Amanda Lee

Ankle brachial index combined with Framingham risk score to predict cardiovascular events and mortality - A meta-analysis

CONTEXT Prediction models to identify healthy individuals at high risk of cardiovascular disease have limited accuracy. A low ankle brachial index (ABI) is an indicator of atherosclerosis and has the potential to improve prediction. OBJECTIVE To determine if the ABI provides information on the risk of cardiovascular events and mortality independently of the Framingham risk score (FRS) and can improve risk prediction. DATA SOURCES Relevant studies were identified. A search of MEDLINE (1950 to February 2008) and EMBASE (1980 to February 2008) was conducted using common text words for the term ankle brachial index combined with text words and Medical Subject Headings to capture prospective cohort designs. Review of reference lists and conference proceedings, and correspondence with experts was conducted to identify additional published and unpublished studies. STUDY SELECTION Studies were included if participants were derived from a general population, ABI was measured at baseline, and individuals were followed up to detect total and cardiovascular mortality. DATA EXTRACTION Prespecified data on individuals in each selected study were extracted into a combined data set and an individual participant data meta-analysis was conducted on individuals who had no previous history of coronary heart disease. RESULTS Sixteen population cohort studies fulfilling the inclusion criteria were included. During 480,325 person-years of follow-up of 24,955 men and 23,339 women, the risk of death by ABI had a reverse J-shaped distribution with a normal (low risk) ABI of 1.11 to 1.40. The 10-year cardiovascular mortality in men with a low ABI (< or = 0.90) was 18.7% (95% confidence interval [CI], 13.3%-24.1%) and with normal ABI (1.11-1.40) was 4.4% (95% CI, 3.2%-5.7%) (hazard ratio [HR], 4.2; 95% CI, 3.3-5.4). Corresponding mortalities in women were 12.6% (95% CI, 6.2%-19.0%) and 4.1% (95% CI, 2.2%-6.1%) (HR, 3.5; 95% CI, 2.4-5.1). The HRs remained elevated after adjusting for FRS (2.9 [95% CI, 2.3-3.7] for men vs 3.0 [95% CI, 2.0-4.4] for women). A low ABI (< or = 0.90) was associated with approximately twice the 10-year total mortality, cardiovascular mortality, and major coronary event rate compared with the overall rate in each FRS category. Inclusion of the ABI in cardiovascular risk stratification using the FRS would result in reclassification of the risk category and modification of treatment recommendations in approximately 19% of men and 36% of women. CONCLUSION Measurement of the ABI may improve the accuracy of cardiovascular risk prediction beyond the FRS.

Blood viscosity and risk of cardiovascular events: the Edinburgh Artery Study.

We examined the relationships of whole blood viscosity and its major determinants to incident cardiovascular events (ischaemic heart disease and stroke) in a prospective study of a random population sample of 1592 men and women aged 55–74 years (the Edinburgh Artery Study). 272 fatal and non‐fatal cardiovascular events occurred during 5 years of follow‐up (cumulative incidence 17.1%). Age and sex adjusted mean levels of blood viscosity (3.70 v 3.55 mPa.s), haematocrit (46.2 v 45.7%), haematocrit‐corrected blood viscosity (3.57 v 3.48 mPa.s), plasma viscosity (1.35 v 1.33 mPa.s) and fibrinogen (2.88 v 2.67 g/l) were significantly higher in subjects who experienced events than in subjects who did not. The relationships of these rheological variables to cardiovascular events were at least as strong as those of conventional risk factors (smoking habit, diastolic blood pressure, and low‐density lipoprotein cholesterol). After adjustment for these conventional risk factors, the associations of blood viscosity and haematocrit remained significant for stroke, but not for total events; whereas the associations of plasma viscosity and fibrinogen remained significant for total events and for stroke.

Prescribing practices and asthma control with hydrofluoroalkane-beclomethasone and fluticasone: A real-world observational study

BACKGROUND Long-term randomized trials comparing asthma outcomes between inhaled corticosteroids in real-world populations are lacking. As such, rigorously conducted observational studies to complement the findings of randomized trials are needed. OBJECTIVE We sought to compare asthma-related outcomes over 1 year as recorded in a large primary care database for patients aged 5 to 60 years receiving a first prescription (initiation population) or dose increase (step-up population) of hydrofluoroalkane (HFA)-beclomethasone or fluticasone. METHODS We used a retrospective matched cohort study in which patients were matched on baseline demographic and disease severity measures. Coprimary outcomes were asthma control (a composite measure comprising no unplanned visit or hospitalization for asthma, oral corticosteroids, or antibiotics for lower respiratory tract infection) and exacerbation rate. RESULTS More than 80% of patients in each population achieved asthma control; 10% and 16% of patients in the initiation and step-up populations, respectively, received add-on or combination therapy during the year. Fluticasone was prescribed at significantly higher doses than HFA-beclomethasone for both populations (P <or= .001). In the initiation population (n = 1319 in each cohort) the adjusted odds ratio for achieving asthma control with HFA-beclomethasone was 1.30 (95% CI, 1.02-1.65) relative to fluticasone. In the step-up population (cohorts: n = 250) the adjusted odds ratio for achieving asthma control with HFA-beclomethasone was 1.22 (95% CI, 0.66-2.26). Exacerbation rates were similar between cohorts. CONCLUSIONS In a real-world setting patients receiving HFA-beclomethasone had a similar or better chance of achieving asthma control at lower prescribed doses than with fluticasone.

Steroid sex hormones and peripheral arterial disease in the Edinburgh Artery Study

Although treatment with high dose exogenous sex hormones affects cardiovascular risk, the role of physiological levels of endogenous sex hormones in the development of atherosclerotic disease in men and women is unknown. Forty men and 43 women wit peripheral arterial disease and 88 age- and sex-matched controls were selected from participants in the Edinburgh Artery Study, a random survey of 1592 men and women ages 55-74 years from the general population. Compared with sex-matched controls, male cases had higher systolic blood pressure (155.5 mmHg vs. 138.7 mmHg; p < or = 0.01) and waist hip ratio (0.92 vs. 0.89; p < or = 0.05) and female cases had higher lifetime smoking (square root of packyears 2.14 vs. 1.03; p < or = 0.05). Mean estrone levels were slightly higher in male cases than controls (101.9 pmol/Liter vs. 92.1 pmol/Liter; p = 0.09), but this association lost significance after multivariate adjustment for age and body mass index. Mean levels of total and free testosterone, estradiol, and sex hormone binding globulin were not significantly different in cases compared with controls in either sex (p > 0.1). These results, in accordance with previous prospective studies on coronary artery disease, do not support a role for physiological levels of endogenous sex hormones in the development of peripheral arterial disease in men or postmenopausal women.

The distribution of COPD in UK general practice using the new GOLD classification

The new Global Initiative for Chronic Obstructive Lung Disease (GOLD) 2011 document recommends a combined assessment of chronic obstructive pulmonary disease (COPD) based on current symptoms and future risk. A large database of primary-care COPD patients across the UK was used to determine COPD distribution and characteristics according to the new GOLD classification. 80 general practices provided patients with a Read code diagnosis of COPD. Electronic and hand searches of patient medical records were undertaken, optimising data capture. Data for 9219 COPD patients were collected. For the 6283 patients with both forced expiratory volume in 1 s (FEV1) and modified Medical Research Council scores (mean±sd age 69.2±10.6 years, body mass index 27.3±6.2 kg·m−2), GOLD 2011 group distributions were: A (low risk and fewer symptoms) 36.1%, B (low risk and more symptoms) 19.1%, C (high risk and fewer symptoms) 19.6% and D (high risk and more symptoms) 25.3%. This is in contrast with GOLD 2007 stage classification: I (mild) 17.1%, II (moderate) 52.2%, III (severe) 25.5% and IV (very severe) 5.2%. 20% of patients with FEV1 ≥50% predicted had more than two exacerbations in the previous 12 months. 70% of patients with FEV1 <50% pred had fewer than two exacerbations in the previous 12 months. This database, representative of UK primary-care COPD patients, identified greater proportions of patients in the mildest and most severe categories upon comparing 2011 versus 2007 GOLD classifications. Discordance between airflow limitation severity and exacerbation risk was observed. GOLD 2011 COPD classification criteria identified more patients in the mildest and more severe groups than GOLD 2007 http://ow.ly/t4uiO

Practice development plans to improve the primary care management of acute asthma: randomised controlled trial

BackgroundOur professional development plan aimed to improve the primary care management of acute asthma, which is known to be suboptimal.MethodsWe invited 59 general practices in Grampian, Scotland to participate. Consenting practices were randomised to early and delayed intervention groups. Practices undertook audits of their management of all acute attacks (excluding children under 5 years) occurring in the 3 months preceding baseline, 6-months and 12-months study time-points. The educational programme [including feedback of audit results, attendance at a multidisciplinary interactive workshop, and formulation of development plan by practice teams] was delivered to the early group at baseline and to the delayed group at 6 months. Primary outcome measure was recording of peak flow compared to best/predicted at 6 months. Analyses are presented both with, and without adjustment for clustering.Results23 consenting practices were randomised: 11 to early intervention. Baseline practice demography was similar. Six early intervention practices withdraw before completing the baseline audit. There was no significant improvement in our primary outcome measure (the proportion with peak flow compared to best/predicted) at either the 6 or 12 month time points after adjustment for baseline and practice effects. However, the between group difference in the adjusted combined assessment score, whilst non-significant at 6 months (Early: 2.48 (SE 0.43) vs. Delayed 2.26 (SE 0.33) p = 0.69) reached significance at 12 m (Early:3.60 (SE 0.35) vs. Delayed 2.30 (SE 0.28) p = 0.02).ConclusionWe demonstrated no significant benefit at the a priori 6-month assessment point, though improvement in the objective assessment of attacks was shown after 12 months. Our practice development programme, incorporating audit, feedback and a workshop, successfully engaged the healthcare team of participating practices, though future randomised trials of educational interventions need to recognise that effecting change in primary care practices takes time. Monitoring of the assessment of acute attacks proved to be a feasible and responsive indicator of quality care.

Hyperinsulinaemia: A Risk Factor for Peripheral Arterial Disease in the Non-Diabetic General Population:

Background Peripheral arterial disease is a common complication of diabetes mellitus, and hyperinsulinaemia has been associated with an increased incidence of intermittent claudication in diabetic subjects. Our aim was to investigate the relationship between hyperinsulinaemia and peripheral arterial disease in the non-diabetic general population. Methods Eighty-three cases with peripheral arterial disease and 88 age- and sex-matched controls were selected from non-diabetic participants in the Edinburgh Artery Study, a survey of 1592 men and women aged 55-74 years randomly selected from the general population. Results Mean plasma insulin, 1 h after a 75 g oral glucose load, was higher in cases than in controls (73.6 versus 59.8 mU/l; P < 0.05). The relationship between insulin and disease was independent of blood pressure [odds ratio (OR) 2.04; 95% Cl 1.11-3.74; P ≤ 0.05] and partially independent of low- and high-density lipoprotein cholesterol and triglycerides (OR 1.86; 95% Cl 0.99-3.48; P ≤ 0.1). Mean 1 h insulin was higher in current or ex-smokers than in those who had never smoked (P ≤ 0.05) and when smoking was added to the multivariate model, the relationship between insulin and disease diminished (OR 1.64: 95% Cl 0.83-3.23; P > 0.1). Conclusions In the non-diabetic general population, peripheral arterial disease is associated with post-glucose hyperinsulinaemia, independently of blood pressure, lipoproteins and triglycerides. Some of this association may be mediated by a relationship between hyperinsulinaemia and smoking.

Physiotherapy breathing retraining for asthma: a randomised controlled trial

Summary Background Despite effective pharmacotherapy, asthma continues to impair quality of life for most patients. Non-pharmacological approaches, including breathing retraining, are therefore of great interest to patients. However, clinicians rarely advocate breathing retraining and access to this intervention is restricted for most patients due to the limited availability of suitable physiotherapists and poor integration of breathing retraining into standard care. We aimed to assess the effectiveness of a digital self-guided breathing retraining intervention. Methods In this randomised controlled trial, we recruited patients from 34 general practices in the UK. Eligibility criteria for patients with asthma were broad, comprising a physician diagnosis of asthma, age of 16–70 years, receipt of at least one anti-asthma medication in the previous year, and impaired asthma-related quality of life (Asthma Quality of Life Questionnaire [AQLQ] score of <5·5). We developed a self-guided intervention, which was delivered as a DVD plus a printed booklet (DVDB). Participants were randomly assigned to receive either the DVDB intervention, three face-to-face breathing retraining sessions, or standard care, in a 2:1:2 ratio, for 12 months. Randomisation was achieved using the Southampton Clinical Trials Unit telephone randomisation service by use of random number generators. The primary outcome was the AQLQ score in the intention-to-treat population at 12 months. The trial was powered to show equivalence between the two active intervention groups, and superiority of both intervention groups over usual care. Secondary outcomes included patient-reported and physiological measures of asthma control, patient acceptability, and health-care costs. This trial was registered with International Standard Randomised Controlled Trial Number registry, number ISRCTN88318003. Findings Between Nov 5, 2012 and Jan 28, 2014, invitations to participate in the study were sent to 15 203 patients with general practitioner-diagnosed asthma, of whom 655 were recruited into the study. AQLQ scores at 12 months were significantly higher in the DVDB group (mean 5·40, SD 1·14) than in the usual care group (5·12, SD 1·17; adjusted mean difference 0·28, 95% CI 0·11 to 0·44), and in the face-to-face group (5·33, SD 1·06) than in the usual care group (adjusted mean difference 0·24, 95% CI 0·04 to 0·44); AQLQ scores were similar between the DVDB group and the face-to-face group (0·04, 95% CI −0·16 to 0·24). There were no significant differences between the randomisation groups in FEV1 or fraction of exhaled nitric oxide. 744 adverse events occurred in 272 patients: 101 (39%) of 261 patients in the DVDB group, 55 (42%) of 132 patients in the face-to-face group, and 132 (50%) of 262 in the usual care group, with patients reporting one or more event. 11 (4%) patients in the DVDB group, four (3%) patients in the face-to-face group, and 20 (8%) patients in the usual care group had a serious adverse event. Interpretation Breathing retraining programmes improve quality of life in patients with incompletely controlled asthma despite having little effect on lung function or airway inflammation. Such programmes can be delivered conveniently and cost-effectively as a self-guided digital audiovisual programme, so might also reduce health-care costs. Funding UK National Institute of Health Research.

A comparison of computerised strain gauge plethysmography with D-dimer testing in screening for deep-vein thrombosis

There has been a significant increase in the amount of diagnostic testing performed to confirm or refute a diagnosis of deep‐vein thrombosis (DVT), often in low‐risk patients. d‐dimer testing and computer‐assisted strain gauge plethysmography (SGP) are rapid, inexpensive methods of excluding DVT and, in combination with a clinical probability score for DVT, both have been used to accurately exclude DVT. d‐dimer testing, SGP and a combination of both in excluding DVT were compared in 243 ambulant outpatients who followed a prespecified investigation protocol. The negative‐predictive value of d‐dimer testing alone was 100%, 93·9% (95% CI 93·6–94·1) and 80% (95% CI 73·7–86·3) in patients with a low, moderate and high pretest probability (PTP) score for DVT respectively. The corresponding results for SGP were 95·6% (95% CI 95·5–95·7), 86·1% (95% CI 85·9–86·4) and 77·8% (95% CI 75·9–79·7) in patients with a low, moderate and high PTP score for DVT respectively. d‐dimer testing provided a rapid, cost‐effective method for excluding DVT in low‐risk ambulant patients, which was superior to SGP. Combined use of the modalities did not improve any aspect of clinical decision making.

Effect of Theophylline as Adjunct to Inhaled Corticosteroids on Exacerbations in Patients With COPD: A Randomized Clinical Trial

Importance Chronic obstructive pulmonary disease (COPD) is a major global health issue and theophylline is used extensively. Preclinical investigations have demonstrated that low plasma concentrations (1-5 mg/L) of theophylline enhance antiinflammatory effects of corticosteroids in COPD. Objective To investigate the effectiveness of adding low-dose theophylline to inhaled corticosteroids in COPD. Design, Setting, and Participants The TWICS (theophylline with inhaled corticosteroids) trial was a pragmatic, double-blind, placebo-controlled, randomized clinical trial that enrolled patients with COPD between February 6, 2014, and August 31, 2016. Final follow-up ended on August 31, 2017. Participants had a ratio of forced expiratory volume in the first second to forced vital capacity (FEV1/FVC) of less than 0.7 with at least 2 exacerbations (treated with antibiotics, oral corticosteroids, or both) in the previous year and were using an inhaled corticosteroid. This study included 1578 participants in 121 UK primary and secondary care sites. Interventions Participants were randomized to receive low-dose theophylline (200 mg once or twice per day) to provide plasma concentrations of 1 to 5 mg/L (determined by ideal body weight and smoking status) (n = 791) or placebo (n = 787). Main Outcomes and Measures The number of participant-reported moderate or severe exacerbations treated with antibiotics, oral corticosteroids, or both over the 1-year treatment period. Results Of the 1567 participants analyzed, mean (SD) age was 68.4 (8.4) years and 54% (843) were men. Data for evaluation of the primary outcome were available for 1536 participants (98%) (772 in the theophylline group; 764 in the placebo group). In total, there were 3430 exacerbations: 1727 in the theophylline group (mean, 2.24 [95% CI, 2.10-2.38] exacerbations per year) vs 1703 in the placebo group (mean, 2.23 [95% CI, 2.09-2.37] exacerbations per year); unadjusted mean difference, 0.01 (95% CI, −0.19 to 0.21) and adjusted incidence rate ratio, 0.99 (95% CI, 0.91-1.08). Serious adverse events in the theophylline and placebo groups included cardiac, 2.4% vs 3.4%; gastrointestinal, 2.7% vs 1.3%; and adverse reactions such as nausea (10.9% vs 7.9%) and headaches (9.0% vs 7.9%). Conclusions and Relevance Among adults with COPD at high risk of exacerbation treated with inhaled corticosteroids, the addition of low-dose theophylline, compared with placebo, did not reduce the number COPD exacerbations over a 1-year period. The findings do not support the use of low-dose theophylline as adjunctive therapy to inhaled corticosteroids for the prevention of COPD exacerbations. Trial Registration isrctn.org Identifier: ISRCTN27066620