Cardiovascular Disease Risk Scores and Incident Dementia and Cognitive Decline in Older Men and Women.

INTRODUCTION: Risk factors for cardiovascular disease (CVD) also increase the risk of dementia. However, whether commonly used CVD risk scores are associated with dementia risk in older adults who do not have a history of CVD, and potential gender differences in this association, remains unclear. The aim of this study was to determine whether CVD risk scores are prospectively associated with cognitive decline and dementia in initially healthy older men and women. METHODS: A total of19,114 participants from a prospective cohort of individuals aged 65+ years without known CVD or dementia were recruited. The atherosclerotic cardiovascular disease risk score (ASCVDRS), Systematic Coronary Risk Evaluation 2-Older Persons (SCORE2-OP), and the Framingham risk score (FRS) were calculated at baseline. Risk of dementia (according to DSM-IV criteria) and cognitive decline (defined as a >1.5 standard deviation decline in global cognition, episodic memory, psychomotor speed, or verbal fluency from the previous year) were assessed using hazard ratio. RESULTS: Over a median follow-up of 6.4 years, 850 individuals developed dementia and 4,352 cognitive decline. Men and women in the highest ASCVDRS tertile had a 41% (95% CI 1.08, 1.85) and 45% (1.11, 1.89) increased risk of dementia compared to the lowest tertile, respectively. Likewise, men and women in the highest SCORE2-OP tertile had a 64% (1.24, 2.16) and 60% (1.22, 2.11) increased risk of dementia compared to the lowest tertile, respectively. Findings were similar, but the risk was slightly lesser when examining risk of cognitive decline for both ASCVDRS and SCORE2-OP. However, FRS was only associated with the risk of cognitive decline among women (highest vs. lowest tertiles: 1.13 [1.01-1.26]). CONCLUSION: These findings suggest the utility of the ASCVDRS and SCORE2-OP in clinical practice, to not only assess future risk of CVD, but also as potential early indicators of cognitive impairment, even in relatively healthy older men and women.

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.

Social isolation, social support, loneliness and cardiovascular disease risk factors: A cross-sectional study among older adults.

BACKGROUND: Social health reflects one's ability to form interpersonal relationships. Poor social health is a risk factor for cardiovascular disease (CVD), however an in-depth exploration of the link through CVD risk factors is lacking. AIM: To examine the relationship between social health (social isolation, social support, loneliness) and CVD risk factors among healthy older women and men. METHODS: Data were from 11,498 healthy community-dwelling Australians aged ≥70 years from the ASPirin in Reducing Events in the Elderly (ASPREE) trial and the ASPREE Longitudinal Study of Older Persons sub-study. Ten-year CVD risk was estimated using the Atherosclerotic CVD Risk Scale (ASCVDRS) and the Framingham Risk Score (FRS). RESULTS: Physical inactivity and experiencing depressive symptoms were the only CVD risk factors that consistently differed by all three social health constructs. Loneliness was associated with greater ASCVDRS (women: ß = 0.01, p < 0.05; men: ß = 0.03, p < 0.001), social isolation with greater FRS (women: ß = 0.02, p < 0.01; men: ß = 0.03, p < 0.01) and the social health composite of being lonely (regardless of social isolation and/or social support status) with greater ASCVDRS (women: ß = 0.01, p = 0.02; men: ß = 0.03, p < 0.001). Among men, loneliness was also associated with greater FRS (ß = 0.03, p < 0.001) and social support with greater ASCVDRS (ß = 0.02, p = 0.01). Men were more socially isolated, less socially supported and less lonely than women. CONCLUSION: Social isolation, social support and loneliness displayed diverse relationships with CVD risk factors and risk scores, emphasising the importance of distinguishing between these constructs. These findings inform on potential avenues to manage poor social health and CVD risk among older adults.

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.

Long-term blood pressure variability and frailty risk in older adults.

INTRODUCTION: In healthy older adults, the relationship between long-term, visit-to-visit variability in blood pressure (BP) and frailty is uncertain. METHODS: Secondary analysis of blood pressure variability (BPV) and incident frailty in >13 000 participants ≥65-70 years enrolled in the ASPirin in Reducing Events in the Elderly (ASPREE) trial and its observational follow-up (ASPREE-XT). Participants were without dementia, physical disability, or cardiovascular disease at baseline. BPV was estimated using standard deviation of mean BP from three annual visits (baseline through the second annual follow-up). Frailty was defined using Fried phenotype and a frailty deficit accumulation index (FDAI). Participants with frailty during the BPV estimation period were excluded from the main analysis. Adjusted Cox proportional hazards regression evaluated the association between BPV and incident frailty, and linear mixed models for change in frailty scores, through a maximum of 9 years of follow-up. RESULTS: Participants in the highest systolic BPV tertile were at higher risk of frailty compared to those in the lowest (referent) tertile of systolic BPV [Fried hazard ratio (HR) 1.17, 95% confidence interval (CI) 1.04-1.31; FDAI HR 1.18, 95% CI 1.07-1.30]. Findings were consistent when adjusted for multiple covariates and when stratified by antihypertensive use. Linear mixed models showed that higher systolic BPV was associated with increasing frailty score over time. Diastolic BPV was not consistently associated. CONCLUSIONS: High systolic BPV, independent of mean BP, is associated with increased risk of frailty in healthy older adults. Variability of BP across visits, even in healthy older adults, can convey important risk information beyond mean BP. TRIAL REGISTRATION: ClinicalTrials.gov NCT01038583 and ISRCTN83772183.

Daily low-dose aspirin and blood pressure in community-dwelling older adults.

High-quality randomized trial evidence is lacking on whether low-dose aspirin exerts significant effects on blood pressure (BP) in older adults. The authors assessed longitudinal BP changes in participants enrolled in ASPirin in Reducing Events in the Elderly (ASPREE), a randomized, placebo-controlled trial of 100 mg daily aspirin in 19 114 community-dwelling Australian and U.S. adults without cardiovascular disease (CVD), dementia, or independence-limiting physical disability. Participants' BP was recorded at baseline and annual study visits, and managed by their usual care provider. BP trajectories for aspirin versus placebo during 4.7 years of follow-up were examined for systolic and diastolic BP separately, using linear mixed models to account for between and within-individual variability in BP. Analyses by subgroups were also explored with inclusion of interaction terms in the models. The difference in mean change in systolic BP between aspirin and placebo during study follow-up was -0.03 mm Hg (95% confidence interval [CI]: -0.13, 0.07; p = .541) (aspirin minus placebo), while the mean difference for change in diastolic BP was -0.05 mm Hg (95% CI: -0.11, 0.01; p = .094). These small, non-significant differences in BP change between the aspirin and placebo groups were consistent across baseline levels of BP and antihypertensive treatment status (treated/untreated). Likewise, subgroups of age, sex, chronic kidney disease, diabetes, and frailty revealed no interaction effect between the subgroup, aspirin treatment, and time. Interval-censored Cox proportional hazards regression showed no difference in rates of incident treated hypertension between aspirin and placebo-treated participants. The authors conclude that daily low-dose aspirin does not significantly affect BP in older adults when managed by usual care.

Comorbidities and Symptom Status in Moderate and Severe Aortic Stenosis: A Multicenter Clinical Cohort Study.

Background: Symptoms associated with severe aortic stenosis (AS) are used to guide management. Objectives: The purpose of this study was to examine the pattern of symptoms, comorbidities, and cardiac damage in moderate and severe AS. Methods: A total of 846,198 echocardiographic investigations from 330,940 individuals aged >18 years were selected for the most recent echocardiogram, moderate or severe AS (mean gradient 20.0-39.9 mm Hg, aortic valve peak gradient 3.0-3.9 m/s and aortic valve area >1.0 cm2; or ≥ 40.0 mm Hg, ≥4.0 m/s or ≤1.0 cm2, respectively), and a cardiologist consultation. Natural Language Processing was applied to letters to extract comorbidities, dyspnea, chest pain, and syncope. Patients with prior aortic valve replacement were excluded. Results: 2,213 patients (0.7% overall, 32.8% females) had moderate and 3,416 (1.0%, 47.3% females) had severe AS. Comorbidities were common, including hypertension, (56.6% moderate AS, 53.1% severe AS, P = 0.01), coronary disease (46.0% and 46.8%, respectively, P = 0.58) and atrial fibrillation (29.6% and 34.8%, respectively, P < 0.001). Symptoms were also common in both moderate (n = 915, 41.3%) and severe (n = 1,630, 47.7%) AS (P < 0.001). Comorbidities were more likely in symptomatic vs asymptomatic patients (P < 0.001). Dyspnea was more likely in severe AS, whereas angina and syncope were similar in moderate vs severe AS. In multivariable analysis, only dyspnea was associated with severe (vs moderate) AS (OR: 1.73, 95% CI: 1.41-2.13, P < 0.001). In both adjusted and unadjusted models, the degree of cardiac damage did not relate to presence of any symptoms but was associated with AS severity. Conclusions: Dyspnea is common in both moderate and severe AS, is associated with comorbidities and is not related to the degree of cardiac damage. Symptom-guided management decisions in AS may need revision.

Early vs. Late Readmission following Percutaneous Coronary Intervention: Predictors and Impact on Long-Term Outcomes.

BACKGROUND: Readmissions within 1 year after percutaneous coronary intervention (PCI) are common (18.6-50.4% in international series) and a burden to patients and health services, however their long-term implications are not well characterised. We compared predictors of 30-day (early) and 31-day to 1-year (late) unplanned readmission and the impact of unplanned readmission on long-term clinical outcomes post-PCI. METHODS: Patients enrolled in the GenesisCare Cardiovascular Outcomes Registry (GCOR-PCI) from 2008 to 2020 were included in the study. Multivariate logistic regression analysis was performed to identify predictors of early and late unplanned readmission. A Cox proportion hazards regression model was used to explore the impact of any unplanned readmission during the first year post-PCI on the clinical outcomes at 3 years. Finally, patients with early and late unplanned readmission were compared to determine which group was at the highest risk of adverse long-term outcomes. RESULTS: The study comprised 16,911 consecutively enrolled patients who underwent PCI between 2009-2020. Of these, 1422 patients (8.5%) experienced unplanned readmission within 1-year post-PCI. Overall, the mean age was 68.9 ± 10.5 years, 76.4% were male and 45.9% presented with acute coronary syndromes. Predictors of unplanned readmission included increasing age, female gender, previous CABG, renal impairment and PCI for acute coronary syndromes. Unplanned readmission within 1 year of PCI was associated with an increased risk of MACE (adjusted HR 1.84 (1.42-2.37), p < 0.001) and death over a 3-year follow-up (adjusted HR 1.864 (1.34-2.59), p < 0.001) compared with those without readmission within 1-year post-PCI. Late compared with early unplanned readmission within the first year of PCI was more frequently associated with subsequent unplanned readmission, MACE and death between 1 and 3 years post-PCI. CONCLUSIONS: Unplanned readmissions in the first year following PCI, particularly those occurring more than 30 days after discharge, were associated with a significantly higher risk of adverse outcomes, such as MACE and death at 3 years. Strategies to identify patients at high risk of readmission and interventions to reduce their greater risk of adverse events should be implemented post-PCI.

GFR Variability, Survival, and Cardiovascular Events in Older Adults.

Rationale & Objective: Variability in estimated glomerular filtration rate (eGFR) over time is often observed, but it is unknown whether this variation is clinically important. We investigated the association between eGFR variability and survival free of dementia or persistent physical disability (disability-free survival) and cardiovascular disease (CVD) events (myocardial infarction, stroke, hospitalization for heart failure, or CVD death). Study Design: Post hoc analysis. Setting & Participants: 12,549 participants of the ASPirin in Reducing Events in the Elderly trial. Participants were without documented dementia, major physical disability, previous CVD, and major life-limiting illness at enrollment. Predictors: eGFR variability. Outcomes: Disability-free survival and CVD events. Analytical Approach: eGFR variability was estimated using the standard deviation of eGFR measurements obtained from participants' baseline, first, and second annual visits. Associations between tertiles of eGFR variability with disability-free survival and CVD events occurring after the eGFR variability estimation period were examined. Results: During median follow-up of 2.7 years after the second annual visit, 838 participants died, developed dementia, or acquired a persistent physical disability; 379 had a CVD event. The highest tertile of eGFR variability had an increased risk of death/dementia/disability (HR, 1.35; 95% CI, 1.14-1.59) and CVD events (HR, 1.37; 95% CI, 1.06-1.77) compared with the lowest tertile after covariate adjustment. These associations were present in patients with and without chronic kidney disease at baseline. Limitations: Limited representation of diverse demographics. Conclusions: In older, generally healthy adults, higher variability in eGFR over time predicts increased risk of future death/dementia/disability and CVD events.

An assessment of the quality of care for children in eighteen randomly selected district and sub-district hospitals in Bangladesh.

BACKGROUND: Quality hospital care is important in ensuring that the needs of severely ill children are met to avert child mortality. However, the quality of hospital care for children in developing countries has often been found poor. As the first step of a country road map for improving hospital care for children, we assessed the baseline situation with respect to the quality of care provided to children under-five years age in district and sub-district level hospitals in Bangladesh. METHODS: Using adapted World Health Organization (WHO) hospital assessment tools and standards, an assessment of 18 randomly selected district (n=6) and sub-district (n=12) hospitals was undertaken. Teams of trained assessors used direct case observation, record review, interviews, and Management Information System (MIS) data to assess the quality of clinical case management and monitoring; infrastructure, processes and hospital administration; essential hospital and laboratory supports, drugs and equipment. RESULTS: Findings demonstrate that the overall quality of care provided in these hospitals was poor. No hospital had a functioning triage system to prioritise those children most in need of immediate care. Laboratory supports and essential equipment were deficient. Only one hospital had all of the essential drugs for paediatric care. Less than a third of hospitals had a back-up power supply, and just under half had functioning arrangements for safe-drinking water. Clinical case management was found to be sub-optimal for prevalent illnesses, as was the quality of neonatal care. CONCLUSION: Action is needed to improve the quality of paediatric care in hospital settings in Bangladesh, with a particular need to invest in improving newborn care.

Health-Related Quality of Life (HRQoL) and the Effect on Outcome in Patients Presenting with Coronary Artery Disease and Treated with Percutaneous Coronary Intervention (PCI): Differences Noted by Sex and Age.

Background and aim: poor quality of life (QoL) has been identified as an independent risk factor for mortality and major cardiac events (MACE) in patients with cardiovascular disease (CVD). The aim of this study was to assess health-related quality of life (HRQoL) at baseline and its association with outcome in patients with coronary artery disease presenting for percutaneous coronary intervention (PCI). The outcome was measured by mortality and MACE at 1-year, and whether there was any difference for sex and different age groups. Methods and results: all patients prospectively enrolled into the GenesisCare Outcome Registry (GCOR) over a 11-year period were included in the study. The EQ-5D-5L and VAS patient survey were used for assessment of baseline HRQoL. Of the 15,198 patients, only 6591 (43.4%) completed the self-assessment. Women had significantly more impairment of all five dimensions of the EQ-5D-5L survey, and their self-reported QoL was significantly lower than men (68.3 in women vs. 71.9 in men, p < 0.001). Poor QoL was strongly associated with increased mortality (HR 2.85; 95% CI 1.76 to 4.62, p < 0.001) and MACE (HR 1.40; 95% CI 1.10 to 1.79, p = 0.01). A similar trend was noted for women and men, but did not reach significance in women due to the smaller number of female patients. Conclusion: poor HRQoL is associated with subsequent mortality and MACE in patients undergoing PCI. By not assessing quality of life as a standard of care, an opportunity is lost to identify high-risk patients who may benefit from targeted interventions to improve health outcomes.

The Association of Sex with Unplanned Cardiac Readmissions following Percutaneous Coronary Intervention in Australia: Results from a Multicentre Outcomes Registry (GenesisCare Cardiovascular Outcomes Registry).

Background and aim: Unplanned cardiac readmissions in patients with percutaneous intervention (PCI) is very common and is seen as a quality indicator of in-hospital care. Most studies have reported on the 30-day cardiac readmission rates, with very limited information being available on 1-year readmission rates and their association with mortality. The aim of this study was to investigate the impact of biological sex at 1-year post-PCI on unplanned cardiac readmissions. Methods and results: Patients enrolled into the GenesisCare Cardiovascular Outcomes Registry (GCOR-PCI) from December 2008 to December 2020 were included in the study. A total of 13,996 patients completed 12 months of follow-up and were assessed for unplanned cardiac readmissions. All patients with unplanned cardiac readmissions in the first year of post-PCI were followed in year 2 (post-PCI) for survival status. The rate of unplanned cardiac readmissions was 10.1%. Women had a 29% higher risk of unplanned cardiac readmission (HR 1.29, 95% CI 1.11 to 1.48; p = 0.001), and female sex was identified as an independent predictor of unplanned cardiac readmissions. Any unplanned cardiac readmission in the first year was associated with a 2.5-fold higher risk of mortality (HR 2.50, 95% CI 1.67 to 3.75; p < 0.001), which was similar for men and women. Conclusion: Unplanned cardiac readmissions in the first year post-PCI was strongly associated with increased all-cause mortality. Whilst the incidence of all-cause mortality was similar between women and men, a higher incidence of unplanned cardiac readmissions was observed for women, suggesting distinct predictors of unplanned cardiac readmissions exist between women and men.

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.

Sex Differences in Baseline Characteristics Do Not Predict Early Outcomes after Percutaneous Coronary Intervention: Results from the Australian GenesisCare Cardiovascular Outcomes Registry (GCOR).

OBJECTIVE: The effect of baseline differences between men and women on early outcomes after percutaneous coronary intervention (PCI). DESIGN, SETTING, PARTICIPANTS: This is an observational study of all participants in the GenesisCare Cardiovascular Outcomes Registry, undergoing PCI. The registry holds data for both emergency and elective procedures. Data was collected on 10,989 consecutive patients from 12 Australian Private Hospitals, including baseline demographics, co-morbidities, risk factors, PCI procedures, and lesion characteristics. MAIN OUTCOME MEASURES: Outcome was measured for complications (in-hospital death, peri-procedural myocardial infarctions, and bleeding events), at discharge and at 30-days for death, myocardial infarction, target lesion revascularisation (TLR), major adverse cardiac events (MACE), and unplanned readmissions. RESULTS: Women represented 23% of the study population, were significantly older, with a higher rate of hypertension and hyperlipidaemia. Heart failure was more common in women and was associated with a significantly higher average ejection fraction than in men. Women had a lower rate of pre-existing coronary artery disease (CAD), had less complex CAD, and needed fewer stents. Periprocedural complications were similar, but major bleeding was more common in women. The 30-day outcome was similar between men and women for death, myocardial infarction, target lesion revascularisation (TLR), major adverse cardiovascular events (MACE), and unplanned readmissions. CONCLUSIONS: Although significant differences were observed between women and men in both clinical presentation and complexity of disease, the 30-day outcome was similar for death and MACE. Women had a higher rate of major bleeding events, and lower adherence to statins and dual antiplatelet therapy (DAPT).

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.

Long-Term Outcomes of Contemporary Percutaneous Coronary Intervention with the Xience Drug-Eluting Stent: Results from a Multicentre Australian Registry.

Introduction: Several large registries have evaluated outcomes after percutaneous coronary intervention (PCI) in the USA, however there are no contemporary data regarding long-term outcomes after PCI, particularly comparing new generation drug-eluting stents (DES) with other stents in Australia. Additionally, approval of new-generation drug-eluting stents (DES) is almost exclusively based on non-inferiority trials comparing outcomes with early generation DES, and there are limited data comparing safety and efficacy outcomes of new-generation DES with bare metal stents (BMS). This study reports in-hospital and long-term outcomes after PCI with the Xience DES from a large national registry, the GenesisCare Outcomes Registry (GCOR). Methods: The first 1500 patients consecutively enrolled from January 2015 to January 2019 and treated exclusively with either Xience DES or BMS and eligible for 1-year follow-up were included. Baseline patient and procedural data, major adverse cardiovascular events (MACE) in-hospital, at 30 days and 1-year, and medications were reported and analysed with respect to Xience DES (n = 1000) or BMS (n = 500) use. Results: In this cohort the mean age was 68.4 ± 10.7 years, 76.9% were male, 24.6% had diabetes mellitus and 45.9% presented with acute coronary syndromes. Of the overall cohort of 4765 patients from this period including all DES types, and patients who received multiple DES or a combination of DES and BMS, DES were exclusively used in 3621 (76.0%) patients, and BMS were exclusively used in 596 (12.5%). In comparison to international cohorts, adverse clinical event rates were low at 30 days in terms of mortality (0.20%), target lesion revascularisation (TLR, 0.27%) and MACE (0.47%), and at 12 months for mortality (1.26%) TLR (1.16%) and MACE (1.78%). Conclusions: Clinical practice and long-term outcomes of PCI with the Xience DES in Australia are consistent with international series. Recent trends indicate DES use has increased in parallel with good outcomes despite an increasingly complex patient and lesion cohort.

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.

Cardiovascular risk prediction in healthy older people.

Identification of individuals with increased risk of major adverse cardiovascular events (MACE) is important. However, algorithms specific to the elderly are lacking. Data were analysed from a randomised trial involving 18,548 participants ≥ 70 years old (mean age 75.4 years), without prior cardiovascular disease events, dementia or physical disability. MACE included coronary heart disease death, fatal or nonfatal ischaemic stroke or myocardial infarction. Potential predictors tested were based on prior evidence and using a machine-learning approach. Cox regression analyses were used to calculate 5-year predicted risk, and discrimination evaluated from receiver operating characteristic curves. Calibration was also assessed, and the findings internally validated using bootstrapping. External validation was performed in 25,138 healthy, elderly individuals in the primary care environment. During median follow-up of 4.7 years, 594 MACE occurred. Predictors in the final model included age, sex, smoking, systolic blood pressure, high-density lipoprotein cholesterol (HDL-c), non-HDL-c, serum creatinine, diabetes and intake of antihypertensive agents. With variable selection based on machine-learning, age, sex and creatinine were the most important predictors. The final model resulted in an area under the curve (AUC) of 68.1 (95% confidence intervals 65.9; 70.4). The model had an AUC of 67.5 in internal and 64.2 in external validation. The model rank-ordered risk well but underestimated absolute risk in the external validation cohort. A model predicting incident MACE in healthy, elderly individuals includes well-recognised, potentially reversible risk factors and notably, renal function. Calibration would be necessary when used in other populations.

Long-Term Blood Pressure Variability and Kidney Function in Participants of the ASPREE Trial.

BACKGROUND: Whether long-term blood pressure variability (BPV) predicts kidney function decline in generally healthy older adults is unknown. We investigated this association in ASPirin in Reducing Events in the Elderly (ASPREE) trial participants. METHODS: Between 2010 and 2014, Australian and US individuals aged ≥70 years (≥65 if US minority) were recruited and followed with annual study visits for a median of 4.7 years. Time-to-event analyses and linear mixed effects models were used to examine associations between incident chronic kidney disease (CKD), and trajectories of estimated glomerular filtration rate (eGFR) and log albumin-creatinine ratio (log ACR) with systolic BPV as a continuous measure, and, by tertile of SD of systolic blood pressure (BP). BPV was estimated using systolic BP measures from baseline through the second annual visit, and kidney outcomes were assessed following this period. RESULTS: Incident CKD occurred in 1,829 of 6,759 participants (27.2%), and more commonly in BPV tertiles 2 (27.4%) and 3 (28.3%) than tertile 1 (25.5%); however, the risk was not significantly increased after covariate adjustment (tertile 3 hazard ratio = 1.02; 95% confidence interval: 0.91-1.14). Analysis of eGFR (n = 16,193) and log ACR trajectories (n = 15,213) showed individuals in the highest BPV tertile having the lowest eGFR and highest log ACR, cross-sectionally. However, the trajectories of eGFR and log ACR did not differ across BPV tertiles. CONCLUSIONS: CKD and markers of reduced kidney function occur more commonly in individuals with higher BPV; however, BPV does not influence trajectory of decline in kidney function over time in older adults who are in generally good health. CLINICAL TRIALS REGISTRATION: Trial Number NCT01038583 and ISRCTN83772183.

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.