Gaps in Hypertension Guidelines in Low- and Middle-Income Versus High-Income Countries

Introduction

Hypertension, a leading cause of other cardiovascular diseases, is also a leading cause of disability and death worldwide.¹ Over 1 billion people are diagnosed with hypertension, such that 1 in 3 individuals has elevated blood pressure in numerous countries.² About 90% of the burden of cardiovascular disease is borne by the low-and middle-income countries (LMIC) that have only ≈10% of the research capacity and healthcare resources to confront the scourge.³

Hypertension had been regarded as a disease of the affluent people of the world.^4,5 However, it has emerged in the LMIC where it affected ≈1 in 5 adults in 2013.⁵ This rate has been projected to increase such that 3 in 4 adults will be living with hypertension by 2025 in LMIC.^6,7 Awareness and levels of hypertension control in LMIC are still low when compared with that in HIC.⁸ For instance, hypertension control in United States is 52% compared with 5% to 10% in Africa.⁹ The major reason for this disparity could be the lack of awareness of access and adherence to implementable hypertension guidelines in LMIC.¹⁰

Furthermore, hypertension management is complicated by choice, availability, and affordability of appropriate medications. The cultural aspects of life-long use of medications for hypertension, variable needs of individual patients, and inconsistent designs and outcomes from clinical trials have also compounded the management.¹¹ The different genetic architectures of individuals with hypertension^12,13 may determine the choice and response to treatment. Some of these antihypertensive agents are costly and not evenly accessible and distributed in LMIC.

Therefore, guidelines that work in HIC settings may not be acceptable, effective, implementable, and applicable to LMIC because of the lack of supporting resources. In addition to broad international guidelines tailored to the needs of large regions with similar socioeconomic implementation contexts, it may be crucial for every country to further adapt implementation aspects and dissemination channels of key recommendations by engaging and empowering all relevant stakeholders thereby enhancing adherence and impact.

This review is necessitated by the need to bring hypertension control to the individual’s doorstep by developing and deploying such pragmatic hypertension guidelines in these countries to significantly reduce the burden of associated cardiovascular morbidities and mortalities.

We performed a systematic review to compare the quantity and quality of published clinical practice guidelines for hypertension in individual LMIC to HIC over the past decade in terms of their number, quality of evidence, socioeconomic and ethical–legal contextualization, ability to be implemented and dissemination to actively engage and empower all relevant stakeholders. Overall, we aimed to identify the gaps and to propose suitable solutions to enhance the quality and impact of hypertension guidelines in LMIC.

Methodology

Using the Preferred Reporting Items for Systematic Review and Meta-Analyses guidelines,¹⁴ a systematic review was performed with hypertension, high blood pressure, and guideline as the primary search items. Secondary search items included clinical practice, implementation, translation, and prevention, whereas the tertiary search items included World Health Organization, United States, American, International, European, African, Asian, Japanese, South and Latin American, Society, Association, League and Group.

Inclusion and Exclusion Criteria

The review included guidelines published from January 1, 2005, to December 31, 2015, in PubMed, Google Scholar, African Journals Online, Excerpta Medica Database, and Directory of Open Access Journals databases. Guidelines in other languages that we were unable to translate into English were excluded.

Eligible guidelines were also searched country by country and region by region. For instance, the following countries categorized as low-income countries were searched online for hypertension guidelines: Cambodia, Chad, South Sudan, Tanzania, Zimbabwe, Comoros, Haiti, Benin, Nepal, Mali, Sierra Leone, Burkina Faso, Afghanistan, Uganda, Rwanda, Mozambique, Togo, Guinea-Bissau, North Korea, Ethiopia, Eritrea, Guinea, Gambia, Madagascar, Niger, Democratic Republic of Congo, Liberia, Central African Republic, Burundi, Malawi, and Somalia. Some unpublished guidelines obtained by direct contact with clinicians in some countries were also included. Duplicates were excluded.

The guidelines were characterized according to income level, evidence class, recommendation level, and number of reviews performed during the study period.

Data Extraction, Critical Appraisal, and Synthesis

Google translate was used to translate the Brazilian hypertension guideline from Portuguese to English.

To determine the quality and the developmental processes of the guidelines, 2 independent reviewers extracted information on each guideline in terms of compliance with the Institute of Medicine’s (IOM) ^15,16 standards for developing clinical practice guidelines that include transparency, conflicts of interest, multidisciplinary approach, systematic reviews, strength or recommendations, external review, and regular updates. Other quality indices include coverage of the cardiovascular quadrangle¹⁷ (surveillance and research, prevention, acute care, and rehabilitation), contextualization and translatability, attention to socioeconomic, ethical, legal, and psychological issues, and deployment through multiple dissemination channels to all stakeholders. Stakeholders included physicians, nonphysician healthcare providers, primary caregivers, policy makers, payers, patients, the populace, and implementation partners. Proportions of quality indices fulfilled in LMIC guidelines were compared with those in HIC.¹⁸

Results

Fifty hypertension guidelines are found Figures S1 and S2 in the online-only Data Supplement, including 20 from PubMed and 30 from Google Scholar databases. Six additional unpublished guidelines were obtained after consultation with colleagues involved in hypertension control and management across the globe through the Global Alliance for Chronic Diseases.^19–24 No guideline was found in African Journals Online, Excerpta Medica Database, and Directory of Open Access Journals databases. After the removal of duplicates, 39 guidelines from 28 countries were left. Of these, 16 were excluded because they were not written in English and could not be translated. Only 1 was found from the 31 countries in the low-income category, whereas 9 guidelines were found from middle-income countries. The remaining 13 were from HIC. Five guidelines from the United States were excluded leaving the American Society of Hypertension/International Society of Hypertension, which is the only one officially endorsed. Eighteen guidelines were included for qualitative and quantitative syntheses.

The guidelines were characterized according to organizations that developed them, year of publication, number of reviews, level of evidence, clinical spectrum addressed, and adherence to IOM recommendations (Tables 1 through 3). Appraisal was also based on country of origin (Table 4; Tables S1 through S3). Many guidelines from HIC were not named after individual countries unlike those from LMIC that were specific for the individual countries. Rather, guidelines from HIC were adopted by the countries in which the associations that developed them are based.

None of the guidelines retrieved utilized the Grading of Recommendations Assessment, Development and Evaluation system.⁴² Few guidelines covered the entire spectrum of the cardiovascular quadrangle (Table 4), ethical, social, legal, psychological, and economic considerations, or elaborated plans to deploy and disseminate recommendations to all relevant stakeholders (Table 4; Tables S1 and S2). None of them applied translatability weighting to their recommendations (Table S2).

More of the hypertension guidelines from HIC followed the IOM recommendations. However, the South African Hypertension Guideline²⁶ and the 2010 Chinese guideline from LMIC were developed with strict adherence to the IOM recommendations (Table 3). The 2010 Chinese guidelines⁸ described the treatment of hypertension in chronic kidney disease, stroke, and coronary artery disease. The recommendations were based on high level of evidence (randomized controlled trials), meta-analysis, and local studies.⁸ Guidelines from Nigeria and Mexico have not been updated because they were published (Table 1).²⁵ Compared with the guidelines from HIC, the spectrum of the associated clinical issues addressed and the choice of antihypertensive agents were not clearly discussed (Table 2; Table S1).

Significantly more guidelines from HICs were developed with involvement of high-quality systematic reviews of relevant evidence (63.5% versus 10.0%; P=0.033). Overall, the proportions of guidelines that applied IOM recommendations, underwent frequent reviews, and developed active dissemination channels to engage all relevant stakeholders were higher among the HIC (Table S3).

Discussion

It is clear from this review that there is dearth of hypertension guidelines in the LMIC, particularly in low-income countries where only one existed.²¹ The available guidelines in the middle-income countries are just limited to several countries; 4 of which were not published in peer-reviewed journals and not accessible in any of the online databases.^19,20,22 This is not in accordance with the recommendation of the World Health Assembly and the World Health Organization Regional Committee for Africa that countries in the region should be encouraged to establish country-specific recommendations for the prevention and management of hypertension.^5,25

There is an urgent need for this as the genomics,⁴³ socioeconomic context, and healthcare policies of these countries vary from region to region, especially on healthcare financing and implementation of lifestyle modifications^44,45 such as smoking cessation and reduction in alcohol consumption. However, healthy lifestyle is an essential component of any effective hypertension treatment guideline, and it is recommended for the entire populace.⁴⁶ The process of generating LMIC-specific fine-tuning of recommendations can be facilitated and fast-tracked by first generating guidelines with unique recommendations that are broadly implementable in the socioeconomic setting of LMIC.

Currently, guidelines from LMIC are not unique to LMIC setting as they were adopted from the existing HIC guidelines without due considerations about their implementability.²⁶ They were not based on contextually relevant locally derived evidence. Indeed, as alluded to in the 2012 South African Hypertension guidelines,²⁶ the HIC guidelines have some recommendations that LMIC may not be able to implement because of the socioeconomic context within the countries.¹¹

Moreover, many of the LMIC guidelines did not specify the level of evidence and did not address hypertension management in special situations such as chronic kidney disease, coronary heart disease, heart failure, diabetes mellitus, and stroke. The choice of medications and the target BP levels for hypertension in special situations were also not addressed.

Conversely, more HIC guidelines underwent frequent reviews, applied IOM recommendations, and developed active dissemination channels. However, guidelines from HIC also have rooms for improvement. For instance, the American Society of Hypertension/International Society of Hypertension guideline³⁵ did not follow all the IOM recommendations. Even, the authors recommend that the readers should not consider the guideline as an evidence-based set of recommendations. Although, this guideline addressed the management of hypertension in people with comorbidities, the evidence for its recommendations is mostly based on the expert opinion. However, the American College of Cardiology Foundation/American Heart Association hypertension guideline³⁶ complied with some of the IOM recommendations for the development of formal guidelines. Its focus is mainly on the management of hypertension in the elderly and so it is not comprehensive. Other guidelines that address management in the elderly include the European Society of Hypertension/European Society of Cardiology,³¹ National Institute for Clinical Excellence,⁴⁰ and Canadian Hypertension Education Program³⁷ hypertension guidelines.

The American Heart Association, South African Hypertension guidelines, and National Institute for Clinical Excellence guidelines are the only hypertension guidelines that recommend specific drugs for the management of resistant hypertension.⁴⁰ Despite the fact that the Joint National Committee 8 strictly followed the IOM recommendations, its recommendations are not officially endorsed and are not comprehensive.³² This is because its development was based only on randomized controlled trials, unlike the European Society of Hypertension/European Society of Cardiology guideline that included data from meta-analysis and observational studies.³¹ The European Society of Hypertension/European Society of Cardiology guideline that is comprehensive enough addressing detection, evaluation, and treatment of hypertension can be useful, where there is limitation to direct application by virtue of different health systems, standard of care, and availability of antihypertensive agents, especially in the LMIC.³¹

For implementation of these guidelines, both in LMIC and HIC, nonpharmacological and multidisciplinary approaches to the total care of the patients were advocated.³¹ However, the multidisciplinary approach was limited to the physicians in their respective fields with little attention to the nurses, the pharmacists, and the dieticians in the guidelines from the LMIC (Table S1). Nearly all the guidelines from the HIC put this into consideration except the 2010 Guidelines of the Taiwan Society of Cardiology for the management of hypertension (Table S1). Indeed, almost all the guidelines regard management of comorbidities as a component of hypertension treatment.

Other considerations in the development of these guidelines such as translation, legal, and social issues were poorly addressed. In addition, there was no consideration of the psychological and economic situations of the targeted population. Socioeconomic situations of the targeted populace were only considered by the National Institute for Clinical Excellence and IV Brazilian hypertension guidelines, whereas only the Canadian Hypertension Education Program guidelines put the dissemination channels and hypertension surveillance into consideration (Table S2). Each guideline is expected to be updated every 3 years⁴⁷ to include new evidence or treatment. Among the guidelines available for review as at the time of this publication, only the guidelines from Japan, Europe, and the United States are up-to-date.

Strengths and Weaknesses

Our search strategy included all countries, and we critically appraised all available guidelines using rigorous and comprehensive criteria. However, only the hypertension guidelines written in or translated to the English language were included in this review. Other guidelines written in other languages^{29,41,48–55} might have been missed.⁵⁶ Furthermore, because we used the IOM recommendation to assess the quality of the guidelines, we did not use other similar parameters such as the Global Rating Scale.⁵⁷ The World Health Organization/International Society of Hypertension guideline (2003)⁴⁷ was excluded because it was not covered in the stipulated time frame for our review.

We did not include the World Heart Federation Global cardiovascular disease Roadmap⁵⁸ in this review because it is not a guideline per se. It enumerates the challenges to hypertension control and suggests some ways to overcome them in the delivery of hypertension care to the populace. However, it did not demonstrate the developmental process of the recommendations that are to be delivered and the contextualization and other pertinent implementation issues for hypertension guidelines. If these are faulty, hypertension control will still be a Herculean task.

Conclusions and Future Plans

Hypertension guidelines are necessary for proper and adequate prevention, early detection, evaluation, treatment and control of hypertension.^44,59 However, they must meet basic criteria including validity, reliability/reproducibility, clinical applicability, clinical flexibility, socioeconomic, and ethical–legal contextualization, clarity, multidisciplinary process, scheduled review, and rigorous dissemination plan.⁶⁰ Unfortunately, none of the available guidelines meet all of these criteria. This could explain why hypertension is still difficult to control in many regions of the world, as possible valuable channels for the dissemination and implementation of guidelines are not harnessed.

It is obvious from this review that efforts are needed to develop hypertension guideline(s) for the LMIC (Table 5). The expected guideline(s) should be broad based, flexible, adaptable, socioculturally acceptable, and economically attainable for better health-related outcomes in patients with hypertension. As exemplified by National Institute for Clinical Excellence guideline, patients’ participation should be incorporated to enhance adherence to these recommendations.

Because de novo guideline development is time consuming, labor intensive, and costly, any guideline that fulfills most of the criteria used for this review may be considered as a template for the development of guidelines for LMIC, while incorporating local evidence only as available. This will be a more realistic approach to avoid duplication of efforts while waiting for direct high-level evidence to accrue from the LMIC. Such guidelines should be socioculturally acceptable and cost-effective for successful implementation in the resource-poor regions of the world.

Developing and disseminating evidence-based pragmatic guidelines with concise implementable recommendations relevant to LMIC needs and socioeconomic context is urgently needed. With the active involvement of all stakeholders, the recommended care and commodities could be made acceptable, accessible, available, appropriate, affordable, and effective to reduce the global burden of hypertension.

Footnotes