INTRODUCTION — Hypertension is a common problem in older adults (age greater than 60 to 65 years), reaching a prevalence as high as 70 to more than 80 percent [1-3]. In the United States, for example, hypertension, defined as systolic blood pressure ≥130 mmHg and/or diastolic blood pressure ≥80 mmHg was observed in 76 percent of adults aged 65 to 74 years and 82 percent of adults aged 75 years or older who were participants in the National Health and Nutrition Examination Survey (NHANES) [1].
Hypertension control rates are lower among older patients. In the same study mentioned above, control of blood pressure to <130/<80 mmHg among those taking antihypertensive drug therapy was achieved by 54, 50, 46, and 33 percent of individuals aged 20 to 54 years, 55 to 64 years, 65 to 74 years, and 75 or more years, respectively [1].
A related issue is the risk of developing hypertension over time in an older adult who is normotensive. This issue was addressed in two reports from the Framingham Heart Study that defined hypertension as a systolic pressure ≥140 and/or a diastolic pressure ≥90 mmHg:
●One study examined the incidence of hypertension (defined as blood pressure greater than 140/90 mmHg or use of antihypertensive drug) over a four-year period among individuals who initially had optimal (less than 120/80 mmHg), normal (120 to 129/80 to 84 mmHg), or high-normal (130 to 139/85 to 89 mmHg) blood pressure [4]. There was a progressive increase in the frequency of development of hypertension in patients over age 65 years (16, 26, and 50 percent in the optimal, normal, and high-normal groups, respectively). Similar findings were noted in younger individuals, but the rates of progression were lower.
●The second report estimated that individuals aged 55 to 65 years who do not have hypertension have a 90 percent lifetime risk of developing mild hypertension (blood pressure 140 to 159/90 to 99 mmHg) and a 40 percent lifetime risk of developing more severe hypertension (blood pressure ≥160/≥100 mmHg) [5].
Isolated systolic hypertension and the efficacy of antihypertensive drug therapy in older adults are presented in this topic. The diagnosis and evaluation of hypertension and our recommendations about goal blood pressure are discussed elsewhere:
●(See "Overview of hypertension in adults".)
●(See "Initial evaluation of adults with hypertension".)
●(See "Goal blood pressure in adults with hypertension".)
ISOLATED SYSTOLIC HYPERTENSION — Isolated systolic hypertension (ISH) has often been defined as a systolic blood pressure above 160 mmHg, with a diastolic blood pressure below 90 mmHg [6-8]. However, using definitions from the 2017 American College of Cardiology/American Heart Association Blood Pressure Guideline [2], a systolic pressure of 130 mmHg is the upper limit of normal at all ages.
ISH mostly occurs in older patients. Data from the Framingham Heart Study and the National Health and Nutrition Examination Survey (NHANES) have shown that the systolic pressure rises and the diastolic pressure falls after age 60 years in both normotensive and untreated hypertensive subjects [9] and that ISH accounts for 60 to 80 percent of cases of hypertension in older adults [10,11]. Furthermore, the systolic and pulse pressures appear to be the major predictors of coronary disease in older adults; in contrast, diastolic pressure is the major predictor under age 50 years, and all three indices were equal predictors between the ages of 50 and 59 years [12].
The elevation in pulse pressure in patients with ISH is primarily due to diminished arterial compliance. ISH may also result from an increase in cardiac output due to anemia, hyperthyroidism, aortic insufficiency, arteriovenous fistula, or Paget disease of bone [13].
ISH (when defined as a systolic pressure ≥140 mmHg and diastolic pressure <90 mmHg) is associated with a two- to fourfold increase in the risk of myocardial infarction, left ventricular hypertrophy, kidney dysfunction, stroke, and cardiovascular mortality [14,15]. Even in patients who also have diastolic hypertension, the cardiovascular risk correlates more closely with the systolic than the diastolic blood pressure [16].
Importance of diastolic pressure — Among older adults, coronary heart disease risk varies directly with the systolic and pulse pressures and inversely with the diastolic pressure (ie, lower diastolic pressures are associated with increased risk) [6,12,17,18]. (See "Goal blood pressure in adults with hypertension".)
The relative importance of the systolic, diastolic, and pulse pressures is different in younger patients [12,17]. (See "Increased pulse pressure".)
However, the observations concerning worse outcomes in older adult patients with lower diastolic pressures primarily came from population studies or from baseline blood pressures in clinical trials, not after treatment in clinical trials. In the SHEP trial, for example, the mean baseline blood pressure was 170/77 mmHg and the attained blood pressure was 143/68 mmHg in the treated group and 155/72 in the placebo group; the mean age was 72 years [19]. Despite the low attained diastolic pressure, the treated group had significantly better outcomes, including fewer coronary heart disease events. A similar mean systolic blood pressure and higher diastolic blood pressure (143/78 mmHg) were attained in the treated group in the HYVET trial of the very old (mean age 84 years) [20]. (See 'SHEP trial' below and 'HYVET trial' below.)
When treating older adult patients with isolated systolic hypertension, there are no clear data that provide guidance related to the minimum diastolic blood pressure that can be tolerated. An analysis from the SHEP trial found significant increases in cardiovascular events in the active treatment group when the diastolic blood pressure was ≤60 mmHg [21]. A J-curve was also noted in other studies. In the observational Rotterdam study, for example, an increased stroke risk began at diastolic pressures below 65 mmHg [22]. In the INVEST trial of hypertensive patients with coronary artery disease, an increased risk of myocardial infarction began at diastolic pressures between 61 and 70 mmHg and increased approximately 2.5-fold at diastolic pressures ≤60 mmHg; however, this association was blunted among those who had undergone coronary revascularization [23].
These observations do not prove a cause-and-effect relationship between lower diastolic pressures and adverse outcomes. In a meta-analysis that included two trials of isolated systolic hypertension, a J-shaped curve for mortality was noted with both systolic pressure (figure 1) and diastolic pressure (figure 2) [24]. However, a J-curve was seen in treated and untreated patients and was not specific for cardiovascular mortality. The authors concluded that the J-curve is probably explained by poor health associated with lower blood pressures, not an adverse effect of antihypertensive therapy (figure 3).
In summary, although adverse outcomes that can be ascribed only to excessive blood pressure lowering with antihypertensive drugs are probably not common in patients with isolated systolic hypertension, cardiovascular events can occur if the diastolic pressure is reduced below the level needed to maintain perfusion to vital organs, particularly the heart. We suggest a minimum posttreatment diastolic pressure, when using typical office-based measurements, of 60 mmHg overall. (See 'Goal blood pressure' below.)
EVIDENCE FOR EFFICACY OF BLOOD PRESSURE LOWERING — Treatment of hypertension in all patients, independent of age, consists of lifestyle modifications and antihypertensive therapy.
Lifestyle modifications — As in younger patients, lifestyle modifications (eg, dietary salt restriction, weight loss in patients with obesity) can lower the blood pressure in older adult patients with hypertension. In particular, dietary sodium intake should be moderately restricted to 100 to 120 mEq/day (2300 to 2800 mg/day) since the pressor effect of sodium excess and the antihypertensive efficacy of sodium restriction progressively increase with age [25]. (See "Overview of hypertension in adults", section on 'Nonpharmacologic therapy' and "Diet in the treatment and prevention of hypertension".)
The efficacy of salt restriction and weight loss in older adult patients with hypertension was demonstrated in the TONE trial including 975 older persons (aged 60 to 80) who had a blood pressure <145/<85 mmHg on one antihypertensive drug; of these, 585 had obesity [26]. Patients were randomly assigned to usual care or salt restriction, and for subjects with obesity, weight loss or a combination intervention of salt restriction and weight loss. Those assigned to salt restriction had a 40 mEq/day decrease in sodium excretion; in those with obesity, a regimen of diminished caloric intake and increased physical activity was associated with a persistent weight loss of 4.7 kg. These parameters remained unchanged in the usual care group. After three months of intervention, withdrawal of the antihypertensive drug was attempted.
The primary endpoint was a diagnosis of high blood pressure, treatment with antihypertensive drugs, or a cardiovascular event at 30 months. Compared with usual care, blood pressure reduction was 2.6/1.1 mmHg greater with salt restriction alone, 3.2/0.3 mmHg greater with weight loss alone, and 4.5/2.6 mmHg greater with both interventions. The primary endpoint occurred less often in patients receiving active interventions compared with those receiving usual care; specifically, rates were lower with salt restriction alone (62 versus 76 percent) and, in those with obesity, weight reduction alone (61 versus 74 percent), and the combination of salt restriction and weight reduction (56 versus 84 percent).
Older patients may have difficulty complying with dietary salt restriction for two reasons:
●They may ingest more salt to compensate for a decrease in taste sensitivity.
●They may depend more upon processed, prepackaged foods that are high in sodium rather than fresh foods that are low in sodium.
Antihypertensive therapy — Randomized trials have provided clear evidence of benefit from treating hypertension in older adult patients, including those over the age of 80 years (table 1) [6,19,20,27-30]. Most of these trials involved patients with isolated systolic hypertension, but some had diastolic hypertension. In addition, trials of patients with diastolic hypertension included some older adult patients.
Meta-analysis — A 2000 meta-analysis included eight outcome trials of 15,693 patients ≥60 years of age with isolated systolic hypertension (including SHEP, Syst-Eur, and MRC described below) [6]. At a median follow-up of 3.8 years, the number of patients who needed to be treated for five years to prevent one major cardiovascular event was 26. The number needed to be treated was lower in men (18 versus 38 in women [percent of patients benefitting 5.6 and 2.6 percent, respectively]), patients aged 70 or more years (19 versus 39 in patients under age 70 years [percent of patients benefitting 5.3 and 2.6 percent, respectively]), and those with previous cardiovascular events (16 versus 37 without such a history [percent of patients benefitting 6.3 and 2.6 percent, respectively]).
Total mortality correlated directly with systolic blood pressure at study entry, but inversely with diastolic blood pressure. However, the diastolic blood pressure was not significantly associated with outcome for combined fatal and nonfatal events.
These results underestimate the true benefit of effectively treating versus not treating isolated systolic hypertension, as illustrated by findings in the SHEP trial described in the next section [19]. Only approximately 70 percent of treated patients reached goal blood pressure during the study, yet the outcomes of the nonresponders were included in the analysis. In addition, increases in blood pressure necessitated the institution of antihypertensive medications in 13 percent of placebo-treated patients at one year and 44 percent at five years.
The trials in the meta-analysis all had baseline mean systolic pressures of 160 mmHg or more [6]. In addition, these trials failed to achieve a systolic pressure less than 140 mmHg, although two trials with favorable outcomes attained a mean systolic pressure between 140 and 145 mmHg. No trials have been performed in patients with isolated systolic hypertension with baseline systolic pressures of 140 to 159 mmHg [31].
SHEP trial — The Systolic Hypertension in the Elderly Program (SHEP) trial included 4376 older adult patients (mean age 72 years) with a mean blood pressure of 170/77 mmHg at baseline [19]. The patients were randomly assigned to antihypertensive therapy or placebo; the aim of therapy was at least a 20 mmHg reduction in systolic pressure to a level below 160 mmHg. Treatment began with 12.5 mg/day of chlorthalidone, which was then increased to 25 mg/day if necessary. Almost one-half of patients reached goal pressure solely with low-dose chlorthalidone. Atenolol or reserpine was added if a further antihypertensive response was required.
The attained blood pressures were 143/68 mmHg with active therapy and 155/72 mmHg with placebo. Despite the potential risk of the relatively low diastolic pressures, the incidence of stroke at four to five years was significantly lower in treated patients (5.5 versus 8.2 percent with placebo) (figure 4). A similar one-third to one-quarter reduction was noted in the incidence of cardiac events, although this trend was not quite statistically significant [32]. These benefits were noted in both men and women and in all age groups, including patients over the age of 80 years, who were the focus of the HYVET trial. (See 'HYVET trial' below.)
Further analyses demonstrated that active therapy was associated with a reduction in left ventricular mass index (-13 versus +6 percent with placebo) [33] and that the reduction in cardiovascular events was not seen in the 7.2 percent of patients who developed hypokalemia (serum potassium less than 3.5 mEq/L) [34].
Syst-Eur trial — The Syst-Eur trial randomly assigned 4695 patients over age 59 years (mean age 70 years) with isolated systolic hypertension (mean initial sitting blood pressure of 174/86 mmHg) to therapy with placebo or nitrendipine plus, if necessary, enalapril and hydrochlorothiazide [28]. The fall in blood pressure was greater with active therapy (23/7 versus 13/2 mmHg).
At four years, significant reductions were noted in stroke (7.9 versus 13.7 total endpoints per 1000 patient-years), and fatal and nonfatal cardiac endpoints. It was estimated that treatment of 1000 patients for five years would prevent 53 cardiovascular endpoints and 29 strokes. Subgroup analysis found that the mortality benefit increased significantly with a higher systolic blood pressure at study entry, fell with increasing age [35], and was more pronounced in patients with diabetes mellitus [36]. (See "Treatment of hypertension in patients with diabetes mellitus".)
In a subset of Syst-Eur, the vascular dementia project of over 2400 patients, antihypertensive therapy significantly lower the incidence of dementia compared to placebo (3.8 versus 7.7 cases per 1000 patient-years) [37]. It was estimated that treatment of 1000 patients for five years would prevent 19 cases of dementia.
MRC trial — A Medical Research Council (MRC) trial included 3496 older adult patients (age 65 to 74 years) with systolic hypertension with or without diastolic hypertension (mean blood pressure 185/91 mmHg) who were randomly assigned to one of three regimens: hydrochlorothiazide (25 to 50 mg/day) plus amiloride; atenolol; or placebo [38]. The patients were followed for a mean of 5.8 years. Compared to placebo, both treatment groups had a similar reduction in diastolic pressure. The reduction in systolic pressure was less in the atenolol group for the first two years, but not thereafter due at least in part to a higher rate of receiving supplemental antihypertensive drugs.
Hydrochlorothiazide plus amiloride significantly reduced the incidence of stroke, coronary events, and all cardiovascular events by 31, 44, and 35 percent, respectively. In contrast, atenolol did not produce significant reductions in these endpoints. Similar findings have been noted in other trials in which beta blockers were associated with worse cardiovascular outcomes than other antihypertensive drugs, an effect that was primarily limited to patients over age 60 years [39,40].
HYVET trial — The benefit of treating hypertension in very old patients was directly addressed in the HYVET trial [20]. In HYVET, 3845 patients who were at least 80 years of age (mean age 84 years) and had a sustained systolic blood pressure of at least 160 mmHg (mean 173/91 mmHg) were randomly assigned to placebo or the thiazide diuretic indapamide. The angiotensin-converting enzyme (ACE) inhibitor, perindopril, or matching placebo was added in individuals who failed to meet the target blood pressure of 150/80 mmHg. At two years, the mean blood pressure was 15.0/6.1 mmHg lower with active therapy (approximately 143/78 versus 158/84 mmHg).
The primary endpoint was fatal or nonfatal stroke. At two years, active therapy was associated with a significant reduction in fatal stroke (6.5 versus 10.7 percent) and an almost significant reduction in all strokes (12.4 versus 17.7 percent, p<0.06). Death from all causes was reduced from 59.6 per 1000 persons per year in the placebo group to 47.2 per 1000 persons per year in the active treatment group.
The authors suggested that the results of HYVET support a target blood pressure of less than 150/80 mmHg in treated patients over age 80 years and that the efficacy of further reductions in blood pressure need to be established.
More versus less intensive blood pressure lowering — Goal blood pressure in older adults was studied in the Systolic Pressure Intervention Trial (SPRINT). A detailed discussion of SPRINT is presented in another topic. (See "Goal blood pressure in adults with hypertension".)
The results from SPRINT in the subgroup of individuals aged 75 years or older are discussed below. (See 'Goal blood pressure' below.)
DRUG THERAPY — Drug therapy should be started in older adult hypertensive patients if lifestyle changes are not sufficient.
General principles — A number of issues need to be considered before initiating antihypertensive drug therapy in older adults (see 'Problem of orthostatic hypotension' below and 'Problem of frailty' below):
●Lower initial doses (approximately one-half that in younger patients) should be used to minimize the risk of side effects.
●Older adult patients may have sluggish baroreceptor and sympathetic neural responses, as well as impaired cerebral autoregulation. Thus, in the absence of a hypertensive emergency or urgency, blood pressure should be lowered to goal gradually over a period of two to four months [41,42], rather than hours to days, in order to minimize the risk of ischemic symptoms, particularly in patients with orthostatic hypotension. This approach is consistent with recommendations made by the European Society of Hypertension/European Society of Cardiology [43]. Even more caution is advised in the very old, although the benefits from careful therapy probably outweigh the risks in these patients [18,20].
●Many trials showing benefit from the treatment of hypertension in older adults were performed in relatively fit patients. However, the Systolic Pressure Intervention Trial (SPRINT) included a large number of community-dwelling hypertensive older adults (aged 75 years or older) who were less fit or frail at the time of enrollment. As noted below, the benefits from more intensive blood pressure lowering were present in fit, less fit, and frail older adult patients. Thus, while it is important to be cautious and avoid overtreating frail older adults, this group also appears to benefit from better control of systolic blood pressure. (See 'Goal blood pressure' below.)
When treating older adults and especially frail older adults hypertensive, extra caution is appropriate in the setting of significant orthostatic hypotension, as described in the next section.
Problem of orthostatic hypotension — A potential limiting factor to the use of antihypertensive drugs is that orthostatic (postural) and/or postprandial hypotension are found in as many as 20 percent of older adult patients with isolated systolic hypertension [44,45]. Hypertensive older adults with orthostatic hypotension are significantly more likely to fall than those without orthostatic hypotension [46,47]. In addition, antihypertensive treatment in older adult patients is associated with an increased risk of hip fracture during the first one to two months following initiation of therapy [48].
As a result, supine and standing pressures should be measured in older adult patients prior to the initiation of antihypertensive therapy (whether blood pressures are measured in the office or at home). Orthostatic hypotension is diagnosed when, within two minutes of quiet standing, one or more of the following is present:
●At least a 20 mmHg fall in systolic blood pressure
●At least a 10 mmHg fall in diastolic blood pressure
●Symptoms of cerebral hypoperfusion, such as dizziness
Weakness, fatigue, or dizziness following meals may signal postprandial hypotension, which can be verified by timely measurement of blood pressure. This is discussed in detail separately. (See "Mechanisms, causes, and evaluation of orthostatic hypotension".)
Problem of frailty — The randomized trials that showed benefit from the treatment of hypertension in older adults included relatively fit patients since frail patients often have difficulty with participation in such trials. Some observational studies suggest that older adults who are frail may not benefit from antihypertensive therapy. The following studies illustrate a range of findings:
●In a cohort of 1127 frail nursing home residents from France and Italy (aged 80 years and older), two-year mortality rates were highest among those who were treated with two or more antihypertensive drugs and had a systolic pressure less than 130 mmHg (32 percent) [49]. In comparison, mortality was lower among individuals who had higher blood pressure despite taking two or more antihypertensive drugs (20 percent) and among those taking fewer medications who had systolic pressures above and below 130 mmHg (20 and 18 percent, respectively). The adjusted hazard ratio for death was greater for those who had a systolic pressure less than 130 mmHg while being treated with two or more drugs compared with the other three groups (HR 1.78, 95% CI 1.34-2.37). This association may have been due to a higher prevalence of heart failure and coronary heart disease among those who had lower systolic pressure treated with dual therapy (35 versus 14 percent, and 35 versus 18 percent, respectively).
●In an observational study of 2340 adults older than 65 years, the association between blood pressure and mortality was examined according to whether or not individuals were frail (defined as an inability to walk 6 meters in less than 8 seconds) [50]. Among frail adults, there was no association between blood pressure and mortality. In addition, a higher blood pressure was associated with a lower risk of death among the most frail (ie, those who could not walk the distance at all). The expected association of a higher blood pressure with a greater mortality risk was observed among the fit individuals.
However, the Systolic Pressure Intervention Trial (SPRINT) found a similar benefit from more as compared with less intensive blood pressure lowering in both fit and frail older adults (aged 75 years or older). These results are presented below. (See 'Goal blood pressure' below.)
Choice of antihypertensive drugs — The 2015 American Heart Association statement on the treatment of blood pressure in ischemic heart disease, the 2013 European Society of Hypertension/European Society of Cardiology guidelines on the management of hypertension, and meta-analyses from 2008 and 2009 concluded that the amount of blood pressure reduction is the major determinant of reduction in cardiovascular risk in both younger and older patients with hypertension, not the choice of antihypertensive drug [43,51-53]. When differences in outcomes have been noted, as in the ALLHAT trial, the drug producing better outcomes had better blood pressure control. (See "Choice of drug therapy in primary (essential) hypertension".)
This general principle of equivalent efficacy in terms of cardiovascular outcomes applies to monotherapy but does not appear to apply to combined antihypertensive therapy. As described below, the combination of an angiotensin inhibitor and a long-acting dihydropyridine calcium channel blocker appears to provide a significant reduction in cardiovascular events at the same attained blood pressure as an angiotensin inhibitor and a thiazide diuretic. (See 'ACCOMPLISH trial of combination therapy' below.)
ALLHAT trial — The ALLHAT trial of over 41,000 patients with mild hypertension and at least one other risk factor for coronary heart disease found that low-to-moderate-dose chlorthalidone (12.5 to 25 mg/day) was associated with fewer cardiovascular complications than amlodipine and lisinopril [54]. A doxazosin arm was discontinued early because of a higher rate of adverse outcomes. (See "Choice of drug therapy in primary (essential) hypertension".)
Approximately 57 percent of the patients were greater than 65 years of age. With respect to clinical outcomes at follow-up at nearly five years, the following results were reported in the patients 65 years and older:
●The incidence of fatal coronary heart disease and nonfatal myocardial infarction (ie, the primary outcome) and all-cause mortality was the same for all three agents.
●A higher rate of heart failure was observed with amlodipine, compared with chlorthalidone (RR 1.33, 95% CI 1.18-1.49); the relative risk was similar to that in the entire ALLHAT population (figure 5).
●Compared with chlorthalidone, lisinopril had significantly higher rates of combined cardiovascular disease outcomes (RR 1.13) (figure 6), combined coronary heart disease (RR 1.11), and heart failure (RR 1.20) (figure 7). There was also a nonsignificant trend for a higher rate of stroke with lisinopril (RR 1.13, with a 95% CI 0.98-1.30) (figure 8). Each of these values was similar to those in the entire ALLHAT population.
Thus, all three antihypertensive agents were associated with the same cardiovascular and overall mortality and incidence of nonfatal myocardial infarction, a finding consistent with smaller comparative trials in older adults, such as STOP-Hypertension-2 [55]. The lower rates of some secondary outcomes with chlorthalidone in ALLHAT may have reflected at least in part lower attained blood pressures, rather than a specific drug benefit [54]. In addition, the superiority of chlorthalidone as compared with lisinopril in preventing certain secondary endpoints may have been due to the presence of a substantial number of Black participants who experienced inferior antihypertensive responses to lisinopril compared with chlorthalidone; chlorthalidone and lisinopril produced similar results in White participants [56]. (See "Choice of drug therapy in primary (essential) hypertension".)
Long-acting calcium channel blockers — Long-acting calcium channel blockers have proven efficacy and safety in older adult patients with hypertension, particularly those with isolated systolic hypertension. This has been demonstrated in a variety of clinical trials in older adult patients with hypertension, including ALLHAT [54], Syst-Eur trial [28], STOP Hypertension-2 [55], the Syst-China trial [29], and the ACCOMPLISH trial [57].
Angiotensin inhibition — In ALLHAT, the angiotensin-converting enzyme (ACE) inhibitor lisinopril produced, for certain cardiovascular endpoints, inferior outcomes compared with chlorthalidone at 12.5 to 25 mg daily, an effect that may have been due at least in part to greater blood pressure reduction with chlorthalidone [54]. In contrast, ACE inhibitors were associated with a lower rate of adverse cardiovascular events than thiazide diuretics at the same degree of blood pressure control in the Second Australian National Blood Pressure (ANBP2) trial of older adult patients with hypertension [58]. However, there are potentially important concerns about the design of this trial [59,60]. (See 'ALLHAT trial' above.)
Many older adult hypertensive patients have a specific indication for an ACE inhibitor or angiotensin II receptor blocker (ARB), including heart failure, prior myocardial infarction, and proteinuric chronic kidney disease. (See appropriate topic reviews.)
Beta blockers — There is evidence that, in the absence of a specific indication for their use (eg, heart failure, myocardial infarction), beta blockers should not be considered for primary therapy of hypertension, particularly in older adult patients [39,61,62]. They may be worse than other agents for the prevention of stroke (particularly among smokers) and, perhaps with atenolol, death. (See "Choice of drug therapy in primary (essential) hypertension".)
ACCOMPLISH trial of combination therapy — The ACCOMPLISH trial evaluated the efficacy of initial combination therapy in 11,506 hypertensive patients (mean age 68 years, mean blood pressure 145/80 mmHg) who were at high risk for cardiovascular events; almost all of whom were being treated with antihypertensive drugs [57]. The patients were randomly assigned (without a washout period) to combination therapy with benazepril (20 mg/day) plus either amlodipine (5 mg/day) or hydrochlorothiazide (12.5 mg/day); dose escalation was performed as necessary. The primary endpoint was achieved significantly less often in the benazepril-amlodipine group (9.6 versus 11.8 percent, hazard ratio 0.80, 95% CI 0.72-0.90). Patients 65 years and older as well as 70 years and older had the same relative benefit from benazepril-amlodipine as did the overall study population. Office blood pressure control and 24-hour blood pressure measurements were similar in the two groups.
The ACCOMPLISH trial is discussed in detail elsewhere. (See "Choice of drug therapy in primary (essential) hypertension".)
Summary of antihypertensive drug choice — For the treatment of hypertension with monotherapy, there is agreement from a 2008 meta-analysis and major society guidelines that, in the absence of a specific indication for use of a particular class of antihypertensive drugs (eg, ACE inhibitors and beta blockers for heart failure), it is the attained blood pressure, not the particular drug, that is the primary determinant of outcome with single-agent antihypertensive therapy [43,52,63]. (See "Choice of drug therapy in primary (essential) hypertension".)
In general, three classes of drugs are considered first-line therapy for the treatment of hypertension in older adult patients: low-to-moderate-dose thiazide diuretics (eg, 12.5 to 25 mg/day of chlorthalidone), long-acting calcium channel blockers (most often dihydropyridines), and ACE inhibitors or ARBs [64]. A long-acting dihydropyridine or a thiazide diuretic is generally preferred in older adult patients because of increased efficacy in blood pressure lowering [43].
Among older adult patients in whom there is a reasonable likelihood of requiring a second drug (eg, more than 10/5 mmHg above goal or failure to attain goal blood pressure with monotherapy), we and many hypertension experts practice according to the results of the ACCOMPLISH trial described above in which there was significant improvement in outcomes at the same attained blood pressure with benazepril plus amlodipine compared with benazepril plus hydrochlorothiazide. (See 'ACCOMPLISH trial of combination therapy' above.)
Thus, we prefer initial therapy with a long-acting dihydropyridine calcium channel blocker. If additional therapy is required, a long-acting ACE inhibitor/ARB can be added to achieve the desired combination regimen. This suggestion differs slightly from the American College of Cardiology/American Heart Association (ACC/AHA) and European Society of Hypertension/European Society of Cardiology (ESH/ESC) guidelines, which suggest that monotherapy can consist of either an ACE inhibitor (or ARB), long-acting calcium channel blocker, or a thiazide diuretic and that combination therapy can consist of any two of these three drugs [2,65]. (See 'Long-acting calcium channel blockers' above and "Choice of drug therapy in primary (essential) hypertension".)
With all drugs, orthostatic hypotension should be avoided because of the increased risk of falling in older patients. (See 'Problem of orthostatic hypotension' above.)
Uncontrolled hypertension — Older hypertensive patients are less likely than younger patients to attain a systolic blood pressure less than 130 mmHg with antihypertensive therapy, although older and younger patients achieve a systolic pressure less than 140 mmHg with equal frequency [66-68]. In the United States, control of blood pressure to <130/<80 mmHg among those taking antihypertensive drug therapy was achieved by 54, 50, 46, and 33 percent of individuals aged 20 to 54 years, 55 to 64 years, 65 to 74 years, and 75 or more years, respectively [1].
Additional observations come from a report of the National Health and Nutrition Examination Survey (NHANES) including 13,375 hypertensive adults who had a mean age of 59 years [69]. Uncontrolled hypertension was defined, at that time, as a blood pressure ≥140/≥90 mmHg in patients treated with one or two antihypertensive medications.
The following findings were noted from 2005 to 2008:
●Among all patients on one to two antihypertensive medications, the risk of being uncontrolled increased by 28 percent with each 10-year increase in age.
●Patients who were uncontrolled on one or two antihypertensive drugs were more likely to be older and to have an estimated 10-year coronary heart disease risk of >20 percent than those who were controlled.
●These patients accounted for 72 percent of all treated patients with uncontrolled hypertension; the remaining 28 percent had resistant hypertension as defined in the following section. (See 'Resistant hypertension' below.)
These observations suggest that clinicians are reluctant to add a second and third antihypertensive drug in older patients with uncontrolled hypertension, despite their high risk for clinical complications from persistent hypertension. However, older hypertensives are more likely to be frail, to have orthostatic hypotension, and to have lower diastolic blood pressures than younger hypertensive patients, all of which may limit antihypertensive therapy. (See 'Problem of orthostatic hypotension' above.)
Thus, while substantial progress has been made in closing the gap in hypertension control between all younger and older adults with hypertension [66], it may not be possible or prudent to fully close the gap. However, the combination of antihypertensive therapy and lifestyle modifications described above should result in blood pressure control in a greater proportion of older patients. (See 'Lifestyle modifications' above.)
Resistant hypertension — In the same NHANES report as in the preceding section, apparent treatment-resistant hypertension was defined as a blood pressure ≥140/≥90 mmHg in patients taking three or more antihypertensive medications [69]. These patients accounted for 28 percent of treated patients with uncontrolled hypertension in 2005 to 2008, which represented an increase from 16 percent in 1988 to 1994. Clinical characteristics associated with resistant hypertension included older age, obesity, chronic kidney disease, and a Framingham 10-year coronary risk score of more than 20 percent.
Issues related to resistant hypertension, including the general approach to therapy, are discussed in detail elsewhere. (See "Definition, risk factors, and evaluation of resistant hypertension" and "Treatment of resistant hypertension".)
GOAL BLOOD PRESSURE — Goal blood pressure depends in part upon the age of the patient and whether or not he or she has significant risk factors for cardiovascular and kidney disease. Goal blood pressure, and specifically our recommended goal blood pressure for different patient populations, is discussed in detail elsewhere. In general, however, our recommendation for most hypertensive older adults is to attain a systolic pressure of 125 to 135 mmHg if standard manual blood pressure measurements are used, or a systolic pressure of 120 to 125 mmHg if unattended, automated oscillometric measurements are used. (See "Blood pressure measurement in the diagnosis and management of hypertension in adults" and "Goal blood pressure in adults with hypertension" and "Treatment of hypertension in patients with diabetes mellitus" and "Antihypertensive therapy and progression of nondiabetic chronic kidney disease in adults" and "Antihypertensive therapy for secondary stroke prevention".)
Goal blood pressure in older adults was examined in the Systolic Pressure Intervention Trial (SPRINT) [70]. SPRINT enrolled a subgroup of more than 2600 ambulatory adults aged 75 years or older with a baseline blood pressure of 142/71 mmHg (consistent with isolated systolic hypertension), including 349 categorized as being fit, 1456 as less fit, and 815 as frail according to a validated frailty index. At 3.1 years, rates of both the primary cardiovascular endpoint and all-cause mortality were significantly lower among those assigned more intensive (mean achieved unattended, automated systolic blood pressure 123) versus less intensive (mean achieved automated, unattended systolic blood pressure 135) blood pressure lowering (2.6 versus 3.8 percent and 1.8 versus 2.6 percent, respectively). The benefit from more intensive blood pressure control was present in both fit and frail older adults. Serious adverse events were similar in the two treatment groups and did not depend upon frailty.
A meta-analysis of 10,857 hypertensive adults aged 65 years or older combined these results from SPRINT with three other large randomized goal blood pressure trials [71]. After a mean follow up of 3.1 years, more intensive, versus less intensive, blood pressure lowering reduced the rates of major adverse cardiovascular events (3.7 versus 5.2 percent), cardiovascular mortality (1.1 versus 1.7 percent), and heart failure (1.3 versus 2.0 percent). Rates of stroke and myocardial infarction were also lower, but the results were not statistically significant.
Blood pressure goals may not be easy to achieve, particularly in older patients with a baseline systolic pressure greater than 160 mmHg. If attaining goal blood pressure proves difficult or overly burdensome for the patient, the systolic pressure that is reached with two or three antihypertensive agents (even if above target) may be a reasonable interim goal. Once maximally tolerated therapy is reached and blood pressure control remains suboptimal, then additional efforts to engage older adults in healthful lifestyle change can facilitate better blood pressure control.
One potential limitation to achieving goal blood pressure is that lowering the blood pressure may impair mental function, leading to manifestations such as confusion or sleepiness. In such patients, antihypertensive therapy should be reduced, and the systolic pressure should be allowed to rise to a level at which these symptoms resolve.
Another concern when treating older adult patients with isolated systolic hypertension is that the low diastolic pressure after therapy may impair tissue perfusion (particularly coronary perfusion) and possibly increase cardiovascular risk [6,12,17,18]. However, as noted above, lower diastolic blood pressures are associated with worse outcomes (both cardiovascular and noncardiovascular) in both treated and untreated patients (figure 2) [24]. These findings suggest that the worse outcomes are probably explained by poor health associated with lower blood pressures, not an adverse effect of antihypertensive therapy. (See 'Importance of diastolic pressure' above.)
Despite these observations, there may be a threshold diastolic blood pressure below which adverse cardiovascular outcomes might increase in older adult patients, particularly coronary heart disease outcomes. When treating patients with isolated systolic hypertension, some suggest a minimum posttreatment diastolic pressure of 55 to 60 mmHg (using office-based blood pressure) [21,23]. However, lowering the systolic pressure to goal, even if the diastolic pressure falls below this threshold, may reduce the risk of stroke (while potentially increasing coronary events) [72], and therefore shared decision-making is appropriate.
SOCIETY GUIDELINE LINKS — Links to society and government-sponsored guidelines from selected countries and regions around the world are provided separately. (See "Society guideline links: Hypertension in adults".)
INFORMATION FOR PATIENTS — UpToDate offers two types of patient education materials, "The Basics" and "Beyond the Basics." The Basics patient education pieces are written in plain language, at the 5th to 6th grade reading level, and they answer the four or five key questions a patient might have about a given condition. These articles are best for patients who want a general overview and who prefer short, easy-to-read materials. Beyond the Basics patient education pieces are longer, more sophisticated, and more detailed. These articles are written at the 10th to 12th grade reading level and are best for patients who want in-depth information and are comfortable with some medical jargon.
Here are the patient education articles that are relevant to this topic. We encourage you to print or e-mail these topics to your patients. (You can also locate patient education articles on a variety of subjects by searching on "patient info" and the keyword(s) of interest.)
●Beyond the Basics topics (see "Patient education: High blood pressure in adults (Beyond the Basics)" and "Patient education: High blood pressure treatment in adults (Beyond the Basics)" and "Patient education: High blood pressure, diet, and weight (Beyond the Basics)")
SUMMARY AND RECOMMENDATIONS
●The prevalence of hypertension among older adults (age greater than 60 to 65 years) is reportedly as high as 70 to more than 80 percent. (See 'Introduction' above.)
●Isolated systolic hypertension (ISH), which is common in older adults, has been often defined as a systolic blood pressure equal to or above 160 mmHg, with a diastolic blood pressure below 90 mmHg. Some expert panels, however, have defined 130 mmHg as the upper limit of normal at all ages. (See 'Isolated systolic hypertension' above.)
●Older hypertensive patients should attempt lifestyle modification to lower the blood pressure. If goal blood pressure is not attained with lifestyle modification, antihypertensive therapy should be initiated. (See 'Lifestyle modifications' above.)
●In the absence of a hypertensive emergency or urgency, blood pressure reduction should always be gradual in older adults, aiming for control within two to four months. All patients should receive nonpharmacologic therapy, particularly dietary salt restriction and weight loss in patients with obesity. Drug therapy should be started if lifestyle changes are not sufficient. A potential limiting factor to the use of antihypertensive drugs is that orthostatic (postural) and/or postprandial hypotension is common among older hypertensive patients. (See 'Lifestyle modifications' above and 'Drug therapy' above.)
●Among older hypertensive patients who require antihypertensive medication and who do not have an indication for a specific drug, we recommend initial monotherapy with a low-dose thiazide-type diuretic, a long-acting calcium channel blocker, or an angiotensin-converting enzyme (ACE) inhibitor/angiotensin II receptor blocker (ARB) (Grade 1B). A long-acting dihydropyridine or a thiazide diuretic is generally preferred because of increased blood pressure-lowering efficacy in this population. Among older adult patients in whom there is a reasonable likelihood of requiring a second drug (eg, systolic pressure more than 10/5 mmHg above goal), we suggest initial therapy with a long-acting dihydropyridine calcium channel blocker (Grade 2C). This is because, if additional therapy is required, a long-acting ACE inhibitor/ARB can be added to achieve the desired combination regimen of a long-acting ACE inhibitor/ARB plus a long-acting dihydropyridine calcium channel blocker. (See 'Summary of antihypertensive drug choice' above.)
●Goal blood pressure is presented in detail separately. In general, however, our recommendation for most hypertensive older adults is to attain a systolic pressure of 125 to 135 mmHg if standard manual office blood pressure measurements are used, or a systolic pressure of 120 to 125 mmHg if automated oscillometric measurements are used. If attaining goal blood pressure proves difficult or overly burdensome for the patient, the systolic pressure that is reached with two or three antihypertensive agents (even if above target) may be a reasonable interim goal. (See "Goal blood pressure in adults with hypertension" and "Antihypertensive therapy and progression of nondiabetic chronic kidney disease in adults", section on 'Blood pressure goal' and "Antihypertensive therapy for secondary stroke prevention" and "Treatment of hypertension in patients with diabetes mellitus".)
