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

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

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

Identifying the research, advocacy, policy and implementation needs for the prevention and management of respiratory syncytial virus lower respiratory tract infection in low- and middle-income countries

Introduction: The high burden of respiratory syncytial virus (RSV) infection in young children disproportionately occurs in low- and middle-income countries (LMICs). The PROUD (Preventing RespiratOry syncytial virUs in unDerdeveloped countries) Taskforce of 24 RSV worldwide experts assessed key needs for RSV prevention in LMICs, including vaccine and newer preventive measures. Methods: A global, survey-based study was undertaken in 2021. An online questionnaire was developed following three meetings of the Taskforce panellists wherein factors related to RSV infection, its prevention and management were identified using iterative questioning. Each factor was scored, by non-panellists interested in RSV, on a scale of zero (very-low-relevance) to 100 (very-high-relevance) within two scenarios: (1) Current and (2) Future expectations for RSV management. Results: Ninety questionnaires were completed: 70 by respondents (71.4% physicians; 27.1% researchers/scientists) from 16 LMICs and 20 from nine high-income (HI) countries (90.0% physicians; 5.0% researchers/scientists), as a reference group. Within LMICs, RSV awareness was perceived to be low, and management was not prioritised. Of the 100 factors scored, those related to improved diagnosis particularly access to affordable point-of-care diagnostics, disease burden data generation, clinical and general education, prompt access to new interventions, and engagement with policymakers/payers were identified of paramount importance. There was a strong need for clinical education and local data generation in the lowest economies, whereas upper-middle income countries were more closely aligned with HI countries in terms of current RSV service provision. Conclusion: Seven key actions for improving RSV prevention and management in LMICs are proposed

Global, regional, and national burden of disorders affecting the nervous system, 1990–2021: a systematic analysis for the Global Burden of Disease Study 2021

BackgroundDisorders affecting the nervous system are diverse and include neurodevelopmental disorders, late-life neurodegeneration, and newly emergent conditions, such as cognitive impairment following COVID-19. Previous publications from the Global Burden of Disease, Injuries, and Risk Factor Study estimated the burden of 15 neurological conditions in 2015 and 2016, but these analyses did not include neurodevelopmental disorders, as defined by the International Classification of Diseases (ICD)-11, or a subset of cases of congenital, neonatal, and infectious conditions that cause neurological damage. Here, we estimate nervous system health loss caused by 37 unique conditions and their associated risk factors globally, regionally, and nationally from 1990 to 2021.MethodsWe estimated mortality, prevalence, years lived with disability (YLDs), years of life lost (YLLs), and disability-adjusted life-years (DALYs), with corresponding 95% uncertainty intervals (UIs), by age and sex in 204 countries and territories, from 1990 to 2021. We included morbidity and deaths due to neurological conditions, for which health loss is directly due to damage to the CNS or peripheral nervous system. We also isolated neurological health loss from conditions for which nervous system morbidity is a consequence, but not the primary feature, including a subset of congenital conditions (ie, chromosomal anomalies and congenital birth defects), neonatal conditions (ie, jaundice, preterm birth, and sepsis), infectious diseases (ie, COVID-19, cystic echinococcosis, malaria, syphilis, and Zika virus disease), and diabetic neuropathy. By conducting a sequela-level analysis of the health outcomes for these conditions, only cases where nervous system damage occurred were included, and YLDs were recalculated to isolate the non-fatal burden directly attributable to nervous system health loss. A comorbidity correction was used to calculate total prevalence of all conditions that affect the nervous system combined.FindingsGlobally, the 37 conditions affecting the nervous system were collectively ranked as the leading group cause of DALYs in 2021 (443 million, 95% UI 378–521), affecting 3·40 billion (3·20–3·62) individuals (43·1%, 40·5–45·9 of the global population); global DALY counts attributed to these conditions increased by 18·2% (8·7–26·7) between 1990 and 2021. Age-standardised rates of deaths per 100 000 people attributed to these conditions decreased from 1990 to 2021 by 33·6% (27·6–38·8), and age-standardised rates of DALYs attributed to these conditions decreased by 27·0% (21·5–32·4). Age-standardised prevalence was almost stable, with a change of 1·5% (0·7–2·4). The ten conditions with the highest age-standardised DALYs in 2021 were stroke, neonatal encephalopathy, migraine, Alzheimer's disease and other dementias, diabetic neuropathy, meningitis, epilepsy, neurological complications due to preterm birth, autism spectrum disorder, and nervous system cancer.InterpretationAs the leading cause of overall disease burden in the world, with increasing global DALY counts, effective prevention, treatment, and rehabilitation strategies for disorders affecting the nervous system are needed

Predictive performance of echocardiographic parameters for cardiovascular events among elderly treated hypertensive patients

BACKGROUND: Hypertension leads to cardiac structural and functional changes, commonly assessed by echocardiography. In this study, we assessed the predictive performance of different echocardiographic parameters including left ventricular hypertrophy (LVH) on future cardiovascular outcomes in elderly hypertensive patients without heart failure. METHODS: Data from LVH substudy of the Second Australian National Blood Pressure trial were used. Echocardiograms were performed at entry into the study. Cardiovascular outcomes were identified over short term (median 4.2 years) and long term (median 10.9 years). LVH was defined using threshold values of LV mass (LVM) indexed to either body surface area (BSA) or height2.7: >115/95g/m2 (LVH-BSA115/95) or ≥49/45g/m2.7 (LVH-ht49/45) in males/females, respectively, and ≥125g/m2 (LVH-BSA125) or ≥51g/m2.7 (LVH-ht51) for both sexes. RESULTS: In the 666 participants aged ≥65 years in this analysis, LVH prevalence at baseline was 33%–70% depending on definition; and after adjusting for potential risk factors, only LVH-BSA115/95 predicted both short- and long-term cardiovascular outcomes. Participants having LVH-BSA115/95 (69%) at baseline had twice the risk of having any first cardiovascular event over the short term (hazard ratio, 95% confidence interval: 2.00, 1.12–3.57, P = 0.02) and any fatal cardiovascular events (2.11, 1.21–3.68, P = 0.01) over the longer term. Among other echocardiographic parameters, LVM and LVM indexed to either BSA or height2.7 predicted cardiovascular events over both short and longer term. CONCLUSIONS: In elderly treated hypertensive patients without heart failure, determining LVH by echocardiography is highly dependent on the methodology adopted. LVH-BSA115/95 is a reliable predictor of future cardiovascular outcomes in the elderly

Association of depression with mortality in an elderly treated hypertensive population

Background: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

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

Rate of Change in Renal Function and Mortality in Elderly Treated Hypertensive Patients

Background and objectives Evidence relating the rate of change in renal function, measured as eGFR, after antihypertensive treatment in elderly patients to clinical outcome is sparse. This study characterized the rate of change in eGFR after commencement of antihypertensive treatment in an elderly population, the factors associated with eGFR rate change, and the rate's association with all-cause and cardiovascular mortality. Design, setting, participants, & measurements Data from the Second Australian National Blood Pressure study were used, where 6083 hypertensive participants aged =65 years were enrolled during 1995-1997 and followed for a median of 4.1 years (in-trial). Following the Second Australian National Blood Pressure study, participants were followed-up for a further median 6.9 years (post-trial). The annual rate of change in the eGFR was calculated in 4940 participants using creatinine measurements during the in-trial period and classified into quintiles (Q) on the basis of the following eGFR changes: rapid decline (Q1), decline (Q2), stable (Q3), increase (Q4), and rapid increase (Q5). Results A rapid decline in eGFR in comparison with those with stable eGFRs during the in-trial period was associated with older age, living in a rural area, wider pulse pressure at baseline, receiving diuretic-based therapy, taking multiple antihypertensive drugs, and having blood pressure &lt;140/90 mmHg during the study. However, a rapid increase in eGFR was observed in younger women and those with a higher cholesterol level. After adjustment for baseline and in-trial covariates, Cox-proportional hazard models showed a significantly greater risk for both all-cause (hazard ratio, 1.28; 95% confidence interval, 1.09 to 1.52; P=0.003) and cardiovascular (hazard ratio, 1.40; 95% confidence interval, 1.11 to 1.76; P=0.004) mortality in the rapid decline group compared with the stable group over a median of 7.2 years after the last eGFR measure. No significant association with mortality was observed for a rapid increase in eGFR. Conclusions In elderly persons with treated hypertension, a rapid decline in eGFR is associated with a higher risk of mortality