Pathophysiology, Diagnosis, and Management of Hypertension in the Elderly

Abstract

There is a high prevalence of systemic arterial hypertension in the elderly; 70% of adults >65 years have this disease. A key mechanism in the development of hypertension in the elderly is increased arterial stiffness. This accounts for the increase in systolic blood pressure and pulse pressure and fall in diastolic blood pressure (isolated systolic hypertension) that are commonly seen in the elderly, compared with younger persons. The diagnosis of hypertension is made on the basis of in-office blood pressure measurements together with ambulatory and home blood pressure recordings. Lifestyle changes are the cornerstone of management of hypertension.

Comprehensive guidelines regarding blood pressure threshold at which to start pharmacotherapy as well as target blood pressure levels have been issued by both European and American professional bodies. In recent years, there has been considerable interest in intensive lowering of blood pressure in older patients with hypertension. Several large, randomized controlled trials have suggested that a strategy of aiming for a target systolic blood pressure of <120 mm Hg (intensive treatment) rather than a target of <140 mm Hg (standard treatment) results in significant reduction in the incidence of adverse cardiovascular events and total mortality. A systolic blood pressure treatment of <130 mm Hg should be considered favorably in non-institutionalized, ambulatory, free living older patients. In contrast, in the older patient with a high burden of comorbidities and limited life expectancy, an individualized team-based approach, based on clinical judgment and patient preference should be adopted. An increasing body of evidence for older adults with hypertension suggests that intensive blood pressure lowering may prevent or at least partially prevent cognitive decline.

Hypertension, an elevation of systemic arterial blood pressure, is one of the primary modifiable risk factors for cardiovascular disease. Both the prevalence and severity of hypertension increase with age. ¹ According to the U.S. National Health and Nutrition Examination Survey, 70% of adults aged ≥65 years have hypertension. ² In 2020, approximately 17% of the American population was ≥65 years old; and this percentage is expected to reach 24% by the year 2060. ³ Similarly, the number of Europeans older than 65 years is predicted to double during the next 50 years to approximately 150 million. ⁴ For the same elevation of blood pressure, risk of cardiovascular events increases with age and treatment of hypertension in elderly people is therefore of particular importance. ⁵ Indeed, antihypertensive treatment in adults ≥65 years of age produces similar proportional reductions in the risk for total major cardiovascular events as that observed in younger adults, ⁶ but the absolute benefits of treatment were more pronounced in older subjects because of higher average risk. ⁷ For these reasons, hypertension in the elderly will be an increasingly important medical topic.

In the current review, we discuss the pathophysiology, diagnosis, and management of elderly patients with systemic arterial hypertension.

Pathophysiology of Hypertension in the Elderly

A key mechanism in the development of hypertension in the elderly is increased arterial stiffness that occurs with aging. ⁸ The increased stiffness is believed to originate from a gradual mechanical senescence of the elastic network, alterations in cross-linking of extracellular matrix components, fibrosis, and calcification of elastic fibers. ⁹ The stiffening of large arteries reduces their capacitance and accelerates pulse wave velocity. During ventricular systole, a pressure (pulse) wave is generated and travels from the heart to the periphery at a speed (known as pulse wave velocity) that depends on the elastic properties of the conduit arteries. ⁸ When pulse wave velocity is greatly increased (>13 m/s), ¹⁰ the reflected wave reaches the aortic valve before closure. This augments systolic blood pressure, pulse pressure, and afterload and reduces diastolic blood pressure. This phenomenon accounts for the increase in systolic blood pressure and pulse pressure and the fall in diastolic blood pressure (isolated systolic hypertension) that are commonly seen in the elderly, compared with younger persons. ⁸

Endothelial dysfunction is another important contributor to blood pressure elevation in the elderly. ¹¹ With aging, elevation in vasoconstrictors such as endothelin-1 and decreasing bioavailability of the vasodilator nitric oxide occur. ⁸ These biochemical changes have been associated with increased arterial stiffness and the development of isolated systolic hypertension. ¹¹

It has been suggested that there is a potentially important relation between arterial stiffness and diastolic dysfunction, left atrial remodeling, and subsequent cardiovascular risk. Abhayaratna et al reported that, in an elderly cohort at high risk for cardiovascular events by clinical profile, increased arterial stiffness was associated with more severe left ventricular diastolic dysfunction (LVDD). ¹² The latter condition is commonly seen in the community setting especially among elderly individuals, and is a strong predictor of cardiovascular events and incident heart failure. Hypertension has been reported as the most important risk factor for LVDD in the community. Importantly, LVDD is considered a critical link between hypertension and heart failure, particularly in individuals with heart failure and preserved left ventricular ejection fraction. ¹³

Diagnosis

The diagnosis of hypertension is made on basis of blood pressure measurements recorded in the office or out of the office (ambulatory blood pressure monitoring – ABMP).

According to the 2018 European Society of Cardiology (ESC)/European Society of Hypertension (ESH), hypertension is defined as an office systolic blood pressure value of at least 140 mm Hg and/or diastolic blood pressure of at least 90 mm Hg. ¹⁴ Isolated systolic hypertension is defined as systolic blood pressure >140 mm Hg and diastolic blood pressure <90 mm Hg. The ESC/ESH classification of office blood pressures and definitions of hypertension grades are shown in Table 1 . The same classification used for younger and middle-aged people is also used for older people. The equivalent American Heart Association (AHA)/American College of Cardiology (ACC) classification system is shown in Table 2 . ¹⁵ Of note, the threshold blood pressure for the diagnosis of hypertension for the AHA/ACC was somewhat lower (>130/80 mm Hg) than for the ESC/ESH.

Table 1. Categories of office blood pressure and definition of hypertension grade per ESC/ESH.

Category ESC/ESH	Systolic blood pressure (mm Hg)		Diastolic blood pressure (mm Hg)
Optimal	<120	and	<80
Normal	120–129	and/or	80–84
High normal	130–139	and/or	85–89
Hypertension
Grade 1	140–159	and/or	90–99
Grade 2	160–179	and/or	100–109
Grade 3	≥180	and/or	≥110
Isolated systolic hypertension	≥140	and	<90

Abbreviations: ESC, European Society of Cardiology; ESH, European Society of Hypertension.

Source: Adapted from Williams et al 2018. ¹⁴

Table 2. Categories of office blood pressure and definition of hypertension stage per AHA/ACC guidelines.

Category AHA/ACC	Systolic blood pressure (mm Hg)		Diastolic blood pressure (mm Hg)
Normal	<120	and	<80
Elevated	120–129	and	<80
Hypertension
Stage 1	130–139	or	80–89
Stage 2	≥140	or	> 90

Abbreviations: ACC, American College of Cardiology; AHA, American Heart Association.

Source: Adapted from Whelton et al 2017. ²⁴

It is axiomatic that, for precise diagnosis and classification of hypertension, blood pressure must be measured accurately. Measuring blood pressure might appear a simple and easily performed task. However, unfortunately blood pressure measurement is often suboptimally performed in clinical practice. In turn, this can lead to medical errors that inappropriately alter management decisions in 20 to 45% of cases. ^{16 17} Many measurement errors can be minimized by appropriate patient preparation and standardized techniques. ¹⁶ Accordingly, it would appear pertinent in this review to outline several key steps for proper blood pressure measurements.

First, office blood pressure measurements should only be taken after the patient has been sitting relaxed in a chair for more than 5 minutes with feet on the ground and the arm resting. Next, the patient should avoid caffeine, exercise, and smoking at least 30 minutes before the measurement. Neither the patient nor the observer should talk during the rest period or during the measurement. Removing all clothing covering the location of the cuff placement is advised. Measurements made while the patient is sitting or lying on the examination table do not fulfil these requirements. ¹⁵

It is important to use a blood pressure measurement device that has been validated periodically. Validated, semi-automated, or automated upper arm cuff devices should be used rather than auscultation to simplify measurement and prevent observer error. ¹⁵ The patient's arm (e.g., resting on a desk) is supported. The middle of the cuff is positioned on the patients' arm on the level of right atrium (midpoint of the sternum). The correct cuff size is used, such that the bladder encircles 80% of the arm. At the first visit the blood pressure is recorded in both arms. The arm that gives the higher reading for subsequent readings is used. Separate repeated measurements are separated by 1 to 2 minutes. To establish a diagnosis of hypertension, ≥2 readings of elevated blood pressure on ≥2 occasions are needed.

ABPM is a fully automated technique in which blood pressure is monitored noninvasively for a prolonged period of time – usually 24 hours and has the unique benefit of detecting dynamic daytime blood pressure responses (e.g., to exercise, meals, drugs) and blood pressure patterns (e.g., nocturnal hypertension, morning blood pressure surges). ABPM is more predictive of adverse cardiovascular events complicating hypertension than is office blood pressure recording. ^{15 18 19}

Special Subgroups of Hypertension in the Elderly

Pseudohypertension – Increased arterial stiffness in the elderly can lead to erroneous diagnoses. The phenomenon of “pseudohypertension” is defined as a falsely increased systolic blood pressure that results from the failure of stiff arteries to collapse during blood pressure cuff inflations. ^{8 20} Pseudohypertension should be suspected in elderly individuals with resistant hypertension, absence of organ damage and/or symptoms of overmedication. Thus, considering the possible diagnosis of pseudohypertension is advised to prevent overtreating blood pressure in elderly patients with hypertension. ⁸ The Osler maneuver is a simple bedside procedure that can be used to diagnose pseudohypertension. The maneuver is performed by assessing the palpability of the pulseless radial or brachial artery distal to a point of occlusion of the artery manually or by cuff pressure. ²⁰ This maneuver has, however, a low sensitivity and specificity. Confirmation of pseudohypertension requires direct intraarterial measurement. In a systematic evaluation of pseudohypertension, discrepancies of up to 64 mm Hg were demonstrated between cuff and intraarterial pressures in certain elderly patients. ²¹

White coat hypertension – The term white coat hypertension was introduced by Thomas G. Pickering to describe the condition, in which untreated patients have high blood pressure readings at their doctor's office but normal blood pressure levels outside the medical setting. ¹⁸ The diagnosis of this condition is made by ABPM. The prevalence of white coat hypertension is higher with increasing age. ¹⁵ The major clinical relevance of white coat hypertension is that it has typically been associated with minimal to only slightly increased risk of cardiovascular disease and all-cause mortality risk. ^{17 21} If ABPM resources are not readily available, home blood pressure monitoring (HBPM) is a reasonable but less desirable alternative. ¹⁵

Masked hypertension – Masked hypertension is defined as normal blood pressure in the office but with high blood pressure at home. Masked hypertension is associated with a cardiovascular and all-cause mortality risk twice as high as that seen in normotensive individuals, with a risk range similar to patients with sustained hypertension. ^{14 15 19} It is frequent in the elderly and associated with a high vascular risk profile. ¹⁹ These considerations should encourage more widespread use of ABPM or HBPM in elderly patients. ¹⁸

Resistant hypertension – is defined as blood pressure that remains above goal in spite of the concurrent use of three antihypertensive agents of different classes. This type of hypertension is more prevalent in the elderly. ¹⁹ Among the factors to consider in resistant hypertension are poor patient adherence, sleep apnea, and other secondary forms of hypertension.

Dippers – Blood pressure is routinely measured during waking hours. A nighttime fall in blood pressure (nocturnal blood pressure drop of 10–23%) is normal. There is concern that some older patients on antihypertensive therapy may have an exaggerated nocturnal “dipping,” leading to decreased cerebral perfusion. These patients are often referred to as excessive dippers and may have a higher risk of cardiovascular events. ⁷

Secondary hypertension – Important consideration regarding secondary causes of hypertension in the older patient is the frequent use of prescription and over-the-counter drugs that have the potential to increase the blood pressure. For example, nonsteroidal anti-inflammatory drugs and steroids increase blood pressure and are commonly used in the elderly for the treatment of osteoarthritis and other musculoskeletal conditions, headache, and neuromuscular disorders. Obstructive sleep apnea is an often unrecognized cause of an increased blood pressure in older age. ⁸ Other potential causes of secondary hypertension in the elderly include chronic renal insufficiency, obstructive uropathy, and thyroid disease. ^{7 8}

Management

Lifestyle Changes

Lifestyle changes are the cornerstone of management of hypertension in the elderly – these are exhaustively discussed in the relevant professional society guidelines. Current recommendations advocate for regular physical activity, weight control, smoking cessation, stress reduction, prudent diet, and reduced alcohol intake. ^{14 15 22}

Weight loss is a core recommendation and should be achieved through a combination of reduced calorie intake and increased physical activity. There is an apparent dose–response relationship of approximately 1 mm Hg per kg weight loss. ¹⁵ The DASH (Dietary Approach to Stop Hypertension) eating plan is the diet best demonstrated to be effective in lowering blood pressure. ²³ In hypertensives, the DASH diet has produced overall reduction of systolic blood pressure of approximately 11 mm Hg and the diet is especially effective in blacks. ²³ Older patients are more likely to have salt sensitive hypertension. Thus, sodium restriction is more likely to reduce blood pressure in older than in younger individuals. ⁷ The Trial of Nonpharmacologic interventions in the Elderly (TONE) found that restricting sodium intake to, at most, 2 g per day reduced the systolic blood pressure by 4 mm Hg after 30 months of follow-up. When used together, the combination of weight loss and sodium restriction enabled almost half of the older participants to remain off antihypertensive drug therapy for the duration of the trial. ²⁴

The salutary effect of exercise on hypertension in the older population has been well documented. The average reduction in systolic blood pressure with aerobic exercise is approximately 5 to 8 mm Hg in adult hypertensive patients. ²⁵

Pharmacotherapy

Various relevant professional societies have recently issued guidelines on blood pressure threshold for initiation of pharmacotherapy in older patients and the desired blood pressure target and, in addition, provided varying definitions of the terms “elderly” and “very old” ( Table 3 ). It is noted that there is a 20 mm Hg difference between ACC/AHA and ACP/AAFP (American College of Physicians/American Academy of Family Practitioners) guidelines. ²⁶

Table 3. Comparison of blood pressure thresholds and targets between ACC/AHA, ACP/AAFP, and ESC/ESH guidelines.

	Definition of older patients	BP Threshold for initiation of pharmacotherapy	BP target
ACC/AHA 2017	≥65 y	BP ≥130/80 mm Hg	BP <130/80 mm Hg
ACP/AAFP 2017	≥60 y	SBP ≥150 mm Hg	SBP <150 mm Hg
ESC/ESH 2018	Elderly 65–79 y Very old ≥80 y	Elderly BP ≥140/90 mm Hg Very old BP ≥160/90 mm Hg	SBP 130–139 mm Hg DBP 70–79 mm Hg

Abbreviations: AAFP, American Academy of Family Practitioners; ACC, American College of Cardiology; ACP, American College of Physicians; AHA, American Heart Association; BP, blood pressure; DBP, diastolic blood pressure; ESC, European Society of Cardiology; ESH, European Society of Hypertension; SBP, systolic blood pressure.

Thiazide diuretics, angiotensin-enzyme-inhibitors, angiotensin II receptor blockers, and calcium channel blockers have all shown a decrease in adverse cardiovascular events in older patients. ²² Unless there are compelling indications (such as a history of myocardial infarction or chronic heart failure), betablockers should not be considered as first-line treatment as they may worsen cardiovascular outcomes in those over 60 years of age. ⁵ Loop diuretics and α blockers should be avoided given their association with falls. ²²

Considerable impetus to the treatment of hypertension in the very elderly was provided by the results of the HYVET trial, published in the New England Journal of Medicine in 2008. ²⁷ In this study, 3,845 patients ≥80 years old and with sustained systolic blood pressure ≥160 mm Hg were randomized to receive either the diuretic, indapamide, or matching placebo. The ACEI, perindopril, or matching placebo were added if necessary to achieve the target blood pressure of 150/80 mm Hg. The primary end point was fatal or non-fatal stroke. The study was stopped at a mean follow-up of 1.8 years because of the efficacy of therapy. There was a 30% reduction in the primary end point rate and a 21% reduction in total mortality. In addition, there was also a 64% reduction in the rate of incident heart failure. In general, the rate of serious adverse events was low and less frequent with active treatment than with placebo. ²⁷ However, the benefits of antihypertensive treatment in the elderly in the HYVET trial cannot be extrapolated to all patients ≥80 years of age. Significant cognitive impairment, loss of autonomy, cardiovascular comorbidities, and major frailty were exclusion criteria for this study. Therefore, the findings of HYVET cannot be extended to frail elderly patients with important comorbidities and who are on multiple medications. ⁷

In recent years, there has been considerable interest in intensive lowering of blood pressure in patients with hypertension, including in those ≥60 years of age. A landmark study in this area is the Systolic Blood Pressure Intervention Trial (SPRINT), the results of which were published in the New England Journal of Medicine in 2015. ²⁸ In this trial, 9,361 persons (mean age 68 years) with a systolic blood pressure of 130 mm Hg or higher and increased cardiovascular risk (but without diabetes mellitus) were randomly assigned to a systolic blood pressure target of <120 mm Hg (intensive treatment) or a target of <140 mm Hg (standard treatment). The primary composite outcome was myocardial infarction, other acute coronary syndromes, stroke, heart failure or death from cardiovascular causes. At 1 year, the mean systolic blood pressure was 121.4 mm Hg in the intensive treatment group and 136.2 mm Hg in the standard treatment group. The intervention was stopped early after a median follow-up of 3.26 years owing to a significantly lower rate of the primary composite outcome in the intensive treatment group. In addition, the intensive treatment group had lower rates of several other important outcomes, including heart failure (38% lower relative risk) and death from cardiovascular causes (43% lower relative risk). ²⁸ However, the SPRINT study excluded patients with advanced frailty, cognitive decline, loss of autonomy, and living in a nursing home. Moreover, patients with decompensated heart failure, history of stroke, or diabetes mellitus were also excluded. Accordingly, it is hard to extrapolate the findings of this study to frail, nursing home residents with hypertension and multiple comorbidities. Moreover, serious adverse events of hypotension, syncope, electrolyte abnormalities, and acute kidney injury or acute renal failure, but not injuries falls or bradycardia, occurred more frequently in the intensive treatment group than in the standard treatment group. ²⁸

In 2016, Williamson and colleagues reported on the outcome of those patients in the SPRINT aged ≥75 years. Of these 2,636 patients (mean age 79.9 years), 1,317 were randomized to the intensive treatment group and 1,319 to the standard treatment group. The primary composite outcome was as defined for the main SPRINT trial. It was found that the intensive treatment reduced the incident cardiovascular disease by 33% and total mortality by 32%. ²⁹

Even more compelling evidence for a strategy of intensive blood pressure lowering in elderly hypertensive patients was provided by the results of the STEP trial, published in the New England Journal of Medicine in 2021. ³⁰ Zhang et al randomized 8,511 patients aged 60 to 80 years with hypertension to intensive treatment (systolic blood pressure target 110–130 mm Hg) or standard treatment (130–150 mm Hg). Primary outcome was a composite of stroke, acute coronary syndrome, acute decompensated heart failure, coronary revascularization, atrial fibrillation, or death from a cardiovascular cause. Mean follow-up was 3.34 years; the study was stopped because of the efficacy of therapy. ³⁰ There was a 26% benefit for intensive treatment compared with standard treatment. The incidence of hypotension was higher in the intensive treatment group. As with the SPRINT patients, those in the STEP trial were generally quite robust. Patients with previous stroke, diabetes mellitus with HbA1C >8%, class III-IV heart failure, significant valvular heart disease, or severe cognitive impairment were all excluded. In addition, STEP trial only included people of Han ethnicity, which limits the generalizability of their findings. ³⁰

From the above considerations, it should be apparent that a strategy of intensive blood pressure lowering is not the correct one for every older patient with hypertension. A systolic blood pressure treatment of <130 mm Hg should be considered favorably in non-institutionalized, ambulatory, free living older patients. In contrast, in the older patient with a high burden of comorbidities and limited life expectancy, an individualized team-based approach, based on clinical judgment and patient preference should be adopted. ^{31 32}

Effect of Intensive Blood Pressure Lowering on Cognitive Decline

An increasing body of evidence for older adults with hypertension suggests that intensive blood pressure lowering may prevent or at least partially prevent cognitive decline. ^{32 33}

This is of particular interest as there are currently no proven treatments to reduce the risk of mild cognitive impairment (MCI) and dementia. The SPRINT MIND investigators performed baseline and follow-up cognitive assessments in 9,361 randomized patients. ³⁴ MCI was significantly reduced in the intensive compared with the standard treatment group. ³⁴ During the extended trial and posttrial follow-up (median = 5.1 years) the composite of dementia and MCI was significantly less common in the intensive treatment group. In addition, in an MRI substudy of 670 SPRINT patients, targeting a systolic blood pressure of <120 mm Hg compared with <140 mm Hg was significantly associated with less progression of cerebral small vessel ischemic disease, as reflected by white matter lesions that are characteristically associated with Alzheimer disease. ³⁵ Lowering blood pressure might be the only way in which cognitive impairment can be improved or prevented during the process of aging. ³³

Conclusion

Comprehensive guidelines regarding blood pressure threshold at which to start pharmacotherapy as well as target blood pressure levels have been issued by both European and American professional bodies. In recent years, there has been considerable interest in intensive lowering of blood pressure in older patients with hypertension. Several large, randomized controlled trials have suggested that a strategy of aiming for a target systolic blood pressure of <120 mm Hg (intensive treatment) rather than a target of <140 mm Hg (standard treatment) results in significant reduction in the incidence of adverse cardiovascular events and total mortality. A systolic blood pressure treatment of <130 mm Hg should be considered favorably in non-institutionalized, ambulatory, free living older patients. In contrast, in the older patient with a high burden of comorbidities and limited life expectancy, an individualized team-based approach, based on clinical judgment and patient preference should be adopted. An increasing body of evidence for older adults with hypertensions suggest that intensive blood pressure lowering may prevent or at least partially prevent cognitive decline.

The salient points of the current review are summarized in an illustrative chart ( Fig. 1 ).

Fig. 1.

Salient points of the current review.