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&lt;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&lt;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&lt;0·0001) than ischaemic stroke (-0·42, -0·48 to -0·36; p &lt;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.</p

Alcohol intake as a risk factor for acute stroke: the INTERSTROKE Study

Background and Objectives: There is uncertainty about the association between alcohol consumption and stroke, particularly for low-moderate intake. We explored these associations in a large international study. Methods: INTERSTROKE, a case-control study, is the largest international study of risk factors for acute stroke. Alcohol consumption was self-reported and categorised by drinks/week as low (1-7), moderate (7-14 for females, 7-21 for males) or high (&gt;14 for females, &gt;21 for males). Heavy episodic drinking (HED) was defined as &gt;5 drinks on ≥1 day per month. Multivariable conditional logistic regression was used to determine associations. Results: We included 12,913 cases and 12,935 controls; 25.0% (n=6,449) were current drinkers, 16.7% (n=4,318) former and 58.3% (n=15,076) never drinkers. Current drinkers were younger, male, smokers, active and with higher-paid occupations. Current drinking was associated with all stroke (OR 1.14; 95% CI 1.04-1.26) and intracerebral hemorrhage (ICH) (OR 1.50, 95% CI 1.21-1.84) but not ischaemic stroke (OR 1.06; 95% CI 0.95-1.19). HED pattern was associated with all stroke (OR 1.39; 95% CI 1.21-1.59), ischaemic stroke (OR 1.29; 95% CI 1.10-1.51) and ICH (OR 1.76; 95% CI 1.31-2.36). High level of alcohol intake was consistently associated with all stroke, ischaemic stroke and ICH. Moderate intake was associated with all stroke and ICH, but not ischaemic stroke. Low alcohol intake was not associated with stroke overall but there were regional differences; low intake was associated with reduced odds of stroke in Western Europe/North America (OR 0.66; 95%CI 0.45-0.96) and increased odds in India (OR 2.18; 95%CI 1.42-3.36)(p-interaction 0.037). Wine consumption was associated with reduced odds of all stroke and ischaemic stroke but not ICH. The magnitudes of association were greatest in those without hypertension and current smokers. Discussion: High and moderate intake were associated with increased odds of stroke, while low intake was not associated with stroke. However, there were important regional variations, which may relate to differences in population characteristics of alcohol consumers, types or patterns of consumption

Cardiovascular disease and functional ability in older adults

Preservation of functional independence is important to older adults. The consequences of functional impairment (increased dependence on others for activities of daily living and requirement for nursing home care) place a significant burden on older people, their families and health care systems. Prevention of functional impairment is of considerable importance, and requires the systematic identification of modifiable determinants of loss of independence in activities of daily living to develop interventions to prevent this loss. My thesis addresses the association of cardiovascular disease and cardiovascular risk factors with functional impairment in older adults, identifies the importance of functional outcome measures in cardiovascular research and proposes an approach to evaluating the effect of vascular risk factor modification on loss of function. Employing a number of different methodological and statistical approaches (with a particular focus on hypertension), I report the association between vascular risk factors and functional impairment in community dwelling older adults in cohort studies and systematic review of clinical trials, I explore attitudes of individuals to the importance of measuring functional outcomes in trials of cardiovascular prevention, and evaluate different methodological approaches to estimating the effect of interventions with effects on multiple outcomes. Finally, I describe a protocol for a randomised controlled trial to determine whether lowering blood pressure in older adults with mild hypertension (without cardiovascular disease) reduces the risk of functional impairment. Findings from my thesis emphasise the importance of modifiable vascular risk factors in the development (and prevention) of loss of independence for activities of daily living, mediated largely through clinical and covert cardiovascular disease. Despite this association, and the importance of functional outcome measures to the general public, cardiovascular prevention trials rarely report functional outcome measures. My thesis proposes a paradigm change in selecting outcome measures for cardiovascular prevention trials in older adults, to include functional outcomes.2016-12-0

Developing inclusive research methodologies: testing the voice centred relational method of qualitative data analysis in a collaborative research project on early school leaving

Committed to developing collaborative research processes and practices, this study sought to establish research partnerships between academic researchers, activists working in a context of social exclusion and those experiencing social exclusion. Responding to ideological and methodological challenges to democratise research processes and practices, the paper discusses the process of establishing collaborative research partnerships while assessing a methodological adaptation of the Voice Centred Relational (VCR) method of data analysis. The VCR method was used to interpret data on different experiences of school with a particular focus on early school leaving among a group of teenagers in a rural area in the West of Ireland. The VCR method claims to clarify conventions for the interpretation of qualitative data. Arguably, this removes some of the technical barriers that inhibit the possibility for the researched to become active interpreters of the data that they present to researchers. In order to test this and other claims of the VCR method, a collaborative research study was designed which included research participants in the analytical and interpretive practice of data analysis. This paper reports on the process of establishing a collaborative interpretive community and on the practice of adapting social science analytical methods so that deeper inclusion in the practice of research is realised for researchers and researched alike

Lipid lowering therapy, low-density lipoprotein level and risk of intracerebral hemorrhage – a meta-analysis

The association of lipid lowering therapy and intracerebral hemorrhage risk is controversial. 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. 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. 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.peer-reviewed2020-03-1