Clinical Outcomes of Renal Transplant Recipients Undergoing Percutaneous Coronary Intervention.

BACKGROUND: Clinical outcomes of patients with renal transplant (RT) undergoing percutaneous coronary intervention (PCI) remain poorly elucidated. METHOD: Between 2014 and 2021, data were analysed for the following three groups of patients undergoing PCI enrolled in a multicentre Australian registry: (1) RT recipients (n=226), (2) patients on dialysis (n=992), and (3) chronic kidney disease (CKD) patients (estimated glomerular filtration rate [eGFR], 30‒60 mL/min per 1.73 m2) without previous RT (n=15,534). Primary outcome was 30-day major adverse cardiac and cerebrovascular events (MACCEs)-composite of mortality, myocardial infarction, stent thrombosis, target vessel revascularisation, and stroke. RESULTS: RT recipients were younger than dialysis and patients with CKD (61±10 vs 68±12 vs 78±8.2 years, p<0.001). Patients with RT less frequently had severe left ventricular dysfunction compared with dialysis and CKD groups (6.7% vs 14% and 8.5%); however more, often presented with acute coronary syndrome (58% vs 52% and 48%), especially STEMI (all p<0.001). Patients with RT and CKD had lower rates of 30-day MACCE (4.4% and 6.8% vs 11.6%, p<0.001) than the dialysis group. Three-year survival was similar between RT and CKD groups, however was lower in the dialysis group (80% and 83% vs 60%, p<0.001). After adjustment, dialysis was an independent predictor of 30-day MACCE (odds ratio [OR] 1.90, 95% confidence interval [CI] 1.44‒2.50, p<0.001), however RT was not (OR 0.91, CI 0.42‒1.96, p=0.802). Both RT (hazard ratio [HR] 2.07, CI 1.46‒2.95, p<0.001) and dialysis (HR 1.35, CI 1.02‒1.80, p=0.036) heightened the hazard of long-term mortality. CONCLUSIONS: RT recipients have more favourable clinical outcomes following PCI compared with patients on dialysis. However, despite having similar short-term outcomes to patients with CKD, the hazard of long-term mortality is significantly greater for RT recipients.

Blood Pressure Lowering in Patients With Central Hypertension: A randomized Clinical Trial.

BACKGROUND: Cuff blood pressure (BP) is recommended for guiding hypertension management. However, central BP has been proposed as a superior clinical measurement. This study aimed to determine whether controlling hypertension as measured by central BP was beneficial in reducing left ventricular mass index beyond control of standard cuff hypertension. METHODS: This multicenter, open-label, blinded-end point trial was conducted in individuals treated for uncomplicated hypertension with controlled cuff BP (<140/90 mm Hg) but elevated central BP (≥0.5 SD above age- and sex-specific normal values). Participants were randomized to 24-months intervention with spironolactone 25 mg/day (n=148) or usual care control (n=153). The primary outcome was change in left ventricular mass index measured by cardiac MRI. Cuff and central BPs were measured by clinic, 7-day home and 24-hour ambulatory BPs. RESULTS: At 24-months, there was a greater reduction in left ventricular mass index (-3.2 [95% CI, -5.0 to -1.3] g/m2; P=0.001) with intervention compared with control. Cuff and central BPs were lowered by a similar magnitude across all BP measurement modes (eg, clinic cuff systolic BP, -6.16 [-9.60 to -2.72] mm Hg and clinic central systolic BP, -4.96 [-8.06 to -1.86] mm Hg; P≥0.48 all). Secondary analyses found that changes in left ventricular mass index correlated to changes in BP, with the magnitude of effect nearly identical for BP measured by cuff (eg, 24-hour systolic BP, ß, 0.17 [0.02-0.31] g/m2) or centrally (24-hour systolic BP, ß, 0.16 [0.01-0.32] g/m2). CONCLUSIONS: Among individuals with central hypertension, spironolactone had beneficial effects in reducing LV mass. Secondary analyses showed that changes in LV mass were equally well associated with lower measured standard cuff BP and central BP. REGISTRATION: URL: https://www.anzctr.org.au/; Unique identifier: ACTRN12613000053729.

Prevalence and Predictors of Emergency Medical Service Use in Patients Undergoing Primary Percutaneous Coronary Intervention for ST-Elevation Myocardial Infarction.

AIM: We aim to describe prevalence of Emergency Medical Service (EMS) use, investigate factors predictive of EMS use, and determine if EMS use predicts treatment delay and mortality in our ST-elevation myocardial infarction (STEMI) cohort. METHOD: We prospectively collected data on 5,602 patients presenting with STEMI for primary percutaneous coronary intervention (PCI) transported to PCI-capable hospitals in Victoria, Australia, from 2013-2018 who were entered into the Victorian Cardiac Outcomes Registry (VCOR). We linked this dataset to the Ambulance Victoria and National Death Index (NDI) datasets. We excluded late presentation, thrombolysed, and in-hospital STEMI, as well as patients presenting with cardiogenic shock and out-of-hospital cardiac arrest. RESULTS: In total, 74% of patients undergoing primary PCI for STEMI used EMS. Older age, female gender, higher socioeconomic status, and a history of prior ischaemic heart disease were independent predictors of using EMS. EMS use was associated with shorter adjusted door-to-balloon (53 vs 72 minutes, p<0.001) and symptom-to-balloon (183 vs 212 minutes, p<0.001) times. Mode of transport was not predictive of 30-day or 12-month mortality. CONCLUSIONS: EMS use in Victoria is relatively high compared with internationally reported data. EMS use reduces treatment delay. Predictors of EMS use in our cohort are consistent with those prevalent in prior literature. Understanding the patients who are less likely to use EMS might inform more targeted education campaigns in the future.

Ambulatory blood pressure after 12 weeks of quadruple combination of quarter doses of blood pressure medication vs. standard medication.

BACKGROUND: A combination of four ultra-low-dose blood pressure (BP) medications lowered office BP more effectively than initial monotherapy in the QUARTET trial. The effects on average ambulatory BP changes at 12 weeks have not yet been reported in detail. METHODS: Adults with hypertension who were untreated or on monotherapy were eligible for participation. Overall, 591 participants were randomized to either the quadpill (irbesartan 37.5 mg, amlodipine 1.25 mg, indapamide 0.625 mg, and bisoprolol 2.5 mg) or monotherapy control (irbesartan 150 mg). The difference in 24-h, daytime, and night-time systolic and diastolic ambulatory BP at 12 weeks along further metrics were predefined secondary outcomes. RESULTS: Of 576 participants, 289 were randomized to the quadpill group and 287 to the monotherapy group. At 12 weeks, mean 24-h ambulatory SBP and DBP were 7.7 [95% confidence interval (95% CI) 9.6-5.8] and 5.3 (95% CI: 6.5-4.1) mmHg lower in the quadpill vs. monotherapy group (P < 0.001 for both). Similar reductions in the quadpill group were observed for daytime (8.1/5.7 mmHg lower) and night-time (6.3/4.0 mmHg lower) BP at 12 weeks (all P < 0.001) compared to monotherapy. The rate of BP control (24-h average BP < 130/80 mmHg) at 12 weeks was higher in the quadpill group (77 vs. 50%; P < 0.001). The reduction in BP load was also more pronounced with the quadpill. CONCLUSION: A quadruple quarter-dose combination compared with monotherapy resulted in greater ambulatory BP lowering across the entire 24-h period with higher ambulatory BP control rates and reduced BP variability at 12 weeks. These findings further substantiate the efficacy of an ultra-low-dose quadpill-based BP lowering strategy.

Comparison of Characteristics and Outcomes in Patients With Acute Decompensated Heart Failure Admitted Under General Medicine and Cardiology Units.

BACKGROUND: Acute decompensated heart failure (ADHF) is a leading cause of cardiovascular disease hospitalisations associated with significant morbidity and mortality. In hospitals, HF patients are typically managed by cardiology or physician teams, with differences in patient demographics and clinical outcomes. This study utilises contemporary HF registry data to compare patient characteristics and outcomes in those with ADHF admitted into General Medicine and Cardiology units. METHODS: The Victorian Cardiac Outcomes Registry was utilised to identify patients hospitalised with ADHF 30-day period in each of four consecutive years. We compared patient characteristics, pharmacological management and outpatient follow-up of patients admitted to General Medicine and Cardiology units. Primary outcome measures included in-hospital mortality, 30-day readmission, and 30-day mortality. RESULTS: Between 2014 and 2017, a total of 1,253 patients with ADHF admissions were registered, with 53% admitted in General Medicine units and 47% in Cardiology units. General Medicine patients were more likely to be older (82 vs 71 years; p<0.001), female (51% vs 34%; p<0.001), and have higher prevalence of comorbidities and preserved left ventricular function (p<0.001). There were no differences in primary outcome measures between General Medicine and Cardiology in terms of: in-hospital mortality (5.0% vs 3.9%; p=0.35), 30-day readmission (23.4% vs 23.6%; p=0.93), and 30-day mortality (10.0% vs 8.0%; p=0.21). CONCLUSIONS: Hospitalised patients with HF continue to have high mortality and rehospitalisation rates. The choice of treatment by General Medicine or Cardiology units, based on the particular medical profile and individual needs of the patients, provides equivalent outcomes.

Therapeutic Inertia With Initial Low-Dose Quadruple Combination Therapy for Hypertension: Results From the QUARTET Trial.

BACKGROUND: Low-dose combinations are a promising intervention for improving blood pressure (BP) control but their effects on therapeutic inertia are uncertain. METHODS: Analysis of 591 patients randomized to an ultra-low-dose quadruple pill or initial monotherapy. The episode of therapeutic inertia was defined as a patient visit with a BP of >140/90 mm Hg without intensification of antihypertensive treatment. We compared the frequency of therapeutic inertia episodes between Quadpill and initial monotherapy as a proportion of the total population (intention-to-treat analysis with the denominator being all participants randomized) and as a proportion of people with uncontrolled BP (with the denominator being participants with uncontrolled BP). RESULTS: Therapeutic inertia occurred in fewer participants randomized to Quadpill compared with monotherapy. For example, among the 390 participants with a 6-month follow-up, therapeutic inertia according to unattended BP was 21/192 (11%) versus 45/192 (23%), P=0.002. There were similar rates of therapeutic inertia among those with uncontrolled unattended BP in each group (all P>0.4). Consistent observations were seen with the use of attended office BP measures. The major determinants of not intensifying treatment during follow-up were BP readings that were close to target and large improvements in BP compared with the previous visit. CONCLUSIONS: Among all treated individuals, low-dose Quadpill reduced the number of therapeutic inertia episodes compared with initial monotherapy. After the first follow-up visit, most high BP values did not lead to treatment intensification in both groups. Education is needed about the importance of treatment intensification despite a significant improvement in BP or BP being close to target. REGISTRATION: URL: https://anzctr.org.au/Trial/Registration/TrialReview.aspx?ACTRN=ACTRN12616001144404; Unique identifier: ACTRN12616001144404.

Sex differences in long-term survival after total arterial coronary artery bypass grafting.

OBJECTIVES: It is uncertain if the evidence on improved long-term survival of total arterial coronary artery bypass grafting applies to female patients. This study aims to compare the long-term survival outcomes of using total arterial revascularization (TAR) versus at least 1 saphenous vein graft separately for men and women. METHODS: This retrospective analysis of the Australian and New Zealand Society of Cardiac-Thoracic Surgical Database had administrative linkage to the National Death Index. We identified all patients undergoing primary isolated coronary bypass from June 2001 to January 2020 inclusive. Following sex stratification, propensity score matching with 36 variables and Cox proportional hazard regression were used to facilitate adjusted comparisons. A Cox interaction-term analysis was performed to investigate the impact of sex on TAR survival benefit. The primary outcome was all-cause mortality. RESULTS: Of the 69 624 eligible patients receiving at least 2 grafts, 13 019 (18.7%) were female patients. Matching generated 14 951 male and 3530 female pairs. Compared to vein-dependent procedures, TAR was associated with significantly reduced incidence of long-term all-cause mortality for both male (hazard ratio, 0.86; 95% confidence interval, 0.81-0.91; P < 0.001) and female (hazard ratio, 0.82; 95% confidence interval, 0.73-0.91; P < 0.001) cohorts. Interaction-term analysis indicated no significant subgroup effect from sex (P = 0.573) on the survival advantage of TAR. The treatment effect provided by TAR remained significant across most sex-stratified disease subgroups. CONCLUSIONS: TAR, when compared to the use of at least 1 saphenous vein graft, provides comparable superior long-term survival outcomes in both females and males.

No-Reflow Prediction in Acute Coronary Syndrome During Percutaneous Coronary Intervention: The NORPACS Risk Score.

BACKGROUND: Suboptimal coronary reperfusion (no reflow) is common in acute coronary syndrome percutaneous coronary intervention (PCI) and is associated with poor outcomes. We aimed to develop and externally validate a clinical risk score for angiographic no reflow for use following angiography and before PCI. METHODS: We developed and externally validated a logistic regression model for prediction of no reflow among adult patients undergoing PCI for acute coronary syndrome using data from the Melbourne Interventional Group PCI registry (2005-2020; development cohort) and the British Cardiovascular Interventional Society PCI registry (2006-2020; external validation cohort). RESULTS: A total of 30 561 patients (mean age, 64.1 years; 24% women) were included in the Melbourne Interventional Group development cohort and 440 256 patients (mean age, 64.9 years; 27% women) in the British Cardiovascular Interventional Society external validation cohort. The primary outcome (no reflow) occurred in 4.1% (1249 patients) and 9.4% (41 222 patients) of the development and validation cohorts, respectively. From 33 candidate predictor variables, 6 final variables were selected by an adaptive least absolute shrinkage and selection operator regression model for inclusion (cardiogenic shock, ST-segment-elevation myocardial infarction with symptom onset >195 minutes pre-PCI, estimated stent length ≥20 mm, vessel diameter <2.5 mm, pre-PCI Thrombolysis in Myocardial Infarction flow <3, and lesion location). Model discrimination was very good (development C statistic, 0.808; validation C statistic, 0.741) with excellent calibration. Patients with a score of ≥8 points had a 22% and 27% risk of no reflow in the development and validation cohorts, respectively. CONCLUSIONS: The no-reflow prediction in acute coronary syndrome risk score is a simple count-based scoring system based on 6 parameters available before PCI to predict the risk of no reflow. This score could be useful in guiding preventative treatment and future trials.

Electrocardiographic patterns and clinical outcomes of acute coronary syndrome cardiogenic shock in patients undergoing percutaneous coronary intervention - A propensity score analysis.

OBJECTIVES: To determine the influence of presenting electrocardiographic (ECG) changes on prognosis in acute coronary syndrome cardiogenic shock (ACS-CS) patients undergoing percutaneous coronary angiography (PCI). BACKGROUND: The effect of initial ECG changes such as ST-elevation myocardial infarction (STEMI) versus non-STEMI among patients ACS-CS on prognosis remains unclear. METHODS: We analysed data from consecutive patients with ACS-CS enrolled in the Victorian Cardiac Outcomes registry between 2014 and 2020. Inverse probability of treatment weighting analysis (IPTW) was used to assess the effect of ECG changes on 30-day mortality. RESULTS: Of 1564 patients with ACS-CS who underwent PCI, 161 had non-STEMI and 1403 had STEMI on ECG. The mean age was 66 ± 13 years, and 74 % (1152) were males. Patients with non-STEMI compared to STEMI were older (70 ± 12 vs 65 ± 13 years), had higher rates of diabetes (34 % vs 21 %), prior coronary artery bypass graft surgery (14 % vs 3.3 %), peripheral arterial disease (10.6 % vs 4.1 %, p < 0.01), and lower baseline eGFR (53.8 [37.1, 75.4] vs 65.3 [46.3, 87.8] ml/min/1.73m2), all p ≤ 0.01. Non-STEMI patients were more likely to have a culprit left circumflex artery (29 % vs 20 %) and more often underwent multivessel percutaneous coronary intervention (30 % vs 20 %) but had lower rates of out-of-hospital cardiac arrest (21 % vs 39 %), all p ≤ 0.01. Propensity score analysis with IPTW confirmed that non-STEMI ECG was associated with lower odds for 30-day all-cause mortality (OR 0.47 [0.32, 0.69], p < 0.001), and 30-day major adverse cardiovascular and cerebrovascular events (OR 0.48 [0.33, 0.70]). CONCLUSIONS: In patients undergoing PCI, Non-STEMI as compared to STEMI on index ECG was associated with approximately half the relative risk of both 30-day mortality and 30-day MACCE and could be a useful variable to integrate in ACS-CS risk scores.

Association between long-term use of calcium channel blockers (CCB) and the risk of breast cancer: a retrospective longitudinal observational study protocol.

INTRODUCTION: Calcium channel blockers (CCB), a commonly prescribed antihypertensive (AHT) medicine, may be associated with increased risk of breast cancer. The proposed study aims to examine whether long-term CCB use is associated with the development of breast cancer and to characterise the dose-response nature of any identified association, to inform future hypertension management. METHODS AND ANALYSIS: The study will use data from 2 of Australia's largest cohort studies; the Australian Longitudinal Study on Women's Health, and the 45 and Up Study, combined with the Rotterdam Study. Eligible women will be those with diagnosed hypertension, no history of breast cancer and no prior CCB use at start of follow-up (2004-2009). Cumulative dose-duration exposure to CCB and other AHT medicines will be captured at the earliest date of: the outcome (a diagnosis of invasive breast cancer); a competing risk event (eg, bilateral mastectomy without a diagnosis of breast cancer, death prior to any diagnosis of breast cancer) or end of follow-up (censoring event). Fine and Gray competing risks regression will be used to assess the association between CCB use and development of breast cancer using a generalised propensity score to adjust for baseline covariates. Time-varying covariates related to interaction with health services will also be included in the model. Data will be harmonised across cohorts to achieve identical protocols and a two-step random effects individual patient-level meta-analysis will be used. ETHICS AND DISSEMINATION: Ethical approval was obtained from the following Human research Ethics Committees: Curtin University (ref No. HRE2022-0335), NSW Population and Health Services Research Ethics Committee (2022/ETH01392/2022.31), ACT Research Ethics and Governance Office approval under National Mutual Acceptance for multijurisdictional data linkage research (2022.STE.00208). Results of the proposed study will be published in high-impact journals and presented at key scientific meetings. TRIAL REGISTRATION NUMBER: NCT05972785.

The ASPREE Healthy Ageing Biobank: Methodology and participant characteristics.

ASPirin in Reducing Events in the Elderly (ASPREE), a placebo-controlled prevention trial of low dose aspirin, provided the opportunity to establish a biospecimen biobank from initially healthy persons aged 70+ years for future research. The ASPREE Healthy Ageing Biobank (ASPREE Biobank) collected, processed and stored blood and urine samples at -80degC or under nitrogen vapour at two timepoints, three years apart, from a willing subset of Australian ASPREE participants. Written informed consent included separate opt-in questions for biomarker and genetic testing. Fractionated blood and urine were aliquoted into multiple low-volume, barcoded cryotubes for frozen storage within 4 hours of collection. Specially designed and outfitted mobile laboratories provided opportunities for participation by people in regional and rural areas. Detailed, high quality demographic, physiological and clinical data were collected annually through the ASPREE trial. 12,219 participants contributed blood/urine at the first timepoint, 10,617 of these older adults provided 3-year follow-up samples, and an additional 1,712 provided saliva for DNA. The mean participant age was 74 years, 54% were female and 46% lived outside major cities. Despite geographical and logistical challenges, nearly 100% of blood/urine specimens were processed and frozen within 4 hours of collection into >1.4 million aliquots. After a median of 4.7 years, major clinical events among ASPREE Biobank participants included 332 with dementia, 613 with cardiovascular disease events, 1259 with cancer, 357 with major bleeds and 615 had died. The ASPREE Biobank houses and curates a large number of biospecimens collected prior to the clinical manifestations of major disease, and 3-year follow-up samples, all linked to high quality, extensive phenotypic information. This provides the opportunity to identify or validate diagnostic, prognostic and predictive biomarkers, and potentially study biological effectors, of ageing-related diseases or maintenance of older-age good health.

Utilisation of Chronic Disease and Mental Health Management Services and Cardioprotective Medication Prescriptions in Primary Care for Patients With Cardiovascular Diseases and Cancer: A Cross-Sectional Study.

BACKGROUND: Cardiovascular disease (CVD) is a leading cause of morbidity and mortality among cancer survivors. Mental health is considered an important risk factor affecting the treatment of cardiovascular disease. However, little is known about the use of secondary prevention strategies for CVD in patients with both cancer and CVD. This study aimed to compare the utilisation of primary care chronic disease management plans, mental health care and guideline-indicated cardioprotective medications among CVD patients with and without cancer. METHODS: Retrospective cross-sectional study utilising clinical data of patients with CVD from 50 Australian primary care practices. Outcomes included the use of chronic disease management plans, mental health care, guideline-indicated cardioprotective medications and influenza vaccination. Logistic regression, accounting for demographic and clinical covariates and clustering effects by practices, was used to compare the two groups. RESULTS: Of the 15,040 patients with CVD, 1,486 patients (9.9%) concurrently had cancer. Patients with cancer, compared to those without, were older (77.6 vs 71.8 years, p<0.001), more likely to drink alcohol (62.6% vs 55.7%, p<0.001), have lower systolic (130.3±17.8 vs 132.5±21.1 mmHg, p<0.001) and diastolic (72.2±11 vs 75.3±34 mmHg, p<0.001) blood pressure. Although suboptimal for both groups, patients with cancer were significantly more likely to have general practice management plans (GPMPs) (51.4% vs 43.2%, p<0.001), coordination of team care arrangements (TCAs) (46.2% vs 37.0%, p<0.001), have a review of either GPMP or TCA (42.8% vs 34.7%, p<0.001), have a mental health treatment consultation (15.4% vs 10.5%, p=0.004) and be prescribed blood pressure-lowering medications (70.1% vs 66.0%, p=0.002). However, there were no statistical differences in the prescription of lipid-lowering or antiplatelet medications. After adjustments for covariates and multiple testing, patients with cancer did not show a difference in GPMPs, TCAs, and a review of either, but were more likely to receive mental health treatment consultations than those without cancer (odds ratio 1.76; 95% confidence interval 1.42-2.19). CONCLUSIONS: Less than half of patients with CVD had a GPMP, TCA or review of either. Although those patients with cancer were more likely to receive these interventions, still around half the patients did not. Medicare-funded GPMPs, TCAs and a review of either GPMP or TCA were underutilised, and future studies should seek to identify ways of improving access to these services.

Platelet versus fresh frozen plasma transfusion for coagulopathy in cardiac surgery patients.

BACKGROUND: Platelets (PLTS) and fresh frozen plasma (FFP) are often transfused in cardiac surgery patients for perioperative bleeding. Their relative effectiveness is unknown. METHODS: We conducted an entropy-weighted retrospective cohort study using the Australian and New Zealand Society of Cardiac and Thoracic Surgeons National Cardiac Surgery Database. All adults undergoing cardiac surgery between 2005-2021 across 58 sites were included. The primary outcome was operative mortality. RESULTS: Of 174,796 eligible patients, 15,360 (8.79%) received PLTS in the absence of FFP and 6,189 (3.54%) patients received FFP in the absence of PLTS. The median cumulative dose was 1 unit of pooled platelets (IQR 1 to 3) and 2 units of FFP (IQR 0 to 4) respectively. After entropy weighting to achieve balanced cohorts, FFP was associated with increased perioperative (Risk Ratio [RR], 1.63; 95% Confidence Interval [CI], 1.40 to 1.91; P<0.001) and 1-year (RR, 1.50; 95% CI, 1.32 to 1.71; P<0.001) mortality. FFP was associated with increased rates of 4-hour chest drain tube output (Adjusted mean difference in ml, 28.37; 95% CI, 19.35 to 37.38; P<0.001), AKI (RR, 1.13; 95% CI, 1.01 to 1.27; P = 0.033) and readmission to ICU (RR, 1.24; 95% CI, 1.09 to 1.42; P = 0.001). CONCLUSION: In perioperative bleeding in cardiac surgery patient, platelets are associated with a relative mortality benefit over FFP. This information can be used by clinicians in their choice of procoagulant therapy in this setting.

Multimorbidity impacts cardiovascular disease risk following percutaneous coronary intervention: latent class analysis of the Melbourne Interventional Group (MIG) registry.

BACKGROUND: Multimorbidity is strongly associated with disability or functional decline, poor quality of life and high consumption of health care services. This study aimed (1) To identify patterns of multimorbidity among patients undergoing first recorded percutaneous coronary intervention (PCI); (2) To explore the association between the identified patterns of multimorbidity on length of hospital stay, 30-day and 12- month risk of major adverse cardiac and cerebrovascular events (MACCE) after PCI. METHODS: A retrospective cohort study of the Melbourne Interventional Group (MIG) registry. This study included 14,025 participants who underwent their first PCI from 2005 to 2015 in Victoria, Australia. Based on a probabilistic modelling approach, Latent class analysis was adopted to classify clusters of people who shared similar combinations and magnitude of the comorbidity of interest. Logistic regression models were used to estimate odd ratios and 95% confidence interval (CI) for the 30-day and 12-month MACCE. RESULTS: More than two-thirds of patients had multimorbidity, with the most prevalent conditions being hypertension (59%) and dyslipidaemia (60%). Four distinctive multimorbidity clusters were identified each with significant associations for higher risk of 30-day and 12-month MACCE. The cluster B had the highest risk of 30-day MACCE event that was characterised by a high prevalence of reduced estimated glomerular filtration rate (92%), hypertension (73%) and reduced ejection fraction (EF) (57%). The cluster C, characterised by a high prevalence of hypertension (94%), dyslipidaemia (88%), reduced eGFR (87%), diabetes (73%) and reduced EF (65%) had the highest risk of 12-month MACCE and highest length of hospital stay. CONCLUSION: Hypertension and dyslipidaemia are prevalent in at least four in ten patients undergoing coronary angioplasty. This study showed that clusters of patients with multimorbidity had significantly different risk of 30-day and 12-month MACCE after PCI. This suggests the necessity for treatment approaches that are more personalised and customised to enhance patient outcomes and the quality of care delivered to patients in various comorbidity clusters. These results should be validated in a prospective cohort and to evaluate the potential impacts of these clusters on the prevention of MACCE after PCI.

Cardiovascular Disease Risk Scores and Incident Dementia and Cognitive Decline in Older Men and Women.

INTRODUCTION: Risk factors for cardiovascular disease (CVD) also increase the risk of dementia. However, whether commonly used CVD risk scores are associated with dementia risk in older adults who do not have a history of CVD, and potential gender differences in this association, remains unclear. The aim of this study was to determine whether CVD risk scores are prospectively associated with cognitive decline and dementia in initially healthy older men and women. METHODS: A total of19,114 participants from a prospective cohort of individuals aged 65+ years without known CVD or dementia were recruited. The atherosclerotic cardiovascular disease risk score (ASCVDRS), Systematic Coronary Risk Evaluation 2-Older Persons (SCORE2-OP), and the Framingham risk score (FRS) were calculated at baseline. Risk of dementia (according to DSM-IV criteria) and cognitive decline (defined as a >1.5 standard deviation decline in global cognition, episodic memory, psychomotor speed, or verbal fluency from the previous year) were assessed using hazard ratio. RESULTS: Over a median follow-up of 6.4 years, 850 individuals developed dementia and 4,352 cognitive decline. Men and women in the highest ASCVDRS tertile had a 41% (95% CI 1.08, 1.85) and 45% (1.11, 1.89) increased risk of dementia compared to the lowest tertile, respectively. Likewise, men and women in the highest SCORE2-OP tertile had a 64% (1.24, 2.16) and 60% (1.22, 2.11) increased risk of dementia compared to the lowest tertile, respectively. Findings were similar, but the risk was slightly lesser when examining risk of cognitive decline for both ASCVDRS and SCORE2-OP. However, FRS was only associated with the risk of cognitive decline among women (highest vs. lowest tertiles: 1.13 [1.01-1.26]). CONCLUSION: These findings suggest the utility of the ASCVDRS and SCORE2-OP in clinical practice, to not only assess future risk of CVD, but also as potential early indicators of cognitive impairment, even in relatively healthy older men and women.

Long-term blood pressure variability and frailty risk in older adults.

INTRODUCTION: In healthy older adults, the relationship between long-term, visit-to-visit variability in blood pressure (BP) and frailty is uncertain. METHODS: Secondary analysis of blood pressure variability (BPV) and incident frailty in >13 000 participants ≥65-70 years enrolled in the ASPirin in Reducing Events in the Elderly (ASPREE) trial and its observational follow-up (ASPREE-XT). Participants were without dementia, physical disability, or cardiovascular disease at baseline. BPV was estimated using standard deviation of mean BP from three annual visits (baseline through the second annual follow-up). Frailty was defined using Fried phenotype and a frailty deficit accumulation index (FDAI). Participants with frailty during the BPV estimation period were excluded from the main analysis. Adjusted Cox proportional hazards regression evaluated the association between BPV and incident frailty, and linear mixed models for change in frailty scores, through a maximum of 9 years of follow-up. RESULTS: Participants in the highest systolic BPV tertile were at higher risk of frailty compared to those in the lowest (referent) tertile of systolic BPV [Fried hazard ratio (HR) 1.17, 95% confidence interval (CI) 1.04-1.31; FDAI HR 1.18, 95% CI 1.07-1.30]. Findings were consistent when adjusted for multiple covariates and when stratified by antihypertensive use. Linear mixed models showed that higher systolic BPV was associated with increasing frailty score over time. Diastolic BPV was not consistently associated. CONCLUSIONS: High systolic BPV, independent of mean BP, is associated with increased risk of frailty in healthy older adults. Variability of BP across visits, even in healthy older adults, can convey important risk information beyond mean BP. TRIAL REGISTRATION: ClinicalTrials.gov NCT01038583 and ISRCTN83772183.

Real-world long-term survival after non-emergent percutaneous coronary intervention to unprotected left main coronary artery - From the Melbourne Interventional Group (MIG) registry.

BACKGROUND: Current evidence suggests that percutaneous coronary intervention for unprotected left main coronary artery disease (LMPCI) in selected patients is a safe alternative to coronary artery bypass grafting. However, real-world long-term survival data is limited. METHODS: We analyzed 24,644 patients from the MIG (Melbourne Interventional Group) registry between 2005 and 2020. We compared baseline clinical and procedural characteristics, in-hospital and 30-day outcomes, and long-term survival between unprotected LMPCI and non-LMPCI among patients without ST-segment elevation myocardial infarction, cardiogenic shock, or cardiac arrest. RESULTS: Unprotected LMPCI patients (n = 185) were significantly older (mean age 72.0 vs. 64.6 years, p < 0.001), had higher prevalence of impaired ejection fraction (EF <50 %; 27.3 % vs. 14.9 %, p < 0.001) and lower estimated glomerular filtration rate < 60 ml/min/1.73m2 (40.9 % vs. 21.5 %, p < 0.001), and had greater use of intravascular ultrasound (21 % vs. 1 %, p < 0.001) and drug-eluting stents (p < 0.001). LMPCI was associated with longer hospital stay (4 days vs. 2 days, p < 0.001). There was no significant difference in other in-hospital outcomes, 30-day mortality (0.6 % vs. 0.6 %, p = 0.90), and major adverse cardiac events (1.7 % vs. 3 %, p = 0.28). Although the unadjusted Kaplan-Meier survival to 8 years was significantly less with LMPCI compared to non-LMPCI (p < 0.01), LMPCI was not a predictor of long-term survival up to 8 years after Cox regression analysis (HR 0.67, 95 % CI 0.40-1.13, p = 0.13). CONCLUSION: In this study, non-emergent unprotected LMPCI was uncommonly performed, and IVUS was underutilized. Despite greater co-morbidities, LMPCI patients had comparable 30-day outcomes to non-LMPCI, and LMPCI was not an independent predictor of long-term mortality.

Development and Validation of Scores to Predict Prolonged Mechanical Ventilation after Cardiac Surgery.

OBJECTIVES: To optimize the early prediction of prolonged postoperative mechanical ventilation after cardiac surgery (>24 hours postoperatively). DESIGN: The authors performed a retrospective analysis. SETTING: The Australian and New Zealand Society of Cardiac and Thoracic Surgeons (ANZSCTS) database was utilized. PARTICIPANTS: All patients included in the ANZSCTS database between January 2015 and December 2018 were analyzed. INTERVENTIONS: No interventions were performed in this observational study. MEASUREMENTS AND MAIN RESULTS: A previously developed model was modified to allow retrospective risk calculation and model assessment (Modified Hessels score). The database was split into development and validation sets. A new risk model was developed using forward and backward stepwise elimination (ANZ-PreVent score). The authors assessed 48,382 patients, of whom 5004 (10.3%) were ventilated mechanically for >24 hours post-operatively. The Modified Hessels score demonstrated good performance in this database, with a c-index of 0.78 (95% CI 0.77-0.78) and a Brier score of 0.08. The newly developed ANZ-PreVent score demonstrated better performance (validation cohort, n = 12,229), with a c-index of 0.84 (95% CI 0.83-0.85) (p < 0.0001) and a Brier score of 0.07. Both scores performed better than the severity of illness scores commonly used to predict outcomes in intensive care. CONCLUSIONS: The authors validated a modified version of an existing prediction score and developed the ANZ-PreVent score, with improved performance for identifying patients at risk of ventilation for >24 hours. The improved score can be used to identify high-risk patients for targeted interventions in future randomized controlled trials.

Daily low-dose aspirin and incident type 2 diabetes in community-dwelling healthy older adults: a post-hoc analysis of efficacy and safety in the ASPREE randomised placebo-controlled trial.

BACKGROUND: Inflammation has been implicated in the pathogenesis of diabetes. This study investigated the randomised treatment effect of low-dose aspirin on incident type 2 diabetes and fasting plasma glucose (FPG) concentrations among older adults. METHODS: ASPREE was a double-blind, placebo-controlled trial of daily oral low-dose aspirin. The study population included community-dwelling individuals aged 70 years or older (≥65 years for US minority ethnic groups) in the USA and Australia who were free of cardiovascular disease, independence-limiting physical disability, or dementia. For the post-hoc analysis, we excluded participants with diabetes at baseline or with incomplete or missing incident diabetes data during follow-up. Participants were randomly assigned 1:1 to oral 100 mg daily enteric-coated aspirin or placebo. Incident diabetes was defined as self-reported diabetes, commencement of glucose-lowering medication, or a FPG concentration of 7·0 mmol/L or more assessed at annual follow-up visits among participants with no diabetes at baseline. We used Cox proportional hazards models and mixed-model repeated measures to assess the effect of aspirin on incident diabetes and FPG concentrations in the intention-to-treat population. We assessed major bleeding in participants who had taken at least one dose of study medication. FINDINGS: Between March 10, 2010, and Dec 24, 2014, a total of 16 209 participants were included (8086 [49·9%] randomly assigned to aspirin and 8123 [50·1%] randomly assigned to placebo). During a median follow-up of 4·7 years (IQR 3·6-5·7), 995 (in 6·1% individuals) incident cases of type 2 diabetes were recorded (459 in the aspirin group and 536 in the placebo group). Compared with placebo, the aspirin group had a 15% reduction in risk of incident diabetes (hazard ratio 0·85 [95% CI 0·75 to 0·97]; p=0·013) and a slower rate of increase in FPG concentration at year 5 (between-group difference estimate -0·048 mmol/L [95% CI -0·079 to -0·018]; p=0·0017). Major bleeding (major gastrointestinal bleeding, intracranial bleeding, and clinically significant bleeding at other sites) occurred in 510 (3·2%) of 16 104 participants (300 [3·7%] in the aspirin group and 210 [2·6%] in the placebo group). Compared with placebo, the aspirin group had a 44% increase in risk of major bleeding (hazard ratio 1·44 [95% CI 1·21 to 1·72]; p<0·0001). INTERPRETATION: Aspirin treatment reduced the incidence of type 2 diabetes and slowed the increase in FPG concentration but increased major bleeding among community-dwelling older adults. Given the increasing prevalence of type 2 diabetes among older adults, the potential for anti-inflammatory agents such as aspirin to prevent type 2 diabetes or improve glucose levels warrants further study with a comprehensive assessment of all potential safety events of interest. FUNDING: US National Institute on Aging, US National Cancer Institute, National Health and Medical Research Council of Australia, Monash University, and the Victorian Cancer Agency.

Low-density-lipoprotein cholesterol and mortality outcomes among healthy older adults: A post-hoc analysis of ASPREE trial.

BACKGROUND: The prognostic implication of cholesterol levels in older adults remains uncertain. This study aimed to examine the relationship between low-density-lipoprotein-cholesterol (LDL-c) and mortality outcomes in older individuals. METHODS: This post-hoc analysis examined the associations of LDL-c levels with mortality risks from all-cause, CVD, cancer, and combined non-CVD/non-cancer conditions in a cohort of individuals aged ≥65 years from the ASPREE trial (NCT01038583). At baseline, participants had no diagnosed dementia, physical disability, or cardiovascular disease (CVD), and were not taking lipid-lowering agents. Outcome analyses were performed using multivariable Cox models. RESULTS: We analysed 12,334 participants (mean age:75.2 years). Over a median 7-year follow-up, 1250 died. Restricted cubic splines found a U-shaped relation for LDL-c and all-cause mortality, cancer mortality, and non-cancer/non-CVE mortality (nadir: 3.3-3.4 mmol/L); the risk of CVD mortality was similar at LDL-c below 3.3 mmol/L and increased above 3.3 mmol/L. The similar trends were observed in analyses modelling LDL-c by quartiles. When modelling LDL-c as a continuous variable, the risk of all-cause mortality, cancer mortality, and non-cancer/non-CVD mortality was decreased by 9%, 16% and 18% respectively per 1-mmol/L higher LDL-c, and the risk of CVD mortality was increased by 19% per 1-mmol/L higher LDL-c. Reduced all-cause and non-CVD/non-cancer mortality risks were only significant in males but not females (Pinteraction <0.05). CONCLUSIONS: There were U-shaped relationships between LDL-c and all-cause mortality, cancer mortality, and non-cancer/non-CVD mortality in healthy older adults. Higher LDL-c levels were associated with an increased risk of CVD mortality. Future studies are warranted to confirm our results.