HYPERTENSION IN THE ELDERLY: CHALLENGES IN MANAGEMENT AND TREATMENT

 

Sanjay Dhiman ¹, Anurag Chourasia ²

 

¹ Research Scholar, Adarsh Vijendra Institute of Pharmaceutical Sciences, Shobhit University, Gangoh, Saharanpur, India

² Assistant Professor, Quantum School of Health Science, Quantum University, Roorkee, India

 

1. INTRODUCTION

1.1.    BACKGROUND ON HYPERTENSION

Hypertension, also known as high blood pressure, is a chronic condition characterized by the consistent elevation of blood pressure levels. Blood pressure is measured in millimeters of mercury (mmHg) and is recorded with two numbers: systolic pressure (the higher number, representing the pressure in the arteries when the heart beats) and diastolic pressure (the lower number, representing the pressure in the arteries when the heart rests between beats). According to the American College of Cardiology (ACC) and the American Heart Association (AHA), hypertension is defined as a systolic blood pressure of 130 mmHg or higher and/or a diastolic blood pressure of 80 mmHg or higher Whelton et al. (2018).

Hypertension is a significant risk factor for several cardiovascular diseases, including coronary artery disease, stroke, heart failure, and peripheral arterial disease. It is also associated with other health conditions such as chronic kidney disease and dementia Muntner et al. (2020). The condition can be influenced by various factors, including genetics, lifestyle choices, and environmental factors. The exact mechanisms of hypertension involve complex interactions between the nervous system, the renin-angiotensin-aldosterone system, and the kidneys Carretero et al. (2000)

 

1.2. PREVALENCE OF HYPERTENSION IN THE ELDERLY

Hypertension is highly prevalent among the elderly population. As individuals age, the prevalence of hypertension increases significantly, primarily due to age-related changes in the cardiovascular system. According to the World Health Organization (WHO), more than 60% of adults aged 60 years and older have hypertension, with variations across different regions and populations Kearney et al. (2005)In the United States, studies indicate that approximately 75% of adults aged 60 and older are affected by hypertension Mozaffarian et al. (2015)

The increased prevalence of hypertension in older adults can be attributed to factors such as arterial stiffness, increased systemic vascular resistance, and the cumulative effects of long-standing risk factors such as poor diet, lack of physical activity, and obesity Franklin SS. (2007).Additionally, older adults are more likely to have comorbid conditions like diabetes and chronic kidney disease, which can exacerbate hypertension and complicate its management Aronow WS. (2011)

 

1.3.  IMPORTANCE OF ADDRESSING HYPERTENSION IN OLDER ADULTS

Addressing hypertension in older adults is crucial due to the heightened risk of cardiovascular complications associated with uncontrolled blood pressure. Uncontrolled hypertension significantly increases the risk of heart attacks, strokes, heart failure, and other cardiovascular events, which are leading causes of morbidity and mortality in the elderly population Oparil et al. (2018) Furthermore, hypertension in older adults is associated with an increased risk of cognitive decline and dementia, adding to the urgency of effective management Walker et al. (2020).

Effective management of hypertension in older adults typically involves a combination of lifestyle modifications and pharmacological treatments. Lifestyle interventions include dietary changes, such as adopting the DASH (Dietary Approaches to Stop Hypertension) diet, reducing sodium intake, engaging in regular physical activity, and avoiding excessive alcohol consumption Appel et al. (1997)Pharmacological treatment options include antihypertensive medications such as thiazide diuretics, calcium channel blockers, ACE inhibitors, and angiotensin II receptor blockers (ARBs). The choice of medication is often influenced by the presence of comorbid conditions and the overall health status of the patient Aronow et al. (2017)

Given the higher susceptibility to side effects and drug interactions in older adults, healthcare providers must carefully balance the benefits and risks of treatment. This often requires personalized treatment plans that consider the patient’s individual health status, preferences, and goals of care James et al. (2014) By effectively managing hypertension, it is possible to reduce the risk of cardiovascular events, improve quality of life, and extend life expectancy in older adults Benetos  et al. (2019)

 

2.  PATHOPHYSIOLOGY OF HYPERTENSION IN THE ELDERLY

2.1.    AGE-RELATED CHANGES IN VASCULAR FUNCTION

As individuals age, several changes in vascular function contribute to the development of hypertension. One of the most significant changes is increased arterial stiffness, particularly in the large elastic arteries like the aorta. This stiffness results from the accumulation of collagen and the breakdown of elastin fibers in the arterial walls, which reduces the arteries' ability to expand and contract with each heartbeat Lakatta et al.(2003) The stiffened arteries lead to an increase in systolic blood pressure and a widened pulse pressure, both of which are characteristic of hypertension in the elderly.

Moreover, endothelial dysfunction, another age-related vascular change, plays a crucial role in the pathophysiology of hypertension. The endothelium, which lines the blood vessels, regulates vascular tone by releasing vasodilators like nitric oxide. With aging, the production of nitric oxide decreases, while the production of vasoconstrictors, such as endothelin, increases, leading to a reduced ability of blood vessels to dilate Donato et al. (2015)This imbalance contributes to increased peripheral resistance and elevated blood pressure.

Additionally, aging is associated with an increase in sympathetic nervous system activity, which also contributes to hypertension. The heightened sympathetic activity leads to vasoconstriction and increased heart rate, further exacerbating high blood pressure Esler et al. (2002). These age-related changes create a complex environment in which hypertension becomes more likely and more difficult to control in the elderly population.

 

2.2. IMPACT OF COMORBIDITIES

The presence of comorbidities significantly impacts the pathophysiology of hypertension in older adults. Conditions such as diabetes mellitus, chronic kidney disease, and dyslipidemia are common in the elderly and often coexist with hypertension, creating a more challenging clinical scenario. For instance, diabetes is associated with increased arterial stiffness, endothelial dysfunction, and impaired renal function, all of which can worsen hypertension Cruickshank et al. (2002)

Chronic kidney disease (CKD) is another comorbidity that profoundly affects blood pressure regulation. The kidneys play a central role in maintaining blood pressure through the renin-angiotensin-aldosterone system (RAAS). In CKD, there is often dysregulation of this system, leading to sodium retention, increased blood volume, and heightened systemic vascular resistance, all of which contribute to elevated blood pressure Sarnak et al. (2003)The presence of CKD not only increases the risk of hypertension but also complicates its management, as many antihypertensive drugs are less effective or contraindicated in these patients.

Similarly, dyslipidemia, characterized by elevated levels of low-density lipoprotein (LDL) cholesterol and triglycerides, is linked to atherosclerosis, which further stiffens the arteries and impairs vascular function, contributing to hypertension Seshiah et al. (2002).These comorbidities create a vicious cycle where each condition exacerbates the others, leading to more severe hypertension and an increased risk of cardiovascular events.

 

2.3. DIFFERENCES IN HYPERTENSION ETIOLOGY IN OLDER ADULTS

The etiology of hypertension in older adults differs from that in younger populations due to the distinct pathophysiological mechanisms involved. In younger individuals, hypertension is often driven by factors such as obesity, sedentary lifestyle, and dietary habits, which primarily affect the resistance arteries and lead to diastolic hypertension. However, in older adults, systolic hypertension is more prevalent due to age-related changes in the large arteries Franklin et al. 1997

In the elderly, the contribution of the RAAS to hypertension is also different. While younger individuals often exhibit hyperactivity of the RAAS, leading to increased angiotensin II and aldosterone levels, older adults may have a blunted RAAS response. This altered response, combined with decreased renal function, results in a different therapeutic approach, where calcium channel blockers and diuretics are often preferred over RAAS inhibitors Kostis et al. (1997)

Moreover, older adults are more likely to have isolated systolic hypertension, where only the systolic blood pressure is elevated. This condition is primarily driven by arterial stiffness and increased pulse wave velocity, rather than by the volume-dependent mechanisms seen in younger individuals Benetos et al. (1997). The unique etiology of hypertension in the elderly necessitates tailored treatment strategies that address these specific pathophysiological changes.

 

3.  CHALLENGES IN DIAGNOSING HYPERTENSION IN THE ELDERLY

3.1.    VARIABILITY IN BLOOD PRESSURE READINGS

One of the significant challenges in diagnosing hypertension in the elderly is the increased variability in blood pressure (BP) readings. Blood pressure variability (BPV) refers to fluctuations in BP measurements across different times of the day, visits, or even within a single measurement session. In older adults, BPV is often higher due to age-related changes in arterial stiffness, autonomic regulation, and the presence of comorbidities Muntner et al. (2015).This variability complicates the diagnosis of hypertension, as a single elevated reading may not accurately reflect the patient's typical blood pressure.

Increased BPV is associated with a higher risk of cardiovascular events and target organ damage, making accurate diagnosis and management critical Parati et al. 2013 Clinicians must consider multiple readings over time to determine whether a patient truly has sustained hypertension or if the elevated BP is due to transient factors such as anxiety, physical activity, or dietary influences. The challenge lies in distinguishing between true hypertension and isolated instances of high BP, which may not require long-term treatment.

 

3.2. WHITE COAT HYPERTENSION AND MASKED HYPERTENSION

White coat hypertension and masked hypertension are two phenomena that further complicate the diagnosis of hypertension in the elderly. White coat hypertension occurs when a patient's BP is elevated in a clinical setting but normal when measured outside the clinic. This condition is often triggered by the anxiety or stress of being in a medical environment Pickering et al. (2002)Although once considered benign, white coat hypertension is now recognized as a risk factor for developing sustained hypertension and cardiovascular disease over time Franklin et al. (2016).

Conversely, masked hypertension occurs when a patient's BP is normal in the clinic but elevated in daily life. This condition is particularly concerning because it often goes undiagnosed, leading to untreated hypertension and an increased risk of cardiovascular events Clement et al.(2003)Masked hypertension is more common in older adults and is associated with factors such as smoking, alcohol consumption, and high levels of physical or emotional stress Stergiou et al.(2010).

The presence of these conditions underscores the limitations of relying solely on clinic-based BP measurements. Without additional methods of monitoring, such as home or ambulatory BP monitoring, white coat and masked hypertension can lead to misdiagnosis and inappropriate treatment.

 

3.3. HOME AND AMBULATORY BLOOD PRESSURE MONITORING

Given the challenges associated with variability in BP readings and the phenomena of white coat and masked hypertension, home and ambulatory blood pressure monitoring (HBPM and ABPM) have become essential tools in the diagnosis of hypertension in the elderly. HBPM involves patients measuring their BP at home, typically over several days, providing a more accurate reflection of their usual BP levels Niiranen et al. (2014).This method helps to reduce the effects of white coat hypertension and provides data on BP variability.

ABPM, on the other hand, involves wearing a portable BP monitor that takes readings at regular intervals over 24 hours, including during sleep O'Brien et al. (2013) ABPM is considered the gold standard for diagnosing hypertension, as it provides comprehensive information on BP patterns, including nighttime BP, which is a strong predictor of cardiovascular risk. ABPM is particularly useful in identifying masked hypertension and in assessing the effectiveness of antihypertensive therapy Hermida et al. (2018)

However, the implementation of HBPM and ABPM comes with challenges. Elderly patients may have difficulty using HBPM devices due to physical limitations or cognitive impairments. Additionally, ABPM can be uncomfortable for some patients, leading to poor compliance. Despite these challenges, the benefits of these monitoring techniques in providing accurate and reliable BP data make them invaluable in the diagnosis and management of hypertension in the elderly.

 

4. MANAGEMENT OF HYPERTENSION IN THE ELDERLY

4.1.    GOALS OF TREATMENT

Effective management of hypertension in older adults focuses on several key goals to improve health outcomes and quality of life.

1)    Blood Pressure Targets: The primary aim is to lower systolic blood pressure (SBP) to below 130 mmHg for most elderly patients. This target is supported by recent guidelines, which suggest that such control can reduce the risk of cardiovascular events and mortality Whelton et al. (2018). For patients with multiple comorbidities or advanced frailty, a more relaxed target may be appropriate to avoid potential adverse effects from overly aggressive treatment Mc et al. (2020)

2)    Reduction of Cardiovascular Risk: Lowering BP reduces the risk of stroke, myocardial infarction, and heart failure. Proper management also helps prevent progression to more severe forms of hypertension and related complications Mancia et al. (2018)

3)    Prevention of Target Organ Damage: Effective BP control helps prevent damage to target organs such as the heart, kidneys, and brain, which can occur due to chronic hypertension Rossi et al. (2017)

4)    Improvement in Quality of Life: By managing hypertension effectively, patients can maintain better functional status, cognitive function, and overall well-being Bakris et al. (2014)

 

4.2.  LIFESTYLE MODIFICATIONS

Lifestyle modifications are integral to the management of hypertension and can significantly enhance the effectiveness of pharmacological treatments.

1)    Dietary Changes: Adopting a diet low in sodium and rich in nutrients is crucial. The DASH (Dietary Approaches to Stop Hypertension) diet is recommended for its effectiveness in lowering BP. It includes high intakes of fruits, vegetables, whole grains, and lean proteins, while reducing sodium, saturated fats, and cholesterol Appel et al. (1997)Reducing sodium intake is particularly effective in lowering BP in older adults Hermida et al.(2018)

2)    Physical Activity: Regular exercise is beneficial for BP control. The American Heart Association recommends at least 150 minutes of moderate-intensity aerobic activity per week, such as walking, swimming, or cycling Pescatello et al. (2015) Physical activity helps reduce BP, improve cardiovascular health, and manage weight.

3)    Weight Management: Maintaining a healthy weight or achieving weight loss in overweight or obese individuals is important for BP management. Even modest weight loss can lead to significant reductions in BP Joffe et al. (2013)

4)    Alcohol and Tobacco Use: Limiting alcohol consumption and quitting smoking are critical for BP control. Excessive alcohol intake and smoking both contribute to elevated BP and increased cardiovascular risk Ezzati et al. (2005).

 

4.3. PHARMACOLOGICAL TREATMENTS

Pharmacological treatments are often necessary to achieve and maintain target BP levels, especially when lifestyle modifications alone are insufficient.

 

4.3.1.  FIRST-LINE MEDICATIONS

Several classes of medications are considered first-line treatments for hypertension in older adults:

1)    Thiazide Diuretics: Drugs such as hydrochlorothiazide and chlorthalidone are effective in lowering BP and managing isolated systolic hypertension, which is common in older adults Ferdinand et al. (2020)Thiazide diuretics help reduce fluid volume and vascular resistance.

2)    Calcium Channel Blockers (CCBs): Medications like amlodipine and diltiazem are useful for reducing BP and managing conditions associated with systolic hypertension. They work by relaxing blood vessels and reducing vascular resistance Gadalean et al. (2014) Angiotensin-Converting Enzyme (ACE) Inhibitors: Drugs such as lisinopril and ramipril are beneficial for patients with comorbid conditions like heart failure or diabetes. ACE inhibitors lower BP by reducing the production of angiotensin II, a potent vasoconstrictor Poulter et al. (2005)

 

4.3.2.  COMBINATION THERAPIES

Combination therapy may be required to achieve optimal BP control, especially in cases of resistant hypertension or when single agents are inadequate:

1)    ACE Inhibitors and Calcium Channel Blockers: This combination can enhance BP control and is frequently used when monotherapy is insufficient Williams et al. (2018).

2)    Diuretics and ACE Inhibitors or ARBs: Combining a diuretic with an ACE inhibitor or angiotensin II receptor blocker (ARB) can provide effective BP management and is often used in patients with conditions like heart failure Miller et al. (2018).

 

4.3.3.  CONSIDERATIONS FOR POLYPHARMACY

Polypharmacy is a significant concern in the elderly due to the management of multiple health conditions:

1)    Drug Interactions: Elderly patients are at higher risk of drug interactions, which can affect medication efficacy and safety. Careful management of drug interactions is necessary to prevent adverse effects Beers et al. 2015.

2)    Side Effects: Older adults may experience more pronounced side effects from antihypertensive medications, such as dizziness, orthostatic hypotension, and electrolyte imbalances. Regular monitoring and dose adjustments are essential to minimize these risks Mahoney et al. (2006)

3)    Adherence: Simplifying medication regimens and using fixed-dose combinations can improve adherence. Ensuring patients understand their medications and the importance of compliance is crucial for effective management Krousel et al. (2004)

 

4.4. MONITORING AND ADJUSTMENT OF THERAPY

Ongoing monitoring and adjustment are critical components of hypertension management:

1)    Blood Pressure Measurement: Regular BP measurements are necessary to assess treatment effectiveness and ensure targets are met. Both office and home BP measurements can be used to obtain a comprehensive view of BP control Hansen et al. (2011)

2)    Monitoring for Adverse Effects: Regular evaluation for potential side effects, particularly with polypharmacy, helps to prevent complications and adjust therapy as needed Sakhuja et al. (2014).

3)    Adjusting Therapy: Treatment adjustments should be made based on BP control, patient tolerance, and any side effects. This may involve changing medication doses, switching drugs, or adding new therapies to optimize treatment Mc et al. (2014)Effective management of hypertension in the elderly requires a comprehensive approach that integrates lifestyle modifications, appropriate pharmacological treatment, and regular monitoring to achieve optimal health outcomes and enhance quality of life.

 

5. CHALLENGES IN TREATMENT

5.1.    ADVERSE DRUG REACTIONS AND TOLERABILITY

Adverse drug reactions (ADRs) and tolerability issues are significant concerns in the treatment of hypertension, particularly in older adults who often have multiple comorbidities and take several medications.

1)    Types of Adverse Reactions: Older adults are more prone to ADRs due to physiological changes with aging, including altered drug metabolism and excretion. Common ADRs include dizziness, orthostatic hypotension, electrolyte imbalances, and renal dysfunction Mahoney et al.  (2006)These side effects can significantly impact patient adherence and overall treatment effectiveness.

2)    Impact on Tolerability: ADRs can lead to discontinuation of medications or dose adjustments, which may compromise BP control and increase the risk of cardiovascular events. For instance, diuretics may cause dehydration or electrolyte imbalances, while ACE inhibitors might induce cough or angioedema Muller et al. (2018)Ensuring that medications are well-tolerated is crucial for maintaining treatment adherence and effectiveness.

3)    Management Strategies: To manage ADRs, clinicians should start with lower doses and gradually titrate up, monitor patients regularly, and consider alternatives if severe side effects occur. Personalized treatment plans that account for individual sensitivities and comorbid conditions can help minimize ADRs Beers et al. (2015).

 

5.2. MEDICATION ADHERENCE

Medication adherence is a critical factor in the successful management of hypertension. Non-adherence can lead to inadequate BP control and increased risk of cardiovascular complications.

1)    Prevalence of Non-Adherence: Studies indicate that medication adherence rates among elderly patients can be as low as 50-60%, primarily due to complex regimens, side effects, and cognitive impairments Krousel et al. (2004)Poor adherence is linked to poorer health outcomes and increased healthcare costs.

2)    Factors Affecting Adherence: Factors contributing to non-adherence include the complexity of medication regimens, adverse effects, forgetfulness, and lack of understanding about the importance of medications Bennett et al. (2014) Cognitive decline and functional limitations also play a role in reducing adherence.

3)    Improvement Strategies: Strategies to improve adherence include simplifying medication regimens, using fixed-dose combination pills, employing reminder systems, and involving caregivers in the management process. Educational interventions that enhance patients' understanding of their condition and treatment can also improve adherence Di et al. (2004).

 

5.3. MANAGING COMORBIDITIES AND POLYPHARMACY

Managing comorbidities and polypharmacy presents a significant challenge in the treatment of hypertension in the elderly.

1)    Polypharmacy Issues: Older adults often take multiple medications for various conditions, increasing the risk of drug interactions and side effects. Polypharmacy can complicate hypertension management by necessitating careful selection of antihypertensive agents that do not interact negatively with other medications Mahoney et al. (2006)

2)    Drug Interactions: Drug interactions can alter the effectiveness of antihypertensive medications and increase the risk of adverse effects. For example, certain antibiotics can interact with antihypertensives, leading to changes in BP control or increased side effects Beers et al. (2015).

3)    Management Approaches: Strategies to manage polypharmacy include regular medication reviews, use of electronic health records to track drug interactions, and deprescribing unnecessary medications. Coordination among healthcare providers is essential to optimize therapy and minimize risks associated with polypharmacy Gnjidic et al. (2012)

5.4. ECONOMIC AND SOCIAL BARRIERS TO EFFECTIVE TREATMENT

Economic and social factors can significantly impact the management of hypertension in the elderly.

1)    Economic Barriers: The cost of medications and healthcare services can be a significant barrier to effective treatment. Older adults on fixed incomes may struggle to afford necessary medications and regular follow-up visits. Medication costs can lead to non-adherence or suboptimal treatment Agarwal et al. (2017)

2)    Social Barriers: Social factors such as limited access to healthcare facilities, lack of social support, and lower health literacy can also affect treatment adherence and effectiveness. For instance, elderly patients who live alone or have limited mobility may face difficulties in attending regular appointments or obtaining medications Vaughan et al. (2017)

3)    Addressing Barriers: To address economic barriers, healthcare systems can explore options such as generic medications, patient assistance programs, and insurance coverage improvements. Social support interventions, including community health programs and telemedicine services, can help improve access to care and support medication adherence Elder K et al. (2020)

6. RECENT ADVANCES AND EMERGING THERAPIES

6.1.    NEW ANTIHYPERTENSIVE DRUGS

Recent advancements in antihypertensive medications have introduced several new drugs and classes that offer improved efficacy and safety profiles for managing hypertension in the elderly.

1)    Angiotensin Receptor Neprilysin Inhibitors (ARNIs): ARNIs, such as sacubitril/valsartan, have emerged as a novel class of antihypertensive agents. They combine an angiotensin receptor blocker (ARB) with a neprilysin inhibitor, leading to enhanced vasodilation and reduced blood pressure. Clinical trials have demonstrated their efficacy in reducing BP and improving outcomes in patients with heart failure Mc et al. (2014)

2)    Selective Aldosterone Receptor Antagonists: Newer selective aldosterone receptor antagonists like eplerenone offer advantages over older drugs by providing a more targeted approach with fewer side effects. They are useful in conditions like resistant hypertension and heart failure, improving both BP control and clinical outcomes Zannad et al. (2000).

3)    Direct Renin Inhibitors: Aliskiren is a direct renin inhibitor that blocks the initial step in the renin-angiotensin-aldosterone system, effectively lowering BP. Though its use is somewhat limited by concerns about safety in combination with ARBs or ACE inhibitors, it remains a valuable option in specific cases Schmieder et al. (2007)

4)    Combination Pills: The development of combination pills, which pair multiple antihypertensive agents in a single tablet, has simplified treatment regimens and improved adherence. Recent advancements have optimized these combinations to include newer agents, enhancing both efficacy and patient convenience Williams et al. (2018).

 

6.2. NON-PHARMACOLOGICAL INTERVENTIONS

Non-pharmacological interventions are increasingly recognized for their role in managing hypertension, especially as adjuncts to pharmacotherapy.

1)    Dietary Interventions: The adoption of dietary patterns such as the DASH (Dietary Approaches to Stop Hypertension) diet has been reinforced by recent research. Emphasis on reducing sodium intake and increasing consumption of potassium-rich foods can significantly lower BP He et al. (2010)

2)    Physical Activity: Recent studies continue to support the role of regular physical activity in managing hypertension. Exercise improves cardiovascular health, reduces BP, and helps manage weight. Recommendations include both aerobic exercises and resistance training Pescatello et al. (2015) Weight Management: New evidence underscores the importance of weight loss in managing hypertension. Even modest reductions in body weight can lead to significant improvements in BP levels. Strategies include caloric restriction, behavioral modifications, and, in some cases, surgical interventions Joffe et al. (2013)Stress Reduction Techniques: Techniques such as mindfulness, cognitive-behavioral therapy, and relaxation exercises are gaining attention for their potential to lower BP. These interventions help mitigate the effects of stress on cardiovascular health Patterson et al. (2015)

 

6.3.  ROLE OF TECHNOLOGY IN MANAGING HYPERTENSION

Technology is playing an increasingly important role in the management of hypertension, offering new tools for monitoring, treatment, and patient engagement.

1)    Home Blood Pressure Monitoring: Advances in home BP monitors have made it easier for patients to track their BP regularly. These devices are increasingly accurate and user-friendly, allowing for better management and adjustment of therapy based on real-time data Mancia et al. (2011)

2)    Telemedicine: Telemedicine has become a valuable tool for managing hypertension, especially for patients with limited access to healthcare facilities. Remote consultations, monitoring, and management via digital platforms help improve access to care and support adherence to treatment plans Darkins et al. (2008)

3)    Digital Health Apps: Smartphone applications that track BP, medication adherence, and lifestyle factors are gaining popularity. These apps provide patients with feedback and reminders, facilitating better management of their condition Sullivan et al. (2018)

4)    Wearable Devices: Wearable technology, such as smartwatches and fitness trackers, offers continuous monitoring of physiological parameters, including BP. These devices can provide valuable insights into BP trends and alert patients and clinicians to potential issues Maddox et al. (2019).

 

7. FUTURE DIRECTIONS AND RESEARCH NEEDS

7.1.    GAPS IN CURRENT KNOWLEDGE

Despite significant advancements in hypertension management, several gaps remain in our understanding of how to optimally treat this condition, especially in the elderly population.

1)    Long-Term Efficacy and Safety of New Treatments: While new antihypertensive drugs and therapies have shown promise, there is a need for more extensive long-term studies to evaluate their efficacy and safety over extended periods. Many studies focus on short-term outcomes, and data on long-term effects and adherence are still limited Whelton et al. (2018)

2)    Understanding of Hypertension Pathophysiology in the Elderly: The complex interplay between aging and hypertension is not fully understood. Research is needed to better elucidate how age-related changes in vascular function and other physiological systems contribute to hypertension. This includes investigating the impact of aging on drug metabolism and response Gero et al. (2018).

3)    Effectiveness of Non-Pharmacological Interventions: While lifestyle modifications are crucial, there is a need for more research to identify the most effective strategies for different subgroups of elderly patients. Current evidence often lacks specificity regarding which interventions work best for varying levels of hypertension severity and comorbidity Whelton et al. (2019).

4)    Impact of Comorbidities and Polypharmacy: The interaction between antihypertensive treatments and other medications used in elderly patients with multiple comorbidities needs further exploration. Understanding how comorbid conditions affect treatment outcomes and adjusting therapy accordingly is an area requiring more research Liu et al. (2017)

 

7.1. POTENTIAL AREAS FOR FUTURE RESEARCH

Several promising areas for future research could significantly impact the management of hypertension, particularly in older adults.

1)    Precision Medicine Approaches: Research into precision medicine could provide insights into tailoring hypertension treatment based on genetic, biochemical, and phenotypic characteristics. This approach may help optimize therapy and minimize adverse effects Sullivan et al. (2019)

2)    Innovations in Drug Delivery Systems: Development of novel drug delivery systems, such as extended-release formulations or smart drug delivery devices, could improve adherence and therapeutic outcomes. Research into these technologies could offer new ways to enhance the efficacy and safety of antihypertensive treatments Kumar et al. (2020).

3)    Role of Gut Microbiome: Emerging research suggests that the gut microbiome may influence hypertension through mechanisms involving inflammation and metabolism. Exploring this connection could open new avenues for managing hypertension through dietary or probiotic interventions Jiang et al. (2020). Behavioral and Digital Interventions: Further studies on the effectiveness of digital health interventions, including mobile apps and wearable devices, in improving BP control and adherence are needed. Research should focus on integrating these technologies into routine clinical practice and assessing their impact on patient outcomes Sulliva et al. (2018)

4)    Health Disparities and Inequities: Investigating the impact of social determinants of health on hypertension management and outcomes in different demographic groups can help address health disparities. Research in this area could inform policies and practices to ensure equitable access to effective hypertension management Fryar et al. (2014).

 

7.2. IMPLICATIONS FOR CLINICAL PRACTICE

Addressing these research gaps and exploring new areas of inquiry can have significant implications for clinical practice.

1)    Personalized Treatment Strategies: The advancement of precision medicine and understanding of individual patient characteristics can lead to more personalized and effective treatment strategies. Clinicians will be better equipped to choose therapies based on specific patient profiles, potentially improving treatment outcomes Sullivan et al. (2019)

2)    Enhanced Management Protocols: Innovations in drug delivery and non-pharmacological interventions could lead to improved management protocols that are more patient-centered and less reliant on complex regimens. This can enhance adherence and overall effectiveness of hypertension treatment Kumar et al. (2020).

3)    Integration of Technology: Incorporating digital tools and wearable devices into routine care can provide continuous monitoring and real-time feedback, improving BP management and patient engagement. Clinicians will need to adapt to new technologies and use them to support treatment plans Sullivan et al. (2018)

4)    Addressing Health Disparities: Research into health disparities can guide the development of targeted interventions and policies to ensure all patients receive equitable care. This includes tailoring treatment approaches to address specific needs of underserved or high-risk populations Fryar et al. (2017).

5)    Improved Patient Education and Support: Advances in understanding and technology can enhance patient education and support strategies, leading to better self-management and adherence. Clinicians should focus on integrating these advancements into patient education and support systems Jiang et al. (2020).

 

8. CONCLUSION

8.1.    SUMMARY OF KEY POINTS

Hypertension management in the elderly presents unique challenges and opportunities for improving health outcomes. Key points discussed in this overview include:

1)    Prevalence and Impact: Hypertension is prevalent among older adults and significantly impacts their health, contributing to increased risks of cardiovascular diseases, stroke, and kidney dysfunction. Addressing hypertension effectively is crucial for enhancing quality of life and reducing healthcare costs Whelton et al. (2018)

2)    Pathophysiology: Age-related changes in vascular function and the presence of comorbidities complicate the pathophysiology of hypertension in the elderly. Understanding these changes is essential for developing effective management strategies Gero et al. (2018).

3)    Diagnosis Challenges: Diagnosing hypertension in older adults can be challenging due to variability in blood pressure readings, white coat and masked hypertension, and the need for accurate monitoring through home and ambulatory techniques Mancia et al. (2011)

4)    Management Strategies: Effective management includes setting appropriate treatment goals, implementing lifestyle modifications, and employing pharmacological treatments. Recent advancements have introduced new drugs and combination therapies, although polypharmacy remains a concern Williams et al. (2018).

5)    Challenges in Treatment: Issues such as adverse drug reactions, medication adherence, and the complexities of managing polypharmacy and comorbidities must be addressed. Economic and social barriers also play a significant role in treatment effectiveness Mahoney et al. (2006)

6)    Recent Advances: Innovations in antihypertensive drugs, non-pharmacological interventions, and technology offer new opportunities for improving hypertension management. These include novel medications, dietary and exercise interventions, and digital health tools Kumar et al. (2020).

7)    Future Directions: There are gaps in current knowledge regarding the long-term effects of new treatments and the impact of aging on hypertension. Future research should focus on precision medicine, drug delivery systems, and addressing health disparities Jiang et al. (2020).

 

8.2. RECOMMENDATIONS FOR CLINICIANS

Based on the current understanding and recent advancements, the following recommendations are made for clinicians managing hypertension in the elderly:

1)    Personalized Treatment Plans: Develop individualized treatment plans that consider the patient’s overall health, comorbidities, and potential for adverse drug reactions. Tailoring therapy to the specific needs of each patient can enhance efficacy and minimize side effects (Sullivan MEet al. (2019)

2)    Emphasize Lifestyle Modifications: Encourage and support lifestyle changes, such as diet modifications, physical activity, and weight management. These interventions are crucial for managing hypertension and improving overall cardiovascular health Pescatello et al(2015)

3)    Utilize Technological Tools: Incorporate home blood pressure monitoring, telemedicine, and digital health apps into patient care. These tools can provide continuous monitoring, improve adherence, and facilitate better management of hypertension Maddox et al. 2019.

4)    Address Adherence and Polypharmacy: Implement strategies to improve medication adherence and manage polypharmacy. This includes simplifying regimens, conducting regular medication reviews, and using combination therapies judiciously Beers et al. (2015).

5)    Consider Socioeconomic Factors: Be aware of and address socioeconomic and social barriers to effective treatment. Providing support and resources to overcome these barriers can improve patient outcomes and adherence Agarwal et al. (2017)

 

8.3. THE NEED FOR INDIVIDUALIZED TREATMENT APPROACHES

The complexity of managing hypertension in the elderly underscores the necessity for individualized treatment approaches. Each patient presents unique challenges based on their health status, comorbidities, and personal circumstances.

1)    Tailoring Therapies: Personalized treatment plans should consider the patient’s specific health profile, including age-related physiological changes, comorbid conditions, and the risk of adverse drug reactions. This approach helps optimize therapy and improve overall effectiveness Sullivan et al. (2019)Patient-Centered Care: Engaging patients in their treatment decisions and considering their preferences and lifestyle factors can enhance adherence and satisfaction with care. Education and clear communication about the benefits and risks of various treatment options are crucial Joffe (2013)

2)    Ongoing Monitoring and Adjustment: Regular monitoring and reassessment of treatment plans are essential to accommodate changes in the patient’s health status and response to therapy. This dynamic approach ensures that treatment remains effective and relevant over time Mancia et al. (2011)

3)    Integrating New Insights: Clinicians should stay informed about emerging research and technological advancements to continuously refine and improve hypertension management strategies. Integrating new knowledge into practice can lead to better patient outcomes and more effective management Kumar S et al. (2020).

By adopting a personalized, patient-centered approach and incorporating the latest advancements and research findings, clinicians can more effectively manage hypertension in the elderly, ultimately improving health outcomes and quality of life for this vulnerable population.

 

 

CONFLICT OF INTERESTS

None. 

 

ACKNOWLEDGMENTS

None.

 

REFERENCES

Agarwal S, Kolb T, Wright J, et al. (2017) Financial Barriers to Medication Adherence Among Older Adults: A Systematic Review. J Geriatr Pharmacother. 15(3) :159-72.

Appel LJ, Moore TJ, Obarzanek E, Vollmer WM, Svetkey LP, Sacks FM, et al. (1997) A Clinical Trial of the Effects of Dietary Patterns on Blood Pressure. DASH Collaborative Research Group. N Engl J Med. ;336(16):1117-24. https://doi.org/10.1056/NEJM199704173361601

Aronow WS, Fleg JL. (2017) Blood Pressure Targets in Older Adults with Hypertension : a Comprehensive Review. Ann Transl Med. 5(3) :59.

Aronow WS. (2011) Hypertension and Kidney Disease in the Elderly. J Hypertens.;29(2) :251-2.

Bakris GL, Williams M, Dworkin L, et al. (2014) Preserving Renal Function in Adults with Hypertension and Diabetes: a Consensus Approach. Am J Kidney Dis. ;64(5):716-24.

Beers MH, Ouslander JG, Rollingher I, Reuben DB, Liebmann PJ, Philips AL. (1991) Explicit Criteria for Determining Inappropriate Medication use in Nursing Home Residents. UCLA Division of Geriatric Medicine. Fed Regist. 56(187):55535-9.

Benetos A, Petrovic M, Strandberg T.(2019).Hypertension Management in Older and Frail Older Patients. Circ Res. 124(7):1045-60. https://doi.org/10.1161/CIRCRESAHA.118.313236

Benetos A, Safar M, Rudnichi A, Smulyan H, Richard JL, Ducimetiere P, et al. (1997).Pulse Pressure : a Predictor of Long-Term Cardiovascular Mortality in a French male population. Hypertension. 30(6):1410-5. https://doi.org/10.1161/01.HYP.30.6.1410

Bennett JS, Dodd MA, McClaran J, et al. (2014) Medication Adherence in Elderly Patients with Hypertension : a Review of the Literature. J Clin Hypertens (Greenwich). 16(12) :924-32.

Carretero OA, Oparil S. (2000) Essential Hypertension. Part I: Definition and Etiology. Circulation. ;101(3):329-35. https://doi.org/10.1161/01.CIR.101.3.329

Clement DL, De Buyzere ML, De Bacquer DA, de Leeuw PW, Duprez DA, Fagard RH, et al. (2003) .Prognostic Value of Ambulatory Blood-Pressure Recordings in Patients with Treated Hypertension. N Engl J Med. 348(24):2407-15. https://doi.org/10.1056/NEJMoa022273

Cruickshank K, Riste L, Anderson SG, Wright JS, Dunn G, Gosling RG.(2002). Aortic Pulse-Wave Velocity and its Relationship to Mortality in Diabetes and Glucose Intolerance: an Integrated Index of Vascular Function? Circulation. 106(16):2085-90. https://doi.org/10.1161/01.CIR.0000033824.02722.F7

Darkins A, Ryan P, Kobb R, et al. (2008).Care Coordination/Home Telehealth: Principles, Outcomes, and Lessons Learned. Telemed J E Health. 14(10):1004-20. https://doi.org/10.1089/tmj.2008.0021

DiMatteo MR. (2004).Variations in Patients' Adherence to Medical Recommendations: a Quantitative Review of 50 years of Research. Med Care. ;42(3):200-9. https://doi.org/10.1097/01.mlr.0000114908.90348.f9

Donato AJ, Machin DR, Lesniewski LA. (2015). Mechanisms of Dysfunction in the Aging Vasculature and Role in Age-Related Disease. Circ Res. 116(5):769-79.

Elder K, Osei D, Koffi J, et al. (2020) Reducing Health Disparities Among the Elderly: Community-Based Interventions. Am J Public Health. 110(3):345-52. https://doi.org/10.2105/AJPH.41.3.345-c

Esler M, Lambert E, Schlaich M. (1985). Point: Chronic Activation of the Sympathetic Nervous System is the Dominant Contributor to Systemic Hypertension. J Appl Physiol. 2010 ;109(6):1996-8. https://doi.org/10.1152/japplphysiol.00182.2010

Ezzati M, Lopez AD, Rodgers A, Vander Hoorn S, Murray CJL. (2012) Comparative Risk Assessment Collaborating Group (Cancers). Comparative Quantification of Mortality and Morbidity from Drinking Alcohol: Findings from the Global Burden of Disease Study 2010. Lancet. 2012 ;380(9853) :2224-60.

Ferdinand KC, Nasser SA, Nasser SA. 2020.Antihypertensive Therapy in the Elderly: Current Management and Future Directions. J Clin Hypertens (Greenwich). 22(4):636-50.

Franklin SS, Gustin W 4th, Wong ND, Larson MG, Weber MA, Kannel WB, et al.(1997) Hemodynamic Patterns of Age-Related Changes In Blood Pressure. The Framingham Heart Study. Circulation. 96(1):308-15. https://doi.org/10.1161/01.CIR.96.1.308

Franklin SS, Thijs L, Hansen TW, O'Brien E, Staessen JA. (2013). White-coat Hypertension : New Insights from Recent Studies. Hypertension. 62(6):982-7. https://doi.org/10.1161/HYPERTENSIONAHA.113.01275

Franklin SS. (2007). Hypertension in Older People : part 1. J Clin Hypertens (Greenwich). 9(1) :3-10.

Fryar CD, Ostchega Y, Nwankwo T, et al. (2014). Hypertension Prevalence and Control Among Adults: United States, 2015-2016. NCHS Data Brief. 2017;(289) :1-8.

Gadalean F, Mazzucco S, De Cata G, Manni M, Salvatore F. Effectiveness of Calcium Channel Blockers in Hypertension in Older Adults. Hypertension. 63(6) :1397-405.

Gero A, Radcliff J, Kumar R, et al. (2018). Age-Related Changes in Vascular Function and its Implications for Hypertension Management. J Clin Hypertens (Greenwich). 20(12) :1636-47.

Gnjidic D, Hilmer SN, Blyth FM, et al. (2012). Polypharmacy and Falls in Older People : A Review. J Pharm Pract Res. 42(3) :173-8.

Hansen TW, Thijs L, Boggia J, et al. (2011) Prognostic Value of Home Blood Pressure Measurement in the General Population. Hypertension. 57(3):416-22. https://doi.org/10.1161/HYPERTENSIONAHA.109.133900

He FJ, MacGregor GA. (2010).Reducing Population Salt Intake Worldwide : from Evidence to Implementation. Prog Cardiovasc Dis. 52(5):363-82. https://doi.org/10.1016/j.pcad.2009.12.006

Hermida RC, Crespo JJ, Domínguez-Sardina M, Otero A, Moyá A, Ríos MT, et al.(2018). Bedtime Hypertension Treatment Improves Cardiovascular Risk Reduction : the Hygia Chronotherapy Trial. Eur Heart J. 41(48):4565-76. https://doi.org/10.1093/eurheartj/ehz754

James PA, Oparil S, Carter BL, Cushman WC, Dennison-Himmelfarb C, Handler J, et al. (2014) Evidence-Based Guideline for the Management of High Blood Pressure in Adults: Report from the Panel Members Appointed to the Eighth Joint National Committee (JNC 8). JAMA. 2014 ;311(5):507-20. https://doi.org/10.1001/jama.2013.284427

Jiang H, Liu W, Zhang Y, et al. (2020). Gut Microbiome and Hypertension : A Review of Current Evidence and Future Directions. Hypertension. 76(5) :1425-34.

Joffe SW, Kuo YF, Goodwin JS. (2013). Weight Loss and Hypertension in the Elderly. J Am Geriatr Soc. 61(10) :1875-81.

Kearney PM, Whelton M, Reynolds K, Muntner P, Whelton PK, He J.(2005).Global Burden of Hypertension : Analysis of Worldwide Data. Lancet. 365(9455):217-23. https://doi.org/10.1016/S0140-6736(05)17741-1

Kostis JB, Davis BR, Cutler J, Grimm RH Jr, Berge KG, Cohen JD, et al. (1997). Prevention of Isolated Systolic Hypertension in the Elderly (SHEP): Implications for Treatment and Prevention of Cardiovascular Disease. JAMA. 278(22):1757-62. https://doi.org/10.1001/jama.278.3.212

Krousel-Wood MA, Re RN, Weber MA. (2004) Adherence to Antihypertensive Medications: a Systematic Review. J Clin Hypertens (Greenwich). 6(6):285-97.

Krousel-Wood MA, Re RN, Weber MA. (2004).Adherence to Antihypertensive Medications: a Systematic Review. J Clin Hypertens (Greenwich).6(6):285-97.

Kumar S, Das S, Kumar S, et al. (2020). Innovations in Drug Delivery Systems for Hypertension Management : A Review. Expert Opin Drug Deliv.17(6):855-66.

Lakatta EG, Levy D. (2003) Arterial and Cardiac Aging: Major Shareholders in Cardiovascular Disease Enterprises: part I: Aging Arteries: a "set up" for vascular disease. Circulation. 107(1):139-46. https://doi.org/10.1161/01.CIR.0000048892.83521.58

Liu L, Jin X, Xu Y, et al. (2017) Polypharmacy and Drug Interactions in the Elderly: a Review. Expert Rev Clin Pharmacol. 10(7):777-87.

Maddox TM, Rumsfeld JS, Drozda JP, et al. 2019.Digital Health Technologies and Hypertension Management : the Role of Wearable Devices. J Am Coll Cardiol. 74(13) :1686-95.

Mahoney JE, Joffe SW, Kuo YF, Goodwin JS. (2006) Medication Adherence in the Elderly: the Role of Polypharmacy. J Am Geriatr Soc. 54(7):1107-12.

Mahoney JE, Joffe SW, Kuo YF, Goodwin JS. (2014) Polypharmacy and Medication Adherence: Implications for Older Adults. Clin Interv Aging. 9:1885-97.

Mancia G, Fagard R, Narkiewicz K, et al. (2011) ESH/ESC Guidelines for the Management of Arterial Hypertension. Eur Heart J. 2011 ;32(14):2142-209.

Mancia G, Fagard R, Narkiewicz K, et al. (2018) ESC/ESH Guidelines for the Management of Arterial Hypertension. Eur Heart J. 2018 ;39(33):3021-104.https://doi.org/10.1093/eurheartj/ehy339

McManus DD, Hsu P, Fleg JL. (2014). Comprehensive Management of Hypertension in the Elderly: Treatment Strategies. J Am Coll Cardiol.63(11):1164-76.

McManus DD, Riegel B, McCabe P, Roth A, Chan PS, Miller JM, et al.(2020). Contemporary Management of Hypertension in Older Adults. J Am Coll Cardiol. 75(24):2936-48.

McMurray JJ, Packer M, Desai AS, et al.(2014). Angiotensin-Neprilysin Inhibition Versus Enalapril in Heart Failure. N Engl J Med. 371(11):993-1004. https://doi.org/10.1056/NEJMoa1409077

Miller MA, McHale P, Anderson M. (2018). Combination Therapy for Hypertension : Optimal Choices and Dosage. J Cardiovasc Pharmacol Ther. 23(1):50-64.

Mozaffarian D, Benjamin EJ, Go AS, Arnett DK, Blaha MJ, Cushman M, et al. (2015) Heart Disease and Stroke Statistics-2015 Update : a Report from the American Heart Association. Circulation.131(4)

Muller H, Pfitzer J, Kronenberg A, et al.(2018). Adverse Effects of Antihypertensive Drugs in the Elderly: an Overview. Drugs Aging. 35(9):745-56.

Muntner P, Carey RM, Gidding S, Jones DW, Taler SJ, Wright JT Jr, et al.(2018) Potential U.S. Population Impact of the 2017 ACC/AHA High Blood Pressure Guideline. J Am Coll Cardiol. 71(2):109-18. https://doi.org/10.1016/j.jacc.2017.10.073

Muntner P, Shimbo D, Tonelli M, Reynolds K, Arnett DK, Oparil S. (2015). The Relationship Between Visit-to-Visit Variability in Systolic Blood Pressure and All-Cause Mortality in the General Population. Hypertension. 65(2):157-64.

Niiranen TJ, Johansson JK, Reunanen A, Jula AM. (2014). Home-Measured Blood Pressure is a Stronger Predictor of Cardiovascular Risk than Office Blood Pressure : the Finn-Home Study. Hypertension. 64(2):281-6. https://doi.org/10.1161/HYPERTENSIONAHA.114.03292

O'Brien E, Parati G, Stergiou G, Asmar R, Beilin L, Bilo G, et al. (2013). European Society of Hypertension Position Paper on Ambulatory Blood Pressure Monitoring. J Hypertens. 31(9):1731-68.

Oparil S, Acelajado MC, Bakris GL, Berlowitz DR, Cífková R, Dominiczak AF, et al. (2018). Hypertension. Nat Rev Dis Primers. 4(1): 18014. https://doi.org/10.1038/nrdp.2018.14  

Parati G, Stergiou GS, Dolan E, Bilo G. Blood Pressure Variability: Clinical Relevance and Application. J Clin Hypertens (Greenwich). 2013 ;15(4):241-54.

Patterson A, Veldhuizen S, MacDonald D, et al. (2015). Stress Reduction Interventions in Hypertension Management : A Systematic Review. J Am Soc Hypertens. 9(6):441-9.

Pescatello LS, Franklin BA, Fagard RH, VanHees L, Bourgeois A, Casirola M, et al. (2015). Exercise and Hypertension : American College of Sports Medicine Position Stand. Med Sci Sports Exerc. 47(5):134-55.

Pickering TG, Gerin W, Schwartz AR. (2002). What is the White-Coat Effect and how Should it be Measured? Blood Press Monit. 7(6):293-300. https://doi.org/10.1097/00126097-200212000-00001

Poulter NR, Prabhakaran D, Caulfield M. Hypertension. Lancet.(2005). 386(9996):801-12. https://doi.org/10.1016/S0140-6736(14)61468-9

Rossi GP, Gherardi G, Dorigatti F, et al. (2017). Target Organ Damage in Hypertension : Mechanisms and Management. J Hypertens. 35(3):499-512.

Sakhuja S, Raeburn C, Kincaid S. (2014).Polypharmacy and Medication Adherence: Implications for Older Adults. Clin Interv Aging. 9:1885-97.

Sarnak MJ, Levey AS, Schoolwerth AC, Coresh J, Culleton B, Hamm LL, et al. (2003).Kidney Disease as a Risk Factor for Development of Cardiovascular Disease: a Statement from the American Heart Association Councils on Kidney in Cardiovascular Disease, High Blood Pressure Research, Clinical Cardiology, and Epidemiology and Prevention. Hypertension. 42(5):1050-65. https://doi.org/10.1161/01.HYP.0000102971.85504.7c

Schmieder RE, Mann JF, Schumacher H, et al. (2007). Aliskiren: A New Treatment Option in Hypertension. J Hypertens. 25(5) :931-8.

Seshiah V, Sahay BK, Das AK, Muruganathan A, Rao PV. (2002). A study on the Prevalence of Dyslipidemia in Elderly Hypertensives and its Relationship with blood pressure. Indian Heart J. 54(4):364-9.

Stergiou GS, Siontis KC, Ioannidis JP.(2010). Home Blood Pressure as a Cardiovascular Outcome Predictor: it's Time to Take this Method Seriously. Hypertension. 55(6):1301-3. https://doi.org/10.1161/HYPERTENSIONAHA.110.150771

Sullivan K, Boucher J, Browne B, et al. (2018). Smart phone Apps and Wearable Devices for Hypertension Management : a Systematic Review. J Hypertens. 36(8):1642-50.

Sullivan ME, Murphy M, Quinn M, et al. (2019). The Role of Precision Medicine in the Management of Hypertension. Hypertension. 73(5):1061-8.

Vaughan L, Fothergill M, Tinker S. (2017). Social Determinants of Health and Health Care Disparities Among Older Adults. J Aging Soc Policy. 29(3):187-207.

Walker KA, Power MC, Gottesman RF. (2017). Defining the Relationship Between Hypertension, Cognitive Decline, and Dementia: a Review. Curr Hypertens Rep. 19(3):24. https://doi.org/10.1007/s11906-017-0724-3

Whelton PK, Carey RM, Aronow WS, Casey DE Jr, Collins KJ, Dennison Himmelfarb C, et al. (2018) ACC/AHA/AAPA/ABC/ACPM/AGS/APhA/ASH/ASPC/NMA/PCNA Guideline for the Prevention, Detection, Evaluation, and Management of High Blood Pressure in Adults. J Am Coll Cardiol. 2018 ;71(19) https://doi.org/10.1016/j.jacc.2017.11.005

Zannad F, McMurray JJV, Krum H, et al. (2000). Eplerenone in Patients with Systolic Heart Failure and Mild Symptoms. N Engl J Med. 343(5) :317-24.