Hypertension In The Very Elderly Trial Research Articles

New Guidance Covers Ways to Prevent and Treat Hypertension in Elderly Patients

FOR THE FIRST TIME, CLINICIANS have guidelines on the prevention and treatment of hypertension specifically in individuals aged 65 years or older. The guidance, released in April, comes from an expert panel convened by the American College of Cardiology and the American Heart Association (Aronow WS et al. J Am Coll Cardiol. 2011;57[20]:2037-2114). Although hypertension is prevalent in this older population, found in 64% of men and 78% of women, control is far less common, said Wilbert S. Aronow, MD, clinical professor of medicine at New York Medical College/Westchester Medical Center and a cochair of the expert panel. “If you take a population age 70 or older, one-third of men and onefourth of women are adequately treated,” Aronow said. “And many clinicians are still unwilling to treat patients with hypertension; they believe it will increase mortality.” That belief has been reinforced over the years by studies suggesting that lowering blood pressure, while reducing risks of stroke and vascular complications, might increase risks for other adverse conditions. Moreover, rigorous study of hypertension control in the very old (those aged 80 years and older) has been nonexistent. But a 2008 study changed the landscape. The study, Hypertension in the Very Elderly Trial (HYVET), looked at treatment of 3845 patients aged 80 years or older randomized to antihypertensive therapy (indapamide [sustained release] with or without perindopril) or placebo. Compared with those receiving placebo, those enrolled in the active treatment group reduced their sitting mean systolic and diastolic blood pressures by 15.0 and 6.1 mm Hg and saw a 64% reduction in the rate of heart failure, a 23% reduction in the rate of death from cardiovascular causes, and a 21% reduction in the rate of death from any cause (Beckett NS et al. N Engl J Med. 2008;358[18]:1887-1898). And while the HYVET investigators were unable to show treatment benefit regarding the study’s primary end point of fatal or nonfatal stroke (the trial was stopped after about 2 years of follow-up for ethical reasons), the findings were compelling enough for Aronow to suggest developing and issuing guidelines for this patient population.

Office Management of Hypertension in Older Persons

Antihypertensive drug therapy reduces cardiovascular events in older persons. In the Hypertension in the Very Elderly Trial, at 1.8-year follow-up, patients aged 80 years and older treated with antihypertensive drug therapy had a 30% reduction in fatal or nonfatal stroke ( P = .06), a 39% reduction in fatal stroke ( P = .05), a 21% reduction in all-cause mortality ( P = .02), a 23% reduction in death from cardiovascular causes ( P = .06), and a 64% reduction in heart failure ( P < .001). The goal of treatment of hypertension is to lower the blood pressure to less than 140/90 mm Hg in older persons and to less than 130/80 mm Hg in older persons with diabetes or chronic kidney disease if tolerated. The selection of antihypertensive drug therapy in persons with associated medical conditions depends on their medical conditions. Large meta-analyses of published trials show that thiazide diuretics, angiotensin-converting enzyme inhibitors, calcium channel blockers, angiotensin receptor antagonists, and beta-blockers do not significantly differ in their ability to lower blood pressure and to exert cardiovascular protection in older and younger persons. If the blood pressure is more than 20/10 mm Hg above the goal blood pressure, drug therapy should be initiated with 2 antihypertensive drugs. Other coronary risk factors must be treated.

Blood pressure control in the Hypertension in the Very Elderly Trial (HYVET)

To report blood pressure control in the Hypertension in the Very Elderly Trial, a placebo-controlled trial of hypertensive (systolic blood pressure (SBP) 160-199 mm Hg, diastolic blood pressure (DBP) <110 mm Hg) participants over the age of 80 years, given treatment in three steps: indapamide slow release 1.5 mg alone, indapamide plus 2 mg perindopril and indapamide plus 4 mg perindopril. The difference in control between participants with combined systolic and diastolic hypertension (SDH, DBP90 mm Hg) and those with isolated systolic hypertension (ISH, DBP<90 mm Hg) is determined together with the effects of increments in the treatment regimen. At 2 years, the active treatment lowered blood pressure by 16.5/6.9 mm Hg more than that on placebo in participants with SDH and by 19.3/4.8 mm Hg more in those with ISH. The 2-year falls in pressure on placebo alone were 13.2/8.5 mm Hg in SDH and 8.2/1.5 mm Hg in ISH participants. With full titration of active treatment, 62% of SDH participants achieved goal SBP (<150 mm Hg) by 2 years and 71% of those with ISH. The corresponding results for DBP control (<80 mm Hg) were 40 and 78%. The addition of active perindopril 2 mg roughly doubled the percentage controlled, as did increasing to 4 from 2 mg. Blood pressure control was good with ISH and better than with SDH. The fall in SBP accounted for the observed 30% reduction in strokes, but the 21% reduction in total mortality and 64% reduction in heart failure were greater than predicted.

GUIDELINE-DRIVEN POLYPHARMACY IN ELDERLY, MULTIMORBID PATIENTS IS BASICALLY FLAWED: THERE ARE ALMOST NO GUIDELINES FOR THESE PATIENTS

To the Editor: Older adults suffering from multiple diseases are likely to receive polypharmacy; of people aged 65 and older, 44% of men and 57% of women take five or more drugs, and 12% take 10 or more drugs.1 Such situations may cause more harm than good, with up to 100,000 deaths in the United States annually attributable to medications.2 The motivation of doctors to treat all diagnoses according to guidelines is seen as a major cause of polypharmacy. A guideline recommends three drugs per disease on average. At a mean number of 3.3 diagnoses at age 80 and older,3 this means 10 drugs, and reality is in line with this simple math. Deviation from guidelines becomes unacceptable to doctors as they are educated to adhere to them, yet there is increasing discontent about this situation contributing to the polypharmacy debacle, and the obvious solution—prioritization—inevitably results in deviations from guidelines, maybe even blamed as “ageism.” Here lies the basic conceptual flaw, because there are almost no guidelines for older adults. Of 838 guidelines of the Association of the Scientific Medical Societies in Germany (154 specialty societies as members) database, only three are concerned with this age group (on urinary incontinence, psychosomatic geriatrics, and nutrition). Many guidelines contain sections on special patient groups, such as older adults. In the 2007 European Society of Cardiology/Hypertension Hypertension Guidelines, only 27 lines are devoted to this fast-growing population segment. The paucity of guidelines mainly reflects the lack of data for older adults. They rarely participate in clinical trials,4 and extrapolation from data for younger people is often not justified because biological diversity rises exponentially at higher age. Deviation from nonexisting guidelines (if they are strictly defined as evidence-based recommendations), thus, is no true problem. Exceptions are granted (e.g., for the treatment of arterial hypertension in the very elderly for which the recent Hypertension in the Very Elderly Trial (HYVET) generated groundbreaking evidence).5 One could wait for guidelines for very old adults, and scientists and patient interest groups frequently recommend conducting more clinical trials in older adults. In most situations, this could be an eternal endeavor; comorbidity and individual involution status generate millions of combinations of therapeutically relevant conditions. It appears to be impossible to study all of them properly. Thus, there will probably never be appropriate guideline sets for very old adults. The answer has much to do with skills and experiences that have guided medicine in the pre-evidence-based medicine (EBM) era; their intuitive integration was the basis for regarding medicine as an art. Despite the strengths of EBM, it is not applicable to younger patients if their individual morbidity pattern is incompatible with the data available, yet medicine can be successful if evidence is integrated and aligned with experiences and skills. Without evidence-based guidelines for older adults at hand, careful reasoning, patient assessment, treatment observation, and integration, as mentioned above, are the clues to success. Focusing on polypharmacy, these integrative processes should principally lead to drug prioritization as the only answer, although this prioritization needs to be structured and transparent. One of the most prominent prioritization tools is the Beers list.6 Unfortunately, clear proof of its utility in terms of safety and efficacy endpoints is still lacking.7 One reason could be the absence of a positive listing of drugs proven to be beneficial in older adults (see the HYVET example mentioned above). Paradoxically, undertreatment may be an important problem even in polypharmacy situations. Thus, drugs should be classified for negative and positive risk:benefit ratios. The “FORTA (fit forthe aged)” classification8 is the first proposal covering positive and negative aspects of drug appropriateness in older adults. Drugs chronically used in older adults are labeled from A through D, with A-labeled drugs being indispensable and associated with a positive risk:benefit ratio in older adults (e.g., angiotensin-converting-enzyme inhibitors in hypertension treatment), and D-labeled drugs those to avoid, thus similar to those in the Beers list. C-labeled drugs have a questionable risk:benefit profile, to be avoided first in polypharmacy situations. B-labeled drugs are those with some restrictions regarding their risk:benefit ratio, to be used if no A-labeled drugs are available or sufficient. Other proposals for prioritization tools are welcome, but they should take into consideration underused drugs and not only consist of negative listings. These facts and such tools should encourage and even legally empower physicians to deviate from “nonexisting guidelines” for the very old adults. Conflict of Interest: MW was employed by AstraZeneca R&D, Mölndal, as Director of Discovery Medicine (translational medicine) from 2004 to 2006 while on sabbatical leave from his professorship at the University of Heidelberg. After return to this position in January 2007, he received lecturing and consulting fees from Sanofi-Aventis, Novartis, Takeda, Roche, Pfizer, Bristol-Myers, Daichii-Sankyo, Lilly, and Novo-Nordisk. Author Contributions: MW is the sole author of this letter. Sponsor's Role: None.

Immediate and late benefits of treating very elderly people with hypertension: results from active treatment extension to Hypertension in the Very Elderly randomised controlled trial

Objective To assess if very elderly people with hypertension obtain early benefit from antihypertensive treatment.Design One year open label active treatment extension of randomised controlled trial (Hypertension in the Very...

Why and How We Should Treat Elderly Patients with Hypertension?

Double-blind, randomized, placebo-controlled studies have documented that antihypertensive drug therapy decreases cardiovascular events in older persons. In the Hypertension in the Very Elderly Trial, patients aged 80 years and older treated with antihypertensive drug therapy had at 1.8-year follow-up, a 30% insignificant decrease in fatal or nonfatal stroke, a 39% significant decrease in fatal stroke, a 21% significant decrease in all-cause mortality, a 23% insignificant decrease in death from cardiovascular causes, and a 64% significant decrease in heart failure. The goal of treatment of hypertension in older persons is to decrease the blood pressure to < 140/90 mm Hg and to <130/80 mm Hg in older persons with diabetes or chronic renal disease. Elderly persons with diastolic hypertension should have their diastolic blood pressure reduced to 80 to 85 mm Hg. There are no randomized controlled clinical trials supporting a target blood pressure of less than 130/80 mm Hg in elderly persons. The optimum diastolic blood pressure goal in elderly persons is unclear. Diuretics should be used as initial therapy in persons with no associated medical conditions. The selection of antihypertensive drug therapy in persons with associated medical conditions depends on their medical conditions. If the blood pressure is >20/10 mm Hg above the goal blood pressure, drug therapy should be initiated with 2 antihypertensive drugs. Other coronary risk factors must be treated.

Modelling Cognitive Decline in the Hypertension in the Very Elderly Trial [HYVET] and Proposed Risk Tables for Population Use

IntroductionAlthough, on average, cognition declines with age, cognition in older adults is a dynamic process. Hypertension is associated with greater decline in cognition with age, but whether treatment of hypertension affects this is uncertain. Here, we modelled dynamics of cognition in relation to the treatment of hypertension, to see if treatment effects might better be discerned by a model that included baseline measures of cognition and consequent mortalityMethodology/Principal FindingsThis is a secondary analysis of the Hypertension in the Very Elderly Trial (HYVET), a double blind, placebo controlled trial of indapamide, with or without perindopril, in people aged 80+ years at enrollment. Cognitive states were defined in relation to errors on the Mini-Mental State Examination, with more errors signifying worse cognition. Change in cognitive state was evaluated using a dynamic model of cognitive transition. In the model, the probabilities of transitions between cognitive states is represented by a Poisson distribution, with the Poisson mean dependent on the baseline cognitive state.The dynamic model of cognitive transition was good (R2 = 0.74) both for those on placebo and (0.86) for those on active treatment. The probability of maintaining cognitive function, based on baseline function, was slightly higher in the actively treated group (e.g., for those with the fewest baseline errors, the chance of staying in that state was 63% for those on treatment, compared with 60% for those on placebo). Outcomes at two and four years could be predicted based on the initial state and treatment.Conclusions/SignificanceA dynamic model of cognition that allows all outcomes (cognitive worsening, stability improvement or death) to be categorized simultaneously detected small but consistent differences between treatment and control groups (in favour of treatment) amongst very elderly people treated for hypertension. The model showed good fit, and suggests that most change in cognition in very elderly people is small, and depends on their baseline state and on treatment. Additional work is needed to understand whether this modelling approach is well suited to the valuation of small effects, especially in the face of mortality differences between treatment groups.Trial RegistrationClinicalTrials.gov NCT0012281

Treatment of hypertension in patients 80 years and older: the lower the better? A meta-analysis of randomized controlled trials

Results of randomized controlled trials are consistent in showing reduced rates of stroke, heart failure and cardiovascular events in very old patients treated with antihypertensive drugs. However, inconsistencies exist with regard to the effect of these drugs on total mortality. We performed a meta-analysis of available data on hypertensive patients 80 years and older by selecting total mortality as the main outcome. Secondary outcomes were coronary events, stroke, cardiovascular events, heart failure and cause-specific mortality. The common relative risk (RR) of active treatment versus placebo or no treatment was assessed using a random-effect model. Linear meta-regression was performed to explore the relationship between intensity of antihypertensive therapy and blood pressure (BP) reduction and the log-transformed value of total mortality odds ratios (ORs). The overall RR for total mortality was 1.06 (95% confidence interval 0.89-1.25), with significant heterogeneity between hypertension in the very elderly trial (HYVET) and the other trials. This heterogeneity was not explained by differences in the follow-up duration between trials. The meta-regression suggested that a reduction in mortality was achieved in trials with the least BP reductions and the lowest intensity of therapy. Antihypertensive therapy significantly reduced (P < 0.001) the risk of stroke (35%), cardiovascular events (27%) and heart failure (50%). Cause-specific mortality was not different between treated and untreated patients. Treating hypertension in very old patients reduces stroke and heart failure with no effect on total mortality. The most reasonable strategy is the one associated with significant mortality reduction; thiazides as first-line drugs with a maximum of two drugs.

The effect of treatment based on a diuretic (indapamide) ACE inhibitor (perindopril) on fractures in the Hypertension in the Very Elderly Trial (HYVET)

fractures may have serious implications in an elderly individual, and fracture prevention may include a careful choice of medications. the Hypertension in the Very Elderly Trial (HYVET) was a double-blind placebo-controlled trial of a thiazide-like diuretic (indapamide 1.5 mg SR) with the optional addition of the angiotensin-converting enzyme (ACE) inhibitor (perindopril 2-4 mg). Fracture was a secondary end point of the trial. HYVET recruited participants from Eastern and Western Europe, China, Australasia, and Tunisia. all participants were > or =80 years of age and hypertensive. participants were randomised to receive a thiazide-like diuretic (indapamide 1.5 mg SR) +/- ACE inhibitor (perindopril 2-4 mg) or matching placebos. Incident fractures were validated and analysed based on time to first fracture. there were 3,845 participants in HYVET and a total 102 reported fractures (42 in the active and 60 in the placebo group). When taking only validated first fractures, 90 were included in the analyses (38 in the active and 52 in the placebo group). Cox proportional hazard regression, adjusted for key baseline risk factors, resulted in a point estimate of 0.58 (95% CI 0.33-1.00, P = 0.0498). despite the lowering of blood pressure, treatment with a thiazide-like diuretic and an ACE inhibitor does not increase and may decrease fracture rate.

“The Lower the BP the Better” Paradigm in the Elderly

If a man will begin with certainties, he shall end in doubts; but if he will be content to begin with doubts, he shall end in certainties.— —Francis Bacon, The Advancement of Learning, year 1605 Hypertension is a growing public health problem in elderly people, with a prevalence up to 80% in individuals aged ≥70 years. Isolated systolic hypertension accounts for 60% to 75% of cases, systolic blood pressure (BP) being the dominant prognostic marker.1 Unfortunately, the rate of hypertension control only minimally improved over last year’s in elderly subjects when compared with the younger people.2 Several randomized clinical trials tested the benefit of treatment in elderly patients with isolated systolic hypertension or systolic-diastolic hypertension. Staessen et al3 reviewed 8 randomized clinical trials carried out in patients with isolated systolic hypertension and aged ≥60 years. Active treatment reduced total mortality by 13%, cardiovascular (CV) mortality by 18%, all CV complications by 26%, stroke by 30%, and coronary events by 23%. The benefits of treatment in octogenarians remained unproved for years up to the results of the Hypertension in the Very Elderly Trial, in which 3845 patients aged ≥80 years with systolic BP ≥160 mm Hg were randomized to indapamide or placebo. Perindopril or matching placebo was added if necessary to achieve the target BP of 150/80 mm Hg. The trial was stopped after less than 2 years of follow-up because of a beneficial effect of treatment on several outcomes including all-cause mortality, although the primary study outcome, fatal or nonfatal stroke, was only marginally reduced (by …

Association of depression with subsequent mortality, cardiovascular morbidity and incident dementia in people aged 80 and over and suffering from hypertension. Data from the Hypertension in the Very Elderly Trial (HYVET)

depression is common in elderly people and may be associated with increased cardiovascular risk and incident dementia. participants in the Hypertension in the Very Elderly Trial (HYVET) completed a depression screening instrument, the Geriatric Depression Score (GDS), at baseline and annually. We examined the association of GDS score with incident stroke, mortality and dementia using Cox proportional hazards models (hazard ratios, HR and 95% confidence intervals, CI) adjusted for treatment group and other potential confounders. 2,656 HYVET participants completed the GDS. The mean follow-up was 2.1 years. A GDS score > or =6 was associated with increased risks of all-cause (HR 1.8, 95% CI 1.4-2.3) and cardiovascular mortality (HR 2.10, 95% CI 1.5-3.0), all stroke (HR 1.8, 95% CI 1.2-2.8) and all cardiovascular events (HR 1.6, 95% CI 1.2-2.1). Risk of incident dementia also tended to be increased (HR 1.28, 95% CI 0.95-1.73). Each additional GDS point at baseline also gave rise to a significantly increased risk of fatal and non-fatal cardiovascular events, all-cause mortality and dementia. there was a strong association between baseline depression scores and later fatal and non-fatal cardiovascular endpoints over a mean follow-up of 2 years in a hypertensive very elderly group. The mechanism of this association warrants further study.

The Clock Is Ticking: The Case for Achieving More Rapid Control of Hypertension

The Clock Is Ticking: The Case for Achieving More Rapid Control of Hypertension

Managing hypertension in the very elderly: effect of adverse drug reactions (ADRs) on achieving targets

The Hypertension in the Very Elderly trial (HYVET), demonstrated the benefit of antihypertensive treatment in patients >or=80 years. However, patients in this age group are at increased risk of drug interactions and adverse effects. We conducted a retrospective cohort study, in hypertensive patients aged >or=80 years, to determine whether it is possible to follow the HYVET guidelines in an everyday clinical setting. We identified 100 patients aged >or=80 years referred to the Hypertension Clinic, University Hospital Birmingham, over a 10-year period. Most patients were referred to the clinic because of poorly controlled blood pressure despite treatment and all had 24 h ambulatory blood pressure monitoring (ABPM) as part of their assessment. All patients tolerated ABPM, and a 'white coat' effect was demonstrated in 33 patients. In 64 out of 100 patients (57 on treatment), the ABPM confirmed poor blood pressure control. Despite this, 26 of these patients had an antihypertensive either stopped (15), and /or reduced (3) or left unchanged (9) at clinic because of documented adverse drug reactions (ADRs). In 36 out of 100 patients, no additional antihypertensive therapy was needed because the blood pressure was either well-controlled on treatment (28), over-treated (4), or normotensive with a white coat effect (4). Despite this, antihypertensive agents were either stopped (10), and or reduced (5) because of ADRs in half the patients (14) from the well-controlled group. In conclusion, 40% patients had documented ADRs overall which limited further intervention, suggesting that implementation of the HYVET recommendations in clinical practice may be difficult.

Reappraisal of the European guidelines on hypertension management. The European Society of Hypertension Task Force document: a short review

The European Society of Hypertension Task Force document on reappraisal of the 2007 European guidelines on hypertension addresses a number of studies published in the last 2 years to estimate their contribution to the expanding knowledge on hypertension. The importance of total cardiovascular risk with inclusion of subclinical cardiac, vascular, and renal organ damage was reemphasized, followed by a critical reappraisal of recommendations for the initiation of antihypertensive drug treatment in patients with high normal blood pressure (BP) and grade 1 hypertension. Whereas there is sufficient evidence for reducing BP below 140/90 mmHg in most hypertensives, the recommendation of previous guidelines to aim at a lower BP in diabetics and in patients at very high cardiovascular risk is not consistently supported by trial evidence. Moreover, the J-curve phenomenon may occur in patients at high cardiovascular risk. With regard to the choice of antihypertensive drugs, the conclusions of the 2007 guidelines that diuretics, angiotensin-converting enzyme inhibitors, calcium antagonists, angiotensin receptor antagonists, and beta-blockers are suitable for initiation and maintenance of antihypertensive treatment are reinforced. Furthermore, apart from starting with combination therapy in certain conditions, adding a drug from another class to the initially prescribed one is preferred to increasing the dose of the first one. Some of the drug combinations recommended in 2007 are now regarded as more recommendable. In addition to the benefits of antihypertensive treatment in the elderly, the HYVET (Hypertension in the Very Elderly Trial) has shown that antihypertensive treatment also has benefits in octogenarians. The document ends with a number of issues in urgent need to be approached by new trials.

Cardiovascular and biochemical risk factors for incident dementia in the Hypertension in the Very Elderly Trial

Several cardiovascular and biochemical factors including hypertension have been associated with cognitive decline and dementia, although both epidemiological and intervention evidence is mixed with the majority of studies examining those in midlife or younger elderly and the recent Hypertension in the Very Elderly Trial showing no significant association between blood pressure lowering and incident dementia. It has also been suggested that risk factors may differ in the very elderly. The aim of these analyses was to examine the impact of baseline cardiovascular and biochemical factors upon incident dementia and cognitive decline in a very elderly hypertensive group. Participants of the Hypertension in the Very Elderly Trial were aged at least 80 years and hypertensive. Cognitive function was assessed at baseline and annually with diagnostic information collected for dementia and relationships between baseline total and high-density lipoprotein cholesterol, creatinine, glucose, haemoglobin, heart failure, atrial fibrillation, diabetes, previous stroke and later dementia/cognitive decline were examined. There were 3336 participants with longitudinal cognitive function data. In multivariate analyses higher creatinine was associated with a lower risk of incident dementia and cognitive decline. Higher total and lower high-density lipoprotein cholesterol were associated with lower risk of cognitive decline. Other variables were not significant. In very elderly hypertensive patients heart failure, diabetes, atrial fibrillation, prior stroke, glucose and haemoglobin levels did not demonstrate a relationship with cognitive decline or dementia. Higher creatinine (excluding moderate renal impairment) was associated with a lower risk of dementia and cognitive decline. The findings for total and high-density lipoprotein cholesterol add to the varied literature in this area and together these findings may add weight to the suggestion that risk factor profiles differ in the very elderly.

Treatment of hypertension in an elderly outpatient population in the Netherlands

Background: The treatment of older patients with hypertension has been controversial—in addition to uncertainty regarding appropriate blood pressure (BP) targets in the very old, there are concerns that excessive BP lowering could result in adverse events such as falls, stroke, and cognitive problems. The Hypertension in the Very Elderly Trial (HYVET), however, found that lowering BP in patients aged ≥80 years was associated with decreased morbidity and mortality. Objective: This study compared the findings of HYVET with data from a population of elderly outpatients with hypertension in a clinical practice setting. Methods: This was a retrospective study of prospectively collected data from patients aged ≥80 years with a history of hypertension who visited a geriatric diagnostic day clinic in the Netherlands in 2004. The data were analyzed to determine how many patients were being prescribed antihypertensive medication, how many would have been eligible for HYVET, how many achieved adequate BP control, and whether reaching BP goals was associated with the number and type of antihypertensive medications received or with eligibility for HYVET. Results: During 2004, 518 patients aged ≥80 years visited the geriatric diagnostic day clinic, of whom 147 met the criteria for inclusion in this study. One hundred forty-one patients (95.9%) were receiving antihypertensive medication, although only 52 (35.4%) would have been eligible for HYVET. Dementia, which was an exclusion criterion in HYVET, was the major reason for ineligibility (70 [47.6%]). Greater proportions of patients in this study had comorbidities compared with the HYVET population (stroke: 22.4% vs 6.7%, respectively; myocardial infarction: 7.5% vs 3.1%; heart failure: 11.6% vs 2.9%; diabetes mellitus: 21.1% vs 6.8%). At the time of the clinic visit, 50.3% of patients had adequate BP control, as defined in HYVET (systolic BP <150 mm Hg and diastolic BP <80 mm Hg). Levels of BP control were similar in patients who would and would not have been ineligible for HYVET. Only the mean (SD) number of antihypertensive medications received was significantly associated with the achievement of BP control compared with failure to achieve adequate BP control (2.2 [1.0] vs 1.8 [1.1], respectively; P < 0.05). Conclusions: Based on the findings of this study, the benefits of treating elderly patients with hypertension in clinical practice may be lower than those reported by HYVET. The study results support the current recommendation that all patients with hypertension should be treated with >1 antihypertensive medication if adequate control is not achieved at low doses of a single medication.

Hypertension, dementia, and antihypertensive treatment: Implications for the very elderly

A wealth of longitudinal epidemiologic evidence links high blood pressure or hypertension to cognitive decline and incident dementia. Some (but not all) studies have suggested that antihypertensive treatment is beneficial, reducing risk of decline and dementia. There are plausible mechanisms to support the possibility that hypertension may increase the risk of dementia. There is also evidence suggesting that the two dementia types thought to be most common, Alzheimer's disease and vascular dementia, have overlapping risk factors. Seven placebo-controlled trials of antihypertensive treatment have assessed cognitive function, incident dementia, or both, with mixed outcomes. The Hypertension in the Very Elderly Trial (HYVET), despite showing reductions in mortality and stroke with active treatment, found no significant reduction of incident dementia, although the trial was stopped early. Meta-analyses used to explore this area further are inconclusive, and comparative trials are now required.

Sociodemographic and lifestyle risk factors for incident dementia and cognitive decline in the HYVET

previous studies have suggested that smoking, living alone and having a high body mass index may increase risk of developing dementia whereas a normal body mass index, having received education and moderate alcohol consumption may decrease risk. Dementia risk also increases with age and is thought to be higher in hypertensives. we used data collected in the Hypertension in the Very Elderly Trial (HYVET), and cognitive function was assessed using the Mini-Mental State Examination (MMSE) at baseline and annually. Participants with a fall in MMSE to <24 or with a fall of 3 points in any 1 year were investigated further. The association of baseline sociodemographic, medical and lifestyle factors with incident dementia or decline in MMSE scores was assessed by regression models. incident dementia occurred in 263 of 3,336 participants over a mean follow-up of 2 years. In multivariate analyses, being underweight, BMI < 18.5 (HR 1.90, 95% CI 1.06-3.39) or obese, BMI >30 (HR 1.84, 95% CI 1.24-2.72), increased risk of incident dementia as did piracetam use (HR 2.72, 95% CI 1.60-4.63). Receiving formal education was associated with a reduced risk (HR 0.59, 95% CI 0.45-0.78). There was no association with smoking, alcohol and gender. Similar results were found when examining mean annual change in the MMSE score. our results for BMI and education agree with those from other studies. The increased risk associated with piracetam may reflect awareness of memory problems before any diagnosis of dementia has been made. Trial participants may be healthier than the general population and further studies in the general population are required.

BLOOD PRESSURE AND MORTALITY IN VERY OLD PEOPLE

To the Editor: In a small population-based cohort study of 348 adults aged 85 and older, Molander et al. showed that systolic blood pressure (SBP) less than 120 mmHg was significantly associated with mortality, after adjusting for age, sex, activities of daily living, Mini-Mental State Examination score, atrial fibrillation, and diabetes mellitus, and concluded that optimal SBP for this age group could be greater than 140 mmHg.(1) Although the authors noted the limitations to their study, we have concerns about the conclusions and their potential clinical implications. First, blood pressure in a subgroup of very old adults, particularly with heart failure, could be a reflection of failing physiological systems. Although a remote high blood pressure is a well-known risk factor for heart failure(2) and cardiovascular events,(3,4) lower blood pressure paradoxically portends poorer prognosis in patients with heart failure. (5,6) Thus, the study sample appears to have included at least two distinct groups of very old adults—a group with heart failure, in which lower blood pressure is a marker of failing cardiovascular system and is associated with higher mortality, and a group without heart failure, in which high blood pressure might remain as a risk factor for cardiovascular morbidity and mortality. Such differential effect of blood pressure should be examined before the authors' conclusions are propagated in clinical practice. In addition, the authors did not measure blood pressure serially over the follow-up period. This would assess whether those with declining blood pressure are midway in their trajectory to death. Second, there were alarming differences in functional status and comorbidities between those with SBP less than 120 mmHg and those with SBP above 160 mmHg. In particular, dementia and heart failure were three times as prevalent in the former group as in the latter group. Although the authors attempted to control for confounders using multivariable regression, the stepwise selection did not include biologically plausible confounders, such as heart failure and dementia. Furthermore, mortality with dementia and lower blood pressure in heart failure patients remains high beyond the first year,(5–7) and excluding deaths within the first year does not eliminate this effect completely. Finally, the authors did not address survival bias, which plagues observational studies on blood pressure in very old people. In the Second National Health and Nutrition Examination Survey Mortality Study, those who had fatal stroke were older and more likely to be male and had higher blood pressure than those who did not.(8) This might have biased the study results by selectively including older adults who survived the effects of high blood pressure and are still robust until age 85 in the group with SBP above 160 mmHg, as reflected in Table 2. Taking these into account, we are concerned that the findings from this observational study may mislead clinicians into not treating high blood pressure in many older adults who are likely to benefit from blood pressure reduction. The benefit of antihypertensive treatment in those aged 80 and was recently demonstrated in the Hypertension in the Very Elderly Trial.(9) What this study by Molander et al. really tells us is that those with SBP less than 120 mmHg have extensive comorbidities and poor prognosis and therefore require comprehensive geriatric-oriented evaluations for reasons for their low blood pressure to maximize their function.

Vascular risk factors and cognitive function among 3763 participants in the Hypertension in the Very Elderly Trial (HYVET): a cross-sectional analysis

It is well known that the global population is aging and that those over the age of 80 are the fastest growing part of this expansion. Also known is that prevalence of hypertension and cognitive decline both increase with increasing age. The Hypertension in the Very Elderly Trial (HYVET) was a double blind placebo-controlled trial of antihypertensive treatment (indapamide SR 1.5 mg +/- perindopril 2-4 mg) and recruited only those hypertensives who were aged 80 or over and were without a diagnosis of dementia at baseline. Systolic blood pressure had to be in the range 160-199 mmHg and diastolic pressure <110 mmHg. Cognitive function was assessed at baseline using the Mini-mental State Examination prior to randomization into the trial. Also collected at baseline was information relating to sociodemographic, clinical, cardiovascular and biochemical factors which may impact upon cognitive function. This paper reports on the baseline cognitive function data from the HYVET trial and its relationship to these factors. The mean age of the 3763 HYVET participants who had full cognitive function data at baseline was 83.6 years; 60 percent were female. The median MMSE score at baseline was 26 and, in multivariate analyses, higher at younger age, with male gender, higher educational level, having higher creatinine, higher total cholesterol and lower high-density lipoprotein cholesterol. This is the first such study to examine a large number of very elderly hypertensives and it shows some similar patterns to those seen in younger elderly groups.