The expert consensus document in the elderly1 is designed to cover topics that have incomplete evidence-based information regarding clinical practice, and therefore often must be altered significantly on the basis of future randomized controlled trials (RCTs). Hence, it is not uncommon for consensus documents to have both strengths and potential weaknesses.
For example, the guidelines stress the importance of using 24-hour ambulatory blood pressure (BP) measurement as the ideal method of diagnosing both masked and white-coat hypertension1; indeed, errors of detection are magnified in the elderly population with isolated systolic hypertension (ISH) because of increased BP variability contributing to white-coat hypertension and white-coat effect. The consensus statement1 emphasizes these points but neglects to mention that recruitment of elderly subjects for RCTs exclusively by clinic BP will perpetuate the inclusion of those with white-coat hypertension and excessive white-coat effect and exclude those with masked hypertension. These errors of recruitment may lead to mistakes in defining optimal target BP treatment goals for the elderly hypertensive subjects in general and for specific subgroups in particular, such as those with diabetes, chronic kidney disease, and cerebrovascular and cardiovascular disease.
Guidelines for initiating and defining the target goal of antihypertensive therapy in the elderly have been updated.1 Indeed, to date, there have been no intervention trials involving the elderly that used systolic BP (SBP) target goals of <140 or <150 mm Hg, but instead used SBP target goals of <160 mm Hg; surprisingly, national and international guidelines used target goals of <140 mm Hg for all ages, largely on the basis of expert opinion rather than on outcome of RCTs. The new consensus statement1 confirms that antihypertensive therapy should be started in uncomplicated hypertension in persons age 65–79 years with a SBP of ≥140 mm Hg or a diastolic BP (DBP) of ≥90 mm Hg, with a target goal of <140/90 mm Hg (again, based on expert opinion only); however, in persons age ≥80 years, the threshold for starting therapy and target goal was raised to a SBP of ≥150 mm Hg. Importantly, BP should also be measured with the patient in the standing position for 1–3 minutes to evaluate for postural hypotension (not an infrequent finding in the elderly), and these standing values can be used to determine target goals.1 Furthermore, this consensus statement implies (again, based on expert opinion) that physiological rather than chronological age of ≥80 years can be considered in lowering SBP to <140–145 mm Hg with 2 or 3 antihypertensive agents that are well tolerated.1
There has been doubt as to the age limit beyond which there was no benefit or even increased risk for treating geriatric hypertension. In 1991, the landmark double-blinded, placebo-controlled Systolic Hypertension in the Elderly Program (SHEP) study first established that older patients with ISH and a mean age of 72 years benefited from antihypertensive lowering of stage 2 ISH (≥160 mm Hg). The Hypertension in the Very Elderly Trial (HYVET) study,2 voted the outstanding BP trial of 2008, involved the very old (age 80–105 years, mean age 83 years) and utilized a randomized, double-blind, placebo-controlled protocol in 3845 subjects with sustained SBP of ≥160 mm. This study of stage 2 ISH and systolic-diastolic hypertension showed that there was a significant reduction in both fatal (45%) and all strokes (34%) and heart failure (−72%), and reduction in both cardiovascular (−27%) and all-cause mortality (−28%).2 Therefore, there is overwhelming evidence that effective pharmacological lowering of BP by a mean decrease of 12/4 mm Hg reduced cardiovascular events in this elderly population.2 On the other hand, there are questions that remain unanswered in the HYVET study.1 The majority of recruited subjects for HYVET were healthy and robust; would an increasing number of frail elderly give different results? Second, what is the optimal BP target goal for maximizing therapeutic benefit in the HYVET study? Furthermore, RCTs in subjects recruited with ambulatory BP monitoring or home BP monitoring are needed to answer these important questions.
The question of which class of drugs is best suited to start first in patients with ISH remains controversial.1 Diuretics and calcium channel blockers have been shown to be effective in the elderly in lowering BP and in reducing cardiovascular events in major intervention studies.1 Of the diuretics, chlorthalidone, with a substantially longer half-life than hydrochlorothiazide, is twice as potent at the same dosage and is especially effective in controlling nighttime hypertension.1 Beta-blockers have been used for the treatment of hypertension, but evidence for the reduction in cardiovascular disease events in older patients with uncomplicated hypertension has been unconvincing.3
Combination therapy is favored over monotherapy for many reasons: increased efficacy, avoidance of side effects because of lower dosage and reciprocal drug effects, convenience when given in a single pill, and further reduction in morbidity and mortality when compared with single antihypertensive agents, as proven in RCTs.1 Indeed, most elderly hypertensives need combination therapy to reach therapeutic goal; when goal therapy is ≥20/10 mm Hg above SBP/DBP target goal, it may be preferable to start with combination therapy.1 Importantly, using blockade of the renin-angiotensin-aldosterone-system (RAAS) is a logical foundation for therapy; combining the RAAS inhibitor with either a diuretic or calcium channel blocker is scientifically logical, and tends to restore dose responsiveness regardless of the activity of the RAAS and/or the extent of salt sensitivity.
Elderly individuals with complicated hypertension (ie, with associated coronary heart disease, left ventricular hypertrophy, diastolic or systolic cardiac dysfunction, heart failure, atrial fibrillation, stroke, diabetes, or chronic renal failure) will require specific therapy for their primary complication, in addition to antihypertensive medication. Whether lowering BP to <130/80 mm Hg in these high-risk cardiovascular disease patients further reduces morbidity and mortality remains controversial. There is probable heterogeneity of responses1; patients who are prone to develop stroke, macroproteinuric chronic kidney disease, heart failure, or aortic aneurysms will profit by having their hypertension lowered to <30/80 mm Hg, whereas those with coronary heart disease may not benefit from BP <130/70, and may indeed be at greater risk with these lower levels of BP because of reduction in coronary blood flow, resulting in ischemia.4
Resistant hypertension is defined as failure of a rational 3-drug regimen, including an adequate dose of a diuretic to reduce BP <140/90 mm Hg.1 The many causes of resistant hypertension include ≥stage 2 ISH, older age with increased arterial stiffness, black race, obesity, diabetes, sleep apnea, excessive alcohol intake, stage ≥3 chronic kidney disease (especially with macroalbuminuria), secondary causes of hypertension, and living in the southeastern United States. It should also be noted that not every patient with resistant hypertension, as defined above, is at the same risk; in a Spanish population study,5 as many as one-third of patients with resistant hypertension were found to have white-coat resistance, and therefore many of them may have been overtreated. Therefore, there is a special need to use 24-hour ambulatory BP monitoring on patients with resistant hypertension.5 The use of aldosterone inhibitors has been especially effective in successfully reversing resistant hypertension. Not only is hyperaldosteronism present in ∼20% of patients with resistant hypertension, but also, in the absence of elevated blood aldosterone levels, the response rate to these inhibitors (spironolactone or eplerenone) when added as a fourth agent results in a mean reduction of 20/10 mm Hg of SBP/DBP; this represents approximately twice as large a response as obtained with the addition of other classes of antihypertensive agents.6
Indeed, as with most consensus documents, the present encyclopedic treatise on hypertension in the elderly, reviewing 740 recent and past publications, has major strengths and some weaknesses.