Serum vitamin C status of people in New South Wales: retrospective analysis of findings at a public referral hospital.

OBJECTIVES: To examine the relationship between vitamin C status and demographic factors in New South Wales on the basis of serum vitamin C test results undertaken at the central pathology laboratory in Sydney, and to assess associations with age, gender, social disadvantage, and geographic remoteness. DESIGN, SETTING: Retrospective observational study; analysis of vitamin C test results undertaken at the Royal Prince Alfred Hospital, 1 January 2017 - 31 December 2021. MAIN OUTCOME MEASURES: Vitamin C status (normal, serum concentration ≥ 40 µmol/L; hypovitaminosis C, 12-39 µmol/L; significant deficiency, < 12 µmol/L); associations of vitamin C status with year of testing, age, gender, socio-economic status (Index of Relative Socio-Economic Advantage and Disadvantage quintile), and geographic remoteness (Australian Statistical Geography Standard); rate of hypovitaminosis C or significant deficiency test results (relative to findings of normal levels; per 100 000 estimated resident population) by Statistical Area 3. RESULTS: Of 17 507 vitamin C tests undertaken during 2017-2021, 4573 were excluded (multiple tests for individuals); of 12 934 included results, 6654 were for women (51.5%), 9402 for people living in major cities (73.5%), and 81 for people in remote or very remote areas (0.6%). In multivariable multinomial regression analyses, significant deficiency (relative to normal test results) was more likely for men than women (adjusted odds ratio [aOR], 1.39; 95% confidence interval [CI], 1.27-1.52); the likelihood of hypovitaminosis C (IRSAD quintile 1 v 5, aOR, 1.35; 95% CI, 1.19-1.53) or significant deficiency (aOR, 2.07; 95% CI, 1.79-2.40) generally increased with postcode-level socio-economic disadvantage. Several of the population areas with the highest low vitamin C rates were areas of greatest disadvantage in NSW. CONCLUSIONS: The prevalence of vitamin C deficiency among older people and people living in areas of socio-economic disadvantage indicates that population assessment of vitamin C levels would be appropriate.

Clinical Pathway for Coronary Atherosclerosis in Patients Without Conventional Modifiable Risk Factors: JACC State-of-the-Art Review.

Reducing the incidence and prevalence of standard modifiable cardiovascular risk factors (SMuRFs) is critical to tackling the global burden of coronary artery disease (CAD). However, a substantial number of individuals develop coronary atherosclerosis despite no SMuRFs. SMuRFless patients presenting with myocardial infarction have been observed to have an unexpected higher early mortality compared to their counterparts with at least 1 SMuRF. Evidence for optimal management of these patients is lacking. We assembled an international, multidisciplinary team to develop an evidence-based clinical pathway for SMuRFless CAD patients. A modified Delphi method was applied. The resulting pathway confirms underlying atherosclerosis and true SMuRFless status, ensures evidence-based secondary prevention, and considers additional tests and interventions for less typical contributors. This dedicated pathway for a previously overlooked CAD population, with an accompanying registry, aims to improve outcomes through enhanced adherence to evidence-based secondary prevention and additional diagnosis of modifiable risk factors observed.

Optimised plasma sample preparation and LC-MS analysis to support large-scale proteomic analysis of clinical trial specimens: Application to the Fenofibrate Intervention and Event Lowering in Diabetes (FIELD) trial.

PURPOSE: Robust, affordable plasma proteomic biomarker workflows are needed for large-scale clinical studies. We evaluated aspects of sample preparation to allow liquid chromatography-mass spectrometry (LC-MS) analysis of more than 1500 samples from the Fenofibrate Intervention and Event Lowering in Diabetes (FIELD) trial of adults with type 2 diabetes. METHODS: Using LC-MS with data-independent acquisition we evaluated four variables: plasma protein depletion, EDTA or citrated anti-coagulant blood collection tubes, plasma lipid depletion strategies and plasma freeze-thaw cycles. Optimised methods were applied in a pilot study of FIELD participants. RESULTS: LC-MS of undepleted plasma conducted over a 45 min gradient yielded 172 proteins after excluding immunoglobulin isoforms. Cibachrome-blue-based depletion yielded additional proteins but with cost and time expenses, while immunodepleting albumin and IgG provided few additional identifications. Only minor variations were associated with blood collection tube type, delipidation methods and freeze-thaw cycles. From 65 batches involving over 1500 injections, the median intra-batch quantitative differences in the top 100 proteins of the plasma external standard were less than 2%. Fenofibrate altered seven plasma proteins. CONCLUSIONS AND CLINICAL RELEVANCE: A robust plasma handling and LC-MS proteomics workflow for abundant plasma proteins has been developed for large-scale biomarker studies that balance proteomic depth with time and resource costs.

Factors associated with fragility fractures in type 2 diabetes: An analysis of the randomised controlled Fenofibrate Intervention and Event Lowering in Diabetes (FIELD) study.

AIMS: Fracture risk is elevated in some type 2 diabetes patients. Bone fragility may be associated with more clinically severe type 2 diabetes, although prospective studies are lacking. It is unknown which diabetes-related characteristics are independently associated with fracture risk. In this post-hoc analysis of fracture data from the Fenofibrate Intervention and Event Lowering in Diabetes (FIELD) trial (ISRCTN#64783481), we hypothesised that diabetic microvascular complications are associated with bone fragility. MATERIALS AND METHODS: The FIELD trial randomly assigned 9795 type 2 diabetes participants (aged 50-75 years) to receive oral co-micronised fenofibrate 200 mg (n = 4895) or placebo (n = 4900) daily for a median of 5 years. We used Cox proportional hazards models to identify baseline sex-specific diabetes-related parameters independently associated with incident fractures. RESULTS: Over 49,470 person-years, 137/6138 men experienced 141 fractures and 143/3657 women experienced 145 fractures; incidence rates for the first fracture of 4∙4 (95% CI 3∙8-5∙2) and 7∙7 per 1000 person-years (95% CI 6∙5-9∙1), respectively. Fenofibrate had no effect on fracture outcomes. In men, baseline macrovascular disease (HR 1∙52, 95% CI 1∙05-2∙21, p = 0∙03), insulin use (HR 1∙62, HR 1∙03-2∙55, p = 0∙03), and HDL-cholesterol (HR 2∙20, 95% CI 1∙11-4∙36, p = 0∙02) were independently associated with fracture. In women, independent risk factors included baseline peripheral neuropathy (HR 2∙04, 95% CI 1∙16-3∙59, p = 0∙01) and insulin use (HR 1∙55, 95% CI 1∙02-2∙33, p = 0∙04). CONCLUSIONS: Insulin use and sex-specific complications (in men, macrovascular disease; in women, neuropathy) are independently associated with fragility fractures in adults with type 2 diabetes.

Australian Atherosclerosis Society Position Statement on Lipoprotein(a): Clinical and Implementation Recommendations.

This position statement provides guidance to cardiologists and related specialists on the management of adult patients with elevated lipoprotein(a) [Lp(a)]. Elevated Lp(a) is an independent and causal risk factor for atherosclerotic cardiovascular disease (ASCVD) and calcific aortic valve disease (CAVD). While circulating Lp(a) levels are largely determined by ancestry, they are also influenced by ethnicity, hormones, renal function, and acute inflammatory events, such that measurement should be done after accounting for these factors. Further, circulating Lp(a) concentrations should be estimated using an apo(a)-isoform independent assay that employs appropriate calibrators and reports the results in molar units (nmol/L). Selective screening strategies of high-risk patients are recommended, but universal screening of the population is currently not advised. Testing for elevated Lp(a) is recommended in all patients with premature ASCVD and those considered to be at intermediate-to-high risk of ASCVD. Elevated Lp(a) should be employed to assess and stratify risk and to enable a decision on initiation or intensification of preventative treatments, such as cholesterol lowering therapy. In adult patients with elevated Lp(a) at intermediate-to-high risk of ASCVD, absolute risk should be reduced by addressing all modifiable behavioural, lifestyle, psychosocial and clinical risk factors, including maximising cholesterol-lowering with statin and ezetimibe and, where appropriate, PCSK9 inhibitors. Apheresis should be considered in patients with progressive ASCVD. New ribonucleic acid (RNA)-based therapies which directly lower Lp(a) are undergoing clinical trials.

Participant experiences of intervention to detect and manage familial hypercholesterolaemia in Australian general practice: A qualitative descriptive study.

BACKGROUND AND OBJECTIVES: General practitioners (GPs) are ideally placed to have a much larger role in detection and management of familial hypercholesterolaemia (FH) among their patients. The aim of this study was to seek the reflections of practice staff and newly diagnosed patients with FH on the implementation of an FH model of care in the general practice setting. METHOD: Qualitative descriptive methodology was used. Interviews were conducted with 36 practice staff and 51 patients from 15 practices participating in the study. RESULTS: Data were analysed thematically and coded into themes - efficacy of GP training, screening for FH, model of care, patient awareness and cascade testing. DISCUSSION: Findings reflect the real-world clinical experience of Australian general practice and the acceptability of the model of care for both patients with FH and practice staff. Patient health literacy is a barrier to both management of FH and cascade testing. A systematic approach to cascade testing is required.

Cost impact of undertaking detection and management of familial hypercholesterolaemia in Australian general practice.

BACKGROUND AND OBJECTIVES: Familial hypercholesterolaemia (FH) can be effectively detected and managed in primary care, but the health economic evidence for this is scarce. The aim of this study was to examine management pathways and cost implications of FH screening and management in Australian general practice. METHOD: Cost-effectiveness outcomes were projected using a life table model. Data was used from 133 patients in 15 Australian general practice clinics from an earlier screening and management study. Costing and mortality data were sourced from governmental sources and published literature. RESULTS: Most patients had a regular general practice consultation at baseline (82%), though the proportion seen under a chronic disease management item at follow-up increased to 23%. The median cost of management was $275 per annum in the first year of management. Managing patients with statins up to the age of 60 years yielded an increase of 248,954 life-years at a cost of $759 million, representing a cost per life-year gained of $3047. DISCUSSION: Screening and management of FH in general practice has the potential for substantial health benefits while requiring relatively modest investments from the health system.

Corrigendum to Synopsis of an integrated guidance for enhancing the care of familial hypercholesterolaemia: An Australian perspective [American Journal of Preventive Cardiology 6 (2021) 100151].

[This corrects the article DOI: 10.1016/j.ajpc.2021.100151.].

Hypertriglyceridemia: rationale, design and implementation of the Australian Hypertriglyceridemia Registry.

PURPOSE OF REVIEW: Hypertriglyceridemia (HTG) is a risk factor for atherosclerotic cardiovascular disease (ASCVD), aortic stenosis, hepatic steatosis and pancreatitis. We briefly review the aetiology and treatment of HTG and familial chylomicronemia syndrome (FCS), as well as the implementation of a clinical quality registry for improving care, the Australian Hypertriglyceridemia (AUSTRIG) Registry. RECENT FINDINGS: There is a need to improve the detection of individuals with severe HTG and FCS, who could benefit from more intense and novel treatments to prevent end-organ damage. Patient registries provide valuable data for advancing care of individuals with severe HTG at high risk of acute pancreatitis, steatohepatitis and ASCVD. However, there is a paucity of registries of such patients. We outline the design and implementation of the AUSTRIG Registry. SUMMARY: Clinical registries can be employed in many ways for improving outcomes for patients with HTG, through the collation and analysis of data for enabling health service planning, clinical trials and audits, and for better informing and empowering registrants.

Overcoming enzalutamide resistance in metastatic prostate cancer by targeting sphingosine kinase.

BACKGROUND: Intrinsic resistance to androgen receptor signalling inhibitors (ARSI) occurs in 20-30% of men with metastatic castration-resistant prostate cancer (mCRPC). Ceramide metabolism may have a role in ARSI resistance. Our study's aim is to investigate the association of the ceramide-sphingosine-1-phosphate (ceramide-S1P) signalling axis with ARSI resistance in mCRPC. METHODS: Lipidomic analysis (∼700 lipids) was performed on plasma collected from 132 men with mCRPC, before commencing enzalutamide or abiraterone. AR gene aberrations in 77 of these men were identified by deep sequencing of circulating tumour DNA. Associations between circulating lipids, radiological progression-free survival (rPFS) and overall survival (OS) were examined by Cox regression. Inhibition of ceramide-S1P signalling with sphingosine kinase (SPHK) inhibitors (PF-543 and ABC294640) on enzalutamide efficacy was investigated with in vitro assays, and transcriptomic and lipidomic analyses of prostate cancer (PC) cell lines (LNCaP, C42B, 22Rv1). FINDINGS: Men with elevated circulating ceramide levels had shorter rPFS (HR=2·3, 95% CI=1·5-3·6, p = 0·0004) and shorter OS (HR=2·3, 95% CI=1·4-36, p = 0·0005). The combined presence of an AR aberration with elevated ceramide levels conferred a worse prognosis than the presence of only one or none of these characteristics (median rPFS time = 3·9 vs 8·3 vs 17·7 months; median OS time = 8·9 vs 19·8 vs 34·4 months). SPHK inhibitors enhanced enzalutamide efficacy in PC cell lines. Transcriptomic and lipidomic analyses indicated that enzalutamide combined with SPHK inhibition enhanced PC cell death by SREBP-induced lipotoxicity. INTERPRETATION: Ceramide-S1P signalling promotes ARSI resistance, which can be reversed with SPHK inhibitors. FUNDING: None.

Relationship of low molecular weight fluorophore levels with clinical factors and fenofibrate effects in adults with type 2 diabetes.

People with diabetes are at risk of chronic complications and novel biomarkers, such as Advanced glycation end-products (AGEs) may help stratify this risk. We assessed whether plasma low-molecular weight AGEs, also known as LMW-fluorophores (LMW-F), are associated with risk factors, predict complications, and are altered by fenofibrate in adults with type 2 diabetes. Plasma LMW-F were quantified at baseline, after six weeks fenofibrate, and one year post-randomisation to fenofibrate or placebo. LMW-F associations with existing and new composite vascular complications were determined, and effects of fenofibrate assessed. LMW-F correlated positively with age, glycated haemoglobin (HbA1c), pulse pressure, kidney dysfunction and inflammation; and negatively with urate, body mass index, oxidative stress and leptin, albeit weakly (r = 0.04-0.16, all p < 0.01). Independent determinants of LMW-F included smoking, diastolic blood pressure, prior cardiovascular disease or microvascular complications, Caucasian ethnicity, kidney function, HbA1c and diabetes duration (all p ≤ 0.01). Baseline LMW-F tertiles correlated with on-trial macrovascular and microvascular complications (trend p < 0.001) on univariate analyses only. Six weeks of fenofibrate increased LMW-F levels by 21% (p < 0.001). In conclusion, LMW-F levels correlate with many risk factors and chronic diabetes complications, and are increased with fenofibrate. LMW-F tertiles predict complications, but not independently of traditional risk factors.

Awareness of familial hypercholesterolaemia in Australian primary care: A qualitative descriptive study.

BACKGROUND AND OBJECTIVES: A lack of public and health professional awareness about familial hypercholesterolaemia (FH) leads to an estimated 90,000 Australians remaining undiagnosed. The aim of this study was to establish the level of knowledge and awareness of FH in Australian general practices. METHOD: A qualitative descriptive methodology was used to explore baseline knowledge and perceptions of practice staff about diagnosing and managing FH. Overall, 63 interviews were conducted with general practice staff at 15 practices taking part in a National Health and Medical Research Council partnership grant study (GNT1142883). RESULTS: Data were analysed thematically and coded into themes - knowledge/awareness/recall, management, use of guidelines/referrals, and contacting family members. Most general practitioners treated the high cholesterol component as their primary focus. Guidelines and referrals were rarely used. DISCUSSION: This research reflected a lack of knowledge, awareness and use of guidelines similar to that shown in other published studies. Improved primary care infrastructure, knowledge and awareness of FH need to be addressed.

The relationship of neutrophil elastase and proteinase 3 with risk factors, and chronic complications in type 2 diabetes: A Fenofibrate Intervention and Event Lowering in Diabetes (FIELD) sub-study.

INTRODUCTION: Neutrophil elastase (NE) and proteinase 3 (PR3) are novel inflammation biomarkers. We investigated their associations with chronic complications, determinants of biomarker levels and effects of fenofibrate in patients with type 2 diabetes mellitus (T2DM) from Fenofibrate Intervention and Event Lowering in Diabetes study. METHODS: Plasma NE and PR3 levels were quantified at baseline (n = 2000), and relationships with complications over 5-years assessed. Effects of fenofibrate on biomarker levels (n = 200) were determined at four follow-up visits. RESULTS: Higher waist-to-hip ratio, homocysteine and C-reactive protein and lower apoA-II were determinants of higher NE and PR3 levels. Higher NE levels were associated with on-trial stroke and cardiovascular mortality, and higher PR3 levels with on-trial stroke, but associations were not significant after adjustment for confounding factors. Although higher NE and PR3 levels were associated with baseline total microvascular disease, only NE levels were associated with on-trial neuropathy or amputation. These associations were not significant after adjusting for multiple comparisons. NE and PR3 levels did not change with fenofibrate. CONCLUSIONS: In T2DM plasma NE and PR3 levels are associated with vascular risk factors, and total microvascular disease at baseline, but on rigorous analyses were not associated with on-trial complications. Levels were not changed by fenofibrate.

Synopsis of an integrated guidance for enhancing the care of familial hypercholesterolaemia: an Australian perspective.

INTRODUCTION: Familial hypercholesterolaemia (FH) is a common, heritable and preventable cause of premature coronary artery disease, with significant potential for positive impact on public health and healthcare savings. New clinical practice recommendations are presented in an abridged guidance to assist practitioners in enhancing the care of all patients with FH. MAIN RECOMMENDATIONS: Core recommendations are made on the detection, diagnosis, assessment and management of adults, children and adolescents with FH. There is a key role for general practitioners (GPs) working in collaboration with specialists with expertise in lipidology. Advice is given on genetic and cholesterol testing and risk notification of biological relatives undergoing cascade testing for FH; all healthcare professionals should develop skills in genomic medicine. Management is under-pinned by the precepts of risk stratification, adherence to healthy lifestyles, treatment of non-cholesterol risk factors, and appropriate use of low-density lipoprotein (LDL)-cholesterol lowering therapies, including statins, ezetimibe and proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors. Recommendations on service design are provided in the full guidance. POTENTIAL IMPACT ON CARE OF FH: These recommendations need to be utilised using judicious clinical judgement and shared decision making with patients and families. Models of care need to be adapted to both local and regional needs and resources. In Australia new government funded schemes for genetic testing and use of PCSK9 inhibitors, as well as the National Health Genomics Policy Framework, will enable adoption of these recommendations. A broad implementation science strategy is, however, required to ensure that the guidance translates into benefit for all families with FH.

Essentials of a new clinical practice guidance on familial hypercholesterolaemia for physicians.

Familial hypercholesterolaemia (FH) is a common, heritable and preventable cause of premature coronary artery disease. New clinical practice recommendations are presented to assist practitioners in enhancing the care of all patients with FH. Core recommendations are made on the detection, diagnosis, assessment and management of adults, children and adolescents with FH. Management is under-pinned by the precepts of risk stratification, adherence to healthy lifestyles, treatment of non-cholesterol risk factors and appropriate use of low-density lipoprotein (LDL)-cholesterol-lowering therapies including statins, ezetimibe and proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors. The recommendations need to be utilised using judicious clinical judgement and shared decision-making with patients and families. New government-funded schemes for genetic testing and use of PCSK9 inhibitors, as well as the National Health Genomics Policy Framework, will enable adoption of the recommendations. However, a comprehensive implementation science and practice strategy is required to ensure that the guidance translates into benefit for all families with FH.

Improving detection and management of familial hypercholesterolaemia in Australian general practice.

OBJECTIVE: Familial hypercholesterolaemia (FH) is characterised by elevated low-density lipoprotein (LDL)-cholesterol and increased risk of cardiovascular disease. However, FH remains substantially underdiagnosed and undertreated. We employed a two-stage pragmatic approach to identify and manage patients with FH in primary healthcare. METHODS: Medical records for 232 139 patients who attended 15 general practices at least once in the previous 2 years across five Australian States were first screened for potential risk of FH using an electronic tool (TARB-Ex) and confirmed by general practitioner (GP) clinical assessment based on phenotypic Dutch Lipid Clinic Network Criteria (DLCNC) score. Follow-up GP consultation and management was provided for patients with phenotypic FH. RESULTS: A total of 1843 patients were identified by TARB-Ex as at potential risk of FH (DLCNC score ≥5). After GP medical record review, 900 of these patients (49%) were confirmed with DLCNC score ≥5 and classified as high-risk of FH. From 556 patients subsequently clinically assessed by GPs, 147 (26%) were diagnosed with phenotypic FH (DLCNC score >6). Follow-up GP consultation and management for 77 patients resulted in a significant reduction in LDL-cholesterol (-16%, p<0.01). A higher proportion of these patients attained the treatment target of 50% reduction in LDL-cholesterol (74% vs 62%, p<0.001) and absolute levels of LDL-cholesterol goals compared with baseline (26% vs 12%, p<0.05). CONCLUSIONS: A pragmatic approach integrating electronic medical record tools and clinical GP follow-up consultation is a feasible method to identify and better manage patients with FH in the primary healthcare setting. TRIAL REGISTRATION NUMBER: 12616000630415.

Gaps in the Care of Familial Hypercholesterolaemia in Australia: First Report From the National Registry.

BACKGROUND: Familial hypercholesterolaemia (FH) is under-diagnosed and under-treated worldwide, including Australia. National registries play a key role in identifying patients with FH, understanding gaps in care and advancing the science of FH to improve care for these patients. METHODS: The FH Australasia Network has established a national web-based registry to raise awareness of the condition, facilitate service planning and inform best practice and care services in Australia. We conducted a cross-sectional analysis of 1,528 FH adults enrolled in the registry from 28 lipid clinics. RESULTS: The mean age at enrolment was 53.4±15.1 years, 50.5% were male and 54.3% had undergone FH genetic testing, of which 61.8% had a pathogenic FH-causing gene variant. Only 14.0% of the cohort were family members identified through cascade testing. Coronary artery disease (CAD) was reported in 28.0% of patients (age of onset 49.0±10.5 years) and 64.9% had at least one modifiable cardiovascular risk factor. The mean untreated LDL-cholesterol was 7.4±2.5 mmol/L. 80.8% of patients were on lipid-lowering therapy with a mean treated LDL-cholesterol of 3.3±1.7 mmol/L. Among patients receiving lipid-lowering therapies, 25.6% achieved an LDL-cholesterol target of <2.5 mmol/L without CAD or <1.8 mmol/L with CAD. CONCLUSION: Patients in the national FH registry are detected later in life, have a high burden of CAD and risk factors, and do not achieve guideline-recommended LDL-cholesterol targets. Genetic and cascade testing are under-utilised. These deficiencies in care need to be addressed as a public health priority.

Integrated Guidance for Enhancing the Care of Familial Hypercholesterolaemia in Australia.

Familial hypercholesterolaemia (FH) is a dominant and highly penetrant monogenic disorder present from birth that markedly elevates plasma low-density lipoprotein (LDL)-cholesterol concentration and, if untreated, leads to premature atherosclerosis and coronary artery disease (CAD). There are approximately 100,000 people with FH in Australia. However, an overwhelming majority of those affected remain undetected and inadequately treated, consistent with FH being a leading challenge for public health genomics. To further address the unmet need, we provide an updated guidance, presented as a series of systematically collated recommendations, on the care of patients and families with FH. These recommendations have been informed by an exponential growth in published works and new evidence over the last 5 years and are compatible with a contemporary global call to action on FH. Recommendations are given on the detection, diagnosis, assessment and management of FH in adults and children. Recommendations are also made on genetic testing and risk notification of biological relatives who should undergo cascade testing for FH. Guidance on management is based on the concepts of risk re-stratification, adherence to heart healthy lifestyles, treatment of non-cholesterol risk factors, and safe and appropriate use of LDL-cholesterol lowering therapies, including statins, ezetimibe, proprotein convertase subtilisin/kexin type 9 inhibitors and lipoprotein apheresis. Broad recommendations are also provided for the organisation and development of health care services. Recommendations on best practice need to be underpinned by good clinical judgment and shared decision making with patients and families. Models of care for FH need to be adapted to local and regional health care needs and available resources. A comprehensive and realistic implementation strategy, informed by further research, including assessments of cost-benefit, will be required to ensure that this new guidance benefits all Australian families with or at risk of FH.

Dietary management of cardiovascular risk including type 2 diabetes.

PURPOSE OF REVIEW: Recent changes or confirmations linking patterns of eating and specific dietary interventions in the management of cardiovascular risk factors including associations with prevalent and incident type 2 diabetes. RECENT FINDINGS: Recently published guidance for dietary management of cardiovascular risk and type 2 diabetes have mostly common features. Major findings include a trend to replace strict quantitative advice on nutrients with qualitative advice on food consumption with exceptions for diabetes, global advice to increase intake of plant foods, confirmation to substitute mono and polyunsaturated oils for saturated and trans fats, new advisory on supplemental omega-3 intake, less limitation on dairy foods and fermented dairy foods encouraged, reduced emphasis on specific cholesterol-rich foods allowing greater consumption of eggs except for people with diabetes, processed meat consumption limited allowing modest intake of lean red meat, distinguishing between 'healthy' and 'unhealthy' carbohydrates including sugars, and maintaining advice on healthy bodyweight, reducing salt intake and encouraging water as preferred beverage. SUMMARY: The new guidance for healthier patterns of food consumption supported by evidence is more readily understood by health practitioners and translatable to consumers and patients.

Uric acid predicts long-term cardiovascular risk in type 2 diabetes but does not mediate the benefits of fenofibrate: The FIELD study.

AIM: To explore the relationship between baseline uric acid (UA) levels and long-term cardiovascular events in adults with type 2 diabetes (T2D) and to determine whether the cardioprotective effects of fenofibrate are partly mediated through its UA-lowering effects. METHODS: Data from the Fenofibrate Intervention and Event Lowering in Diabetes (FIELD) trial were utilized, comprising 9795 adults with T2D randomly allocated to treatment with fenofibrate or matching placebo. Plasma UA was measured before and after a 6-week, active fenofibrate run-in phase in all participants. Cox proportional hazards models were used to explore the relationships between baseline UA, pre-to-post run-in reductions in UA and long-term cardiovascular outcomes. RESULTS: Mean baseline plasma UA was 0.33 mmol/L (SD 0.08). Baseline UA was a significant predictor of long-term cardiovascular events, with every 0.1 mmol/L higher UA conferring a 21% increase in event rate (HR 1.21, 95% CI 1.13-1.29, P < .001). This remained significant after adjustment for treatment allocation, cardiovascular risk factors and renal function. The extent of UA reduction during fenofibrate run-in was also a significant predictor of long-term cardiovascular events, with every 0.1 mmol/L greater reduction conferring a 14% lower long-term risk (HR 0.86, 95% CI 0.76-0.97, P = .015). This effect was not modified by treatment allocation (Pinteraction = .77). CONCLUSIONS: UA is a strong independent predictor of long-term cardiovascular risk in adults with T2D. Although greater reduction in UA on fenofibrate is predictive of lower cardiovascular risk, this does not appear to mediate the cardioprotective effects of fenofibrate.