Hypertension In The Very Elderly Trial Research Articles

Commentary on recent guidelines for treating hypertension.

The American College of Cardiology Foundation/American Heart Association 2011 expert consensus document on hypertension in the elderly recommended a blood pressure < 140/90 mm Hg in adults younger than 80 years of age at high risk for cardiovascular events [1]. On the basis of data from the Hypertension in the Very Elderly Trial [2], these guidelines state that the systolic blood pressure (SBP) should be reduced to 140–145 mm Hg if tolerated in adults aged 80 years and older [1]. I concur with these guidelines [3–7].

Treating hypertension in the very elderly—benefits, risks, and future directions, a focus on the hypertension in the very elderly trial

Although the number of individuals reaching 80 who are considered to be healthy is increasing, the very elderly are likely to have long-term conditions, to report symptoms and/or be taking at least one regular medication. The impact of antihypertensive treatment has to be taken into account in this context. The treatment regimen in Hypertension in the Very Elderly Trial with a goal blood pressure of <150/80 mmHg has been shown to provide benefits in terms of a reduction in risk of total mortality, stroke, and cardiovascular events with potential benefits and no evidence of increased risk for fracture, dementia, depression, and quality-of-life outcomes. Questions remain as to the level of benefit that would be accrued in the frailer elderly and those at extreme age, for example, over 90.

Increased pulse pressure linked to dementia

High blood pressure (BP) has been associated with increased risk of dementia. Concerns have been raised about lowering BP too far in the very elderly and thereby increasing risk. There is some evidence to suggest a potential 'J'-shaped relationship between DBP and risk of cognitive impairment. This was investigated using data from the HYpertension in the Very Elderly Trial (HYVET). HYVET was a double-blind, placebo-controlled trial of antihypertensives in patients aged at least 80 years with an untreated SBP of 160-199 mmHg. Active medication was indapamide sustained release 1.5 mg+/- perindopril 2-4 mg to reach goal pressure of less than 150/80 mmHg. Incident dementia was a secondary endpoint and was not significantly different between the two treatment groups. The relationship between pressure and incident dementia was assessed using Cox proportional hazards regression with BP entered as either a discrete (quartile analysis) or continuous predictor variable. Achieved BP was calculated as the mean of all pressures from the 9 month visit onwards. During a mean follow-up of 2.2 years 263 incident cases of dementia were diagnosed. After adjustment for various covariates, baseline DBP was inversely related to incident dementia (P=0.0064). Achieved DBP did not predict later dementia in the placebo group (P=0.43), but showed a U-shaped relationship in the active treatment group (P=0.0195). The relationship between incident dementia and DBP did however not differ significantly between the placebo and active treatment groups (P=0.38). SBP was not associated with incident dementia, at baseline (P=0.62) or during follow-up (placebo group P=0.13, active group P=0.36). Wider achieved pulse pressure (PP) was associated with increased risk of dementia in both treatment groups (placebo P=0.032, active P=0.0046). The same tendency was observed for baseline PP (P=0.095). Wider PP may possibly indicate an increased risk for dementia. Active treatment may act to change the shape of the relationship between DBP and dementia. Future studies need to focus on exploring the ideal goal pressure for this age group.

Abstract 512: Drugs in the Elderly: Threats and Opportunities

Taking 10 and more drugs is unpredictable and may cause more harm than good, given that up to 100,000 medication-related deaths in the United States annually. An early attempt to improve drug safety in the aged population was the establishment of criteria for drugs to avoid by Beers in 1997. The evidence for the effectiveness of the Beers list is not compelling.. There should also be a positive labelling of drugs that are indispensable in elderly people as data on morbidity, mortality, and safety are available or emerging for this particular group. There is increasing clinical evidence for beneficial action of, for example, antihypertensive drugs (e.g., Hypertension in the Very Elderly Trial) in elderly people. Drugs should be labelled taking into consideration their usefulness for elderly people (Table 1) This classification would be an extension of the Beers approach into the positive listing of valuable drugs. This seems necessary as overtreatment and undertreatment are both typical problems of the aged population. Undertreatment, for example, relates to the poor control of arterial hypertension elderly people and may leave more than half of the patients un- or undertreated. The FORTA classification for antihypertensive drugs as an example is as follows: diuretics B, betablockers B, renin-angiotensin-system blockers A, long acting dihydropyridine calcium channel blockers (CCB) A, CCBs, verapamil type D, spironolactone C, alphablockers C, clonidine D, minoxidil D. The typical use of the scheme would address general practitioners struggling with polypharmacy. They would then synthesize the recommendations into a rank order of drugs that they could use to cut the list short.

Treatment of Hypertension in the Elderly

Numerous double-blind, randomized, placebo-controlled studies have shown that antihypertensive drug therapy reduces cardiovascular events in elderly 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 percent reduction in fatal or nonfatal stroke, a 39 percent reduction in fatal stroke, a 21 percent reduction in all-cause mortality, a 23 percent reduction in death from cardiovascular causes, and a 64 percent reduction in heart failure. The goal of treatment of hypertension in elderly persons is to lower the blood pressure to less than 140/90 mmHg and to less than 130/80 mmHg in older persons with diabetes or chronic renal insufficiency. All antihypertensive drugs may predispose the elderly person to develop symptomatic orthostatic hypotension and postprandial hypotension and syncope or falls. Adverse effects depend upon the antihypertensive drugs used, the doses of these drugs, the comorbidities in the elderly patients taking these drugs, and drug-drug interactions.

Hypertension-Related Stroke Prevention in the Elderly

Hypertension is a major risk factor for cardiovascular events, including ischemic stroke and hemorrhagic stroke. Reduction of blood pressure by lifestyle measures and antihypertensive drug therapy reduces stroke in elderly men and women. The use of diuretics, beta blockers, calcium channel blockers, angiotensin-converting enzyme inhibitors, or angiotensin receptor blockers causes a similar reduction in reducing coronary events and stroke for a given reduction in blood pressure. The American College of Cardiology Foundation/American Heart Association 2011 expert consensus document on hypertension in the elderly recommended that the blood pressure should be reduced to less than 140/90mm Hg in adults younger than 80years at high risk for cardiovascular events. On the basis of data from the Hypertension in the Very Elderly trial, these guidelines recommended that the systolic blood pressure should be reduced to 140 to 145mm Hg if tolerated in adults aged 80years and older. The 2013 European Society of Hypertension guidelines recommended that reducing blood pressure to less than 130/80mm Hg in adults at high risk for cardiovascular events was unsupported by prospective trial data. The systolic blood pressure should be reduced to less than 140mm Hg in these adults and to between 140 to 150mm Hg in adults aged 80years and older.

Prevalence and covariates of electrocardiographic left ventricular hypertrophy in the Hypertension in the Very Elderly Trial

To estimate the prevalence and covariates of electrocardiographic left ventricular hypertrophy (LVH) in the Hypertension in the Very Elderly Trial. A total of 2993 hypertensive people aged at least 80 years with technically codable ECGs without pacing, bundle branch block, or ECG myocardial infarction were studied. LVH was assessed using Sokolow-Lyon (SL-LVH), Cornell voltage (CV-LVH), and Cornell product criterion (CP-LVH). The prevalence of LVH varied from 2.4 to 17.5% depending on sex, race, and ECG criterion. The highest prevalence of SL-LVH (12.0%) was in Chinese men and in white women for both CV-LVH (17.5%) and CP-LVH (12.9%). Increasing SBP was an independent covariate of the presence of LVH in Chinese women independently of the criterion used (β = 0.052-0.069, P < 0.001), of SL-LVH in Chinese men (β = 0.047 P = 0.006). In white women, CP-LVH was associated with increasing age (β = 0.055, P = 0.027) and SBP (β = 0.023, P = 0.040). Increasing BMI was associated inversely with SL-LVH; the association in white men only was not significant. In white men, a history of diabetes was directly and history of antihypertensive drug treatment inversely related to CV-LVH and CP-LVH. SL-ECG was associated inversely to serum uric acid concentration in Chinese women and to serum hemoglobin concentration in Chinese men. Prevalence and covariates of electrocardiographic LVH varied by sex, race, and ECG criterion. CP-LVH may prove to be the most useful measure of LVH in this study owing to its close relationship to SBP, at least in women, and independence from BMI.

The Hypertension in the Very Elderly Trial - latest data.

Early trials in the field of hypertension focused on adults in their fifties and sixties. However, with the passage of time, a progressive effort has been made to expand the evidence base for treatment in older adults. 2008 saw publication of data from the Hypertension in the Very Elderly Trial which demonstrated significant mortality and morbidity benefits from antihypertensive therapy in octogenarians. More recently, additional data from this cohort has been published suggesting that appropriate anti-hypertensive therapy may lead to a reduction in incident cognitive impairment and fractures, whilst a 1 year open label extension of the main study confirmed many of the original trial findings. This review provides an overview of the Hypertension in the Very Elderly Trial whilst also discursively evaluating the latest data.

Does White Coat Hypertension Require Treatment Over Age 80?

White coat hypertension is considered to be a benign condition that does not require antihypertensive treatment. Ambulatory blood pressure (ABP) was measured in 284 participants in the Hypertension in the Very Elderly Trial (HYVET), a double-blind randomized trial of indapamide sustained release 1.5 mg±perindopril 2 to 4 mg versus matching placebo in hypertensive subjects (systolic blood pressure 160–199 mm Hg) aged &gt;80 years. ABP recordings (Diasys Integra II) were obtained in 112 participants at baseline and 186 after an average follow-up of 13 months. At baseline, clinic blood pressure (CBP) exceeded the morning ABP by 32/10 mm Hg. Fifty percent of participants fulfilled the established criteria for white coat hypertension. The highest ABP readings were in the morning (average 140/80 mm Hg), the average night-time pressure was low at 124/72 mm Hg, and the average 24-hour blood pressure was 133/77 mm Hg. During follow-up, the systolic/diastolic blood pressure placebo-active differences averaged 6/5 mm Hg for morning ABP, 8/5 mm Hg for 24-hour ABP, and 13/5 mm Hg for CBP. The lowering of blood pressure over 24 hours supports the reduction in blood pressure with indapamide sustained release±perindopril as the explanation for the reduction in total mortality and cardiovascular events observed in the main HYVET study. Because we estimate that 50% had white coat hypertension in the main study, this condition may benefit from treatment in the very elderly.

Optimal Blood Pressure Goals in Patients with Hypertension at High Risk for Cardiovascular Events

The 2013 European Society of Hypertension guidelines recommended that lowering the blood pressure to less than 130/80 mmHg in patients with hypertension at high risk for cardiovascular events was unsupported by prospective trial data, and that the systolic Blood Pressure (BP) should be decreased to less than 140 mmHg in these patients and the systolic BP reduced to between 140 to 150 mmHg in patients aged 80 years and older with an initial systolic BP of 160 mmHg or higher provided they are in good physical and mental condition. The American College of Cardiology Foundation/American Heart Association 2011 expert consensus document on hypertension in the elderly recommended that the BP should be lowered to less than 140/90 mmHg in adults with hypertension younger than 80 years at high risk for cardiovascular events. On the basis of data from the Hypertension in the Very Elderly trial, these guidelines recommended that the systolic BP should be reduced to 140 to 145 mmHg if tolerated in adults aged 80 years and older. This article discusses the clinical trial data supporting these guidelines in patients at high risk for cardiovascular events because of coronary artery disease, diabetes mellitus, chronic kidney disease, and heart failure.

Risk: benefit of treating high blood pressure in older adults

Older people (those aged 65 years or over) comprise over 15% of the UK's population and this cohort is growing. Whilst at greatest risk from systemic arterial hypertension (hypertension), its resultant end organ damage and clinically significant cardiovascular disease, this group was initially neglected in clinical trials and thereby denied treatment, with the lack of evidence cited as justification. However since the 1960s, when the first landmark trials in severe diastolic hypertension were published, there has been a progressive attempt to understand the pathophysiology of hypertension and to expand the evidence base for treatment in older adults. In contrast to the participants of the very first randomized trials who had a mean age of 51 years, the recent Hypertension in the Very Elderly Trial demonstrated significant mortality and morbidity benefits from the treatment of both mixed systolic and diastolic hypertension, as well as isolated systolic hypertension in octogenarians. This review highlights the progressive evidence base behind the relative risks and benefits of treating hypertension in older adults.

SHORT-form 36 (SF-36) scales and association with total mortality and cardiovascular events in the hypertension in the very elderly trial (HYVET)

SHORT-form 36 (SF-36) scales and association with total mortality and cardiovascular events in the hypertension in the very elderly trial (HYVET)

Kidney function in the very elderly with hypertension: data from the hypertension in the very elderly (HYVET) trial

numerous reports have linked impaired kidney function to a higher risk of cardiovascular events and mortality. There are relatively few data relating to kidney function in the very elderly. the Hypertension in the Very Elderly Trial (HYVET) was a randomised placebo-controlled trial of indapamide slow release 1.5mg ± perindopril 2-4 mg in those aged ≥80 years with sitting systolic blood pressures of ≥160 mmHg and diastolic pressures of <110 mmHg. Kidney function was a secondary outcome. HYVET recruited 3,845 participants. The mean baseline estimated glomerular filtration rate (eGFR) was 61.7 ml/min/1.73 m(2). When categories of the eGFR were examined, there was a possible U-shaped relationship between eGFR, total mortality, cardiovascular mortality and events. The nadir of the U was the eGFR category ≥60 and <75 ml/min/1.73 m(2). Using this as a comparator, the U shape was clearest for cardiovascular mortality with the eGFR <45 ml/min/1.73 m(2) and ≥75 ml/min/1.73 m(2) showing hazard ratios of 1.88 (95% CI: 1.2-2.96) and 1.36 (0.94-1.98) by comparison. Proteinuria at baseline was also associated with an increased risk of later heart failure events and mortality. although these results should be interpreted with caution, it may be that in very elderly individuals with hypertension both low and high eGFR indicate increased risk.

Benefits of Treatment in Very Old People with Hypertension

In the Hypertension in the Very Elderly Trial (HYVET), participants (age, ≥80) with systolic blood pressure (BP) ≥160 mm Hg who received

Editorial What should the optimal blood pressure goal be in patients with diabetes mellitus or chronic kidney disease?

Editorial What should the optimal blood pressure goal be in patients with diabetes mellitus or chronic kidney disease?

Current Approaches to the Treatment of Hypertension in Older Persons

Hypertension is a major risk factor for cardiovascular disease and is present in 69% of patients with a first myocardial infarction, in 77% of patients with a first stroke, in 74% of patients with chronic heart failure, and in 60% of patients with peripheral arterial disease. Double–blind, randomized, placebo–controlled trials have demonstrated that antihypertensive drug therapy reduces cardiovascular events in patients aged 65 to 79 years. In the Hypertension in the Very Elderly Trial, patients aged ≥ 80 years who were treated with antihypertensive drug therapy had, at 1.8–year follow–up, a 30% reduction in fatal or nonfatal stroke (P = 0.06), a 39% reduction in fatal stroke (P = 0.05), a 21% reduction in all–cause mortality (P = 0.02), a 23% reduction in cardiovascular death (P = 0.06), and a 64% reduction in heart failure (P < 0.001). Although the optimal blood pressure (BP) treatment goal in the elderly has not been determined, existing epidemiologic and clinical trial data suggest that a reasonable therapeutic BP goal should be < 140/90 mm Hg in persons aged < 80 years and a systolic BP of 140 to 145 mm Hg if tolerated in persons aged ≥ 80 years. Nonpharmacologic lifestyle measures should be encouraged both to prevent development of hypertension and as adjunctive therapy in persons with hypertension. Diuretics, angiotensin–converting enzyme inhibitors, angiotensin receptor blockers, β–blockers, and calcium channel blockers have all shown benefit in reducing cardiovascular events in randomized trials. The choice of specific drugs depends on efficacy, tolerability, presence of specific comorbidities, and cost. Adverse effects from treatment, such as electrolyte disturbances, renal dysfunction, and excessive orthostatic BP reduction, should be avoided.

Hypertension and orthostatic hypotension in older patients

Hypertension and orthostatic hypotension in older patients

Treating Hypertension in the Very Elderly

To review the evidence for strict blood pressure (BP) management in the very elderly, defined as patients aged 80 years and older. A literature search was performed using PubMed (1950 through November 2010) for the MeSH terms hypertension and elderly; subterms of identified MeSH terms (ie, explosion) for the elderly were also searched. A broader search was conducted of PubMed articles published in the past 4 years. Searches were conducted for additional primary literature referenced in identified articles; an updated Cochrane Database review was also performed. All identified studies that specifically included very elderly patients and BP were reviewed. The BP goal established in the Seventh Report of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure (JNC 7) is less than 140/90 mm Hg, regardless of age, unless a compelling indication exists. Although evidence suggests that lowering BP will lower the risk of stroke, lower BP in the very elderly may result in higher mortality. Many physicians are reluctant to treat BP in accordance with the JNC 7 goal in very elderly patients for a variety of reasons, including concerns about fall risk, lack of benefit in mortality reduction, and concerns about drug interactions and adverse effects. Results from a randomized controlled trial and meta-analysis have demonstrated reductions in stroke, heart failure, and cardiovascular events in the very elderly. The American College of Cardiology Foundation/American Heart Association recently published guidelines for elderly patients that suggest treating the very elderly carefully and with different BP goals than previously recommended. Optimal management of hypertension in the very elderly remains a concern. Few studies have evaluated hypertension in this population, and studies that included patients over 80 enrolled too few to draw conclusions. Although the HYVET (Hypertension in the Very Elderly Trial) study did have adequate power to evaluate the very elderly, because this study was stopped early because of significant findings in mortality, unanswered questions remain regarding optimal BP targets.

Drug Trials and Older People

Older people are by far the largest users of prescription medications in Europe and North America – an unsurprising fact when we remember that older people are the ones that bear the greatest burden of disease. Recent observational reports have once again highlighted the association between multiple prescriptions and potential side effects in this age group, yet when we turn to the trials literature to guide our prescribing choices in older people, we find a woeful lack of suitable evidence to guide our practice. Many drug trials still specifically exclude older people, trial populations have far less co-morbid disease and co-prescription than real-world populations, and overly restrictive inclusion and exclusion criteria lead to unrepresentative study populations and can be seen as a manifestation of covert ageism. Worst of all, only a few trials report data on the effects of study treatments on physical function, overall quality of life or common problems of age (e.g. falls); without this information, it is impossible for clinicians and older patients to balance the benefits of treatment against the likely harms. It is in this context that Crome et al.’s report from the EU-funded PREDICT (increasing the PaRticipation of the ElDerly In Clinical Trials) study is timely. The authors carried out a survey of clinicians and other professionals involved in the drug trials and clinical care of older people across nine European countries, soliciting their views on the adequacy of current trial arrangements, asking about their attitudes to ageism in clinical trials, and seeking their views on what could be done to improve the situation. A spread of countries was included, with northern, eastern and southern European representation. This Europewide view is of particular importance, given not only the proposed focus on healthy ageing as part of the EU 8th Framework Programme funding stream for science, but also the increased participation in clinical trials by a wider range of countries; for example, the large HYVET (Hypertension in the Very Elderly Trial) blood pressure trial in older people enrolled many patients from Eastern Europe. The results showed considerable agreement across the nine countries, with a majority of respondents agreeing that older people were disadvantaged by current trial arrangements, and that the current arrangements were not satisfactory. In terms of differences, it is of particular interest that pharmaceutical company staff were least likely to view the current arrangements as unsatisfactory, and were more likely to believe that exclusion due to co-morbidity and polypharmacy were justified. Such attitudes are perhaps understandable; clinical trials cost pharmaceutical companies a great deal of money, and the need for larger sample sizes caused by the heterogeneity of age along with the high adverse event rate, further increase the costs to industry of testing new medications. Respondents from countries more recently admitted to the EU tended to view exclusion of older people as less of a problem. Geriatrics is a relatively young medical specialty, and is better established in some countries (e.g. the UK) than in others. Could this go some way to explaining the difference in attitudes shown in the PREDICT COMMENTARY Drugs Aging 2011; 28 (8): 679-68

Ideal lipid profile and genes for an extended life span

The world population is aging and a rapid increase is being seen in the very elderly (aged >80 years). Cholesterol levels in general rise with age and high cholesterol has been associated with extreme longevity. The relationship between lipids and cardiovascular events in the extreme elderly is unclear. A number of genetic factors associated with lipid metabolism have also been described as having potential antiaging roles, including the genes encoding lipoprotein-associated factors - apolipoprotein E and cholesterol ester transfer protein; adipose tissue metabolism - adiponectin, leptin, glycaemia; and blood pressure - angiotensinogen. Clinical trials of lipid-lowering therapies have recruited subgroups of moderately elderly patients, but only the Prospective Study of Pravastatin in the Elderly at Risk (PROSPER) trial specifically recruited an elderly population. There is no direct equivalent of the Hypertension in the Very Elderly trial (HYVET) study of antihypertensive patients in the extreme elderly. No heterogeneity has been seen with the effects of statin therapy in the elderly compared with younger age groups on classical cardiovascular endpoints of coronary heart disease and stroke. The optimal cholesterol target, long-term tolerability and the specific effects of statins on other vascular-associated diseases of aging, for example arterial aneurysms, microvascular renal and cerebral disease (dementias), remain to be determined.