The impact of cardiovascular risk factors on aortic stiffness and wave reflections depends on age: The Anglo-Cardiff Collaborative Trial (ACCT III)

Ageing exerts differential effects on arterial stiffness and wave reflections. However, the impact of cardiovascular risk factors on arterial stiffness and wave reflections and, particularly, how such effects are influenced by ageing has not been assessed within a single large population, covering a sufficiently wide age range. Therefore, we determined the extent to which age alters the impact of traditional cardiovascular risk factors on arterial stiffness and wave reflections. Aortic stiffness and wave reflections were assessed in 4421 individuals (age range 18 to 92 years). When treated as continuous variables, clinic systolic, diastolic, and pulse pressures and glucose levels were independently associated with stiffness, and, with the exception of diastolic pressure, these associations were more marked in older individuals. In contrast, clinic systolic and diastolic pressures and smoking were independently associated with wave reflections, with stronger associations observed in younger individuals. The impact of traditional cardiovascular risk factors on arterial stiffness and wave reflections is strongly dependent on age and is largely driven by blood pressure. Additional studies are required to assess the impact of these arterial measures on cardiovascular outcome within a single population

Clinical trial of focal segmental glomerulosclerosis in children and young adults

This NIH-funded multicenter randomized study of focal segmental glomerulosclerosis (FSGS) treatment compared the efficacy of a 12-month course of cyclosporine to a combination of oral pulse dexamethasone and mycophenolate mofetil in children and adults with steroid-resistant primary FSGS. Of the 192 patients enrolled, 138 were randomized to cyclosporine (72) or to mycophenolate/dexamethasone (66). The primary analysis compared the levels of an ordinal variable measuring remission during the first year. The odds ratio (0.59) for achieving at least a partial remission with mycophenolate/dexamethasone compared to cyclosporine was not significant. Partial or complete remission was achieved in 22 mycophenolate/dexamethasone- and 33 cyclosporine-treated patients at 12 months. The main secondary outcome, preservation of remission for 26 weeks following cessation of treatment, was not significantly different between these two therapies. During the entire 78 weeks of study, 8 patients treated with cyclosporine and 7 with mycophenolate/dexamethasone died or developed kidney failure. Thus, our study did not find a difference in rates of proteinuria remission following 12 months of cyclosporine compared to mycophenolate/dexamethasone in patients with steroid-resistant FSGS. However, the small sample size might have prevented detection of a moderate treatment effect

Clinical trials treating focal segmental glomerulosclerosis should measure patient quality of life

Optimal therapy of patients with steroid-resistant primary focal segmental glomerulosclerosis (FSGS) remains controversial. This report describes the initial study design, baseline characteristics, and quality of life of patients enrolled in the FSGS Clinical Trial, a large multicenter randomized study of this glomerulopathy comparing a 12-month regimen of cyclosporine to the combination of mycophenolate mofetil and oral dexamethasone. Patients with age ranging 2–40 years, with an estimated glomerular filtration rate >40 ml/min per 1.73 m2, a first morning urine protein-to-creatinine ratio over one, and resistant to corticosteroids were eligible. The primary outcome was complete or partial remission of proteinuria over 52 weeks after randomization. In all, 192 patients were screened, of whom 138 were randomized for treatment. Ethnic distributions were 53 black, 78 white, and 7 other. By self- or parent-proxy reporting, 26 of the 138 patients were identified as Hispanic. The baseline glomerular filtration rate was 112.4 (76.5, 180.0) ml/min per 1.73 m2, and urine protein was 4.0 (2.1, 5.3) g/g. Overall, the quality of life of the patients with FSGS was lower than healthy controls and similar to that of patients with end-stage renal disease. Thus, the impact of FSGS on quality of life is significant and this measurement should be included in all trials

Genome-wide association study identifies six new loci influencing pulse pressure and mean arterial pressure.

Numerous genetic loci have been associated with systolic blood pressure (SBP) and diastolic blood pressure (DBP) in Europeans. We now report genome-wide association studies of pulse pressure (PP) and mean arterial pressure (MAP). In discovery (N = 74,064) and follow-up studies (N = 48,607), we identified at genome-wide significance (P = 2.7 × 10(-8) to P = 2.3 × 10(-13)) four new PP loci (at 4q12 near CHIC2, 7q22.3 near PIK3CG, 8q24.12 in NOV and 11q24.3 near ADAMTS8), two new MAP loci (3p21.31 in MAP4 and 10q25.3 near ADRB1) and one locus associated with both of these traits (2q24.3 near FIGN) that has also recently been associated with SBP in east Asians. For three of the new PP loci, the estimated effect for SBP was opposite of that for DBP, in contrast to the majority of common SBP- and DBP-associated variants, which show concordant effects on both traits. These findings suggest new genetic pathways underlying blood pressure variation, some of which may differentially influence SBP and DBP

Large expert-curated database for benchmarking document similarity detection in biomedical literature search

Document recommendation systems for locating relevant literature have mostly relied on methods developed a decade ago. This is largely due to the lack of a large offline gold-standard benchmark of relevant documents that cover a variety of research fields such that newly developed literature search techniques can be compared, improved and translated into practice. To overcome this bottleneck, we have established the RElevant LIterature SearcH consortium consisting of more than 1500 scientists from 84 countries, who have collectively annotated the relevance of over 180 000 PubMed-listed articles with regard to their respective seed (input) article/s. The majority of annotations were contributed by highly experienced, original authors of the seed articles. The collected data cover 76% of all unique PubMed Medical Subject Headings descriptors. No systematic biases were observed across different experience levels, research fields or time spent on annotations. More importantly, annotations of the same document pairs contributed by different scientists were highly concordant. We further show that the three representative baseline methods used to generate recommended articles for evaluation (Okapi Best Matching 25, Term Frequency-Inverse Document Frequency and PubMed Related Articles) had similar overall performances. Additionally, we found that these methods each tend to produce distinct collections of recommended articles, suggesting that a hybrid method may be required to completely capture all relevant articles. The established database server located at https://relishdb.ict.griffith.edu.au is freely available for the downloading of annotation data and the blind testing of new methods. We expect that this benchmark will be useful for stimulating the development of new powerful techniques for title and title/abstract-based search engines for relevant articles in biomedical research.Peer reviewe

Use of arterial transfer functions for the derivation of central aortic waveform characteristics in subjects with type 2 diabetes and cardiovascular disease - Response to Hope et al

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M19 The impact of co-morbidities on physical function and health status in chronic obstruction pulmonary disease (COPD)

Background Co-morbidities are of increasing importance in patients with COPD. However, the implications for function and health status have not been fully established. We hypothesised that the number of co-morbidities would relate to physical capacity, health status and impairments as measured by the comprehensive geriatric assessment (CGA) in COPD but not comparator subjects. Method As part of the longitudinal Assessment of Risk in Chronic Airways Disease Evaluation (ARCADE), 500 patients with stable COPD (confirmed with spirometry) were compared to 141 comparator subjects (past or current smokers) free from respiratory disease. In all subjects previously diagnosed co-morbidities including; hypertension, hypercholesterolemia, angina, myocardial infarction, Stroke/TIA, atrial fibrillation, diabetes, and osteoporosis were recorded using a standardised health questionnaire. Spirometry, BMI, six minute walk distance (6MWD), the Timed Up and Go (TUG), and the number of impairments were determined using the CGA. Patients with COPD also completed the St George’s Respiratory Questionnaire (SGRQ). Results Patients and comparators were similar in age, gender and BMI, but differed in FEV1% predicted 59 (20) and 105 (14) respectively (p < 0.01). Patients had more co-morbidities median (range) 2 (0–6) than comparators 1 (0–3) (p < 0.01). Of the patients, 24% had no co-morbidity, 54% had 1–2 co-morbidities and 22% had over 3 co-morbidities, while 54% of comparators had no co-morbidities and 45% had 1–2 co-morbidities (p < 0.01). Patients also had more impairments (CGA score), reduced 6MWD and increased TUG (all p < 0.001). The number of co-morbidities related to age, BMI, 6MWD, TUG, fibrinogen, the CGA and SGRQ and but not FEV1 in patients with COPD, and only to CGA score in comparators (Table 1)

The Framingham risk score in chronic obstructive pulmonary disease (COPD)

Patients with chronic obstructive pulmonary disease (COPD) have increased risk of cardiovascular (CV) events and mortality beyond that attributable to smoking. Although identifying CV risk in COPD is difficult, aortic pulse wave velocity (aPWV), a validated measure of arterial stiffness and an independent predictor of cardiovascular (CV) outcomes, is elevated in patients with COPD. We hypothesised that patients with COPD would have greater Framingham risk score and aPWV than controls and that aPWV would relate to Framingham risk score. Methods At baseline 524 patients with COPD and 143 controls (free from lung disease) were assessed for; lung function (forced expiratory volume (FEV1), forced vital capacity (FVC) and their ratio), blood pressure (BP), BMI, aPWV and blood pressure (BP). In addition, medical and smoking history were recorded and used to calculate the Framingham risk score and vascular age. Results Patients and controls were similar in age, gender and BMI, but patients had greater aPWV, Framingham risk score and vascular age (Table 1), which remained after adjustment for age, and MAP. In COPD, Framingham risk related to age r=0.295, aPWV r=2.34, SBP r=0.194 and FEV1% predicted r=0.112, (all p<0.01). In controls, Framingham risk score related only to age r=383, aPWV r=0.189 and systolic BP r=0.195 p<0.05. Conclusions The association between the Framingham risk score and aPWV suggests that either may be useful to identify individuals with COPD at risk of future CV events. The presence of increased vascular age which related to aPWV suggests that patients with COPD may have premature vascular aging which may explain the excess CV risk. Further follow-up of this cohort will evaluate the prognostic utility of these measures of CV risk