Cerebrovascular risk factors and their time-dependent effects on stroke survival in the EMMA cohort study

To investigate the time-dependent effects of traditional risk factors on functional disability in all-cause mortality post-stroke, we evaluated data from a long-term stroke cohort. Baseline cerebrovascular risk factors (CVRF) and functionality at 1 and 6 months were evaluated in survivors from a prospective stroke cohort using the modified Rankin scale (m-RS), which classifies participants as improvement of disability, unchanged disability (at least moderate), and worsening disability. Cox regression models considering baseline risk factors, medication use, and functionality 6 months after stroke were fitted to identify their time-dependent effects up to 12 years of follow-up. Adjusted hazard ratios (HR) with 95% confidence intervals (CI) are presented. Among 632 survivors (median age 68, 54% male, 71% first-ever episode), age and functional disability (unchanged and worsening) 6 months after ischemic stroke had time-dependent effects on all-cause mortality risk up to 12 years of follow-up. The most impacting risk factors were unchanged (at least moderate) (HR, 2.99; 95%CI: 1.98-4.52) and worsening disability (HR, 2.85; 95%CI: 1.26-6.44), particularly in the first two years after a stroke event (Time 1: ≥6 mo to <2.5 y). Worsening disability also impacted mortality in the period from ≥2.5 to <7.5 years (Time 2) of follow-up (HR, 2.43 (95%CI: 1.03-5.73). Other baseline factors had a fixed high-risk effect on mortality during follow-up. Post-stroke and continuous medication use had a fixed protective effect on mortality. Functional disability was the main contributor with differential risks of mortality up to 12 years of follow-up.

Patient and Public Involvement and Engagement (PPIE): first steps in the process of the engagement in research projects in Brazil

Patient and Public Involvement and Engagement (PPIE) - sometimes called Community Engagement and Involvement (CEI) - comes as a big challenge but one that can be very helpful for health care professionals and stakeholders in planning better health policies for attending to the main needs of the community. PPIE involves three pillars: public involvement, public engagement, and participation. Public involvement occurs when members of the general population are actively involved in developing the research question, designing, and conducting the research. Public engagement tells people about new studies, why they are important, the impact of results, the possible implication of the main findings for the community, and the possible impact of these new findings in society, as well as, in the dissemination of knowledge to the general population. Participation is being a volunteer in the study. Our experience with PPIE, to the best of our knowledge the first initiative in Brazil, is a partnership with the University of Birmingham, the University of Liverpool, and the NIHR Global Health Group on Atrial Fibrillation (AF) Management focusing on the AF care pathway exploring the important aspects of diagnosis and treatment in the primary care system from a low-middle income area in São Paulo. The involvement of patients/public in the research represents a new step in the process of inclusion of all segments of our society based on patient illness and the gaps in knowledge aiming to open new horizons for continuous improvement and better acceptance of research projects.

The relationship of systemic markers of haemostasis with retinal blood vessel responses in cardiovascular disease and/or diabetes.

Background Hypercoagulability is a leading factor in diabetes and cardiovascular disease. Retinal vessel responses to flickering light are an important tool for assessing ocular function. We hypothesised a significant relationship between systemic markers of haemostasis and retinal vessel function. Methods Intra-ocular pressure and retinal microcirculation function were measured in 116 patients with diabetes and/or cardiovascular disease using unstimulated and stimulated arterial and venous retinal vessel responses to flickering light. Haemostasis was evaluated by platelet microparticles, soluble P selectin, and five functional markers of fibrin clot formation and lysis, hyperglycaemia by HbA1c. Results Intra-ocular pressure was linked to the rates of clot formation (p = 0.006) and clot dissolution (p = 0.013) whilst central retinal vein equivalent was linked to HbA1c (p = 0.017). In the first of three flickering light cycles only, arterial baseline diameter fluctuation was linked to the lag time to clot formation (p = 0.017), whilst maximum venous dilatation was linked to HbA1c (p = 0.001) and clot density (p = 0.011). HbA1c was linked to venous dilatation amplitude (p = 0.003). There were no significant links between any ocular index and any platelet index. Conclusions In addition to glycaemia, several haemostasis measures, but no measures of platelet activity, are linked to ocular and retinal blood vessel indices in patients with diabetes and/or cardiovascular disease. These associations may have pathophysiological significance.

Oxidised LDL lipids, statins and a blood-brain barrier.

Elevated cholesterol in mid-life has been associated with increased risk of dementia in later life. We have previously shown that low density lipoprotein (LDL) is more oxidised in the plasma of dementia patients although total cholesterol levels remained unchanged. Increased systemic oxidative modification (oxLDL) and nitration is also observed during hypercholesterolemia. We have investigated the hypothesis that disruption of blood brain barrier (BBB) function by oxLDL and their lipids may increase risk of neurodegeneration in later life and that statin intervention can mitigate the effects of hyperlipidaemia in mid-life. LDL isolated from statin-naïve hypercholesterolaemic subjects had higher mobility by agarose gel electrophoresis (Rf;0.53±0.06) and 8-isoprostane F2α concentration (43.5±8.42pg/ml) compared to control subjects (Rf; 0.46±0.05 and 24.2±5.37pg/ml respectively; p<0.05). Compared to HMVEC treatment with the LDL-lipids (5µM) from normolipidaemic subjects, LDL-lipids from hypercholesterolaemic subjects increased barrier permeability (103.4±12.5 Ωcm2 v 66.7±7.3 Ωcm2,P<0.01) and decreased cellular glutathione levels (18.5nmol/mg v 12.3nmol/mg) compared to untreated cells (26.2±3.6nmol/mg). LDL-lipids isolated from normolipidaemic subjects shows reduced risk to damage a BBB model compared with LDL-lipids from hypercholesterolaemic subjects. Moreover, a three month statin-intervention reduced the propensity for LDL-lipids from subjects with hyperlipidaemia to damage HMVEC. Post-statin treatment the cytotoxic and pro-inflammatory effects of LDL lipids disappeared. These data support the hypothesis that in vivo intervention with statins modifies LDL lipid oxidation, exerting a protective effect against in microvascular damage independent of cholesterol concentration.