Prescribed opioid use is associated with adverse cardiovascular outcomes in community-dwelling older persons.

AIMS: Prescribed opioids are commonly used in the older community-dwelling population for the treatment of chronic pain. Although the harmful effects of opioid abuse and overdose are well understood, little is known about the long-term cardiovascular (CV) effects of prescribed opioids. The aim of this study was to investigate the CV effects associated with prescribed opioid use. METHODS AND RESULTS: A post hoc analysis of participants in the Aspirin in Reducing Events in the Elderly (ASPREE) trial was conducted. Participants in the ASPREE trial included community-dwelling older adults without a prior history of CV disease (CVD). Prescribed opioid use was defined as opioid use at baseline and/or at the first annual visit (AV1). Cox proportional hazards regression was used to calculate hazard ratios and 95% confidence intervals (95% CI) for associations between opioid use and CVD events following AV1. Of the 17 701 participants included (mean age 75.2 years, 58.2% female), 813 took opioids either at baseline or at AV1. Over a median follow-up period of 3.58 years (IQR 2.50-4.62), CVD events, most notably heart failure hospitalization, occurred in 7% (n = 57) amongst opioid users and 4% (n = 680) amongst non-opioid users. After adjustment for multiple covariates, opiate use was associated with a 1.67-fold (CI 1.26-2.23, P < 0.001) increase in the hazard ratio for CVD events. CONCLUSIONS: These findings identify opioid use as a non-traditional risk factor for CVD events in community-dwelling older adults.

Variation in Mean Arterial Pressure Increases Falls Risk in Elderly Physically Frail and Prefrail Individuals Treated With Antihypertensive Medication.

BACKGROUND: Impaired cerebral blood flow has been associated with an increased risk of falls. Mean arterial pressure (MAP) and variability in MAP have been reported to affect cerebral blood flow but their relationships to the risk of falls have not previously been reported. METHODS: Utilising data from the Aspirin in Reducing Events in the Elderly trial participants, we estimated MAP and variability in MAP, defined as within-individual SD of MAP from baseline and first 2 annual visits. The relationship with MAP was studied in 16 703 participants amongst whom 1539 falls were recorded over 7.3 years. Variability in MAP was studied in 14 818 of these participants who experienced 974 falls over 4.1 years. Falls were confined to those involving hospital presentation. Cox regression was used to calculate hazard ratio and 95% CI for associations with falls. RESULTS: Long-term variability in MAP was not associated with falls except amongst frail or prefrail participants using antihypertensive medications. Within this group each 5 mm Hg increase in long-term variability in MAP increased the risk of falls by 16% (hazard ratio, 1.16 [95% CI, 1.02-1.33]). Amongst the antihypertensive drugs studied, beta-blocker monotherapy (hazard ratio, 1.93 [95% CI, 1.17-3.18]) was associated with an increased risk of falls compared with calcium channel blockers. CONCLUSIONS: Higher levels of long-term variability in MAP increase the risk of serious falls in older frail and prefrail individuals taking antihypertensive medications. The observation that the relationship was limited to frail and prefrail individuals might explain some of the variability of previous studies linking blood pressure indices and falls.

Prevalence of, and risk factors for, diabetes and prediabetes in Bangladesh: Evidence from the national survey using a multilevel Poisson regression model with a robust variance.

To estimate the age-standardized prevalence of diabetes and prediabetes and identify factors associated with these conditions at individual, household, and community levels. Data from 11952 Bangladeshi adults aged 18-95 years available from the most recent Bangladesh Demographic and Health Survey 2017-18 were used. Anthropometric measurements and fasting blood glucose samples were taken as part of the survey. Prevalence estimates of diabetes and prediabetes were age-standardized with direct standardization, and risk factors were identified using multilevel mix-effects Poisson regression models with robust variance. The overall age-standardised prevalence of diabetes was 9.2% (95%CI 8.7-9.7) (men: 8.8%, women: 9.6%), and prediabetes was 13.3% (95%CI 12.7-13.9) (men: 13.0%, women: 13.6%). Among people with diabetes, 61.5% were unaware that they had the condition. 35.2% took treatment regularly, and only 30.4% of them had controlled diabetes. Factors associated with an increased prevalence of having diabetes were increasing age, male, overweight/obesity, hypertension, being in the highest wealth quintile, and living in the Dhaka division. People currently employed and living in the Rangpur division were less likely to have diabetes than those currently not employed and living in the Barishal division. Diabetes and prediabetes affect a substantial proportion (over one-quarter) of the Bangladeshi adult population. Continuing surveillance and effective prevention and control measures, focusing on obesity reduction and hypertension management, are urgently needed.

Comparison of statins for primary prevention of cardiovascular disease and persistent physical disability in older adults.

PURPOSE: Recent epidemiological evidence has suggested that use of lipid-lowering medications, particularly statins, was associated with reduced cardiovascular disease (CVD) events and persistent physical disability in healthy older adults. However, the comparative efficacy of different statins in this group remains unclear. This study aimed to compare different forms of statins in their associations with CVD and physical disability in healthy older adults. METHODS: This post hoc analysis included data from 5981 participants aged ≥ 70 years (≥ 65 if US minorities; median age:74.0) followed for a median of 4.7 years, who had no prior CVD events or physical disability and reported using a statin at baseline. The incidence of the composite and components of major adverse cardiovascular events and persistent physical disability were compared across different statins according to their type, potency, and lipophilicity using multivariable Cox proportional-hazards models. RESULTS: Atorvastatin was the most used statin type at baseline (37.9%), followed by simvastatin (29.6%), rosuvastatin (25.5%), and other statins (7.0%, predominantly pravastatin). In comparisons of specific statins according to type and lipophilicity (lipophilic vs. hydrophilic statin), observed differences in all outcomes were small and not statistically significant (all p values > 0.05). High-potency statin use (atorvastatin and rosuvastatin) was marginally associated with lower risk of fatal CVD events compared with low-/moderate-potency statin use (hazard ratio: 0.59; 95% confidence interval: 0.35, 1.00). CONCLUSION: There were minimal differences in CVD outcomes and no significant difference in persistent physical disability between various forms of statins in healthy older adults. Future investigations are needed to confirm our results.

Antihypertensive drug class in combination with lipid lowering treatment for primary prevention of cardiovascular disease in the elderly.

BACKGROUND: Antihypertensives and lipid-lowering therapy (LLT) are often used concurrently. OBJECTIVES: To determine whether there was a difference in clinical outcomes when older patients with LLT were prescribed angiotensin-converting-enzyme-inhibitors (ACE-Is) compared with diuretics. METHODS: This analysis included 648 LLT older users free of cardiovascular disease (CVD) from a trial comparing ACE-I versus diuretic-based therapy. Comparisons were made between LLT+ACE-I (n = 335) and LLT+diuretic groups (n = 313) using multivariable Cox proportional-hazard models. Primary endpoints were all-cause and CVD mortality (in-trial [4.1-year]+post-trial [6.9-year]) and secondary endpoints (in-trial) were the composite of all-cause mortality and first CVD events and its components, CVD mortality and incident diabetes. RESULTS: There were no significant differences between the two groups for the primary endpoints over the in-trial plus post-trial follow-up, nor was there a difference for any secondary outcomes over the in-trial follow-up. CONCLUSIONS: The LLT+ACE-I and LLT+diuretic combinations showed similar effects in CVD-free older individuals. Randomised trials are needed to provide conclusive evidence.

Prevalence, awareness, treatment, and control of hypertension in Bangladesh: Findings from National Demographic and Health Survey, 2017-2018.

The purpose of this study was to estimate the age-standardised prevalence, awareness, treatment, and control of hypertension and to identify their risk factors in Bangladeshi adults. Data from 12 904 adults aged 18-95 years, available from the most recent nationally representative 2017-2018 Bangladesh Demographic and Health Survey were used. Hypertension was defined as having systolic blood pressure ≥140 mmHg and/or a diastolic blood pressure ≥90 mmHg, and/or taking anti-hypertensive drugs to control blood pressure. Age-standardized prevalence of hypertension and management were estimated with direct standardisation. A multilevel mixed-effects Poisson regression model with a robust variance was used to identify risk factors associated with hypertension and its awareness, treatment, and control. The overall age-standardized prevalence of hypertension was 26.2% (95% CI, 25.5-26.9); (men: 23.5%, women: 28.9%). Among those with hypertension (n = 3531), 36.7% were aware that they had the condition, and only 31.1% received anti-hypertensive medication. The prevalence of controlled hypertension was 12.7% among those with hypertension and 43.6% among those treated for hypertension (n = 1306). Factors independently associated with hypertension were increasing age, higher body mass index, being women, having diabetes, and residing in selected administrative divisions. A declining trend of hypertension control was observed with increasing age and low education. Hypertension is highly prevalent (one in four) in Bangladeshi adults, while awareness, treatment, and control are low. Irrespective of the risks associated with hypertension and its management, programs to increase its awareness, treatment, and control should be given high priority in reducing hypertension prevalence and improving hypertension control in Bangladesh.

Sex differences in Cardiac electronic device implantation: Outcomes from an Australian multi-centre clinical quality registry.

BACKGROUND: There is uncertainty regarding whether outcomes after Cardiac Implantable Electronic Devices (CIED) differ between women and men. There are no prospectively collected data regarding Australian CIED outcomes. This study aimed to determine whether the characteristics and outcomes of Australian patients undergoing CIED implantation differ by sex. METHODS: We prospectively followed 5,360 patients undergoing CIED implantation between 2015 and 2019 in a large multi-centre Australian registry. Patient characteristics, procedural data, medications and clinical outcomes to 1 year were analysed. RESULTS: The mean age was 76.2 + 11.2 years, and 2022 (37.7%) were female. Women were older than men at device implantation (77.0 ±â€¯11.6 years vs. 75.5 ±â€¯10.9 years, p < 0.001). Most implants were de novo (79.7%). Pacing was more commonly for sick sinus syndrome in women than men (54.4% vs. 47.2%, p < 0.001) and less often for A-V block (28.3% vs. 35.1%, p < 0.001). Adverse events at 30 days were low compared to international cohorts, for mortality (0.06%) and major complications (0.6%). There were no significant sex differences (women vs. men) for death (HR 1.33, 95% CI 0.58-3.13, p = 0.49) or major complications (HR 1.41, 95% 95% CI 0.65-3.03, p = 0.39). At 1-year, there was no difference in major complications or risk-adjusted all-cause mortality (HR 1.05, 95% CI 0.70-1.29, p = 0.77) between women and men. CONCLUSIONS: Clinical practice and 30-day outcomes after CIED implantation in Australia are consistent with international reports. There were no differences in procedural complication rates or clinical outcomes at 1-year between women and men, regardless of age or CIED system implanted.

Long-Term Blood Pressure Variability and Risk of Cognitive Decline and Dementia Among Older Adults.

Background Blood pressure variability (BPV) in midlife increases risk of late-life dementia, but the impact of BPV on the cognition of adults who have already reached older ages free of major cognitive deficits is unknown. We examined the risk of incident dementia and cognitive decline associated with long-term, visit-to-visit BPV in a post hoc analysis of the ASPREE (Aspirin in Reducing Events in the Elderly) trial. Methods and Results ASPREE participants (N=19 114) were free of dementia and significant cognitive impairment at enrollment. Measurement of BP and administration of a standardized cognitive battery evaluating global cognition, delayed episodic memory, verbal fluency, and processing speed and attention occurred at baseline and follow-up visits. Time-to-event analysis using Cox proportional hazards regression models were used to calculate hazard ratios (HR) and corresponding 95% CI for incident dementia and cognitive decline, according to tertile of SD of systolic BPV. Individuals in the highest BPV tertile compared with the lowest had an increased risk of incident dementia and cognitive decline, independent of average BP and use of antihypertensive drugs. There was evidence that sex modified the association with incident dementia (interaction P=0.02), with increased risk in men (HR, 1.68; 95% CI, 1.19-2.39) but not women (HR, 1.01; 95% CI, 0.72-1.42). For cognitive decline, similar increased risks were observed for men and women (interaction P=0.15; men: HR, 1.36; 95% CI, 1.16-1.59; women: HR, 1.14; 95% CI, 0.98-1.32). Conclusions High BPV in older adults without major cognitive impairment, particularly men, is associated with increased risks of dementia and cognitive decline. Registration URL: https://www.clinicaltrials.gov; Unique identifier: NCT01038583; isrctn.com. Identifier: ISRCTN83772183.

The effect of taking blood pressure lowering medication at night on cardiovascular disease risk. A systematic review.

To investigate the effect of night-time BP-lowering drug treatment on the risk of major CVD and mortality, we systematically reviewed randomized controlled trials comparing night-time versus morning dosing. Two studies were found relevant to the clinical question (the MAPEC and Hygia trials). They were similar in study design and population and were conducted by the same study group. As the Hygia trial had more power with a significantly larger sample size, we did not perform a meta-analysis. Both studies reported a reduction of ~50% in major CVD events and all-cause mortality with night-time dosing and a reduction of 60% in CVD mortality. The results from these studies support the implementation of night-time BP-lowering drug treatment in the prevention of CVD and mortality. However there is an on-going discussion on the validity and methodology of MAPEC and Hygia trials, the interpretation of the results should be cautious. Stronger evidence is needed prior to changing clinical practice. Questions that remain to be answered relate to the generalisability of the results across different populations at different levels of BP related risk and the importance of morning versus evening timing of medication on CVD prevention as determined though a well-designed randomised controlled trial.

Long-Term Blood Pressure Variability and Risk of Cardiovascular Disease Events Among Community-Dwelling Elderly.

High office blood pressure variability (OBPV) in midlife increases the risk of cardiovascular disease (CVD), but the impact of OBPV in older adults without previous CVD is unknown. We conducted a post hoc analysis of ASPREE trial (Aspirin in Reducing Events in the Elderly) participants aged 70-years and older (65 for US minorities) without history of CVD events at baseline, to examine risk of incident CVD associated with long-term, visit-to-visit OBPV. CVD was a prespecified, adjudicated secondary end point in ASPREE. We estimated OBPV using within-individual SD of mean systolic BP from baseline and first 2 annual visits. Cox proportional hazards regression was used to calculate hazard ratios (HR) and 95% CI for associations with CVD events. In 16 475 participants who survived to year 2 without events, those in the highest tertile of OBPV had increased risk of CVD events after adjustment for multiple covariates, when compared with participants in the lowest tertile (HR, 1.36 [95% CI, 1.08-1.70]; P=0.01). Similar increased risk was observed for ischemic stroke (HR, 1.56 [95% CI, 1.04-2.33]; P=0.03), heart failure hospitalization, or death (HR, 1.73 [95% CI, 1.07-2.79]; P=0.02), and all-cause mortality (HR, 1.27 [95% CI, 1.04-1.54]; P=0.02). Findings were consistent when stratifying participants by use of antihypertensive drugs, while sensitivity analyses suggested the increased risk was especially for individuals whose BP was uncontrolled during the OBPV estimation period. Our findings support increased OBPV as a risk factor for CVD events in healthy older adults with, or without hypertension, who have not had such events previously. Registration- URL: https://www.clinicaltrials.gov; Unique identifiers: NCT01038583; URL: https://www.isrctn.com; Unique identifiers: ISRCTN83772183.

Antihypertensive medication use and blood pressure control among treated older adults.

The association of different antihypertensive regimens with blood pressure (BP) control is not well-described among community-dwelling older adults with low comorbidity. We examined antihypertensive use and BP control in 10 062 treated hypertensives from Australia and the United States (US) using baseline data from the ASPirin in Reducing Events in the Elderly (ASPREE) trial. Renin-angiotensin system (RAS) drugs were the most prevalently used antihypertensive in both countries (Australia: 81.7% of all regimens; US: 62.9% of all regimens; P < .001). Diuretics were the next most commonly used antihypertensive in both countries, but were more often included in regimens of US participants (48.9%, vs 33.3% of regimens in Australia; P < .001). Among all antihypertensive classes and possible combinations, monotherapy with a RAS drug was the most common regimen in both countries, but with higher prevalence in Australian than US participants (35.9% vs 20.9%; P < .001). For both monotherapy and combination users, BP control rates across age, ethnicity, and sex were consistently lower in Australian than US participants. After adjustment for age, sex, ethnicity, and BMI, significantly lower BP control rates remained in Australian compared to US participants for the most commonly used classes and regimens (RAS blocker monotherapy: BP control = 45.5% vs 54.2%; P = .002; diuretic monotherapy: BP control = 45.2% vs 64.5%; P = .001; and RAS blocker/diuretic combo: BP control = 50.2% vs 65.6%; P = .001). Our findings highlight variation in antihypertensive use in older adults treated for hypertension, with implications for BP control. Differences in BP control that were observed may be influenced, in part, by reasons other than choice of specific regimens.

Factors Associated With Treatment and Control of Hypertension in a Healthy Elderly Population Free of Cardiovascular Disease: A Cross-sectional Study.

BACKGROUND: Despite readily available treatments, control of blood pressure (BP) with population aging remains suboptimal. Further, there are gaps in the understanding of the management of high BP in the aged. We explored antihypertensive treatment and control among elderly hypertensive participants free from overt cardiovascular disease (CVD), and identified factors related to both "untreated" and "treated but uncontrolled" high BP. METHODS: We analyzed baseline data from 19,114 individuals aged ≥65 years enrolled from Australia and United States (US) in the ASPirin in Reducing Events in the Elderly study. Hypertension was defined as an average systolic/diastolic BP ≥140/90 mm Hg and/or the use of any BP lowering medication. "Controlled hypertension" was defined if participants were receiving antihypertensive medication and BP <140 and 90 mm Hg. Descriptive analyses were used to summarize hypertension control rates; logistic regression was used to investigate relationships with treatment and BP control. RESULTS: Overall, 74% (14,213/19,114) of participants were hypertensive; and of these 29% (4,151/14,213) were untreated. Among those treated participants, 53% (5,330/10,062) had BP ≥140/90 mm Hg. Participants who were untreated were more likely to be men, have higher educational status, and be in good physical health, and less likely to have significant comorbidities. The factors related to "treated but uncontrolled" BP included older age, male, Black race (vs. White), using antihypertensive monotherapy (vs. multiple) and residing in Australia (vs. US). CONCLUSIONS: High levels of "untreated" and "treated but uncontrolled" BP occur in healthy elderly people without CVD, suggesting there are opportunities for better BP control in the primary prevention of CVD in this population. CLINICAL TRIALS REGISTRATION: NCT01038583.

Lack of a significant legacy effect of baseline blood pressure 'treatment naivety' on all-cause and cardiovascular mortality in the Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial.

OBJECTIVES: To investigate legacy effects at 14-year follow-up of all-cause and cardiovascular disease (CVD) mortality in 'treatment-naive' or 'previous treatment' groups based on blood pressure (BP)-lowering treatment status at baseline. METHODS: A post-hoc observational study of the Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial. We excluded participants with a previous history of CVD events. Cox proportional hazard model and 95% confidence interval were used to estimate the effects of treatment naive on mortality outcomes. Moreover, a subgroup analysis by estimated 10-year Framingham risk score was performed. RESULTS: In multivariable models adjusting for baseline and in-trial characteristics (BP values and number of BP medications as time-dependent variables), there was no statistically significant difference in 5 and 14-year all-cause mortality with a hazard ratio of 0.93 (95% confidence interval 0.80-1.09) and hazard ratio 0.95 (0.88-1.03) and in 5 and 14-year CVD mortality hazard ratio 0.94 (0.72-1.23) and hazard ratio 0.93 (0.80-1.08). In subgroup by absolute CVD risk, no heterogeneity of the association between treatment naive and short-term or long-term all-cause or CVD mortality were found. All comparisons are between the treatment-naive and previous treatment groups. CONCLUSION: Physicians are concerned about 'legacy effects' of not treating individuals with a BP of 140 mmHg or over and low absolute risk. When treatment intensification was taken into consideration in the primary prevention population in this study, no adverse legacy effect as a result of baseline BP 'treatment naivety' was evident in 14 years of follow-up. The nonsignificant associations were consistent across the CVD risk subgroups. However, the results may be biased due to unobserved residual confounding and therefore should be interpreted with caution.

Change in Blood Pressure Variability Among Treated Elderly Hypertensive Patients and Its Association With Mortality.

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.

Association of depression with mortality in an elderly treated hypertensive population.

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 < 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.

Short- and long-term association of lipid-lowering drug treatment and cardiovascular disease by estimated absolute risk in the Second Australian National Blood Pressure study.

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.

Feasibility of engaging "Village Doctors" in the Community-based Integrated Management of Childhood Illness (C-IMCI): experience from rural Bangladesh.

BACKGROUND: Informal health care providers particularly "village doctors" are the first point of care for under-five childhood illnesses in rural Bangladesh. We engaged village doctors as part of the Multi-Country Evaluation (MCE) of Integrated Management of Childhood Illness (IMCI) and assessed their management of sick under-five children before and after a modified IMCI training, supplemented with ongoing monitoring and supportive supervision. METHODS: In 2003-2004, 144 village doctors across 131 IMCI intervention villages in Matlab Bangladesh participated in a two-day IMCI training; 135 of which completed pre- and post-training evaluation tests. In 2007, 38 IMCI-trained village doctors completed an end-of-project knowledge retention test. Village doctor prescription practices for sick under-five children were examined through household surveys, and routine monitoring visits. In-depth interviews were done with mothers seeking care from village doctors. RESULTS: Village doctors' knowledge on the assessment and management of childhood illnesses improved significantly after training; knowledge of danger signs of pneumonia and severe pneumonia increased from 39% to 78% (P < 0.0001) and from 17% to 47% (P < 0.0001) respectively. Knowledge on the correct management of severe pneumonia increased from 62% to 84% (P < 0.0001), and diarrhoea management improved from 65% to 82% (P = 0.0005). Village doctors retained this knowledge over three years except for home management of pneumonia. No significant differences were observed in prescribing practices for diarrhoea and pneumonia management between trained and untrained village doctors. Village doctors were accessible to communities; 76% had cell phones; almost all attended home calls, and did not charge consultation fees. Nearly all (91%) received incentives from pharmaceutical representatives. CONCLUSIONS: Village doctors have the capacity to learn and retain knowledge on the appropriate management of under-five illnesses. Training alone did not improve inappropriate antibiotic prescription practices. Intensive monitoring and efforts to target key actors including pharmaceutical companies, which influence village doctors dispensing practices, and implementation of mechanisms to track and regulate these providers are necessary for future engagement in management of under-five childhood illnesses.

Night-time ambulatory blood pressure is the best pretreatment blood pressure predictor of 11-year mortality in treated older hypertensives.

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.

Visit-to-visit (long-term) and ambulatory (short-term) blood pressure variability to predict mortality in an elderly hypertensive population.

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.

Calcium channel blockers and breast cancer incidence: An updated systematic review and meta-analysis of the evidence.

Controversy exists regarding the potential association between taking calcium channel blockers (CCBs) and the development of breast cancer. As a positive association would have important public health implications due to the widespread use of CCBs, this study aimed to incorporate new evidence to determine whether an association is likely to exist. We searched MEDLINE, EMBASE and the Cochrane Library to 28 June 2016 for relevant literature. References and citing articles were checked and authors contacted as necessary. Two authors independently selected articles and extracted data. Twenty-nine studies were reviewed; 26 were non-randomised studies (NRS). Meta-analysis of study data where adjustment for 'confounding by indication' was judged to be present suggests that an association, if any, is likely to be modest in magnitude (pooled odds/risk ratio 1.09 (95% confidence interval (CI) 1.03-1.15, I2=0%, 8 sub-studies; pooled hazard ratio 0.99 (95% CI 0.94-1.03, I2=35%, 9 sub-studies)). There are credible study data showing an increased relative risk with long-term use of CCBs, but the results of our meta-analysis and of meta-regression of log relative risk against minimum follow-up time are mixed. The current summative evidence does not support a clear association between taking CCBs and developing breast cancer. However, uncertainty remains, especially for long-term use and any association might not be uniform between different populations and/or breast cancer sub-types. We thus recommend further NRS in settings where CCB use is highly prevalent and population-based cancer, prescription and health-registries exist, to resolve this continuing uncertainty. PROSPERO, CRD42015026712.