Hypertension In The Very Elderly Trial Research Articles

Exploring the Challenges of Recruiting Older People for a Randomised Trial Assessing the Feasibility of Treating White Coat Hypertension in the UK General Practices: A Mixed-methods study.

There is a recognised association between white coat hypertension (WCH) and adverse cardiovascular outcomes in older adults. However, there is no consensus on the management of WCH in this group. The objective of the Hypertension in the Very Elderly Trial (HYVET-2) study was to assess the feasibility of randomising 100 patients > 75years with WCH from General Practice in the UK to treatment or usual care. The study did not randomise any patients. In this follow-up study, we sought to explore the reasons for not recruiting. Furthermore, using a mixed-methods study design, staff from 29 General Practice (GP) sites and the Clinical Research Network (CRN) in Kent, Surrey, and Sussex (KSS), UK, were sent an online questionnaire about local research facilities and infrastructure, and HYVET-2 study methodology and target population demographics. Nineteen (19) individuals responded to the online questionnaires (15 primary care staff, 4 CRN staff). Moreover, using a framework approach, we identified six themes summarising challenges to HYVET-2 recruitment. These themes are established approaches of primary care towards managing WCH in older people, target patient demographics, study design complexity, patient- facing study documents, limited research resources in primary care, and identification of eligible patients using existing coding. Our experience showed that recruiting older people from primary care to a WCH study was not feasible. A national scoping survey amongst primary care physicians in the UK, as well as robust patient and public involvement (PPI) targeting older people with WCH, might improve recruitment in future studies addressing the management of WCH in older people.

1983 Exploring barriers to recruiting older people to a white-coat hypertension study

Abstract Introduction There is a recognised association between white coat hypertension (WCH) and adverse cardiovascular outcomes in older adults. However, there is no consensus on the management of WCH in this group. The objective of the Hypertension in the Very Elderly Trial (HYVET-2) study was to assess the feasibility of randomising 100 patients >75years with WCH from General Practice in the UK to treatment or usual care. The study did not randomise any patients. In this follow up study, we sought to explore the reasons for not recruiting. Methods Using a mixed-methods study design, staff from 29 General Practice (GP) sites and the Clinical Research Network (CRN) in Kent, Surrey, and Sussex (KSS) were sent an online questionnaire about local research facilities and infrastructure, and HYVET-2 study methodology and target population demographics. Results Nineteen (19) individuals responded the questionnaires (15 primary care staff, 4 CRN staff). Using a framework approach, we identified six themes summarising challenges to HYVET-2 recruitment. These themes were: established approaches of primary care towards managing WCH in older people, target patient demographics, study design complexity, patient-facing study documents, limited research resources in primary care and identification of eligible patients using existing coding. Conclusion Our experience showed that recruiting older people to a WCH study from primary care was not feasible. A national scoping survey amongst primary care physicians in the UK, and a robust patient and public involvement (PPI) targeting older people with WCH might improve recruitment in future studies of WCH in older people.

S-02-4: BLOOD PRESSURE, ANTIHYPERTENSIVES AND DEMENTIA, AN INDIVIDUAL PATIENT DATA META-ANALYSIS

Background: A large number of observational studies show links between hypertension or higher blood pressure (BP) in mid-life and an increased risk of later dementia. In late life, the evidence is more mixed with some studies indicating higher BP is associated with higher dementia risk and some finding U-shaped associations between BP and incident dementia in older age. The clinical trials of antihypertensives to lower BP have shown largely negative results when examining the relationship between antihypertensive use and incident dementia. However, the trials were designed to examine cardiovascular endpoints and several stopped early for cardiovascular benefit thus limiting their statistical power and ability to accrue dementia outcomes. To overcome some of these limitations a pooled individual patient data meta-analysis of five seminal double-blind placebo-controlled randomised trials was undertaken to better define the effects of BP lowering treatment for the prevention of dementia. Methods: The double-blind placebo-controlled randomised antihypertensive trials; Action in Diabetes and Vascular disease: preterAx and diamicroN-MR Controlled Evaluation (ADVANCE), Hypertension in the Very Elderly Trial (HYVET), Perindopril Protection Against Recurrent Stroke Study (PROGRESS), Systolic Hypertension in the Elderly Program (SHEP), and SYSTolic Hypertension in EURope Trial (SYST-EUR) were merged into a single database. Multilevel logistic regression was used to evaluate the treatment effect on incident dementia. Effect modification was assessed for key population characteristics including age, baseline systolic BP, sex, baseline Mini-Mental State Exam (MMSE) score and presence of prior stroke. Results: All trials were balanced across randomised groups. The combined sample was n = 28,008 recruited from 20 countries. Mean baseline age was 69.1 (Standard Deviation 9.3). Median follow-up 4.3 years. Incident dementia occurred in 2.9% and 3.3% of those in active and placebo groups, respectively. Multilevel logistic regression reported an adjusted odds ratio 0.87 (95% confidence interval 0.75, 0.99) in favour of antihypertensive treatment reducing risk of incident dementia with a mean BP lowering of 10/4mmHg. Further multinomial regression taking account of death as a competing risk found similar results. There was no effect modification by age, sex, baseline systolic BP, baseline MMSE or prior stroke. Discussion: This is the first single-stage individual patient data meta-analysis from double-blind placebo-controlled clinical trials. It provides high-quality evidence to support the benefits of antihypertensive treatment in late-mid and later life to lower the risk of dementia. Questions remain as to the potential benefit from antihypertensive treatment commenced earlier in the life-course to reduce the long-term risk of dementia.

Left ventricular hypertrophy and incident cognitive decline in older adults with hypertension

The association between raised blood pressure and increased risk of subsequent cognitive decline is well known. Left ventricular hypertrophy (LVH), as a marker of hypertensive target organ damage, may help identify those at risk of cognitive decline. We assessed whether LVH was associated with subsequent cognitive decline or dementia in hypertensive participants aged ≥80 years in the randomized, placebo-controlled Hypertension in the Very Elderly Trial. LVH was assessed using 12-lead electrocardiography (ECG) based on the Cornell Product (CP-LVH), Sokolow-Lyon (SL-LVH), and Cornell Voltage (CV-LVH) criteria. The Mini-Mental State Examination (MMSE) was used to assess cognitive function at baseline and annually. A fall in MMSE to <24 or an annual fall of >3 points were defined as cognitive decline and triggered dementia screening (Diagnostic Statistical Manual IV). Death was defined as a competing event. Fine-Gray regression models were used to examine the relationship between baseline LVH and cognitive outcomes. There were 2645 in the analytical sample, including 201 (7.6%) with CP-LVH, 225 (8.5%) SL-LVH and 251 (9.5%) CV-LVH. CP-LVH was associated with increased risk of cognitive decline, subdistribution hazard ratio (sHR)1.3 (95% confidence interval (CI) 1.01–1.67) in multivariate analyses. SL-LVH and CV-LVH were not associated with cognitive decline (sHR1.06 (95% CI 0.82–1.37) and sHR1.13 (95% CI 0.89–1.43), respectively). LVH was not associated with dementia. LVH may be related to subsequent cognitive decline, but evidence was inconsistent depending on ECG criterion and there were no associations with incident dementia. Additional work is needed to understand the relationships between blood pressure, LVH assessment and cognition.

Left ventricular hypertrophy and incident cognitive impairment in elderly hypertensive patients: Hypertension in the Very Elderly Trial

AbstractBackgroundWe assessed whether left ventricular hypertrophy (LVH), as an indicator of hypertensive target organ damage, was associated with subsequent cognitive decline.MethodWe used data collected in the Hypertension in the Very Elderly Trial (HYVET). HYVET was a double‐blind placebo‐controlled trial of antihypertensives in hypertensive older adults (≥80 years). Trial treatment was not associated with cognitive decline, allowing us to analyze the trial data as a cohort. The baseline characteristics of the analytical sample and those who were excluded due to missing electrocardiography (ECG) values or cognitive outcomes were compared. LVH was assessed using a 12‐lead ECG based on Cornell product criterion. The Mini‐Mental State Examination (MMSE) was used to assess cognitive function at baseline and annually. A fall in MMSE to ≤24 or an annual fall of ≥three points was defined as cognitive decline. Proportional hazard regression, including a competing risk Fine‐Gray model to account for competing outcomes (stroke, heart failure, myocardial infarction, other fatal cardiovascular disease), was used to examine the relationship between baseline LVH and cognitive outcomes. Sensitivity analyses were run in those with baseline MMSE ≥24, considered unlikely to have pre‐existing cognitive decline. To evaluate attrition bias, we ran inverse probability weighting (IPW) models.ResultThere were 1944 in the analytical sample, 164 with LVH. Mean follow‐up was 3.9 or 4.2 years accounting or not accounting for competing outcomes. The analytical sample differed from those excluded, e.g. they had higher diastolic blood pressures and were more likely to be female (Table 1). LVH was associated with increased risk of 1) cognitive decline (Table 2), hazard ratio (HR)1.44 (95%confidence interval (CI)1.12:1.84), 2) combined cardiovascular events and cognitive decline, HR1.51 (95% CI 1.2:1.91), and 3) cognitive decline using the Fine‐Gray model, HR1.41 (95%CI 1.08:1.84). Sensitivity and IPW analyses yielded similar results.ConclusionCP criterion defined LVH was associated with an increased risk of cognitive decline in older adults with hypertension. The potential for selection bias and healthy individual bias (trial participants) should be noted. Further work should explore the potential for LVH as an indicator of target organ damage beyond the heart.

Author Response: Systolic Blood Pressure Postural Changes Variability is Associated With Greater Dementia Risk.

The authors thank Dr. Pinar Soysal for this comment on our article.1 We agree that the original standard diagnostic criteria of orthostatic hypotension (OHYPO), commonly based on supine-to-stand BP, are a reduction in systolic blood pressure (SBP) of at least 20 mm Hg or DBP of at least 10 mm Hg.2 The studies Dr. Pinar Soysal mentions assessed orthostatic BP response from a supine-to-standing position, which is not the case of the Health ABC Study. Indeed, given that the prevalence of OHYPO is higher in older adults and many of whom have comorbidities that may affect mobility, a sit-to-stand testing often offers a safer method to transfer a patient into an upright position without triggering an acute fall or syncopal event. Because of the reduced acute change in gravitational stress, the sit-to-stand test makes conventional BP cutoffs to diagnose OHYPO challenging to reach. An insignificant number of participants in the Health ABC Study had baseline OHYPO using that definition. Very recently, optimal diagnostic thresholds for the diagnosis of OHYPO with a sit-to-stand test have been proposed by Shaw et al.3 A sit-to-stand SBP drop of ≥15 mm Hg had optimal test characteristics (sensitivity = 80%; specificity = 89%), as did a DBP drop of ≥7 mm Hg (sensitivity and specificity both = 87%).3 We, therefore, used this threshold—consistent with previous large studies—including the Hypertension in the Very Elderly Trial (HYVET).4,5

Atrial fibrillation and the risk of cardiovascular disease and mortality in the Hypertension in the Very Elderly Trial

To assess the prognostic value of electrocardiographic atrial fibrillation in older hypertensive people in the randomized, placebo-controlled Hypertension in the Very Elderly Trial. Hypertension in the Very Elderly Trial randomized 3845 hypertensive people aged 80 years and over, 3273 with electrographic data on the presence or absence of atrial fibrillation at baseline and without established cardiovascular disease. Multivariate Cox proportional hazard models were used to estimate hazard ratios with 95% confidence intervals (CIs) for all-cause mortality, incident fatal and nonfatal major cardiovascular events, all-stroke and all-heart failure. The mean follow-up time was 2.1 years. Baseline prevalence of atrial fibrillation was 5.8%. Compared with people without atrial fibrillation at baseline, after adjustments the presence of atrial fibrillation was associated with increased risk of mortality (hazard ratio = 2.49, 95% CI = 1.80-3.44, P < 0.001), of nonfatal and fatal cardiovascular events (hazard ratio = 2.47, 95% CI = 1.71-3.55, P < 0.001), all-stroke (hazard ratio = 2.47, 95% CI = 1.34-4.56, P = 0.004) and all-heart failure (hazard ratio 2.33, 95% CI = 1.10-4.93, P = 0.027). Atrial fibrillation is an important risk factor to consider when assessing older hypertensive adults as it is associated with increased risk of mortality, nonfatal and fatal cardiovascular events, stroke and heart failure.

154 Blood Pressure Target in Management of Postural Hypotension in Elderly: Evidence Free Zone?

Abstract Optimizing of polypharmacy in the elderly patient presenting with falls requires making judgement calls between stopping or reducing anti-hypertensives with the increased risk of stroke and cardiovascular disease versus continuing the medications with the consequent orthostatic hypotension, electrolyte abnormalities and worsening of cognition due to reduced perfusion pressure in patients with dementia. The trial evidence in this cohort of patients is scant and conflicting. The Milan 75+ Cohort study published in Age and Ageing, Volume 44, Nov. 2015 by Giulia Ogliari et al showed a U shaped relationship between BP and mortality with the lowest mortality at systolic blood pressure of 165 mm Hg. The Hypertension in the Very Elderly Trial (HYVET) published in New England Journal of Medicine in March 2008 by Nigel S Beckett et al showed reduction in any cause death by 21% in the intensive treatment group, while the Cochrane Systematic Review by Vijaya M Musini et al published in 2009 showed no reduction in total mortality in the very elderly patient with increased withdrawals due to adverse effects in the treatment group. There are questions on the applicability of trial evidence with the HYVET trial having lower level of patients with diabetes and cardiovascular disease and the SPRINT trial including mainly younger patients with good baseline renal function and little cardiovascular disease. The combination of frailty showed improved outcome in HYVET but had no effect in SPRINT trial. The number needed to treat to avoid one significant event in patients with a blood pressure of &amp;gt;170 is 125 for death, 67 for stroke and 48 for heart failure. In this context issues such as patient preference, degree of frailty, cognitive impairment, and life expectancy have to be taken in account before deciding on the suggested treatment for the individual patient.

Cost-Effectiveness of Antihypertensive Therapy in Patients Older Than 80 Years: Cohort Study and Markov Model

BackgroundBlood pressure and antihypertensive treatment (AHT) generally increase with age, but there is uncertainty concerning the value of treatment at very advanced ages. ObjectivesTo estimate the cost-effectiveness of AHT in people aged 80 years and older. MethodsA Markov model compared AHT with no blood pressure treatment for prevention of cardiovascular disease. Outcomes were new stroke, coronary heart disease, and diabetes, with falls included as a potential complication of AHT. Costs were evaluated from a health system perspective. Incidence, mortality, and costs of healthcare utilization were estimated from linked primary and secondary care electronic health records for 98 220 individuals aged 80 years and older. Clinical effectiveness estimates were from the Hypertension in the Very Elderly Trial. Deterministic and probabilistic sensitivity analyses were conducted. ResultsIn the base case, AHT was associated with an additional 725 quality-adjusted life-years (QALYs) and £4.3 million per 1000, with an incremental cost-effectiveness ratio (ICER) of £5977 per QALY. The ICER was most sensitive to the cost of falls and relative risk reduction in stroke incidence. Probabilistic sensitivity analysis gave 95% uncertainty intervals: £5057 to £8398 per QALY in men and £4955 to £8218 per QALY in women. AHT for secondary prevention in participants with coronary heart disease gave an ICER of £9903 per QALY. ConclusionsAHT is estimated to be cost-effective in individuals aged 80 years and older, even if health benefits are smaller or side effects costlier than in the base case. Benefits and harms for vulnerable subgroups require further evaluation.

Treatment of White Coat HYpertension in the Very Elderly Trial (HYVET 2) - Feasibility of a Randomized Controlled Trial (Study Protocol)

The results of HYpertension in the Very Elderly Trial (HYVET) were crucial in providing evidence of benefit of the treatment of hypertension in those 80 years or older. Following a subsequent sub study analysis of the HYVET data there is a suggestion that 50% of patients in the main study had White Coat Hypertension (WCH), defined as clinic BP readings >140/90 mmHg and ambulatory BP readings <135/85 mmHg. Currently, definitive evidence in support of treatment for such individuals is not available. HYVET 2 has been designed in order to assess the feasibility of conducting a randomized controlled trial which might determine whether the treatment of WCH in the very elderly is clinically beneficial. One hundred participants aged ≥75 years diagnosed with WCH will be recruited from General Practices (GPs) in UK. Randomization will be 1:1 to a treatment arm (indapamide and perindopril) and control arm (no treatment) and follow up will be for 52 weeks. HYVET 2 will report on feasibility outcomes including participant recruitment, adherence and withdrawal rates, willingness of GPs to recruit and randomize patients and the frequency of a composite of cardiovascular events. Simple descriptive statistics will be presented.

Orthostatic hypotension and symptomatic subclinical orthostatic hypotension increase risk of cognitive impairment: an integrated evidence review and analysis of a large older adult hypertensive cohort.

Systematically reviewing the literature found orthostatic hypotension (OH) to be associated with an increased risk of incident dementia but limited data were available in those at highest risk, the hypertensive oldest-old. Our aim was to analyse the relationship between OH and incident cognitive decline or dementia in this group and to synthesize the evidence base overall. Participants aged ≥80 years, with hypertension, were from the Hypertension in the Very Elderly Trial (HYVET) cohort. Orthostatic hypotension was defined as a fall of ≥15 mmHg in systolic and or ≥7 mmHg in diastolic pressure after 2 min standing from a sitting position. Subclinical orthostatic hypotension with symptoms (SOH) was defined as a fall <OH but with unsteadiness, light-headedness, or faintness in the week before blood pressure measurement. Proportional hazard regression was used to examine the relationship between baseline OH, SOH, and cognitive outcomes. There were 3121 in the analytical sample, 538 with OH. Orthostatic hypotension was associated with increased risk of cognitive decline (906 events), hazard ratio (HR) 1.36 (95% confidence interval 1.14-1.59). For incident dementia (241 events), HR 1.34 (0.98-1.84). When competing risk of cardiovascular events were taken into account results were HR 1.39 (1.19-1.62) and HR 1.34 (1.05-1.73), respectively. Subclinical orthostatic hypotension was associated with an increased risk of cognitive decline HR 1.56 (1.12-2.17) and dementia HR 1.79 (1.00-3.20). Combining the results from the HYVET cohort in a meta-analysis with the existing published literature in this area found a 21% (9-35%) increased risk of dementia with OH. Orthostatic hypotension indicates an increased risk of dementia and cognitive decline. SOH may also be considered a risk factor, at least in older hypertensive adults. Questions remain regarding the mechanisms and whether interventions to reduce impact of OH could protect cognition.

What Should the Systolic Blood Pressure Treatment Goal be in Patients Aged 60 Years and Older with Hypertension in 2016?

The Hypertension in the Very Elderly Trial (HYVET) randomized 3, 845 patients aged 80 years and older, mean age 83.6 years, with a systolic blood pressure (SBP) of ≥ 160 mmHg to indapamide plus perindopril if needed versus double-blind placebo [1]. The target SBP reached was 150 mmHg, and the lowest SBP reached was 143 mmHg. Median follow-up was 1.8 years. Compared to patients randomized to placebo, patients randomized to antihypertensive drug therapy had a 30% reduction in fatal or nonfatal stroke, a 39% reduction in fatal stroke, a 21% reduction in all-cause mortality, a 23% reduction in cardiovascular death, and a 64% reduction in heart failure

Antihypertensive treatment decreases arterial stiffness at night but not during the day. Results from the Hypertension in the Very Elderly Trial

The main Hypertension in the Very Elderly Trial (HYVET) demonstrated a very marked reduction in cardiovascular events by treating hypertensive participants 80 years or older with a low dose, sustained release prescription of indapamide (indapamide SR, 1.5 mg) to which was added a low dose of an angiotensin converting enzyme inhibitor in two-thirds of cases (perindopril 2–4 mg). This report from the ambulatory blood pressure sub-study investigates whether changes in arterial stiffness and ambulatory blood pressure (BP) could both explain the benefits observed in the main trial. A total of 139 participants were randomized to placebo [67] and to active treatment [72] and had both day and night observations of BP and arterial stiffness as determined from the Q wave Korotkoff diastolic (QKD) interval. The QKD interval was 5.6 ms longer (p = 0.017) in the actively treated group at night than in the placebo group. This was not true for the more numerous daytime readings so that 24-h results were similar in the two groups. The QKD interval remained longer at night in the actively treated group even when adjusted for systolic pressure, heart rate and height. The reduced arterial stiffness at night may partly explain the marked benefits observed in the main trial.

Recommendations for Intensive Blood Pressure Lowering in High-Risk Patients, the Canadian Viewpoint.

Recent publication of the Systolic Blood Pressure Intervention Trial (SPRINT) in close temporal proximity to 2 meta-analyses affirming the benefits of intensive blood pressure (BP) control collectively signify the need to reevaluate BP targets in hypertensive patients at high risk for cardiovascular events.1–3 This commentary discusses how this recent evidence has affected Canadian clinical practice guidelines, describes the process used to update these guidelines in light of this evidence, and outlines the major issues deliberated by Canadian Hypertension Education Program (CHEP) Task Force members during this process. In the SPRINT trial, which studied 9361 subjects aged ≥50 years at increased risk for cardiovascular events, intensive systolic BP control (to <120 mm Hg) reduced the incidence of cardiovascular events and mortality by 25% (5.2% versus 6.8%; hazard ratio 0.75; 95% confidence interval 0.64–0.89) compared with standard systolic BP control (135–139 mm Hg).1 Furthermore, a meta-analysis of 55 randomized controlled trials (265 576 subjects) demonstrated that the reduction in cardiovascular events realized from a 10-mm Hg systolic BP reduction is similar across different quintiles of baseline systolic BP (<130, 130–139, 140–149, 150–159, ≥160 mm Hg).2 In a second meta-analysis of 14 treat-to-target trials (44 989 subjects), a 7-mm Hg mean systolic BP reduction (from 140 to 133 mm Hg) led to a 14% (95% confidence interval 0.78–0.96) reduction in major cardiovascular events.3 In aggregate, these data support the implementation of intensive BP control in high-risk patients. Canadian hypertension clinical practice guidelines are crafted and disseminated by the multidisciplinary 75-member CHEP Recommendations Task Force, a process that is funded by Hypertension Canada.4 CHEP has produced annually updated recommendations for the diagnosis and management of high BP since 1999.5 The CHEP process consists of the following: 1. A Cochrane librarian conducts literature searches in collaboration with Task Force members. These searches are designed to inform …

Characterizing Frailty Status in the Systolic Blood Pressure Intervention Trial.

The Systolic Blood Pressure Intervention Trial (SPRINT) is testing whether a lower systolic blood pressure (BP) target of 120 mm Hg leads to a reduction in cardiovascular morbidity and mortality among hypertensive, nondiabetic adults. Because there may be detrimental effects of intensive BP control, particularly in older, frail adults, we sought to characterize frailty within SPRINT to address ongoing questions about the ability of large-scale trials to enroll representative samples of noninstitutionalized, community-dwelling, older adults. We constructed a 36-item frailty index (FI) in 9,306 SPRINT participants, classifying participants as fit (FI ≤ 0.10), less fit (0.10 < FI ≤ 0.21), or frail (FI > 0.21). Recurrent event models were used to evaluate the association of the FI with the incidence of self-reported falls, injurious falls, and all-cause hospitalizations. The distribution of the FI was comparable with what has been observed in population studies, with 2,570 (27.6%) participants classified as frail. The median FI was 0.18 (interquartile range = 0.14 to 0.24) in participants aged 80 years and older (N = 1,159), similar to the median FI of 0.17 reported for participants in the Hypertension in the Very Elderly Trial. In multivariable analyses, a 1% increase in the FI was associated with increased risk for self-reported falls (hazard ratio [HR] = 1.030), injurious falls (HR = 1.035), and all-cause hospitalizations (HR = 1.038) (all p values < .0001). Large clinical trials assessing treatments to reduce cardiovascular disease risk, such as SPRINT, can enroll heterogeneous populations of older adults, including the frail elderly, comparable with general population cohorts.

O-004: Impact of blood pressure lowering treatment on frailty in the HYpertension in the Very Elderly Trial (HYVET)

O-004: Impact of blood pressure lowering treatment on frailty in the HYpertension in the Very Elderly Trial (HYVET)

Blood Pressure Goals and Targets in the Elderly.

The American College of Cardiology (ACC)/American Heart Association (AHA) 2011 expert consensus document on hypertension in the elderly recommends that the blood pressure be reduced to less than 140/90mmHg in adults aged 60-79years and the systolic blood pressure to 140 to 145mmHg if tolerated in adults aged 80years and older. I strongly support these guidelines based on clinical trial data, especially from the Systolic Hypertension in the Elderly trial and from the Hypertension in the Very Elderly trial (HYVET). Other guidelines supporting reducing the blood pressure to less than 140/90mmHg in adults aged 60 to 79years of age include the European Society of Hypertension (ESH)/European Society of Cardiology (ESC) 2013 guidelines, the minority report from the 2013 Eighth Joint National Committee (JNC 8) guidelines, the 2013 Canadian Hypertension Education Program guidelines, the 2011 UK guidelines, the 2014 American Society of Hypertension (ASH)/International Society of Hypertension (ISH) guidelines, and the 2015 AHA/ACC/ASH scientific statement on treatment of hypertension in patients with coronary artery disease. I support these guidelines. In adults aged 80years and older, a blood pressure below 150/90mmHg has been recommended by these guidelines, with a target goal of less than 140/90mmHg considered in those with diabetes mellitus or chronic kidney disease. I support these guidelines. The 2013 JNC 8 guidelines recommend reducing the blood pressure to less than 140/90mmHg in adults aged 60years and older with diabetes mellitus or chronic kidney disease but to less than 150/90mmHg in adults aged 60years and older without diabetes mellitus or chronic kidney disease. I strongly disagree with this recommendation and am very much concerned that the higher systolic blood pressure goal recommended by JNC 8 guidelines in adults aged 60years and older without diabetes mellitus or chronic kidney disease will lead to an increase in cardiovascular events and mortality in these adults.

Higher blood pressure as a risk factor for diseases other than stroke and ischemic heart disease.

Hypertension is an established risk factor for stroke, ischemic heart disease,1,2 and renal dysfunction.3 The management and prevention of hypertension are important to the prevention of these diseases. Recent evidence has suggested that hypertension also plays a central role in the underlying pathophysiological condition or at prodromal stages before the development of these diseases. Accumulating evidence also indicates that hypertension seems to be linked with common noncardiovascular diseases including dementia, cancer, oral health diseases (OHDs), and osteoporosis. In this brief review, we organize the reported results about the associations between hypertension and these diseases, discussing mainly epidemiological surveys, with the goal of clarifying the relationships between these diseases and hypertension. ### Atrial Fibrillation Atrial fibrillation (AF) is one of the most common types of chronic arrhythmia and is a risk factor for ischemic stroke.4 The Framingham Heart Study revealed that hypertension increases the risk of AF by factors of 1.5 for men and 1.4 for women.5 The Women’s Health Study and a cohort study of Norwegian men showed that high-normal blood pressure (BP) was associated with incident AF.6,7 All of these cohort studies were conducted in Westerners, and these associations were also confirmed in a recent Japanese cohort study.8 In that investigation, compared with normal BP and normal weight, systolic prehypertension with overweight was shown to be associated with an increased risk of incident AF ( P for interaction=0.04). Arterial stiffness, left ventricular hypertrophy, and increased left atrial size are important mediators of the relationship between BP and incident AF.9 Higher systolic BP (SBP) and overweight may mutually exacerbate left ventricular hypertrophy and hypertension, and consequently, they may synergistically increase the risk of AF. ### Chronic Kidney Disease and High BP Chronic kidney disease (CKD) is characterized by a progressive decline in an individual’s glomerular filtration rate over several decades, …

No evidence that frailty modifies the positive impact of antihypertensive treatment in very elderly people: an investigation of the impact of frailty upon treatment effect in the HYpertension in the Very Elderly Trial (HYVET) study, a double-blind, placebo-controlled study of antihypertensives in people with hypertension aged 80 and over.

BackgroundTreatment for hypertension with antihypertensive medication has been shown to reduce stroke, cardiovascular events, and mortality in older adults, but there is concern that such treatment may not be appropriate in frailer older adults. To investigate whether there is an interaction between effect of treatment for hypertension and frailty in older adults, we calculated the frailty index (FI) for all available participants from the HYpertension in the Very Elderly Trial (HYVET) study, a double-blind, placebo-controlled study of antihypertensives in people with hypertension aged 80 and over, and obtained frailty adjusted estimates of the effect of treatment with antihypertensive medication on risk of stroke, cardiovascular events, and mortality.MethodsParticipants in HYVET were randomised 1:1 to active treatment with indapamide sustained release 1.5 mg ± perindopril 2 to 4 mg or to matching placebo. Data relating to blood pressure, comorbidities, cognitive function, depression, and quality of life were collected at entry into the study and at subsequent follow-up visits. The FI was calculated at entry, based on 60 potential deficits. The distribution of FI was similar to that seen in population studies of adults aged 80 years and above (median FI, 0.17; IQR, 0.11–0.24). Cox regression was used to assess the impact of FI at entry to the study on subsequent risk of stroke, total mortality, and cardiovascular events. Models were stratified by region of recruitment and adjusted for sex and age at entry. Extending these models to include a term for a possible interaction between treatment for hypertension and FI provided a formula for the treatment effect as a function of FI. For all three models, the point estimates of the hazard ratios for the treatment effect decreased as FI increased, although to varying degrees and with varying certainty.ResultsWe found no evidence of an interaction between effect of treatment for hypertension and frailty as measured by the FI. Both the frailer and the fitter older adults with hypertension appeared to gain from treatment.ConclusionsFurther work to examine whether antihypertensive treatment modifies frailty as measured by the FI should be explored.Trial registrationClinicalTrials.gov NCT00122811 (July 2005)Electronic supplementary materialThe online version of this article (doi:10.1186/s12916-015-0328-1) contains supplementary material, which is available to authorized users.

Subgroup and per-protocol analyses from the Hypertension in the Very Elderly Trial.

The results of the Hypertension in the Very Elderly Trial showed positive benefits from blood pressure-lowering treatment in those aged 80 and over. An analysis by the pre-specified subgroups [age, sex, history of cardiovascular disease (CVD) and initial SBP] was performed. The Hypertension in the Very Elderly Trial was a randomized, double-blind, placebo-controlled trial of 3845 participants aged 80 and over with SBPs of 160-199 mmHg and diastolic pressures below 110 mmHg recruited from Europe, China, Australasia and Tunisia. Active treatment was indapamide sustained-release 1.5 mg with the addition of perindopril 2-4 mg as required to reach a target blood pressure of less than 150/80 mmHg. For total mortality, benefits were consistent: men [hazard ratio 0.82, 95% confidence interval (CI) 0.62-1.11], women (hazard ratio 0.77, 95% CI 0.66-0.99), those aged 80-84.9 (hazard ratio 0.76, 95% CI 0.60-0.96), those aged 85 and over (hazard ratio 0.87, 95% CI 0.64-1.20), those with a history of CVD (hazard ratio 0.76, 95% CI 0.48-1.20) and those without (hazard ratio 0.81, 95% CI 0.65-0.99), and similarly across a range of baseline SBPs. The point estimates for cardiovascular mortality, strokes, heart failure and cardiovascular events were all in favour of benefit. In the per-protocol analysis, strokes were reduced by 34% (P = 0.026), total mortality by 28% (P = 0.001), cardiovascular event by 37% (P < 0.001) and heart failure by 72% (P < 0.001). In hypertensive patients aged 80 or more, treatment based on indapamide (sustained-release) 1.5 mg showed consistent benefits across pre-specified subgroups including those without established CVD (the majority), supporting the need for treatment even at this advanced age. There were too few aged 90 or over to determine benefit from treatment at extreme age.