Does sticky blood predict a sticky end? Associations of blood viscosity, haematocrit and fibrinogen with mortality in the West of Scotland

There is increasing evidence that blood viscosity and its major determinants (haematocrit, plasma viscosity and fibrinogen) are associated with an increased risk of incident cardiovascular events; however, their associations with mortality are not established. We therefore studied the associations of these variables with cardiovascular events and total mortality in 1238 men and women aged 25-64 years, followed for 13 years in the first North Glasgow MONICA (MONItoring CArdiovascular disease) survey and West of Scotland centres in the Scottish Heart Health Study. After adjustment for age and sex, increasing whole blood viscosity, plasma viscosity, haematocrit and fibrinogen (analysed by both von Clauss and heat precipitation assays) were significantly associated with mortality. Only the association for fibrinogen (von Clauss assay) remained significant after adjustment for major cardiovascular risk factors. We conclude that clottable fibrinogen may be independently associated with mortality. However, the significance of this association, and the extent to which viscosity is associated with mortality, remain to be established in larger studies and meta-analyses

Utility of electronic patient records in primary care for stroke secondary prevention trials

BACKGROUND: This study aimed to inform the design of a pragmatic trial of stroke prevention in primary care by evaluating data recorded in electronic patient records (EPRs) as potential outcome measures. The study also evaluated achievement of recommended standards of care; variation between family practices; and changes in risk factor values from before to after stroke.METHODS: Data from the UK General Practice Research Database (GPRD) were analysed for 22,730 participants with an index first stroke between 2003 and 2006 from 414 family practices. For each subject, the EPR was evaluated for the 12 months before and after stroke. Measures relevant to stroke secondary prevention were analysed including blood pressure (BP), cholesterol, smoking, alcohol use, body mass index (BMI), atrial fibrillation, utilisation of antihypertensive, antiplatelet and cholesterol lowering drugs. Intraclass correlation coefficients (ICC) were estimated by family practice. Random effects models were fitted to evaluate changes in risk factor values over time.RESULTS: In the 12 months following stroke, BP was recorded for 90%, cholesterol for 70% and body mass index (BMI) for 47%. ICCs by family practice ranged from 0.02 for BP and BMI to 0.05 for LDL and HDL cholesterol. For subjects with records available both before and after stroke, the mean reductions from before to after stroke were: mean systolic BP, 6.02 mm Hg; diastolic BP, 2.78 mm Hg; total cholesterol, 0.60 mmol/l; BMI, 0.34 Kg/m2. There was an absolute reduction in smokers of 5% and heavy drinkers of 4%. The proportion of stroke patients within the recommended guidelines varied from less than a third (29%) for systolic BP, just over half for BMI (54%), and over 90% (92%) on alcohol consumption.CONCLUSIONS: Electronic patient records have potential for evaluation of outcomes in pragmatic trials of stroke secondary prevention. Stroke prevention interventions in primary care remain suboptimal but important reductions in vascular risk factor values were observed following stroke. Better recording of lifestyle factors in the GPRD has the potential to expand the scope of the GPRD for health care research and practice

Is blood pressure reduction a valid surrogate endpoint for stroke prevention? an analysis incorporating a systematic review of randomised controlled trials, a by-trial weighted errors-in-variables regression, the surrogate threshold effect (STE) and the biomarker-surrogacy (BioSurrogate) evaluation schema (BSES)

<p>Abstract</p> <p>Background</p> <p>Blood pressure is considered to be a leading example of a valid surrogate endpoint. The aims of this study were to (i) formally evaluate systolic and diastolic blood pressure reduction as a surrogate endpoint for stroke prevention and (ii) determine what blood pressure reduction would predict a stroke benefit.</p> <p>Methods</p> <p>We identified randomised trials of at least six months duration comparing any pharmacologic anti-hypertensive treatment to placebo or no treatment, and reporting baseline blood pressure, on-trial blood pressure, and fatal and non-fatal stroke. Trials with fewer than five strokes in at least one arm were excluded. Errors-in-variables weighted least squares regression modelled the reduction in stroke as a function of systolic blood pressure reduction and diastolic blood pressure reduction respectively. The lower 95% prediction band was used to determine the minimum systolic blood pressure and diastolic blood pressure difference, the surrogate threshold effect (STE), below which there would be no predicted stroke benefit. The STE was used to generate the surrogate threshold effect proportion (STEP), a surrogacy metric, which with the R-squared trial-level association was used to evaluate blood pressure as a surrogate endpoint for stroke using the Biomarker-Surrogacy Evaluation Schema (BSES3).</p> <p>Results</p> <p>In 18 qualifying trials representing all pharmacologic drug classes of antihypertensives, assuming a reliability coefficient of 0.9, the surrogate threshold effect for a stroke benefit was 7.1 mmHg for systolic blood pressure and 2.4 mmHg for diastolic blood pressure. The trial-level association was 0.41 and 0.64 and the STEP was 66% and 78% for systolic and diastolic blood pressure respectively. The STE and STEP were more robust to measurement error in the independent variable than R-squared trial-level associations. Using the BSES3, assuming a reliability coefficient of 0.9, systolic blood pressure was a B + grade and diastolic blood pressure was an A grade surrogate endpoint for stroke prevention. In comparison, using the same stroke data sets, no STEs could be estimated for cardiovascular (CV) mortality or all-cause mortality reduction, although the STE for CV mortality approached 25 mmHg for systolic blood pressure.</p> <p>Conclusions</p> <p>In this report we provide the first surrogate threshold effect (STE) values for systolic and diastolic blood pressure. We suggest the STEs have face and content validity, evidenced by the inclusivity of trial populations, subject populations and pharmacologic intervention populations in their calculation. We propose that the STE and STEP metrics offer another method of evaluating the evidence supporting surrogate endpoints. We demonstrate how surrogacy evaluations are strengthened if formally evaluated within specific-context evaluation frameworks using the Biomarker- Surrogate Evaluation Schema (BSES3), and we discuss the implications of our evaluation of blood pressure on other biomarkers and patient-reported instruments in relation to surrogacy metrics and trial design.</p

Is primary care a neglected piece of the jigsaw in ensuring optimal stroke care? Results of a national study

<p>Abstract</p> <p>Background</p> <p>Stroke is a major cause of mortality and morbidity with potential for improved care and prevention through general practice. A national survey was undertaken to determine current resources and needs for optimal stroke prevention and care.</p> <p>Methods</p> <p>Postal survey of random sample of general practitioners undertaken (N = 204; 46% response). Topics included practice organisation, primary prevention, acute management, secondary prevention, long-term care and rehabilitation.</p> <p>Results</p> <p>Service organisation for both primary and secondary prevention was poor. Home management of acute stroke patients was used at some stage by 50% of responders, accounting for 7.3% of all stroke patients. Being in a structured cardiovascular management scheme, a training practice, a larger practice, or a practice employing a practice nurse were associated with structures and processes likely to support stroke prevention and care.</p> <p>Conclusion</p> <p>General practices were not fulfilling their potential to provide stroke prevention and long-term management. Systems of structured stroke management in general practice are essential to comprehensive national programmes of stroke care.</p

Beyond the Evidence of the New Hypertension Guidelines. Blood pressure measurement – is it good enough for accurate diagnosis of hypertension? Time might be in, for a paradigm shift (I)

Despite widespread availability of a large body of evidence in the area of hypertension, the translation of that evidence into viable recommendations aimed at improving the quality of health care is very difficult, sometimes to the point of questionable acceptability and overall credibility of the guidelines advocating those recommendations. The scientific community world-wide and especially professionals interested in the topic of hypertension are witnessing currently an unprecedented debate over the issue of appropriateness of using different drugs/drug classes for the treatment of hypertension. An endless supply of recent and less recent "drug-news", some in support of, others against the current guidelines, justifying the use of selected types of drug treatment or criticising other, are coming out in the scientific literature on an almost weekly basis. The latest of such debate (at the time of writing this paper) pertains the safety profile of ARBs vs ACE inhibitors. To great extent, the factual situation has been fuelled by the new hypertension guidelines (different for USA, Europe, New Zeeland and UK) through, apparently small inconsistencies and conflicting messages, that might have generated substantial and perpetuating confusion among both prescribing physicians and their patients, regardless of their country of origin. The overwhelming message conveyed by most guidelines and opinion leaders is the widespread use of diuretics as first-line agents in all patients with blood pressure above a certain cut-off level and the increasingly aggressive approach towards diagnosis and treatment of hypertension. This, apparently well-justified, logical and easily comprehensible message is unfortunately miss-obeyed by most physicians, on both parts of the Atlantic. Amazingly, the message assumes a universal simplicity of both diagnosis and treatment of hypertension, while ignoring several hypertension-specific variables, commonly known to have high level of complexity, such as: - accuracy of recorded blood pressure and the great inter-observer variability, - diversity in the competency and training of diagnosing physician, - individual patient/disease profile with highly subjective preferences, - difficulty in reaching consensus among opinion leaders, - pharmaceutical industry's influence, and, nonetheless, - the large variability in the efficacy and safety of the antihypertensive drugs. The present 2-series article attempts to identify and review possible causes that might have, at least in part, generated the current healthcare anachronism (I); to highlight the current trend to account for the uncertainties related to the fixed blood pressure cut-off point and the possible solutions to improve accuracy of diagnosis and treatment of hypertension (II)

Testing devices for the prevention and treatment of stroke and its complications

We are entering a challenging but exciting period when many new interventions may appear for stroke based on the use of devices. Hopefully these will lead to improved outcomes at a cost that can be afforded in most parts of the world. Nevertheless, it is vital that lessons are learnt from failures in the development of pharmacological interventions (and from some early device studies), including inadequate preclinical testing, suboptimal trial design and analysis, and underpowered studies. The device industry is far more disparate than that seen for pharmaceuticals; companies are very variable in size and experience in stroke, and are developing interventions across a wide range of stroke treatment and prevention. It is vital that companies work together where sales and marketing are not involved, including in understanding basic stroke mechanisms, prospective systematic reviews, and education of physicians. Where possible, industry and academics should also work closely together to ensure trials are designed to be relevant to patient care and outcomes. Additionally, regulation of the device industry lags behind that for pharmaceuticals, and it is critical that new interventions are shown to be safe and effective rather than just feasible. Phase IV postmarketing surveillance studies will also be needed to ensure that devices are safe when used in the ‘real-world’ and to pick up uncommon adverse events

Secondary prevention after ischaemic stroke: the ASPIRE-S study

BACKGROUND: Survivors of ischaemic stroke (IS) are at high-risk for future vascular events. Comprehensive information on the adequacy of secondary prevention after IS is lacking despite the knowledge that appropriate secondary prevention improves long-term patient outcomes. ASPIRE-S (Action on Secondary Prevention Interventions and Rehabilitation in Stroke) aimed to prospectively assess secondary prevention in patients 6 months following IS. METHODS: Consenting patients admitted with IS to three Dublin hospitals were recruited over 1 year, from October 2011. At 6 months post IS a comprehensive assessment was completed, modelled on the EUROASPIRE protocol for evaluation of the adequacy of secondary prevention in post-discharge cardiac patients. This assessment included measurements of blood pressure, body mass index and fasting lipid and glucose profiles. Secondary preventive medications and smoking status were also documented. RESULTS: Three hundred two patients (58 % male) participated, of whom 256 (85 %) were followed-up at 6 months. Mean age was 69 years (range 22–95). At follow-up, 68 % of patients had a BMI >25 kg/m(2) and 16.4 % were still smoking. Almost two-thirds (63.4 %) had a blood pressure >140/90 and 23 % had low-density-lipoprotein >2.5 mmol/L. 28 % of diabetic patients had HbA1c ≥7 %. Ninety seven percent of patients were on anti-platelet and/or anticoagulant therapy. Of those with atrial fibrillation, 82 % were anti-coagulated (mean INR of 2.4). Ninety-five percent were on lipid-lowering therapy and three-quarters were on anti-hypertensive therapy. CONCLUSION: This prospective multi-centre survey of IS patients demonstrated a high prevalence of remaining modifiable risk factors at 6 months post stroke, despite the widespread prescription of secondary preventive medications. There is scope to improve preventive measures after IS (in particular blood pressure) by incorporating evidence-based guidelines into quality assurance cycles in stroke care