Epidemiology of Hypertension in Older Adults

Hypertension is one of the primary modifiable risk factors for cardiovascular (CV) disease and its prevalence and severity both increase with age. According to the US National Health and Nutrition Examination Survey (NHANES), 70% of adults ≥65 years have hypertension.¹ This number will continue to rise as our population ages as 15% of the US population was ≥65 years old in 2014 and this is expected to increase to 20% by 2050.²

Despite having the highest prevalence of hypertension and greatest risk for CV morbidity and mortality, older adults are frequently undertreated for elevated blood pressure (BP). This group has been traditionally excluded or underrepresented in clinical trials due to concerns regarding frailty, fall risk, poor renal function, abnormal hemodynamic adaptation, and higher risk for autonomic dysfunction, cognitive impairment, and polypharmacy. With advancing age, the gap between chronological and biological age widens and chronological age may be a poor surrogate for biological age.³ Furthermore, chronological age cutoffs used to identify older patients across guidelines are inconsistent and BP treatment targets remain controversial.

Hypertension Guidelines Reviewed

Hypertension guidelines published by several major medical societies highlight the challenges of managing BP in older patients. In January 2017, the American College of Physicians (ACP) and American Academy of Family Physicians (AAFP) released guidelines for BP management in adults ≥60 years. Pharmacotherapy is recommended for persistently elevated systolic BP (SBP) ≥150 mmHg to reduce the risk of atherosclerotic cardiovascular disease (ASCVD) (Table 1).⁴

Table 1: A Comparison of Blood Pressure Thresholds and Targets between ACC/AHA, ACP/AAFP, and ESC/ESH Guidelines

	ACC/AHA 2017	ACP/AAFP 2017	ESC/ESH 2018
Definition of Older Patients	≥65 years	≥60 years	Elderly 65-79 years Very Old ≥80 years
BP Threshold for Initiation of Pharmacotherapy	≥130/80 mmHg	SBP ≥150 mmHg	Elderly ≥140/90 mmHg Very Old ≥160/90 mmHg
Blood Pressure Target	<130/80 mmHg	SBP <150 mmHg	SBP 130-139 mmHg DBP 70-79mmHg

In November 2017, the American College of Cardiology/American Heart Association (ACC/AHA) hypertension guideline introduced new definitions for BP management (Table 1). Blood pressure is now categorized as normal, elevated, and stage 1 or 2 hypertension. Normal BP is defined as <120/80 mmHg while elevated BP is 120-129/< 80 mmHg. Stage 1 hypertension is defined as SBP 130-139 mmHg and/or diastolic BP (DBP) 80-89 mmHg. Stage 2 hypertension is defined as SBP ≥140 mmHg and/or DBP ≥ 90 mmHg. Based primarily on results from the Systolic Blood Pressure Intervention Trial (SPRINT), for most adults ≥65 years old, a more aggressive SBP target <130 mmHg is recommended.^5-7 However, the ACC/AHA guideline advises clinical judgement and patient preference to determine BP targets in older patients with limited life expectancy and multiple co-morbidities. It acknowledges the lack of randomized controlled trials (RCTs) for patients with history of frequent falls, advanced cognitive impairment, and those living in nursing homes or skilled nursing facilities.⁸

The 2018 European Society of Cardiology/European Society of Hypertension (ESC/ESH) BP guideline categorizes older adults in two subgroups; 'elderly' refers to patients between the ages of 65 and 79 years while 'very old' refers to those ≥80 years (Table 1). The guideline recommends that pharmacologic treatment should be offered to all older patients with an SBP of ≥160 mmHg. A lower therapeutic target of SBP 130-139 and DBP 70-79 mmHg can also be considered in 'elderly' (those ≥65 years, but not >80 years) patients. Pharmacologic therapy may also be considered in fit individuals >80 years with an initial SBP ≥160 mmHg and/or DBP ≥90 mmHg while targeting a BP of 130-139/70-79 mmHg.⁹ These decisions should be based on clinical assessment of biological age and a thorough review of comorbidities. Treatment side effects must be closely monitored, particularly for those who are frail.

Even though the definitions and treatment thresholds differ between the American and European guidelines, both acknowledge the importance of BP treatment in older adults to lower atherosclerotic cardiovascular disease (ASCVD) risk but recommend a cautious approach and close monitoring of these patients. The hypertension treatment goals for older patients according to American and European guidelines are listed in Table 1.

Hypertension Management in Older Adults with History of Coronary Artery Disease (CAD)

The 2017 ACC/AHA guideline recommends a target BP of <130/80 mmHg for older patients (age ≥65) with stable ischemic heart disease (SIHD).⁸ Notably, the DBP target only achieved level of evidence (LOE) C (limited data, meta-analysis) and was based solely on expert opinion. Furthermore, less intensive BP thresholds for older patients with SIHD were not systematically addressed. The guideline encourages clinical judgment and patient preference to guide BP management in this group, particularly when there is a high burden of comorbidities and reduced life expectancy.⁸ BP treatment thresholds for older adults with CAD remain controversial due to a lack of RCTs.

In SPRINT, older patients (age ≥75) assigned to intensive BP lowering achieved a greater reduction in the primary CV endpoint (nonfatal myocardial infarction (MI), acute coronary syndrome not resulting in an MI, nonfatal stroke, nonfatal acute decompensated heart failure, and CV mortality) compared to younger subjects [hazard ratio (HR) 0.66 vs 0.8].¹⁰ A subsequent analysis of this subgroup was published in 2016, but did not examine whether patients with CAD derived additional benefit from intensive BP lowering.⁵ The rate of all reported serious adverse events (SAEs) was similar between the intensive and standard treatment arms. However, the analysis did not report SAEs that were possibly or directly linked to the intervention that might have shown higher event rates in the intensive treatment group. In a secondary analysis from SPRINT, patients ≥75 years with a history of CV disease had a greater risk of the composite CV outcome (MI, non-MI acute coronary syndrome, stroke, acute decompensated heart failure, and CV mortality) at lower DBP (<55 mm Hg) compared to patients ˂75 years.¹¹ Comparatively, in patients without CV disease, low DBP was associated with a higher hazard of the composite CV outcome regardless of age. Taken together, these findings suggest that age and history of CV disease should be integrated into clinical decision-making.

Many studies of hypertensive older patients suggest a "J-shaped" curve with elevated CV risk associated with low systolic and diastolic BPs. Prior to the 2017 guideline update, the 2015 ACC/AHA BP recommendations for CAD patients >80 years old encouraged avoiding a SBP <130 mmHg and/or DBP <65 mmHg.¹² The rationale for these recommendations came from observational studies that found an association between low systolic and diastolic BPs and increased CV risk. INternational VErapamil SR Trandolapril STudy (INVEST) included a substantial number of very old hypertensive patients with stable CAD.^13,14 Among the 22,576 patients enrolled, 2180 were >80 years old. Patients with stable CAD and hypertension were randomized to either verapamil- or atenolol-based treatment strategies. Trandolapril, with or without hydrochlorothiazide, was added to achieve BP targets <140/90 mmHg or <130/85 mmHg for patients with diabetes or renal insufficiency, respectively. No difference was observed in the primary outcome (first occurrence of all-cause death, nonfatal MI, or nonfatal stroke) between the two treatment arms.¹³ In this age-based subgroup analysis, higher primary event rates were linked to increasing age. The SBP at the HR nadir also increased with age and was highest for subjects >80 years old (140 mmHg, Figure 1). Patients aged 70-80 years had a slightly lower SBP nadir (135 mmHg), while the two youngest age groups each had a much lower SBP (110 mmHg) at their respective nadirs. The DBP at the HR nadir was similar for all age groups (75 mmHg) except for the very old (age>80), for whom it was <70 mmHg (Figure 1).

Figure 1

More recently, data from the prospective longitudinal registry of 32,703 hypertensive patients with stable CAD (CLARIFY) was published.¹⁵ Systolic and diastolic BPs before each CV event were averaged and categorized into 10 mmHg increments. The primary outcome was a composite of CV death, MI, or stroke. Using the 120-129 mmHg SBP and 70-79 mmHg DBP subgroups as a reference, multivariable adjusted Cox proportional hazards models were applied to calculate estimated HRs.¹⁵ After a median follow-up of 5 years, SBP ≥140 mmHg and DBP ≥80 mmHg were each associated with an increased risk of CV events. SBP <120 mmHg (adjusted HR 1.56) and DBP <70 mmHg (adjusted HR 1.41 for DBP of 60-69mmHg and 2.01 for DBP of less than 60 mmHg) were also linked to an increased risk for the primary endpoint. In the subgroup analysis of patients >75 years old, SBP < 120 mmHg (HR 1.47) and DBP <60 mmHg (HR 1.64) was associated with an increased risk of CV events.¹⁵

A current analysis from SPRINT explored the impact of baseline DBP on the primary CV outcome based on SBP intervention.¹⁶ This study confirmed a "U-shaped" association between DBP and CV risk. However, regardless of initial DBP, intensive SBP lowering was associated with lower CV event rates.¹⁶ Even in the lowest DBP quintile (<68 mmHg, mean 61 mmHg), a 22% lower risk of the primary CV outcome was observed, although it did not achieve statistical significance (HR 0.78, CI 0.57, 1.07).¹⁶ While the analysis did not evaluate trends based on age classifications, the average for this quintile was 74.7 years.¹⁶

The current guidelines recommend aggressive BP lowering for older patients, including those with SIHD. The evidence for intensive SBP and DBP treatment in this population is inconclusive. To date, prospective randomized trials to define appropriate thresholds have not been performed. Until more conclusive data is published, individualized targets based on comorbidities, quality of life, and patient preferences should be applied when making a BP treatment plan in this group.

Hypertension Management in Older Adults with History of Atrial Fibrillation and Stroke

Hypertension is the most common comorbidity among older patients with atrial fibrillation and both are associated with an increased risk of stroke. In the landmark ARISTOTLE (Apixaban for Reduction in Stroke and Other Thromboembolic Events) trial of nearly 18,000 older patients (mean age 70 years) with nonvalvular atrial fibrillation, 88% had a history of hypertension requiring medical treatment.¹⁷ Interestingly, any elevated office systolic BP (≥140 mmHg) or diastolic BP (≥90 mmHg) reading during the trial duration was associated with a 53% increased risk of ischemic stroke (HR 1.53, 95% CI 1.25-1.86) and 85% increased risk of hemorrhagic stroke (HR 1.85, 95% CI 1.26-2.72).¹⁷ These findings highlight the importance of BP control among older patients with concomitant hypertension and nonvalvular atrial fibrillation.

Hypertension management is also the most important intervention for secondary prevention of stroke.¹⁸ BP reduction among all-comers with a prior history of stroke lowered the risk of a recurrent event in clinical trials, but the evidence in older patients is scarce.¹⁹ Moreover, there is concern that long-term antihypertensive treatment may compromise cerebral perfusion in post-stroke older patients (≥70 years) with carotid disease.²⁰ The 2014 American Heart Association/American Stroke Association guideline for stroke prevention acknowledges that a target BP level for those with history of stroke or transient ischemic attack is uncertain. It recommends that BP goals should be individualized and that it is reasonable to target SBP <140mmHg and DBP <90 mmHg (class of recommendation IIa and LOE B).¹⁸ Consistent with the 2014 guideline, the 2017 ACC/AHA hypertension guideline recommends antihypertensive treatment for patients with a history of stroke with a BP of 140/90 mmHg or higher (Class I, LOE B-R), but also suggests that a BP goal of <130/80 mmHg may be reasonable (class IIb, LOE B-R).⁸

Masked and White Coat Hypertension in Older Adults

Masked hypertension (MH) is the presence of out-of-office hypertension in the setting of in-office normotension. White coat hypertension (WCH) refers to in-office hypertension in the setting of normotension on ambulatory BP (ABPM) or home BP (HBPM) monitoring.^21,22 Both MH and WCH are frequently observed in older patients and carry different prognostic significance.

An analysis from the SHEAF (Self measurement of blood pressure at Home in the Elderly: Assessment and Follow-up) study revealed that among 4,939 elderly French adults (mean age 70 years) with treated hypertension, MH was present in 9.3% participants and associated with a two-fold increased risk of CV events (HR 2.06, 95% CI 1.22-3.47) during 3.2 years of follow-up.²³ This risk was similar in magnitude to what was observed among subjects with uncontrolled hypertension, i.e. elevated BP in both office and home (HR 1.96, 95% CI 1.27-3.02).²³ Conversely, participants with WCH (13.3% of the cohort) had ASCVD risk that was similar to those with normal in office and home BPs (HR 1.18, 95% CI 0.67-2.10).²³ Pierdomenico and colleagues recently reported similar findings from an Italian cohort of 1191 older patients (mean age 68 years) with treated hypertension who underwent ABPM.²⁴ MH was observed in 12% of the cohort and was independently associated with a 60% higher risk of CV events (HR 1.60, 95% CI 1.12-2.29) during 9.1 years of follow-up.²⁴ WCH was observed more frequently (19% of the cohort) but was not associated with an increased CV event risk (HR 1.09, 95% CI 0.74-1.60).²⁴ In a registry-based, multicenter study conducted in Spain, ambulatory and clinic BP measurements were compared with regard to their predictive ability for all-cause and CV mortality. In this cohort of nearly 64,000 patients, ambulatory BP measurements were found to be a stronger predictor of all-cause and CV mortality.²⁵ MH was associated with an increased risk of all-cause and CV mortality and an even greater risk of death than sustained hypertension.²⁵

These studies highlight the increased CV risk associated with MH and the relative uncertainty of the CV risk associated with WCH among older patients with treated hypertension. The threshold to use HBPM or ABPM should be low in older adults given the potential prognostic implications of these two phenotypes. Recently, the Centers for Medicare Services approved additional coverage for ABPM in the older adult population. The Antihypertensive Treatment in Masked Hypertension for Target Organ Protection (ANTI-MASK) trial is a randomized, placebo-controlled trial seeking to evaluate the effects of allisartan isoproxil 80 mg once daily with a primary endpoint of improvement in the rate of target organ damage (left ventricular hypertrophy, large arterial stiffness, and microalbuminuria). The trial aims to recruit 300 adults with a history of MH, but the recruitment status of the trial is unclear.²⁶

The MASked-unconTrolled hypERtension Management Based on Office BP or on Out-of-office (Ambulatory) BP Measurement (MASTER) trial is currently recruiting patients to compare office BP vs. 24-hour ABPM to guide management of MH.²⁷ Primary endpoints include change in left ventricular mass and microalbuminuria. Findings from these trials should provide some insights for monitoring and treatment of patients with MH.

Special Considerations to Achieving Target Blood Pressure in Older Adults: Side Effects of Pharmacotherapy, Comorbidities, and Orthostatic Hypotension

A recent evaluation of the National Health and Nutrition Examination Survey database revealed that nearly 50% of hypertensive US adults ≥ 80 years of age have uncontrolled hypertension.²⁸ Treatment of elevated BP in older adults to guideline-recommended systolic BP goal of <130mmHg is challenging due to the increased risk of medication side effects and drug-drug interactions. Antihypertensive agents like immediate release nifedipine and peripheral alpha1-antagonists (doxazosin, prazosin, and terazosin) are associated with a heightened risk of orthostatic hypotension while central alpha2-agonists like clonidine, guanfacine, and methyldopa can lead to significant central nervous system side effects in older adults.²⁹ Concomitant use of peripheral alpha1-antagonists with loop diuretics in older women increases the risk of urinary incontinence. Renin angiotensin system antagonists (ACE-inhibitors, ARBs, or aliskiren) and potassium sparing diuretics like amiloride or triamterene can lead to an increased risk of hyperkalemia.²⁹ However, when used with caution, the three first-line agents for hypertension management, including diuretics, ACE-inhibitors and calcium channel blockers, have excellent safety profiles and are generally well tolerated by older adults.

A high degree of heterogeneity in clinical comorbidities, cognitive impairment, and variable life expectancy further add to the complexity of hypertension management in this patient population. Among older patients with multiple clinical comorbidities, high frailty, or advanced cognitive impairment, an accurate assessment of prognosis, risk tolerance, and treatment goals is of paramount importance. Such patients typically reside in nursing homes and assisting living facilities; a population that is not represented in large RCTs and therefore have no demonstrated safety data for intensive BP lowering.^5,30 Additionally, older patients may develop orthostatic hypotension with initiation of multiple antihypertensive agents.³¹ Careful initiation of a single agent followed by sequential titration of the dose and addition of other agents can decrease the risk of adverse outcomes with intensive BP lowering. Along these lines, the 2017 ACC/AHA BP guideline recommends that for older adults (≥65 years of age) with hypertension and a high burden of comorbidity and limited life expectancy, clinical judgment, patient preference, and a team-based approach to assess risk/benefit is reasonable for decisions regarding intensity of BP lowering and choice of antihypertensive drugs (class IIa, LOE C – expert opinion).⁸

Conclusion

Hypertension is highly prevalent and frequently undertreated in older adults. Management of hypertension in this heterogenous population, including those with established CAD, atrial fibrillation, and stroke, requires a comprehensive assessment and shared decision making between clinician and patient that focuses on patient preferences, medical comorbidities, life expectancy, treatment goals, and an appropriate balance between risks and benefits.

References

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Clinical Topics: Acute Coronary Syndromes, Arrhythmias and Clinical EP, Diabetes and Cardiometabolic Disease, Geriatric Cardiology, Heart Failure and Cardiomyopathies, Prevention, Atherosclerotic Disease (CAD/PAD), Atrial Fibrillation/Supraventricular Arrhythmias, Statins, Acute Heart Failure, Hypertension

Keywords: Primary Prevention, Secondary Prevention, Acute Coronary Syndrome, Aging, American Heart Association, Amiloride, Amides, Angiotensin-Converting Enzyme Inhibitors, Antihypertensive Agents, Atenolol, Atrial Fibrillation, Biphenyl Compounds, Blood Pressure, Blood Pressure Determination, Calcium Channel Blockers, Cardiovascular Diseases, Brain Ischemia, Cerebrovascular Circulation, Clonidine, Coronary Artery Disease, Comorbidity, Cohort Studies, Diabetes Mellitus, Diastole, Diuretics, Diuretics, Potassium Sparing, Doxazosin, Drug Interactions, Expert Testimony, Follow-Up Studies, Frail Elderly, Fumarates, Goals, Guanfacine, Heart Failure, Hemodynamics, Hydrochlorothiazide, Hyperkalemia, Hypertension, Hypertrophy, Left Ventricular, Hypotension, Orthostatic, Imidazoles, Indoles, Ischemic Attack, Transient, Life Expectancy, Masked Hypertension, Medicare, Methyldopa, Morbidity, Myocardial Infarction, Nifedipine, Nursing Homes, Nutrition Surveys, Patient Preference, Physicians, Family, Phenotype, Polypharmacy, Prazosin, Prevalence, Proportional Hazards Models, Prognosis, Prospective Studies, Pyridones, Pyrazoles, Quality of Life, Registries, Renal Insufficiency, Renin-Angiotensin System, Risk Assessment, Risk Factors, Secondary Prevention, Skilled Nursing Facilities, Societies, Medical, Sodium Potassium Chloride Symporter Inhibitors, Stroke, Triamterene, Vascular Stiffness, Verapamil, White Coat Hypertension

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