The 10 essential questions regarding lipoprotein(a).

PURPOSE OF REVIEW: Lp(a) is one of the most atherogenic lipoproteins, and significant progress has been made to understand its pathophysiology over the last 20 years. There are now selective therapies in late-stage clinical trials to lower Lp(a). Yet there are many outstanding questions about Lp(a). This review outlines 10 of the most burning questions and tries to answer some of them. RECENT FINDINGS: Antisense oligonucleotide (ASO) treatment is currently the most advanced therapy to lower plasma Lp(a) by 60-80%. There are, however, also two small molecule medications in early stage of development with similar efficacy. SUMMARY: This review aims to answer important preclinical and clinical questions about the metabolism and physiological role of Lp(a) and also outlines possible therapeutic approaches with nutraceuticals, currently available lipid-lowering therapies and new medications. In addition, ways are illustrated to use Lp(a) as a marker to better predict cardiovascular risk.

Prognostic utility of serum NT-proBNP (fragments 1-76aa and 13-71aa) and galectin-3 in predicting death and re-hospitalisation due to cardiovascular events in patients with heart failure.

Patients with heart failure (HF) are at a higher risk of rehospitalisation. In this study, we investigated the prognostic utility of galectin-3 (Gal-3) and NT-proBNP fragments (1-76aa and 13-71aa) as biomarkers to predict outcomes for patients with HF. We collected blood samples from patients with HF (n = 101). Gal-3 and NT-proBNP fragments (1-76aa and 13-71aa) concentrations were measured by immunoassay. Survival analysis and Cox proportional regression models were used to determine the prognostic utility of Gal-3 and NT-proBNP fragments. In patients with increased baseline levels of NT-proBNP1-76 the time to primary endpoint (cardiovascular death or re-hospitalisation) was significantly shorter (p = 0.0058), but not in patient with increased baseline levels of Gal-3 or NTproBNP13-71. Patients with increased levels of NT-proBNP13-71aa at 1 month showed reduced time to the primary endpoint (p = 0.0123). Our findings demonstrated that Gal-3 and NT-proBNP can be used as prognostic biomarkers to stratify patients with HF.

Australian and New Zealand Living Guideline cholesterol-lowering therapy for people with chronic kidney disease (CARI Guidelines): Reducing the evidence-practice gap.

AIM: People with chronic kidney disease experience high rates of cardiovascular disease. Cholesterol-lowering therapy is a mainstay in the management but there is uncertainty in the treatment effects on patient-important outcomes, such as fatigue and rhabdomyolysis. Here, we summarise the updated CARI Australian and New Zealand Living Guidelines on cholesterol-lowering therapy in chronic kidney disease. METHODS: We updated a Cochrane review and monitored newly published studies weekly to inform guideline development according to international standards. The Working Group included expertise from nephrology, cardiology, Indigenous Health, guideline development and people with lived experience of chronic kidney disease. RESULTS: The guideline recommends people with chronic kidney disease (eGFR ≥15 mL/min/1.73 m2) and an absolute cardiovascular risk of 10% or higher should receive statin therapy (with or without ezetimibe) to reduce the risk of cardiovascular events and death (strong recommendation, moderate certainty evidence). The guidelines also recommends a lower absolute cardiovascular risk threshold (≥5%) for Aboriginal and Torres Strait Islander Peoples and Maori with chronic kidney disease to receive statin therapy (with or without ezetimibe) (strong recommendation, low certainty evidence). The evidence was actively surveyed from 2020-2023 and updated as required. No changes to guideline recommendations were made, with no new data on the balance and benefits of harms. CONCLUSIONS: The development of living guidelines was feasible and provided the opportunity to update recommendations to improve clinical decision-making in real-time. Living guidelines provide the opportunity to transform chronic kidney disease guidelines.

Omega-3 fatty acids and cardiovascular prevention: is the jury still out?

The cardiovascular benefits of omega-3 polyunsaturated fatty acids (O3FA) remain a point of confusion in clinical medicine. Recently two large, randomised trials were published with discordant findings regarding the overall benefits of omega-3 supplementation, resulting in unnecessary confusion and therapeutic nihilism. Epidemiological studies clearly show high intake of fish and measured O3FA (mainly eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA)) in tissues are inversely associated with cardiovascular events and total mortality. These fatty acids are 'essential' and depend almost entirely on intake with very little production from within the body. The efficacy of supplementation depends on background tissue levels, in contradistinction to drug therapy. Insufficient dosing of omega-3 supplementation using less than 1 g/day and lack of titration to target by failing to measure O3FA levels in the blood may explain these conflicting trial outcomes. We review the current evidence regarding O3FA supplementation and cardiovascular outcomes, describe possible reasons for the discrepant results in the literature including recent controversial data around the mineral oil comparator used in REDUCE-IT and discuss the potential use of the omega-3 index to guide management and optimise supplementation in those at greatest risk.

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.

Barriers to and Facilitators of Implementing Guidelines for Detecting Familial Hypercholesterolaemia in Australia.

BACKGROUND: Familial hypercholesterolaemia (FH) is a genetic condition that is a preventable cause of premature cardiovascular morbidity and mortality. High-level evidence and clinical practice guidelines support preventative care for people with FH. However, it is estimated that less than 10% of people at risk of FH have been detected using any approach across Australian health settings. The aim of this study was to identify the implementation barriers to and facilitators of the detection of FH in Australia. METHODS: Four, 2-hour virtual focus groups were facilitated by implementation scientists and a clinicians as part of the 2021 Australasian FH Summit. Template analysis was used to identify themes. RESULTS: There were 28 workshop attendees across four groups (n=6-8 each), yielding 13 barriers and 10 facilitators across three themes: (1) patient related, (2) provider related, and (3) system related. A "lack of care pathways" and "upskilling clinicians in identifying and diagnosing FH" were the most interconnected barriers and facilitators for the detection of FH. CONCLUSIONS: The relationships between barriers and facilitators across the patient, provider, and system themes indicates that a comprehensive implementation strategy is needed to address these different levels. Future research is underway to develop a model for implementing the Australian FH guidelines into practice.

Lp(a) and the Risk for Cardiovascular Disease: Focus on the Lp(a) Paradox in Diabetes Mellitus.

Lipoprotein(a) (Lp(a)) is one of the strongest causal risk factors of atherosclerotic disease. It is rich in cholesteryl ester and composed of apolipoprotein B and apo(a). Plasma Lp(a) levels are determined by apo(a) transcriptional activity driven by a direct repeat (DR) response element in the apo(a) promoter under the control of (HNF)4α Farnesoid-X receptor (FXR) ligands play a key role in the downregulation of APOA expression. In vitro studies on the catabolism of Lp(a) have revealed that Lp(a) binds to several specific lipoprotein receptors; however, their in vivo role remains elusive. There are more than 1000 publications on the role of diabetes mellitus (DM) in Lp(a) metabolism; however, the data is often inconsistent and confusing. In patients suffering from Type-I diabetes mellitus (T1DM), provided they are metabolically well-controlled, Lp(a) plasma concentrations are directly comparable to healthy individuals. In contrast, there exists a paradox in T2DM patients, as many of these patients have reduced Lp(a) levels; however, they are still at an increased cardiovascular risk. The Lp(a) lowering mechanism observed in T2DM patients is most probably caused by mutations in the mature-onset diabetes of the young (MODY) gene and possibly other polymorphisms in key transcription factors of the apolipoprotein (a) gene (APOA).

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.

Management of Fetal Supraventricular Tachycardia: Case Series from a Tertiary Perinatal Cardiac Center.

BACKGROUND: Fetal supraventricular tachycardia is a relatively uncommon cardiac rhythm abnormality which is often associated with adverse perinatal outcomes if untreated. Although there are several treatment modalities and protocols in use globally, there is no consensus as to the most effective antiarrhythmic to manage this condition. AIM: This study aimed to evaluate perinatal outcomes following prenatal maternal therapy for fetal supraventricular tachycardia. MATERIALS AND METHODS: This was a 20-year retrospective cohort study. Institutional records were reviewed for antenatal therapy choice and maternal and fetal outcomes. RESULTS: Sixty-nine cases met diagnostic criteria for fetal SVT, of which 56 (81%) received maternal antiarrhythmic therapy. Digoxin was the most common, but least effective, first-line therapy in 28 patients, achieving successful rate reversion in 35.7%. Thirty-one patients (55%) required second-line therapy, and this was most successful with digoxin and flecainide polytherapy achieving rate reversion in 17 of 18 cases (94.5%) at a median of 3 days (1.5-7). Hydrops was present in 23 (33%) cases at initial presentation, 16 of which achieved rate reversion. There was minimal difference in treatment efficacy comparing single- or multiple-agent treatment in the setting of hydrops (50% vs. 42.8%). Side effects occurred in 14/56 treated patients (25%) but were severe in only 8 (14.3%) women, most commonly with digoxin and flecainide polytherapy (6 of 8 cases). There were 3 (4%) fetal deaths amongst the study cohort. CONCLUSIONS: Digoxin and flecainide polytherapy were well tolerated and successfully achieved rhythm and rate control in fetuses with prenatally diagnosed supraventricular tachycardia. The presence of hydrops was a poor prognostic feature.

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.

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.

Familial Hypercholesterolaemia in 2020: A Leading Tier 1 Genomic Application.

Familial hypercholesterolaemia (FH) is caused by a major genetic defect in the low-density lipoprotein (LDL) clearance pathway. Characterised by LDL-cholesterol elevation from birth, FH confers a significant risk for premature coronary artery disease (CAD) if overlooked and untreated. With risk exposure beginning at birth, early detection and intervention is crucial for the prevention of CAD. Lowering LDL-cholesterol with lifestyle and statin therapy can reduce the risk of CAD. However, most individuals with FH will not reach guideline recommended LDL-cholesterol targets. FH has an estimated prevalence of approximately 1:250 in the community. Multiple strategies are required for screening, diagnosing and treating FH. Recent publications on FH provide new data for developing models of care, including new therapies. This review provides an overview of FH and outlines some recent advances in the care of FH for the prevention of CAD in affected families. The future care of FH in Australia should be developed within the context of the National Health Genomics Policy Framework.

Lipid-related genetic polymorphisms significantly modulate the association between lipids and disability progression in multiple sclerosis.

OBJECTIVE: To investigate whether lipid-related or body mass index (BMI)-related common genetic polymorphisms modulate the associations between serum lipid levels, BMI and disability progression in multiple sclerosis (MS). METHODS: The association between disability progression (annualised Expanded Disability Status Scale (EDSS) change over 5 years, ΔEDSS) and lipid-related or BMI-related genetic polymorphisms was evaluated in a longitudinal cohort (n=184), diagnosed with MS. We constructed a cumulative genetic risk score (CGRS) of associated polymorphisms (p<0.05) and examined the interactions between the CGRS and lipid levels (measured at baseline) in predicting ΔEDSS. All analyses were conducted using linear regression. RESULTS: Five lipid polymorphisms (rs2013208, rs9488822, rs17173637, rs10401969 and rs2277862) and one BMI polymorphism (rs2033529) were nominally associated with ΔEDSS. The constructed lipid CGRS showed a significant, dose-dependent association with ΔEDSS (ptrend=1.4×10-6), such that participants having ≥6 risk alleles progressed 0.38 EDSS points per year faster compared with those having ≤3. This CGRS model explained 16% of the variance in ΔEDSS. We also found significant interactions between the CGRS and lipid levels in modulating ΔEDSS, including high-density lipoprotein (HDL; pinteraction=0.005) and total cholesterol:high-density lipoprotein ratio (TC:HDL; pinteraction=0.030). The combined model (combination of CGRS and the lipid parameter) explained 26% of the disability variance for HDL and 27% for TC:HDL. INTERPRETATION: In this prospective cohort study, both lipid levels and lipid-related polymorphisms individually and jointly were associated with significantly increased disability progression in MS. These results indicate that these polymorphisms and tagged genes might be potential points of intervention to moderate disability progression.

Dilated Cardiomyopathy in Pregnancy: Outcomes From an Australian Tertiary Centre for Maternal Medicine and Review of the Current Literature.

BACKGROUND: Peripartum cardiomyopathy is associated with significant risks of decline in left ventricular function and adverse maternal and fetal outcome in subsequent pregnancy. The risks of pregnancy in women with dilated cardiomyopathy are unclear. We aimed to assess the outcome of pregnancy in women with dilated cardiomyopathy seen at our institution and to review the literature on this subject. METHODS: A retrospective audit of the outcomes of 14 pregnancies to 12 women with dilated cardiomyopathy. RESULTS: There were no cardiac events and no woman had a decline in left ventricular function during pregnancy. There was a high rate of prematurity and adverse fetal outcome related to this, including four neonatal deaths. CONCLUSION: Maternal outcomes in this small series were satisfactory though only three women had moderate-severe left ventricular dysfunction at baseline. There was a high rate of premature delivery and adverse neonatal outcome.

Status of PCSK9 Monoclonal Antibodies in Australia.

Proprotein convertase subtilisin/kexin type 9 (PCSK9) monoclonal antibodies (mAb) have progressed from showing marked low density lipoprotein cholesterol lowering in early phase trials through to reducing cardiovascular events in large clinical outcome trials. Recently in Australia, the indication for evolocumab has been expanded to include both heterozygous and homozygous familial hypercholesterolaemia under the Pharmaceutical Benefits Scheme (PBS). With prices remaining high currently their use in non-familial hypercholesterolaemia in Australia remains by private prescription only at this stage. This manuscript summarises the major outcomes trials of the PCSK9 mAbs and the secondary analyses that have assessed their benefits in high risk patient groups, and describes the consensus of authors on which patients would most likely benefit from PCSK9 mAb therapy.

Chronic myeloid leukaemia and tyrosine kinase inhibitor therapy: assessment and management of cardiovascular risk factors.

Several BCR-ABL1 tyrosine kinase inhibitors (TKIs) are approved for the first-line treatment of chronic phase chronic myeloid leukaemia (CML). Disease control is achieved in the vast majority of patients and disease-specific survival is excellent. Consequently, there is now emphasis on managing comorbidities and minimising treatment-related toxicity. Second-generation TKIs have cardiovascular risks that are greater than with imatinib treatment, but these risks must be balanced against the superior CML responses encountered with more potent TKIs. Cardiovascular risk should be assessed at baseline using a locally validated model based on the Framingham risk equation. Clinicians involved in the care of CML patients should be aware of the vascular complications of TKIs and manage cardiovascular risk factors early to mitigate treatment-related risks. Reversible risk factors, such as dyslipidaemia, smoking, diabetes and hypertension, should be addressed. We summarise the available data on cardiovascular complications in CML patients treated with TKIs. Using the latest evidence and collective expert opinion, we provide practical advice for clinicians to assess, stratify and manage cardiovascular risk in people with CML receiving TKI therapy.

Lipoprotein (a): a historical appraisal.

Initially, lipoprotein (a) [Lp(a)] was believed to be a genetic variant of lipoprotein (Lp)-B. Because its lipid moiety is almost identical to LDL, Lp(a) has been deliberately considered to be highly atherogenic. Lp(a) was detected in 1963 by Kare Berg, and individuals who were positive for this factor were called Lpa+ Lpa+ individuals were found more frequently in patients with coronary heart disease than in controls. After the introduction of quantitative methods for monitoring of Lp(a), it became apparent that Lp(a), in fact, is present in all individuals, yet to a greatly variable extent. The genetics of Lp(a) had been a mystery for a long time until Gerd Utermann discovered that apo(a) is expressed by a variety of alleles, giving rise to a unique size heterogeneity. This size heterogeneity, as well as countless mutations, is responsible for the great variability in plasma Lp(a) concentrations. Initially, we proposed to evaluate the risk of myocardial infarction at a cut-off for Lp(a) of 30-50 mg/dl, a value that still is adopted in numerous epidemiological studies. Due to new therapies that lower Lp(a) levels, there is renewed interest and still rising research activity in Lp(a). Despite all these activities, numerous gaps exist in our knowledge, especially as far as the function and metabolism of this fascinating Lp are concerned.

An adverse lipid profile and increased levels of adiposity significantly predict clinical course after a first demyelinating event.

OBJECTIVE: To investigate the prospective associations between adiposity and lipid-related variables and conversion to multiple sclerosis (MS), time to subsequent relapse and progression in disability. METHODS: A cohort of 279 participants with a first clinical diagnosis of central nervous system demyelination was prospectively followed to 5-year review. Height, weight, waist and hip circumference were measured, and serum samples taken for measurement of lipids and apolipoproteins. Survival analysis was used for conversion to MS and time to relapse, and linear regression for annualised change in disability (Expanded Disability Status Scale). RESULTS: Higher body mass index (BMI; adjusted HR (aHR): 1.22 (1.04 to 1.44) per 5 kg/m2 increase), hip circumference (aHR: 1.32 (1.12 to 1.56) per 10 cm increase) and triglyceride levels (aHR: 1.20 (1.03 to 1.40) per unit increase) were associated with increased risk of subsequent relapse, while adiposity and lipid-related measures were not associated with conversion to MS. In addition, higher BMI (ß: 0.04 (0.01 to 0.07) per 5 kg/m2 increase), hip circumference (ß: 0.04 (0.02 to 0.08) per 10 cm increase), waist circumference (ß: 0.04 (0.02 to 0.07) per 10 cm increase), total cholesterol to high-density lipoprotein ratio (TC/HDL ratio; ß: 0.05 (0.001 to 0.10) and non-HDL; ß: 0.04 (0.001 to 0.08) at study entry) were associated with a higher subsequent annual change in disability. CONCLUSIONS: Higher levels of adiposity, non-HDL and TC/HDL ratio were prospectively associated with a higher rate of disability progression, and higher adiposity and triglycerides were associated with relapse but not with conversion to MS. Improving the lipid profile and losing weight into the healthy range could reduce the accumulation of disability.

Negative predictive value of dobutamine stress echocardiography for perioperative risk stratification in patients with cardiac risk factors and reduced exercise capacity undergoing non-cardiac surgery.

BACKGROUND: Guidelines recommend functional testing for myocardial ischaemia in the perioperative setting in patients with greater than one recognised cardiac risk factor and self-reported reduced exercise capacity. AIM: To determine the clinical utility of dobutamine stress echocardiography (DSE) for perioperative risk stratification in patients undergoing major non-cardiac surgery. METHODS: Data on 79 consecutive patients undergoing DSE for perioperative risk stratification at a single centre were retrospectively reviewed to determine rates of major adverse cardiac events (MACE) during the index hospitalisation and 30 days post-discharge. Echocardiography and outcome data were obtained through a folder audit and echolab database. RESULTS: Out of the 79 DSE performed for perioperative risk stratification, 11 (14%) were positive (DSE +ve) and 68 (86%) were negative (DSE -ve). Management in the DSE +ve group included medical optimisation without invasive intervention (n = 7(64%)), diagnostic coronary angiography (n = 3(27%)) and coronary artery bypass graft (n = 1(9%)). None of the patients underwent percutaneous coronary intervention preoperatively. Perioperative MACE in the DSE +ve group was 36% compared to 4% in the DSE-ve group (P = 0.006). DSE +ve was a powerful predictor of perioperative inpatient MACE (OR 12.4, 95% CI 2.3-67, P = 0.003). The positive predictive value of DSE +ve status was 36%, whereas the negative predictive value of DSE-ve status for perioperative MACE was 96%. CONCLUSION: DSE for perioperative risk stratification had a high clinical utility in patients undergoing major non-cardiac surgery. In particular, a normal DSE had a high negative predictive value for perioperative MACE.

Effectiveness of the cardiac-diabetes transcare program: protocol for a randomised controlled trial.

BACKGROUND: This paper presents a protocol for a randomised controlled trial of the Cardiac-Diabetes Transcare program which is a transitional care, multi-modal self-management program for patients with acute coronary syndrome comorbid with type 2 diabetes. Prior research has indicated people hospitalised with dual cardiac and diabetes diagnoses are at an elevated risk of hospital readmissions, morbidity and mortality. The primary aim of this study is to evaluate the effectiveness (and cost-effectiveness) of a Cardiac-Diabetes Transcare intervention program on 6-month readmission rate in comparison to usual care. METHODS/DESIGN: A two-armed, randomised controlled trial with blinded outcome assessment will be conducted to evaluate the comparative effectiveness of two modes of care, including a Usual Care Group and a Cardiac-Diabetes Transcare Intervention (in addition to usual care) Group. The primary outcome is 6-month readmission rate, although a range of secondary outcomes will be collected (including self-efficacy) at baseline, 1, 3 and 6 month reassessments. The intervention group will receive in-hospital education tailored for people recovering from an acute coronary syndrome-related hospital admission who have comorbid diabetes, and they will also receive home visits and telephone follow-up by a trained Research Nurse to reinforce and facilitate disease-management-related behaviour change. Both groups will receive usual care interventions offered or referred from participating hospital facilities. A sample size of 432 participants from participating hospitals in the Australian states of Queensland and Victoria will be recruited for 90% power based on the most conservative scenarios modelled for sample size estimates. DISCUSSION: The study outlined in this protocol will provide valuable insight into the effectiveness of a transitional care intervention targeted for people admitted to hospital with cardiac-related presentations commencing in the inpatient hospital setting and transition to the home environment. The purpose of theory-based intervention comprising face-to-face sessions and telephone follow up for patients with acute coronary syndrome and type 2 diabetes is to increase self-efficacy to enhance self-management behaviours and thus improve health outcomes and reduce hospital readmissions. TRIAL REGISTRATION: This study has been registered with the Australian New Zealand Clinical Trials Registry dated 16/12/2014: ACTRN12614001317684 .