising on essential and optimal standards. Optimal standards of care are designed for regions of high resource settings based on evidence-based standards of care in the European and American regions, having lower target BP levels, while essential standards, which are based on minimum standards of care, have been designed with the challenges of low-to middle-income regions in mind.⁶ While the overall purpose of the guidelines is universal, there may be differences between the essential and optimal approaches to the management of hypertension.⁶

Since a healthy lifestyle can prevent or reduce the risk of hypertension, lifestyle modification, as outlined in Table 1, remains the cornerstone of hypertension management. In addition, adopting a healthy lifestyle enhances the effects of antihypertensive treatment.⁶ Figures 1-3 are adapted from the 2020 ISH hypertension guidelines.⁶

Ethnic considerations for the management of hypertension:⁶

• Annual screening for hypertension from 18 years of age, where possible.
• Angiotensin II receptor blockers (ARBs) may be preferred as angioedema is about three times more likely to occur with angiotensin converting enzyme (ACE) inhibitors among black patients.

Hypertension in the time of a global pandemic

The novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) which was first detected in Wuhan, China, in December 2019 marked the start of the global coronavirus (COVID-19) pandemic.¹⁷ Extreme measures to contain the spread of infection were taken globally.⁵

The association between COVID-19 and hypertension

While we continue to learn new facts about this novel virus, early observations indicated that patients with NCDs like hypertension, diabetes, chronic kidney disease, cardiovascular disease and obesity have higher morbidity and mortality rates.^5,18 Early reports from countries such as Italy, where mortality rates were high, revealed that severe COVID-19 infection was more likely to occur in elderly patients with hypertension.¹⁸ Although the pathogenesis of this novel virus is not fully understood, the entry point of the SARS-CoV-2 virus into human cells appears to be via the angiotensin-converting enzyme II (ACE-2) receptor. This raised the hypothesis of a possible link between hypertension and severe COVID-19 infection.^18,19 Interestingly, the year 2020 marks the 20th anniversary of the discovery of ACE-2. Being a vital element in regulating critical physiologic processes like blood pressure, the rationale for ACE-2 being an entry for the SARS-CoV-2 virus remains a mystery.²⁰

The RAAS has an established role in regulating blood pressure. In this cascade, renin converts angiotensinogen to angiotensin I. Angiotensin-converting enzyme (ACE) then converts angiotensin I to angiotensin II, inducing vasoconstriction and hypertension.^21-23

Although the components involved in the RAAS cascade facilitate control of vascular function in both health and disease, some of these components may have opposing functions. An example is the metabolism of angiotensin II by enzymes including the ACE homologue, angiotensin-converting enzyme 2 (ACE-2) to produce the vasodilator, angiotensin(1-7).^22,23 Evidence suggests that ACE-2, which is overexpressed in the lungs, kidney, the endothelium and heart, may have an essential role in maintaining the balance of the RAAS.²³ However, unlike ACE, ACE-2, is not antagonised by conventional ACE-inhibitors.^22,23 By binding to the ACE-2 receptor, the SARS-CoV-2 virus enters most human cell lines, including cells lining the alveoli and those in the cardiovascular system leading to the down-regulation of ACE-2 and the local accumulation of angiotensin II.^18,24 This activation of the RAAS has been proposed as a mechanism for severe respiratory illness and lung injury, the key features of COVID-19.¹⁸ In a recent meta-analysis of more than 6000 patients with COVID-19, in addition to poor outcomes, hypertension was associated with increased mortality, acute respiratory disease syndrome, need for intensive care and disease progression.²⁴ Hypertensive patients were reported to having a two-fold increase in mortality compared to non-hypertensive individuals.²⁵

The observed interaction between the SARS-CoV-2 virus and ACE-2 which may enhance the effect of the virus, has provided grounds for the association between hypertension and COVID-19.⁵

The impact of COVID-19 on hypertension management

Ten months into the global pandemic, the devastating effect it has on the world continues, with potential lingering adverse repercussions. Global shutdown led to significant global economic loss, with many left unemployed and stressed as a result. Strict quarantine measures contribute to physical inactivity and unhealthy eating, the key drivers for increasing the risk of new and uncontrolled hypertension. The imposition of severe lockdown restricted the public to only seek medical attention for urgent matters in order to protect healthcare workers and ensure resources are available to treat COVID-19 patients.^5,24 The goal of guidelines for hypertension is to provide easily accessible information to healthcare providers to ensure best practices. However, the COVID-19 pandemic has posed many challenges for optimal care.²⁴ Amidst the fear of the unknown, the world is focused on this novel coronavirus, much to the possible detriment of other illnesses, including hypertension.⁵

Lifestyle interventions: diet and exercise

Due to measures to control the pandemic, the prevalence of hypertension is likely to increase due to less physical activity and poor attention to diet.²⁴ The importance of lifestyle interventions in the management and prevention of hypertension cannot be overemphasized. Dietary Approaches to Stop Hypertension (DASH) has been shown to bring about the most significant reductions in blood pressure across all patient demographics. Of note, reductions in systolic blood pressure as much as 20mmHg has been noted in black patients. Physical activity of 90-150 min/week at 65-75% of maximum heart rate has shown decreases in systolic blood pressure of 5-8 mmHg.²⁴

Adherence to antihypertensive medication

Adherence is defined as “the extent to which a person’s behaviours such as taking a medication, following a diet or executing lifestyle changes corresponds with agreed recommendations from a healthcare provider”.⁶ The high prevalence of hypertension worldwide, despite the accessibility of antihypertensive medications and the availability of hypertension treatment guidelines, is alarming, as less than 1 in 5 people with hypertension have their condition under control.⁶,⁸,²⁶ Even before the pandemic, only 1 in 5 people with hypertension had the problem under control.⁸ It is estimated that as many as 80% of patients with hypertension are non-adherent and approximately one in four patients do not fill their initial prescription.²⁴ While the prevalence of uncontrolled hypertension is higher in low- to middle-income countries, the varying incidence in high-income countries must not be overlooked. Among South African patients with hypertension, between 13% and 75% are uncontrolled.⁶,⁷ The high rates of uncontrolled hypertension are an important indicator of poor prognosis, which correlates to the significant burden hypertension has on deaths due to cardiovascular disease, kidney disease, stroke, metabolic syndrome, hypertensive retinopathy and dementia.³,⁶,⁷ Hypertension is one of the modifiable risk factors for stroke and the treatment thereof can reduce the incidence of stroke by up to 40%. Therefore, poor compliance to antihypertensive medication is linked to a higher risk of stroke.²⁷ In the face of COVID-19, the implication of noncompliance among hypertensive patients is highly significant due to the associated increased mortality risk.²⁵

It appears that the fear of contracting COVID-19 has overshadowed the importance of maintaining control of hypertension as patients are avoiding going to hospitals, clinics, doctor’s rooms or pharmacies for routine check-ups.⁵,²⁴ Retrospective data suggests a two-fold increase in mortality in hypertensive patients not taking medication, compared to patients controlled on their antihypertensives, highlighting that compliance in blood pressure control is crucial.²⁵

The proposed association between SARS-CoV-2 and ACE-2 sparked concern over the use of ACE-inhibitors (ACE-Is) and angiotensin II receptor blockers (ARBs) in facilitating severe COVID-19 infections via the mechanism of upregulating ACE-2 expression.¹⁸ Animal studies have been unable to produce consistent results on the effect of ACE-Is and ARBs on ACE-2 levels. Together with the limited data from human studies, the clinical approach to managing patients on these antihypertensives with COVID-19 has been inconsistent. Since the beginning of the pandemic, various retrospective cohort studies conducted in China, Europe and the USA did not reveal higher rates of infection, greater severity of disease, or increased mortality among COVID-19 patients treated with ACE-Is or ARBs.¹⁸ In light of the theoretical risks of RAAS inhibitors and COVID-19 co-infection, randomised trials have been initiated to evaluate clinical outcomes for COVID-19 patients treated with ACE-Is or ARBs.¹⁸ Therefore, until further data becomes available, healthcare professionals are advised that, based on insufficient evidence, antihypertensive medications should not be discontinued because of COVID-19 concerns.¹⁸

Patients should be reminded that their chronic condition is still of great importance. Furthermore, doctors are still available for consultations, including telephonic consultations. Where possible, patients should be encouraged to monitor their blood pressure at home, remain compliant with their medication and to adopt healthy lifestyles.⁵ These interventions can potentially avoid the projected increased rates of uncontrolled hypertension, obesity and cardiovascular events in the years to come as a result of the COVID-19 pandemic.²⁴ The most successful methods to manage noncompliance, albeit challenging for low-to middle-income countries, is complex, involving a combination of patient counselling, self-monitoring, reinforcements and supervision. ⁶

Affordability and the healthcare system

It is widely recognised that affordability is one of the key drivers of non-compliance. Global guidelines such as the recently developed ISH guidelines are cognisant thereof, making provision for low-to middle-income countries. The COVID-19 pandemic has however created greater barriers for affordability.^6,24

In a short space of time, the COVID-19 pandemic has crippled healthcare systems across the world. Issues of limited resources, however, plagued South Africa prior to COVID-19.²⁸ With its divided health system, the majority of South Africans are catered for by the public sector.²⁹ With almost half of the adult South African population living below the upper-bound poverty line and 23% of South Africans being unemployed, poverty is a major challenge in the public sector. It adds to the vulnerability of hypertensive patients especially if they are impacted by financial limitations.^30-32 Advocating healthy lifestyles such as nutritious foods, physical activity and timely access to healthcare is not a simple fait when there is a lack of affordability for basic needs.³² Since better knowledge of hypertension has been reported to improve compliance to antihypertensive treatment, efforts to educate patients should be at the forefront of disease management in poorer communities.³²

In contrast, a well-resourced private sector provides healthcare services mainly to those who have medical aid.²⁹ However, affordability is also a factor affecting adherence to antihypertensives among the private sector as medical aids may not fully cover the cost of treatment and the subsequent co-payment represents a financial barrier.³³ Affordability issues are further potentiated by the economic strain as a result of the global shutdown leaving many unemployed.²⁴ Generic medicines represent an important policy to allow for access to affordable, essential medicines, supported by South African legislation and its regulations. The availability of generic medication serves a dual role, offering availability and accessibility to life-saving medication for the public sector and improving affordability in the private sector.²⁶

Concomitant medication

Blood pressure may be affected by the concomitant use of other medications as well as intake of alcohol.⁶ Celecoxib and non-selective NSAIDs can increase BP up to 3/1 mmHg and can antagonise the effect of RAAS-inhibitors and beta-blockers. Anti-retroviral drugs can exacerbate hypertension.⁶ Given the impact of the COVID-19 pandemic worldwide, an increase in mental health disorders can be expected.³⁴ Selective noradrenaline and serotonin reuptake inhibitors (SNRIs) can increase BP by 2/1 mmHg.⁶ It must, however, be noted that there may be other medications that can induce or exacerbate these effects which can vary from person-to-person with greater increases noted in the elderly, patients with higher BP at baseline, or in patients with kidney disease.⁶

Embracing digital healthcare

While COVID-19 poses many barriers to healthcare, its unanticipated spread forced many changes, including embracing digital healthcare to a greater extent.³⁵ The model of healthcare has shifted from “bedside” to a “webside” approach in an effort to contain the spread of COVID-19 while not forgetting about other illnesses.^35,36 Virtual clinics, where possible, should form the basis for ongoing healthcare and patient education through telephone and video chat consultations.³⁶ Furthermore, virtual gyms are trending online, encouraging the public to remain healthy and fit even during lockdown.³⁷ While the digital space offers a platform for healthcare when social contact is frowned upon, it must not be forgotten that the majority of South Africa’s population may be left out.^35,36

Poverty, low literacy, disability and limited electronic skills are some examples of the digital divide in South Africa.³⁵ Therefore, for those who have to attend hospitals or community clinics, every opportunity should be aimed at patient education and medication compliance.³²

Conclusion

The impact of the COVID-19 pandemic on the world will forever be etched in history.⁵ Parallel to the global COVID-19 pandemic, a NCD public health crisis continues in the background. Identified as the main cardiovascular risk factor, uncontrolled hypertension is a growing concern.³⁶ While the world collectively deals with COVID-19, it is prudent to avoid these patients becoming unfortunate collateral damage.⁵ Such an unprecedented time requires quick action, including embracing digital healthcare to ensure the continuous management of chronic conditions such as hypertension in the midst of the COVID-19 pandemic.

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