The circulating proteome and brain health: Mendelian randomisation and cross-sectional analyses.

Decline in cognitive function is the most feared aspect of ageing. Poorer midlife cognitive function is associated with increased dementia and stroke risk. The mechanisms underlying variation in cognitive function are uncertain. Here, we assessed associations between 1160 proteins' plasma levels and two measures of cognitive function, the digit symbol substitution test (DSST) and the Montreal Cognitive Assessment in 1198 PURE-MIND participants. We identified five DSST performance-associated proteins (NCAN, BCAN, CA14, MOG, CDCP1), with NCAN and CDCP1 showing replicated association in an independent cohort, GS (N = 1053). MRI-assessed structural brain phenotypes partially mediated (8-19%) associations between NCAN, BCAN, and MOG, and DSST performance. Mendelian randomisation analyses suggested higher CA14 levels might cause larger hippocampal volume and increased stroke risk, whilst higher CDCP1 levels might increase intracranial aneurysm risk. Our findings highlight candidates for further study and the potential for drug repurposing to reduce the risk of stroke and cognitive decline.

Blood pressure variability in acute stroke: Risk factors and association with functional outcomes at 1 month.

BACKGROUND AND PURPOSE: Blood pressure variability, in acute stroke, may be an important modifiable determinant of functional outcome after stroke. In a large international cohort of participants with acute stroke, it was sought to determine the association of blood pressure variability (in the early period of admission) and functional outcomes, and to explore risk factors for increased blood pressure variability. PATIENTS AND METHODS: INTERSTROKE is an international case-control study of risk factors for first acute stroke. Blood pressure was recorded at the time of admission, the morning after admission and the time of interview in cases (median time from admission 36.7 h). Multivariable ordinal regression analysis was employed to determine the association of blood pressure variability (standard deviation [SD] and coefficient of variance) with modified Rankin score at 1-month follow-up, and logistic regression was used to identify risk factors for blood pressure variability. RESULTS: Amongst 13,206 participants, the mean age was 62.19 ± 13.58 years. When measured by SD, both systolic blood pressure variability (odds ratio 1.13; 95% confidence interval 1.03-1.24 for SD ≥20 mmHg) and diastolic blood pressure variability (odds ratio 1.15; 95% confidence interval 1.04-1.26 for SD ≥10 mmHg) were associated with a significant increase in the odds of poor functional outcome. The highest coefficient of variance category was not associated with a significant increase in risk of higher modified Rankin score at 1 month. Increasing age, female sex, high body mass index, history of hypertension, alcohol use, and high urinary potassium and low urinary sodium excretion were associated with increased blood pressure variability. CONCLUSION: Increased blood pressure variability in acute stroke, measured by SD, is associated with an increased risk of poor functional outcome at 1 month. Potentially modifiable risk factors for increased blood pressure variability include low urinary sodium excretion.

Tobacco use and risk of acute stroke in 32 countries in the INTERSTROKE study: a case­control study

BACKGROUND Smoking is a major risk factor for the global burden of stroke. We have previously reported a global population attributable risk (PAR) of stroke of 12.4% associated with current smoking. In this study we aimed to explore the association of current tobacco use with different types of tobacco exposure and environmental tobacco smoke (ETS) exposure on the risk of stroke and stroke subtypes, and by regions and country income levels. METHODS The INTERSTROKE study is a case­control study of acute first stroke and was undertaken with 13,462 stroke cases and 13,488 controls recruited between January 11, 2007 and August 8, 2015 in 32 countries worldwide. Association of risk of tobacco use and ETS exposure were analysed with overall stroke, ischemic and intracerebral hemorrhage (ICH), and with TOAST etiological stroke subtypes (large vessel, small vessel, cardioembolism, and undetermined). FINDINGS Current smoking was associated with an increased risk of all stroke (odds ratio [OR] 1.64, 95% CI 1.46­1.84), and had a stronger association with ischemic stroke (OR 1.85, 95% CI 1.61­2.11) than ICH (OR 1.19 95% CI 1.00­1.41). The OR and PAR of stroke among current smokers varied significantly between regions and income levels with high income countries (HIC) having the highest odds (OR 3.02 95% CI 2.24­4.10) and PAR (18.6%, 15.1­22.8%). Among etiological subtypes of ischemic stroke, the strongest association of current smoking was seen for large vessel stroke (OR 2.16, 95% CI 1.63­2.87) and undetermined cause (OR 1.97, 95% CI 1.55­2.50). Both filtered (OR 1.73, 95% CI 1.50­1.99) and non-filtered (OR 2.59, 95% CI 1.79­3.77) cigarettes were associated with stroke risk. ETS exposure increased the risk of stroke in a dose-dependent manner, exposure for more than 10 h per week increased risk for all stroke (OR 1.95, 95% CI 1.69­2.27), ischemic stroke (OR 1.89, 95% CI 1.59­2.24) and ICH (OR 2.00, 95% CI 1.60­2.50). INTERPRETATION There are significant variations in the magnitude of risk and PAR of stroke according to the types of tobacco used, active and ETS exposure, and countries with different income levels. Specific strategies to discourage tobacco use by any form and to build a smoke free environment should be implemented to ease the global burden of stroke. FUNDING The Canadian Institutes of Health Research, Heart and Stroke Foundation of Canada, Canadian Stroke Network, Swedish Research Council, Swedish Heart and Lung Foundation, The Health & Medical Care Committee of the Regional Executive Board, Region Västra Götaland, and through unrestricted grants from several pharmaceutical companies with major contributions from Astra Zeneca, Boehringer Ingelheim (Canada), Pfizer (Canada), MERCK, Sharp and Dohme, Swedish Heart and Lung Foundation, UK Chest, and UK Heart and Stroke.

Pre-morbid sleep disturbance and its association with stroke severity: results from the international INTERSTROKE study.

BACKGROUND AND PURPOSE: Whilst sleep disturbances are associated with stroke, their association with stroke severity is less certain. In the INTERSTROKE study, the association of pre-morbid sleep disturbance with stroke severity and functional outcome following stroke was evaluated. METHODS: INTERSTROKE is an international case-control study of first acute stroke. This analysis included cases who completed a standardized questionnaire concerning nine symptoms of sleep disturbance (sleep onset latency, duration, quality, nocturnal awakening, napping duration, whether a nap was planned, snoring, snorting and breathing cessation) in the month prior to stroke (n = 2361). Two indices were derived representing sleep disturbance (range 0-9) and obstructive sleep apnoea (range 0-3) symptoms. Logistic regression was used to estimate the magnitude of association between symptoms and stroke severity defined by the modified Rankin Score. RESULTS: The mean age of participants was 62.9 years, and 42% were female. On multivariable analysis, there was a graded association between increasing number of sleep disturbance symptoms and initially severe stroke (2-3, odds ratio [OR] 1.44, 95% confidence interval [CI] 1.07-1.94; 4-5, OR 1.66, 95% CI 1.23-2.25; >5, OR 2.58, 95% CI 1.83-3.66). Having >5 sleep disturbance symptoms was associated with significantly increased odds of functional deterioration at 1 month (OR 1.54, 95% CI 1.01-2.34). A higher obstructive sleep apnoea score was also associated with significantly increased odds of initially severe stroke (2-3, OR 1.48; 95% CI 1.20-1.83) but not functional deterioration at 1 month (OR 1.19, 95% CI 0.93-1.52). CONCLUSIONS: Sleep disturbance symptoms were common and associated with an increased odds of severe stroke and functional deterioration. Interventions to modify sleep disturbance may help prevent disabling stroke/improve functional outcomes and should be the subject of future research.

Tobacco use and risk of acute stroke in 32 countries in the INTERSTROKE study: a case-control study.

Background: Smoking is a major risk factor for the global burden of stroke. We have previously reported a global population attributable risk (PAR) of stroke of 12.4% associated with current smoking. In this study we aimed to explore the association of current tobacco use with different types of tobacco exposure and environmental tobacco smoke (ETS) exposure on the risk of stroke and stroke subtypes, and by regions and country income levels. Methods: The INTERSTROKE study is a case-control study of acute first stroke and was undertaken with 13,462 stroke cases and 13,488 controls recruited between January 11, 2007 and August 8, 2015 in 32 countries worldwide. Association of risk of tobacco use and ETS exposure were analysed with overall stroke, ischemic and intracerebral hemorrhage (ICH), and with TOAST etiological stroke subtypes (large vessel, small vessel, cardioembolism, and undetermined). Findings: Current smoking was associated with an increased risk of all stroke (odds ratio [OR] 1.64, 95% CI 1.46-1.84), and had a stronger association with ischemic stroke (OR 1.85, 95% CI 1.61-2.11) than ICH (OR 1.19 95% CI 1.00-1.41). The OR and PAR of stroke among current smokers varied significantly between regions and income levels with high income countries (HIC) having the highest odds (OR 3.02 95% CI 2.24-4.10) and PAR (18.6%, 15.1-22.8%). Among etiological subtypes of ischemic stroke, the strongest association of current smoking was seen for large vessel stroke (OR 2.16, 95% CI 1.63-2.87) and undetermined cause (OR 1.97, 95% CI 1.55-2.50). Both filtered (OR 1.73, 95% CI 1.50-1.99) and non-filtered (OR 2.59, 95% CI 1.79-3.77) cigarettes were associated with stroke risk. ETS exposure increased the risk of stroke in a dose-dependent manner, exposure for more than 10 h per week increased risk for all stroke (OR 1.95, 95% CI 1.69-2.27), ischemic stroke (OR 1.89, 95% CI 1.59-2.24) and ICH (OR 2.00, 95% CI 1.60-2.50). Interpretation: There are significant variations in the magnitude of risk and PAR of stroke according to the types of tobacco used, active and ETS exposure, and countries with different income levels. Specific strategies to discourage tobacco use by any form and to build a smoke free environment should be implemented to ease the global burden of stroke. Funding: The Canadian Institutes of Health Research, Heart and Stroke Foundation of Canada, Canadian Stroke Network, Swedish Research Council, Swedish Heart and Lung Foundation, The Health & Medical Care Committee of the Regional Executive Board, Region Västra Götaland, and through unrestricted grants from several pharmaceutical companies with major contributions from Astra Zeneca, Boehringer Ingelheim (Canada), Pfizer (Canada), MERCK, Sharp and Dohme, Swedish Heart and Lung Foundation, UK Chest, and UK Heart and Stroke.

Bleeding Risk Prediction in Patients Treated with Antithrombotic Drugs According to the Anatomic Site of Bleeding, Indication for Treatment, and Time Since Treatment Initiation.

Background Reasons for the relatively poor performance of bleeding prediction models are not well understood but may relate to differences in predictors for various anatomical sites of bleeding. Methods We pooled individual participant data from four randomized controlled trials of antithrombotic therapy in patients with coronary and peripheral artery diseases, embolic stroke of undetermined source (ESUS), or atrial fibrillation. We examined discrimination and calibration of models for any major bleeding, major gastrointestinal (GI) bleeding, and intracranial hemorrhage (ICH), according to the time since initiation of antithrombotic therapy, and indication for antithrombotic therapy. Results Of 57,813 patients included, 1,948 (3.37%) experienced major bleeding, including 717 (1.24%) major GI bleeding and 274 (0.47%) ICH. The model derived to predict major bleeding at 1 year from any site (c-index, 0.69, 95% confidence interval [CI], 0.68-0.71) performed similarly when applied to predict major GI bleeding (0.71, 0.69-0.74), but less well to predict ICH (0.64, 0.61-0.69). Models derived to predict GI bleeding (0.75, 0.74-0.78) and ICH (0.72, 0.70-0.79) performed better than the general major bleeding model. Discrimination declined over time since the initiation of antithrombotic treatment, stabilizing at approximately 2 years for any major bleeding and major GI bleeding and 1 year for ICH. Discrimination was best for the model predicting ICH in the ESUS population (0.82, 0.78-0.92) and worst for the model predicting any major bleeding in the coronary and peripheral artery disease population (0.66, 0.65-0.69). Conclusion Performance of risk prediction models for major bleeding is affected by site of bleeding, time since initiation of antithrombotic therapy, and indication for antithrombotic therapy.

Variations in the prevalence of atrial fibrillation, and in the strength of its association with ischemic stroke, in countries with different income levels: INTERSTROKE case-control study

BACKGROUND: The contribution of atrial fibrillation (AF) to the etiology and burden of stroke may vary by country income level. AIMS: We examined differences in the prevalence of AF and described variations in the magnitude of the association between AF and ischemic stroke by country income level. METHODS: In the INTERSTROKE case­control study, participants with acute first ischemic stroke were recruited across 32 countries. We included 10,363 ischemic stroke cases and 10,333 community or hospital controls who were matched for age, sex, and center. Participants were grouped into high-income (HIC), upper-middle-income (subdivided into two groups­UMIC-1 and UMIC-2), and lower-middle-income (LMIC) countries, based on gross national income. We evaluated the risk factors for AF overall and by country income level, and evaluated the association of AF with ischemic stroke. RESULTS: AF was documented in 11.9% (n = 1235) of cases and 3.2% (n = 328) of controls. Compared to HIC, the prevalence of AF was significantly lower in UMIC-2 (aOR 0.35, 95% CI 0.29­0.41) and LMIC (aOR 0.50, 95% CI 0.41­0.60) on multivariable analysis. Hypertension, female sex, valvular heart disease, and alcohol intake were stronger risk factors for AF in lower-income countries, and obesity a stronger risk factor in higher-income countries. The magnitude of association between AF and ischemic stroke was significantly higher in lower-income countries compared to higher-income countries. The population attributable fraction for AF and stroke varied by region and was 15.7% (95% CI 13.7­17.8) in HIC, 14.6% (95% CI 12.3­17.1) in UMIC-1, 5.7% (95% CI 4.9­6.7) in UMIC-2, and 6.3% (95% CI 5.3­7.3) in LMIC. CONCLUSION: Risk factors for AF vary by country income level. AF contributes to stroke burden to a greater extent in higher-income countries than in lower-income countries, due to a higher prevalence and despite a lower magnitude of odds ratio.

Bias assessment and correction for Levin's population attributable fraction in the presence of confounding.

In 1953, Morton Levin introduced a simple approach to estimating population attributable fractions (PAF) depending only on risk factor prevalence and relative risk. This formula and its extensions are still in widespread use today, particularly to estimate PAF in populations where individual data is unavailable. Unfortunately, Levin's approach is known to be asymptotically biased for the PAF when the risk factor-disease relationship is confounded even if relative risks that are correctly adjusted for confounding are used in the estimator. Here we describe a simple re-expression of Miettinen's estimand that depends on the causal relative risk, the unadjusted relative risk and the population risk factor prevalence. While this re-expression is not new, it has been underappreciated in the literature, and the associated estimator may be useful in estimating PAF in populations when individual data is unavailable provided estimated adjusted and unadjusted relative risks can be transported to the population of interest. Using the re-expressed estimand, we develop novel analytic formulae for the relative and absolute asymptotic bias in Levin's formula, solidifying earlier work by Darrow and Steenland that used simulations to investigate this bias. We extend all results to settings with non-binary valued risk factors and continuous exposures and discuss the utility of these results in estimating PAF in practice.

Variations in the prevalence of atrial fibrillation, and in the strength of its association with ischemic stroke, in countries with different income levels: INTERSTROKE case-control study.

BACKGROUND: The contribution of atrial fibrillation (AF) to the etiology and burden of stroke may vary by country income level. AIMS: We examined differences in the prevalence of AF and described variations in the magnitude of the association between AF and ischemic stroke by country income level. METHODS: In the INTERSTROKE case-control study, participants with acute first ischemic stroke were recruited across 32 countries. We included 10,363 ischemic stroke cases and 10,333 community or hospital controls who were matched for age, sex, and center. Participants were grouped into high-income (HIC), upper-middle-income (subdivided into two groups-UMIC-1 and UMIC-2), and lower-middle-income (LMIC) countries, based on gross national income. We evaluated the risk factors for AF overall and by country income level, and evaluated the association of AF with ischemic stroke. RESULTS: AF was documented in 11.9% (n = 1235) of cases and 3.2% (n = 328) of controls. Compared to HIC, the prevalence of AF was significantly lower in UMIC-2 (aOR 0.35, 95% CI 0.29-0.41) and LMIC (aOR 0.50, 95% CI 0.41-0.60) on multivariable analysis. Hypertension, female sex, valvular heart disease, and alcohol intake were stronger risk factors for AF in lower-income countries, and obesity a stronger risk factor in higher-income countries. The magnitude of association between AF and ischemic stroke was significantly higher in lower-income countries compared to higher-income countries. The population attributable fraction for AF and stroke varied by region and was 15.7% (95% CI 13.7-17.8) in HIC, 14.6% (95% CI 12.3-17.1) in UMIC-1, 5.7% (95% CI 4.9-6.7) in UMIC-2, and 6.3% (95% CI 5.3-7.3) in LMIC. CONCLUSION: Risk factors for AF vary by country income level. AF contributes to stroke burden to a greater extent in higher-income countries than in lower-income countries, due to a higher prevalence and despite a lower magnitude of odds ratio.

Cognitive performance following stroke, transient ischaemic attack, myocardial infarction, and hospitalisation: an individual participant data meta-analysis of six randomised controlled trials.

BACKGROUND: Survivors of stroke are often concerned about cognitive problems, and information on the risk of cognitive problems often comes from small studies. We aimed to estimate years of cognitive ageing associated with stroke compared with transient ischaemic attack, myocardial infarction, and other hospitalisations in a large population. METHODS: Using data from six randomised controlled trials (ORIGIN, ONTARGET, TRANSCEND, COMPASS, HOPE-3, and NAVIGATE ESUS), we completed an individual participant data meta-analysis using data requested from the Public Health Research Institute to estimate the association of stroke (by type and severity), transient ischaemic attack, myocardial infarction, and other hospitalisations with cognitive performance measured at the end of each trial. We included participants in any of these randomised controlled trials with a cognitive assessment at baseline and at least one other timepoint. Cognitive performance was measured with the Mini-Mental State Examination or the Montreal Cognitive Assessment, transformed into Z scores. We estimated Z score differences in end of trial cognitive performance between people with and without events and calculated corresponding years of cognitive ageing in these trials, and additionally calculated using a population representative cohort-the Cognitive Function and Ageing Study. FINDINGS: In 64 106 participants from 55 countries, compared with no event, stroke was associated with 18 years of cognitive ageing (1487 strokes included in the model, 95% CI 10 to 28; p<0·0001) and transient ischaemic attack with 3 years (660 transient ischaemic attacks included in the model, 0 to 6; p=0·021). Myocardial infarction (p=0·60) and other hospitalisations (p=0·26) were not associated with cognitive ageing. The mean difference in SD compared with people without an event was -0·84 (95% CI -0·91 to -0·76; p<0·0001) for disabling stroke, and -0·12 (-0·19 to -0·05; p=0·0012) for non-disabling stroke. Haemorrhagic stroke was associated with worse cognition (-0·75, -0·95 to -0·55; p<0·0001) than ischaemic stroke (-0·42, -0·48 to -0·36; p <0·0001). INTERPRETATION: Stroke has a substantial effect on cognition. The effects of transient ischaemic attack were small, whereas myocardial infarction and hospitalisation had a neutral effect. Prevention of stroke could lead to a reduction in cognitive ageing in those at greatest risk. FUNDING: Population Health Research Institute and Chief Scientist Office of Scotland.

Factors associated with weight loss and health gains in a structured lifestyle modification programme for adults with severe obesity: a prospective cohort study.

Background: Individual responses to behavioural weight loss interventions can vary significantly, and a better understanding of the factors associated with successful treatment might help to target interventions for those who will benefit the most. We sought to identify demographic and clinical characteristics that predicted intervention "success" (defined as ≥5% weight loss) and other health gains in patients with severe obesity attending a ten-week structured lifestyle modification programme. Methods: We conducted a prospective cohort study of all 1122 patients (751 (66.9%) female, mean age 47.3 ± 11.9 years, mean body mass index (BMI) 46.7 ± 7.8 kgm-2) referred from our hospital-based obesity clinic, who started the structured lifestyle programme between 2012-2019. We compared routine clinical measures such as weight, fitness, blood pressure, lipids and HbA1c at baseline and follow-up. We also used validated questionnaires to quantify anxiety, depression and health-related quality of life. Results: Of 1122 patients who started, 877 (78.2%) completed the programme and attended for follow up. Of these, 12.8% lost ≥5% body weight. The amount of weight lost was a strong and consistent predictor of improvements in metabolic, cardiovascular, and mental health, even after adjusting for age, sex, programme attendance and baseline fitness. Older age, male sex, being physically active and having lower anxiety and depression scores at baseline predicted greater weight loss. Younger age, depression and longer wait time to start the intervention were associated with drop-out. Conclusions: In adults with severe obesity completing a structured lifestyle modification programme, older age and good mental health were associated with programme completion and attaining ≥5% weight loss. The magnitude of weight lost was a strong predictor of improvements in cardiovascular, metabolic and mental health associated with programme completion.

Potassium intake: the Cinderella electrolyte.

Dietary guidelines recommend intake targets for some essential minerals, based on observational and experimental evidence relating mineral intake levels to health outcomes. For prevention of cardiovascular disease, reducing sodium intake and increasing potassium intake are the principal tools. While reducing sodium intake has received greatest public health priority, emerging evidence suggests that increasing potassium intake may be a more important target for cardiovascular prevention. Increased potassium intake reduces blood pressure and mitigates the hypertensive effects of excess sodium intake, and the recent large Phase III SSaSS trial reported that increasing potassium intake (and reducing sodium intake) in populations with low potassium intake and high sodium intake, through salt substitution (25% KCl, 75%NaCl), reduces the risk of stroke in patients at increased cardiovascular risk. As key sources of potassium intake include fruit, vegetables, nuts, and legumes, higher potassium intake may be associated with healthy dietary patterns. The current review makes the case that increasing potassium intake might represent a more advantageous dietary strategy for prevention of cardiovascular disease. Future research should focus on addressing the independent effect of potassium supplementation in populations with low or moderate potassium intake, and determine effective strategies to increase potassium intake from diet.

Early Metformin in Gestational Diabetes: A Randomized Clinical Trial.

Importance: Gestational diabetes is a common complication of pregnancy and the optimal management is uncertain. Objective: To test whether early initiation of metformin reduces insulin initiation or improves fasting hyperglycemia at gestation weeks 32 or 38. Design, Setting, and Participants: Double-blind, placebo-controlled trial conducted in 2 centers in Ireland (one tertiary hospital and one smaller regional hospital). Participants were enrolled from June 2017 through September 2022 and followed up until 12 weeks' postpartum. Participants comprised 510 individuals (535 pregnancies) diagnosed with gestational diabetes based on World Health Organization 2013 criteria. Interventions: Randomized 1:1 to either placebo or metformin (maximum dose, 2500 mg) in addition to usual care. Main Outcomes And Measures: The primary outcome was a composite of insulin initiation or a fasting glucose level of 5.1 mmol/L or greater at gestation weeks 32 or 38. Results: Among 510 participants (mean age, 34.3 years), 535 pregnancies were randomized. The primary composite outcome was not significantly different between groups and occurred in 150 pregnancies (56.8%) in the metformin group and 167 pregnancies (63.7%) in the placebo group (between-group difference, -6.9% [95% CI, -15.1% to 1.4%]; relative risk, 0.89 [95% CI, 0.78-1.02]; P = .13). Of 6 prespecified secondary maternal outcomes, 3 favored the metformin group, including time to insulin initiation, self-reported capillary glycemic control, and gestational weight gain. Secondary neonatal outcomes differed by group, with smaller neonates (lower mean birth weights, a lower proportion weighing >4 kg, a lower proportion in the >90% percentile, and smaller crown-heel length) in the metformin group without differences in neonatal intensive care needs, respiratory distress requiring respiratory support, jaundice requiring phototherapy, major congenital anomalies, neonatal hypoglycemia, or proportion with 5-minute Apgar scores less than 7. Conclusion and relevance: Early treatment with metformin was not superior to placebo for the composite primary outcome. Prespecified secondary outcome data support further investigation of metformin in larger clinical trials. Trial Registration: ClinicalTrials.gov Identifier: NCT02980276; EudraCT: 2016-001644-19.

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.

Comparing functional and quality of life outcomes in transcatheter aortic valve implantation and surgical aortic valve replacement for aortic stenosis: a systematic review and meta-analysis.

BACKGROUND: To compare functional and health related quality of life outcomes post-transcatheter aortic valve implantation (TAVI) and surgical aortic valve replacement (SAVR) in patients with critical aortic stenosis (AS) across low to high-risk surgical candidates. These patient-centred factors will be compared between both groups in the short to medium term time frames and will aid in shared decision making between patients and healthcare workers. MATERIALS AND METHODS: We conducted a systematic review and meta-analysis of randomised controlled trials which compared TAVI with SAVR and reported on quality of life (QoL) and functional scores. The scores used were the Kansas City Cardiomyopathy Questionnaire (KCCQ), Euroqol-5DL (EQ5DL), the short form-36/12 (SF-36/12) and the NYHA. RESULTS: We identified eight trials with a total of 8898 participants. Both groups showed improvements from baseline at one month. At one month there was a statistically significant difference in standardised mean difference (SMD) in favour of TAVI for EQ5DL (SMD 0.37, 95% CI 0.26,0.49), KCCQ (SMD 0.53,95% CI 0.48, 0.58), SF physical summary (SMD 0.55, 95% CI 0.31 - 0.78) and SF mental summary (SMD 0.34, 95% CI 0.27 - 0.40). At one year there was no statistically significant difference between any of these QoL metrics. For NYHA, no significant difference in odds ratio of class III/IV was observed at one month between TAVI and SAVR (OR 0.94, 95% CI 0.83, 1.07), however, TAVI was associated with reduced odds ratio of NYHA class I/II at one year (OR 0.87, 95% CI 0.78, 0.98). CONCLUSION: Both groups were associated with improvements in QoL and functional outcomes with TAVI reporting more significant improvements in QoL at one-month post-procedures. No significant improvements between groups were seen at one year. This is the largest meta-analysis comparing post-operative health-related quality of life outcomes post SAVR and TAVI and has major implications in shared decision making for the treatment of aortic stenosis.

Acute stress symptoms 1-2 weeks after stroke predict the subsequent development of post-traumatic stress symptoms: A prospective cohort study.

OBJECTIVE: To date no research has examined the potential influence of acute stress symptoms (ASD) on subsequent development of post-traumatic stress disorder (PTSD) symptoms in stroke survivors. Our objective was to examine whether acute stress symptoms measured 1-2 weeks post-stroke predicted the presence of post-traumatic stress symptoms measured 6-12 weeks later. DESIGN: Prospective within-groups study. METHODS: Fifty four participants who completed a measure of acute stress disorder at 1-2 weeks following stroke (time 1) and 31 of these participants completed a measure of posttraumatic stress disorder 6-12 weeks later (time 2). Participants also completed measures of stroke severity, functional impairment, cognitive impairment, depression, anxiety, pre-morbid intelligence and pain across both time points. RESULTS: Some 22% met the criteria for ASD at baseline and of those, 62.5% went on to meet the criteria for PTSD at follow-up. Meanwhile two of the seven participants (28.6%) who met the criteria for PTSD at Time 2, did not meet the ASD criteria at Time 1 (so that PTSD developed subsequently). A hierarchical multiple regression analysis indicated that the presence of acute stress symptoms at baseline was predictive of post-traumatic stress symptoms at follow-up (R2 = .26, p < .01). Less severe stroke was correlated with higher levels of post-traumatic stress symptoms at Time 2 (rho = .42, p < .01). CONCLUSIONS: The results highlight the importance of early assessment and identification of acute stress symptoms in stroke survivors as a risk factor for subsequent PTSD. Both ASD and PTSD were prevalent and the presence of both disorders should be assessed.

Behavioral Sleep Interventions and Cardiovascular Risk Factors: Systematic Review and Meta-analysis of Randomized Controlled Trials.

BACKGROUND/OBJECTIVES: Chronic sleep disturbance has been consistently associated with cardiovascular disease. We sought to determine whether behavioral interventions to improve sleep have been associated with improvements in 4 common cardiovascular disease risk factors: hypertension, diabetes mellitus (DM), obesity, and smoking. METHODS: Randomized controlled trials evaluating the prospective effect of behavioral sleep interventions on (a) blood pressure in participants with hypertension/prehypertension, (b) glycemic control in participants with DM/pre-DM, (c) anthropometrics in participants who were overweight/obese, and (d) smoking status in smokers were eligible. Where feasible, we undertook random-effects meta-analyses of standardized mean differences in cardiovascular disease risk factor change. RESULTS: Overall, 3 trials met the inclusion criteria for blood pressure, 4 for glycemic control, 9 for overweight/obesity, and 2 for smoking. On meta-analysis, interventions with sleep as the sole behavioral target were associated with a significant reduction in hemoglobin A1c% (-0.84; 95% confidence interval [CI], -1.34 to -0.34), but not a significant reduction in systolic blood pressure (-0.18; 95% CI, -0.55 to 0.20) versus controls. In addition, any interventions with sleep as a behavioral target were associated with significant reductions in hemoglobin A1c% (-0.71; 95% CI, -1.01 to -0.42) and weight (-0.78; 95% CI, -1.11 to -0.45), but not systolic blood pressure (-0.72; 95% CI, -1.82 to 0.37). Trials evaluating smoking status were not amenable to meta-analysis. CONCLUSION: Behavioral interventions to improve sleep were associated with improved glycemic control in patients with DM. It is also possible that these interventions improve weight in individuals who were overweight/obese. A low number of trials and small sample sizes indicate that further large, well-designed randomized controlled trials of interventions are warranted.

Diet, cardiovascular disease, and mortality in 80 countries.

AIMS: To develop a healthy diet score that is associated with health outcomes and is globally applicable using data from the Prospective Urban Rural Epidemiology (PURE) study and replicate it in five independent studies on a total of 245 000 people from 80 countries. METHODS AND RESULTS: A healthy diet score was developed in 147 642 people from the general population, from 21 countries in the PURE study, and the consistency of the associations of the score with events was examined in five large independent studies from 70 countries. The healthy diet score was developed based on six foods each of which has been associated with a significantly lower risk of mortality [i.e. fruit, vegetables, nuts, legumes, fish, and dairy (mainly whole-fat); range of scores, 0-6]. The main outcome measures were all-cause mortality and major cardiovascular events [cardiovascular disease (CVD)]. During a median follow-up of 9.3 years in PURE, compared with a diet score of ≤1 points, a diet score of ≥5 points was associated with a lower risk of mortality [hazard ratio (HR) 0.70; 95% confidence interval (CI) 0.63-0.77)], CVD (HR 0.82; 0.75-0.91), myocardial infarction (HR 0.86; 0.75-0.99), and stroke (HR 0.81; 0.71-0.93). In three independent studies in vascular patients, similar results were found, with a higher diet score being associated with lower mortality (HR 0.73; 0.66-0.81), CVD (HR 0.79; 0.72-0.87), myocardial infarction (HR 0.85; 0.71-0.99), and a non-statistically significant lower risk of stroke (HR 0.87; 0.73-1.03). Additionally, in two case-control studies, a higher diet score was associated with lower first myocardial infarction [odds ratio (OR) 0.72; 0.65-0.80] and stroke (OR 0.57; 0.50-0.65). A higher diet score was associated with a significantly lower risk of death or CVD in regions with lower than with higher gross national incomes (P for heterogeneity <0.0001). The PURE score showed slightly stronger associations with death or CVD than several other common diet scores (P < 0.001 for each comparison). CONCLUSION: A diet comprised of higher amounts of fruit, vegetables, nuts, legumes, fish, and whole-fat dairy is associated with lower CVD and mortality in all world regions, especially in countries with lower income where consumption of these foods is low.