Randomised controlled trials of antihypertensive therapy: does exclusion of orthostatic hypotension alter treatment effect? A systematic review and meta-analysis.

BACKGROUND AND PURPOSE: Management of antihypertensive therapy is challenging in patients with symptomatic orthostatic hypotension, a population often excluded from randomised controlled trials of antihypertensive therapy. In this systematic review and meta-analysis, we sought to determine whether the association of antihypertensive therapy and adverse events (e.g. falls, syncope), differed among trials that included or excluded patients with orthostatic hypotension. METHODS: We performed a systematic review and meta-analysis of randomised controlled trials comparing blood pressure lowering medications to placebo, or different blood pressure targets on falls or syncope outcomes and cardiovascular events. A random-effects meta-analysis was used to estimate a pooled treatment-effect overall in subgroups of trials that excluded patients with orthostatic hypotension and trials that did not exclude patients with orthostatic hypotension, and tested P for interaction. The primary outcome was fall events. RESULTS: 46 trials were included, of which 18 trials excluded orthostatic hypotension and 28 trials did not. The incidence of hypotension was significantly lower in trials that excluded participants with orthostatic hypotension (1.3% versus 6.2%, P < 0.001) but not incidences of falls (4.8% versus 8.8%; P = 0.40) or syncope (1.5% versus 1.8%; P = 0.67). Antihypertensive therapy was not associated with an increased risk of falls in trials that excluded (OR 1.00, 95% CI; 0.89-1.13) or included (OR 1.02, 95% CI; 0.88-1.18) participants with orthostatic hypotension (P for interaction = 0.90). CONCLUSIONS: The exclusion of patients with orthostatic hypotension does not appear to affect the relative risk estimates for falls and syncope in antihypertensive trials.

Antiplatelet therapy and incident cognitive impairment or dementia-a systematic review and meta-analysis of randomised clinical trials.

OBJECTIVE: The benefit of antiplatelet therapy in preventing cognitive impairment or dementia is uncertain. We investigated the association between antiplatelet therapy and incident cognitive impairment or dementia in randomised clinical trials. METHODS: We searched PubMed, EMBASE and CENTRAL for randomised clinical trials published from database inception through 1 February 2023. Trials that evaluated the association of antiplatelet therapy with incident cognitive impairment or dementia were included. For single-agent antiplatelet, the control group was placebo. For dual agent antiplatelet therapy, the control group was single-agent monotherapy. A random-effects meta-analysis model was used to report pooled treatment effects and 95% confidence intervals (CIs). The primary outcome was incident cognitive impairment or dementia. Secondary outcomes included change in cognitive test scores. RESULTS: A total of 11 randomised clinical trials were included (109,860 participants). All reported the incidence of cognitive impairment or dementia on follow-up. The mean (SD) age of trial participants was 66.2 (7.9) years. Antiplatelet therapy was not significantly associated with a reduced risk of cognitive impairment or dementia (11 trials; 109,860 participants) (3.49% versus 4.18% of patients over a mean trial follow-up of 5.8 years; odds ratio [OR], 0.94 [95% CI, 0.88-1.00]; absolute risk reduction, 0.2% [95% CI, -0.4% to 0.009%]; I2 = 0.0%). Antiplatelet therapy was not significantly associated with mean change in cognitive test scores. CONCLUSION: In this meta-analysis, antiplatelet therapy was not significantly associated with a lower risk of incident cognitive impairment or dementia, but the CIs around this outcome do not exclude a modest preventative effect.

Anger or emotional upset and heavy physical exertion as triggers of stroke: the INTERSTROKE study.

AIMS: In INTERSTROKE, we explored the association of anger or emotional upset and heavy physical exertion with acute stroke, to determine the importance of triggers in a large, international population. METHODS AND RESULTS: INTERSTROKE was a case-control study of first stroke in 32 countries. Using 13 462 cases of acute stroke we adopted a case-crossover approach to determine whether a trigger within 1 hour of symptom onset (case period), vs. the same time on the previous day (control period), was associated with acute stroke. A total of 9.2% (n = 1233) were angry or emotional upset and 5.3% (n = 708) engaged in heavy physical exertion during the case period. Anger or emotional upset in the case period was associated with increased odds of all stroke [odds ratio (OR) 1.37, 99% confidence interval (CI), 1.15-1.64], ischaemic stroke (OR 1.22, 99% CI, 1.00-1.49), and intracerebral haemorrhage (ICH) (OR 2.05, 99% CI 1.40-2.99). Heavy physical exertion in the case period was associated with increased odds of ICH (OR 1.62, 99% CI 1.03-2.55) but not with all stroke or ischaemic stroke. There was no modifying effect by region, prior cardiovascular disease, risk factors, cardiovascular medications, time, or day of symptom onset. Compared with exposure to neither trigger during the control period, the odds of stroke associated with exposure to both triggers were not additive. CONCLUSION: Acute anger or emotional upset was associated with the onset of all stroke, ischaemic stroke, and ICH, while acute heavy physical exertion was associated with ICH only.

Role of Proxy Respondents in International Stroke Research: Experience of the INTERSTROKE Study.

INTRODUCTION: Measuring patient-reported information in stroke research is challenging. To overcome this, use of proxy respondents is often a necessary strategy. In this study, we report on use and effect of proxy respondents on patient case-mix in a large international epidemiologic stroke study (INTERSTROKE). METHODS: This was a cross-sectional study of 13,458 cases of acute first stroke in 32 countries. A standardized study questionnaire recording behavioural cardiovascular risk factors was administered to the patient, and if unable to communicate adequately, a valid proxy, or both. We used logistic regression to evaluate the association of age, sex, education, occupation, stroke severity, and region with need for proxy respondent, and report odds ratio (OR) with 95% confidence interval (CI). RESULTS: Among 13,458 participants with acute stroke, questionnaires were completed by patients alone in 41.4% (n = 5,573), combination of patient and proxy together in 21.7% (n = 2,918), and proxy alone in 36.9% (n = 4,967). Use of proxy alone was greater in participants with severe stroke (4.7% with modified-Rankin score of 0 vs. 80.5% in those with score 5; OR 187.13; 95% CI: 119.61-308.22), older persons (43.8% of those aged 80 years and over vs. 33.2% of those aged less than 40 years; age per decade OR 1.09; 95% CI: 1.06-1.12), women (40.7% vs. 34.3% of men; OR 1.32 95% CI: 1.22-1.43), and those less educated (58.9% of those never educated vs. 25.7% of those who attended third level education; OR 7.84; 95% CI: 6.78-9.08). CONCLUSION: Use of proxy respondents enhances the generalizability of international research studies of stroke, by increasing representation of women, patients with severe stroke, older age, and lower education.

Are clinical trials randomising households to lifestyle interventions to delay cognitive decline feasible? A pilot study to determine the beliefs, preferences, and deterrents for households impacted by dementia based on semi-structured interviews.

INTRODUCTION: While lifestyle risk factors are implicated in the development and progression of cognitive impairment, interventional trials of individual participants have yielded unconvincing evidence. We sought to explore the development of lifestyle interventions targeting the household-unit. METHODS: Semi-structured interviews were carried out among eight households affected by cognitive impairment (i.e. member of the household had cognitive impairment). Interviews took place online using a secure, web-based video platform recommended for patient clinician interaction. Interview content was analysed, and important themes identified. RESULTS: Eighteen participants were interviewed within households, of which eight (one per household) had cognitive impairment and others were spouses or first-degree relatives living in the same home. Several themes emerged; 1) household members without cognitive impairment were more likely to report poor sleep habits, and sleep was perceived to be the hardest behaviour to change; 2) diet generated most interest as a potential lifestyle intervention target as most participants believed there is a strong link with nutrition and cognition; 3) physical activity is challenging to adapt due to lack of motivation and focus when individuals are cognitively impaired. Barriers to study participation, including risk of harm, complexity of intervention and deviation from routine emerged during discussions. CONCLUSIONS: This study identified beliefs and preferences of households towards lifestyle intervention trials. Findings from this study may be used to inform future clinical trial protocols and future qualitative studies should explore acceptability and feasibility of digital intervention applications.

Functional Abilities of an International Post-Stroke Population: Standard Assessment of Global Everyday Activities (SAGEA) Scale.

BACKGROUND AND OBJECTIVES: Function is an important outcome after stroke; traditional assessments may not capture functional deficits important to patients. We examined the validity of the Standard Assessment of Global Everyday Activities (SAGEA), a patient-reported outcome that assesses activities important to patients and for use in international clinical trials. METHODS: The NAVIGATE-ESUS trial evaluated rivaroxaban compared to aspirin in preventing recurrent stroke in 7213 participants. The Modified Rankin Scale (mRS), the National Institutes of Health Stroke Scale (NIHSS), and the SAGEA were collected at entry. Chi square tests were used to compare proportions and Spearman rank correlations were used to compare between measures. SAGEA was compared to the Modified Frailty Index (MFI) and the occurrence of infarct to examine criterion validity RESULTS: Participants were 67 years, 2/3 were male, and at baseline 30% had no disability and 58% had slight disability according to mRS scores. SAGEA was weakly correlated with the mRS (r=0.37), the NIHSS (r=0.29) and the MFI (r=0.30). Of the 2154 with an mRS score of 0, 61% reported difficulty on the SAGEA. The largest discrepancies between SAGEA and other measures were because of cognitive functional deficits detected by the SAGEA that were not identified on other assessments. A larger number of MRI identified infarcts (acute and covert) were associated with a higher SAGEA score (p=0.007). CONCLUSIONS: The SAGEA is a simple, globally applicable measure of cognitive and functional abilities that identifies issues that other commonly used assessments of disability and function do not capture.

Rivaroxaban versus aspirin on functional and cognitive outcomes after embolic stroke of undetermined source: NAVIGATE ESUS trial.

BACKGROUND: The effect of interventions on functional impairment is an important outcome in stroke prevention trials and should be considered as an adjunct to counting discrete events. In the NAVIGATE-ESUS trial, 7213 patients with recent embolic strokes of undetermined source were randomized to rivaroxaban (15 mg once daily) or aspirin (100 mg daily). After 11 months there was no effect on the prevention of recurrent stroke. AIMS: To determine the effect of rivaroxaban compared to aspirin on functional and cognitive outcomes. METHODS: Function and cognition were measured at baseline, 1 year, and study end using the Standard Assessment of Global Everyday Activities (SAGEA), a 15-item scale assessing cognitive, instrumental, and basic activities of daily living as well as mobility, and the Montreal Cognitive Assessment (MoCA). Changes in scores were calculated by subtracting either study end or 1-year scores from baseline, and differences in distributions were compared using the Mann-Whitney U test. SAGEA and MoCA scores were also correlated with recurrent stroke. RESULTS: Follow-up SAGEA scores were available in 6378 (88%) participants. There was no difference in change in function for those allocated to rivaroxaban compared to aspirin (Mann-Whitney U test, p = 0.8), with both distributions having a median (25p,75p) change of 0 (-2,1). Overall, more of those who experienced a recurrent stroke (n=247; mostly minor ischemic), reported functional difficulty at study end versus entry, compared with those who did not (51% versus 30%, chi-square test, p< 0.001), and this was consistent across global regions. There was no difference in the change in cognition by treatment group, nor were recurrent strokes associated with a change in cognition. CONCLUSIONS: Rivaroxaban, compared to aspirin, was not associated with changes in functional or cognitive status in patients with recent ESUS. The SAGEA scale detected changes in functional status associated with recurrent strokes in an international stroke population.

Association of Oral Anticoagulation With Stroke in Atrial Fibrillation or Heart Failure: A Comparative Meta-Analysis.

Background and Purpose: Atrial fibrillation and heart failure with reduced ejection fraction (HFrEF) are common sources of cardioembolism. While oral anticoagulation is strongly recommended for atrial fibrillation, there are marked variations in guideline recommendations for HFrEF due to uncertainty about net clinical benefit. This systematic review and meta-analysis evaluates the comparative association of oral anticoagulation with stroke and other cardiovascular risk in populations with atrial fibrillation or HFrEF in sinus rhythm and identify factors mediating different estimates of net clinical benefit. Methods: PubMed and Embase were searched from database inception to November 20, 2019 for randomized clinical trials comparing oral anticoagulation to control. A random-effects meta-analysis was used to estimate a pooled treatment-effect overall and within atrial fibrillation and HFrEF trials. Differences in treatment effect were assessed by estimating I2 among all trials and testing the between-trial-population P-interaction. The primary outcome measure was all stroke. Secondary outcome measures were ischemic stroke, hemorrhagic stroke, mortality, myocardial infarction, and major hemorrhage. Results: Twenty-one trials were eligible for inclusion, 15 (n=19 332) in atrial fibrillation (mean follow-up: 23.1 months), and 6 (n=9866) in HFrEF (mean follow-up: 23.9 months). There were differences in primary outcomes between trial populations, with all-cause mortality included for 95.2% of HFrEF trial population versus 0.38% for atrial fibrillation. Mortality was higher in controls groups of HFrEF populations (19.0% versus 9.6%) but rates of stroke lower (3.1% versus 7.0%) compared with atrial fibrillation. The association of oral anticoagulation with all stroke was consistent for atrial fibrillation (odds ratio, 0.51 [95% CI, 0.42­0.63]) and HFrEF (odds ratio, 0.61 [95% CI, 0.47­0.79]; I2=12.4%; P interaction=0.31). There were no statistically significant differences in the association of oral anticoagulation with cardiovascular events, mortality or bleeding between populations. Conclusions: The relative association of oral anticoagulation with stroke risk, and other cardiovascular outcomes, is similar for patients with atrial fibrillation and HFrEF. Differences in the primary outcomes employed by trials in HFrEF, compared with atrial fibrillation, may have contributed to differing conclusions of the relative efficacy of oral anticoagulation.

Renal Impairment and Risk of Acute Stroke: The INTERSTROKE Study.

BACKGROUND: Previous studies reported an association of renal impairment with stroke, but there are uncertainties underpinning this association. AIMS: We explored if the association is explained by shared risk factors or is independent and whether there are regional or stroke subtype variations. METHODS: INTERSTROKE is a case-control study and the largest international study of risk factors for first acute stroke, completed in 27 countries. We included individuals with available serum creatinine values and calculated estimated glomerular filtration rate (eGFR). Renal impairment was defined as eGFR <60 mL/min/1.73 m2. Multivariable conditional logistic regression was used to determine the association of renal function with stroke. RESULTS: Of 21,127 participants, 41.0% were female, the mean age was 62.3 ± 13.4 years, and the mean eGFR was 79.9 ± 23.5 mL/min/1.73 m2. The prevalence of renal impairment was higher in cases (22.9% vs. 17.7%, p < 0.001) and differed by region (p < 0.001). After adjustment, lower eGFR was associated with increased odds of stroke. Renal impairment was associated with increased odds of all stroke (OR 1.35; 95% CI: 1.24-1.47), with higher odds for intracerebral hemorrhage (OR 1.60; 95% CI: 1.35-1.89) than ischemic stroke (OR 1.29; 95% CI: 1.17-1.42) (pinteraction 0.12). The largest magnitudes of association were seen in younger participants and those living in Africa, South Asia, or South America (pinteraction < 0.001 for all stroke). Renal impairment was also associated with poorer clinical outcome (RRR 2.97; 95% CI: 2.50-3.54 for death within 1 month). CONCLUSION: Renal impairment is an important risk factor for stroke, particularly in younger patients, and is associated with more severe stroke and worse outcomes.

Stroke Severity in Transcatheter Aortic Valve Implantation Versus Surgical Aortic Valve Replacement: A Systematic Review and Meta-Analysis.

OBJECTIVES: An assessment of the comparative incidence of fatal or disabling stroke may influence choice of intervention for patients with severe aortic stenosis. We explored whether transcatheter aortic valve implantation (TAVI) is associated with a lower incidence of fatal or disabling stroke, compared to surgical aortic valve replacement (SAVR). MATERIALS & METHODS: We classified stroke into two categories; fatal or disabling, or non-disabling, and completed meta-analyses for each. We explored randomised controlled trials to assess the effect publication year, predicted operative risk, and route of TAVI access. RESULTS: There was no difference between treatment groups per 100 person years of follow up for disabling or non-disabling stroke outcomes. In a stratified analysis by year of publication, there was a lower rate of fatal or disabling stroke with TAVI in trials published after 2015, compared to those published in 2015 or before (p-interaction = 0.01 at 30 days). Higher proportions of transfemoral route access (>90%), more common in recent trials, were associated with a lower rate of fatal or disabling stroke (p-interaction = 0.03 at 30 days). Lower average surgical risk scores were associated with lower rates of fatal or disabling stroke (p = 0.02 at 30 days). CONCLUSION: We found that treatment of aortic stenosis with TAVI compared with SAVR was not associated with an overall reduced risk in fatal or disabling stroke. Subgroup analyses suggested a lower risk of fatal or disabling stroke with TAVI in situations which reflect contemporary practice.

Virtual geriatric clinics and the COVID-19 catalyst: a rapid review.

BACKGROUND: During the current COVID-19 health crisis virtual geriatric clinics have become increasingly utilised to complete outpatient consultations, although concerns exist about feasibility of such virtual consultations for older people. The aim of this rapid review is to describe the satisfaction, clinic productivity, clinical benefit, and costs associated with the virtual geriatric clinic model of care. METHODS: A rapid review of PubMed, MEDLINE and CINAHL databases was conducted up to April 2020. Two independent reviewers extracted the information. Four subdomains were focused on: satisfaction with the virtual geriatric clinic, clinic productivity, clinical benefit to patients, costs and any challenges associated with the virtual clinic process. RESULTS: Nine studies with 975 patients met our inclusion criteria. All were observational studies. Seven studies reported patients were satisfied with the virtual geriatric clinic model of care. Productivity outcomes included reports of cost-effectiveness, savings on transport, and improved waiting list metrics. Clinical benefits included successful polypharmacy reviews, and reductions in acute hospitalisation rates. Varying challenges were reported for both clinicians and patients in eight of the nine studies. Hearing impairments and difficulty with technology added to anxieties experienced by patients. Physicians missed the added value of a thorough physical examination and had concerns about confidentiality. CONCLUSION: Virtual geriatric clinics demonstrate evidence of productivity, benefit to patients, cost effectiveness and patient satisfaction with the treatment provided. In the current suboptimal pandemic climate, virtual geriatric clinics may allow Geriatricians to continue to provide an outpatient service, despite the encountered inherent challenges.

Are large simple trials for dementia prevention possible?

New trials of dementia prevention are needed to test novel strategies and agents. Large, simple, cardiovascular trials have successfully discovered treatments with moderate but worthwhile effects to prevent heart attack and stroke. The design of these trials may hold lessons for the dementia prevention. Here we outline suitable populations, interventions and outcomes for large simple trials in dementia prevention. We consider what features are needed to maximise efficiency. Populations could be selected by age, clinical or genetic risk factors or clinical presentation. Patients and their families prioritise functional and clinical outcomes over cognitive scores and levels of biomarkers. Loss of particular functions or dementia diagnoses therefore are most meaningful to participants and potential patients and can be measured in large trials. The size of the population and duration of follow-up needed for dementia prevention trials will be a major challenge and will need collaboration between many clinical investigators, funders and patient organisations.

Association of Blood Pressure Lowering With Incident Dementia or Cognitive Impairment: A Systematic Review and Meta-analysis.

Importance: The benefit of blood pressure lowering for the prevention of dementia or cognitive impairment is unclear. Objective: To determine the association of blood pressure lowering with dementia or cognitive impairment. Data Sources and Study Selection: Search of PubMed, EMBASE, and CENTRAL for randomized clinical trials published from database inception through December 31, 2019, that evaluated the association of blood pressure lowering on cognitive outcomes. The control groups consisted of either placebo, alternative antihypertensive agents, or higher blood pressure targets. Data Extraction and Synthesis: Data were screened and extracted independently by 2 authors. Random-effects meta-analysis models were used to report pooled treatment effects and CIs. Main Outcomes and Measures: The primary outcome was dementia or cognitive impairment. The secondary outcomes were cognitive decline and changes in cognitive test scores. Results: Fourteen randomized clinical trials were eligible for inclusion (96 158 participants), of which 12 reported the incidence of dementia (or composite of dementia and cognitive impairment [3 trials]) on follow-up and were included in the primary meta-analysis, 8 reported cognitive decline, and 8 reported changes in cognitive test scores. The mean (SD) age of trial participants was 69 (5.4) years and 40 617 (42.2%) were women. The mean systolic baseline blood pressure was 154 (14.9) mm Hg and the mean diastolic blood pressure was 83.3 (9.9) mm Hg. The mean duration of follow-up was 49.2 months. Blood pressure lowering with antihypertensive agents compared with control was significantly associated with a reduced risk of dementia or cognitive impairment (12 trials; 92 135 participants) (7.0% vs 7.5% of patients over a mean trial follow-up of 4.1 years; odds ratio [OR], 0.93 [95% CI, 0.88-0.98]; absolute risk reduction, 0.39% [95% CI, 0.09%-0.68%]; I2 = 0.0%) and cognitive decline (8 trials) (20.2% vs 21.1% of participants over a mean trial follow-up of 4.1 years; OR, 0.93 [95% CI, 0.88-0.99]; absolute risk reduction, 0.71% [95% CI, 0.19%-1.2%]; I2 = 36.1%). Blood pressure lowering was not significantly associated with a change in cognitive test scores. Conclusions and Relevance: In this meta-analysis of randomized clinical trials, blood pressure lowering with antihypertensive agents compared with control was significantly associated with a lower risk of incident dementia or cognitive impairment.

Lipid Lowering Therapy, Low-Density Lipoprotein Level and Risk of Intracerebral Hemorrhage - A Meta-Analysis.

BACKGROUND: The association of lipid lowering therapy and intracerebral hemorrhage risk is controversial. METHODS: We performed a cumulative meta-analysis of lipid lowering trials that reported intracerebral hemorrhage. Statin, fibrate, ezetimibe, PCSK9, and CETP trials were included. We explored whether the association of lipid lowering therapy and risk of intracerebral hemorrhage may vary by baseline low-density lipoprotein (LDL) level, mean change in LDL or baseline cardiovascular risk of population. RESULTS: Among 39 trials (287,651 participants), lipid lowering therapy was not associated with a statistically significant increased risk of intracerebral hemorrhage (ICH) in primary and secondary prevention trials combined (odds ratio [OR], 1.12; 95% confidence interval [CI], .98-1.28). Lipid lowering was associated with an increased risk of ICH in secondary prevention trials (OR, 1.18; 95% CI, 1.00-1.38), but not in primary prevention trials (OR, 1.01; 95% CI, .78-1.30), but the test for interaction was not significant (P for interaction = .31). Meta-regression of baseline LDL or difference in LDL reduction between active and control did not explain significant heterogeneity between studies for ICH risk. Of 1000 individuals treated for 1 year for secondary prevention, we estimated 9.17 (95% CI, 5.78-12.66) fewer ischemic strokes and .48 (95% CI, .06-1.02) more ICH, and a net reduction of 8.69 in all stroke per 1000 person-years. CONCLUSIONS: The benefits of lipid lowering therapy in prevention of ischemic stroke greatly exceed the risk of ICH. Concern about ICH should not discourage stroke clinicians from prescribing lipid lowering therapy for secondary prevention of ischemic stroke.

Diet and Major Renal Outcomes: A Prospective Cohort Study. The NIH-AARP Diet and Health Study.

BACKGROUND: Chronic kidney disease (CKD) is prevalent and associated with significant morbidity and mortality. Dietary modification may be an approach to reducing CKD. DESIGN: In this prospective cohort study, we evaluated the association between diet quality, sodium and potassium intakes, and major renal outcomes. A total of 544,635 community-dwelling adults, aged 51 to 70 years, living in 6 states and 2 urban areas in the United States, from the National Institutes of Health-American Association of Retired Persons Diet and Health Study. Using a food frequency questionnaire completed at baseline, we assessed diet quality using the Alternate Healthy Eating Index (AHEI), Healthy Eating Index (HEI), Mediterranean Diet Score (MDS), Recommended Food Score, and Dietary Approaches to Stop Hypertension (DASH) scores. This was also used to estimate daily sodium and potassium intakes. MAIN OUTCOME MEASURES: Multivariable adjusted competing risks regression calculated sub-hazard ratios (sHRs) for a composite of death due to a renal cause and dialysis, with death due to a nonrenal cause as the competing event. RESULTS: During a mean of 14.3-year follow-up, a total of 4,848 participants died from a renal cause or initiated dialysis. Four diet quality scores (AHEI, HEI, MDS, and DASH) were significantly associated with the composite renal outcome; the Recommended Food Score was not. Compared to the lowest score quintile, the highest quintiles of AHEI (sHR 0.71; 95% confidence interval [CI] 0.65-0.79), HEI (sHR 0.82; 95% CI 0.74-0.91), MDS (sHR 0.84; 95% CI 0.74-0.95), and DASH (sHR 0.85; 95% CI 0.77-0.94) were associated with a reduced hazard of the composite. The highest sodium quintile (sHR 1.17; 95% CI 1.02-1.33 for sodium intake > 3.6 g/day) was associated with an increased hazard, whereas the highest potassium quintile (sHR 0.83 [0.73-0.95]) with a reduced hazard. CONCLUSIONS: Our findings support an association between healthy dietary patterns and reduced risk of major renal outcomes and provide observational evidence to inform dietary guideline recommendations for CKD prevention.

Effectiveness of educational interventions for informal caregivers of individuals with dementia residing in the community: systematic review and meta-analysis of randomised controlled trials.

OBJECTIVE: This study aims to assess whether educational programmes for caregivers of individuals with dementia living in the community are effective on caregiver burden, quality of life (QoL), depression and transitions to long stay care compared with usual care. METHOD: MEDLINE, EMBASE, PsycINFO, CINAHL, AgeLine, CENTRAL and ERIC were searched with no restrictions on language or publication status in February 2013. Randomised controlled trials (RCTs) were eligible. Participants were informal caregivers undertaking day to day care of an individual with dementia living in the community. Interventions were educational programmes aimed at teaching skills relevant to dementia caring. Two authors independently assessed studies for eligibility, assessed risk of bias and extracted data. RESULTS: We screened 1390 citations and included seven RCTs with 764 participants. Meta-analysis of five trials showed a moderate effect on carer burden (Standardised Mean Difference (SMD) = -0.52; 95% confidence interval (CI) -0.79 to -0.26; I(2) = 40%). Meta-analysis of two trials showed a small effect on depression (SMD = -0.37; 95% CI -0.65 to -0.09; I(2) = 0%). There was no effect on number of transitions to long stay care (relative risk 1.29; 95% CI 0.80 to 2.08). Effect on QoL was not estimable as studies varied in reporting of sub-domains and constructs within scales. CONCLUSION: Educational programmes have a moderate effect on caregiver burden and a small effect on depression. Evidence of an effect on QoL and transitions to long stay care remains unclear.

Antithrombotic therapy after acute ischemic stroke in patients with atrial fibrillation.

BACKGROUND AND PURPOSE: For patients with atrial fibrillation and ischemic stroke (IS), current guidelines recommend oral anticoagulation (OAC) alone for secondary prevention of IS. In a large prospective cohort of patients with acute IS and atrial fibrillation, we determine the association between antithrombotic regimen on discharge and risk of major vascular events. METHODS: Prospective cohort of consecutive patients included in the Ontario Stroke Registry. Multivariable Cox proportional hazard models were used to determine the association between antithrombotic regimen on discharge and time to death or admission for recurrent IS, myocardial infarction, or major bleeding. RESULTS: Two thousand one hundred sixty-two patients were hospitalized atrial fibrillation and acute IS. At discharge, 8.0% were prescribed no antithrombotic therapy, 21.6% antiplatelet therapy alone, 39.3% OAC (warfarin) alone, and 31.1% combination OAC and antiplatelet therapy. Compared with OAC alone (hazard ratio [HR], 1.0), no antithrombotic therapy (HR, 1.51; 95% confidence interval, 1.23-1.86) and antiplatelet therapy (HR, 1.31; 95% confidence interval, 1.14-1.50) were associated with an increased risk of the primary composite outcome, whereas combination OAC and antiplatelet therapy was associated with a trend toward a reduced risk (HR, 0.91; 95% confidence interval, 0.80-1.04 overall and HR, 0.79; 95% confidence interval, 0.61-1.02 in those with coronary heart disease). Results were consistent in those with severe stroke: HR 1.58 (95% CI, 1.21-2.06), 1.34 (95% CI, 1.09-1.63), and 0.91 (95% CI, 0.74-1.11), respectively. CONCLUSIONS: Contrary to current guidelines, 30% of patients with atrial fibrillation and recent IS are not prescribed any OAC therapy on discharge, whereas a further 30% are prescribed combination OAC and antiplatelet therapy. Combination OAC and antiplatelet therapy in patients at high cardiovascular risk requires evaluation in clinical trials, particularly with the newer OACs, given their more favorable risk-benefit ratio compared with warfarin.

Vascular risk factors, cardiovascular disease and functional impairment in community-dwelling adults.

BACKGROUND: Older adults report preservation of functional independence as one of the most important constructs of successful ageing. Vascular risk factors may increase the risk of functional impairment due to clinical and subclinical vascular disease. OBJECTIVE: To describe the association between vascular risk factors and impaired ability to perform daily living activities, independent of established cardiovascular disease. METHODS: We conducted an analysis of the Clarity Cohort, which is a cross-sectional study of 9,816 community-dwelling Irish adults. Of the total cohort, 3,499 completed standardized self-reported health questionnaires, which included questions on activities of daily living. Functional impairment was defined as self-reported impairment in self-care, mobility or household tasks. Using logistic regression analyses, we determined the association between vascular risk factors and functional impairment, independent of demographics, prior coronary artery disease, stroke, congestive heart failure, and peripheral vascular disease. RESULTS: Functional impairment was reported in 40.4% (n = 1,413) of the cohort overall and in 23% of those with established cardiovascular disease. The mean age was 66.2 ± 10.3 years, 52% of the cohort were aged over 65 and 45.6% were male. Some difficulty with instrumental activities of daily living was reported by 35.4% (n = 1,240) while 29.4% (n = 1,029) reported some difficulty with basic activities of daily living. On multivariable analysis, older age [OR 1.03 (1.02, 1.04) per year], current smoking [OR 1.43 (1.08, 1.89)], atrial fibrillation [OR 1.68 (1.07, 2.65)], former alcohol use [OR 1.87 (1.36, 2.57)] and prior stroke [OR 1.91 (1.24, 2.93)] were associated with an increased risk of functional impairment. Older age leaving education [OR 0.96 (0.94, 0.99)], non-use of alcohol [OR 0.76 (0.61, 0.93)] and increased high-density lipoprotein levels [OR 0.70 (0.56, 0.88)] were associated with reduced risk of functional impairment. CONCLUSIONS: Independent of established cardiovascular disease, some vascular risk factors are associated with functional impairment. Modification of these risk factors is expected to have a large impact on preservation of functional independence through prevention of overt and covert vascular disease.