Smoking data quality of primary care practices in comparison with smoking data from the New Zealand Maori and Pacific abdominal aortic aneurysm screening programme: an observational study.

BACKGROUND: Quality smoking data is crucial for assessing smoking-related health risk and eligibility for interventions related to that risk. Smoking information collected in primary care practices (PCPs) is a major data source; however, little is known about the PCP smoking data quality. This project compared PCP smoking data to that collected in the Maori and Pacific Abdominal Aortic Aneurysm (AAA) screening programme. METHODS: A two stage review was conducted. In Stage 1, data quality was assessed by comparing the PCP smoking data recorded close to AAA screening episodes with the data collected from participants at the AAA screening session. Inter-rater reliability was analysed using Cohen's kappa scores. In Stage 2, an audit of longitudinal smoking status was conducted, of a subset of participants potentially misclassified in Stage 1. Data were compared in three groups: current smoker (smoke at least monthly), ex-smoker (stopped > 1 month ago) and never smoker (smoked < 100 cigarettes in lifetime). RESULTS: Of the 1841 people who underwent AAA screening, 1716 (93%) had PCP smoking information. Stage 1 PCP smoking data showed 82% concordance with the AAA data (adjusted kappa 0.76). Fewer current or ex-smokers were recorded in PCP data. In the Stage 2 analysis of discordant and missing data (N = 313), 212 were enrolled in the 29 participating PCPs, and of these 13% were deceased and 41% had changed PCP. Of the 93 participants still enrolled in the participating PCPs, smoking status had been updated for 43%. Data on quantity, duration, or quit date of smoking were largely missing in PCP records. The AAA data of ex-smokers who were classified as never smokers in the Stage 2 PCP data (N = 27) showed a median smoking cessation duration of 32 years (range 0-50 years), with 85% (N = 23) having quit more than 15 years ago. CONCLUSIONS: PCP smoking data quality compared with the AAA data is consistent with international findings. PCP data captured fewer current and ex-smokers, suggesting ongoing improvement is important. Intervention programmes based on smoking status should consider complementary mechanisms to ensure eligible individuals are not missed from programme invitation.

The Prevalence and Management of Atrial Fibrillation in New Zealand Maori Detected through an Abdominal Aortic Aneurysm Screening Program.

BACKGROUND: Atrial fibrillation (AF) screening was incorporated into an abdominal aortic aneurysm screening (AAA) program for New Zealand (NZ) Maori. METHODS: AF screening was performed as an adjunct to AAA screening of Maori men aged 60-74 years and women aged 65-74 years registered with primary health care practices in Auckland, NZ. Pre-existing AF was determined through coded diagnoses or medications in the participant's primary care record. Subsequent audit of the record assessed accuracy of pre-screening coding, medication use and clinical follow-up. RESULTS: Among 1,933 people successfully screened, the prevalence of AF was 144 (7.4%), of which 46 (2.4% of the cohort) were patients without AF coded in the medical record. More than half of these were revealed to be known AF but that was not coded. Thus, the true prevalence of newly detected AF was 1.1% (n=21). An additional 48 (2.5%) of the cohort had been coded as AF but were not in AF at the time of screening. Among the 19 at-risk screen-detected people with AF, 10 started appropriate anticoagulation therapy within 6 months. Of the nine patients who did not commence anticoagulation therapy, five had a subsequent adverse clinical outcome in the follow-up period, including one with ischaemic stroke; two had contraindications to anticoagulants. Among those with previously diagnosed AF, the proportion receiving anticoagulation therapy rose from 57% pre-screening to 83% at 6 months post-screening (p<0.0001); among newly diagnosed AF the proportion rose from 0% to 53% (p<0.01). CONCLUSIONS: AF screening is a feasible low-cost adjunct to AAA screening with potential to reduce ethnic inequities in stroke incidence. However, effective measures are needed to ensure that high-risk newly diagnosed AF is managed according to best practice guidelines.

Reduction of dietary sodium to less than 100 mmol in heart failure (SODIUM-HF): an international, open-label, randomised, controlled trial.

BACKGROUND: Dietary restriction of sodium has been suggested to prevent fluid overload and adverse outcomes for patients with heart failure. We designed the Study of Dietary Intervention under 100 mmol in Heart Failure (SODIUM-HF) to test whether or not a reduction in dietary sodium reduces the incidence of future clinical events. METHODS: SODIUM-HF is an international, open-label, randomised, controlled trial that enrolled patients at 26 sites in six countries (Australia, Canada, Chile, Colombia, Mexico, and New Zealand). Eligible patients were aged 18 years or older, with chronic heart failure (New York Heart Association [NYHA] functional class 2-3), and receiving optimally tolerated guideline-directed medical treatment. Patients were randomly assigned (1:1), using a standard number generator and varying block sizes of two, four, or six, stratified by site, to either usual care according to local guidelines or a low sodium diet of less than 100 mmol (ie, <1500 mg/day). The primary outcome was the composite of cardiovascular-related admission to hospital, cardiovascular-related emergency department visit, or all-cause death within 12 months in the intention-to-treat (ITT) population (ie, all randomly assigned patients). Safety was assessed in the ITT population. This study is registered with ClinicalTrials.gov, NCT02012179, and is closed to accrual. FINDINGS: Between March 24, 2014, and Dec 9, 2020, 806 patients were randomly assigned to a low sodium diet (n=397) or usual care (n=409). Median age was 67 years (IQR 58-74) and 268 (33%) were women and 538 (66%) were men. Between baseline and 12 months, the median sodium intake decreased from 2286 mg/day (IQR 1653-3005) to 1658 mg/day (1301-2189) in the low sodium group and from 2119 mg/day (1673-2804) to 2073 mg/day (1541-2900) in the usual care group. By 12 months, events comprising the primary outcome had occurred in 60 (15%) of 397 patients in the low sodium diet group and 70 (17%) of 409 in the usual care group (hazard ratio [HR] 0·89 [95% CI 0·63-1·26]; p=0·53). All-cause death occurred in 22 (6%) patients in the low sodium diet group and 17 (4%) in the usual care group (HR 1·38 [0·73-2·60]; p=0·32), cardiovascular-related hospitalisation occurred in 40 (10%) patients in the low sodium diet group and 51 (12%) patients in the usual care group (HR 0·82 [0·54-1·24]; p=0·36), and cardiovascular-related emergency department visits occurred in 17 (4%) patients in the low sodium diet group and 15 (4%) patients in the usual care group (HR 1·21 [0·60-2·41]; p=0·60). No safety events related to the study treatment were reported in either group. INTERPRETATION: In ambulatory patients with heart failure, a dietary intervention to reduce sodium intake did not reduce clinical events. FUNDING: Canadian Institutes of Health Research and the University Hospital Foundation, Edmonton, Alberta, Canada, and Health Research Council of New Zealand.

Atrial fibrillation incidence and outcomes in two cohorts of octogenarians: LiLACS NZ.

BACKGROUND: Atrial fibrillation (AF), the most common cardiac arrhythmia in the general population, has significant healthcare burden. Little is known about AF in octogenarians. OBJECTIVE: To describe the prevalence and incidence rate of AF in New Zealand (NZ) octogenarians and the risk of stroke and mortality at 5-year follow-up. DESIGN: Longitudinal Cohort Study. SETTING: Bay of Plenty and Lakes health regions of New Zealand. SUBJECTS: Eight-hundred-seventy-seven (379 indigenous Maori, 498 non-Maori) were included in the analysis. METHODS: AF, stroke/TIA events and relevant co-variates were established annually using self-report and hospital records (and ECG for AF). Cox proportional-hazards regression models were used to determine the time dependent AF risk of stroke/TIA. RESULTS: AF was present in 21% at baseline (Maori 26%, non-Maori 18%), the prevalence doubled over 5-years (Maori 50%, non-Maori 33%). 5-year AF incidence was 82.6 /1000-person years and at all times AF incidence for Maori was twice that of non-Maori. Five-year stroke/TIA prevalence was 23% (22% in Maori and 24% non- Maori), higher in those with AF than without. AF was not independently associated with 5-year new stroke/TIA; baseline systolic blood pressure was. Mortality was higher for Maori, men, those with AF and CHF and statin use was protective. In summary, AF is more prevalent in indigenous octogenarians and should have an increased focus in health care management. Further research could examine treatment in more detail to facilitate ethnic specific impact and risks and benefits of treating AF in octogenarians.

Relationship Between Soluble Transferrin Receptor and Clinical Outcomes in Patients With Heart Failure According to Ejection Fraction Phenotype: The New Zealand PEOPLE Study.

BACKGROUND: Iron deficiency (ID) is highly prevalent in patients with heart failure (HF) but its impact on prognosis in HF with preserved ejection fraction (HFpEF) remains unclear. We assessed whether ID defined by soluble transferrin receptor (sTfR) criteria is independently associated with all-cause mortality in patients with HFpEF, and evaluated its comparative prognostic performance to ID definitions in common clinical use. METHODS AND RESULTS: Data were analyzed from 788 patients (36% HFpEF) in a prospective multicenter HF cohort study. Baseline plasma samples were analyzed with respect to 4 definitions of ID: sTfR of ≥1.59 mg/L (IDsTfR1), sTfR of ≥1.76 mg/L (IDsTfR2), ferritin of <100 µg/L, or ferritin of 100-300 µg/L + transferrin saturation of <20% (IDFerritin), and transferrin saturation of <20% (IDTsat). In multivariable Cox models IDsTfR2 (hazard ratio [HR] 1.84, 95% confidence interval [CI] 1.23-2.75) and IDTsat (HR, 1.69, 95% CI 1.10-2.59) were both independently associated with all-cause mortality in patients with HFpEF, whereas IDsTfR1 (HR 1.41, 95% CI 0.92-2.16) and IDFerritin (HR 1.19, 95% CI 0.77-1.85) were not. On inclusion of patients with HF with reduced EF, IDsTfR1 (HR 1.45, 95% CI 1.13-1.86) gained significance, but IDFerritin (HR 1.21, 95% CI 0.95-1.54) did not. For each pair of definitions intra-patient concordance was approximately 65%. CONCLUSION: ID defined by sTfR criteria is independently associated with all-cause mortality in patients with HFpEF. Poor concordance between ID definitions suggests that iron biomarkers do not reflect the same pathological process in the complex relationship between iron and HF. Therefore, which definition should guide iron replacement needs further evaluation.

Genetically determined NLRP3 inflammasome activation associates with systemic inflammation and cardiovascular mortality.

AIMS: Inflammation plays an important role in cardiovascular disease (CVD) development. The NOD-like receptor protein-3 (NLRP3) inflammasome contributes to the development of atherosclerosis in animal models. Components of the NLRP3 inflammasome pathway such as interleukin-1ß can therapeutically be targeted. Associations of genetically determined inflammasome-mediated systemic inflammation with CVD and mortality in humans are unknown. METHODS AND RESULTS: We explored the association of genetic NLRP3 variants with prevalent CVD and cardiovascular mortality in 538 167 subjects on the individual participant level in an explorative gene-centric approach without performing multiple testing. Functional relevance of single-nucleotide polymorphisms on NLRP3 inflammasome activation has been evaluated in monocyte-enriched peripheral blood mononuclear cells (PBMCs). Genetic analyses identified the highly prevalent (minor allele frequency 39.9%) intronic NLRP3 variant rs10754555 to affect NLRP3 gene expression. rs10754555 carriers showed significantly higher C-reactive protein and serum amyloid A plasma levels. Carriers of the G allele showed higher NLRP3 inflammasome activation in isolated human PBMCs. In carriers of the rs10754555 variant, the prevalence of coronary artery disease was significantly higher as compared to non-carriers with a significant interaction between rs10754555 and age. Importantly, rs10754555 carriers had significantly higher risk for cardiovascular mortality during follow-up. Inflammasome inducers (e.g. urate, triglycerides, apolipoprotein C3) modulated the association between rs10754555 and mortality. CONCLUSION: The NLRP3 intronic variant rs10754555 is associated with increased systemic inflammation, inflammasome activation, prevalent coronary artery disease, and mortality. This study provides evidence for a substantial role of genetically driven systemic inflammation in CVD and highlights the NLRP3 inflammasome as a therapeutic target.

Association of Factor V Leiden With Subsequent Atherothrombotic Events: A GENIUS-CHD Study of Individual Participant Data.

BACKGROUND: Studies examining the role of factor V Leiden among patients at higher risk of atherothrombotic events, such as those with established coronary heart disease (CHD), are lacking. Given that coagulation is involved in the thrombus formation stage on atherosclerotic plaque rupture, we hypothesized that factor V Leiden may be a stronger risk factor for atherothrombotic events in patients with established CHD. METHODS: We performed an individual-level meta-analysis including 25 prospective studies (18 cohorts, 3 case-cohorts, 4 randomized trials) from the GENIUS-CHD (Genetics of Subsequent Coronary Heart Disease) consortium involving patients with established CHD at baseline. Participating studies genotyped factor V Leiden status and shared risk estimates for the outcomes of interest using a centrally developed statistical code with harmonized definitions across studies. Cox proportional hazards regression models were used to obtain age- and sex-adjusted estimates. The obtained estimates were pooled using fixed-effect meta-analysis. The primary outcome was composite of myocardial infarction and CHD death. Secondary outcomes included any stroke, ischemic stroke, coronary revascularization, cardiovascular mortality, and all-cause mortality. RESULTS: The studies included 69 681 individuals of whom 3190 (4.6%) were either heterozygous or homozygous (n=47) carriers of factor V Leiden. Median follow-up per study ranged from 1.0 to 10.6 years. A total of 20 studies with 61 147 participants and 6849 events contributed to analyses of the primary outcome. Factor V Leiden was not associated with the combined outcome of myocardial infarction and CHD death (hazard ratio, 1.03 [95% CI, 0.92-1.16]; I2=28%; P-heterogeneity=0.12). Subgroup analysis according to baseline characteristics or strata of traditional cardiovascular risk factors did not show relevant differences. Similarly, risk estimates for the secondary outcomes including stroke, coronary revascularization, cardiovascular mortality, and all-cause mortality were also close to identity. CONCLUSIONS: Factor V Leiden was not associated with increased risk of subsequent atherothrombotic events and mortality in high-risk participants with established and treated CHD. Routine assessment of factor V Leiden status is unlikely to improve atherothrombotic events risk stratification in this population.

Role of transthoracic echocardiogram in acute heart failure.

Acute Heart Failure (AHF) is an increasingly common condition with a poor prognosis. In contrast to CHF where advances in medical therapy and devices has led to significant improvement in morbidity and mortality, the prognosis for AHF has not changed significantly in the last few decades despite efforts to find effective treatment. There are multiple factors that contribute to the high mortality and morbidity of AHF; it can be a diagnostic challenge, determining whether decongestion has been achieved can be difficult, and persisting congestion is commonly present at discharge contributing to early decompensation and rehospitalisation. Transthoracic echocardiogram (TTE) is a unique imaging modality that is non-invasive, can be done at the bedside, in real time during procedures, is affordable and easy to access both in community and inpatient settings. Small hand held 'point of care' scans are increasingly available and being used as an adjunct to improve clinical examination. Consequently, the use of echocardiography to improve outcomes for patients with cardiac disease continues to evolve. In chronic heart failure TTE has established roles in the quantification of HF phenotype, and determination of treatment initiation, escalation and success. However, the role of echocardiogram in AHF is not as well established with society guidelines relying on expert consensus for their recommendations. Use of TTE at all stages of AHF has potential to reduce morbidity and mortality. This review discusses the evidence for use of TTE to improve the diagnosis, prognosis and management of AHF.

A Pharmaceutical Dispensing-based Index of Mortality Risk From Long-term Conditions Performed as well as Hospital Record-based Indices.

OBJECTIVE: The objective of this study was to develop and validate a mortality risk index from multimorbidity using pharmaceutical dispensing data. DESIGN: The P3 (Pharmaceutical Prescribing Profile) mortality risk index was created (development n=2,331,645) using pharmaceutical dispensing records for the last 12 months for long-term conditions. ß coefficients from a Cox proportional hazards model for mortality provided component scores for 30 medication categories. Index validity was tested (validation n=1,000,166) for risk of mortality and overnight hospitalization over 1 year, and predictive ability calculated for the P3 index relative to the hospital admission-based Charlson and M3 indices (all models adjusted for age/sex). SETTING: This study was carried out in the setting of routine health data sources for the New Zealand adult general population, for an index date of January 1, 2012. RESULTS: The P3 index performed equivalently to Charlson for 1-year mortality risk [c-statistics=0.920 and 0.921, respectively; difference=-0.001; 95% confidence interval (CI): -0.004, 0.001]; P3 outperformed Charlson for overnight hospitalization risk (c-statistics=0.712 and 0.682; difference=0.029; 95% CI: 0.028, 0.031). Adding P3 to a model already containing the M3 index led to only marginal improvement for mortality (difference in c-statistics=0.004; 95% CI: 0.002, 0.005) but some improvement for hospitalization risk (difference in c-statistics=0.020; 95% CI: 0.018, 0.021). CONCLUSIONS: The P3 index provides an appropriate alternative to measures like the Charlson and M3 index when analysts only have access to pharmaceutical dispensing data for determining multimorbidity. The P3 index had a performance advantage over Charlson when analyzing risk for overnight hospital admissions.

Target Doses of Secondary Prevention Medications Are Not Being Achieved in Patients With Reduced Left Ventricular Ejection Fraction After Acute Coronary Syndrome (ANZACS-QI 34).

BACKGROUND: Patients with reduced left ventricular ejection fraction (EF<40%) are at high risk for adverse outcomes and benefit from evidence based doses of angiotensin converting enzyme inhibitors (ACEi), angiotensin II receptor blockers (ARB) and beta blockers. Our aim was to investigate the dispensing and uptitration of these medications following acute coronary syndrome (ACS), according to left ventricular ejection fraction. METHODS: Patients presenting with ACS who underwent coronary angiography during 2015 were recorded in the All New Zealand Acute Coronary Syndrome Quality Improvement (ANZACS-QI) registry. Medication dispensing data on discharge and at 1-year follow-up were obtained using anonymised linkage to the national pharmaceutical dataset. Doses of medications dispensed were compared to target doses recommended in clinical guidelines. RESULTS: 4,082 patients were included in the study, of whom 602 (15%) had reduced ejection fraction (rEF). More patients with rEF were prescribed ACEi/ARB on discharge compared to those with preserved ejection fraction (pEF) (89% vs. 68%). Beta blocker dispensing on discharge was also higher in the rEF group (94% vs. 83%). In the rEF subgroup, 76% were maintained on ACEi/ARB and 85% on beta blockers by 1 year of follow-up. However, at discharge only 31% and 29% were on ≥50% of target doses of ACEi/ARB and beta blocker doses respectively, and by 1 year this increased only slightly to 34% and 35% respectively. CONCLUSIONS: There is suboptimal dispensing of evidence-based medications in the year following ACS. Further intervention is required to improve medication uptitration and adherence, particularly of beta blockers and ACEI/ARBs in those with reduced ejection fraction.

Polygenic Risk Scores in Coronary Artery Disease and Atrial Fibrillation.

Coronary artery disease (CAD) and atrial fibrillation (AF) are two highly prevalent cardiovascular disorders that are associated with substantial morbidity and mortality. Conventional clinical risk factors for these disorders may not be identified prior to mid-adult life when pathophysiological processes are already established. A better understanding of the genetic underpinnings of disease should facilitate early detection of individuals at risk and preventative intervention. Single rare variants of large effect size that are causative for CAD, AF, or predisposing factors such as hypertension or hyperlipidaemia, may give rise to familial forms of disease. However, in most individuals, CAD and AF are complex traits in which combinations of genetic and acquired factors play a role. Common genetic variants that affect disease susceptibility have been identified by genome-wide association studies, but the predictive value of any single variant is limited. To address this issue, polygenic risk scores (PRS), comprised of suites of disease-associated common variants have been devised. In CAD and AF, incorporation of PRS into risk stratification algorithms has provided incremental prognostic information to clinical factors alone. The long-term health and economic benefits of PRS-guided clinical management remain to be determined however, and further evidence-based data are required.

COVID-19 and Acute Heart Failure: Screening the Critically Ill - A Position Statement of the Cardiac Society of Australia and New Zealand (CSANZ).

Up to one-third of COVID-19 patients admitted to intensive care develop an acute cardiomyopathy, which may represent myocarditis or stress cardiomyopathy. Further, while mortality in older patients with COVID-19 appears related to multi-organ failure complicating acute respiratory distress syndrome (ARDS), the cause of death in younger patients may be related to acute heart failure. Cardiac involvement needs to be considered early on in critically ill COVID-19 patients, and even after the acute respiratory phase is passing. This Statement presents a screening algorithm to better identify COVID-19 patients at risk for severe heart failure and circulatory collapse, while balancing the need to protect health care workers and preserve personal protective equipment (PPE). The significance of serum troponin levels and the role of telemetry and targeted transthoracic echocardiography (TTE) in patient investigation and management are addressed, as are fundamental considerations in the management of acute heart failure in COVID-19 patients.

ProBNP That Is Not Glycosylated at Threonine 71 Is Decreased with Obesity in Patients with Heart Failure.

BACKGROUND: Heart failure (HF) is a leading cause of morbidity and mortality worldwide. Plasma concentrations of B-type natriuretic peptide (BNP) or its amino terminal congener (NT-proBNP) are used for HF diagnosis and risk stratification. Because BNP concentrations are inexplicably lowered in obese patients, we investigated the relationship between proBNP glycosylation, plasma NT-proBNP, and body mass index (BMI) in HF patients. METHODS: Three assays were developed to distinguish between total proBNP (glycosylated plus nonglycosylated proBNP), proBNP not glycosylated at threonine 71 (NG-T71), and proBNP not glycosylated in the central region (NG-C). Intraassay and interassay CVs were <15%; limits of detection were <21 ng/L; and samples diluted in parallel. RESULT: Applying these assays and an NT-proBNP assay to plasma samples from 106 healthy volunteers and 238 HF patients determined that concentrations [median (interquartile range)] of proBNP, NG-T71, and NT-proBNP were greater in HF patients compared with controls [300 (44-664), 114 (18-254), and 179 (880-3459) ng/L vs 36 (18-229), 36 (18-175), and 40 (17-68) ng/L, respectively; all P < 0.012]. NG-C was undetectable in most samples. ProBNP concentrations in HF patients with BMI more or less than 30 kg/m2 were not different (P = 0.85), whereas HF patients with BMI >30 kg/m2 had lower NT-proBNP and NG-T71 concentrations (P < 0.003) and higher proBNP/NT-proBNP and proBNP/NG-T71 ratios (P = 0.001 and P = 0.02, respectively) than those with BMI <30 kg/m2. CONCLUSIONS: Increased BMI is associated with decreased concentrations of proBNP not glycosylated at T71. Decreased proBNP substrate amenable to processing could partially explain the lower NT-proBNP and BNP concentrations observed in obese individuals, including those presenting with HF.

Mortality associated with heart failure with preserved vs. reduced ejection fraction in a prospective international multi-ethnic cohort study.

Aims: Whether prevalence and mortality of patients with heart failure with preserved or mid-range (40-49%) ejection fraction (HFpEF and HFmREF) are similar to those of heart failure with reduced ejection fraction (HFrEF), as reported in some epidemiologic studies, remains highly controversial. We determined and compared characteristics and outcomes for patients with HFpEF, HFmREF, and HFrEF in a prospective, international, multi-ethnic population. Methods and results: Prospective multi-centre longitudinal study in New Zealand (NZ) and Singapore. Patients with HF were assessed at baseline and followed over 2 years. The primary outcome was death from any cause. Secondary outcome was death and HF hospitalization. Cox proportional hazards models were used to compare outcomes for patients with HFpEF, HFmrEF, and HFrEF. Of 2039 patients enrolled, 28% had HFpEF, 13% HFmrEF, and 59% HFrEF. Compared with HFrEF, patients with HFpEF were older (62 vs. 72 years), more commonly female (17% vs. 48%), and more likely to have a history of hypertension (61% vs. 78%) but less likely to have coronary artery disease (55% vs. 41%). During 2 years of follow-up, 343 (17%) patients died. Adjusting for age, sex, and clinical risk factors, patients with HFpEF had a lower risk of death compared with those with HFrEF (hazard ratio 0.62, 95% confidence interval 0.46-0.85). Plasma (NT-proBNP) was similarly related to mortality in both HFpEF, HFmrEF, and HFrEF independent of the co-variates listed and of ejection fraction. Results were similar for the composite endpoint of death or HF and were consistent between Singapore and NZ. Conclusion: These prospective multinational data showed that the prevalence of HFpEF within the HF population was lower than HFrEF. Death rate was comparable in HFpEF and HFmrEF and lower than in HFrEF. Plasma levels of NT-proBNP were independently and similarly predictive of death in the three HF phenotypes. Trial Registration: Australian New Zealand Clinical Trial Registry (ACTRN12610000374066).

Plasma levels of soluble VEGF receptor isoforms, circulating pterins and VEGF system SNPs as prognostic biomarkers in patients with acute coronary syndromes.

BACKGROUND: Development of collateral circulation in coronary artery disease is cardio-protective. A key process in forming new blood vessels is attraction to occluded arteries of monocytes with their subsequent activation as macrophages. In patients from a prospectively recruited post-acute coronary syndromes cohort we investigated the prognostic performance of three products of activated macrophages, soluble vascular endothelial growth factor (VEGF) receptors (sFlt-1 and sKDR) and pterins, alongside genetic variants in VEGF receptor genes, VEGFR-1 and VEGFR-2. METHODS: Baseline levels of sFlt-1 (VEGFR1), sKDR (VEGFR2) and pterins were measured in plasma samples from subgroups (n = 513; 211; 144, respectively) of the Coronary Disease Cohort Study (CDCS, n = 2067). DNA samples from the cohort were genotyped for polymorphisms from the VEGFR-1 gene SNPs (rs748252 n = 2027, rs9513070 n = 2048) and VEGFR-2 gene SNPs (rs2071559 n = 2050, rs2305948 n = 2066, rs1870377 n = 2042). RESULTS: At baseline, levels of sFlt-1 were significantly correlated with age, alcohol consumption, NTproBNP, BNP and other covariates relevant to cardiovascular pathophysiology. Total neopterin levels were associated with alcohol consumption at baseline. 7,8 dihydroneopterin was associated with BMI. The A allele of VEGFR-2 variant rs1870377 was associated with higher plasma sFlt-1 and lower levels of sKDR at baseline. Baseline plasma sFlt-1 was univariately associated with all cause mortality with (p < 0.001) and in a Cox's proportional hazards regression model sFlt-1 and pterins were both associated with mortality independent of established predictors (p < 0.027). CONCLUSIONS: sFlt-1 and pterins may have potential as prognostic biomarkers in acute coronary syndromes patients. Genetic markers from VEGF system genes warrant further investigation as markers of levels of VEGF system components in these patients. TRIAL REGISTRATION: Australian New Zealand Clinical Trials Registry. ACTRN12605000431628 . 16 September 2005, Retrospectively registered.

Burden of atrial fibrillation in Maori and Pacific people in New Zealand: a cohort study.

BACKGROUND: Atrial fibrillation (AF) is a major risk factor for ischaemic stroke and cardiovascular events. In New Zealand (NZ), Maori (indigenous New Zealanders) and Pacific people experience higher rates of AF compared with non-Maori/non-Pacific people. AIM: To describe a primary care population with AF in NZ. Stroke risk and medication adherence according to ethnicity are also detailed. METHODS: Electronic medical records for adults (≥20 years, n = 135 840, including 19 918 Maori and 43 634 Pacific people) enrolled at 37 NZ general practices were analysed for AF diagnosis and associated medication prescription information. RESULTS: The overall prevalence of non-valvular AF (NVAF) in this population was 1.3% (1769), and increased with age (4.4% in people ≥55 years). Maori aged ≥55 years were more likely to be diagnosed with NVAF (7.3%) than Pacific (4.0%) and non-Maori/non-Pacific people (4.1%, P < 0.001). Maori and Pacific NVAF patients were diagnosed with AF 10 years earlier than non-Maori/non-Pacific patients (median age of diagnosis: Maori = 60 years, Pacific = 61 years, non-Maori/non-Pacific = 71 years, P < 0.001). Overall, 67% of NVAF patients were at high risk for stroke (CHA2 DS2 -VASc ≥ 2) at the time of AF diagnosis. Almost half (48%) of Maori and Pacific NVAF patients aged <65 years were at high risk for stroke, compared with 22% of non-Maori/non-Pacific (P < 0.001). Irrespective of ethnic group, adherence to AF medication was suboptimal in those NVAF patients with a high risk of stroke or with stroke history. CONCLUSION: AF screening and stroke thromboprophylaxis in Maori and Pacific people could start below the age of 65 years in NZ.

Clinical Characteristics and Burden of Risk Factors Among Patients With Early Onset Acute Coronary Syndromes: The ANZACS-QI New Zealand National Cohort (ANZACS-QI 17).

BACKGROUND: Cardiovascular (CV) risk factor profiles of people experiencing acute coronary syndromes (ACS) vary with age, and in New Zealand (NZ), Maori and people of Pacific Island descent typically present with ACS at a younger age. We aimed to explore age- and ethnicity-related differences in CV risk factors in a large NZ cohort with first-time ACS. METHODS: The All NZ Acute Coronary Syndrome Quality Improvement program (ANZACS-QI) registry collects comprehensive data for patients admitted with ACS at NZ hospitals. This analysis includes patients with no prior atherosclerotic CV disease enrolled from 1 July, 2012 to 30 June, 2015. RESULTS: 14,190 patients had confirmed ACS, 8493 (60%) patients with no prior CVD comprised the study cohort. The mean age was 64 years, 25% were aged <55years, and 66% were male. Those aged <55years were more likely than older patients to be current smokers (48% vs 19%), have higher body mass index (BMI) (48% vs 34% with BMI≥30kg/m2), and higher total cholesterol:HDL ratios (≥4.0, 70% vs 50%), all p<0.001. Sixteen per cent of those <55years had diabetes; these patients often had a BMI≥30kg/m2 (67%) and higher median HbA1c than older patients with diabetes (69mmol/mol vs 55mmol/mol). Maori and people of Pacific Island descent were overrepresented in the younger age group; these patients had a very high risk factor burden. CONCLUSIONS: A quarter of NZ patients admitted to hospital with a first-time CV disease event are aged <55years. Younger patients have a very high risk factor burden: half are current smokers, half have a BMI≥30kg/m2, and 16% have diabetes.

C-Type Natriuretic Peptides in Coronary Disease.

AIMS: C-type natriuretic peptide (CNP) is a paracrine growth factor expressed in the vascular endothelium. Although upregulated in atheromatous arteries, the predictive value of plasma CNP products for outcome in coronary disease is unknown. This study aimed to compare the prognostic value of plasma CNP products with those of other natriuretic peptides in individuals with coronary artery disease, and investigate their associations with cardiac and renal function. METHODS AND RESULTS: Plasma concentrations of CNP and amino-terminal proCNP (NT-proCNP) were measured at baseline in 2129 individuals after an index acute coronary syndrome admission and related to cardiac and renal function, other natriuretic peptides [atrial NP (ANP) and B-type NP (BNP)] and prognosis (primary end point, mortality; secondary end point, cardiac readmission). Median follow-up was 4 years. At baseline, and in contrast to CNP, ANP, and BNP, plasma NT-proCNP was higher in males and weakly related to cardiac function but strongly correlated to plasma creatinine. All NPs were univariately associated with mortality. Resampling at 4 and 12 months in survivors showed stable concentrations of NT-proCNP whereas all other peptides declined. When studied by diagnosis (myocardial infarction, unstable angina) at index admission using a multivariate model, NT-proBNP predicted mortality and readmission in myocardial infarction. In unstable angina, only NT-proCNP predicted both mortality and cardiac readmission. CONCLUSIONS: In contrast to the close association of NT-proBNP with cardiac function, and predictive value for outcome after myocardial infarction, plasma NT-proCNP is highly correlated with renal function and is an independent predictor of mortality and cardiac readmission in individuals with unstable angina.

Differing prognostic value of pulse pressure in patients with heart failure with reduced or preserved ejection fraction: results from the MAGGIC individual patient meta-analysis.

AIMS: Low pulse pressure is a marker of adverse outcome in patients with heart failure (HF) and reduced ejection fraction (HF-REF) but the prognostic value of pulse pressure in patients with HF and preserved ejection fraction (HF-PEF) is unknown. We examined the prognostic value of pulse pressure in patients with HF-PEF [ejection fraction (EF) ≥ 50%] and HF-REF. METHODS AND RESULTS: Data from 22 HF studies were examined. Preserved left ventricular ejection fraction (LVEF) was defined as LVEF ≥ 50%. All-cause mortality at 3 years was evaluated in 27 046 patients: 22 038 with HF-REF (4980 deaths) and 5008 with HF-PEF (828 deaths). Pulse pressure was analysed in quintiles in a multivariable model adjusted for the previously reported Meta-Analysis Global Group in Chronic Heart Failure prognostic variables. Heart failure and reduced ejection fraction patients in the lowest pulse pressure quintile had the highest crude and adjusted mortality risk (adjusted hazard ratio 1.68, 95% confidence interval 1.53-1.84) compared with all other pulse pressure groups. For patients with HF-PEF, higher pulse pressure was associated with the highest crude mortality, a gradient that was eliminated after adjustment for other prognostic variables. CONCLUSION: Lower pulse pressure (especially <53 mmHg) was an independent predictor of mortality in patients with HF-REF, particularly in those with an LVEF < 30% and systolic blood pressure <140 mmHg. Overall, this relationship between pulse pressure and outcome was not consistently observed among patients with HF-PEF.

Validation of thoracic impedance cardiography by echocardiography in healthy late pregnancy.

BACKGROUND: Assessment of stroke volume (SV) is often necessary in clinical and research settings. The clinically established method for SV assessment in pregnancy is echocardiography, but given its limitations, it is not always an appropriate measurement tool. Thoracic impedance cardiography (ICG) allows continuous, non-invasive SV assessment. However, SV determination relies on assumptions regarding the thoracic shape that may mean the algorithm is not valid in pregnancy. The available data regarding the validity of ICG against an established reference standard using modern SV algorithms are both limited and conflicting. We aimed to test the validity of ICG in a clinically realistic setting in late pregnancy using echocardiography. METHODS: Twenty-nine women in late pregnancy underwent standard echocardiography assessments with simultaneous ICG measurement. Agreement between devices was tested using Bland-Altman analysis. RESULTS: Bland-Altman analysis of the relationship between ICG and echocardiography demonstrated that the 95% limits of agreement exceeded acceptable or expected ranges. Measures of maternal and fetal anthropometry do not account for the lack of agreement. CONCLUSIONS: Absolute values of SV as determined by ICG are not valid in pregnancy. Further work is required to examine the ability of ICG to assess relative changes in maternal haemodynamics in late pregnancy.