Matthew Walters

University of Glasgow, Glasgow, Scotland, United Kingdom

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Publications (123)541.38 Total impact

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    ABSTRACT: Death after stroke is common, but little is known about end-of-life care processes in acute stroke units.
    Palliative medicine. 09/2014;
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    ABSTRACT: Objectives: To perform a genome-wide association study (GWAS) using the Immunochip array in 3,420 cases of ischemic stroke and 6,821 controls, followed by a meta-analysis with data from more than 14,000 additional ischemic stroke cases. Methods: Using the Immunochip, we genotyped 3,420 ischemic stroke cases and 6,821 controls. After imputation we meta-analyzed the results with imputed GWAS data from 3,548 cases and 5,972 controls recruited from the ischemic stroke WTCCC2 study, and with summary statistics from a further 8,480 cases and 56,032 controls in the METASTROKE consortium. A final in silico "look-up" of 2 single nucleotide polymorphisms in 2,522 cases and 1,899 controls was performed. Associations were also examined in 1,088 cases with intracerebral hemorrhage and 1,102 controls.
    Neurology 08/2014; 83(8):678-685. · 8.30 Impact Factor
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    ABSTRACT: Hypertension is a key risk factor for cardiovascular disease, and new treatments are needed. Uric acid reduction lowers blood pressure (BP) in adolescents, suggesting a direct pathophysiological role in the development of hypertension. Whether the same relationship is present in older adults is unknown. We explored change in BP after allopurinol initiation using data from the UK Clinical Practice Research Datalink. Data were extracted for patients with hypertension aged >65 years who were prescribed allopurinol with pretreatment and during treatment BP readings. Data from comparable controls were extracted. The change in BP in patients with stable BP medication was the primary outcome and was compared between groups. Regression analysis was used to adjust for potential confounding factors, and a propensity-matched sample was generated. Three hundred sixty-five patients who received allopurinol and 6678 controls were included. BP fell in the allopurinol group compared with controls (between-group difference in systolic and diastolic BP: 2.1 mm Hg; 95% confidence interval, -0.6 to 4.8; and 1.7 mm Hg; 95% confidence interval, 0.4-3.1, respectively). Allopurinol use was independently associated with a fall in both systolic and diastolic BP on regression analysis (P<0.001). Results were consistent in the propensity-matched sample. There was a trend toward greater fall in BP in the high-dose allopurinol group, but change in BP was not related to baseline uric acid level. Allopurinol use is associated with a small fall in BP in adults. Further studies of the effect of high-dose allopurinol in adults with hypertension are needed.
    Hypertension 08/2014; · 6.87 Impact Factor
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    ABSTRACT: Central blood pressure (CBP) and carotid intima-media thickness (CIMT) are surrogate measures of cardiovascular risk. Allopurinol reduces serum uric acid and oxidative stress and improves endothelial function and may therefore reduce CBP and CIMT progression. This study sought to ascertain whether allopurinol reduces CBP, arterial stiffness and CIMT progression in patients with ischaemic stroke or transient ischaemic attack (TIA). We performed a randomised, double-blind, placebo-controlled study, examining the effect of 1-year treatment with allopurinol (300 mg daily), on change in CBP, arterial stiffness and CIMT progression at 1 year and change in endothelial function and circulating inflammatory markers at 6 months. Patients aged over 18 years with recent ischaemic stroke or TIA were eligible. Eighty participants were recruited, mean age 67.8 years (SD 9.4). Systolic CBP [-6.6 mm Hg (95% CI -13.0 to -0.3), p=0.042] and augmentation index [-4.4% (95% CI -7.9 to -1.0), p=0.013] were each lower following allopurinol treatment compared with placebo at 12 months. Progression in mean common CIMT at 1 year was less in allopurinol-treated patients compared with placebo [between-group difference [-0.097 mm (95% CI -0.175 to -0.019), p=0.015]. No difference was observed for measures of endothelial function. Allopurinol lowered CBP and reduced CIMT progression at 1 year compared with placebo in patients with recent ischaemic stroke and TIA. This extends the evidence of sustained beneficial effects of allopurinol to these prognostically significant outcomes and to the stroke population, highlighting the potential for reduction in cardiovascular events with this treatment strategy. ISRCTN11970568.
    Heart (British Cardiac Society) 05/2014; · 5.01 Impact Factor
  • Hypertension 03/2014; 63(3):e15. · 6.87 Impact Factor
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    ABSTRACT: BACKGROUND: Mood disorders are commonly seen in those with cerebrovascular disease. Literature to-date has tended to focus on depression and on patients with stroke, with relatively little known about post-stroke anxiety or mood disorder in those with transient ischaemic attack (TIA). We aimed to describe prevalence of depression and anxiety symptoms in stroke and TIA cohorts and to explore association with clinical and socio-demographic factors. METHODS: We used a city wide primary care stroke registry (Glasgow Local Enhanced Service for Stroke - LES). All community dwelling stroke-survivors were included. We described cross-sectional prevalence of depression and anxiety symptoms using the Hospital Anxiety and Depression Scale (HADS). Data on clinical and demographic details was collected and univariable and multivariable analyses performed to describe associations with HADS scores. We examined those with a diagnosis of 'stroke' and 'TIA' as separate cohorts. RESULTS: From 13,283 potentially eligible stroke patients in the registry, we had full HADS data on 4,079. Of the 3,584 potentially eligible TIA patients, we had full HADS data on 1,247 patients. Across the stroke cohort, 1181 (29%) had HADS anxiety scores suggestive of probable or possible anxiety; 993 (24%) for depression. For TIA patients, 361 (29%) had anxiety and 254 (21%) had depression. Independent predictors of both depression and anxiety symptoms were female sex, younger age and higher socioeconomic deprivation score (all p < 0.001). CONCLUSION: Using HADS, we found a high prevalence of anxiety and depression symptoms in a community-based cohort of patients with cerebrovascular disease.
    BMC Neurol. 01/2014; 14:198.
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    ABSTRACT: Introduction: Antiplatelet therapy is routinely prescribed early after ischemic stroke. Many patients will already be taking antiplatelet therapy and it is unknown whether these patients should continue the same antiplatelet treatment or switch to a different regimen. We compared outcomes in patients who continued the same regimen after ischemic stroke to those who changed.Methods: Data from 10304 subjects were extracted from the Virtual International Stroke Trials Archive. 8550 subjects were excluded (12 incomplete data, 4823 no antiplatelet therapy recorded pre-stroke, 3715 no recorded antiplatelets post-stroke). Propensity score matching was employed to create a matched sample for comparison of those who continued the same regimen to those who changed. The nature of change in antiplatelet regimen was not explored. We compared the rate of recurrent stroke (primary endpoint), bleeding complications (defined as intracranial haemorrhage not including haemorrhagic transformation or any major bleed) and day-90 outcomes (using the modified Rankin and National Institutes of Health Stroke Scales). We used logistic regression analysis and adjusted for important clinical factors. Patients who suffered an outcome event prior to resuming antiplatelet therapy were not included in the analysis.Results: 963 subjects changed antiplatelet regimen post stroke and 791 continued the same regimen. In the propensity matched sample (n=791 per group), a recurrent ischemic event occurred in 3.7% of subjects who changed regimen and 3.8% who continued unchanged (OR=1.078; 95% CI 0.62-1.88, p=0.790). The odds of better functional outcome were higher in the change group according to both day-90 mRS (OR=1.31; 95% CI 1.07-1.59, p=0.008) and NIHSS. The rate of intracranial bleeding and major bleeding within the first 90 days was similar in both groups (1.2% vs. 1.2% (p=0.939) and 2.4% vs. 3.2% (p=0.409) respectively).Conclusion: In patients who suffer ischemic stroke whilst taking antiplatelets, a change in antiplatelet regimen was not associated with reduced recurrent stroke rate or bleeding. Day 90 functional outcome was better in the change group but this may be due to a confounding variable.
    Stroke 01/2014; 45:A135. · 6.16 Impact Factor
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    ABSTRACT: Current guidelines recommend early referral and initiation of intensive cardiovascular (CV) risk reduction in individuals with a positive family history of coronary heart disease (CHD). We hypothesized that a family history of premature CHD and stroke [CV disease (CVD)] would lead to earlier referral of hypertensive patients to secondary care clinic, leading to better control of risk factors, mitigating the excess risk seen in these individuals. We studied the association of a positive family history of CVD in 10 787 individuals with longitudinal changes in risk factors and long-term cause-specific mortality in the Glasgow Blood Pressure Clinic using generalized estimating equations and the Cox proportional hazard models, respectively. The total time at risk was 193 756 person-years with a median survival time of 29.2 years. A positive family history of CVD was associated with an earlier presentation to the clinic, a lower burden of traditional CV risk factors, and similar longitudinal blood pressure reduction and drug adherence compared with those without. But despite these positive features, all-cause [hazard ratio (HR) = 1.12, 95% confidence interval 1.01-1.25] and CV (HR = 1.20, 1.04-1.38) mortality independent of baseline risk factors were worse. Consistent results were observed in propensity score-matched analysis. Inclusion of family history of CVD did not improve mortality risk discrimination over and above traditional risk factors. Our study suggests that despite earlier referral and treatment of individuals with a positive family history of premature CVD, excess risk persists, indicating the need for continued and sustained efforts to reduce risk factors and drug adherence in these individuals.
    European Heart Journal 12/2013; · 14.72 Impact Factor
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    ABSTRACT: Most studies of poststroke anxiety prevalence are hospital based, so knowledge of anxiety in community stroke survivors is limited. Few studies address the association between poststroke anxiety and patient age. No study has explored the relationship between poststroke anxiety prevalence and social deprivation. This study aims to describe population level prevalence data of poststroke anxiety and to explore association of poststroke anxiety prevalence with patient age, gender, and social deprivation. Observational study of 3831 community stroke survivors attending general practice reviews from April 1, 2009 to March 31, 2010 in Greater Glasgow, United Kingdom. Univariate and multivariate analyses investigated the association between poststroke anxiety prevalence (Hospital Anxiety and Depression Scale: anxiety sub-scale [HADS-A]), age, gender, and deprivation variables. Six hundred eighteen (16·1%) of 3831 community-dwelling stroke survivors had definite abnormal mood on HADS-A (≥11), with 952 (31·5%) scoring ≥8. Sixty-five (35·5%) of stroke survivors aged under 50 years had definite abnormal mood on HADS-A compared with 59 (7·2%) of over 80 year olds. Three hundred forty (19·8%) of women had definite abnormal mood on HADS-A compared with 278 (13·1%) of men. Three hundred seventy-two (22·6%) of most deprived stroke survivors had definite abnormal mood on HADS-A compared with 49 (7·6%) of least deprived. Age, gender, and social deprivation all contributed significantly to HADS-A score variance. Using a conservative HADS-A cutoff, a high prevalence of definite abnormal anxiety in community stroke survivors is observed. This prevalence increases markedly in younger and more socially deprived stroke survivors.
    International Journal of Stroke 11/2013; · 4.03 Impact Factor
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    ABSTRACT: Use of the modified Rankin scale (mRS) in multicenter trials may be limited by interobserver variability. We assessed the effect of this on trial power and developed a novel group adjudication approach. We generated power and sample size estimates from simulated trials modeled with varying mRS reliability. We conducted a virtual acute stroke trial across 14 UK sites to develop a group adjudication approach. Traditional mRS interviews, performed at local sites, were digitally recorded and scored by adjudication committee. We assessed the effect of translation by comparing scores in translated mRS interviews, originally conducted in English and Mandarin. Agreement was measured using κ and weighted κ (κw) statistics and intraclass correlation coefficient. Statistical simulations suggest that improving mRS reliability from κ=0.25 to κ=0.5 or 0.7 may allow reductions in sample size of n=386 or 490 in a typical n=2000 study. Our virtual acute stroke trial included 370 participants and 563 mRS video assessments. We adjudicated mRS in 538 of 563 (96%) study visits. At 30 and 90 days, 161 of 280 (57.5%) and 131 of 258 (50.8%) clips showed interobserver disagreement. Agreement within the adjudication committee was good (30-day κw=0.85 [95% confidence interval, 0.81-0.86]; 90-day κw=0.86 [95% confidence interval, 0.82-0.88]) without significant or systematic bias in mRS scoring compared with the local mRS. Interobserver reliability of translated mRS assessments was similar to native language clips (native [n=69] κw=0.91 [95% confidence interval, 0.94-0.99]; translated [n=89] κw=0.90 [95% confidence interval, 0.83-0.96]). Achievable improvements in interobserver reliability may substantially reduce study sample size, with associated financial benefits. Central adjudication of mRS assessments is feasible (including across international centers), valid and reliable despite the challenges of mRS assessment in large clinical trials.
    Stroke 09/2013; · 6.16 Impact Factor
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    ABSTRACT: Chloride (Cl(-)) is the major extracellular anion in the body, accompanying sodium (Na(+)), and is primarily derived from dietary sources. Data suggest that increased dietary Cl(-) intake increases blood pressure, yet paradoxically, higher serum Cl(-) appears associated with lower mortality and cardiovascular risk. This implies that serum Cl(-) also reflects risk pathways independent of blood pressure, serum Na(+), and bicarbonate (HCO3(-)). We analyzed 12 968 hypertensive individuals followed up for 35 years, using Cox proportional hazards model to test whether baseline serum Cl(-) was an independent predictor of mortality. To distinguish the effect of Cl(-) from Na(+) and HCO3(-), we adjusted for these electrolytes and also performed the analysis stratified by Na(+)/HCO3(-) and Cl(-) levels. Generalized estimating equation was used to determine the effect of baseline Cl(-) on follow-up blood pressure. The total time at risk was 197 101 person-years. The lowest quintile of serum Cl(-) (<100 mEq/L) was associated with a 20% higher mortality (all-cause, cardiovascular and noncardiovascular) compared with the remainder of the subjects. A 1 mEq/L increase in serum Cl(-) was associated with a 1.5% (hazard ratio, 0.985; 95% confidence interval, 0.98-0.99) reduction in all-cause mortality, after adjustment for baseline confounding variables and Na(+), K(+), and HCO3(-) levels. The group with Na(+)>135 and Cl(-)>100 had the best survival, and compared with this group, the Na(+)>135 and Cl(-)<100 group had significantly higher mortality (hazard ratio, 1.21; 95% confidence interval, 1.11-1.31). Low, not high Serum Cl(-) (<100 mEq/L), is associated with greater mortality risk independent of obvious confounders. Further studies are needed to elucidate the relation between Cl(-) and risk.
    Hypertension 08/2013; · 6.87 Impact Factor
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    ABSTRACT: Recent evidence indicates that long-term visit-to-visit blood pressure variability (BPV) may be an independent cardiovascular risk predictor. The implication of this variability in hypertension clinical practice is unclear. BPV as average real variability (ARV) was calculated in 14 522 treated patients with hypertension in 4 time frames: year 1 (Y1), years 2 to 5 (Y2-5), years 5 to 10 (Y5-10), and years >10 (Y10+) from first clinic visit. Cox proportional hazards models for cause-specific mortality were used in each time frame separately for long-term BPV, across time frames based on ultra long-term BPV, and within each time frame stratified by mean BP. ARV in systolic blood pressure (SBP), termed ARVSBP, was higher in Y1 (21.3±11.9 mm Hg) in contrast to Y2-5 (17.7±9.9 mm Hg), Y5-10 (17.4±9.6 mm Hg), and Y10+ (16.8±8.5 mm Hg). In all time frames, ARVSBP was higher in women (P<0.01) and in older age (P<0.001), chronic kidney disease (P<0.01), and prevalent cardiovascular disease (P<0.01). Higher long-term and ultra long-term BPV values were associated with increased mortality (all-cause, cardiovascular, and noncardiovascular mortality; P for trend, <0.001). This relationship was also evident in subgroups with mean SBP<140 mm Hg in all time frames. Monitoring BPV in clinical practice may facilitate risk reduction strategies by identifying treated hypertensive individuals at high risk, especially those with BP within the normal range.
    Hypertension 08/2013; · 6.87 Impact Factor
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    ABSTRACT: Uric acid may have a role in the development of hypertension and renal dysfunction. We explored the relationship among longitudinal blood pressure, renal function, and cardiovascular outcomes in a large cohort of patients with treated hypertension. We used data from the Glasgow Blood Pressure Clinic database. Patients with a baseline measure of serum uric acid and longitudinal measures of blood pressure and renal function were included. Mortality data were obtained from the General Register Office for Scotland. Generalized estimating equations were used to explore the relationship among quartiles of serum uric acid, blood pressure, and estimated glomerular filtration rate. Cox proportional hazard models were developed to assess mortality relationships. In total, 6984 patients were included. Serum uric acid level did not influence the longitudinal changes in systolic or diastolic blood pressure but was related to change in glomerular filtration rate. In comparison with patients in the first quartile of serum uric acid, the relative decrease in glomerular filtration rate in the fourth was 10.7 (95% confidence interval, 7.9-13.6 mL/min per 1.73 m(2)) in men and 12.2 (95% confidence interval, 9.2-15.2 mL/min per 1.73 m(2)) in women. All-cause and cardiovascular mortality differed across quartiles of serum uric acid in women only (P<0.001; hazard ratios for all-cause mortality 1.38 [95% confidence interval, 1.14-1.67] for the fourth quartile of serum uric acid compared with the first). Serum uric acid level was not associated with longitudinal blood pressure control in adults with treated hypertension but was related to decline in renal function and mortality in women.
    Hypertension 05/2013; · 6.87 Impact Factor
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    ABSTRACT: Very few studies have looked at longitudinal intraindividual blood pressure responses to weather conditions. There are no data to suggest that specific response to changes in weather will have an impact on survival. We analyzed >169 000 clinic visits of 16 010 Glasgow Blood Pressure Clinic patients with hypertension. Each clinic visit was mapped to the mean West of Scotland monthly weather (temperature, sunshine, rainfall) data. Percentage change in blood pressure was calculated between pairs of consecutive clinic visits, where the weather alternated between 2 extreme quartiles (Q1-Q4 or Q4-Q1) or remained in the same quartile (Qn-Qn) of each weather parameter. Subjects were also categorized into 2 groups depending on whether their blood pressure response in Q1-Q4 or Q4-Q1 were concordant or discordant to Qn-Qn. Generalized estimating equations and Cox proportional hazards model were used to model the effect on longitudinal blood pressure and mortality, respectively. Qn-Qn showed a mean 2% drop in blood pressure consistently, whereas Q4-Q1 showed a mean 2.1% and 1.6% rise in systolic and diastolic blood pressure, respectively. However, Q1-Q4 did not show significant changes in blood pressure. Temperature-sensitive subjects had significantly higher mortality (1.35 [95% confidence interval, 1.06-1.71]; P=0.01) and higher follow-up systolic blood pressure (1.85 [95% confidence interval, 0.24-3.46]; P=0.02) compared with temperature-nonsensitive subjects. Blood pressure response to temperature may be one of the underlying mechanisms that determine long-term blood pressure variability. Knowing a patient's blood pressure response to weather can help reduce unnecessary antihypertensive treatment modification, which may in turn increase blood pressure variability and, thus, risk.
    Hypertension 05/2013; · 6.87 Impact Factor
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    ABSTRACT: BACKGROUND: /st>The EuroSCORE associates coronary artery bypass graft (CABG) surgery with higher perioperative risk in the first 3 months after a myocardial infarction (MI). The optimal scheduling of CABG surgery after unstable angina (UA) is unknown. We investigated the preoperative predictors of adverse outcomes in patients undergoing CABG with prior MI or UA and investigated the importance of time interval between the cardiac event and CABG. METHODS: /st>The Hospital Episode Statistics database (April 2006-March 2010) was analysed for elective admissions for CABG. Independent preoperative patient factors influencing length of stay, readmission rates, and mortality, were identified by logistic regression and presented as adjusted odds ratios (ORs). RESULTS: /st>A total of 10 418 patients with prior MI (mortality 1.8%) and 5241 patients with prior UA (mortality 2.2%) were included in the respective cohorts. Multiple risk factors were identified in each population including liver disease and renal failure. The time interval from cardiac event (MI or UA) to elective CABG surgery did not influence perioperative outcomes when analysed as a continuous measure or using the arbitrary 3-month threshold [MI, OR 1.1 (0.78-1.57) and UA, OR 0.65 (0.39-1.09)]. CONCLUSIONS: /st>Our hypothesis generating data suggest that the increased risk currently allocated in the EuroSCORE for an interval of 3 months between MI and CABG should be critically re-evaluated. Furthermore, prior MI should not be discounted as a risk factor if it is more than 3 months old.
    BJA British Journal of Anaesthesia 04/2013; · 4.24 Impact Factor
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    ABSTRACT: OBJECTIVE:: Recent data suggest that self-reported acetaminophen use is associated with increased risk of cardiovascular events and a rise in arterial blood pressure (BP). We investigated the association between acetaminophen use and BP in a large cohort of patients with hypertension using verified prescription data. METHODS:: We extracted data from the UK General Practice Research Database for all hypertensive patients aged 65 years or older who were prescribed acetaminophen and had BP measured both before and during acetaminophen treatment. Patients were grouped according to whether their antihypertensive treatment remained unchanged or not during the study period. The change in SBP and DBP during acetaminophen use was determined and compared with the change in BP in a group of nonacetaminophen-exposed people identified using propensity matching. RESULTS:: A total of 2754 acetaminophen-exposed individuals were included. BP rose slightly during the period of acetaminophen treatment wherein antihypertensive treatment was unchanged [change in SBP 1.6 [95% confidence interval (CI) 0.7-2.5) mmHg and change in DBP 0.5 (95% CI 0.1-1.0) mmHg)]. BP fell when new antihypertensive medications were prescribed. These BP changes were no different to those seen in matched nonacetaminophen-exposed individuals [between-group difference wherein antihypertensive treatment was unchanged was 0.6 (95% CI -0.6 to 1.9) mmHg and 0.5 (-0.1 to 1.1) mmHg for change in SBP and DBP, respectively]. CONCLUSION:: We found no evidence of a sustained rise in blood pressure caused by acetaminophen treatment in a large population of patients with treated hypertension.
    Journal of Hypertension 04/2013; · 4.22 Impact Factor
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    ABSTRACT: BACKGROUND AND PURPOSE: Simple and rapid measures of intraventricular hemorrhage (IVH) volume are lacking. We developed and validated a modification of the original Graeb scale to facilitate rapid assessment of IVH over time. METHODS: We explored the relationship between the modified Graeb scale (mGS), original Graeb scale, measured IVH volume, and outcome using data from the Clot Lysis: Evaluating Accelerated Resolution of Hemorrhage with rtPA B (CLEAR B) study. We also explored its reliability. We then evaluated the relationship between mGS and outcome in a large sample of participants with IVH using data contained within the Virtual International Stroke Trials Archive (VISTA). We defined outcome using the modified Rankin scale (>3 signifying poor outcome). RESULTS: The CLEAR B study included 360 scans from 36 subjects. The mGS score and IVH volume were highly correlated (R = 0.80, P<0.0001, R(2) 0.65). Baseline mGS was predictive of poor outcome (area under receiving operating characteristic curve 0.74, 95% confidence interval, 0.57-0.91), whereas the original Graeb scale was not. The VISTA study included 399 participants. Each unit increase in the mGS led to a 12% increase in the odds of a poor outcome (odds ratio, 1.12; 95% confidence interval, 1.05-1.19). Measures of reliability (intra- and inter- reader) were good in both studies. CONCLUSIONS: The mGS, a semiquantitative scale for IVH volume measurement, is a reliable measure with prognostic validity suitable for rapid use in clinical practice and in research.
    Stroke 01/2013; · 6.16 Impact Factor
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    ABSTRACT: BACKGROUND:: Data are lacking on the optimal scheduling of coronary artery bypass grafting (CABG) surgery after stroke. The authors investigated the preoperative predictors of adverse outcomes in patients undergoing CABG, with a focus on the importance of the time interval between prior stroke and CABG. METHODS:: The Hospital Episode Statistics database (April 2006-March 2010) was analyzed for elective admissions for CABG. Independent preoperative patient factors influencing length of stay, postoperative stroke, and mortality, were identified by logistic regression and presented as adjusted odds ratios (OR). RESULTS:: In all,62,104 patients underwent CABG (1.8% mortality). Prior stroke influenced mortality (OR 2.20 [95% CI 1.47-3.29]), postoperative stroke (OR 1.99 [1.39-2.85]), and prolonged length of stay (OR 1.31 [1.11-1.56]). The time interval between stroke and CABG did not influence mortality or prolonged length of stay. However, a longer time interval between stroke and CABG surgery was associated with a small increase in risk of postoperative stroke (OR per month elapsed 1.02 [1.00-1.04]; P = 0.047). An interaction was evident between prior stroke and myocardial infarction for death (OR 5.50 [2.84-10.8], indicating the importance of the combination of comorbidities. Prominent effects on mortality were also exerted by liver disease (OR 20.8 [15.18-28.51]) and renal failure (OR 4.59 [3.85-5.46]). CONCLUSIONS:: The authors found no evidence that more recent preoperative stroke predisposed patients undergoing CABG surgery to suffer postoperative stroke, death, or prolonged length of stay. The combination of prior stroke and myocardial infarction substantially increased perioperative risk.
    Anesthesiology 01/2013; · 5.16 Impact Factor
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    ABSTRACT: BACKGROUND: Various genome-wide association studies (GWAS) have been done in ischaemic stroke, identifying a few loci associated with the disease, but sample sizes have been 3500 cases or less. We established the METASTROKE collaboration with the aim of validating associations from previous GWAS and identifying novel genetic associations through meta-analysis of GWAS datasets for ischaemic stroke and its subtypes. METHODS: We meta-analysed data from 15 ischaemic stroke cohorts with a total of 12 389 individuals with ischaemic stroke and 62 004 controls, all of European ancestry. For the associations reaching genome-wide significance in METASTROKE, we did a further analysis, conditioning on the lead single nucleotide polymorphism in every associated region. Replication of novel suggestive signals was done in 13 347 cases and 29 083 controls. FINDINGS: We verified previous associations for cardioembolic stroke near PITX2 (p=2·8×10(-16)) and ZFHX3 (p=2·28×10(-8)), and for large-vessel stroke at a 9p21 locus (p=3·32×10(-5)) and HDAC9 (p=2·03×10(-12)). Additionally, we verified that all associations were subtype specific. Conditional analysis in the three regions for which the associations reached genome-wide significance (PITX2, ZFHX3, and HDAC9) indicated that all the signal in each region could be attributed to one risk haplotype. We also identified 12 potentially novel loci at p<5×10(-6). However, we were unable to replicate any of these novel associations in the replication cohort. INTERPRETATION: Our results show that, although genetic variants can be detected in patients with ischaemic stroke when compared with controls, all associations we were able to confirm are specific to a stroke subtype. This finding has two implications. First, to maximise success of genetic studies in ischaemic stroke, detailed stroke subtyping is required. Second, different genetic pathophysiological mechanisms seem to be associated with different stroke subtypes. FUNDING: Wellcome Trust, UK Medical Research Council (MRC), Australian National and Medical Health Research Council, National Institutes of Health (NIH) including National Heart, Lung and Blood Institute (NHLBI), the National Institute on Aging (NIA), the National Human Genome Research Institute (NHGRI), and the National Institute of Neurological Disorders and Stroke (NINDS).
    The Lancet Neurology 10/2012; 11(11):951-962. · 23.92 Impact Factor
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    ABSTRACT: Hematocrit has been inconsistently reported to be a risk marker of cardiovascular morbidity and mortality. The Glasgow Blood Pressure Clinic Study cohort included 10951 hypertensive patients, who had hematocrit measured at their initial clinic visit and followed for ≤35 years. Cox proportional hazards models were used to estimate hazard ratios for all-cause, cardiovascular, ischemic heart disease, stroke, and noncardiovascular mortality. There were 3484 deaths over a follow-up period of 173245 person-years. Hematocrit was higher in men (median, 0.44; interquartile range, 0.42-0.47) than in women (median, 0.41; interquartile range, 0.38-0.43). The lowest risk for all-cause mortality was seen in quartile 2 for men (range, 0.421-0.440) and women (range, 0.381-0.400). Compared with quartile 2, the adjusted hazard ratios for quartiles 1, 3, and 4 were, respectively, 1.11 (range, 0.97-1.28), 1.19 (range, 1.04-1.37), and 1.22 (range, 1.06-1.39) in men and 1.17 (range, 1.01-1.36), 0.97 (range, 0.83-1.13), and 1.19 (range, 1.04-1.37) in women. Men showed a J-shaped pattern for cardiovascular mortality and a linear pattern for noncardiovascular mortality in cause-specific analysis, whereas in women a U-shaped pattern was observed for noncardiovascular mortality only. Higher baseline hematocrit was associated with higher on-treatment blood pressure during follow-up. Baseline hematocrit did not affect the time to reach target blood pressure. The increased risk of death attributed to higher hematocrit was seen in men and women irrespective of their achievement of target blood pressure, indicating that the risk is independent of the effect of hematocrit on blood pressure. Hypertensive patients with hematocrit levels outside of the sex-specific reference ranges identified in this study should be targeted for more aggressive blood pressure and cardiovascular risk reduction treatment.
    Hypertension 07/2012; 60(3):631-8. · 6.87 Impact Factor

Publication Stats

1k Citations
541.38 Total Impact Points

Institutions

  • 2001–2014
    • University of Glasgow
      • • Institute of Cardiovascular and Medical Sciences
      • • College of Medical, Veterinary and Life Sciences
      Glasgow, Scotland, United Kingdom
  • 2011
    • East Coast Community Healthcare CIC
      Beccles, England, United Kingdom