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Background Information is scarce regarding effects of antihypertensive medication on blood pressure variability (BPV) and associated clinical outcomes. We examined whether antihypertensive treatment changes BPV over time and whether such change (decline or increase) has any association with long-term mortality in an elderly hypertensive population. Methods and Results We used data from a subset of participants in the Second Australian National Blood Pressure study (n=496) aged ≥65 years who had 24-hour ambulatory blood pressure recordings at study entry (baseline) and then after a median of 2 years while on treatment (follow-up). Weighted day-night systolic BPV was calculated for both baseline and follow-up as a weighted mean of daytime and nighttime blood pressure standard deviations. The annual rate of change in BPV over time was calculated from these BPV estimates. Furthermore, we classified both BPV estimates as high and low based on the baseline median BPV value and then classified BPV changes into stable: low BPV , stable: high BPV , decline: high to low , and increase: low to high . We observed an annual decline (mean±SD: -0.37±1.95; 95% CI, -0.54 to -0.19; P <0.001) in weighted day-night systolic BPV between baseline and follow-up. Having constant stable: high BPV was associated with an increase in all-cause mortality (hazard ratio: 3.03; 95% CI, 1.67-5.52) and cardiovascular mortality (hazard ratio: 3.70; 95% CI, 1.62-8.47) in relation to the stable: low BPV group over a median 8.6 years after the follow-up ambulatory blood pressure monitoring. Similarly, higher risk was observed in the decline: high to low group. Conclusions Our results demonstrate that in elderly hypertensive patients, average BPV declined over 2 years of follow-up after initiation of antihypertensive therapy, and having higher BPV (regardless of any change) was associated with increased long-term mortality.

ABSTRACTBackground:Both elevated blood pressure and/or depression increase the risk of cardiovascular disease and mortality. This study in treated elderly hypertensive patients explored the incidence of depression, its association (pre-existing and incident) with mortality and predictors of incident depression., Methods: Data from 6,083 hypertensive patients aged ≥65 years enrolled in the Second Australian National Blood Pressure study were used. Participants were followed for a median of 10.8 years (including 4.1 years in-trial) and classified into: "no depression," "pre-existing" and "incident" depression groups based on either being "diagnosed with depressive disorders" and/or "treated with an anti-depressant drug" at baseline or during in-trial period. Further, we redefined "depression" restricted to presence of both conditions for sensitivity analyses. For the current study, end-points were all-cause and any cardiovascular mortality., Results: 313 (5%) participants had pre-existing depression and a further 916 (15%) participants developed depression during the trial period (incidence 4% per annum). Increased (hazard-ratio, 95% confidence-interval) all-cause mortality was observed among those with either pre-existing (1.23, 1.01-1.50; p = 0.03) or incident (1.26, 1.12-1.41; p &lt; 0.001) depression compared to those without. For cardiovascular mortality, a 24% increased risk (1.24, 1.05-1.47; p = 0.01) was observed among those with incident depression. The sensitivity analyses, using the restricted depression definition showed similar associations. Incident depression was associated with being female, aged ≥75 years, being an active smoker at study entry, and developing new diabetes during the study period., Conclusions: This elderly cohort had a high incidence of depression irrespective of their randomised antihypertensive regimen. Both pre-existing and incident depression were associated with increased mortality.

Background: There is currently insufficient evidence to support the use of lipid-lowering drug treatment (LLT) for primary prevention of cardiovascular disease (CVD) in the elderly., Objectives: We examined the relationship of early initiation of LLT with short- and long-term all-cause and CVD mortality in persons older than 65 years in this post hoc study from the Second Australian National Blood Pressure study (ANBP2)., Methods: This was an in- and post-trial observational study. About 4257 hypertensive participants aged 65 to 84 years within Australian family practices were randomized to an angiotensin-converting enzyme inhibitor or a diuretic treatment group. After excluding participants with a prior history of CVD, the cohort was stratified into "LLT" and "no LLT" subgroups based on LLT status at randomization., Results: At randomization, the participants had a mean age of 72 years, average blood pressure of 168/91 mm Hg and estimated 5-year CVD risk of 18.7 ± 8.3%. In the overall study population, the association of LLT with long-term (11-years) all-cause and non-CVD mortality was significant (hazard ratio [HR] 0.78 [95% confidence interval {CI} 0.66-0.92, P = .003] and HR 0.70 [95% CI 0.54-0.90, P = .006], respectively). Magnitudes of the association of LLT with long-term mortality and the association with short-term mortality were similar; however, no statistically significant association with short-term mortality was observed. In the subgroup analysis by baseline 5-year CVD risk, LLT participants in the highest risk tertile had a substantially lower relative risk for short-term all-cause mortality (HR 0.31, 95% CI 0.13-0.71, P for interaction .02) compared to those with lower estimated CVD risk. All analyses were adjusted for baseline and in-trial characteristics., Conclusion: Our study showed a strong association between LLT and reduced long-term all-cause mortality. Thus, our findings support recommendations of the use of LLT in patients over 65 years, particularly those with high CVD risk who were more likely to obtain additional benefits in the short term. The findings also suggested that mortality benefits of LLT for the elderly may take longer to become evident., (Copyright © 2018 National Lipid Association. Published by Elsevier Inc. All rights reserved.)

Although a high level of alcohol consumption is associated with cardiomyopathy, the benefit or risk of moderate alcohol consumption on incident heart failure (HF) is unknown. This study examined the association between alcohol consumption and risk for HF in older adults with hypertension. The study analyzed data from a cohort of 6,083 participants aged 65 to 84 years at baseline (1995 to 2001) followed for a median of 10.8 years during and after the Second Australian National Blood Pressure Study. Frequency and amount of alcohol consumption were self-reported at baseline and during the clinical trial. The percentages of current drinkers, former drinkers, and never-drinkers at baseline were 4,400 (72%), 394 (6%), and 1,289 (21%), respectively. Incident HF was diagnosed in 183 men and 136 women. After adjustment for multiple confounders, alcohol consumption was not significantly associated with HF. Compared with never-drinkers, the adjusted hazard ratios (95% confidence interval) for those who consume 1 to 7, 8 to 14, and >14 drinks/week at baseline were 0.87 (0.59 to 1.30), 0.96 (0.57 to 1.60), and 0.71 (0.25 to 2.02), respectively in women, and 0.81 (0.47 to 1.38), 0.77 (0.43 to 1.38), and 1.04 (0.59 to 1.84), respectively in men. The findings of lack of an association between alcohol consumption and risk of HF persisted in the analyses comparing the risk of HF across each level of drinking at baseline or at follow-up with never-drinkers. In the present study, there was no evidence for benefit or risk of alcohol consumption, reported at baseline or at follow-up, in relation to incident HF in both men and women., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Background: Numerous studies have shown a stronger relationship between ambulatory blood pressure (ABP), particularly night ABP, and cardiovascular events/mortality than for office blood pressure (OBP). A previous clinical trial (Syst-Eur) showed that pretreatment ABP was only a better predictor of outcome than OBP in placebo-treated participants. The current study in treated elderly hypertensives from the Second Australian National Blood Pressure study (ANBP2) examined whether pretreatment ABP was a better predictor of mortality than OBP over long-term (∼11 years) follow-up., Participants and Methods: ANBP2 was a comparative outcome trial in 6083 off-treatment or previously untreated elderly hypertensives. In the ABP substudy, at study entry, participants had ABP and nurse-performed OBP measurements. Cox proportional hazards analysis assessed the relationships between both OBP and ABP at study entry and 11-year all-cause and cardiovascular mortality, with results pooled from both active treatment phases., Results: In 702 participants, over a median of 10.8 years, including 6.7 years after the trial, 167 died (82 cardiovascular). Pretreatment 'night' systolic ABP and pulse pressure were the best predictors of '11-year' cardiovascular mortality (hazard ratios: 1.26; 95% confidence intervals: 1.10-1.45, P=0.001 and 1.18; 1.06-1.31, P=0.003, respectively) and all-cause mortality (hazard ratios: 1.15; 95% confidence intervals:1.05-1.28, P=0.005 and 1.09; 1.10-1.31, P=0.03, respectively). OBP was not a significant predictor of mortality., Conclusion: In actively treated elderly hypertensives participating in ANBP2, all-cause or cardiovascular deaths were significantly related to pretreatment ABP, particularly to night-time systolic ABP and pulse pressure, but not to OBP.

Objectives: To explore the association of different types of blood pressure (BP) variability measures estimated from either short-term ambulatory reading-to-reading or long-term clinic visit-to-visit BP records with long-term survival in an elderly treated hypertensive population., Methods: A subset of patients (n = 508) aged at least 65-years was studied from the Second Australian National Blood Pressure study. We estimated SBP and DBP BP variability as the SD of ambulatory (24-h, daytime, night-time) and clinic visit-to-visit BP directly from all corresponding on-treatment within-individual BP records. Ambulatory 'weighted day-night' variability was calculated as a weighted mean of daytime and night-time SD. Cox-proportional hazard models adjusted for baseline risk factors (Model 1) and corresponding on-treatment BP (Model 2) or average night-time SBP (best predictive BP measure for outcome) (Model 3) were used to determine the relationship between long-term outcome and BP variability., Results: Over a median of 10.6 years, 101 patients died from any cause, of which 51 deaths were cardiovascular. We observed increase in 'daytime' and 'weighted day-night' SBP/DBP variability was significantly associated with increased all-cause mortality in all models. For cardiovascular mortality, only 'weighted day-night' SBP variability significantly predicted risk in all models (Model 3 hazard ratio: 1.09, 95% confidence interval: 1.00-1.19, P = 0.04). Long-term BP variability was not associated with any outcome. On direct comparison, both 'daytime' and 'weighted day-night' BP variability measures provided similar prognostic information., Conclusion: Short-term 'daytime' and 'weighted day-night' SBP variability from ambulatory BP recordings was a better predictor of mortality in elderly treated hypertensive patients than long-term BP variability from visit-to-visit BP recordings.

Background: Available data on the prognosis of heart failure (HF) patients are predominantly limited to patients diagnosed at time of hospitalization., Aims: To describe the long-term survival of incident HF patients and identify clinical characteristics associated with mortality., Methods: The Second Australian National Blood Pressure Study (ANBP2) randomized 6083 hypertensive subjects aged 65-84 years to angiotensin-converting enzyme (ACE) inhibitor or thiazide diuretic-based therapy and followed them for a median of 4.1 years. One hundred forty-five participants who developed HF and 5938 who remained free from HF during the trial period were followed for a median of 6.7 years during a posttrial follow-up., Results: Three quarters, 110 (76%) of HF patients had died at the end of the follow-up. The five- and ten-year survival rates following HF diagnosis during the trial period were 37% and 15%, respectively, in men, compared with 60% and 33%, respectively, in women. In non-heart failure participants, the five- and ten-year survival rates, following enrollment into the study, were 92% and 76%, respectively. Mortality following HF diagnosis increased with advancing age (HR = 1.09, 95% CI: 1.04-1.33). In addition, male gender and preexisting diabetes were predictive of mortality, while ACE inhibitor-based therapy for the initial trial was associated with 39% decrease (HR = 0.61, 95% CI: 0.41-0.91) in mortality compared with a thiazide diuretic-based regimen., Conclusions: Long-term survival in elderly HF patients is poor, especially in men. Mortality in HF patients increased progressively with advancing age, while allocation to the ACE inhibitor-based regimen for the initial trial significantly improved HF outcome., (© 2017 John Wiley & Sons Ltd.)

The objective of this study was to examine the cost-effectiveness of angiotensin-converting enzyme inhibitor (ACEI)-based treatment compared with thiazide diuretic-based treatment for hypertension in elderly Australians considering diabetes as an outcome along with cardiovascular outcomes from the Australian government's perspective.We used a cost-utility analysis to estimate the incremental cost-effectiveness ratio (ICER) per quality-adjusted life-year (QALY) gained. Data on cardiovascular events and new onset of diabetes were used from the Second Australian National Blood Pressure Study, a randomized clinical trial comparing diuretic-based (hydrochlorothiazide) versus ACEI-based (enalapril) treatment in 6083 elderly (age ≥65 years) hypertensive patients over a median 4.1-year period. For this economic analysis, the total study population was stratified into 2 groups. Group A was restricted to participants diabetes free at baseline (n = 5642); group B was restricted to participants with preexisting diabetes mellitus (type 1 or type 2) at baseline (n = 441). Data on utility scores for different events were used from available published literatures; whereas, treatment and adverse event management costs were calculated from direct health care costs available from Australian government reimbursement data. Costs and QALYs were discounted at 5% per annum. One-way and probabilistic sensitivity analyses were performed to assess the uncertainty around utilities and cost data.After a treatment period of 5 years, for group A, the ICER was Australian dollars (AUD) 27,698 (&OV0556; 18,004; AUD 1-&OV0556; 0.65) per QALY gained comparing ACEI-based treatment with diuretic-based treatment (sensitive to the utility value for new-onset diabetes). In group B, ACEI-based treatment was a dominant strategy (both more effective and cost-saving). On probabilistic sensitivity analysis, the ICERs per QALY gained were always below AUD 50,000 for group B; whereas for group A, the probability of being below AUD 50,000 was 85%.Although the dispensed price of diuretic-based treatment of hypertension in the elderly is lower, upon considering the potential enhanced likelihood of the development of diabetes in addition to the costs of treating cardiovascular disease, ACEI-based treatment may be a more cost-effective strategy in this population.