The Importance of Systolic Blood Pressure Elevation in Elderly Persons

The elderly population, defined as persons aged ≥65 years, represents the most rapidly growing segment of the US population. In 1990, elderly persons accounted for 13% of the population and are expected to account for 20% of the population by the year 2040. Hypertension, defined as a systolic blood pressure (SBP) ≥140 mm Hg and/or a diastolic blood pressure (DBP) ≥90 mm Hg, is the second most common condition in the elderly population. Hypertension is a powerful, independent, and modifiable risk factor whose presence increases the risk of atherosclerotic cardiovascular disease (CVD), including stroke, coronary heart disease, congestive heart failure, peripheral vascular disease, renal failure, dementia, and death. The finding that more than 90% of persons will develop hypertension within their lifetime, usually after age 55 years, emphasizes the huge public health problem that hypertension poses to the elderly population.

Compared with the same blood pressure (BP) in younger persons, high BP in the elderly confers a three‐ to four‐fold increase in risk for CVD. Despite the fact that BP control rates continue to improve, with one in every three persons within the United States controlled to <140/90 mm Hg, only 27% of the elderly remain controlled. Perhaps concern for these lower control rates is secondary to the practitioners' reluctance to treat older patients with hypertension because of the unfounded fear that treatment would be associated with an excess of medication‐related side effects. In fact, clinical trials suggest that older persons adhere and respond to treatment as well as, if not better than, younger subjects.

Whereas both SBP and DBP are independently predictive of cardiovascular risk for patients aged ≤50 years, SBP is a better predictor of CVD risk for those >50 years of age. In the Hypertension Optimal Treatment (HOT) trial, the Antihypertensive and Lipid‐Lowering Treatment to Prevent Heart Attack Trial (ALLHAT), and the Controlled ONset Verapamil INvestigation of Cardiovascular Endpoints (CONVINCE) trial, 90% of participants had their DBP reduced to <90 mm Hg while only 60% had their SBP reduced to <140 mm Hg. This inability to control SBP usually limits our ability to control hypertension in elderly persons.

The failure to control SBP is in part related to physician attitudes. A survey of primary care physicians indicated that three fourths failed to initiate antihypertensive therapy in older persons with SBP of 140–159 mm Hg, and most did not pursue controlling SBP to <140 mm Hg. Because most physicians are taught that reducing DBP is more important than controlling SBP, greater emphasis must be placed on managing systolic hypertension.

ISOLATED SYSTOLIC HYPERTENSION

While it has been known for more than three decades that elevation of SBP predicts the risk of CVD better than increases in DBP, no attempt was made to translate this evidence into practice until 1993, when the fifth report of the Joint National Committee on Detection, Evaluation, and Treatment of High Blood Pressure (JNC V) recognized isolated systolic hypertension (ISH) as an important target for BP control. ISH, defined as SBP ≥140 mm Hg and DBP <90 mm Hg, represents the most common form of hypertension in elderly persons. Stage 1 ISH (SBP 140–159 mm Hg with DBP <90 mm Hg), which often goes untreated, is the predominant form of systolic hypertension in the elderly, affecting more than 25% of adults aged ≥60 years. Persons with stage 2 ISH (SBP ≥160 mm Hg, DBP <90 mm Hg) are at greater risk of developing cardiovascular and renal disease than those with stage 1 ISH. The prevalence of ISH increases with age: two thirds of persons ≥60 years of age, and three fourths of those >75 years of age have ISH. ISH remains the major form of uncontrolled hypertension, affecting 87% of subjects by their sixth decade of life.

Age‐related pathophysiologic changes explain the frequent development of ISH in the elderly. ISH is caused by the loss of distensibility of the larger arteries, especially the aorta. While the aorta remains highly distensible in the younger individual, expanding during systole to minimize the rise in BP, progressive stiffening of the arterial tree often occurs in the elderly. This reduction in the compliance of the aorta as we age leads to a progressive elevation in SBP that increases both left ventricular work and the risk for left ventricular hypertrophy. DBP often remains normal or tends to decrease with age, contributing to a higher pulse pressure (SBP‐DBP). Despite the observation that pulse pressure remains the strongest predictor of cardiovascular risk in elderly persons, reducing SBP improved cardiovascular outcome in clinical trials. As SBP elevation remains the major component that defines the risk of widened pulse pressure, controlling SBP continues to be the recommended target to reduce cardiovascular risk in elderly patients.

APPROPRIATE GOALS OF THERAPY IN ELDERLY PERSONS Benefits of Treating ISH

Neither the definition of hypertension nor the goals of treatment change according to age. Treatment should be initiated when SBP is ≥140 mm Hg and/or DBP is ≥90 mm Hg. Recent randomized placebo‐controlled trials have demonstrated significant benefit from drug treatment in elderly patients with ISH. In those with SBP ≥160 mm Hg and DBP <90–95 mm Hg at baseline, a 35%–40% reduction in stroke, a 50% reduction in heart failure, a 30% reduction in coronary events, and a 10%–15% reduction in mortality was achieved with antihypertensive treatment (Table I). To achieve this benefit, SBP was reduced by at least 20 mm Hg from baseline to <160 mm Hg, as in the Systolic Hypertension in the Elderly Program (SHEP), or <150 mm Hg, as in the Isolated Systolic Hypertension in Europe trial (Syst‐Eur) in the elderly trial. In none of the trials was an SBP <140 mm Hg achieved (Table II).

Table I.

Major Clinical Trials Showing Benefit of Treating Isolated Systolic Hypertension

	SHEP (n=4736)	Syst‐Eur (n=4695)	Syst‐China (n=2394)
Baseline	160–219/<90	160–219/<95	160–219/<95
SBP/DBP (mm Hg)
BP reduction	27/9	23/7	20/5
SBP/DBP (mm Hg)
Drug therapy	Chlorthalidone	Nitrendipine	Nitrendipine
	Atenolol	Enalapril	Captopril
		Hydrochlorothiazide	Hydrochlorothiazide
		Outcomes (% Decrease)
Stroke	33	42	38
CAD	27	30	27
CHF	55	29	…
All CV disease	32	31	25
SHEP=Systolic Hypertension in the Elderly Program; Syst‐Eur=Systolic Hypertension in Europe Trial; Syst‐China=Systolic Hypertension in the Elderly: Chinese trial; SBP=systolic blood pressure; DBP=diastolic blood pressure; CAD=coronary artery disease; CHF=congestive heart failure; CV=cardiovascular Reproduced with permission from Jamerson K, Giles G, Sica D, et al. Inhibiting both RAS and SNS for high blood pressure control: myths and facts. J Clin Hypertens (Greenwich). 2000;2(5):331–338.

Table II.

Blood Pressure in SHEP and Syst‐Eur

	SHEP	Syst‐Eur
Entry (mm Hg)	160–219/<90	160–219/<95
Goal (SBP) (mm Hg)	<160 +≥21 ↓	<150 +≥20 ↓
Baseline (mm Hg)	170/77	174/86
Achieved: Rx (mm Hg)	143/68	151/79
Achieved: Placebo (mm Hg)	155/72	161/84
Difference: Rx‐Placebo (mm Hg)	12/4	10/5
SHEP=Systolic Hypertension in the Elderly Program; Syst‐Eur=Systolic Hypertension in Europe Trial; SBP=systolic blood pressure; Rx=treatment Reproduced with permission from Basil JN. Hypertension in the elderly: a review of the importance of systolic pressure elevation. J Clin Hypertens (Greenwich). 2002;4:108–112.

Is there clinical trial evidence to recommend a goal SBP of <140 mm Hg in patients with ISH? While the cardiovascular risk associated with Stage 1 ISH (140–159 mm Hg) is well established, no clinical trial has tested whether treatment is beneficial. The seventh report of the JNC (JNC 7) and a consensus statement from the National High Blood Pressure Education Program still recommend achieving SBP <140 mm Hg. Recommendations to achieve a specific target BP come from epidemiologic observation or post‐hoc analyses of clinical trial data. One such post‐hoc analysis was published almost 10 years after the results of SHEP were originally published. In this analysis of the original cohort, the risk of stroke was calculated according to on‐treatment BP during follow‐up. Those patients on treatment who achieved a targeted SBP <160 mm Hg and at least a 20 mm Hg reduction from baseline had a 33% reduction in stroke. The patients who achieved an SBP of <150 mm Hg did even better, with a 38% risk reduction in stroke. The group that achieved SBP <140 mm Hg had a 22% reduction in stroke risk that, because of the smaller number of participants involved, did not reach statistical significance. Despite the fact that the current recommendation is to reduce SBP to <140 mm Hg in patients with ISH, these data suggest that if SBP is reduced by at least 20 mm Hg from baseline, even if not to the presently recommended goal of <140 mm Hg, clinical outcome is improved (Table II).

Is there any age where one would not treat an elderly patient with ISH? An analysis of the effects of antihypertensive treatment in very elderly participants enrolled in randomized controlled trials supports the benefits of antihypertensive therapy even in patients aged ≥80 years. The oldest of the elderly seem to benefit the most from active treatment.

Nonpharmacologic Treatment of ISH

Lifestyle changes—in particular, weight loss and reduced sodium intake—are beneficial in controlling BP in elderly persons with hypertension and are associated with a reduced need for pharmacologic therapy. Weight reduction is the most effective lifestyle intervention for lowering BP, especially in elderly persons with hypertension who are overweight (Table III). Older persons with hypertension are usually more salt sensitive than younger ones, and successful salt reduction can be achieved in part by limiting a variety of high‐salt‐content processed foods. The Trial Of Nonpharmacologic interventions in the Elderly (TONE) found that restricting salt to 80 mmol (2 g) per day reduced SBP by 4.3 mm Hg and DBP by 2 mm Hg during 30 months of follow‐up. The combination of weight loss and salt restriction reduced BP more than either strategy by itself and enabled almost half of the elderly participants to stop antihypertensive drug therapy. Additional lifestyle changes include adopting a Dietary Approaches to Stop Hypertension (DASH) diet. This diet, which is low in fat but rich in fruits, vegetables, and low‐fat dairy products, has been successful in reducing BP, especially SBP, in older patients with hypertension even when consuming an average salt intake. Reducing alcohol intake and increasing physical activity should also be integral parts of SBP control in the elderly.

Table III.

Lifestyle Modifications

Modification	Approximate Systolic Blood Pressure Reduction Range
Weight reduction	0.5–1 mm Hg/kg loss
Adopt DASH eating plan	8–14 mm Hg
Dietary sodium restriction	2–8 mm Hg
Physical activity	4–9 mm Hg
Moderation of alcohol consumption	2–4 mm Hg
DASH=Dietary Approaches to Stop Hypertension Reproduced with permission from Chobanian AV, Bakris GL, Black HR, et al. The seventh report of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure: the JNC 7 report. JAMA. 2003;289(19):2560–2572.

Pharmacologic Treatment of ISH

Several placebo‐controlled, randomized outcome trials have tested whether pharmacologic treatment of ISH can reduce cardiovascular events and stroke. In the SHEP trial, performed in 4736 subjects ≥60 years of age with SBP ≥160 mm Hg and DBP <90 mm Hg, initial therapy with a thiazide‐type diuretic with or without a β‐blocking agent reduced first stroke by 36%, and cardiovascular events by 27%. Heart failure was reduced by 49% overall with an 81% reduction in those with either a history or evidence of a prior myocardial infarction on electrocardiogram. In the 583 SHEP patients with type 2 diabetes, major cardiovascular events were reduced by 34%. The benefit of diuretic therapy was lost if the serum potassium level was not kept above 3.5 mg/dL.

Syst‐Eur randomized 4695 patients aged ≥60 years with SBP 160–219 mm Hg and DBP <95 mm Hg (European definition of ISH) to the moderately long‐acting dihydropyridine calcium channel blocker nitrendipine, with the addition of the angiotensin‐converting enzyme inhibitor enalapril, and a thiazide‐type diuretic as necessary, or to matching placebos. Over a median of 2 years of follow‐up, active treatment reduced stroke by 42% and all cardiovascular events by 31%.

In a prespecified subgroup of the Losartan Intervention For Endpoint reduction (LIFE) trial, losartan‐based therapy was superior to β‐blocker (atenolol)‐based therapy in the 14% of patients with ISH. All participants enrolled in LIFE had electrocardiographic evidence of left ventricular hypertrophy (ECG‐LVH). Baseline SBP was 174 mm Hg and DBP was 83 mm Hg. Over 4.7 years of follow‐up, SBP was reduced to 146 mm Hg and DBP to 74 mm Hg. Despite equivalent lowering of BP in both the losartan and atenolol groups, a 25% reduction in the combined end point of cardiovascular death, acute myocardial infarction, and stroke occurred in the group randomized to losartan. Of note, hydrochlorothiazide was added in almost all patients in both treatment groups.

A meta‐analysis of eight placebo‐controlled trials in elderly patients with ISH, which included 15,693 patients aged ≥60 years followed for an average of 3.8 years, found that active treatment reduced coronary events by 23%, stroke by 30%, cardiovascular death by 18%, and total death by 13%. In those patients older than age 70 years, the absolute benefit was particularly high; treating 19 patients for 5 years prevented one major fatal or nonfatal cardiovascular event.

Initial therapy with a thiazide‐type diuretic or dihydropyridine‐type calcium channel blocker is superior to placebo‐based therapy in persons with ISH. In addition, in those with ECG‐LVH, an angiotensin receptor blocker‐based strategy was more effective than a β‐blocker‐based regimen. As only 60% of elderly patients treated for ISH were controlled on a single agent in these clinical trials, the majority of elderly patients with ISH will require at least two to three drugs to achieve the SBP goal of <140 mm Hg.

The initial dose of an antihypertensive drug or drugs in an elderly patient should often be one half that used in a younger patient. This allows for the reduced renal or hepatic drug metabolism that often occurs in the elderly. The dose should be slowly increased until the maximum BP reduction occurs at the dose with the fewest side effects. Additional agents should be added until the BP goal is attained. Current recommendations state that BP should be reduced to <140/90 mm Hg in all elderly patients with hypertension and to <130/80 mm Hg in those with diabetes and/or renal insufficiency. In those who cannot achieve these goals, reducing SBP by at least 20 mm Hg from baseline results in an improvement in clinical outcome.

CLINICAL EVALUATION

A thorough history and physical examination should be performed in older patients with SBP elevation. Patients should be specifically questioned about the use of antihypertensive medications and how well their BP has been controlled in the past. In addition, they should specifically be asked about the use of nonsteroidal anti‐inflammatory agents and over‐the‐counter medications, including nasal sprays and cold remedies, as well as alternative therapies that are commonly used by elderly persons and may raise SBP.

Measurement of SBP can pose special problems in the elderly population. Pseudohypertension should be suspected in those with persistently high SBP when there is no evidence of target organ damage or when antihypertensive medication causes hypotensive symptoms in elderly patients with continually elevated cuff‐determined SBP. In these persons, the brachial arteries may be thickened and stiff and the SBP measurement may be an overestimation of actual intra‐arterial pressure.

SBP should be measured in the supine, sitting, and standing positions as the elderly are more prone to postural hypotension, especially after a meal. The occurrence of postural hypotension, that is, the reduction of SBP by 20 mm Hg upon standing, often limits the ability to control systolic hypertension and affects the ability to use sitting pressures to determine BP control. The standing BP, therefore, should be used in elderly persons to determine the dose of antihypertensive medication required and if SBP is controlled.

J‐CURVE HYPOTHESIS

Although achieving a BP of <140/90 mm Hg reduces the risk of vascular disease, the J‐curve hypothesis describes the concern that lowering DBP below a certain critical value while attempting to lower SBP increases the risk of cardiovascular death and morbid events in elderly patients with hypertension. Suggested only by observational and retrospective studies, prospective data validating this hypothesis have been lacking. The HOT study was designed to test whether intensive BP lowering was helpful or harmful in preventing cardiovascular events and death. The Prospective, Randomized, Open with Blinded Endpoint evaluation (PROBE) trial randomly assigned 18,790 persons with hypertension (mean age 61.5 years) from 26 countries to a target DBP of 80 mm Hg, 85 mm Hg, or 90 mm Hg and followed them for an average of 3.8 years. It found no increased cardiovascular risk for the DBP goal <80 mm Hg vs. <90 mm Hg. A retrospective analysis of the SHEP trial found no benefit in outcome in the few patients whose DBP was lowered to <55 mm Hg on antihypertensive therapy. As an increased occurrence of ischemic events has been prospectively observed in both placebo and actively treated patients with very low DBP, a low DBP is thought to serve more as a marker than a cause of cardiovascular events in those with underlying coronary disease. There continues to be disagreement among clinicians as to how low DBP can be lowered as we attempt to achieve the goal for SBP in an older patient. The current evidence suggests exercising caution in lowering DBP to <55 mm Hg when treating older persons with ISH.

CONCLUSION

Hypertension is a major risk factor for elderly persons and confers considerable morbidity and mortality. With the marked growth of the elderly population in the United States, practitioners will continue to see an expanding number of elderly patients with hypertension. ISH remains the most common form of hypertension in the elderly. It is also the most difficult to treat. There is substantial evidence to support the value of treating ISH. Practitioners need to continually focus their efforts on more effective control of SBP and change the past paradigm that suggested a reduction in DBP was more important than a reduction in SBP.

Clinical trials suggest that controlling SBP will be associated with a greater reduction in both cardiovascular and renal disease than if it remains uncontrolled. Greater emphasis must be placed on managing SBP elevation in the elderly population.