Sex differences in outcomes after acute coronary syndrome vary with age: a New Zealand national study.

AIMS: This study investigated age-specific sex differences in short- and long-term clinical outcomes following hospitalization for a first-time acute coronary syndrome (ACS) in New Zealand (NZ). METHODS AND RESULTS: Using linked national health datasets, people admitted to hospital for a first-time ACS between January 2010 and December 2016 were included. Analyses were stratified by sex and 10-year age groups. Logistic and Cox regression were used to assess in-hospital death and from discharge the primary outcome of time to first cardiovascular (CV) readmission or death and other secondary outcomes at 30 days and 2 years. Among 63 245 people (mean age 69 years, 40% women), women were older than men at the time of the ACS admission (mean age 73 vs. 66 years), with a higher comorbidity burden. Overall compared with men, women experienced higher rates of unadjusted in-hospital death (10% vs. 7%), 30-day (16% vs. 12%) and 2-year (44% vs. 34%) death, or CV readmission (all P < 0.001). Age group-specific analyses showed sex differences in outcomes varied with age, with younger women (<65 years) at higher risk than men and older women (≥85 years) at lower risk than men: unadjusted hazard ratio of 2-year death or CV readmission for women aged 18-44 years = 1.51 [95% confidence interval (CI) 1.21-1.84] and aged ≥85 years = 0.88 (95% CI 0.83-0.93). The increased risk for younger women was no longer significant after multivariable adjustment whereas the increased risk for older men remained. CONCLUSION: Men and women admitted with first-time ACS have differing age and comorbidity profiles, resulting in contrasting age-specific sex differences in the risk of adverse outcomes between the youngest and oldest age groups.

Paired risk scores to predict ischaemic and bleeding risk twenty-eight days to one year after an acute coronary syndrome.

OBJECTIVE: The recommended duration of dual anti-platelet therapy (DAPT) following acute coronary syndrome (ACS) varies from 1 month to 1 year depending on the balance of risks of ischaemia and major bleeding. We designed paired ischaemic and major bleeding risk scores to inform this decision. METHODS: New Zealand (NZ) patients with ACS investigated with coronary angiography are recorded in the All NZ ACS Quality Improvement registry and linked to national health datasets. Patients were aged 18-84 years (2012-2020), event free at 28 days postdischarge and without atrial fibrillation. Two 28-day to 1-year postdischarge multivariable risk prediction scores were developed: (1) cardiovascular mortality/rehospitalisation with myocardial infarction or ischaemic stroke (ischaemic score) and (2) bleeding mortality/rehospitalisation with bleeding (bleeding score). FINDINGS: In 27 755 patients, there were 1200 (4.3%) ischaemic and 548 (2.0%) major bleeding events. Both scores were well calibrated with moderate discrimination performance (Harrell's c-statistic 0.75 (95% CI, 0.74 to 0.77) and 0.69 (95% CI, 0.67 to 0 .71), respectively). Applying these scores to the 2020 European Society of Cardiology ACS antithrombotic treatment algorithm, the 31% of the cohort at elevated (>2%) bleeding and ischaemic risk would be considered for an abbreviated DAPT duration. For those at low bleeding risk, but elevated ischaemic risk (37% of the cohort), prolonged DAPT may be appropriate, and for those with low bleeding and ischaemic risk (29% of the cohort) short duration DAPT may be justified. CONCLUSION: We present a pair of ischaemic and bleeding risk scores specifically to assist clinicians and their patients in deciding on DAPT duration beyond the first month post-ACS.

Regional Handling and Prognostic Performance of Circulating Insulin-Like Growth Factor Binding Protein-7 in Heart Failure.

BACKGROUND: Regional handling and the prognostic performance of insulin-like growth factor binding protein (IGFBP)-7, in contrast or in combination with other candidate biomarkers, in chronic heart failure (CHF) remain uncertain. OBJECTIVES: The authors investigated the regional handling of plasma IGFBP-7 and its association with long-term outcomes in CHF in comparison with selected circulating biomarkers. METHODS: Plasma concentrations of IGFBP-7, N-terminal pro-B-type natriuretic peptide (NT-proBNP), high-sensitivity troponin-T, growth differentiation factor-15, and high-sensitivity C-reactive protein were measured prospectively in a cohort with CHF (n = 863). The primary outcome was the composite of heart failure (HF) hospitalization or all-cause mortality. In a separate non-HF cohort (n = 66) undergoing cardiac catheterization, transorgan gradients of plasma IGFBP-7 concentrations were evaluated. RESULTS: Among 863 patients (age 69 ± 14 years, 30% female, 36% HF with preserved ejection fraction), IGFBP-7 (median: 121 [IQR: 99-156] ng/mL) related inversely to left ventricular volumes but directly to diastolic function. Above the optimal cutoff, IGFBP-7 ≥110 ng/mL was independently associated with 32% increased hazard of the primary outcome: 1.32 (95% CI: 1.06-1.64). Among the 5 markers, IGFBP-7 had the highest hazard for a proportional increment in plasma concentrations independent of HF phenotype in single- and double-biomarker models, and provided incremental prognostic value beyond clinical predictors plus NT-proBNP, high-sensitivity troponin-T, and high-sensitivity C-reactive protein (P < 0.05). Assessment of regional concentrations indicated renal secretion of IGFBP-7 in contrast to renal extraction of NT-proBNP, possible cardiac extraction of IGFBP-7 in contrast to secretion of NT-proBNP, and common hepatic extraction of both peptides. CONCLUSIONS: Transorgan regulation of IGFBP-7 is distinct from NT-proBNP. Circulating IGFBP-7 independently predicts adverse outcomes in CHF with a strong prognostic performance when compared with other well-recognized cardiac-specific or noncardiac prognostic markers.

Invasive Management and Outcomes in Acute Coronary Syndromes and Chronic Kidney Disease (ANZACS-QI 70).

AIMS: Guidelines recommend management with an invasive coronary angiogram in acute coronary syndromes (ACS), but most studies excluded patients with advanced chronic kidney disease (CKD). Our aims were to describe, in a comprehensive ACS cohort, the incidence of CKD, coronary angiography utilisation and outcomes, according to CKD stage. METHODS: National datasets were used to identify hospitalised ACS patients (2013 to 2018) in the Northern region of New Zealand. CKD stage was obtained from a linked laboratory dataset. Outcomes included all-cause and cause-specific mortality, and non-fatal myocardial infarction, heart failure and stroke. RESULTS: Thirty-eight percent (38%) of the 23,432 ACS patients had CKD stage 3 or higher: 2,403 (10%) had stages 4/5 CKD. Overall 61% received coronary angiography. Compared with normal renal function the adjusted rate of coronary angiography was lower in CKD stage 3b (RR 0.75, 95% confidence intervals [CIs] 0.69, 0.82) and stages 4/5 without dialysis (RR 0.41, 95% CIs 0.36, 0.46), but similar for those on dialysis (RR 0.89, 95% CIs 0.77, 1.02). All-cause mortality (mean follow-up 3.2 years) increased with CKD stage from 8% (normal kidney function) to 69% (stages 4/5 CKD without dialysis). Compared with coronary angiography, the adjusted all-cause and CVD mortality risks were higher in those without coronary angiography, except for those on dialysis, where these risks converged. CONCLUSIONS: Invasive management fell below an eGFR of 45 mL/min (≤ stage 3b), and nearly half of all deaths occurred in these patients. Clinical trials are needed to assess the role of invasive management in ACS and advanced CKD.

Prognostic modelling of clinical outcomes after first-time acute coronary syndrome in New Zealand.

OBJECTIVE: The Multi-Ethnic New Zealand Study of Acute Coronary Syndromes (MENZACS) was established to investigate the drivers of secondary events after first-time acute coronary syndrome (ACS), including addressing inequitable outcomes by ethnicity. Herein, the first clinical outcomes and prognostic modelling approach are reported. METHODS: First, in 28 176 New Zealanders with first-time ACS from a national registry, a clinical summary score for predicting 1-year death/cardiovascular readmission was created using Cox regression of 20 clinical variables. This score was then calculated in the 2015 participant MENZACS study to represent clinical risk. In MENZACS, Cox regression was used to assess N-terminal pro-B-type natriuretic peptide (NT-proBNP) as a prognostic marker for death/cardiovascular readmission in four models, adjusting for (1) age and sex; (2) age, sex, ethnicity; (3) clinical summary score; (4) clinical summary score and ethnicity. RESULTS: Of the 2015 MENZACS participants (mean age 61 years, 79% male, 73% European, 14% Maori, 5% Pacific people), 2003 were alive at discharge. Of the 2003, 416 (20.8%) experienced all-cause death/cardiovascular readmission over a median of 3.5 years. In a simple model, age, male sex, Maori ethnicity and NT-proBNP levels were significant predictors of outcome. After adjustment for the clinical summary score, which includes age and sex, NT-proBNP and ethnicity were no longer statistically significant: log2(NT-proBNP) hazard ratio (HR) 1.03, 95% confidence interval (95% CI) 0.98 to 1.08, p=0.305; Maori ethnicity HR 1.26, 95% CI 0.97 to 1.62, p=0.084. CONCLUSIONS: In 2015 patients with first-time ACS, recurrent events were common (20.8%). Increasing NT-proBNP levels and Maori ethnicity were predictors of death/cardiovascular readmission, but not after adjustment for the 20 clinical risk factors represented by the clinical summary score. TRIAL REGISTRATION NUMBER: ACTRN12615000676516.

Cardiovascular disease preventive medication dispensing for almost every New Zealander 65 years and over: a preventive treatment paradox?

OBJECTIVE: To describe the dispensing of cardiovascular disease (CVD) preventive medications among older New Zealanders with and without prior CVD or diabetes. METHODS: New Zealanders aged ≥65 years in 2013 were identified using anonymised linkage of national administrative health databases. Dispensing of blood pressure lowering (BPL), lipid lowering (LL) or antithrombotic (AT) medications, was documented, stratified by age and by history of CVD, diabetes, or neither. RESULTS: Of the 593,549 people identified, 32% had prior CVD, 14% had diabetes (of whom half also had prior CVD) and 61% had neither diagnosis. For those with prior CVD, between 79-87% were dispensed BPL and 73-79% were dispensed AT medications, across all age groups. In contrast, LL dispensing was lower than either BPL or AT in every age group, falling from 75% at age 65-69 years to 43% at 85+ years. For people with diabetes, BPL and LL dispensing was similar to those with prior CVD, but AT dispensing was approximately 20% lower. Among people without prior CVD or diabetes, both BPL and AT dispensing increased with age (from 39% and 17% at age 65-69 years to 56% and 35% at 85+ years respectively), whereas LL dispensing was 26-31% across the 65-84 year age groups, falling to 17% at 85+ years. CONCLUSION: The much higher dispensing of BPL and AT compared to LL medications with increasing age suggests a preventive treatment paradox for older people, with the medications most likely to cause adverse effects being dispensed most often.

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.

Impact of chronic kidney disease on mortality and cardiovascular outcomes after acute coronary syndrome: A nationwide data linkage study (ANZACS-QI 44).

AIMS: Chronic kidney disease (CKD) is associated with an increased risk of cardiovascular disease (CVD). We examined the characteristics, management and outcomes of patients with CKD in the All New Zealand Acute Coronary Syndrome Quality Improvement (ANZACS-QI) national registry. METHODS: The cohort comprised New Zealand (NZ) patients with an acute coronary syndrome undergoing coronary angiography between January 2013 and December 2016. Patients were categorized according to their stage of CKD. Outcomes included all-cause and cause-specific mortality and hospitalization with myocardial infarction (MI), stroke and major bleeding. RESULTS: Of the 20 604 patients, 20.3% had normal renal function, with 53.3%, 23.3%, 1.7% and 1.4% having CKD stages 2, 3, 4 and 5 CKD, respectively. Patients with severe CKD were more likely to be Maori or Pacific and live in an area with greater socioeconomic deprivation. Death, recurrent MI or stroke, and major bleeding all increased incrementally with each worsening stage of CKD severity. Compared with those with normal renal function, patients with stage 5 CKD had a much higher all-cause (hazard ratio [HR] 16.41, 95% CI 13.06-20.61), cardiovascular (HR 16.38, 95% CI 12.17-22.04) and non-cardiovascular mortality (HR 13.66 9, 95% CI.56-19.51). In addition, patients with stage 5 CKD were at a higher risk of recurrent MI or stroke (HR 4.73, 95% CI 3.86-5.80) and bleeding (HR 5.84, 95% CI 4.39-7.76). CONCLUSION: CKD was associated with increased mortality and a high incidence of morbidity in patients undergoing coronary angiography in New Zealand. Initiatives to understand and improve outcomes in this group of patients are urgently needed.

Personalized Prediction of Cardiovascular Benefits and Bleeding Harms From Aspirin for Primary Prevention: A Benefit-Harm Analysis.

Background: Whether the benefits of aspirin for the primary prevention of cardiovascular disease (CVD) outweigh its bleeding harms in some patients is unclear. Objective: To identify persons without CVD for whom aspirin would probably result in a net benefit. Design: Individualized benefit-harm analysis based on sex-specific risk scores and estimates of the proportional effect of aspirin on CVD and major bleeding from a 2019 meta-analysis. Setting: New Zealand primary care. Participants: 245 028 persons (43.6% women) aged 30 to 79 years without established CVD who had their CVD risk assessed between 2012 and 2016. Measurements: The net effect of aspirin was calculated for each participant by subtracting the number of CVD events likely to be prevented (CVD risk score × proportional effect of aspirin on CVD risk) from the number of major bleeds likely to be caused (major bleed risk score × proportional effect of aspirin on major bleeding risk) over 5 years. Results: 2.5% of women and 12.1% of men were likely to have a net benefit from aspirin treatment for 5 years if 1 CVD event was assumed to be equivalent in severity to 1 major bleed, increasing to 21.4% of women and 40.7% of men if 1 CVD event was assumed to be equivalent to 2 major bleeds. Net benefit subgroups had higher baseline CVD risk, higher levels of most established CVD risk factors, and lower levels of bleeding-specific risk factors than net harm subgroups. Limitations: Risk scores and effect estimates were uncertain. Effects of aspirin on cancer outcomes were not considered. Applicability to non-New Zealand populations was not assessed. Conclusion: For some persons without CVD, aspirin is likely to result in net benefit. Primary Funding Source: Health Research Council of New Zealand.

Effects of a Voluntary Front-of-Pack Nutrition Labelling System on Packaged Food Reformulation: The Health Star Rating System in New Zealand.

Interpretive, front-of-pack (FOP) nutrition labels may encourage reformulation of packaged foods. We aimed to evaluate the effects of the Health Star Rating (HSR), a new voluntary interpretive FOP labelling system, on food reformulation in New Zealand. Annual surveys of packaged food and beverage labelling and composition were undertaken in supermarkets before and after adoption of HSR i.e., 2014 to 2016. Outcomes assessed were HSR uptake by food group star ratings of products displaying a HSR label; nutritional composition of products displaying HSR compared with non-HSR products; and the composition of products displaying HSR labels in 2016 compared with their composition prior to introduction of HSR. In 2016, two years after adoption of the voluntary system, 5.3% of packaged food and beverage products surveyed (n = 807/15,357) displayed HSR labels. The highest rates of uptake were for cereals, convenience foods, packaged fruit and vegetables, sauces and spreads, and 'Other' products (predominantly breakfast beverages). Products displaying HSR labels had higher energy density but had significantly lower mean saturated fat, total sugar and sodium, and higher fibre, contents than non-HSR products (all p-values < 0.001). Small but statistically significant changes were observed in mean energy density (-29 KJ/100 g, p = 0.002), sodium (-49 mg/100 g, p = 0.03) and fibre (+0.5 g/100 g, p = 0.001) contents of HSR-labelled products compared with their composition prior to adoption of HSR. Reformulation of HSR-labelled products was greater than that of non-HSR-labelled products over the same period, e.g., energy reduction in HSR products was greater than in non-HSR products (-1.5% versus -0.4%), and sodium content of HSR products decreased by 4.6% while that of non-HSR products increased by 3.1%. We conclude that roll-out of the voluntary HSR labelling system is driving healthier reformulation of some products. Greater uptake across the full food supply should improve population diets.