Short, Medium and Long-Term Cause-Specific Mortality Following First-Ever Heart Failure Hospitalisation in New Zealand.

BACKGROUND: Heart failure (HF) is associated with high mortality, but there are limited reports on the underlying cause of death. This study reports short-, medium- and long-term cause-specific mortality following first-ever HF hospitalisation in New Zealand. METHOD: First-ever HF hospitalisations were identified from hospital discharge coding between 2010 and 2013. Mortality outcomes were obtained via anonymised linkage to national datasets. Short (0-30 days), medium (31-364 days), and long-term (1-5 years) mortality rates were identified. Cause of death was identified from death certification coding and classified as cardiovascular and non-cardiovascular. Cox regression analysis was performed to adjust for confounding variables. RESULTS: A cohort of 34,264 individuals with first-ever HF hospitalisation were identified. Mean age was 75.8±13 years and 50.5% were male. A total of 21,637 (63.1%) died within 5 years of hospitalisation; 4,122 (12.0%) within the first 30 days, 6,358 (18.6%) between 31-364 days, and 11,157 (32.6%) between 1 and 5 years. Older age, male gender, Maori ethnicity, higher socioeconomic deprivation and increased comorbidity were independent factors associated with higher all-cause mortality. Cardiovascular causes accounted for 51% of total deaths. Cardiovascular mortality was 6.0%, 9.5%, and 16.7% at 30 days, 31-364 days, and 1-5 years, respectively. The most common causes of non-cardiovascular mortality were neoplasms, chronic respiratory diseases and infections, accounting for 14.6%, 11.0%, and 5.5% of total deaths respectively. Comorbidity was associated with higher non-cardiovascular mortality (hazard ratio [HR] 3.35; 95% confidence interval [CI] 3.16-3.55) but not cardiovascular mortality (HR 0.79; 95% CI 0.72-0.86). CONCLUSIONS: In New Zealand, mortality following first-ever HF hospitalisation is high. Non-cardiovascular death is common and there are ethnic inequities.

Cultural context in New Zealand: incorporating kaupapa Maori values in clinical research and practice.

We examined the importance of understanding and incorporating cultural context within Aotearoa/New Zealand when engaging in clinical research and practice. This paper reports on the qualitative findings of a mixed methods study aimed at determining what effect a cardiac risk reduction exercise and lifestyle management programme, embedded within a kaupapa Maori methodological approach, had on Maori participants. This methodology saw participants able to redevelop a western model cardiac risk reduction programme by introducing a Maori worldview. Our study revealed how the kaupapa Maori approach empowered participants to examine and evaluate not only their own health and lifestyle choices, but those of family and the wider community. Combining biomedical and kaupapa Maori components into the programme was found to benefit participants' mental, physical, spiritual and family well-being.

Temporal trends in the burden of heart failure.

Heart failure is a common healthcare problem associated with high morbidity and mortality. The burden of heart failure is changing; increases secondary to an ageing population may be offset by improved primary cardiovascular prevention and advances in heart failure therapies. In this review, we evaluate recent international trends in heart failure incidence, morbidity and mortality. Although the age-standardised incidence of heart failure has been decreasing since 2000, the incidence in those age groups <55 years is increasing with patients being diagnosed at younger ages. Despite improvements in therapies for heart failure, prognosis still remains poor with up to one-third of patients not surviving beyond 1 year following diagnosis and no improvements in mortality over the past 10 years. The case-mix of heart failure patients is changing with a greater proportion having non-ischaemic aetiology and preserved ejection fraction, and a higher prevalence of non-cardiovascular comorbidity and mortality.

Patterns of multi-morbidity and prediction of hospitalisation and all-cause mortality in advanced age.

Background: multi-morbidity is associated with poor outcomes and increased healthcare utilisation. We aim to identify multi-morbidity patterns and associations with potentially inappropriate prescribing (PIP), subsequent hospitalisation and mortality in octogenarians. Methods: life and Living in Advanced Age; a Cohort Study in New Zealand (LiLACS NZ) examined health outcomes of 421 Maori (indigenous to New Zealand), aged 80-90 and 516 non-Maori, aged 85 years in 2010. Presence of 14 chronic conditions was ascertained from self-report, general practice and hospitalisation records and physical assessments. Agglomerative hierarchical cluster analysis identified clusters of participants with co-existing conditions. Multivariate regression models examined the associations between clusters and PIP, 48-month hospitalisations and mortality. Results: six clusters were identified for Maori and non-Maori, respectively. The associations between clusters and outcomes differed between Maori and non-Maori. In Maori, those in the complex multi-morbidity cluster had the highest prevalence of inappropriately prescribed medications and in cluster 'diabetes' (20% of sample) had higher risk of hospitalisation and mortality at 48-month follow-up. In non-Maori, those in the 'depression-arthritis' (17% of the sample) cluster had both highest prevalence of inappropriate medications and risk of hospitalisation and mortality. Conclusions: in octogenarians, hospitalisation and mortality are better predicted by profiles of clusters of conditions rather than the presence or absence of a specific condition. Further research is required to determine if the cluster approach can be used to target patients to optimise resource allocation and improve outcomes.

Management and Long-Term Outcome of Acute Coronary Syndrome Patients Presenting with Heart Failure in a Contemporary New Zealand Cohort (ANZACS-QI 4).

BACKGROUND: Acute heart failure (HF) associated with an acute coronary syndrome (ACS) predicts adverse outcome. There have been important recent improvements in ACS management. Our aim was to describe the management and outcomes in those with and without HF in a contemporary ACS cohort. METHODS: Consecutive patients presenting with ACS between 2007 and 2011 were enrolled in the All New Zealand Acute Coronary Syndrome Quality Improvement (ANZACS-QI) registry. Outcomes and medication dispensing were obtained using anonymised linkage to national data sets. A summary pharmacotherapy measure of "quadruple therapy" was defined as dispensing of at least one agent from each of the four evidence-based classes - anti-platelet, statin, angiotensin converting enzyme inhibitor/angiotensin receptor blocker and beta blocker. RESULTS: Of 3743 ACS patients 14% had acute HF. Acute heart failure patients were older (69.2±12.6 vs 62.3±12.8 years, p<0.001), less likely to have coronary angiography (66% vs 86%, p<0.001) and revascularisation (46% vs 62%, p<0.001). Immediate post-discharge quadruple therapy was higher for those with than without HF (61% vs 55%, p=0.02) but fell to similar levels by one-year (45% vs 53%, p=0.55). At four years follow-up nearly half of those presenting with ACS and HF had died. After adjustment, HF remained a strong predictor of death within 28 days (OR 2.9, 95%CI 1.5 - 5.5) and beyond 28 days (HR 1.8, 95%CI 1.5 - 2.3). CONCLUSION: Acute heart failure complicating ACS is associated with heightened risk of short-term and long-term mortality. One in three ACS patients with HF did not have coronary angiography and less than half received quadruple therapy a year after presentation.

Atrial fibrillation and cycling: six year follow-up of the Taupo bicycle study.

BACKGROUND: Atrial Fibrillation (AF) is the most common sustained cardiac arrhythmia, and the incidence of AF is increased markedly among elite athletes. It is not clear how lesser levels of physical activity in the general population influence AF. We asked whether participation in the Taupo Cycle Challenge was associated with increased hospital admissions due to AF, and within the cohort, whether admissions for AF were related to frequency and intensity of cycling. METHODS: Participants in the 2006 Lake Taupo Cycle Challenge, New Zealand's largest mass cycling event, were invited to complete an on-line questionnaire. Those who agreed (n = 2590, response rate = 43.1%) were followed up by record linkage via the National Minimum Health Database from December 1 2006 until June 30 2013, to identify admissions to hospital due to AF. RESULTS: The age and gender standardized admission rate for AF was similar in the Taupo cohort (19.60 per 10,000 per year) and the national population over the same period (2006-2011) (19.45 per 10,000 per year). Within the study cohort (men only), for every additional hour spent cycling per week the risk changed by 0.90 (95% confidence interval 0.79 - 1.01). This result did not change appreciably after adjustment for age and height. CONCLUSIONS: Hospital admission due to AF was not increased above the national rate in this group of non-elite cyclists, and within the group the rate of AF did not increase with amount of cycling. The level of activity undertaken by this cohort of cyclists was, on average, not sufficient to increase the risk of hospitalization for AF.

Predicting survival in heart failure: a risk score based on 39 372 patients from 30 studies.

AIMS: Using a large international database from multiple cohort studies, the aim is to create a generalizable easily used risk score for mortality in patients with heart failure (HF). METHODS AND RESULTS: The MAGGIC meta-analysis includes individual data on 39 372 patients with HF, both reduced and preserved left-ventricular ejection fraction (EF), from 30 cohort studies, six of which were clinical trials. 40.2% of patients died during a median follow-up of 2.5 years. Using multivariable piecewise Poisson regression methods with stepwise variable selection, a final model included 13 highly significant independent predictors of mortality in the following order of predictive strength: age, lower EF, NYHA class, serum creatinine, diabetes, not prescribed beta-blocker, lower systolic BP, lower body mass, time since diagnosis, current smoker, chronic obstructive pulmonary disease, male gender, and not prescribed ACE-inhibitor or angiotensin-receptor blockers. In preserved EF, age was more predictive and systolic BP was less predictive of mortality than in reduced EF. Conversion into an easy-to-use integer risk score identified a very marked gradient in risk, with 3-year mortality rates of 10 and 70% in the bottom quintile and top decile of risk, respectively. CONCLUSION: In patients with HF of both reduced and preserved EF, the influences of readily available predictors of mortality can be quantified in an integer score accessible by an easy-to-use website www.heartfailurerisk.org. The score has the potential for widespread implementation in a clinical setting.

Widening ethnic inequities in heart failure incidence in New Zealand.

OBJECTIVE: Ethnic inequities in heart failure (HF) have been documented in several countries. This study describes New Zealand (NZ) trends in incident HF hospitalisation by ethnicity between 2006 and 2018. METHODS: Incident HF hospitalisations in ≥20-year-old subjects were identified through International Classification of Diseases, 10th Revision-coded national hospitalisation records. Incidence was calculated for different ethnic, sex and age groups and were age standardised. Trends were estimated with joinpoint regression. RESULTS: Of 116 113 incident HF hospitalisations, 12.8% were Maori, 5.7% Pacific people, 3.0% Asians and 78.6% Europeans/others. 64% of Maori and Pacific patients were aged <70 years, compared with 37% of Asian and 19% of European/others. In 2018, incidence rate ratios compared with European/others were 6.0 (95% CI 4.9 to 7.3), 7.5 (95% CI 6.0 to 9.4) and 0.5 (95% CI 0.3 to 0.8) for Maori, Pacific people and Asians aged 20-49 years; 3.7 (95% CI 3.4 to 4.0), 3.6 (95% CI 3.2 to 4.1) and 0.5 (95% CI 0.4 to 0.6) for Maori, Pacific people and Asians aged 50-69 years; and 1.5 (95% CI 1.4 to 1.6), 1.5 (95% CI 1.3 to 1.7) and 0.5 (95% CI 0.5 to 0.6) for Maori, Pacific people and Asians aged ≥70 years. Between 2006 and 2018, ethnicity-specific rates diverged in ≥70-year-old subjects due to a decline in European/others (annual percentage change (APC) -2.0%, 95% CI -2.5% to -1.6%) and Asians (APC -3.3%, 95% CI -4.4% to -2.1%), but rates remained unchanged for Maori and Pacific people. In contrast, regardless of ethnicity, rates either increased or remained unchanged in <70-year-old subjects. CONCLUSION: Ethnic inequities in incident HF hospitalisation have widened in NZ over the past 13 years. Urgent action is required to address the predisposing factors that lead to development of HF in Maori and Pacific people.

Proteomic Associations of Adverse Outcomes in Human Heart Failure.

BACKGROUND: Identifying novel molecular drivers of disease progression in heart failure (HF) is a high-priority goal that may provide new therapeutic targets to improve patient outcomes. The authors investigated the relationship between plasma proteins and adverse outcomes in HF and their putative causal role using Mendelian randomization. METHODS AND RESULTS: The authors measured 4776 plasma proteins among 1964 participants with HF with a reduced left ventricular ejection fraction enrolled in PHFS (Penn Heart Failure Study). Assessed were the observational relationship between plasma proteins and (1) all-cause death or (2) death or HF-related hospital admission (DHFA). The authors replicated nominally significant associations in the Washington University HF registry (N=1080). Proteins significantly associated with outcomes were the subject of 2-sample Mendelian randomization and colocalization analyses. After correction for multiple testing, 243 and 126 proteins were found to be significantly associated with death and DHFA, respectively. These included small ubiquitin-like modifier 2 (standardized hazard ratio [sHR], 1.56; P<0.0001), growth differentiation factor-15 (sHR, 1.68; P<0.0001) for death, A disintegrin and metalloproteinase with thrombospondin motifs-like protein (sHR, 1.40; P<0.0001), and pulmonary-associated surfactant protein C (sHR, 1.24; P<0.0001) for DHFA. In pathway analyses, top canonical pathways associated with death and DHFA included fibrotic, inflammatory, and coagulation pathways. Genomic analyses provided evidence of nominally significant associations between levels of 6 genetically predicted proteins with DHFA and 11 genetically predicted proteins with death. CONCLUSIONS: This study implicates multiple novel proteins in HF and provides preliminary evidence of associations between genetically predicted plasma levels of 17 candidate proteins and the risk for adverse outcomes in human HF.

Call to action-the urgent need for a heart health plan in New Zealand.

Cardiovascular diseases are responsible for almost 10,000 deaths annually in Aotearoa New Zealand. Almost a quarter of these are avoidable, increasing to half of all cardiovascular deaths for Maori and Pacific people. Health system reforms are an opportunity to set clear ambitious goals for improved heart health. This has been done for smoking, a cancer plan, mental health and diabetes among other health conditions. Given the scale of avoidable heart disease and avoidable heart health inequity, much of it due to people simply not accessing existing treatment options, there is no excuse not to deliver a national heart health action plan and we urge health policy makers to put it on the agenda.

Titration of medications and outcomes in multi-ethnic heart failure cohorts (with reduced ejection fraction) from Singapore and New Zealand.

AIMS: We investigated titration patterns of angiotensin-converting enzyme inhibitors (ACEis)/angiotensin receptor blockers (ARBs) and beta-blockers, quality of life (QoL) over 6 months, and associated 1 year outcome [all-cause mortality/heart failure (HF) hospitalization] in a real-world population with HF with reduced ejection fraction (HFrEF). METHODS AND RESULTS: Participants with HFrEF (left ventricular ejection fraction <40%) from a prospective multi-centre study were examined for use and dose [relative to guideline-recommended maintenance dose (GRD)] of ACEis/ARBs and beta-blockers at baseline and 6 months. 'Stay low' was defined as <50% GRD at both time points, 'stay high' as ≥50% GRD, and 'up-titrate' and 'down-titrate' as dose trajectories. Among 1110 patients (mean age 63 ± 13 years, 16% women, 26% New York Heart Association Class III/IV), 714 (64%) were multi-ethnic Asians from Singapore and 396 were from New Zealand (mainly European ethnicity). Baseline use of either ACEis/ARBs or beta-blockers was high (87%). Loop diuretic was prescribed in >80% of patients, mineralocorticoid receptor antagonist in about half of patients, and statins in >90% of patients. At baseline, only 11% and 9% received 100% GRD for each drug class, respectively, with about half (47%) achieving ≥50% GRD for ACEis/ARBs or beta-blockers. At 6 months, a large majority remained in the 'stay low' category, one third remained in 'stay high', whereas 10-16% up-titrated and 4-6% down-titrated. Patients with lower (vs. higher) N-terminal pro-beta-type natriuretic peptide levels were more likely to be up-titrated or be in 'stay high' for ACEis/ARBs and beta-blockers (P = 0.002). Ischaemic aetiology, prior HF hospitalization, and enrolment in Singapore (vs. New Zealand) were independently associated with higher odds of 'staying low' (all P < 0.005) for prescribed doses of ACEis/ARBs and beta-blockers. Adjusted for inverse probability weighting, ≥100% GRD for ACEis/ARBs [hazard ratio (HR) = 0.42; 95% confidence interval (CI) 0.24-0.73] and ≥50% GRD for beta-blockers (HR = 0.58; 95% CI 0.37-0.90) (vs. Nil) were associated with lower hazards for 1 year composite outcome. Country of enrolment did not modify the associations of dose categories with 1 year composite outcome. Higher medication doses were associated with greater improvements in QoL. CONCLUSIONS: Although HF medication use at baseline was high, most patients did not have these medications up-titrated over 6 months. Multiple clinical factors were associated with changes in medication dosages. Further research is urgently needed to investigate the causes of lack of up-titration of HF therapy (and its frequency), which could inform strategies for timely up-titration of HF therapy based on clinical and biochemical parameters.

KCNE5 polymorphism rs697829 is associated with QT interval and survival in acute coronary syndromes patients.

INTRODUCTION: The KCNE family is a group of small transmembrane channel proteins involved in potassium ion (K(+)) conductance. The X-linked KCNE5 gene encodes a regulator of the K(+) current mediated by the potassium channel KCNQ1. Polymorphisms in KCNE5 have been associated with altered cardiac electrophysiological properties in human studies. We investigated associations of the common rs697829 polymorphism from KCNE5 with baseline characteristics, baseline electrocardiographic (ECG) measurements, and patient survival in a cohort of post-acute coronary syndromes (ACS) patients (the Coronary Disease Cohort Study cohort). METHODS AND RESULTS: DNA samples (n = 1,740) were genotyped for rs697829 using a TaqMan assay. Baseline ECG data revealed corrected QT (QTc) interval was associated with rs697829 in male, but not female, patients, being extended in the G genotype group (A 416 ± 1.71; G 431 ± 4.25 ms, P = 0.002). Covariate-adjusted survival was poorest in G genotype patients in Cox proportional hazard modeling of mortality data of males (P(overall) = 0.020). Male patients with G genotype had a hazard ratio of 1.44 (1.11-2.33) for death when compared to the A genotype male patients (P = 0.048) after adjustment for age, baseline log-transformed N-terminal pro-B-type natriuretic peptide (NTproBNP), ß-blocker and insulin treatment, QTc interval, history of myocardial infarction, and physical activity score. CONCLUSION: This study suggests an association between rs697829, a common single nucleotide polymorphism (SNP) from KCNE5, and ECG measurements and survival in postacute ACS patients. Prolonged subclinical QT interval may be a marker of adverse outcome in this group of patients.

Identification of clinically relevant cohorts of people with heart failure from electronic health data in Aotearoa: potential, pitfalls and a plan.

Heart failure (HF) is associated with high morbidity and mortality and contributes to substantial burden of disease, significant inequities and high healthcare cost globally as well as in Aotearoa. Management of chronic HF is driven by HF phenotype, defined by left ventricular ejection fraction (EF), as only those with reduced ejection fraction (HFrEF) have been shown to experience reduced mortality and morbidity with long-term pharmacotherapy. To ensure appropriate and equitable implementation of HF management we need to be able to identify clinically relevant cohorts of patients with HF, in particular, those with HFrEF. The ideal HF registry would incorporate and link HF diagnoses and phenotype from primary and secondary care with echocardiography and pharmacotherapy data. In this article we consider several options for identifying such cohorts from electronic health data in Aotearoa, as well as the potential and pitfalls of these options. Given the urgent need to identify people with HF according to EF phenotype, the options for identifying them from electronic health data, and the opportunities presented by health system reform, including a focus on digital solutions, we recommend the following four actions, with oversight from a national HF working group: 1) Establish a HF registry based on random and representative sampling of HF admissions; 2) investigate obtaining HF diagnosis and EF-phenotype from primary care-coded data; 3) amalgamate national echocardiography data; and 4) investigate options to enable the systematic collection of HF diagnosis and EF-phenotype from outpatient attendances. Future work will need to consider reliability and concordance of data across sources. The case for urgent action in Aotearoa is compounded by the stark inequities in the burden of HF, the likely contribution of health service factors to these inequities and the legislative requirement under the Pae Ora (Healthy Futures) Act 2022 that "the health sector should be equitable, which includes ensuring Maori and other population groups - (i) have access to services in proportion to their health needs; and (ii) receive equitable levels of service; and (iii) achieve equitable health outcomes".

Contrasting trends in heart failure incidence in younger and older New Zealanders, 2006-2018.

OBJECTIVE: Studies indicate that age-standardised heart failure (HF) incidence has been decreasing internationally; however, contrasting trends in different age groups have been reported, with rates increasing in younger people and decreasing in the elderly. We aimed to describe age-specific trends in HF incidence in New Zealand (NZ). METHODS: In this nationwide data linkage study, we used routinely collected hospitalisation data to identify incident HF hospitalisations in NZ residents aged ≥20 years between 2006 and 2018. Age-specific and age-standardised incidence rates were calculated for each calendar year. Joinpoint regression was used to compare incidence trends. RESULTS: 116 113 incident HF hospitalisations were identified over the 13-year study period. Between 2006 and 2013, age-standardised incidence decreased from 403 to 323 per 100 000 (annual percentage change (APC) -2.6%, 95% CI -3.6 to -1.6%). This reduction then plateaued between 2013 and 2018 (APC 0.8%, 95% CI -0.8 to 2.5%). Between 2006 and 2018, rates in individuals aged 20-49 years old increased by 1.5% per year (95% CI 0.3 to 2.7%) and decreased in those aged ≥80 years old by 1.2% per year (95% CI -1.7 to -0.7%). Rates in individuals aged 50-79 years old initially declined from 2006 to 2013, and then remained stable or increased from 2013 to 2018. The proportion of HF hospitalisations associated with ischaemic heart disease decreased from 35.1% in 2006 to 28.0% in 2018. CONCLUSION: HF remains an important problem in NZ. The decline in overall incidence has plateaued since 2013 due to increasing rates of HF in younger age groups despite an ongoing decline in the elderly.

Identifying Candidate Circulating RNA Markers for Coronary Artery Disease by Deep RNA-Sequencing in Human Plasma.

Advances in RNA sequencing (RNA-Seq) have facilitated transcriptomic analysis of plasma for the discovery of new diagnostic and prognostic markers for disease. We aimed to develop a short-read RNA-Seq protocol to detect mRNAs, long non-coding RNAs (lncRNAs) and circular RNAs (circRNAs) in plasma for the discovery of novel markers for coronary artery disease (CAD) and heart failure (HF). Circulating cell-free RNA from 59 patients with stable CAD (half of whom developed HF within 3 years) and 30 controls was sequenced to a median depth of 108 paired reads per sample. We identified fragments from 3986 messenger RNAs (mRNAs), 164 long non-coding RNAs (lncRNAs), 405 putative novel lncRNAs and 227 circular RNAs in plasma. Circulating levels of 160 mRNAs, 10 lncRNAs and 2 putative novel lncRNAs were altered in patients compared with controls (absolute fold change >1.2, p < 0.01 adjusted for multiple comparisons). The most differentially abundant transcripts were enriched in mRNAs encoded by the mitochondrial genome. We did not detect any differences in the plasma RNA profile between patients who developed HF compared with those who did not. In summary, we show that mRNAs, lncRNAs and circular RNAs can be reliably detected in plasma by deep RNA-Seq. Multiple coding and non-coding transcripts were altered in association with CAD, including several mitochondrial mRNAs, which may indicate underlying myocardial ischaemia and oxidative stress. If validated, circulating levels of these transcripts could potentially be used to help identify asymptomatic individuals with established CAD prior to an acute coronary event.

Association of genetic variation in the natriuretic peptide system with cardiovascular outcomes.

Polymorphisms within individual natriuretic peptide genes have been associated with risk factors for cardiovascular disease, but their association with clinical outcomes was previously unknown. This study aimed to investigate the association between genetic variants in key genes of the natriuretic peptide system with cardiovascular outcomes in patients with coronary artery disease. Coronary disease patients (n=1810) were genotyped for polymorphisms within NPPA, NPPB, NPPC, NPR1 and NPR2. Clinical history, natriuretic peptide concentrations, echocardiography, all-cause mortality and cardiovascular hospital readmissions were recorded over a median 2.8 years. Minor alleles of NPPA rs5068, rs5065 and rs198358 were associated with less history of hypertension; minor alleles of NPPA rs5068 and rs198358 was also associated with higher circulating natriuretic peptide levels (p=0.003 to p=0.04). Minor alleles of NPPB rs198388, rs198389, and rs632793 were associated with higher circulating BNP and NT-proBNP (p=0.001 to p=0.03), and reduced E/E(1) (p=0.011), or LVESVI (p=0.001) and LVEDVI (p=0.004). Within NPPC, both rs11079028 and rs479651 were associated with higher NT-proBNP and CNP (p=0.01 to p=0.03), and rs479651 was associated with lower LVESVI (p=0.008) and LVEDVI (p=0.018). NPR2 rs10758325 was associated with smaller LVMI (p<0.02). A reduced rate of cardiovascular readmission was observed for minor alleles of NPPA rs5065 (p<0.0001), NPPB rs632793 (p<0.0001), rs198388 (p<0.0001), rs198389 (p<0.0001), and NPR2 rs10758325 (p<0.0001). There were no associations with all-cause mortality. In established cardiovascular disease, natriuretic peptide system polymorphisms were associated with natriuretic peptide levels, hypertension, echocardiographic indices and the incidence of hospital readmission for cardiovascular events.

Screening for left ventricular hypertrophy in patients with type 2 diabetes mellitus in the community.

BACKGROUND: Left ventricular hypertrophy (LVH) is a strong predictor of cardiovascular disease and is common among patients with type 2 diabetes. However, no systematic screening for LVH is currently recommended for patients with type 2 diabetes. The purpose of this study was to determine whether NT-proBNP was superior to 12-lead electrocardiography (ECG) for detection of LVH in patients with type 2 diabetes. METHODS: Prospective cross-sectional study comparing diagnostic accuracy of ECG and NT-proBNP for the detection of LVH among patients with type 2 diabetes. Inclusion criteria included having been diagnosed for > 5 years and/or on treatment for type 2 diabetes; patients with Stage 3/4 chronic kidney disease and known cardiovascular disease were excluded. ECG LVH was defined as either the Sokolow-Lyon or Cornell voltage criteria. NT-proBNP level was measured using the Roche Diagnostics Elecsys assay. Left ventricular mass was assessed from echocardiography. Receiver operating characteristic curve analysis was carried out and area under the curve (AUC) was calculated. RESULTS: 294 patients with type 2 diabetes were recruited, mean age 58 (SD 11) years, BP 134/81 ± 18/11 mmHg, HbA 1c 7.3 ± 1.5%. LVH was present in 164 patients (56%). In a logistic regression model age, gender, BMI and a history of hypertension were important determinants of LVH (p < 0.05). Only 5 patients with LVH were detected by either ECG voltage criteria. The AUC for NT-proBNP in detecting LVH was 0.68. CONCLUSIONS: LVH was highly prevalent in asymptomatic patients with type 2 diabetes. ECG was an inadequate test to identify LVH and while NT-proBNP was superior to ECG it remained unsuitable for detecting LVH. Thus, there remains a need for a screening tool to detect LVH in primary care patients with type 2 diabetes to enhance risk stratification and management.

CYP1A1 MSPI (T6235C) gene polymorphism is associated with mortality in acute coronary syndrome patients.

1. The CYP1A1 T6235C polymorphism (rs4646903) gene polymorphism has been linked to the development of coronary heart disease and cigarette smoking-related lung cancer. The present study investigated associations between survival in acute coronary syndromes (ACS), smoking and the CYP1A1 T6235C polymorphism. 2. Patients with ACS (n = 1251) were genotyped for the CYP1A1 T6235C polymorphism. Patients had a mean age of 67.0 years, 69.8% were male and follow up occurred over a median of 1.9 years. 3. Overall genotype frequencies were CC 2.2%, TC 21.7% and TT 76.1%. The CC genotype was associated with baseline characteristics of a higher incidence of Type 2 diabetes (P = 0.017), elevated body mass index (P = 0.001) and younger age (P = 0.045). Patients with the CC genotype had significantly worse survival than TT/TC patients (P = 0.014), independent of ethnicity and established clinical risk factors. When survival was stratified by smoking history, the T6235C genotype was particularly associated with mortality in past or current smokers (mortality 23.5 vs 9.4% in CC and TT/TC patients, respectively; P = 0.019) compared with those who had never smoked (mortality 11.1 vs 11.5% in CC and TT/TC patients, respectively; P = 0.853). 4. The results indicate that the homozygous CYP1A1 6235C genotype is associated with greater mortality following the onset of ACS, independent of ethnicity and clinical risk factors, but related to smoking history.

Development and validation of a cardiovascular risk score for patients in the community after acute coronary syndrome.

OBJECTIVE: Following acute coronary syndrome (ACS), patients are managed long-term in the community, yet few tools are available to guide patient-clinician communication about risk management in that setting. We developed a score for predicting cardiovascular disease (CVD) risk among patients managed in the community after ACS. METHODS: Adults aged 30-79 years with prior ACS were identified from a New Zealand primary care CVD risk management database (PREDICT) with linkage to national mortality, hospitalisation, pharmaceutical dispensing and regional laboratory data. A Cox model incorporating clinically relevant factors was developed to estimate the time to a subsequent fatal or non-fatal CVD event and transformed into a 5-year risk score. External validation was performed in patients (Coronary Disease Cohort Study) assessed 4 months post-ACS. RESULTS: The PREDICT-ACS cohort included 13 703 patients with prior hospitalisation for ACS (median 1.9 years prior), 69% men, 58% European, median age 63 years, who experienced 3142 CVD events in the subsequent 5 years. Median estimated 5 year CVD risk was 24% (IQR 17%-35%). The validation cohort consisted of 2014 patients, 72% men, 92% European, median age 67 years, with 712 CVD events in the subsequent 5 years. Median estimated 5-year risk was 33% (IQR 24%-51%). The risk score was well calibrated in the derivation and validation cohorts, and Harrell's c-statistic was 0.69 and 0.68, respectively. CONCLUSIONS: The PREDICT-ACS risk score uses data routinely available in community care to predict the risk of recurrent clinical events. It was derived and validated in real-world contemporary populations and can inform management decisions with patients living in the community after experiencing an ACS.

The strong case for government funding of a polypill for the secondary prevention of cardiovascular disease in New Zealand.

Wald and Law, who popularised the term 'polypill' in 2003, proposed giving everyone above a certain age a polypill to reduce the burden of cardiovascular disease (CVD). A more compelling potential application, proposed in 2001 by the World Health Organization, is to use a polypill containing antiplatelet, statin and blood pressure-lowering therapy among people with established CVD, in whom the components are already indicated but in whom guideline implementation and adherence are suboptimal. This article outlines relevant international and New Zealand evidence on the likely benefits and harms of a polypill for the secondary prevention of CVD. The evidence indicates that the benefits are likely to outweigh the harms, particularly given the persistence of substantial treatment gaps and inequities in the management of and outcomes in CVD. The time is long overdue for the polypill to be funded for the secondary prevention of CVD.