Socioeconomic determinants of health, traditional risk factors and cardiovascular outcomes in Australia.

Background: Cardiovascular disease burden is decreasing, but these reductions have not been distributed equally amongst socioeconomic groups. Objectives: The aim of this study was to define the relationships between different domains of socioeconomic health, traditional cardiovascular risk factors and cardiovascular events. Methods: This was a cross-sectional study of local government areas (LGAs) in Victoria, Australia. We used data from a population health survey combined with cardiovascular event data derived from hospital and government data. Four socioeconomic domains: educational attainment, financial wellbeing, remoteness, and psychosocial health, were generated from 22 variables. The primary outcome was a composite of non-STEMI, STEMI, heart failure and cardiovascular deaths per 10,000 persons. Linear regression and cluster analysis were used to assess the relationships between risk factors and events. Results: Across 79 LGAs there were 33,654 interviews conducted. All socioeconomic domains were associated with burden of traditional risk factors, including hypertension, smoking, poor diet, diabetes, and obesity. Financial wellbeing, educational attainment and remoteness were all correlated with cardiovascular events on univariate analysis. After multivariate adjustment for age and sex, financial wellbeing, psychosocial wellbeing, and remoteness were associated with cardiovascular events, while educational attainment was not. After including traditional risk factors only financial wellbeing and remoteness remained correlated with cardiovascular events. Conclusions: Financial wellbeing and remoteness independently be associated with cardiovascular events, while educational attainment and psychosocial wellbeing are attenuated by traditional cardiovascular risk factors. Poor socioeconomic health is clustered in certain areas, which have high cardiovascular event rates.

Colchicine in the Management of Acute Coronary Syndrome: A Meta-analysis.

INTRODUCTION: Colchicine, thought to exert its effect via reduction of inflammation, has recently been studied in patients following acute coronary syndromes (ACS). We performed a meta-analysis of all available randomized controlled trials (RCTs) in this high-risk cohort, evaluating efficacy and safety. METHODS: MEDLINE, PubMed, EMBASE, clinical trial registries, and select conference proceedings were searched for RCTs comparing colchicine to placebo in patients following ACS. The primary outcome was trial-defined major adverse cardiovascular events (MACE). Secondary endpoints included stroke, myocardial infarction (MI), all-cause and cardiovascular death, and urgent revascularization. Analysis was performed at the longest available clinical follow-up. RESULTS: Two RCTs with a pooled sample size of 5540 patients with 2778 (50.1%) receiving colchicine and 2762 (49.9%) placebo were included. In order to maximize consistency, composite efficacy endpoints between trials were modified. Compared to placebo, patients receiving colchicine had reduction in study-defined composite endpoint (5.5% vs. 7.6%) OR 0.67 (95% CI 0.46-0.98, p = 0.04, I2 = 46%). Similarly, there was a significant reduction in cerebrovascular accidents (OR 0.31, 95% CI 0.14-0.69, p = 0.004, I2 = 0%) and repeat revascularization OR 0.36 (95% CI 0.14-0.90, p = 0.03, I2 = 54%). There was no difference between cardiovascular death (OR 0.92, 95% CI 0.52-1.62, p = 0.78, I2 = 0%), non-cardiovascular death OR 1.27 (95% CI 0.72-2.24, p = 0.41, I2 = 0%), MI at longest available follow-up OR 0.89 (95% CI 0.67-1.17, p = 0.39, I2 = 0%) or resuscitated cardiac arrest OR 0.88 (95% CI 0.32-2.43, p = 0.81, I2 = 0%) in those receiving colchicine. CONCLUSIONS: These data suggest colchicine, in addition to guideline-directed medical therapy following acute coronary syndrome reduces MACE, cerebrovascular accidents, and rates of urgent revascularization at 2 years of follow-up.

Non-hyperaemic pressure ratios to guide percutaneous coronary intervention.

The use of fractional flow reserve (FFR) in guiding revascularisation improves patient outcomes and has been well-established in clinical guidelines. Despite this, the uptake of FFR has been limited, likely attributable to the perceived increase in procedural time and use of hyperaemic agents that can cause patient discomfort. This has led to the development of instantaneous wave-free ratio (iFR), an alternative non-hyperaemic pressure ratio (NHPR). Since its inception, the use of iFR has been supported by an increasing body of evidence and is now guideline recommended. More recently, other commercially available NHPRs including diastolic hyperaemia-free ratio and resting full-cycle ratio have emerged. Studies have demonstrated that these indices, in addition to mean distal coronary artery pressure to mean aortic pressure ratio, are mathematically analogous (with specific nuances) to iFR. Additionally, there is increasing data demonstrating the equivalent diagnostic performance of alternative NHPRs in comparison with iFR and FFR. These NHPRs are now integral within most current pressure wire systems and are commonly available in the catheter laboratory. It is therefore key to understand the fundamental differences and evidence for NHPRs to guide appropriate clinical decision-making.

Comparison of diagnostic performance between quantitative flow ratio, non-hyperemic pressure indices and fractional flow reserve.

BACKGROUND: Quantitative flow ratio (QFR) is an estimate of fractional flow reserve (FFR) and is derived from 3-dimensional quantitative coronary angiography. The DILEMMA score is an angiographic technique developed to predict FFR. Unlike other diastolic indices such as instantaneous wave-free ratio (iFR), diastolic pressure ratio (dPR) and dPR25-75, neither QFR nor DILEMMA score require pressure wires. This study sought to compare the diagnostic performance of QFR, diastolic indices and DILEMMA score to predict FFR. METHODS: Between January 2010 and December 2013, patients who underwent invasive coronary angiography and FFR assessments were retrospectively studied. iFR and dPR were derived from FFR pressure tracings. QFR was computed using commercial software. RESULTS: Eighty-five lesions (25% FFR significant) were included in this study. Median FFR was 0.88 (0.81-0.92). QFR (rs=0.801), iFR (rs=0.710), dPR (rs=0.716), dPR25-75 (rs=0.715) and DILEMMA score (rs=-0.623) significantly correlated with FFR (P<0.001). QFR ≤0.8 had a specificity, sensitivity, positive predictive value (PPV) and negative predictive value (NPV) of 95%, 86%, 86% and 95% respectively of predicting significant FFR (P<0.001). Receiver-operating characteristic (ROC) analysis revealed the AUC to predict significant FFR for QFR (0.947), iFR (0.880), dPR (0.883), dPR25-75 (0.880) and DILEMMA score (0.916) were not significantly different. However, QFR was a better predictor of FFR than iFR (0.947 vs. 0.770, P<0.01). CONCLUSIONS: QFR had excellent correlation and accuracy as measured against FFR. When compared to other diastolic indices and DILEMMA score, QFR performed at least as well as the other indices. QFR predicts FFR better than it predicts iFR. QFR is a convenient tool to assess significance of coronary stenosis and a reliable alternative to pressure-wire based indices. Prospective studies are required to investigate the performance and cost-effectiveness of QFR when independently used to guide clinical decision making.

Meta-Analysis of Bleeding Scores Performance for Acute Coronary Syndrome.

BACKGROUND: Bleeding is a common and frequently devastating complication in acute coronary syndrome (ACS). It is critical to evaluate in the current era of ACS management involving invasive strategies and potent anti-thrombotics. Risk models remain under-utilised in this setting but may guide the choice and duration of therapy. We compared their performances for predicting bleeding in ACS patients in this meta-analysis. METHODS: Medline, EMBASE, Cochrane and Scopus were searched for relevant articles from 1980 to 31 December 2017 assessing external validation of risk scores for bleeding after ACS. Two (2) authors independently reviewed the searched studies for eligibility, followed by pooled analyses using random effects models. RESULTS: Amongst 1,843 articles searched, 73 full-texts were reviewed and 17 studies totalling 18,155 patients were included for analysis. C-statistics (95% confidence interval) for predicting in-hospital major bleeding by risk model were Can Rapid risk stratification of Unstable angina patients Suppress ADverse outcomes with Early implementation of the ACC/AHA guidelines (CRUSADE) 0.714 (0.659-0.779), Acute Catheterization and Urgent Intervention Triage strategY (ACUITY) 0.711 (0.626-0.797), Acute Coronary Treatment and Intervention Outcomes Network (ACTION) 0.767 (0.737-0.797), Global Registry of Acute Coronary Events (GRACE) 0.689 (0.473-0.905) and HAS-BLED 0.636 (0.460-0.812). CRUSADE also predicted bleeding during medium-term follow-up c=0.704 (0.644-0.765). It performed better for radial versus femoral access (c=0.826 and 0.734), invasive versus non-invasive strategy (c=0.752 and 0.625) and similarly for ST elevation myocardial infarction (STEMI) and non-ST elevation myocardial infarction (NSTEMI) (c=0.791 and 0.760). Heterogeneities of studies and paucity of studies assessing risk scores beyond CRUSADE were important limitations. CONCLUSIONS: Acute coronary syndrome-specific bleeding scores had moderate discrimination for bleeding, while the GRACE and HAS-BLED scores could not. The ACTION score had the highest pooled c-statistic, while the CRUSADE score was the most widely studied, and also performed better for invasive strategy and radial access subgroups.

Exploring the relationship between biomechanical stresses and coronary atherosclerosis.

The pathophysiology of coronary atherosclerosis is multifaceted. Plaque initiation and progression are governed by a complex interplay between genetic and environmental factors acting through processes such as lipid accumulation, altered haemodynamics and inflammation. There is increasing recognition that biomechanical stresses play an important role in atherogenesis, and integration of these metrics with clinical imaging has potential to significantly improve cardiovascular risk prediction. In this review, we present the calculation of coronary biomechanical stresses from first principles and computational methods, including endothelial shear stress (ESS), plaque structural stress (PSS) and axial plaque stress (APS). We discuss the current experimental and human data linking these stresses to the natural history of coronary artery disease and explore the future potential for refining treatment options and predicting future ischaemic events.

Familial Hypercholesterolemia With Coexisting Renovascular Stenosis and Premature Coronary Artery Disease.

Familial hypercholesterolemia (FH) is a common hereditary lipid disorder associated with substantial risk of premature atherosclerotic cardiovascular disease. We report an interesting newly diagnosed index case of FH in a 31-year-old man who presented to the hospital with an ST-elevated myocardial infarction. He had a background of inadequately treated hypertension and hypercholesterolemia. Further investigations raised the possibility of secondary hypertension after the identification of renal artery stenosis, in addition to other areas of mesenteric arterial stenoses. Our patient's case highlights that early-onset hypertension and hypercholesterolemia in a young individual may be an early manifestation of FH requiring high clinical vigilance and awareness.

Adjuvant effects elicited by novel oligosaccharide variants of detoxified meningococcal lipopolysaccharides on Neisseria meningitidis recombinant PorA protein: a comparison in mice.

Neisseria meningitidis lipopolysaccharide (LPS) has adjuvant properties that can be exploited to assist vaccine immunogenicity. The modified penta-acylated LPS retains the adjuvant properties of hexa-acylated LPS but has a reduced toxicity profile. In this study we investigated whether two modified glycoform structures (LgtE and IcsB) of detoxified penta-acylated LPS exhibited differential adjuvant properties when formulated as native outer membrane vesicles (nOMVs) as compared to the previously described LgtB variant. Detoxified penta-acylated LPS was obtained by disruption of the lpxL1 gene (LpxL1 LPS), and three different glycoforms were obtained by disruption of the lgtB, lgtE or icsB genes respectively. Mice (mus musculus) were immunized with a recombinant PorA P1.7-2,4 (rPorA) protein co-administered with different nOMVs (containing a different PorA serosubtype P1.7,16), each of which expressed one of the three penta-acylated LPS glycoforms. All nOMVs induced IgG responses against the rPorA, but the nOMVs containing the penta-acylated LgtB-LpxL1 LPS glycoform induced significantly greater bactericidal activity compared to the other nOMVs or when the adjuvant was Alhydrogel. Compared to LgtE or IcsB LPS glycoforms, these data support the use of nOMVs containing detoxified, modified LgtB-LpxL1 LPS as a potential adjuvant for future meningococcal protein vaccines.

Perioperative hypothermia in patients undergoing major colorectal surgery.

BACKGROUND: Perioperative hypothermia occurs frequently and can have serious health-related and financial consequences. Despite multiple warming methods available, perioperative hypothermia remains prevalent. To be effective, preventative measures must be timely and target patients most at risk. The aim of this retrospective review was to document the incidence and patterns of hypothermia in patients undergoing major colorectal surgery. METHODS: Hospital records were used to obtain demographic and clinical information on 255 patients undergoing major colorectal surgery over one year. Temperatures were recorded from five perioperative time-points and correlated with potential contributing factors. RESULTS: Most patients (74%) experienced mild hypothermia, which was most common intraoperatively. Elective patients experienced the greatest drop in temperature between admission and commencement of surgery while emergency patients experienced a similar drop intraoperatively. The most significant determinant of intraoperative hypothermia was core temperature at the start of surgery (P < 0.01). Factors increasing hypothermia at the start of surgery were an elective presentation, an arrival temperature below 36.5°C (P < 0.01) and an age greater than 70 years (P < 0.05). CONCLUSIONS: Mild hypothermia in patients undergoing major colorectal surgery is common, despite preventative measures. Core temperatures prior to commencement of the operation should be optimized with both active and passive warming measures, particularly for older patients and those arriving with lower core temperatures. Elective patients should also have their temperatures monitored as closely, if not more closely, than emergency patients. Preventing early declining trends in core temperature may positively influence later perioperative temperatures and improve outcomes.

Neisseria meningitidis native outer membrane vesicles containing different lipopolysaccharide glycoforms as adjuvants for meningococcal and nonmeningococcal antigens.

We evaluated the adjuvant effect of a modified glycoform of lipopolysaccharide (LPS) (LgtB-LpxL1) compared to that of the nonmodified glycoform Lpxl1 serogroup B meningococcal H44/76 native outer membrane vesicles (nOMVs) on immune responses to vaccination with the recombinant meningococcal protein, rPorA, tetanus toxoid, or meningococcal serogroup C capsular polysaccharide. We used LgtB-LpxL1 LPS because the disruption of the lgtB gene, which results in the exposure of N-acetylglucosamine-galactose-glucose residues in the LPS outer core, has been shown to enhance the activation of human dendritic cells in vitro. The responses were compared to those of a monophosphoryl lipid A (MPL)-based adjuvant and to an aluminum hydroxide suspension. The nOMVs induced blood serum IgG responses against each of the three antigens comparable to those obtained with MPL or aluminum salt. However, nOMVs elicited (i) a lower IgG1/IgG2a ratio against rPorA and (ii) serum bactericidal antibody titers superior to those achieved with aluminum salt, reaching similar titers to those obtained with MPL. Similarly, bactericidal antibody titers induced by immunization with meningococcal serogroup C polysaccharide and nOMVs were similar to those obtained using MPL but were better than those with aluminum salt. Immunization with tetanus toxoid and nOMVs resulted in tetanus toxoid-specific IgG responses similar to those obtained when adjuvanted with aluminum salt. These results highlight the potential utility of meningococcal LpxL1 LPS-containing nOMVs as an adjuvant for recombinant meningococcal protein vaccines and suggest their possible use with a variety of other antigens.

The fate of the joint space in Legg-Calvé-Perthes' disease.

OBJECTIVE: This study was undertaken to identify variations in the hip joint space in patients with healed Legg-Calvé-Perthes' disease (LCPD) and to correlate these changes with the radiological outcome of treatment. METHODS: The width of the joint space was measured on radiographs of 121 skeletally mature individuals with healed LCPD. The joint space width at the stage of healing in 79 patients was compared with the joint space at skeletal maturity. The hips were graded by the Stulberg classification and the femoral head radius was measured. Associations between the joint space width, the Stulberg class and the femoral head radius were tested. The reproducibility of measurement was tested by measuring 30 radiographs twice and computing the intra-class correlation coefficient (ICC). The joint space width was measured on radiographs of 25 patients taken both while recumbent and standing, to determine if the joint space alters on weight-bearing. RESULTS: The reproducibility of measurements was satisfactory; no difference was noted in the joint space in recumbent and weight-bearing films. Increased joint space was noted both at healing of the disease and at skeletal maturity; the width was minimally increased in Stulberg Class I hips and considerably increased in Class III, IV and V hips. There was a significant correlation between the increase in joint space and enlargement of the femoral head. CONCLUSIONS: An increase in joint space width occurs quite frequently following LCPD; the increase is most evident in hips with a poor outcome. The implications of this observation need to be elucidated.

Phosphorus and potassium content of enhanced meat and poultry products: implications for patients who receive dialysis.

BACKGROUND AND OBJECTIVES: Uncooked meat and poultry products are commonly enhanced by food processors using phosphate salts. The addition of potassium and phosphorus to these foods has been recognized but not quantified. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: We measured the phosphorus, potassium, and protein content of 36 uncooked meat and poultry products: Phosphorus using the Association of Analytical Communities (AOAC) official method 984.27, potassium using AOAC official method 985.01, and protein using AOAC official method 990.03. RESULTS: Products that reported the use of additives had an average phosphate-protein ratio 28% higher than additive free products; the content ranged up to almost 100% higher. Potassium content in foods with additives varied widely; additive free products all contained <387 mg/100 g, whereas five of the 25 products with additives contained at least 692 mg/100 g (maximum 930 mg/100 g). Most but not all foods with phosphate and potassium additives reported the additives (unquantified) on the labeling; eight of 25 enhanced products did not list the additives. The results cannot be applied to other products. The composition of the food additives used by food processors may change over time. CONCLUSIONS: Uncooked meat and poultry products that are enhanced may contain additives that increase phosphorus and potassium content by as much as almost two- and three-fold, respectively; this modification may not be discernible from inspection of the food label.

Dietary phosphorus restriction in dialysis patients: potential impact of processed meat, poultry, and fish products as protein sources.

BACKGROUND: Dietary intake of phosphorus is derived largely from protein sources and is a critical determinant of phosphorus balance in patients with chronic kidney disease. Information about the phosphorus content of prepared foods generally is unavailable, but it is believed to contribute significantly to the phosphorus burden of patients with chronic kidney disease. DESIGN: Analysis of dietary components. SETTING: We measured the phosphorus content of 44 food products, including 30 refrigerated or frozen precooked meat, poultry, and fish items, generally national brands. OUTCOMES: Measured and reported phosphorus content of foods. MEASUREMENTS: Phosphorus by using Association of Analytical Communities official method 984.27; protein by using Association of Analytical Communities official method 990.03. RESULTS: We found that the ratio of phosphorus to protein content in these items ranged from 6.1 to 21.5 mg of phosphorus per 1 g of protein. The mean ratio in the 19 food products with a label listing phosphorus as an additive was 14.6 mg/g compared with 9.0 mg/g in the 11 items without listed phosphorus. The phosphorus content of only 1 precooked food product was available in a widely used dietary database. LIMITATIONS: Results cannot be extrapolated to other products. Manufacturers also may alter the phosphorus content of foods at any time. Protein content was not directly measured for all foods. CONCLUSION: Better reporting of phosphorus content of foods by manufacturers could result in improved dietary phosphorus control without risk of protein malnutrition.