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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., (© 2024. The Author(s).)

There is a lack of clarity and guidance for screening peripheral artery disease (PAD) in persons with chronic kidney disease (CKD) and end stage kidney disease (ESKD) despite this group being at excess risk of cardiovascular disease (CVD). In this current study, we performed a systematic review and meta-analysis to examine the prevalence and risk factors for PAD in persons with CKD in Australian cohorts. We used the inverse variance heterogeneity meta-analysis with double arcsine transformation to summarize the prevalence of PAD (with 95% CIs). Nine studies and 18 reports from the Australia and New Zealand dialysis and transplant registry with 36 cohorts were included in the review. We found a substantially higher PAD prevalence in cohorts based on an ankle-brachial index (ABI) or toe systolic pressure (TBI) than cohorts based on self-reported history. Higher PAD prevalence was observed in ESKD persons than CKD persons without dialysis (PAD diagnosis based on ABI or TBI: 31% in ESKD persons and 23% in CKD persons, PAD diagnosis based on self-reported history: 17% in ESKD persons and 10% in CKD persons). Older age, Caucasian race, cerebrovascular disease and haemodialysis were associated with the presence of PAD in ESKD persons. Our findings indicated a considerable proportion of PAD in CKD and ESKD persons particularly in those with ESKD. To develop and provide an adequate plan to clinically manage CKD patients with PAD, evidence of cost-effectiveness and clinical benefit of early detection of PAD in persons with CKD in Australia is recommended for future studies., (© 2021 Asian Pacific Society of Nephrology.)

To investigate the effect of night-time BP-lowering drug treatment on the risk of major CVD and mortality, we systematically reviewed randomized controlled trials comparing night-time versus morning dosing. Two studies were found relevant to the clinical question (the MAPEC and Hygia trials). They were similar in study design and population and were conducted by the same study group. As the Hygia trial had more power with a significantly larger sample size, we did not perform a meta-analysis. Both studies reported a reduction of ~50% in major CVD events and all-cause mortality with night-time dosing and a reduction of 60% in CVD mortality. The results from these studies support the implementation of night-time BP-lowering drug treatment in the prevention of CVD and mortality. However there is an on-going discussion on the validity and methodology of MAPEC and Hygia trials, the interpretation of the results should be cautious. Stronger evidence is needed prior to changing clinical practice. Questions that remain to be answered relate to the generalisability of the results across different populations at different levels of BP related risk and the importance of morning versus evening timing of medication on CVD prevention as determined though a well-designed randomised controlled trial.

To investigate if there is evidence for a 'legacy effect' for blood pressure (BP) lowering treatment, that is, worse health outcomes from not initiating drug treatment at a systolic BP threshold of 140 mmHg in middle-age adults. We systematically reviewed studies comparing the effects of delayed BP treatment (placebo/untreated during the trial or no previous treatment at trial entry) vs. early treatment (actively treated during the trial or previous BP treatment at trial entry) on mortality in the short term (5-year in-trial period) and long term (≥10 years in total period). The data were pooled using Peto ORs. A subgroup analysis by 10-year Framingham risk score was performed. Three studies (ALLHAT, Oslo and PREVEND-IT) involving 4746 participants were included. The results were heavily influenced by the ALLHAT trial. We found no significant difference in all-cause mortality between 'delayed BP' and 'early treatment' in the short-term OR 0.95 (95% CI 0.68-1.32) or long-term OR 0.90 (95% CI 0.78-1.04), with similar results for mortality from cardiovascular disease (CVD). The effects of delayed BP lowering treatment on long-term all-cause and CVD mortality did not vary with baseline risk of CVD. The review showed no clinically adverse 'legacy effect' on mortality or major CVD event from not treating middle-aged adults at a systolic BP threshold of 140 mmHg or over. The results were consistent for all CVD risk subgroups. Although these studies are non-randomised post-hoc analyses, they may allay concerns that early treatment of elevated systolic BP is necessary to prevent CVD events in primary prevention populations.

Objectives: To investigate legacy effects at 14-year follow-up of all-cause and cardiovascular disease (CVD) mortality in 'treatment-naive' or 'previous treatment' groups based on blood pressure (BP)-lowering treatment status at baseline., Methods: A post-hoc observational study of the Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial. We excluded participants with a previous history of CVD events. Cox proportional hazard model and 95% confidence interval were used to estimate the effects of treatment naive on mortality outcomes. Moreover, a subgroup analysis by estimated 10-year Framingham risk score was performed., Results: In multivariable models adjusting for baseline and in-trial characteristics (BP values and number of BP medications as time-dependent variables), there was no statistically significant difference in 5 and 14-year all-cause mortality with a hazard ratio of 0.93 (95% confidence interval 0.80-1.09) and hazard ratio 0.95 (0.88-1.03) and in 5 and 14-year CVD mortality hazard ratio 0.94 (0.72-1.23) and hazard ratio 0.93 (0.80-1.08). In subgroup by absolute CVD risk, no heterogeneity of the association between treatment naive and short-term or long-term all-cause or CVD mortality were found. All comparisons are between the treatment-naive and previous treatment groups., Conclusion: Physicians are concerned about 'legacy effects' of not treating individuals with a BP of 140 mmHg or over and low absolute risk. When treatment intensification was taken into consideration in the primary prevention population in this study, no adverse legacy effect as a result of baseline BP 'treatment naivety' was evident in 14 years of follow-up. The nonsignificant associations were consistent across the CVD risk subgroups. However, the results may be biased due to unobserved residual confounding and therefore should be interpreted with caution.

Background: There is currently insufficient evidence to support the use of lipid-lowering drug treatment (LLT) for primary prevention of cardiovascular disease (CVD) in the elderly., Objectives: We examined the relationship of early initiation of LLT with short- and long-term all-cause and CVD mortality in persons older than 65 years in this post hoc study from the Second Australian National Blood Pressure study (ANBP2)., Methods: This was an in- and post-trial observational study. About 4257 hypertensive participants aged 65 to 84 years within Australian family practices were randomized to an angiotensin-converting enzyme inhibitor or a diuretic treatment group. After excluding participants with a prior history of CVD, the cohort was stratified into "LLT" and "no LLT" subgroups based on LLT status at randomization., Results: At randomization, the participants had a mean age of 72 years, average blood pressure of 168/91 mm Hg and estimated 5-year CVD risk of 18.7 ± 8.3%. In the overall study population, the association of LLT with long-term (11-years) all-cause and non-CVD mortality was significant (hazard ratio [HR] 0.78 [95% confidence interval {CI} 0.66-0.92, P = .003] and HR 0.70 [95% CI 0.54-0.90, P = .006], respectively). Magnitudes of the association of LLT with long-term mortality and the association with short-term mortality were similar; however, no statistically significant association with short-term mortality was observed. In the subgroup analysis by baseline 5-year CVD risk, LLT participants in the highest risk tertile had a substantially lower relative risk for short-term all-cause mortality (HR 0.31, 95% CI 0.13-0.71, P for interaction .02) compared to those with lower estimated CVD risk. All analyses were adjusted for baseline and in-trial characteristics., Conclusion: Our study showed a strong association between LLT and reduced long-term all-cause mortality. Thus, our findings support recommendations of the use of LLT in patients over 65 years, particularly those with high CVD risk who were more likely to obtain additional benefits in the short term. The findings also suggested that mortality benefits of LLT for the elderly may take longer to become evident., (Copyright © 2018 National Lipid Association. Published by Elsevier Inc. All rights reserved.)

Objectives: In many current guidelines, blood pressure (BP)-lowering drug treatment for primary prevention of cardiovascular disease (CVD) is based on absolute risk. However, in clinical practice, therapeutic decisions are often based on BP levels alone. We sought to investigate which approach was superior by conducting a post hoc analysis of the Australian National Blood Pressure (ANBP) cohort, a seminal study establishing the efficacy of BP lowering in 'mild hypertensive' persons., Design: A post hoc subgroup analysis of the ANBP trial results by baseline absolute risk tertile., Setting and Participants: 3244 participants aged 35-69 years in a community-based randomised placebo controlled trial of blood pressure-lowering medication., Interventions: Chlorothiazide500 mg versus placebo., Primary Outcome Measures: All-cause mortality and non-fatal events (non-fatal CVD, congestive cardiac failure, renal failure, hypertensive retinopathy or encephalopathy)., Results: Treatment effects were assessed by HR, absolute risk reduction and number needed to treat. Participants had an average 5-year CVD risk in the intermediate range (10.5±6.5) with moderately elevated BP (mean 159/103 mmHg) and were middle aged (52±8 years). In a subgroup analysis, the relative effects (HR) and absolute effects (absolute risk reduction and number needed to treat) did not statistically differ across the three risk groups except for the absolute benefit in all-cause mortality (p for heterogeneity=0.04). With respect to absolute benefit, drug treatment significantly reduced the number of events in the high-risk group regarding any event with a number needed to treat of 18 (10 to 64), death from any cause with 45 (25 to 196) and major CVD events with 23 (12 to 193)., Conclusion: Our analysis confirms that the benefit of treatment was substantial only in the high-risk tertile, reaffirming the rationale of treating elevated blood pressure in the setting of all risk factors rather than in isolation., Competing Interests: Competing interests: CLBH is a PhD candidate at Menzies Institute for Medical Research; she has received a PhD scholarship from Merle Weaver Postgraduate Scholarship. JD is supported by National Health and Medical Research Council Screening and Test Evaluation Program Grant 633003. CMR is supported by a National Health and Medical Research Council Senior Research Fellowship (1045862). MRN has in the last 5 years served on an advisory board for AMGEN., (© Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2018. All rights reserved. No commercial use is permitted unless otherwise expressly granted.)

Background: Many national and international guidelines recommend that the initiation of blood pressure (BP)-lowering drug treatment for the primary prevention of cardiovascular disease (CVD) should no longer be based on BP level alone, but on absolute cardiovascular risk. While BP-lowering drug treatment is beneficial in high-risk individuals at any level of elevated BP, clinicians are concerned about legacy effects on patients with low-to-moderate risk and mildly elevated BP who remain "untreated"., Objective: We aim to investigate the legacy effect of delayed BP-lowering pharmacotherapy in middle-aged individuals (45-65 years) with mildly elevated BP (systolic BP 140-159 mmHg and/or diastolic BP 90-99 mmHg) stratified by absolute risk for primary prevention of CVD, but particularly in the low-risk (<10% five-year absolute risk) group., Methods: Randomized trials of BP-lowering therapy versus placebo or pretreated subjects in active comparator studies with posttrial follow-up will be identified using a 2-step process. First, randomized trials of BP-lowering therapy will be identified by (1) retrieving the references of trials included in published systematic reviews of BP-lowering therapy, (2) retrieving studies published by the Blood Pressure Lowering Treatment Trialists' Collaboration (BPLTTC), and (3) checking studies referenced in the 1993 World Health Organization/International Society of Hypertension meeting memorandum on BP management. Posttrial follow-up studies will then be identified by forward citation searching the randomized trials identified in step 1 through Web of Science. The search will include randomized controlled trials with at least 1-year in-trial period and a posttrial follow-up phase. Age is the major determinant of absolute cardiovascular risk, so the participants in our review will be restricted to middle-aged adults who are more likely to have a lower cardiovascular risk profile. The primary outcome will be all-cause mortality. Secondary outcomes will include cardiovascular mortality, fatal stroke, fatal myocardial infarction, and death due to heart failure., Results: The searches for existing systematic reviews and BPLTTC studies were piloted and modified. The study is expected to be completed before June 2018., Conclusions: The findings of this study will contribute to the body of knowledge concerning the beneficial, neutral, or harmful effects of delayed BP-lowering drug treatment on the primary prevention of CVD in patients with mildly elevated BP and low-to-moderate CVD risk., Trial Registration: PROSPERO International Prospective Register of Systematic Reviews: CRD42017058414; https://www.crd.york.ac.uk/PROSPERO/display&#95;record.asp?ID=CRD42017058414 (Archived by WebCite® at http://www.webcitation.org/6t6sa8O2Q)., (©Chau Le Bao Ho, Sharon Sanders, Jenny Doust, Monique Breslin, Christopher M Reid, Mark Raymond Nelson. Originally published in JMIR Research Protocols (http://www.researchprotocols.org), 01.09.2017.)