Use of ordinal outcomes in vascular prevention trials: comparison with binary outcomes in published trials

Background and Purpose—Vascular prevention trials mostly count “yes/no” (binary) outcome events, eg, stroke/no stroke. Analysis of ordered categorical vascular events (eg, fatal stroke/nonfatal stroke/no stroke) is clinically relevant and could be more powerful statistically. Although this is not a novel idea in the statistical community, ordinal outcomes have not been applied to stroke prevention trials in the past. Methods—Summary data on stroke, myocardial infarction, combined vascular events, and bleeding were obtained by treatment group from published vascular prevention trials. Data were analyzed using 10 statistical approaches which allow comparison of 2 ordinal or binary treatment groups. The results for each statistical test for each trial were then compared using Friedman 2-way analysis of variance with multiple comparison procedures. Results—Across 85 trials (335 305 subjects) the test results differed substantially so that approaches which used the ordinal nature of stroke events (fatal/nonfatal/no stroke) were more efficient than those which combined the data to form 2 groups (P0.0001). The most efficient tests were bootstrapping the difference in mean rank, Mann–Whitney U test, and ordinal logistic regression; 4- and 5-level data were more efficient still. Similar findings were obtained for myocardial infarction, combined vascular outcomes, and bleeding. The findings were consistent across different types, designs and sizes of trial, and for the different types of intervention. Conclusions—When analyzing vascular events from prevention trials, statistical tests which use ordered categorical data are more efficient and are more likely to yield reliable results than binary tests. This approach gives additional information on treatment effects by severity of event and will allow trials to be smaller. (Stroke. 2008;39:000-000.)

The relationship between baseline blood pressure and computed tomography findings in acute stroke: data from the Tinzaparin in Acute Ischaemic Stroke Trial (TAIST)

Background and Purpose—High blood pressure (BP) is present in 80% of patients with acute ischemic stroke and is independently associated with poor outcome. There are few data examining the relationship between admission BP and acute CT findings. Methods—TAIST was a randomized controlled trial assessing 10 days of treatment with tinzaparin versus aspirin in 1489 patients with acute ischemic stroke (48 hr) with admission BP of 220/120 mm Hg. CT brain scans were performed before randomization and after 10 days. The relationships between baseline BP and adjudicated CT findings were assessed. Odds ratios per 10 mm Hg change in BP were calculated. Results—Higher systolic BP (SBP) was associated with abnormal CT scans because of independent associations with chronic changes of leukoariosis (OR, 1.12; 95% CI, 1.05–1.17) and old infarction (OR, 1.12; 95% CI, 1.06 –1.17) at baseline, and signs of visible infarction at day 10 (OR, 1.06; 95% CI, 1.00 –1.13). A lower SBP was associated with signs of acute infarction (OR, 0.94; 95% CI, 0.89–0.99). Hemorrhagic transformation, dense middle cerebral artery sign, mass effect, and cerebral edema at day 10 were not independently associated with baseline BP. Conclusion—Although high baseline BP is independently associated with a poor outcome after stroke, this was not shown to be through an association with increased hemorrhagic transformation, cerebral edema, or mass effect; trial design may be suboptimal to detect this. Higher SBP is associated with visible infarction on day 10 scans. The influence of changing BP in acute stroke on CT findings is still to be ascertained.

Can we improve the statistical analysis of stroke trials? Statistical reanalysis of functional outcomes in stroke trials

Background and Purpose—Most large acute stroke trials have been neutral. Functional outcome is usually analyzed using a yes or no answer, eg, death or dependency versus independence. We assessed which statistical approaches are most efficient in analyzing outcomes from stroke trials. Methods—Individual patient data from acute, rehabilitation and stroke unit trials studying the effects of interventions which alter functional outcome were assessed. Outcomes included modified Rankin Scale, Barthel Index, and “3 questions”. Data were analyzed using a variety of approaches which compare 2 treatment groups. The results for each statistical test for each trial were then compared. Results—Data from 55 datasets were obtained (47 trials, 54 173 patients). The test results differed substantially so that approaches which use the ordered nature of functional outcome data (ordinal logistic regression, t test, robust ranks test, bootstrapping the difference in mean rank) were more efficient statistically than those which collapse the data into 2 groups (2; ANOVA, P0.001). The findings were consistent across different types and sizes of trial and for the different measures of functional outcome. Conclusions—When analyzing functional outcome from stroke trials, statistical tests which use the original ordered data are more efficient and more likely to yield reliable results. Suitable approaches included ordinal logistic regression, test, and robust ranks test.

Good laboratory practice: preventing introduction of bias at the bench

Background and Purpose—As a research community, we have failed to demonstrate that drugs which show substantial efficacy in animal models of cerebral ischemia can also improve outcome in human stroke. Summary of Review—Accumulating evidence suggests this may be due, at least in part, to problems in the design, conduct and reporting of animal experiments which create a systematic bias resulting in the overstatement of neuroprotective efficacy. Conclusions—Here, we set out a series of measures to reduce bias in the design, conduct and reporting of animal experiments modeling human stroke.

Relationship between hyperacute blood pressure and outcome after ischemic stroke: data from the VISTA Collaboration

Background and Purpose—High blood pressure (BP) is associated independently with poor outcome after acute ischemic stroke, although in most analyses “baseline” BP was measured 24 hours or more postictus, and not during the hyperacute period. Methods—Analyses included 1722 patients in hyperacute trials (recruitment 8 hours) from the Virtual Stroke International Stroke Trial Archive (VISTA) Collaboration. Data on BP at enrolment and after 1, 2, 16, 24, 48, and 72 hours, neurological impairment at 7 days (NIHSS), and functional outcome at 90 days (modified Rankin scale) were assessed using logistic regression models, adjusted for confounding variables; results are for 10-mm Hg change in BP. Results—Mean time to enrolment was 3.7 hours (range 1.0 to 7.9). High systolic BP (SBP) was significantly associated with increased neurological impairment (odds ratio, OR 1.06, 95% confidence interval, 95% CI 1.01 to 1.12), and poor functional outcome; odds ratios for both increased with later BP measurements made at up to 24 hours poststroke. Smaller (versus larger) declines in SBP over the first 24 hours were significantly associated with poor NIHSS scores (OR 1.16, 95% CI 1.05 to 1.27) and functional outcome (OR 1.23, 95% CI 1.13 to 1.34). A large variability in SBP was also associated with poor functional outcome. Conclusions—High SBP and large variability in SBP in the hyperacute stages of ischemic stroke are associated with increased neurological impairment and poor functional outcome, as are small falls in SBP over the first 24 hours.

Relationship between therapeutic changes in blood pressure and outcomes in acute stroke: a metaregression

Both low and high blood pressure (BP) during the acute phase of stroke are associated independently with a poor outcome. Several small clinical trials have involved the alteration of BP and this study assessed the relationship between change in BP and functional outcome. Randomised controlled trials of interventions that would be expected, on pharmacological grounds, to alter BP in patients within one week of the onset of acute ischaemic or haemorrhagic stroke were sought using electronic searches. Data were collected on BP and clinical outcome. The relationship between the difference in on-treatment BP and odds ratios (OR) for outcomes was assessed using meta-regression. Thirty-seven trials involving 9,008 patients were included. A ‘U’ or ‘J’ shaped relationship were found between on-treatment BP difference and early death, death at the end of 90 day follow up, and combined death or dependency at the end of follow up. Although outcomes were not significantly reduced at any level of change in BP, the lowest odds occurred at: early death (OR 0.87, 95% confidence interval, CI 0.54 to 1.23) - 8.1 mmHg; death at end of follow up (OR 0.96, 95% CI 0.31 to 1.65) - 14.4 mmHg; and combined death or dependency at end of follow up (OR 0.95, 95% CI 0.11 to 1.72) - 14.6 mmHg. Although large falls or increases in BP are associated with a worse outcome, modest reductions may reduce death, and combined death or dependency, although the confidence intervals are wide and compatible with overall benefit or hazard.

Effect of telmisartan on functional outcome, recurrence, and blood pressure in patients with acute mild ischemic stroke: a PRoFESS subgroup analysis

Background and Purpose—High blood pressure (BP) is common in acute ischemic stroke and associated independently with a poor functional outcome. However, the management of BP acutely remains unclear because no large trials have been completed. Methods—The factorial PRoFESS secondary stroke prevention trial assessed BP-lowering and antiplatelet strategies in 20 332 patients; 1360 were enrolled within 72 hours of ischemic stroke, with telmisartan (angiotensin receptor antagonist, 80 mg/d, n647) vs placebo (n713). For this nonprespecified subgroup analysis, the primary outcome was functional outcome at 30 days; secondary outcomes included death, recurrence, and hemodynamic measures at up to 90 days. Analyses were adjusted for baseline prognostic variables and antiplatelet assignment. Results—Patients were representative of the whole trial (age 67 years, male 65%, baseline BP 147/84 mm Hg, small artery disease 60%, NIHSS 3) and baseline variables were similar between treatment groups. The mean time from stroke to recruitment was 58 hours. Combined death or dependency (modified Rankin scale: OR, 1.03; 95% CI, 0.84–1.26; P0.81; death: OR, 1.05; 95% CI, 0.27–4.04; and stroke recurrence: OR, 1.40; 95% CI, 0.68–2.89; P0.36) did not differ between the treatment groups. In comparison with placebo, telmisartan lowered BP (141/82 vs 135/78 mmHg, difference 6 to 7 mmHg and 2 to 4 mmHg; P0.001), pulse pressure (3 to 4 mmHg; P0.002), and rate-pressure product (466 mmHg.bpm; P0.0004). Conclusion—Treatment with telmisartan in 1360 patients with acute mild ischemic stroke and mildly elevated BP appeared to be safe with no excess in adverse events, was not associated with a significant effect on functional dependency, death, or recurrence, and modestly lowered BP.

Normative reference values for the 20-meter shuttlerun test in a population-based sample of schoolchildren in Bogota, Colombia: The FUPRECOL Study

Our aim was to determine the normative reference values of cardiorespiratory fitness (CRF) and to establish the proportion of subjects with low CRF suggestive of future cardio-metabolic risk.

Asociación entre la escala de riesgo Framingham y el puntaje de calcio coronario

Introducción: Entre las diferentes herramientas clínicas para evaluar la presencia de enfermedad coronaria mediante puntajes, la más usada es la Escala de Riesgo cardiovascular de Framingham. Desde hace unos años, se creó el puntaje de calcio coronario el cual mide el riesgo cardiovascular según la presencia de placas ateromatosas vistas por tomografía computarizada. Se evaluó la asociación entre la escala de Framigham y el puntaje de calcio coronario en una población de sujetos sanos asintomáticos. Metodología: Se realizó un estudio transversal para evaluar la asociación entre el puntaje de calcio coronario y la escala de Framingham en sujetos asintomáticos que se practicaron exámen médico preventivo en la Fundación Cardioinfantil- Instituto de Cardiología (FCI-IC) en el periodo comprendido entre 1 de Julio 2011 hasta el 31 de octubre de 2015. Resultados: Se evaluaron 262 pacientes en total. La prevalencia de riesgo cardiovascular fue bajo en un 77.86% de la población, medio en 18.70% y alto en 3.44%, según la escala de Framingham. El riesgo cardiovascular según el puntaje de Calcio coronario fue nulo 70.99%, bajo en 21.75%, medio en 4.19%, severo en 3.05%. Se encontró una asociación entre ambos puntajes para riesgo estadísticamente significativa (p0,00001) Discusión: El riesgo cardiovascular establecido por escala de Framingham se relaciona de forma significativa con la presencia de placas aterioscleróticas. El estudio demostró que en una muestra de sujetos asintomáticos, hay una alteración estructural coronaria temprana.

Impedancias basales registradas durante la denervación renal por radiofrecuencia en pacientes con hipertensión arterial resistente

Objetivo: Determinar diferencias en las impedancias basales registradas durante los procedimientos de denervación renal por radiofrecuencia de los pacientes sometidos a este procedimiento en la Fundación Cardioinfantil de Bogotá durante los años 2012 a 2015. Materiales y métodos: Estudio observacional, analítico de corte retrospectivo, donde se analizaron todas las impedancias basales medidas durante los procedimientos de denervación renal, buscando diferencias significativas entre los segmentos de las arterias intervenidas, estratificados en proximal, medio distal y superior, lateral, inferior u ostial. Con seguimiento a los pacientes a tres, seis y doce meses en cuanto a presión arterial de consultorio. Resultados: Se evaluaron 150 puntos de denervación renal exitosos, correspondientes a 23 arterias renales de 11 procedimientos. La mediana de edad fue 56 años. Al realizar un modelo de regresión lineal no se encontró ninguna diferencia estadísticamente significativa entre las impedancias de ninguno de los segmentos de las arterias ni sitios anatómicos. Se documentó disminución de presión arterial sistólica a tres meses, seis meses y doce meses de 14 mmHg (RIQ 10-33mmHg), 21 mmHg (RIQ 12-42mmHg) y 19 mmHg (RIQ 11-42 mmHg) respectivamente

Metabolic syndrome and associated factors in a population-based sample of schoolchildren in Colombia: The FUPRECOL Study

In contrast to the definition of metabolic syndrome (MetS) in adults, there is no standard definition of MetS in pediatric populations. We aimed to assess the differences in the prevalence of MetS in children and adolescents aged 9–17 years in the city of Bogota (Colombia) using four different operational definitions for these age groups and to examine the associated variables. A total of 673 children and 1,247 adolescents attending public schools in Bogota (54.4% girls; age range 9–17.9 years) were included. The prevalence of MetS was determined by the definitions provided by the International Diabetes Federation (IDF) and three published studies by Cook et al., de Ferranti et al., and Ford et al. The prevalence of MetS was 0.3%, 6.3%, 7.8%, and 11.0% according to the IDF, Cook et al., Ford et al., and de Ferranti et al. definitions, respectively. The most prevalent components were low high-density lipoprotein cholesterol and high triglyceride levels, whereas the least prevalent components were abdominal obesity and hyperglycemia. Overall, the prevalence of MetS was higher in obese than in non-obese schoolchildren. In conclusion, MetS diagnoses in schoolchildren strongly depend on the definition chosen. These findings may be relevant to health promotion efforts for Colombian youth to develop prospective studies and to define which cut-offs are the best indicators of future morbidity.

Cardiorespiratory fitness and cardiometabolic risk factors in schoolchildren from Colombia: The FUPRECOL Study

The objectives of this study are to investigate the association between cardiorespiratory fitness and cardiovascular risk factors in schoolchildren and to evaluate the degree of association between overall and abdominal adiposity and cardiorespiratory fitness. A total of 1,875 children and adolescents attending public schools in Bogota, Colombia (56.2% girls; age range of 9–17.9 years). A cardiovascular risk score (Z-score) was calculated and participants were divided into tertiles according to low and high levels of overall (sum of the skinfold thicknesses) and abdominal adiposity. Schoolchildren with a high level of overall adiposity demonstrated significant differences in seven of the 10 variables analyzed (i.e. systolic and diastolic blood pressure, triglycerides, triglycerides/HDL-c ratio, total cholesterol, glucose and cardiovascular risk score). Schoolchildren with high levels of both overall and abdominal adiposity and low cardiorespiratory fitness had the least favorable cardiovascular risk factors score. These findings may be relevant to health promotion in Colombian youth.