BACKGROUND:As life expectancy increases, the population of older individuals with coronary artery disease and frailty is growing. We aimed to assess the impact of patient-reported frailty on the treatment and prognosis of elderly early survivors of non-ST-elevation acute coronary syndrome (NSTE-ACS). METHODS:Frailty data were obtained from two prospective trials, POPular Age and the POPular Age Registry, which both assessed elderly NSTE-ACS patients. Frailty was assessed one month after admission with the Groningen Frailty Indicator (GFI) and was defined as a GFI-score of 4 or higher. In these early survivors of NSTE-ACS, we assessed differences in treatment and 1-year outcomes between frail and non-frail patients, considering major adverse cardiovascular events (MACE, including cardiovascular mortality, myocardial infarction, and stroke) and major bleeding. RESULTS:The total study population consisted of 2192 NSTE-ACS patients, aged ≥70 years. The GFI-score was available in 1320 patients (79 ± 5 years, 37% women), of whom 712 (54%) were considered frail. Frail patients were at higher risk for MACE than non-frail patients (9.7% vs. 5.1%, adjusted hazard ratio [HR] 1.57, 95% confidence interval [CI] 1.01-2.43, p = 0.04), but not for major bleeding (3.7% vs. 2.8%, adjusted HR 1.23, 95% CI 0.65-2.32, p = 0.53). Cubic spline analysis showed a gradual increase of the risk for clinical outcomes with higher GFI-scores. CONCLUSIONS:In elderly NSTE-ACS patients who survived 1-month follow-up, patient-reported frailty was independently associated with a higher risk for 1-year MACE, but not with major bleeding. These findings emphasize the importance of frailty screening for risk stratification in elderly NSTE-ACS patients.

BACKGROUND Whether a conservative strategy of medical therapy alone or a strategy of medical therapy plus invasive treatment is more beneficial in older adults with non-ST-segment elevation myocardial infarction (NSTEMI) remains unclear. METHODS We conducted a prospective, multicenter, randomized trial involving patients 75 years of age or older with NSTEMI at 48 sites in the United Kingdom. The patients were assigned in a 1:1 ratio to a conservative strategy of the best available medical therapy or an invasive strategy of coronary angiography and revascularization plus the best available medical therapy. Patients who were frail or had a high burden of coexisting conditions were eligible. The primary outcome was a composite of death from cardiovascular causes (cardiovascular death) or nonfatal myocardial infarction assessed in a time-to-event analysis. RESULTS A total of 1518 patients underwent randomization; 753 patients were assigned to the invasive-strategy group and 765 to the conservative-strategy group. The mean age of the patients was 82 years, 45% were women, and 32% were frail. A primary-outcome event occurred in 193 patients (25.6%) in the invasive-strategy group and 201 patients (26.3%) in the conservative-strategy group (hazard ratio, 0.94; 95% confidence interval [CI], 0.77 to 1.14; P=0.53) over a median follow-up of 4.1 years. Cardiovascular death occurred in 15.8% of the patients in the invasive-strategy group and 14.2% of the patients in the conservative-strategy group (hazard ratio, 1.11; 95% CI, 0.86 to 1.44). Nonfatal myocardial infarction occurred in 11.7% in the invasive-strategy group and 15.0% in the conservative-strategy group (hazard ratio, 0.75; 95% CI, 0.57 to 0.99). Procedural complications occurred in less than 1% of the patients. CONCLUSIONS In older adults with NSTEMI, an invasive strategy did not result in a significantly lower risk of cardiovascular death or nonfatal myocardial infarction (the composite primary outcome) than a conservative strategy over a median follow-up of 4.1 years.

Abstract Objectives Acute heart failure (AHF) hospitalisation is associated with 10% mortality. Outpatient based management (OPM) of AHF appeared effective in observational studies. We conducted a pilot randomised controlled trial (RCT) comparing OPM with standard inpatient care (IPM). Methods We randomised patients with AHF, considered to need IV diuretic treatment for ≥2 days, to IPM or OPM. We recorded all-cause mortality, and the number of days alive and out-of-hospital (DAOH). Quality of life, mental well-being and Hope scores were assessed. Mean NHS cost savings and 95% central range (CR) were calculated from bootstrap analysis. Follow-up: 60 days. Results Eleven patients were randomised to IPM and 13 to OPM. There was no statistically significant difference in all-cause mortality during the index episode (1/11 vs 0/13) and up to 60 days follow-up (2/11 vs 2/13) [p = .86]. The OPM group accrued more DAOH {47 [36,51] vs 59 [41,60], p = .13}. Two patients randomised to IPM (vs 6 OPM) were readmitted [p = .31]. Hope scores increased more with OPM within 30 days but dropped to lower levels than IPM by 60 days. More out-patients had increased total well-being scores by 60 days (p = .04). OPM was associated with mean cost savings of £2658 (95% CR 460–4857) per patient. Conclusions Patients with acute HF randomised to OPM accrued more days alive out of hospital (albeit not statistically significantly in this small pilot study). OPM is favoured by patients and carers and is associated with improved mental well-being and cost savings.

Abstract Introduction Recommendations regarding the threshold levels of cardiac troponin elevations for the definition of peri-operative myocardial infarction and clinically important peri-procedural myocardial injury in patients undergoing cardiac surgery range widely (>10 to ≥70x the upper limit of normal (ULN)) (1,2). Limited evidence is available to support these recommendations. In a recent multicentre cohort study, Devereaux and colleagues (3) characterised appropriate thresholds of high-sensitivity troponin-I (hs-TnI) for defining myocardial injury within 3 days after cardiac surgery. The threshold associated with an increased risk of 30-day mortality after coronary artery bypass grafting (CABG) was 218 xULN (95% confidence interval (CI), 40-318) of the hs-TnI assay. There have been no large studies assessing this threshold using high-sensitivity troponin-T (hs-TnT). Furthermore, the long-term prognostic value of troponin following CABG is unknown. Purpose The aim of our study was to assess the threshold associated with an increased risk of 30-day and 5-year mortality using hs-TnI assays, and to compare these thresholds to those using hs-TnT assays. Methods A retrospective cohort study was carried out using the National Institute for Health Research Health Informatics Collaborative Cardiovascular dataset (4,5) of all consecutive patients who had a troponin measured at five hospitals between 2010 and 2017. Patients who had a troponin measurement within three days following CABG were identified. Results were analysed using multivariable adjusted restricted cubic spline Cox regression. All hazard ratios were adjusted for the following components of the European System for Cardiac Operative Risk Evaluation II (EuroSCORE II); age, gender, renal impairment, poor mobility, chronic lung disease, diabetes, left ventricular function, and pulmonary hypertension. Analyses on troponin were performed using the peak troponin level, which was the highest troponin level measured within the first three days following CABG. All troponin measurements were high-sensitivity and were standardised by using the ratio of the observed troponin value divided by the ULN for each troponin assay. The reference for hazard ratios was a troponin level of 1 xULN. Results A total of 1055 patients (median age 72 years (interquartile range 63 to 78), 79% male) had a troponin measured within three days post-CABG at the five centres between 2010 and 2017. The threshold for hs-TnI associated with an increased mortality risk was 196xULN (95%CI, 42-494) for predicting 30-day mortality (Figure 1A) and 157xULN (95%CI, 32-409) for 5-year mortality (Figure 1B). The thresholds were similar for hs-TnT assays (Figure 1C and 1D). Conclusion The currently recommended troponin thresholds for diagnosing significant myocardial injury following cardiac surgery (>10 to ≥70xULN) are too low. There was good correlation between hs-TnI and hs-TnT measurements for predicting both short- and long-term mortality.Figure 1

Abstract Background/Introduction Elderly constitute a large though specific group of patients presenting with non-ST elevation myocardial infarction (NSTEMI), as they are at higher risk of adverse cardiovascular events, as well as treatment-related complications. However as they underrepresented in clinical trials, the optimal management strategy for older patients with NSTEMI remains unclear. Purpose The aim of this registry was to capture the medical and invasive treatment of elderly NSTEMI patients, find predictors for major adverse cardiovascular events (MACE) and estimate the impact of invasive management and revascularisation. Methods The POPular AGE registry is a prospective, observational multicentre study of patients ≥75 years of age presenting with NSTEMI at multiple sites in the Netherlands, United Kingdom and Austria. Management was at the discretion of the treating physician. MACE consisted of cardiovascular death, acute coronary syndrome (ACS) and stroke. Net adverse clinical events (NACE) was defined as composite of all-cause death, ACS, definite stent thrombosis, stroke, or major bleeding (Bleeding Academic Research Consortium [BARC] bleeding 3 or 5). The population was stratified into an invasively treated group defined as patients who underwent coronary angiography (CAG); and a conservatively-treated group with patients who received medical treatment only. The duration of follow-up was one year. Clinical variables were assessed for their predictive value for MACE and bleeding by means of a Cox proportional hazard regression. Results The total study population consisted of 1190 elderly patients with NSTEMI (median age 80 years [IQR 77–84], 43% female). Invasive treatment with CAG was performed in 67% of the population, of which 49% underwent PCI and 14% coronary artery bypass grafting (CABG). At discharge, the majority of patients (55%) were treated with dual antiplatelet therapy (DAPT). MACE occurred in 15% and major bleeding occurred in 5% of the total population. Age (HR 1.06, 95% CI 1.03–1.09), diabetes mellitus (HR 1.62, 95% CI 1.16–2.24), reduced LVEF (<50%) (HR 1.51, 95% CI 1.03–2.20), Killip class (HR 1.58, 95% CI 1.07–2.33) and electrocardiogram (ECG) changes at admission (HR 1.67, 95% CI 1.20–2.31) were predictors for MACE. MACE occurred more frequently in conservatively-treated than invasively-treated patients (20% vs. 12%, HR 0.52, 95% CI 0.38–0.70, p<0.001). Revascularization with PCI or CABG was associated with lower risk of MACE (PCI; HR 0.47, 95% CI 0.30–0.75, p=0.001 and CABG; HR 0.31, 95% CI 0.13– 0.73, p=0.008). Conclusions In this prospective registry of NSTEMI patients of ≥75 years, MACE and major bleeding were frequent. Age, diabetes mellitus, reduced LVEF, Killip class and ECG changes at admission were independent predictors for MACE. Although subject to selection bias, undergoing CAG and revascularisation, when indicated, were associated with better outcomes. Funding Acknowledgement Type of funding sources: Private company. Main funding source(s): AstraZeneca

well-being. But the initial increase in hope diminished within 60 days, possibly as a result of increased readmissions. The pilot RCT generated important hypotheses that need further testing in a large multicentre RCT

Gail Galasko, PhD provides her perspective as a professor of pharmacology and researcher working in the area of diabetes research. Dr. Galasko encourages those working with diabetes to communicate the bigger picture of diabetes and its complications by raising awareness of some newer research findings in the field.

J. Neurochem. (2012) 122 , 605–618. Abstract Neurons located in the trigeminal subnucleus caudalis (Vc) play crucial roles in pain and sensorimotor functions in the orofacial region. Because of many anatomical and functional similarities with the spinal dorsal horn (SDH), Vc has been termed the medullary dorsal horn ‐ analogous to the SDH. Here, we report that when compared with embryonic SDH neurons in culture, neurons isolated from the Vc region showed significantly slower growth, lower glutamate receptor activity, and more cells undergoing cell death. SDH neuron development was inhibited in co‐cultures of SDH and Vc tissues while Vc neuron development was promoted by co‐culture with SDH tissues. Furthermore, we identified that small (non‐protein) ninhydrin‐reacting molecules purified from either embryonic or post‐natal Vc‐conditioned medium inhibited neuronal growth whereas ninhydrin‐reacting molecules from SDH‐conditioned medium promoted neuronal growth. These findings suggest the involvement of locally released factors in the region‐specific regulation of neuronal development in Vc and SDH, central nervous system regions playing critical roles in pain, and point to novel avenues for investigating central nervous system regionalization and for designing therapeutic approaches to manage neurodegenerative diseases and pain.

Adequate vitamin D is essential for good health. It is important that physicians are aware that deficiency occurs even in areas with plentiful sunshine. We used e-mail distribution lists to anonymously survey physicians (MDs) and non-physicians (non-MDs) of a Southeastern USA medical school in order to determine awareness of conditions associated with vitamin D deficiency, percentage of subjects who had had their vitamin D levels checked, percentage of subjects who were aware they had low vitamin D, MD-recommended doses for supplementation, and MD factors associated with recommending doses >800 IU/day. A minority (21%) of all subjects had their vitamin D level checked and two thirds of those who knew their level reported it low. Multivariate logistic regression showed: 1) having vitamin D checked was associated with personally taking vitamin D, 2) MDs were more likely to take vitamin D than non-MDs, and 3) a trend that MDs who had their vitamin D level checked recommended higher supplementary doses (≥800 IU/day) for their patients. Low self-reported vitamin D levels are prevalent in our sample of MDs and non-MDs living in an area of the USA with plentiful sunshine.

Cushing's syndrome is an endocrine disease characterized by prolonged exposure to high levels of glucocorticosteroids. Cushings syndrome may be due to the systemic administration of exogenous glucocorticosteroids (the most common cause), overproduction of cortisol by the …

The Elecsys NT-proBNP assay is based on two polyclonal antibodies directed at residues 1-21 and 39-50 of the NT-proBNP molecule. Analytical performance was assessed using NCCLS protocol EP-5A using three serum pools in a preliminary study then as part of a multicentre evaluation (16 instruments in 8 hospitals). Using pools of 350 pg/l, 8700 pg/l and 13000 pg/l single site within run %CV was 0.7-1.6 (1010) and 1.2-1.5 (2010) and between run CV 5.3-6.7 (1010) and 4.4-5.0 (2010). In the multicentre evaluation within run CV was 1.0-2.5% with total imprecision 1.5-2.5% and between labs imprecision 3.8-4.0%. Functional sensitivity of <50 pg/l and measuring range to 35000 pg/l. There was excellent agreement between instrument platforms, y=0.97x+2.6; r=1.00 (n=215) for Elecsys 2010 (x) vs. Elecsys 1010 (y) and y=1.02x-0.3; r=1.00 (n=99) for Elecsys 2010 (x) vs. E 170 (y). Serum and heparin plasma samples showed good agreement but lower values were seen in EDTA plasma. Samples were stable for 7 days at room temperature; 21 days at 4 degrees C and for 5 freeze thaw cycles. Samples were obtained from a population of 1205 (671 male, 534 female) apparently healthy individuals screened by echocardiography and symptom questionnaire. There was poor correlation with NT-proANP (ELISA) (rs 0.33) and modest correlation with BNP (rs 0.89) with NT-proBNP values approximately 5 times greater than BNP (Biosite Triage). In a subset of 320 with normal ejection fraction (>50%) and no risk factors, NT-proBNP values increased with age and were higher in women than men.

Background: N-terminal pro-B type natriuretic peptide (NTpBNP) is a potential marker of cardiac failure. Methods: The Roche ElecsysTM 1010 and 2010 assays for NTpBNP were evaluated for precision, sample stability, and correlation between sample types and with other natriuretic peptides. Samples from 290 individuals aged 45-89 years with no cardiovascular risk factors, renal failure, electrocardiogram changes, evidence of structural abnormalities, or wall motion abnormalities on echocardiography and with an ejection fraction >50% were used to provide reference NTpBNP ranges. Results: The intra-assay imprecision was <10% across the analytical range and >3% at all concentrations analysed <30 ng/L. Inter-assay imprecision was 5.3-6.7% on the Elecsys 1010 and 4.4-5.0% on the Elecsys 2010, in the range 380-13000 ng/L. There was no statistically significant change in NTpBNP following storage in whole-blood samples at room temperature for 24 h before centrifugation; serum samples at room temperature for 7 days, at 4°C for up to 11 days on clot-activation gel or 22 days separated from the gel. NTpBNP concentrations were stable throughout five freeze-thaw cycles. There was a close correlation between NTpBNP concentrations in matched serum, EDTA plasma and lithium-heparin plasma samples. NTpBNP and BNP were more closely associated than were N-terminal proatrial natriuretic peptide and NTpBNP. This association was stronger at lower concentrations. NTpBNP concentrations increased with age, with values higher in women than men. Conclusions: NTpBNP is a stable molecule that can be measured easily and precisely using the Roche Elecsys 1010 or 2010 immunoassay analysers.

Left ventricular (LV) hypertrophy (LVH) confers increased cardiovascular risk on patients with hypertension. Echocardiography using new hand-held devices might allow community-based cost-effective screening for LVH in a targeted hypertensive population. Thus, the aim of this study was to test the validity of hand-held ultrasound devices to screen for LVH in the community. Accordingly, 189 patients with hypertension attending a community-based heart failure screening program underwent echocardiography by both hand-held and standard devices by an experienced echocardiographer. LVH was defined as LV mass index ≥134 g.m−2 for men and ≥110 g.m−2 for women using the Devereux-modified American Society of Echocardiography cube equation. No significant differences were noted between the 2 devices in the measurement of LV wall thickness or LV mass index. Agreement for estimation of LVH between the 2 devices was 86% (κ = 0.63). The sensitivity, specificity, and positive and negative predictive values of the hand-held device for predicting LVH were 72%, 91%, 73%, and 90%, respectively. Thus, hand-held echocardiography devices accurately assessed LVH and may be used for community-based screening for LVH in targeted patients with hypertension.

Heart failure is a growing and increasingly important chronic disease of the western world, occurring in at least 2% of the adult population and rising to 3% in those aged over 75 years.1,2 In a recently conducted study in Harrow of 1400 subjects who were invited to undergo echocardiography for assessment of left ventricular (LV) function the overall prevalence of symptomatic and asymptomatic LV dysfunction was 2% and rising to 8% above the age of 65 years (fig 1).3 Although the incidence of most cardiovascular diseases has declined over the past 20 years, the incidence of heart failure has continued to rise, due to the fact that more people are surviving after acute myocardial infarction and also to the increasing number of elderly people.4 A diagnosis of heart failure is associated with high mortality, morbidity, and cost.5 It has a worse prognosis than breast cancer or prostate cancer and is second only to stroke in terms of health care costs.6 Heart failure costs the USA over $8 billion (£5 billion) each year and 5% of all admissions in the UK have a diagnosis of heart failure.7 Indeed, hospital admission accounts for 70% of the cost of heart failure due to the number of day beds that are occupied.5 Figure 1 Prevalence of left ventricular systolic dysfunction (left ventricular ejection fraction < 50%), according to age group.3 Early detection of heart failure caused by left ventricular systolic dysfunction (LVSD) is important as early initiation of drug treatment, including angiotensin converting enzyme inhibitors, β blockers, and aldosterone receptor antagonists, has been shown to reduce mortality, morbidity, and hospitalisation.8,9 Indeed, it has been shown that early initiation of treatment in asymptomatic left ventricular dysfunction will prevent or retard progression to heart failure.10 However, …