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Epidemiology.

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Blood Pressure Control Among Older Adults With Hypertension: Narrative Review and Introduction of a Framework for Improving Care

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C Barrett Bowling, Alexandra Lee, Jeff D Williamson, Blood Pressure Control Among Older Adults With Hypertension: Narrative Review and Introduction of a Framework for Improving Care, American Journal of Hypertension , Volume 34, Issue 3, March 2021, Pages 258–266, https://doi.org/10.1093/ajh/hpab002

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Although antihypertensive medications are effective, inexpensive, and recommended by clinical practice guidelines, a large percentage of older adults with hypertension have uncontrolled blood pressure (BP). Improving BP control in this population may require a better understanding of the specific challenges to BP control at older age. In this narrative review, we propose a framework for considering how key steps in BP management occur in the context of aging characterized by heterogeneity in function, multiple co-occurring health conditions, and complex personal and environmental factors. We review existing literature related to 4 necessary steps in hypertension control. These steps include the BP measure which can be affected by the technique, device, and setting in which BP is measured. Ensuring proper technique can be challenging in routine care. The plan includes setting BP treatment goals. Lower BP goals may be appropriate for many older adults. However, plans must take into account the generalizability of existing evidence, as well as patient and family’s health goals. Treatment includes the management strategy, the expected benefits, and potential risks of treatment. Treatment intensification is commonly needed and can contribute to polypharmacy in older adults. Lastly, monitor refers to the need for ongoing follow-up to support a patient’s ability to sustain BP control over time. Sustained BP control has been shown to be associated with a lower rate of cardiovascular disease and multimorbidity progression. Implementation of current guidelines in populations of older adults may be improved when specific challenges to BP measurement, planning, treating, and monitoring are addressed.

The prevalence of hypertension and the incidence of hypertension-related cardiovascular disease (CVD) increase with older age, making blood pressure (BP) control among older adults an important population health goal. 1 , 2 Although antihypertensive medications are effective, inexpensive, and recommended by clinical practice guidelines, a large percentage of older adults with hypertension have uncontrolled BP. 3 , 4 This may be due in part to several factors. For older adults, BP management occurs in the context of aging characterized by heterogeneity in function, multiple co-occurring health conditions, as well as an often complex set of personal and environmental factors. 5–7 In addition to issues related to aging, there are also specific considerations for measuring and treating hypertension in older age. 8

In this article, we first review hypertension prevalence, treatment, and control in older adults highlighting current clinical practice guideline definitions and their implications for identifying hypertension in older adults. Next we describe the unique considerations for controlling hypertension at older ages and propose a framework for BP management in this population. This framework considers the aging context as well as the specific steps in hypertension management. Based on this framework, we then review the existing literature as it relates to 4 necessary steps in hypertension control: (i) measuring BP, (ii) planning and goal setting, (iii) treating hypertension, and (iv) monitoring BP over time. Lastly, we use this framework to guide a discussion on implementation challenges and opportunities for improving care for older adults with hypertension.

Guideline definitions and treatment goals

The 2017 American College of Cardiology/American Heart Association (ACC/AHA) Guideline for the Prevention, Detection, Evaluation, and Management of High Blood Pressure in Adults classifies BP into 1 of 4 categories: Normal, Elevated, Stage 1, and Stage 2. 4 The guideline defines normal BP as systolic BP (SBP) <120 mm Hg and diastolic BP (DBP) <80 mm Hg. Elevated BP is defined as SBP 120–129 mm Hg and DBP <80 mm Hg. Stage 1 hypertension is defined as SBP 130–139 mm Hg or DBP 80–89 mm Hg and Stage 2 hypertension is defined as SBP ≥140 mm Hg or DBP ≥90 mm Hg. These categories replace the Seventh Report of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure (JNC7) classification, adding the new category Elevated BP, eliminating the prehypertension category, and lowering the BP levels for defining Stage 1 hypertension. 4 , 9 Furthermore, these BP categories are the same for all adults, including the oldest-old.

New to these guidelines are also recommendations for thresholds to initiate BP-lowering medications and BP goals based on CVD risk. Among patients with clinical CVD, guidelines recommend treatment for secondary prevention of CVD events with a BP goal <130 mm Hg/<80 mm Hg. For primary prevention among those without known CVD, guidelines recommend first estimating the 10-year atherosclerotic cardiovascular disease risk. BP-lowering medications are recommended for goal BP levels of <130 mm Hg/<80 mm Hg for patients with an atherosclerotic cardiovascular disease risk of >10%. As 88% of adults over 65 years and 100% of those over 75 years old have an atherosclerotic cardiovascular disease risk of ≥10%, the recommended BP goal for the vast majority of older adults is <130 mm Hg/<80 mm Hg. 4 In addition to antihypertensive medication to achieve these goals, the 2017 ACC/AHA guidelines also recommend nonpharmacological interventions including weight loss among those overweight or obese, a heart-healthy diet, sodium restriction, increased physical activity, and reduction in alcohol consumption. These treatment recommendations are the same for adults of all ages.

Prevalence, treatment, and control

The prevalence of hypertension increases with age. Most epidemiologic studies have used BP ≥140/90 mm Hg to define hypertension. For example, according to an analysis of data from the National Health and Nutrition Examination Survey (NHANES) conducted between 2011 and 2014, the prevalence of hypertension was 10.5%, 29.5%, 52.4%, 63.6%, and 75.1%, among US adults 20–44, 45–54, 55–64, 65–74, and ≥75 years old, respectively. 1 Applying the 2017 ACC/AHA guideline definition of hypertension as BP ≥130/80 mm Hg classified a higher percentage of US adults as having hypertension (45.6% and 31.9% for 2017 ACC/AHA and JNC7, respectively). However, among those 75 years old and older, the difference in those meeting the definition of hypertension (82.3% vs. 75.1%) or who would receive recommendations for antihypertensive medications (82.3% vs. 78.5%) were small. In the general US population, gender differences in the prevalence of hypertension have also been reported with a higher percentage of men compared with women meeting the definition for hypertension. However, after age 65 years the prevalence of hypertension is higher among women than men. 2

The percentage of older adults with awareness of hypertension and receiving treatment are generally high. Awareness of hypertension, defined as BP ≥140/90 mm Hg has been shown to be 67.3%, 79.3%, 85.4%, and 82.1% among US adults 18–44, 45–64, 65–74, and ≥75 years old, respectively. 3 Hypertension awareness has been shown to be more common among those with a usual health care provider, which may explain in part the higher prevalence of awareness at older ages as older adults often require more frequent interactions with the healthcare system. Among those aware they had hypertension, antihypertensive medication use has also been shown to be high among older adults. Among those who reported awareness, the percentage taking antihypertensive medication were 75.8%, 87.7%, 94.1%, and 96.0% at 18–44, 45–64, 65–74, and ≥75 years old. 3

Among older adults with hypertension, the percentage with controlled BP has generally been reported to be less than 50%. A recent analysis reported trends in BP control using NHANES calendar periods across nearly 2 decades. 3 Serial cross-sectional surveys took place over 2-year intervals from 1999–2000 through 2017–2018. Overall, an increasing percentage of adults with controlled BP was seen through 2013–2014, followed by a decrease in calendar periods 2015–2016 and 2017–2018. This trend was also seen among those ≥75 years old ( Figure 1 ). In a pooled analysis from 2015 to 2018, the prevalence ratio for controlled BP among those taking antihypertensive medication was 0.96, 0.84, and 0.63 at ages 45–64, 65–74, and ≥75 years old, compared with 18–44 years old, respectively. 3

Trends in blood pressure (BP) control among US adults ≥75 years old from the National Health and Nutrition Examination Survey (NHANES). 3

Most studies of hypertension have focused on community-dwelling older adults. Therefore, data on the prevalence, treatment, and control of hypertension among special populations of older adults such as the oldest-old or those residing in nursing homes are limited. One analysis of NHANES reported the prevalence among US adults ≥80 years old to be 76.5%, with similar percentage of those with control among those on hypertension medications to those ≥75 years old during the same time period. 10 Importantly, a large increase in antihypertensive polypharmacy, defined as 3 or more classes of BP-lowering medications, was found over time. The percentage of US adults ≥80 years old with antihypertensive polypharmacy was 7.0%, 19.2%, and 30.9% during calendar NHANES assessments occurring in 1988–1994, 1999–2004, and 2005–2010, respectively. 10 Data on the prevalence of hypertension among older nursing home residents are limited. Because of the high prevalence of multimorbidity in the nursing home population, the prevalence of hypertension in combination with other chronic conditions has been described. For example, 1 report showed that 27% of nursing home patients had co-occurring hypertension and dementia. 11 A separate analysis of over 250,000 US nursing home residents with hypertension on antihypertensive medications found that 40% were receiving 2 or more classes of medication. 12 The intensity of treatment did not differ for those with and without moderate–severe cognitive impairment, raising questions about whether hypertension is overtreated among some nursing home residents who have limited life expectancy.

BP control and disabling conditions

As many older adults prioritize remaining independent in late life, it is important to recognize the association between BP control and conditions that reduce cognitive and physical function. Uncontrolled BP is a known risk factor for disabling conditions including stroke, heart failure, and coronary heart disease. 2 Studies have also shown direct associations of hypertension with cognitive and physical function. 13 For example, BP ≥120/80 mm Hg during midlife was found to be associated with a greater risk of developing dementia in later life. 14 Therefore, a life-course perspective is helpful for understanding the detrimental effects of uncontrolled BP that may accumulate over many years leading to disability. 15

The combination of an aging US population, a decreasing percentage with controlled hypertension, and recommendations for lower BP goals will likely result in an expanding population of older adults with uncontrolled BP who are at risk for CVD events. Population health efforts to improve BP control often focus on increasing awareness and treatment. However, awareness and treatment have remained high among older adults. An alternative approach may be to recognize specific challenges to BP control among older adults. We proposed a framework for considering how key steps in BP management occur in the context of common issues with aging ( Figure 2 ).

A framework to improve blood pressure (BP) control that considers how key steps in BP management occur in the context of common aging issues.

Aging context

A sizable proportion of older adults, including many who are frail, will benefit from intensive BP control, defined as a SBP <120 mm Hg. However, other older adults are unlikely to benefit. The World Health Organization (WHO) has developed a model that is useful for helping to identify those who may be less likely to derive benefit from intense efforts to control BP. The WHO International Classification of Functioning (ICF) model describes 4 aging domains: (i) function, (ii) health conditions (i.e., multimorbidity), (iii) personal factors, and (iv) environmental factors. 5 , 16 This model considers the impact of functional limitations on daily activities such as chronic disease self-management tasks. The health conditions domain acknowledges that older adults often experience multiple chronic conditions. 17 , 18 Examples of personal factors include individual health goals, personal financial resources, and availability of family caregivers. Examples of environmental factors include living situations such as independent living vs. nursing home residence, and geographic issues such as neighborhood-level poverty. While these considerations may be important regardless of age, the prevalence of functional limitations and complexity of health conditions are known to increase at older age. 19 Consequently, some older adults rely on personal and environmental factors to maintain independence and manage their health conditions. 20

The interaction of function, co-occurring health conditions, and personal and environmental factors are relevant to BP control. This is illustrated by considering the multiple self-management tasks necessary for BP control. Limitations with physical and cognitive function may reduce one’s capacity to follow physical activity recommendations, adhere to medication scheduling, and refill medications on-time. 21 While some conditions have overlapping treatment goals with hypertension, reinforcing the need for treatment (e.g., angiotensin-converting enzyme inhibitor among those with hypertension, chronic kidney disease, and diabetes), the presence of multimorbidity often makes self-management more complex. 22 , 23 Older adults may not receive guidance on how to reconcile opposing treatment recommendations. 24 This may be especially true when older adults face choices about treating conditions that are symptomatic vs. those that are asymptomatic such as hypertension. 25 The presence or absence of a family caregiver or resources to pay caregivers, can influence one’s ability to overcome functional and cognitive limitations.

In addition to impacts on ability to self-manage BP, functional limitations and multimorbidity may provide important prognostic information. 26 For example, many older adults with poor function and advanced illness are at end-of-life. Those with a life expectancy of less than 2 years are unlikely to live long enough to experience the benefits of intensive BP treatment. 27 , 28 Because of the wide range of functional abilities, health conditions, and personal and environmental resources in older age, a one-size-fits-all approach is unlikely to be effective for setting BP goals or controlling BP.

Steps in BP management

In addition to issues related to older age influencing BP control, there are specific components involved in achieving and sustaining BP control ( Table 1 ). This framework acknowledges that the BP measure can be affected by the technique, device, and setting in which BP is measured. The plan refers to setting a goal BP in the context of the patient and family’s overall health goals. Treatment refers to the management strategy including the use of BP-lowering medications, the expected benefits of treatment, and risk for adverse events. Lastly, monitor refers to need for ongoing follow-up to support a patient’s ability to sustain BP control over time. Below we highlight some of the relevant literature for each of these 4 steps.

Description of steps in hypertension control and relevant considerations for older adults

.	Description .	Relevance to older adults .
Measure	Technique, device, setting	• Proper technique limited by physical and cognitive impairment or geriatric conditions • Competing demands for clinical assessments among older adults with multimorbidity (i.e., proper technique a low priority) • Higher prevalence of treated white coat hypertension at older age
Plan	Setting goals	• Concerns about generalizability of clinical trial evidence for some older adults • Wide range in health goals and willingness to accept tradeoffs between benefits and harms at older age
Treat	Management strategy, benefits vs. harms	• Treatment intensification likely to result in polypharmacy • Physical and cognitive impairment may limit self-management • Dependence on caregivers for self-management support • Falls are a common cause and death and disability in older adults. Fear of precipitating a fall may affect treatment decisions
Monitor	Follow-up over time	• Heterogeneity in life expectancy and time for which BP monitoring may be necessary • Intervening health events and declining function occur at older age and may affect BP control or treatment goals

.	Description .	Relevance to older adults .
Measure	Technique, device, setting	• Proper technique limited by physical and cognitive impairment or geriatric conditions • Competing demands for clinical assessments among older adults with multimorbidity (i.e., proper technique a low priority) • Higher prevalence of treated white coat hypertension at older age
Plan	Setting goals	• Concerns about generalizability of clinical trial evidence for some older adults • Wide range in health goals and willingness to accept tradeoffs between benefits and harms at older age
Treat	Management strategy, benefits vs. harms	• Treatment intensification likely to result in polypharmacy • Physical and cognitive impairment may limit self-management • Dependence on caregivers for self-management support • Falls are a common cause and death and disability in older adults. Fear of precipitating a fall may affect treatment decisions
Monitor	Follow-up over time	• Heterogeneity in life expectancy and time for which BP monitoring may be necessary • Intervening health events and declining function occur at older age and may affect BP control or treatment goals

Abbreviation: BP, blood pressure.

Differences in BP measurement based on the technique and setting are common at all ages, but especially true in this population. The AHA Scientific Statement on Measurement of BP in Humans describes 6 overall steps and 20 specific instructions for the proper technique to obtain seated BP in the office. 29 Large-scale studies have demonstrated that implementing the proper technique is feasible, however approaches used in clinical trials have not been widely adopted in practice. Clinic-level challenges include ensuring a 3- to 5-minute relaxation period, not talking to the patient during the measurement, as well as determining the proper cuff size. At the patient-level, challenges include removing clothing among those with functional limitations or arthritis, bladder emptying among those with prostate or bladder dysfunction, and following instructions for those with cognitive limitations. These challenges may explain the recent report showing higher SBP in the electronic health record compared with BP obtained under a standardized research protocol. 30 Despite these challenges, there are several examples of how outpatient clinics can overcome clinic- and patient-level barriers to care (e.g., blood draws, laboratory calibration, crash cart maintenance) when standardized policies are put into place. This might also involve an expanded use of home blood pressure monitoring following AHA Scientific Statement recommendations for proper technique. 29 While this approach may overcome the clinic-level deficiencies, some patient-level challenges remain. Concerns about device validation have also been reported. 31

Research has shown differences based on the setting in which BP is measured, an important example being the higher prevalence of white coat hypertension with aging. 8 , 32 One way to identify white coat hypertension is by using ambulatory blood pressure monitoring (ABPM). In ABPM, a BP monitor is worn for 24 hours and obtains automatic readings in the out-of-office setting. 8 ABPM has been shown to have similarly feasible in older and younger adults. 33 Using ABPM, white coat hypertension is defined as having elevated clinic BP without elevated daytime BP on ABPM. The term “treated white coat hypertension” has been used to describe elevated clinic BP without elevated daytime BP on ABPM among those on antihypertensive medications. 8 Prior studies have shown that among older adults, clinic BP is higher in relationship to daytime BP resulting in a higher prevalence of treated white coat hypertension at older age. For example, an analysis of data from the Jackson Heart Study, compared the difference in clinic and daytime SBP among Black US adults with hypertension <60 vs. ≥60 years old. 34 The difference between clinic SBP and daytime SBP was on average higher among those ≥60 years old compared with <60 years old (12 mm Hg higher vs. 8 mm Hg higher). The prevalence of white coat hypertension may be greater among special populations of adults. The prevalence of treated white coat hypertension among participants who were all 80 years and older in the HYVET study was 50%. 35 Among nursing home residents, 1 study found that 70% of all nursing home residents with high BP were found to have white coat hypertension when ABPM was conducted. 36 Taken together, these findings suggest that clinic BP obtained as part of routine care may not always reflect the out-of-clinic BP and should be considered when addressing BP control in older adults.

In the proposed framework, the plan refers to setting goals for BP control levels. As described above, the guideline recommended goal BP for the vast majority of older adults is <130 mm Hg/<80 mm Hg. This recommendation is supported by clinical trial evidence including findings from the Systolic Blood Pressure Intervention Trial (SPRINT) which tested intensive vs. standard control. 27 While the results of SPRINT have been extensively reported, 37 it is worth reviewing 3 findings that are relevant to older adults. First, among the prespecified subgroup of participants ≥75 years old, treating to an SBP goal of <120 mm Hg (intensive control) vs. <140 mm Hg (standard control) resulted in lower rates of fatal and nonfatal CVD events and death. 28 This was true in exploratory subgroups in which participants were categorized as fit, less fit, or frail or had a low gait speed and among those ≥80 years old. 38 Second, findings from SPRINT maybe generalizable to a large number of ambulatory older adults, including those with frailty. In SPRINT, 31% of participants ≥75 years old were frail, a similar prevalence seen in community-dwelling older adults. 39 Third, findings from the SPRINT MIND study found a lower incidence of mild cognitive impairment and the combination of mild cognitive impairment or probable dementia with intensive SBP control. 40 There was no difference seen in the primary outcome of probable dementia, perhaps due to the intervention being terminated early and inadequate follow-up time. However, because maintaining cognitive function is such an important goal in aging, findings of lower risk of mild cognitive impairment are clinically relevant for older adults.

While SPRINT is a landmark study and representative of a large percentage of older adults with hypertension, it is not possible for a randomized trial to be generalizable to all older adults. Therefore, it is important to consider the study exclusions most relevant to older adults when planning BP goals. For example, SPRINT excluded adults residing in nursing homes and those with standing hypotension of <110 mm Hg, type 2 diabetes, prior history of stroke, estimated glomerular filtration rate <20 ml/min/1.73 m 2 , dementia, unintentional weight loss, or symptomatic heart failure. 27 As these conditions are common at older age and may be associated with risk for adverse events, it is not known if intensive SBP control would confer the same benefits for some subgroups of older adults. In addition to the exclusion criteria, it has been well documented that barriers exist to inclusion of older adults in research. 41 For example, older adults with functional limitations and limited social support face additional barriers to participation even when not explicitly excluded, reinforcing the need to consider the aging context when making plans for BP treatment goals. 41

After making plans for BP goals, the next step is to choose a management strategy. This includes both nonpharmacological interventions, such as low sodium diets and weight loss, as well as the use of BP-lowering medications. Several nonpharmacological interventions have additional benefits such as improvement of function and should be considered regardless of the need for antihypertensive medication. The clinician and patient should have an understanding of the expected benefits and potential for risk for adverse events when considering antihypertensive medication initiation or intensification. In general, guideline recommendations for specific antihypertensive medications do not differ by age. 4 As the majority of older adults with hypertension are on treatment, treatment decisions less often focus on which antihypertensive medication to initiate, but more on when to intensify treatment by adding medications from other classes. For example, among adults ≥75 years old in SPRINT, 85% of participants in the intensive treatment group and 57% in the standard treatment group required 2 or more antihypertensive medication classes to achieve the targeted BP goals (mean number 2.6 vs. 1.8). 28 The most commonly used antihypertensive medications for both randomization groups were angiotensin-converting enzyme inhibitors/ARBs followed by diuretics and calcium channel blockers. Therefore, in this population it is important to anticipate and manage polypharmacy, specifically antihypertensive polypharmacy, when treating hypertension.

Another aspect of treatment to consider is the risk for adverse events. Falls are leading cause of injury and death among older adults. 42 Although concerns about fall risk likely lead to less intensive hypertension treatment, evidence on the association between hypertension treatment and falls is mixed. Clinical trials, including SPRINT, have not shown intensive BP treatment to be associated with a higher risk of injurious falls. 27 , 43 However, rates of falls have been shown to be lower in trial populations than in observational studies. 44 , 45 Among Medicare beneficiaries ≥70 years old with hypertension, antihypertensive medications use was shown to be associated with a higher risk of serious fall injuries. 44 In a separate study of over 90,000 Medicare beneficiaries, antihypertensive medication initiation or intensification was associated with risk for serious fall injuries within 14 days, but not longer-term risk. 46 In an analysis of data from the REasons for Geographic and Racial Differences in Stroke (REGARDS) study participants on antihypertensive medication, indicators of frailty, but not BP levels or number of antihypertensive medications, was shown to be associated with risk for serious fall injuries. 47 These findings suggest that the risk for falls should not preclude hypertension treatment for most older adults, but careful titration, short-term monitoring, and addressing multiple fall risk factors should be part of comprehensive hypertension treatment.

Population level reports on BP control provide a snapshot in time. However, in practice, clinicians diagnose and treat individuals with hypertension over many visits and patients live with hypertension over many years. Older adults often experience intermittent health events, many unrelated to hypertension, that may affect their ability to achieve BP control. Therefore, monitoring BP control over time with the goal of sustaining BP control is an important step in hypertension management. Recent studies have shown that sustained BP control is associated with better health outcomes. 48 For example, an analysis of the Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial (ALLHAT) linked to Medicare health insurance claims examined the association between sustained SBP control and the progression of multimorbidity, defined by the co-occurrence of up to 14 separate chronic conditions. 49 SBP control was categorized as <140 mm Hg at <50%, 50% to <75%, 75% to <100%, and 100% of visits over a 48-month assessment period. Participants with sustained SBP control at a higher percentage of visits had a slower rate of multimorbidity progression and developed multimorbidity when they were 5–10 years older than their counterparts without sustained SBP control. As older adults often consider their overall health when assessing the risks and benefits of treatment, not just the disease-specific outcomes, evidence on reducing multimorbidity could be used to guide patient-centered discussions about monitoring and improving BP control over time.

Implementation needs

Understanding the unique challenges and opportunities for BP control in older adults may facilitate better implementation of hypertension guidelines in this population. In Table 2 , we describe some differences between clinical trials and routine care related to measuring, planning, treating, and monitoring BP control among older adults. Recognizing these differences can be used to identify implementation opportunities. For example, in clinical trials, strict inclusion criteria are applied to populations to identify eligible participants before any plan for BP treatment is initiated. In clinical practice, identifying patients who might benefit is not done in a coordinated way. Therefore, implementation strategies that include risk stratification tools to identify patients for whom guideline recommended BP is appropriate are needed.

Identifying implementation opportunities that address differences in clinical trials and routine care

.	Clinical trials .	Routine care .	Implementation opportunities .
Measure	• Standardized technique • Calibrated equipment • Certified research staff • Multiple measures • Routine orthostatic BP	• Multiple techniques • Available equipment • Busy clinical staff • Single measure • Additional measures when clinically indicated/symptoms	Develop practical approaches to BP measurement that can be achieved in busy clinic settings or accurately obtained outside of the clinic.
Plan	• Eligibility screening prior to enrollment • BP goals determined by protocol or randomization group	• All comers • Provider variability in knowledge and comfort with guideline recommended goals • Variability in patient and family goals	Use risk stratification tools to identify patients for whom guideline recommended BP is appropriate. Incorporate shared decision-making tools to help align patient goals with BP treatment goals.
Treat	• Determined by standardized protocols or by randomization group • Frequent assessment for study specific adverse events including minor events	• Provider, patient, and clinic variability in drug choice and timing of initiation/intensification • Adverse events are multifactorial in etiology • Adverse events may not be identified unless they result in acute or emergent care	Develop treatment protocols that address polypharmacy, drug–drug, and drug–condition interactions that are common among older adults with multimorbidity. Following existing guidelines for addressing multifactorial geriatric conditions such as falls.
Monitor	• Standard device and setting • Routine interval • Set study endpoint	• Multiple devices and settings • As needed or when acute events occur • No endpoint	Report meaningful metrics for sustained BP control that support patient–provider communication and quality improvement. Follow flexible monitoring schedules that respond to changes in BP control, acute health events, or health goals.

.	Clinical trials .	Routine care .	Implementation opportunities .
Measure	• Standardized technique • Calibrated equipment • Certified research staff • Multiple measures • Routine orthostatic BP	• Multiple techniques • Available equipment • Busy clinical staff • Single measure • Additional measures when clinically indicated/symptoms	Develop practical approaches to BP measurement that can be achieved in busy clinic settings or accurately obtained outside of the clinic.
Plan	• Eligibility screening prior to enrollment • BP goals determined by protocol or randomization group	• All comers • Provider variability in knowledge and comfort with guideline recommended goals • Variability in patient and family goals	Use risk stratification tools to identify patients for whom guideline recommended BP is appropriate. Incorporate shared decision-making tools to help align patient goals with BP treatment goals.
Treat	• Determined by standardized protocols or by randomization group • Frequent assessment for study specific adverse events including minor events	• Provider, patient, and clinic variability in drug choice and timing of initiation/intensification • Adverse events are multifactorial in etiology • Adverse events may not be identified unless they result in acute or emergent care	Develop treatment protocols that address polypharmacy, drug–drug, and drug–condition interactions that are common among older adults with multimorbidity. Following existing guidelines for addressing multifactorial geriatric conditions such as falls.
Monitor	• Standard device and setting • Routine interval • Set study endpoint	• Multiple devices and settings • As needed or when acute events occur • No endpoint	Report meaningful metrics for sustained BP control that support patient–provider communication and quality improvement. Follow flexible monitoring schedules that respond to changes in BP control, acute health events, or health goals.

Despite effective and inexpensive treatments, clinical trial evidence on the benefits of treatment, and guideline recommendations, a large percentage of older adults do not have adequately controlled BP. A framework that recognizes both the broader aging context and the specific challenges and opportunities in BP management may be helpful for improving BP control. Implementation of current guidelines in populations of older adults may be improved when barriers to BP measurement, planning, treating, and monitoring are addressed.

Support was provided through the National Heart, Lung, and Blood Institute (R01HL133618) and the National Institute on Aging (R01AG062502) to C.B.B. This work was also supported by the Durham Center of Innovation to Accelerate Discovery and Practice Transformation (ADAPT) (CIN 13-410) at the Durham VA Health Care System. The views expressed here/in this manuscript are those of the authors and do not necessarily represent the views of the National Heart, Lung, and Blood Institute; the National Institutes of Health; or the Department of Health and Human Services.

The authors declared no conflict of interest.

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Allan J, Sheppard K. Monitoring a pulse in adults. Br J Nurs. 2018; 27:(21)1237-1239 https://doi.org/10.12968/bjon.2018.27.21.1237

British and Irish Hypertension Society. Blood pressure measurement. Using manual blood pressure monitors. 2017. https://tinyurl.com/ybz44moe (accessed 9 January 2019)

Dougherty L, Lister S. The Royal Marsden manual of clinical nursing procedures, 9th edn. Chichester: Wiley Blackwell; 2015

Fetzer SJ. Vital signs and physical assessment, 8th edn. In: Perry AG, Potter PA, Ostendorf WR (eds). St Louis. MO: Mosby; 2014

Foley V. Clinical measurement. In: Delves-Yates C (ed). London: SAGE Publications; 2015

Ford C, Park LJ. Hand hygiene and handwashing: key to preventing the transfer of pathogens. Br J Nurs. 2018; 27:(20)1164-1166 https://doi.org/10.12968/bjon.2018.27.20.1164

Ford C, Park LJ. How to apply and remove medical gloves. Br J Nurs. 2019; 28:(1)26-28 https://doi.org/10.12968/bjon.2019.28.1.26

James GD, Gerber LM. Measuring arterial blood pressure in humans: auscultatory and automatic measurement techniques for human biological field studies. Am J Hum Biol. 2018; 30:(1) https://doi.org/10.1002/ajhb.23063

Lancaster RJ, Westphal J, Jambunathan J. Using SBAR to promote clinical judgment in undergraduate nursing students. J Nurs Educ. 2015; 54:(3)S31-S34 https://doi.org/10.3928/01484834-20150218-08

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Moore T. Observations and monitoring vital signs. In: Moore T, Cunningham S (eds). Abingdon: Routledge; 2017

National Institute for Health and Care Excellence. Hypertension in adults: diagnosis and management. 2011. https://tinyurl.com/z7shd55 (accessed 9 January 2019)

Nursing and Midwifery Council. Future nurse: standards of proficiency for registered nurses. 2018. https://tinyurl.com/yaln93xh (accessed 9 January 2019)

O'Brien EO. Blood pressure measurement, 6th edn. In: Beevers DG, Lip GYH, O'Brien E (eds). Chichester: Wiley Blackwell; 2015

Odell M. Chapter 3. Recognizing and managing the critically ill and ‘at risk’ patient on a ward. In: Mallett J, Albarran JW, Richardson A (eds). Chichester: Wiley Blackwell; 2013

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How to take manual blood pressure

Laura J Park

Graduate Tutor, Adult Nursing, Northumbria University, Newcastle upon Tyne, explain how to reduce the risk of contamination

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Claire Ford

Lecturer, Adult Nursing, Northumbria University, Newcastle upon Tyne, explain how to reduce the risk of contamination

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Jaden Allan

Senior Lecturer, Adult Nursing, Northumbria University

This article focuses on non-invasive blood pressure (BP) measurement, using the manual technique. This vital observation is practised by all nursing fields in primary and secondary healthcare environments.

What is blood pressure?

A BP measurement in its simplest form is a determinant of individual cardiac output (the volume of blood pumped out of the heart and into the aorta per minute) and the systematic vascular resistance (the diameter of the arterial blood vessels) ( Foley, 2015 ).

BP measurement is widely recognised as being a routine observation that can be used as a way to assess cardiac output and its effectiveness for adequate tissue perfusion ( Odell, 2013 ). Thus, the presence of a BP is a requirement for human existence and BP measurement, which includes interpreting results and taking appropriate action, is considered a key clinical skill to acquire and maintain as results can determine patient care ( Doughty and Lister, 2015 ).

Many factors can influence a BP reading, for example, age, sleep, emotions and activity. Consequently, evidence in the literature varies as to what constitutes a normal reading, and optimal parameters are often used instead ( Moore, 2017 ). Dougherty and Lister (2015) state that the normal BP at rest has the range of 110–140 mmHg for systolic and 70–80 mmHg for diastolic BP.

Hypertension (high BP) refers to measurements that exceed the resting systolic parameters and hypotension (low BP) refers to those that fall below resting systolic parameters. Hypertension and hypotension, if left undetected and unmanaged, can have serious implications for an individual, including reduced tissue perfusion if hypotensive and cardiac ischaemia if hypertensive ( Wallymahmed, 2008 ).

BP measurement consists of two readings, which are recorded like a fraction, with one reading on top and the other below, i.e. 120/80 mmHg ( Box 1 ) ( Moore, 2017 ). The uppermost reading, known as the systolic, is the first to be taken: it measures the peak force of blood as it pushes against the walls of the arteries as the heart's left ventricle contracts, pushing blood into the aorta and causing an increase in pressure ( Fetzer, 2014 ; Foley, 2015 ). The lower reading, the diastolic, measures the force exerted on the walls of the arteries as the heart relaxes and refills.

Systolic	120
Diastolic	80

Different arteries can be used to measure BP. However, due to ease of access, the manual technique is generally associated with measuring brachial arterial pressure, a major blood vessel that runs through the upper arms before dividing below the anticubital fossa.

What is involved in taking a manual BP?

Two main pieces of equipment are required to take a manual BP: an aneroid sphygmomanometer and a stethoscope ( Figure 1a and Figure 1b ).

The sphygmomanometer consists of a cuff that houses an inflatable bladder, a manometer (dial) and a mechanism to pump up the cuff, known as the inflation bulb. Measurement of BP involves:

Depressing the inflation bulb, forcing the air inside into the bladder in the cuff
Releasing the bulb, allowing air to re-enter the bulb
The process is then repeated.

The following occurs during this process: the pressure in the bladder situated within the cuff fills to a point where pressure within the cuff exceeds the blood flow in the brachial artery. The cuff, therefore, acts like a tourniquet, by temporarily excluding blood flow to the artery. Opening the valve attached to the inflation bulb slowly releases air from the bladder, the cuff pressure falls and, when the systolic pressure becomes greater than the pressure remaining in the cuff, a sound will be heard through the stethoscope ( Levick, 2010 ).

The sounds that can be heard are referred to as Korotkoff sounds; these can often be described either as a faint tapping, thudding or ticking sound — it is the first Korotkoff sound ( Table 1 ) that is used to determine the systolic reading ( Foley, 2015 ). As air continues to be released from the bladder, pressure in the cuff decreases further, reducing restrictions on the arteries, the blood flow starts to return to normal and the Korotkoff sounds disappear, indicating the diastolic reading ( Fetzer, 2014 ).

Silence will be heard before cuff inflation. Sounds will be heard only when Phase I starts
Phase I	First tapping, thudding sound (volume and clarity of sound vary between patients)
Phase II	Sounds change to a murmur and can be distinguished as a swishing sound
Phase III	The sounds in phase III are louder than phase I and are distinguished as knocking sounds
Phase IV	Sounds become muffled as pressure in the cuff decreases. They can again be distinguished as swishing sounds
Phase V	Silence

Source: Dougherty and Lister, 2015

Electronic versus manual devices

While the manual auscultation technique is considered the gold standard for BP measurement, advances in medical technology have resulted in alternative ways of measuring and monitoring BP ( James and Gerber, 2018 ).

The Nursing and Midwifery Council (2018) and the National Institute for Health and Care Excellence (NICE) (2011) advocate the use of either manual or technological devices, with neither option being favoured over the other. However, there are advantages and disadvantages to both methods—a level of clinical knowledge and skills for manual and electronic measurements are requirements within clinical practice. Moreover, while electronic devices have become the ‘go to method’, it is essential that nurses maintain the skills and confidence in using the manual method ( Moore, 2017 ), especially for patients with hypertension, hypotension or pulse irregularities. Pulse irregularities can cause inaccuracies in electronic readings ( NICE, 2011 ; Foley, 2015 ) and this can lead to false diagnosis and incorrect treatment.

In addition, if there are any doubts over an electronic BP reading, a manual reading should be obtained to verify BP ( Dougherty and Lister, 2015 ). Using clinical judgement when doubts arise is often associated with the art of noticing ( Tanner, 2006 ; Watson and Rebair, 2014 : Lancaster et al, 2015 ). Failure to interpret and, ultimately, respond appropriately to clinical cues to uncover clinical signs of deterioration linked to changes in BP can have serious consequences ( Watson and Rebair, 2014 ; Lancaster et al, 2015 ).

How to take a manual BP

Poor technique is another factor that can lead to inaccuracies in BP measurements. It is therefore important to follow the correct technique ( Dougherty and Lister, 2015 ; O'Brien, 2015 ; Moore, 2017 ; British and Irish Hypertension Society, 2017 ):

Ensure you adhere to infection prevention (i.e. hand hygiene, personal protective equipment (PPE), decontaminate equipment) ( Ford and Park, 2018 ; 2019 )
Communicate with the patient, explain the procedure fully, check their understanding and gain consent. Check if they have a preference for which arm to use. Ask them to remove any clothing covering the arm
Position your patient (i.e. supine, seated or standing) and choose an appropriate arm from which to take the BP reading (i.e. avoid fistulas, broken areas of skin, mastectomy sites and cannula sites)
Ensure the cuff size is correct for the patient. If it is too large, the BP reading can be underestimated. Cuff sizes are often displayed in picture form on the outside of the cuff ( Figure 2 )
Ensure the stethoscope is in full working order: this will require you to twist the head clockwise and gently tap on the diaphragm. If a loud sound can be heard, the stethoscope is working correctly
Locate the patient's brachial artery ( Figure 3a ) ( Allan and Sheppard, 2018 )
Wrap the cuff securely around the patient's bare arm, ensuring that the patient side of the cuff is placed against their skin, with the cuff 's lower edges 2–3 cm above the brachial pulse. The cuffed arm should be at the level of the patient's heart to ensure an accurate reading (a pillow can be used to position the arm if required)
Ensure the patient is rested (the person should be seated comfortably for at least 5 minutes before taking a BP), and ask them not to talk or eat. Ensure their legs are uncrossed (crossed legs can increase blood pressure)
Relocate the brachial pulse; once found, palpate the pulse while inflating the cuff. When the brachial pulse can no longer be felt, deflate the cuff, ensuring that you take note of the reading on the manometer (dial). To estimate the systolic pressure add 20 mmHg to the measurement you recorded; this is known as the patient's approximate systolic BP. Gaining an approximate systolic is considered good practice: it assists in estimating (the approximate pressure when you should hear Phase I of the Korotkoff sounds (the systolic reading), thus reducing the risk of the systolic reading being missed
Place the stethoscope into your ears, with the earbuds facing forward, and position the diaphragm of the stethoscope over the patient's brachial pulse ( Figure 3b )
Inflate the cuff to the approximate systolic previously noted
Slowly deflate the cuff by 2–3 mmHg per second, while simultaneously listening for the first Korotkoff sound (tapping sound that identifies the systolic reading) and the Korotkoff disappearing (this signifies the diastolic reading) ( Table 1 )
Once Korotkoff sounds can no longer be heard, open the valve to deflate the cuff fully. If you need to re-check the BP, ensure you wait 1-2 minutes
Remove the cuff, decontaminate the equipment and document the readings.

Common causes of error

Top tips for using a stethoscope.

Inaccuracies with the readings often result from reduced hearing, which can be caused by the incorrect opening of the diaphragm of the stethoscope and incorrect insertion of the earpieces (i.e. being placed in the ear canal in the wrong direction) ( Wallymahmed, 2008 ; Tomlinson, 2010 ; Dougherty and Lister, 2015 ):

Before inserting the stethoscope make sure that the earpieces are pointing forward towards the bridge of your nose
Once the stethoscope is in situ, check that the diaphragm is open by tapping its surface area gently. If a loud sound can be heard, it is working correctly. If no sound can be heard, turn the stethoscope head 180° and repeat the process
Some stethoscopes have dual auscultation devices (diaphragm and bell). The diaphragm is identified by its flat, larger surface area, which makes it easier to control when using it one handed
Ensure the diaphragm, not the bell, is placed over the brachial artery.

Tops tips for cuff application

Loose and incorrectly placed cuffs are a common problem associated with inaccurate BP measurements. So ensure that:

The midline of the bladder is placed 2–3 cm above the brachial pulse. Most cuffs now have an arrow to indicate the midline point. This needs to point down toward the brachial ( Figure 4a and Figure 4b )
The cuff is secured so it is comfortable and cannot slip off the patient's arm.

Tops tips for using the valve on the inflatable bulb and reading the measurements on the dial

Opening, closing and controlling the valve, in particular the speed, are common problems that lead to inaccurate readings. This can be avoided, so:

Before carrying out the procedure, confirm in which direction the valve is opened and closed
Opening and closing the value slowly comes with practice. Practising a one-handed technique for slowly opening and closing the valve is essential
Ensure that the sphygmomanometer is placed at eye level and that the dial on the meter is visible.

LEARNING OUTCOMES

Understand the reasons for taking blood pressure (BP) and the equipment required
Understand the various techniques for taking BP measurements
Recognise the procedural steps for taking a manual BP
Be aware of common causes of errors when taking a manual BP

International Journal of Cardiovascular Sciences

A bimonthly publication part of the Brazilian Society of Cardiology portfolio of journals connected with ABC Cardiol publishing national and international scientific production in the field of cardiovascular sciences.

ISSN 2359-4802

eISSN 2359-5647

Search Articles

International journal of cardiovascular sciences. 13/feb/2023;36:e20220001., factors associated with elevated blood pressure in nursing workers.

DOI: 10.36660/ijcs.20220001

Introduction

Nurses from the night shift are exposed to sleep deprivation, which is associated with circadian rhythm alteration, lifestyle changes, psychosocial stress, and, consequently, increased risk of blood pressure (BP) deregulation and hypertension.

To analyze risk factors associated with elevated BP levels in nursing workers.

A transversal, quantitative study was conducted with 172 nursing professionals of a large hospital in the state of Minas Gerais, Brazil. The following data were collected: anthropometric and BP measurements, sociodemographic characteristics, clinical variables, and lifestyle habits. Results were evaluated by bivariate analysis and logistic regression. The level of significance adopted in the statistical analysis was 5%.

Participants’ average age was 42.7 ± 9.6 years old; 86.6% (n = 149) were female, and 20.3% (n = 35) had previous diagnosis of hypertension. Overweight and obesity (odds ratio [OR]: 2.187, 95% confidence interval [CI]: 1.060 – 4.509) and night shift (OR: 2.100, CI 95%: 1.061 – 4.158) were statistically significant (p < 0.05) for increased risk of elevated BP level.

Excessive weight and night shift were significant factors for increased BP in nursing workers.

Keywords: Blood pressure ; Nursing team ; Shift work schedule ; Body weight

How to cite this article

Coelho V M , Sinhoroto C O , Magnabosco P , Raponi M B G , Oliveira M A M , Almeida Neto O P , Figueiredo V N . Factors Associated With Elevated Blood Pressure in Nursing Workers. Int J Cardiovasc Sci 2023;36:e20220001.

Coelho, Vivian de Moraes ; Sinhoroto, Camila Oliveira ; Magnabosco, Patrícia ; Raponi, Maria Beatriz Guimarães ; Oliveira, Maria Angélica Melo e ; Almeida Neto, Omar Pereira de ; Figueiredo, Valéria Nasser . Factors Associated With Elevated Blood Pressure in Nursing Workers. Int J Cardiovasc Sci , v. 36, e20220001, Feb. 2023.

Coelho, V. M. , Sinhoroto, C. O. , Magnabosco, P. , Raponi, M. B. G. , Oliveira, M. A. M. , Almeida Neto, O. P. , & Figueiredo, V. N. (2023). Factors Associated With Elevated Blood Pressure in Nursing Workers. Int J Cardiovasc Sci, 36 , e20220001.

Coelho, Vivian de Moraes and Sinhoroto, Camila Oliveira and Magnabosco, Patrícia and Raponi, Maria Beatriz Guimarães and Oliveira, Maria Angélica Melo e and Almeida Neto, Omar Pereira de and Figueiredo, Valéria Nasser . Factors Associated With Elevated Blood Pressure in Nursing Workers. Int J Cardiovasc Sci [online]. 2023, vol. 36, [cited 2024-06-21], e20220001. Available from: <https://ijcscardiol.org/article/factors-associated-with-elevated-blood-pressure-in-nursing-workers/>. ISSN 2359-4802.

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Aderonke Agboji 1 ,
David Anekwe 2 , 3
1 University of Northern British Columbia , Prince George , Canada
2 Department of Physical Therapy , The University of British Columbia , Vancouver , Canada
3 Physical Therapy , University of Northern British Columbia , Prince George , Canada
Correspondence to Dr David Anekwe, Department of Physical Therapy, The University of British Columbia, Vancouver, Canada; david.anekwe{at}ubc.ca

https://doi.org/10.1136/ebnurs-2024-104097

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Commentary on: Considine J, Casey P, Omonaiye O, et al. (2024). Importance of specific vital signs in nurses' recognition and response to deteriorating patients: A scoping review. Journal of Clinical Nursing, 00, 1–18.

Implications for practice and research

There is a need to develop training and protocols that will enhance nurse’s documentation and utilisation of vital signs in clinical decision-making and patient care.

To further guide the creation of training curricula and standards, future studies should examine how nurses prioritise and make decisions about vital sign assessments and their use in patient care.

Vital signs are essential markers of a patient’s physiological state, and these include heart rate, temperature, blood pressure, oxygen saturation, respiration rate and level of consciousness. Consequently, accurate assessment, documentation and interpretation of these markers are vital for …

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Funding The authors have not declared a specific grant for this research from any funding agency in the public, commercial or not-for-profit sectors.

Competing interests None declared.

Provenance and peer review Commissioned; internally peer reviewed.

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Postpartum Remote Blood Pressure Monitoring—When Control Is of the Essence

1 Northwestern University Feinberg School of Medicine, Chicago, Illinois
2 Associate Editor and Web Editor, JAMA Cardiology
Original Investigation Postpartum Ambulatory Blood Pressure and New-Onset Hypertensive Disorders of Pregnancy Alisse Hauspurg, MD, MS; Kripa Venkatakrishnan, MPH; Latima Collins, MD; Malamo Countouris, MD, MS; Jacob Larkin, MD; Beth Quinn, RN; Nuzhat Kabir, BA; Janet Catov, PhD; Lara Lemon, PhD, PharmD; Hyagriv Simhan, MD JAMA Cardiology

New-onset hypertensive disorders of pregnancy (HDP), which include preeclampsia, eclampsia, and gestational hypertension, complicate nearly 1 in 7 pregnancies annually. 1 HDPs are increasing in frequency and are associated with significantly higher risk of adverse maternal and neonatal outcomes in the peripartum period. In addition, there is growing recognition that more intensive prevention measures may be warranted for individuals who experience HDP, given the higher lifetime risk of cardiovascular disease following a pregnancy complicated by HDP. However, many gaps in our understanding and management of HDP remain.

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Biomedicines

Blood Pressure Regulation Evolved from Basic Homeostatic Components

Alon botzer.

1 The Mina & Everard Goodman Faculty of Life Sciences, Bar-Ilan University, Ramat Gan 5290002, Israel; [email protected]

Yoram Finkelstein

2 Neurology and Toxicology Service and Unit, Shaare Zedek Medical Center, Jerusalem 9103102, Israel; [email protected]

Associated Data

Data supporting reported results of this study can be found in publicly archived datasets as specified in links throughout the manuscript.

Blood pressure (BP) is determined by several physiological factors that are regulated by a range of complex neural, endocrine, and paracrine mechanisms. This study examined a collection of 198 human genes related to BP regulation, in the biological processes and functional prisms, as well as gene expression in organs and tissues. This was made in conjunction with an orthology analysis performed in 19 target organisms along the phylogenetic tree. We have demonstrated that transport and signaling, as well as homeostasis in general, are the most prevalent biological processes associated with BP gene orthologs across the examined species. We showed that these genes and their orthologs are expressed primarily in the kidney and adrenals of complex organisms (e.g., high order vertebrates) and in the nervous system of low complexity organisms (e.g., flies, nematodes). Furthermore, we have determined that basic functions such as ion transport are ancient and appear in all organisms, while more complex regulatory functions, such as control of extracellular volume emerged in high order organisms. Thus, we conclude that the complex system of BP regulation evolved from simpler components that were utilized to maintain specific homeostatic functions that play key roles in existence and survival of organisms.

1. Introduction

The multifactorial nature of BP regulation involves many genes with a widespread distribution across numerous cellular subsystems, posing significant challenges in the effort to decipher its complex mechanisms [ 1 ]. Here we implement a comparative approach to review the phylogenetic history of the BP system via an analysis of BP associated genes and their orthologs in 19 organisms, enabling us to gain an evolutionary perspective of the development of the system.

Current evidence proposes that the blood vascular system initially emerged in an ancestor of the tripoblasts over 600 million years ago, as a means to withstand the time-distance constraints of diffusion [ 2 ]. This has advanced over the course of evolution and expanded to a more complex “machinery” to support the functional requirements of high order organisms.

We suggest that the most fundamental organismal function of this machinery is to preserve the internal milieu, namely, to maintain a stable internal environment concerning temperature, electrolytes and water concentrations, as external conditions perpetually change. Internal environment, or “milieu intérieur” is a concept formulated by Claude Bernard, postulating that “the stability of the internal environment (the milieu intérieur) is the condition for the free and independent life”. This is the fundamental principle of homeostasis, a term coined later by Walter Bradford Cannon.

Claude Bernard also stated: “The constancy of the environment presupposes a perfection of the organism such that external variations are at every instant compensated and brought into balance. In consequence, far from being indifferent to the external world, the higher animal is on the contrary in a close and wise relation with it, so that its equilibrium results from a continuous and delicate compensation established as if the most sensitive of balances” [ 3 ].

This work has utilized bioinformatic tools and data mining techniques to investigate the BP system and elucidate the major homeostatic roles it played in the physiology of the corresponding organisms. In fact, we went back, tracing the evolution of genes that are involved in human BP regulation.

2. Materials and Methods

2.1. bp genes, orthologous proteins and target organism selection.

This study investigated a set of 198 genes associated with the BP regulation system. These genes were obtained and identified by means of bioinformatic analyses performed previously by Botzer et al. [ 4 ]. A set of orthologous proteins pertaining to these genes, from 19 organisms (see Figure 1 ) were obtained from two different sources—STRING and InParanoid.

An external file that holds a picture, illustration, etc.
Object name is biomedicines-09-00469-g001a.jpg

Heatmap displays the hierarchical clustering of similarity percentage scores between human BP genes (vertical axis) and their orthologs in 19 organisms (horizontal axis). Green color denotes the more conserved genes across the 19 organisms, aligned at the top of the map (see conservation scale arrow to the right of map). A phylogenetic tree describing the developmental order is placed above the map.

STRING—Search Tool for the Retrieval of Interacting Genes/Proteins, ( http://string-db.org/ (accessed on May 2017)) is a meta-resource that aggregates most of the available information on protein–protein associations and includes both direct physical interactions and protein interactions derived from literature. Since version 9.1, it contains pre-computed orthology relations imported from the eggNOG database [ 5 ]. eggnog—evolutionary genealogy of genes: Non-supervised Orthologous Groups, ( http://eggnogdb.embl.de (accessed on May 2017)) is a public resource that provides Orthologous Groups (OG’s) of proteins at different taxonomic levels. It provides pairwise orthology relationships within OG’s based on analysis of phylogenetic trees. Protein sequences from the selected organisms were extracted and used to compute an all-against-all pair-wise similarity matrix. The comparison uses Smith-Waterman alignments and computational adjustments of the scores, as in BLAST, to prevent spurious hits between low-complexity sequence regions [ 6 ]. InParanoid ( http://InParanoid.sbc.su.se (accessed on February 2018))—gathers proteomes of completely sequenced eukaryotic species and calculates pairwise ortholog relationships among them. This tool implements a two-pass BLAST approach that makes use of high-precision compositional score matrix adjustment, but avoids the alignment truncation that sometimes follows [ 7 ]. Both tools demonstrated similar results, but we decided to pursue analyses with data retrieved from STRING, which included a more comprehensive and updated coverage.

We then composed an organism-to-protein similarity map, consisting of similarity scores between the 198 human BP protein sequences and their ortholog proteins in the 19 target organisms, as obtained from STRING. This map was produced by calculation of pairwise sequence alignment, using EMBOSS Needle Global Alignment tool ( https://www.ebi.ac.uk/Tools/psa/emboss_needle/ (accessed on February 2018)). This tool creates an optimal global alignment of two sequences using the Needleman-Wunsch algorithm, returning a value representing the percent of similarity between sequences, enabling homology to be inferred and the evolutionary relationship between the sequences studied [ 8 ].

Target organism selection was made with the intention to create a span of a wide variety of complexities—starting with the multicellular organism T. adhaerens as the simplest, going through flies, nematodes, fish, amphibians and eventually complex organisms as primates and other mammals (see Figure 1 for a complete list of organisms). We gave emphasis to well-researched model organisms, displaying sufficient and reliable orthology data, as well as extended annotations derived from established biological and genetic knowledge.

2.2. Creation of a Similarity Map and Hierarchical Clustering

The organism-to-protein similarity map enabled us to implement a two-way hierarchical clustering on the similarity matrix scores, also known as hierarchical cluster analysis.

Hierarchical clustering is an algorithm that recursively merges objects based on their pair-wise distance. Neighboring objects are merged first, while objects farthest apart are merged last. The ultimate result is a set of clusters, where each cluster is distinct from each other cluster, and the objects within each cluster are considerably similar to each other. The main output of hierarchical clustering is a dendrogram, which shows the hierarchical relationship between the clusters. This calculation provided us with clusters of organisms on one axis, and of BP proteins in the other axis, suggesting many interesting conclusions relating to the evolutionary order by which the circulatory system has evolved. Hierarchical clustering was performed using the Broad Institute Morpheus tool ( https://software.broadinstitute.org/morpheus/ (accessed on May 2018)), implementing Euclidian distance metric and the Complete linkage method on both axes, emphasizing the maximum of the between-cluster dissimilarities [ 9 ].

2.3. Functional and Tissue Expression Enrichment Analyses

For a detailed in-depth analysis, we chose five organisms that essentially reflect the entire span of complexities of the 19 organisms that appear in the heatmap— Homo sapiens , Mus musculus , Danio rerio , Drosophila melanogaster , and C. elegans .

For each organism, we investigated the resulting clusters of orthologous proteins that were obtained from the hierarchical cluster analysis. These analyses consisted of functional GO term annotations (biological processes) as well as organ/tissue expression enrichment patterns. This was carried out by a set of tools, some of which specialize in human and mouse data, while others focus on other organisms. Table 1 describes the list of the tools we utilized.

Tissue enrichment and functional annotation tools utilized in this work.

Tool	Link to URL	Content
GeneAnalytics	(accessed on February 2018)	Expression-based matching algorithm, provides gene annotations and enrichment in each specific tissue or organ in human or mouse.
GeneOntology	geneontology.org/ (accessed on February 2018)	Provides a computational representation regarding the functional enrichment of genes (proteins produced by genes) from a variety of organisms from human to bacteria.
g:Profiler	(accessed on October 2018)	Finds biological categories enriched in gene lists, functionality, conversions between gene identifiers and mappings to their orthologs.
TissueEnrich	(accessed on October 2018)	Defines tissue-specific genes using RNA-Seq data from the Human Protein Atlas, GTEx, and mouse ENCODE.
Bgee	(accessed on November 2018)	A database used to retrieve and compare gene expression patterns in multiple animal species.
TSEA	(accessed on October 2018)	Tissue specific expression analysis for human and mouse.
MouseMine	(accessed on November 2018)	Provides queries for anatomy and gene ontology enrichments as well as other analyses for mouse.
ZebrafishMine	(accessed on November 2018)	Searches for zebrafish related biological data including genes, proteins, tissues, and more.
ZEOGS	(accessed on November 2018)	Predicts sites of preferential expression of zebrafish gene sets.
FlyMine	(accessed on November 2018)	Integrates many types of data for drosophila and other organisms. runs flexible queries for genes, proteins, ontology terms, and tissue enrichments.
FlyBase	(accessed on December 2018)	Curates and organizes a diverse array of genetic, molecular, genomic, and developmental information in drosophila.
WormBase	(accessed on December 2018)	Provides information concerning the genetics, genomics, and biology of and related nematodes.
WormExp	(accessed on December 2018)	Integrates all published expression data for , runs flexible queries for gene enrichment analyses on selected gene sets.

GO term enrichment tools (primarily GeneOntology) are used to evaluate characteristics of sets of genes by comparing the frequency of GO terms in the sample gene set with the frequency of the same set of GO terms in a reference set, usually a whole genome. The tools apply the binomial test to identify over or under-represented terms in the sample gene set compared to the reference genome set. The default parameters also apply a Bonferroni correction for multiple comparisons. A similar principle is implemented in the tissue enrichment analyses tools utilized for the different organisms, as specified in Figure 2 . Since GO is roughly hierarchical, with “child” terms being more specialized than their “parent” terms, we were compelled to elect the terms in the 4–5 orders of the hierarchy in each cluster-species, in order to obtain broad definitions that enable comparison between the vast span of organisms in the analysis. As a control, the same GO term functional analysis was performed 30 times on randomly selected sets of 200 genes. This random analysis has not yielded any significant enrichment results, emphasizing the validity of the results for the set of blood pressure genes.

An external file that holds a picture, illustration, etc.
Object name is biomedicines-09-00469-g002.jpg

Demonstrates a summary of functional analysis results overlaid on heatmap of Figure 1 . In each box, results pertain to the enriched biological processes for the respective genes-organisms of the cluster. For ease of interpretation, the colored text represents biological process families, reflecting their distribution throughout the map. For full functional analysis results please refer to Supplementary Table S1 .

The heatmap representing the results of the two-way clustered similarity map is presented in Figure 1 . This map has yielded three clusters in the organism axis (columns I to III) and four clusters in the gene axis (rows I to IV).

The order by which the organism axis has aligned as a result of the clustering process is consistent with the natural known developmental order: (1) column I—high complexity mammals—from Pan troglodytes to Equus caballus , (2) column II—medium complexity—from O. anatinus to Danio rerio , (3) column III—low complexity— B. floridae to T. adhaerens . This order, presented in Figure 1 as a phylogenetic tree, is consistent with the developmental order of the blood circulatory mechanism in respect to the affiliated genes; 4—chamber heart system in high-order mammals and avians, 3 and 2—chamber heart in fish and amphibians, diffusion and hemolymph-based systems in insects and simple multi-cellular organisms.

The gene axis was aligned in four clusters, highlighting the more conserved genes across the 19 organisms at the top of the map (row I). The least conserved genes are shown at the bottom of the map (row IV), depicting a majority of zero value similarity scores, due to absence of orthologues genes in low complexity organisms. It is also amenable to discern that row I harbors genes associated with more basal functions, as ion transport, which is assumed to be ancient, hence appears in all organisms; while genes that are linked to a more complex regulatory functions, as control of extracellular volume or endothelial vasoconstriction appear in row IV, hence emerge in more recent organisms only.

Functional gene ontology (GO) term annotation (a statement regarding the function of genes) analysis demonstrates that homeostasis is the most prevalent biological process across most heatmap clusters. Transport processes are significant in row I, while blood circulation and vasculature structure are prevalent in columns I and II. Signaling processes appear most in row IV of columns I and II, rows I—III of columns II and III. Response to stimulus is mainly displayed in column II and slightly in columns I and III. Figure 2 demonstrates a summary of the functional analysis results for the various organisms investigated, displaying the enriched biological processes for each cluster. For full functional analysis results please refer to Supplementary Table S1 .

Tissue and organ expression enrichment analyses reveal that by and large genes in column I clusters are abundant in the kidney and somewhat in the adrenal gland, pancreas, and liver. In column II, gene expression is evident mainly in the kidney and nervous system, and slightly in the pancreas. This expression pattern changes significantly for column III, where gene expression is clearly noticeable exclusively in nervous system tissues. Figure 3 demonstrates a summary of tissue expression for the various organisms investigated. For full expression analysis results please refer to Supplementary Table S2 . Altogether, the functional and expression results of the analysis in zebrafish display the summation of results of analyses in the higher and lower order species. This reflects the unique spot of zebrafish in ontogeny that well supports the rationale to exploit zebrafish as a model organism in biological research [ 10 ].

An external file that holds a picture, illustration, etc.
Object name is biomedicines-09-00469-g003.jpg

Demonstrates a summary of expression analysis results overlaid on heatmap of Figure 1 . In each box, results pertain to the enriched organ/tissue expression for the respective genes-organisms of the cluster. For ease of interpretation, colored text represents tissue/organ types, reflecting their distribution throughout the map. For full functional analysis results please refer to Supplementary Table S2 .

4. Discussion

Regulation of BP is a complex systemic mechanism due to numerous physiological elements, involving: pressure-volume regulation, which is tightly related to pressure-natriuresis [ 11 ], rapid control of vessel resistance by the central nervous system (CNS), specifically modulated by both sympathetic and parasympathetic nervous system—the two branches of the autonomic nervous system (ANS) [ 12 ], neurotransmitters (e.g., noradrenaline (NA), adrenaline) and hormones (e.g., angiotensin) as well as the long-term activity of the renin-angiotensin-aldosterone-system (RAAS). These mechanisms are efficient at maintaining BP within a normal physiological range at Systolic BP of <120 mmHg and Diastolic BP of <80 mmHg [ 13 ].

This study examined a collection of 198 human genes related to BP regulation in the biological processes and functional prisms, as well as gene expression in organ and tissue perspective. In this context, it is unavoidable that the question of homeostasis will arise. This observation, in conjunction with the orthology analysis we performed in 19 target organisms along the phylogenetic tree, evokes numerous interesting conclusions and further questions.

Homeostasis sustains the “internal milieu” of an organism’s cells, tissues, organs, and whole body, within limits that are compatible with survival. This internal milieu reflects the composition of the primordial ocean, first and foremost its electrolyte and water balance [ 14 , 15 ]. Homeostasis in homeothermic land-dwelling organisms is profoundly developed since their fluid balance, blood pH, oxygen tension and particularly their body temperature must be maintained within tight boundaries amid all conditions of their life cycle and in all their habitats. Homeostasis will tend to stabilize BP, maintaining it at a steady state.

The term stress defines any stimulus or succession of stimuli of such magnitude as to tend to disrupt the homeostasis of the organism. When mechanisms of adjustment fail or become incoordinate or disproportionate, the stress should be referred to as an insult. The response of the organism to stress depends largely on biochemical and physiological homeostatic mechanisms [ 16 ]. One of the most important mechanisms for maintaining homeostasis is the negative feedback system; if a physiological disturbance occurs, the body will counteract the disturbance via a negative feedback mechanism and attempt to return the body to its normal steady state.

The more complex the organism, the more complex its adaptation to the ever-changing environmental conditions. Biological systems may undergo functional plasticity in the effort to adapt. This is the mainstay of evolutionary progression [ 17 ].

The results of this study may elucidate the diversity of the modulating response mechanisms during phylogenesis: from the response of primitive organisms to physical stimuli (such as osmotic or heat stressors) to the complex endocrine and neurobehavioral stress response to both physical, mental, and cognitive challenges in human.

4.1. The Function of the CNS in the Maintenance of Homeostasis

The CNS is the organ that orchestrates the response to stressful stimuli through the autonomic, neuroendocrine, and immune systems, as well as through neurobehavioral responses such as fight-or-flight response. Adaptation to stress and to changing environmental conditions involves neural and humoral mediators: neurotransmitters and neuromodulators, hormones and cytokines of the immune system. The goal of this adaptation is to maintain homeostasis and promote survival of the organism [ 18 ].

The stress responses include primarily the activation of the mesolimbic system, the hypothalamo-pituitary-adrenal (HPA) axis and the ANS. The dopaminergic (DA-ergic) activity in the septo-hippocampus is a mainstay of the mesolimbic stress response, due to its close relationship with the hypothalamus (autonomic control), midbrain reticular formation (arousal) and multiple sensory pathways (attention). A DA-ergic pathway originates in the ventro-medial tegmentum of the midbrain and projects to the lateral septal nuclei with abundant indirect interconnections with the cholinergic nucleus of the medial septum, forming a final common pathway of the neural, psychic and endocrine stress response. Indeed, time honored studies corroborate the major importance of catecholamines in the ANS and of the glucocorticoids (GCs) in the adrenal cortex, as well as the CNS septo-hippocampal DA-ergic and cholinergic systems in the stress response. These complex mechanisms of adaptation are critical in the control of homeostasis [ 17 , 19 ]. Additionally, the mesolimbic pathway transports dopamine (DA) from the ventro-medial tegmentum to the nucleus accumbens and amygdala. The nucleus accumbens is found in the ventral medial portion of the striatum and is believed to play a role in reward, desire, and the placebo effect. The amygdala is a key component of the limbic system and is associated with emotion. Unabated DA-ergic stimulation (the absence of negative feedback) has been postulated to be associated with disorders such as binge eating or drug addiction [ 20 , 21 ].

The neuroendocrine system integrates the functions of two major control systems: the nervous system and the endocrine system. Thus, both internal and external fluctuations are monitored by the nervous sense organs, the neural signals of which are processed by the CNS and converted to endocrine outputs.

Furthermore, associated with the neuroendocrine system are distinct circumventricular fenestrations in the blood-brain barrier, mainly the chemoreceptor trigger zone (CTZ) in the area postrema of the medulla oblongata. The CTZ allows hormones and neurotransmitters to enter directly from the blood to the cerebrospinal fluid (CSF), hence enabling the feedback mechanisms with the neurosecretory system itself.

The hypothalamus plays a principal role in the neuroendocrine control system, which together with its connections to the pituitary gland comprise the hypothalamic pituitary system—a neurosecretory system that produces releasing hormones (or releasing factors), emitting them to the pituitary gland. Important pituitary hormones are the adrenocorticotropic hormone (ACTH), which controls the adrenal cortex as well as growth hormone-inhibiting hormone (GHIH), which regulates the endocrine system and affects neurotransmission. Moreover, upper neurons of the ANS are located in the hypothalamus and control the adrenal medulla, an additional crucial endocrine gland. These roles of the CNS in the maintenance of homeostasis are dynamic, empowering the organism to function efficiently.

As seen in the Results section and in Figure 3 , the adrenal gland and pancreas are strongly pronounced in human and mouse in rows II–IV, while the CNS and brain manifest rows I–III in fruitfly and roundworm. Interestingly, in the zebrafish gene enrichment in the CNS and the brain are prominent in all clusters, whereas the pancreas appears in rows III–IV, emphasizing the clear homology of these anatomic properties among the various species. This may suggest that organs that are enriched in expression of highly conserved genes across species reflect shared ancestry.

4.2. The Role of the Adrenal Glands

The adrenal gland comprises two endocrine tissues that differ in function and embryonal origin: The adrenal cortex, a steroidogenic tissue that evolved from the coelomic epithelium; and the adrenal medulla, a catecholamine producing tissue composed of chromaffin cells. The medulla derived from the neuroectoderm, which migrated to the adrenal gland blastema.

The secretion of the adrenal cortex hormones is controlled by ACTH in a closed loop feedback system. It produces numerous steroids secreted in widely varying amounts; these are classified as mineralocorticoids (MCs) and GCs including sex steroids. The main MC is aldosterone, which is the most potent steroid affecting active transport of sodium ions across membranes and thus is crucially important in maintaining electrolyte balance and as a result, in BP homeostasis. Cortisol is the principal GC in human and most mammalian primates and is quantitatively the main secretory product of the adrenal cortex.

The medulla is basically a modified sympathetic ganglion that converts tyrosine into DA, NA, and adrenaline, which are secreted in postsynaptic response to direct neural inputs. These inputs originate in the CNS (cortical cerebral areas) and are transmitted to the adrenal medulla via cholinergic preganglionic sympathetic neurons [ 22 ].

As noted, the primordium of the adrenal cortex coincides with the mesonephric blastema. It develops within the kidney in fish and on the kidney in amphibians. The kidneys of both fish and amphibians are of mesonephric origin [ 23 ].

In fish, chromaffin and cortical adrenal cells are not placed in proximity, but rather intermingle. The interrenal cells, that correspond to the adrenal cortex in mammals, from which GCs and MCs are secreted, do not encapsulate the chromaffin cells, which are the functional equivalent of the adrenal medulla. NA is the main catecholamine stored by the chromaffin cells, albeit variable quantities of adrenaline can also be present.

Amphibians show a closer relationship between cortical and chromaffin cells. The adrenals of amphibians lay on the ventral side of the kidneys, as the mesonephros—the analogue of the mammalian kidney, preserving the contact between the two organs during ontogenesis [ 24 ].

In mammals, where the evolution of the excretory system leads to the development of the metanephros, adrenal cortical cells completely surround the chromaffin cell mass—namely the medulla—and are grouped together to form the adrenal gland. Traces for this can be seen in our detailed expression analysis results ( Supplementary Table S2 ), where row I–II are expressed in the adrenal glands of mammals, and in chromaffin cells and mesonephros of the zebrafish.

4.3. Nervous Regulation of the Cardiovascular System

The circulation is regulated partly by intrinsic and local mechanisms in each tissue and prominently by the nervous system, the action of which is extremely rapid and comprehensive. All the vascularized tissues in vertebrates are supplied with sympathetic nerve fibers. Sympathetic stimulation to the arterioles increases the resistance, thus changing the blood flow through the tissues. Sympathetic stimulation of the larger vessels decreases their blood volume. In a similar manner, cardiac output and BP are remarkably increased by increased sympathetic activity. Both heart rate and stroke volume (the two components of cardiac output) alongside vascular resistance are the main determinants of BP.

The internal environment is monitored by sense organs and organelles: chemoreceptors sensitive to the partial oxygen pressure in the arterial blood, mechanoreceptors sensitive to blood pressure, and chemoreceptors within the central nervous system itself sensitive to hydrogen ion concentration or to various hormones. The input from the sense organs and organelles is transmitted to the CNS, in which it is processed and from which the appropriate outputs are sent to the effectors—muscles and glands. Above all, the vasomotor center (VMC)—in fact a network of neurons within the medulla oblongata, regulates BP and other homeostatic functions by a dual action: vasoconstriction and vasodilation.

Tonic adrenergic discharge to the arterioles sustains arterial pressure, while fluctuations in this tonic discharge constitute the mechanism affecting the feedback regulation of BP carried out by the carotid sinus (baroreceptor) and the carotid body (chemoreceptor that modulates the cardiovascular and respiratory systems via sympathetic tone). The effects of this discharge are of substantial importance in the preparation of the organism to endure emergency.

4.4. Catecholamines and BP Homeostasis

Dopamine (DA), noradrenaline (NA), and adrenaline (known as catecholamines) are physiologically active molecules, acting both as hormones and neurotransmitters, crucial for the sustainment of homeostasis via the ANS. This work considered DA receptor genes (DRs), (DR1-like subtype— DRD1 , DRD5 , and DR2-like— DRD2 , DRD3 , DRD4 ) and adrenergic receptor genes (ARs), (adrenoceptors type alpha— ADRA1A , ADRA1B , ADRA1D , ADRA2A , ADRA2B , ADRA2C , and beta— ADRB1 , ADRB2 , ADRB3 ) appearing in rows II–III, all which play key physiological roles in the nervous and cardiovascular systems, specifically in BP regulation.

Almost all vasomotor nerves are adrenergic. The alpha-adrenoceptors are preeminent in innervation of vascular smooth muscles and also in the lower urinary tract. In the myocardium, beta1-adrenoceptors predominate and stimulate the rate and contractility. In both cases, neurotransmitter NA exerts its physiologic effects by binding to alpha ARs, whereas adrenaline reacts with both alpha and beta ARs, causing vasoconstriction and vasodilation, respectively. Generally, it is the alpha1-AR subtype, which is situated postsynaptically in smooth muscles, that causes vasoconstriction of blood vessels when stimulated. Sympathetic overactivity in hypertension results in an excess stimulation of postsynaptic alpha1 ARs [ 25 ].

DA, a major neurotransmitter in both CNS and PNS holds an essential function in the homeostatic control of BP, by regulation of vascular smooth muscle contraction, epithelial sodium transport, and reactive oxygen species (ROS) production. It is considered a major player in homeostatic regulation of extra-cellular fluid (ECF) volume and BP due to the vast effect it induces on renal hemodynamics as well as humoral agents such as catecholamines, aldosterone, renin, vasopressin and endothelin (e.g., DA inhibits NA release and acts as a vasodilator at normal concentrations by activation of D2 receptors; decreases aldosterone secretion via activation of D3 receptors, while significantly enhancing renin secretion by activation of D1 receptors).

DA also adjusts sodium and fluid intake by means of activities within the gastrointestinal tract and CNS, primarily by regulation of the cardiovascular control centers in the brain stem [ 26 ]. Each DA receptor subtype participates in BP regulation by specific mechanisms for the subtype; DRD2 and DRD5 act within the CNS and PNS.

The mesolimbic DA system is implicated in diurnal profiles of the mean BP. A clear dip in the mean BP and heart rate occurs during the resting period (e.g., nocturnal dip in human) [ 27 ]. An increase in arterial BP can be seen during the transition from non-REM to REM sleep, displaying phasic surges throughout REM sleep that derive from the physiological phase of paradoxical sleep. Furthermore, the mesolimbic DA system is involved in the increases in REM-associated BP fluctuations [ 28 ], a homeostatic adaptation to the fluctuating states of the different sleep and arousal phases. Since the mesolimbic DA system surges are involved in REM-associated increases in BP, the homeostatic effect is the result of a greater ability to deal with emotional stress. The pineal gland translates light signals received by the retina to the rest of the body, for example through the synthesis of the hormone melatonin, which is produced and released at night and helps to regulate the body’s metabolic activity during sleep. NA is involved in regulating this synthesis and release of melatonin in the pineal gland. DA through ADRA1B-DRD4 and ADRB1-DRD4 receptor heteromers inhibits the effects of NE, resulting in a decrease in the production and release of melatonin [ 29 ].

Although there are two classes of DA receptors, DR1-like and DR2-like, the natriuretic effect of DA is primarily mediated by DR1-like receptors [ 30 ]. During sodium loading, DR2-like receptors may contribute to the natriuresis [ 31 ]. Of the three DR2-like receptors it is likely that it is the DRD3 receptor that interacts with the DRD1 receptor because it is the major DR2-like receptor expressed in the renal proximal tubule and the thick ascending limb of Henle [ 32 ]. The DRD1 , DRD3 , DRD4 receptors interact with the renin-angiotensin system (RAAS), affecting epithelial transport and control of secretion of multiple humoral agents and their receptors [ 33 ].

From the comparative perspective, our results show a high degree of conservation (>60%) for catecholamines in vertebrate species analyzed, especially in mammals, as well as in invertebrates such as C. elegans , Drosophila melanogaster , and Ciona intestinalis (~45%).

The vertebrate DR1-like receptors are most closely related to the DOP1 group members of C. elegans and Drosophila melanogaster , both responsible for upregulation of intracellular cAMP in the presence of DA. The vertebrate DR2-like receptors share the most homology with the C. elegans CeDOP2 and the Drosophila melanogaster DD2R , sharing a similar response in the decrease of intracellular cAMP levels when treated with DA [ 34 ]. In Drosophila melanogaster , expression patterns of DOP1 (an ortholog of the vertebrate D1-type DA receptors) were observed in mushroom body neurons, subesophageal ganglion, and in unpaired abdominal ganglia [ 35 ], while DD2R is expressed in the larval and adult nervous systems, and in cell groups that include peptidergic neurons [ 36 ]. In C. elegans it was shown that CeDOP1 is expressed in mechanosensory neurons, motor neurons and the ventral nerve cord, as well as sensory support cells, which are glial-like cells that surround the sensilla (simple invertebrate sense organs that may take the form of a hair or bristle) [ 37 ], while CeDOP2 is expressed in DA-nergic neurons, suggesting it may act as an autoreceptor [ 38 ].

4.5. The Kidney’s Role in Maintaining Homeostasis

Notably, genes in clusters of rows I–III are expressed in the kidney of zebrafish, mouse, and human. Their functional analysis demonstrated that homeostasis and transport are the primary biological processes that characterize these clusters, while signaling and stimulus are secondary.

The cells of the kidney contain many specialized ion channels and transporters, which act in concert to regulate volume and ionic concentration by absorption or secretion of ions into the urine [ 39 ]. The ion channels and transporters play essential roles in organelle to whole organism function. These roles range from regulation of cell volume, membrane excitability and pH, to control of systemic salt and water balance and behavior [ 40 ].

Our work specifically relates to several prominent gene families—solute carriers (primarily electroneutral potassium chloride cotransporters, glucose transporters, bicarbonate transporter proteins), calcium voltage-gated channels, sodium channels, epithelial chloride voltage-gated channels, potassium voltage-gated channels, DRs, and ARs, which are conserved across most species examined (similarity > 50%).

It is especially important to underscore the largest gene family we analyzed in this work (21 members)—Solute Carriers (SLCs), which are responsible for the regulation of various types of substances over the cell membrane. They typically rely on an ion gradient over the cell membrane as a mechanism for transportation [ 41 ]. Interestingly, all SLCs that are found in human are also found in C. elegans and Drosophila melanogaster and even some in T. adhaerens ( SLC8A2, SLC12A3, SLC12A4, SLC4A4, SLC6A2 >50% similarity), indicating that this superfamily is ancient and was present before the divergence of Bilateria (animals with bilateral symmetry).

Another noteworthy gene family we analyzed is the voltage-gated ion channel superfamily, comprising calcium, potassium, and sodium ion channels. As can be seen from the heatmap in Figure 1 , KCNJ1, KCNJ11, KCNJ6 are well conserved (>45%) in all 19 species, including T. adhaerens , along with CACNA1C, CACNA1H, CACNA1A, CACNA2D1 (>40%) in all 19 species. Yu et al. suggested that this family has evolved from a bacterial ancestor channel and accumulated regulatory domains for ligand binding in the course of evolution. The resulting signaling mechanisms control most aspects of cell physiology, complex processes in the brain and movements of muscles, all of which allowed the development of complex multicellular organisms [ 42 ].

Multicellular organisms control their internal environment by altering either the electrolytes concentration (osmolality) or the extracellular volume, maintaining the acid-base balance. In mammals, the main site of this complex regulation is the kidney.

The role of human kidney is maintaining the fragile equilibrium within the internal milieu, namely the ECF and the intra-cellular fluid (ICF). From the evolutionary point of view, the human kidney evolved from primitive mechanisms of the ionic and osmotic homeostasis in fish. The data presented in this work provide evidence that the genes that are implicated in these mechanisms appear in fish, but not in earlier stages of phylogeny.

The ion composition of the ECF is essentially identical in all animal species (including fish, amphibians, reptiles, and mammals) where the kidneys are utilized to regulate homeostasis [ 15 ]. Since salt concentration of the ocean increased over time, saltwater fish began to contain hypo-osmolar internal milieu and constantly exhausted water to the hyperosmolar environment. To endure this challenge, saltwater fish consume considerable amounts of water [ 43 ]; hence the acquired capability of fish to actively preserve the internal milieu is remarkable.

The zebrafish pronephros, which consists of two nephrons with glomeruli, contains two tubules that are analogous in many ways to the segments of the mammalian nephron [ 44 ]. The proximal straight segment of this nephric tubule displays a brush border-like columnar epithelial cells [ 45 ]. This segment plays a crucial role in reabsorption of electrolytes and small molecules through a glomerular filtration barrier [ 46 ]. This is the physiological principle that underlies the mammalian renal function.

Kidney functions are achieved both independently and in conjunction with other organs, particularly the endocrine system via various endocrine hormones, including, among others: renin ( REN ), angiotensin II, aldosterone, antidiuretic hormone ( ADH ), and two atrial natriuretic peptides ( NPPA , NPPB ) which are evolutionarily conserved. These natriuretic peptide hormones are secreted by atrial myocytes in response to stretch, angiotensin II stimulation, endothelin, and sympathetic (beta adrenergic) stimulation [ 47 ].

Blocking ion channels is an important part of anti-hypertensive pharmacotherapy. This is exemplified by the commonly used drugs—nifedipine, amlodipine, diltiazem, and verapamil which block the voltage-gated calcium channels of vascular smooth muscle cells, thus lowering BP; and amiloride that blocks the epithelial sodium channels at the distal convoluted tubule and the collecting duct, thereby inhibiting sodium-potassium exchange, while lowering BP independent of aldosterone [ 48 , 49 ].

4.6. Sensing the Environment in Order to Maintain Homeostatic Balance

An extensive network of sensory organs and organelles play an important role in maintaining homeostatic balance and monitoring the internal environment. These include: mechanoreceptors sensitive to BP, chemoreceptors that react to the partial oxygen pressure in the arterial blood and chemoreceptors within the CNS, which are sensitive to pH and to numerous hormones. Ion channels in the hypothalamus gauge the ECF osmolality and sodium concentration. Baroreceptors situated in numerous circulatory beds along with ion channels and various receptors within the distal tubule in the kidney nephron, regulate blood volume. The input from the sense organs and organelles is transmitted for processing to the CNS, from which appropriate outputs are forwarded to the effector tissues—muscles and glands. The volume effectors are the renin–angiotensin–aldosterone system (RAAS), alongside sympathetic nerve activation (SNA) as well as glomerular filtration rate and physical gradients along the nephron. Homeostatic control mechanisms maintain the balance between fluid gain and fluid loss. Body water homeostasis is mainly regulated through fluid ingestion. Sensory osmoreceptors, found primarily in the hypothalamus, detect changes in plasma osmolarity and contribute to fluid-balance regulation in the body. If the body is fluid deficient, increased plasma osmolarity is sensed by the osmoreceptors. When osmoreceptors detect high plasma osmolarity (a sign of low blood volume/dehydration), they send signals to the hypothalamus, which creates the sensation of thirst. This result also triggers an increase in ADH secretion, causing fluid retention by the kidneys and urine output to be reduced. Macula densa cells in the nephron’s ascending loop of Henle are another type of osmoreceptor. If the macula densa is stimulated by high osmolarity, the juxtaglomerular apparatus (JGA) releases renin into the bloodstream. The subsequent production of angiotensin II acts on the hypothalamus to cause thirst. Angiotensin II causes vasoconstriction and aldosterone release. Aldosterone increases expression of the nephron’s ATPase pumps resulting in increased water reabsorption through sodium cotransport [ 50 ].

4.7. RAAS Evolution

The RAAS is the primary volume-regulating pathway in mammals, acting as the central controller of blood pressure homeostasis in humans. The renin-angiotensin-aldosterone system emerged approximately 450 million years ago, in the Paleozoic era, as marine organisms moved to the land and endured a strong selection pressure to conserve salt and maintain volume homeostasis, which were crucial for survival [ 51 ]. In this work we have examined the sequence homologs for 20 human genes associated with RAAS pathway in 19 model organisms. Interestingly, homologs for all genes were present in all species from Danio rerio (Zebrafish) up to Pan troglodytes (Chimpanzee), with lowest similarity score of 46% for angiotensinogen ( AGT ). Since our data do not provide evidence for the presence of AGT homologs prior to Danio rerio , and due to its central role in the RAAS, this could indicate that the pathway emerged approximately with the appearance of zebrafish. This observation, in conjunction with the fact that zebrafish is the taxon with the most primitive juxtaglomerular apparatus [ 52 ], agrees with the physiological evidence regarding its emergence in bony fishes [ 53 ]. Our work reveals several orthologs for ACE and ACE2 from B. floridae to T. adhaerens , representing primitive chordates, as well as insects and multicellular organisms, which lack most RAAS components and are characterized by an open circulatory system. No ortholog sequence was found in the C. elegans , a fact that challenges the advent and initial roles of the enzyme. Recent genomic data revealed the presence of orthologs in yet additional remote phyla, as placozoa and proteobacteria, suggesting that it emerged early in evolution. Thus, by and large, ACE exists from bacteria up to mammals, exhibiting conserved features such as structure, as well as molecular and biochemical characteristics. In higher order organisms, ACE exerts its effect mainly in the capillaries of the lungs, whereas the evolution of the respiratory system was a key step in the transition of the animal world from marine life to land habitation. Characteristics of mammalian ACE could therefore be the outcome of an extended course of evolutionary specialization of an ancient protease, the functions of which are not yet known [ 54 ].

Adrenal steroids, both MCs and GCs, influence almost all aspects of vertebrate development, as well as regulation of an extensive selection of physiological processes, including development, differentiation, reproduction, and homeostasis [ 24 ]. Their receptors belong to the nuclear receptor super-family of proteins, which are ligand-activated transcription factors, implicated in steroid activity in a myriad of physiological, morphological, and behavioral processes [ 55 ].

GRs and MRs encoded in human by the NR3C1 and NR3C2 genes respectively, are representatives of the two principal functional families of corticosteroid receptors in vertebrates. These have not been found in invertebrates, as confirmed in our work, where orthologs for NR3C1 and NR3C2 appear first only in Danio rerio with similarity >63%. The MR and the GR are known to have descended from the early corticosteroid receptor [ 56 ], which first appeared in jawless fish, at the base of the vertebrate lineage, while distinct MR first appeared in cartilaginous fish [ 57 ]. Interestingly, the ancient GR evolved through duplication, to develop into a GR due to two gene mutations [ 58 ]. It is hypothesized that this evolutionary process would have alleviated the difficulty to adapt to blood pressure elevation caused by increased gravitational effects of land habitation [ 59 ].

5. Conclusions

To conclude this study, it appears that the genes that are involved in BP regulation are primarily implicated in mechanisms associated with the maintenance of homeostasis. Evidence for this can be seen in the conserved genes across the entire range of organisms investigated, performing functions that are notably related to homeostasis, e.g., ion transport, response to stimulus and more, as well as expression patterns in tissues and organs that support homeostatic processes in the respective species.

This work is merely an attempt to cover the broad scope of the evolutionary dissection of the genetic machinery behind BP regulation; nonetheless it highlights the importance of the comparative approach that presupposes that the comprehension of our evolutionary past can highly enlighten our understanding of the genetic background of common disease.

Acknowledgments

Special thanks to John Moult for constructive discussions and a critical perspective. The authors are also indebted to Gil Kotton, Tirza Doniger and Orit Adato for their valuable assistance throughout this work.

Abbreviations

CNS	Central Nervous System
ANS	Autonomous Nervous System
RAAS	Renin Angiotensin Aldosterone System
DA	Dopamine
NA	Noradrenaline
CTZ	Chemoreceptor Trigger Zone
ACTH	Adrenocorticotropic Hormone
GC	Glucocorticoid
GR	Glucocorticoid Receptor
AR	Adrenergic Receptor
ECF	Extracellular Fluid
SLC	Solute Carrier
GO	Gene Ontology

Supplementary Materials

The following are available online at https://www.mdpi.com/article/10.3390/biomedicines9050469/s1 , Table S1: GO term biological processes enrichment per cluster genes and organisms, Table S2: tissue/organ enrichment per cluster genes and organisms.

Author Contributions

Conceptualization, A.B. and R.U.; methodology, A.B. and R.U.; formal analysis, A.B.; investigation, A.B.; resources, R.U.; data curation, A.B.; writing—original draft preparation, A.B.; writing—review and editing, Y.F. and R.U.; visualization, A.B.; supervision, Y.F. and R.U.; project administration, A.B. All authors have read and agreed to the published version of the manuscript.

This research received no external funding.

Institutional Review Board Statement

Not applicable.

Informed Consent Statement

Data availability statement, conflicts of interest.

The authors declare no conflict of interest.

Publisher’s Note: MDPI stays neutral with regard to jurisdictional claims in published maps and institutional affiliations.

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Many factors raise your risk of high blood pressure. You can change some risk factors, such as unhealthy lifestyle habits. A healthy lifestyle can lower your risk for developing high blood pressure.

Other risk factors, such as age, family history and genetics, race and ethnicity, and sex, cannot be changed. But, you can still take steps to reduce your risk of high blood pressure and its complications .

Blood pressure tends to rise with age. Blood vessels naturally thicken and stiffen over time. These changes increase the risk for high blood pressure.

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High blood pressure often runs in families. Much of what we know about high blood pressure has come from genetic studies. Many genes are linked to small increases in high blood pressure risk. Research suggests that as an unborn baby grows in the womb, some DNA changes may also raise the risk for high blood pressure later in life.

Some people have a high sensitivity to salt in their diet, which can play a role in high blood pressure. This can also run in families.

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Lifestyle habits can increase the risk of high blood pressure, including if you:

Eat unhealthy foods often, especially foods that are high in salt and low in potassium. Some people, including Black people, older adults, and people who have chronic kidney disease, diabetes, or metabolic syndrome, are more sensitive to salt in their diet.
Drink too much alcohol or caffeine
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High blood pressure is more common in Black adults than in White, Hispanic, or Asian adults. Compared with other racial or ethnic groups, Black people tend to have higher average blood pressure numbers and get high blood pressure earlier in life. Also , some high blood pressure medicines may not work as well for Black people.

During pregnancy , Black women are more likely than White women to develop preeclampsia . Preeclampsia is a pregnancy disorder that causes sudden high blood pressure and problems with the kidneys and liver.

Men are more likely than women to develop high blood pressure throughout middle age. But in older adults, women are more likely than men to develop high blood pressure.

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Choose heart-healthy foods that are lower in salt (sodium) and are rich in potassium. Fruits and vegetables are high in potassium. For more ways to limit your sodium, visit the DASH Eating Plan page or print out the Tips to Reduce Salt and Sodium handout.
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The evaluation of a nurse-led hypertension management model in an urban community healthcare

A randomized controlled trial.

Editor(s): Ford., Cassandra

a Tangshan Worker's Hospital, Tangshan

b TangShan FuYou BaoJianYuan

c TangShan Chinese Medicine Hospital, Heibei, P.R. China.

∗Correspondence: Jian-Hong Miao, Tangshan Worker's Hospital, No.27, Culture Road, Tangshan, Heibei, P.R. China (e-mail: [email protected] ).

Abbreviations: DBP = diastolic blood pressure, RCT = randomized controlled trial, SBP = systolic blood pressure.

How to cite this article: Miao JH, Wang HS, Liu N. The evaluation of a nurse-led hypertension management model in an urban community healthcare: a randomized controlled trial. Medicine . 2020;99:27(e20967).

Availability of data: Study data will be made available upon request.

The authors have no funding and conflicts of interest to disclose.

The datasets generated during and/or analyzed during the current study are available from the corresponding author on reasonable request.

This is an open access article distributed under the terms of the Creative Commons Attribution-Non Commercial License 4.0 (CCBY-NC), where it is permissible to download, share, remix, transform, and buildup the work provided it is properly cited. The work cannot be used commercially without permission from the journal. http://creativecommons.org/licenses/by-nc/4.0

Background:

Hypertension is a silent disease of the masses with an increasing prevalence and poor control rates. This study aims to establish and test the efficacy of a nurse-led hypertension management model in the community.

Methods:

A single-blind, randomized controlled trial was performed. 156 hypertensive patients with uncontrolled blood pressure were equally and randomly allocated into 2 groups. Patients in the study group received a 12-week period of hypertension management. Blood pressure, self-care behaviors, self-efficacy, and satisfaction were assessed at the start of recruitment, 12 and 16 weeks thereafter.

Results:

After the intervention, blood pressure of patients in the study group had greater improvement in self-care behaviors and a higher level of satisfaction with the hypertensive care compared to the control group (both P < .05).

Conclusions:

The nurse-led hypertension management model is feasible and effective for patients with uncontrolled blood pressure in the community.

1 Introduction

There is an estimated 244.5 million (23.2%) Chinese adults aged ≥18 years who have hypertension, with another 41.3% (estimated 435.3 million) having pre-hypertension based on Chinese guidelines. [1] Among individuals with hypertension, 46.9% were aware of their condition, 40.7% were taking prescribed antihypertensive medications, and 15.3% had controlled hypertension. [1] The prevalence of hypertension in China based on the 2017 ACC/AHA guidelines was twice as high as that based on 2010 Chinese guideline (46.4%), [1] with a prevalence rate increasing by about 10% from 2002 to 2010. [2–4] However, about 15% of hypertension patients in China successfully controlled their blood pressure, which is defined as an average systolic blood pressure (SBP) < 140 mm Hg and an average diastolic blood pressure (DBP) < 90 mm Hg, [1] which is lower than in high-income countries (37%–65%). [5,6]

Doctors and nurses are equally key players in hypertension management. [7–9] A meta-analysis done by Carter et al. [10] showed a 4.8 mm Hg reduction in SBP in hypertensive patients who were following a nurse-led healthcare management. However, the latter has been questioned about its efficacy, [11,12] calling for further evaluation.

Hypertension management at the community level in China is a recent development. Recent studies about the latter had laid a preliminary platform with positive results that needed to be further explored. [13,14]

Randomized controlled trials (RCT) of community-based hypertension interventions [15–17] had been conducted but, due to poor experimental designs and lack of standard operational protocols, they were not reliable results to be considered. Therefore, additional studies were required to reinforce the trend observed, given that most studies about hypertension management in community health centers focused more on doctors than on nurses as leaders empowering the community. [15,16]

This study aimed to test the importance of a nurse-led hypertension management model compared to usual care in community health centers. Efficacy was assessed by analyzing changes in blood pressure and patient reported self-care behaviors, self-efficacy, and satisfaction between groups.

2.1 Ethical consideration

Prior to the recruitment, written informed consent was obtained from each participant. Ethical approval was obtained from our institution's Ethical Board Committee.

2.2.1 Setting and Sample

Participants were randomly allocated into the study group (nurse-led hypertension management model) or the control (usual care) group at a ratio of 1:1. As shown in Table 1 , the 2 groups had equivalent socio-demographic and clinical features.

2.2.2 Inclusion criteria

Participants with a diagnosis of hypertension; with uncontrolled BP (SBP ≥140 mm Hg and/or DBP ≥90 mm Hg at the last 2 clinic visits and at recruitment);≥18 years old; within the service network of the community health center.

2.2.3 Exclusion criteria

Participants who had a diagnosis of secondary hypertension; took medicine that could increase BP; could not communicate or be contacted by phone; had a diagnosis of terminal illness; had co-morbidity in contradiction with the programmed intervention; were pregnant, breastfeeding or planning pregnancy.

Of 687 patients assessed for eligibility, only 156 satisfied the inclusion and exclusion criteria. A total of 31 (19.9%) participants dropped out of the study ( Fig. 1 ). 318 patients did not meet the inclusion criteria while 84 declined their participation. The remaining 129 patients who were not included in the study were those who satisfied the inclusion criteria but followed treatment at other health care facilities. By using intention-to-treat analysis, those who dropped out were also included in data analysis.

The nurse-led hypertension management model was developed from the Chronic Care Model [18,19] and the 4-C Model (comprehensiveness, collaboration, coordination and continuity). [20,21] The nurse-led hypertension management model has adopted 4 components in the Chronic Care Model, [18,19] which is delivery system design, decision support, clinical information system and self-management.

A 36-h pre-intervention training program was conducted in this study to enhance the nurses’ decision-making. [22] The training contents included knowledge and skills for nurse-led hypertension management.

Self-management refers to the self-care behaviors, such as salt intake control, regular engagement in physical activities, home blood pressure monitoring management, and medicine storage, were also included. To emphasize the importance of self-management, a mutually agreed goal and self-care behavioral contract were made after sufficient negotiation.

The trained nurse assisted the patients to understand the importance of self-management, encouraging them to discuss health conditions, plan mutual goals and help patients how to achieve their set goal and perform self-monitoring, by providing and explaining to them relevant information and resources for self-management through illustrated, simple educational booklets. [4,22] During the home visit, the trained nurse would arrange for the general practitioner (a member of the research team) to visit community health center if the patient met the referral criteria.

2.3 Intervention

The intervention in the study was protocol-dependent. The protocol involved home visits, telephone follow-ups and referrals. Previous studies, [4,22,24] the national guidelines for hypertension management [25] and expert consultation were referenced in the protocol development.

Trained nurse, guided by the Omaha System, [23] conducted a 60-minutes home visit to patients within 3 days after recruitment. The patient's knowledge and behavior were assessed, as well as the status of their identified health problems. Based on the results, the trained nurses performed relevant interventions that included teaching/guidance/counseling in lifestyle modification changes, treatment and procedures such as timing and dosage adjustment as well as drug interactions and physical activity, and case management. [23]

Suggested non-pharmacological behaviors, including smoking cessation, alcohol restriction, salt restriction, regular physical activity, and home blood pressure monitoring were evaluated for the last 4 weeks. Self-efficacy was measured using the Chinese version of the Short-Form Chronic Disease Self-Efficacy Scale, [26] which included a rating of the patient's confidence in general disease and symptom management. The scale for each item ranged from 1 (not at all confident) to 10 (totally confident).

When the patient reported uncontrolled blood pressure, a trained nurse would assess his adherence, and/or any current illnesses or living circumstances that may affect his blood pressure. If home blood pressure monitoring was consistent with guidance, it was suggested that the patient have a face-to-face interview with a trained nurse in a community health center. If the patient had symptoms that required medication adjustments or a further health check (SBP ≥180 mm Hg or DBP ≥110 mm Hg), referral to the general practitioner was needed, and relevant information included blood pressure, a self-report and, if necessary, a medication list, pharmacy refill information, and medication adjustments.

After the home visit, follow-up via telephone calls was conducted biweekly by a trained nurse. During the follow-up, the trained nurse monitored the previous health problems and current condition of patients, as well as modifications in their knowledge, behavior, and status. The previously signed self-care behavioral contract was also reviewed, and further modification was discussed. Thereafter, it was recommended by the trained nurse that the patient should participate in a face-to-face follow-up in a community health center, and if the patient met the referral criteria, a referral would be initiated. Each follow-up call of 10 minutes duration on average, was conducted strictly according to the procedure, and was recorded and saved.

Each participant in the Control Group received a free annual health check, health education leaflets, and a follow-up with pharmacological treatment. The follow-ups were arranged by general practitioners if necessary.

2.4 Outcome and measurement

Outcome measures included blood pressure, self-care behaviors, self-efficacy and satisfaction.

2.5 Data collection

Two time points were set to collect patients’ data: T 0 indicated after recruitment, T 1 indicated immediately after the intervention (12 weeks post-recruitment) and T 2 indicated 4 weeks after the intervention (16 weeks post-recruitment). Satisfaction measurement was performed at T 0 and T 1 , and the others were conducted at T 0 , T 1 and T 2 .

Blood pressure was measured twice using the same calibrated sphygmomanometer and stethoscope, and measurement strictly followed assessment guidelines, [25] with the mean value recorded. Self-care behavior was defined as the patients’ adherence to anti-hypertensive drugs (scores ranged from 0 to 3) and suggested non-pharmacological behaviors (scores ranged from 0 to 8).

The adherence form was adopted in previous studies conducted in China. [4,20,22] A higher score meant better adherence. The assessment of adherence to anti-hypertensive drugs depended on time, frequency, and dose.

2.6 Data analysis

The study was a 2-group parallel block RCT with a single-blind design. The calculation of the study sample size was based on a change in SBP. We assumed that α = 0.05 and power = 0.8. The effect size was 0.59, obtained from Chiu and Wong's study, [24] which involved intervention strategies similar to those in the current study. The calculated sample size was 96. A total of 130 participants would allow for a 20% dropout rate. Chi-square test was used for categorical variables, while the unpaired t -test was used for continuous variables. The unpaired t -test was also used to analyze outcomes of the 2 groups. Repeated measures ANOVA was carried out to evaluate the outcome over time, and 1-way repeated measures ANOVA was performed if the difference was significant. For further analysis of the within-group differences at different time points, a Bonferroni post-hoc test was performed. [27] The Mann-Whitney test was used to determine the difference between the 2 groups at each time point in self-care behavior and satisfaction. The Friedman test was used to examine self-care behavior modification over time in each group. Data was analyzed using the SPSS Statistics Version 20.0 (IBM Corp. Armonk, NY). When a significant difference was detected, the Wilcoxon signed-ranks and post hoc tests were further performed. P < .05 was considered as statistically significant.

Table 1 showed the bio-data and demographics of both study and control populations, Both groups had similar socio-demographic and clinical features.

3.1 Blood pressure

Our results showed that both systolic and DBP decreased significantly in patients of the study group with a mean decrease of 15.03 ± 23.75 mm Hg ( P = .032) in systolic and 8.54 ± 8.86 mmHg ( P = .026) in DBP. Both the systolic and DBP in both groups decreased significantly with time ( P < .05). ( Table 2 ).

Therefore, both the nurse-led hypertension management model and usual care had positive effects on blood pressure reduction, which was more significant at T 1 in the study group, compared to the control group. In addition, a sustained effect in blood pressure reduction was shown in the study group.

3.2 Self-care behaviors

As shown in Table 3 , no significant difference was found in the score for adherence to anti-hypertensive drugs between the 2 groups at T 0 , T 1 , and T 2 . The median score for adherence to non-pharmacological suggestions was significantly higher in the study group than in the control group at T 1 ( P = .000) and T 2 ( P = .049).

3.3 Self-efficacy

At T 0 , there were significant differences in self-efficacy between the study and control groups, which were measured at 5.94 and 6.71 respectively ( P = . 015). Thus, they were used as covariates in the statistical testing. Two-way repeated measures ANOVA were performed. There was no significant difference between the 2 groups in interaction effect (time × group), between-group effect or time effect.

3.4 Patient satisfaction

In the study group, there was a median value increase from 4 to 29 ( P = .000), while in the control group, it increased from 0 to 7 ( P = .000). A remarkably higher satisfaction value was seen in the study group than in the control group at T 1 ( P = .000).

4 Discussion

World Health Organization [28] advocated the implementation of non-communicable disease intervention via a primary healthcare approach, community-based interventions were affordable and sustainable way to manage hypertension in Japan [29] and Canada. [30]

In the present study, both systolic and DBP were significantly reduced in the study group compared with those in the control group same. Patients of the study group showed a mean decrease of 15.03 ± 23.75 mm Hg ( P = .032) in systolic and 8.54 ± 8.86 mm Hg ( P = .026) in DBP respectively. The same has been previously demonstrated by Chiu and Wong [24] and Ma et al [17] after a six-month intervention.

A reduction of SBP by 5 mm Hg or of DBP by 2 mm Hg is usually considered as clinically significant. [31] Our data showed that the number of participants in the study group with more than 5 mm Hg reduction in SBP at T 1, was much higher than in the control group. ( Table 3 )

Among participants, satisfaction was higher in the study group than the control group as reflected by other studies. [32–34] Keleher et al [8] and Laurant et al [9] both reported that patients with chronic diseases had a higher level of satisfaction with nurse-led care than with doctor-led care in the primary care setting. [24] This satisfaction may be linked to trained nurses who comprehensively assessed the health condition of patients, conducting home visits to facilitate care, with follow-ups via phone calls. Nurses interacted with general practitioners and managed health resources to such degree that neither time was wasted nor treatment plans were overlapped. Increased interaction, timely management and non-wastage of equipments in the nurse-led intervention model may have been factors associated with satisfaction.

The self-care behaviour of patients is enhanced in this study with a sustained effect throughout. Self-efficacy showed a significant difference between the 2 groups, but no significant difference in interaction effect (time × group), between-group effect or time effect. The latter may be related to the participants’ lower level of education in this study with 67% of participants with less than tertiary level, which correlates with previous study. [32] self-efficacy can also be due a long history of hypertension, with mean duration of 12 years, with poor hypertension control prior to joining the study.

Current study adds to the growing evidence that informed, prepared and motivated patients are key players in the control of their own blood pressure. The model established in the study provides an efficient approach for managing a large volume of hypertensive patients in a community-level setting in which there is a shortage of doctors, where the well-trained nursing staff can emphasize on health promotion and patient-empowerment. In the nurse-led hypertension management model, the training program provided a structured curriculum enabling nurses to enhance their decision-making abilities, thus expanding the nurse's current traditional dependent role in hypertension management, by enabling more independent roles, such as assessment and counseling. A longer interaction by the nurses at 16 weeks will be beneficial to keep following-up the patients and ensure compliance and lifestyle modifications.

The limitations of the present study were that this intervention was tested in a single community health center, which restrained the ability to generalize results. The community health center was in an urban setting; it is unknown if responses would be similar among rural adults who may have lower levels of education. [32] This study was single-blinded, but health care providers may not have been blinded to the intervention strategies which may have lessened the effect of the intervention.

To assess secondary parameters such as self-care, self-efficacy and patient satisfaction, the author proposed that study targeting newly diagnosed hypertensive be conducted.

5 Conclusion

Empowering the nurses to manage hypertension at the community level is feasible with the possibility of good positive outcome to the patients. This current study contributes to the ascending trend of nurse-led program for hypertension management but also provides the platform for more studies to be continued in both the rural and urban settings.

Acknowledgments

The Authors would like to thank the nursing and medical staff of our institutions, Heibei Province.

Author contributions

Mrs. Miao designed the research together with Mrs. Liu.

Mrs. Wang led the formation of the specialised nurses and gathered data.

Mrs. Liu analysed the collected data.

Mrs. Miao led the write-up.

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community; hypertension; management; model; nurse; randomized controlled trial

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Article Contents

Blood Pressure Control Among Older Adults With Hypertension: Narrative Review and Introduction of a Framework for Improving Care

Guideline definitions and treatment goals

Prevalence, treatment, and control

BP control and disabling conditions

Aging context

Steps in BP management

Implementation needs

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How to take manual blood pressure

What is blood pressure?

What is involved in taking a manual BP?

Electronic versus manual devices

How to take a manual BP

Common causes of error

Tops tips for cuff application

Tops tips for using the valve on the inflatable bulb and reading the measurements on the dial

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International Journal of Cardiovascular Sciences

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Postpartum Remote Blood Pressure Monitoring—When Control Is of the Essence

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Blood Pressure Regulation Evolved from Basic Homeostatic Components

Yoram Finkelstein

Associated Data

1. Introduction

2. Materials and Methods

2.2. Creation of a Similarity Map and Hierarchical Clustering

2.3. Functional and Tissue Expression Enrichment Analyses

4. Discussion

4.1. The Function of the CNS in the Maintenance of Homeostasis

4.2. The Role of the Adrenal Glands

4.3. Nervous Regulation of the Cardiovascular System

4.4. Catecholamines and BP Homeostasis

4.5. The Kidney’s Role in Maintaining Homeostasis

4.6. Sensing the Environment in Order to Maintain Homeostatic Balance

4.7. RAAS Evolution

5. Conclusions

Acknowledgments

Abbreviations

Supplementary Materials

Author Contributions

Institutional Review Board Statement

Informed Consent Statement

High Blood Pressure Causes and Risk Factors

Family history and genetics

Lifestyle habits

Other medical conditions

Race or ethnicity

Social and economic factors

Can High Blood Pressure be prevented?

Secondary Logo

The evaluation of a nurse-led hypertension management model in an urban community healthcare

Background:

Methods:

Results:

Conclusions:

1 Introduction

2.1 Ethical consideration

2.2.1 Setting and Sample

2.2.2 Inclusion criteria

2.2.3 Exclusion criteria

2.3 Intervention

2.4 Outcome and measurement

2.5 Data collection

2.6 Data analysis