Background: Physical activity is a target for early and ongoing cardiovascular health maintenance. However, the relationship between life course trajectories of total activity and all comprising domains (leisure, transport, occupational, domestic) with vascular function and structure has not been examined. This study aimed to determine associations between life course activity trajectories and cardiovascular structure and function in mid-adulthood.

Methods: Using the Australian Childhood Determinants of Adult Health Study (four timepoints [ages 9-49y]; baseline in1985), latent class growth mixture modelling was performed to assess trajectories of total and domain-specific activity across the life course (n=2311). Relationships between activity trajectories and outcomes of global longitudinal strain (n=868), carotid intima-media thickness (n=914), carotid plaques (n=867), Young’s Elastic Modulus (n=765), carotid distensibility (n=765), and blood pressure (n=868) were analysed using log-binomial and multivariable regression.

Results: ‘Consistently high’ total activity from childhood to adulthood was associated with a reduction in high-risk (> -20%) global longitudinal strain (RR=0.57; 95%CI=0.24-0.89) compared to ‘persistently low activity.’ Similarly, ‘consistently high’ leisure activity was associated with a reduced risk of carotid plaques (RR=0.56; 95%CI=0.23-0.89). However, ‘high and increasing’ occupational activity was associated with a reduction in high-risk global longitudinal strain (RR=0.46; 95%CI=0.08-0.85) and higher carotid intima-media thickness (β=0.06; 95%CI=0.01-0.11). No associations were observed with Young’s Elastic Modulus, carotid distensibility, or blood pressure.

Conclusion: This study was the first to define life course trajectories of total and domain-specific activity amongst a single cohort. Findings highlight that maintaining high levels of total and leisure-time activity across the life course may reduce risk of vascular structure and function degradation in mid-adulthood.

Background: Cardiorespiratory fitness (CRF) is a modifiable cardiovascular risk factor for both children and adults. However, little is known how variations in CRF over time impact long-term cardiovascular health. Therefore, we examined the relationship between CRF from childhood to mid-adulthood and the American Heart Association’s Life’s Essential 8 (LE8) score, a measure of overall cardiovascular health.
Methods: As part of the longitudinal Childhood Determinants of Adult Health (CDAH) Study, up to 240 participants had their CRF measured as physical work capacity at 170 beats per minute (PWC170) in childhood (1985: aged 9, 12, 15 years), young adulthood (2004–06: age: 26–36 years), and mid-adulthood (2014–19: 36–49 years). In adulthood, participants had their diet, physical activity, smoking status, sleep, body mass index, blood lipids, blood glucose and blood pressure assessed, with LE8 scores created following AHA recommendations. Associations were evaluated using life course epidemiological methods, including linear regression analyses and the Bayesian relative life-course exposure model.
Results: The relationship between CRF measured across the life course and adult LE8 was best characterised by a lifetime growth model, where higher levels of CRF in childhood, and increased CRF between childhood and young adulthood, and between young- and mid-adulthood were associated with greater LE8 scores in midlife. When the relative importance of CRF within this relationship was quantified, CRF was important at each examined life stage, with the effect of CRF in mid-adulthood markedly greater than at other times, highlighting a sensitive period in midlife.
Conclusion: These findings support a life course approach to the prevention of adverse cardiovascular health, highlighting the cardiovascular benefits of greater CRF in both childhood and adulthood, and increasing CRF over time.

Background: Mosaic loss of the Y chromosome (mLOY) occurs in the circulating white blood cells of aging men, is associated with adverse cardiovascular outcomes. However, most studies included men with pre-existing cardiovascular or kidney disease, rather than initially healthy individuals. This study examines the association between mLOY and major adverse cardiac events (MACE) in a well-characterised cohort of initially healthy older men.
Methods: The study included 5,131 men aged >65 years from the ASPREE trial, free of evidenced cardiovascular disease at baseline and recruited between 2010-2014. mLOY was estimated using the Log R Ratio (mLRRY) from genotyping array data, from which the percentage of LOY was calculated. Adjudicated MACE outcomes included CHD death, fatal/non-fatal myocardial infarction (MI) and ischaemic stroke. Cox regression assessed associations between mLOY and MACE, MI and stroke. mLOY was analyzed continuously (per 1 SD increase) and categorically in deciles: D1–D6 (highest 60%, no mLOY), D7–D9 (middle 30%, moderate mLOY), and D10 (lowest 10%, substantial mLOY), using D1–D6 as the reference. Nonlinear associations were examined using restricted cubic splines.
Results: Over a median follow-up of 8.4 years, 9.8% (n=505) experienced MACE, including 5% (n=256) with MI and 4% (n=207) with ischemic stroke. Each 1 SD increase in mLOY was associated with an 8% higher risk of MACE (HR 1.08 CI 0.99-1.17) and a 14% higher risk of MI (HR 1.14, 95% CI 1.02–1.28). Individuals in the highest decile of mLOY (D10) had a 34% higher risk of MACE (HR 1.34, 95% CI 1.00-1.78) and 68% higher risk of MI (HR 1.68, 95% CI 1.16-2.54) compared to D1-D6. No associations was observed for ischemic stroke.
Conclusion: Mosaic LOY is associated with an increased risk of MI but not stroke in initially-healthy older men followed prospectively.

Background: The role of aspirin in reducing lipoprotein(a)-mediated atherothrombotic events in primary prevention is not established. This study sought to assess whether low-dose aspirin benefits individuals with elevated plasma lipoprotein(a)-associated genotypes in the setting of primary prevention.

Methods: The study analyzed 12,815 genotyped individuals ≥70 years of age of European ancestry and without prior cardiovascular disease events enrolled in the ASPREE (ASPirin in Reducing Events in the Elderly) randomized controlled trial of 100 mg/d aspirin. We defined lipoprotein(a)-associated genotypes using rs3798220-C carrier status and quintiles of a lipoprotein(a) genomic risk score (LPA-GRS). We tested for interaction between genotypes and aspirin allocation in Cox proportional hazards models for incidence of major adverse cardiovascular events (MACE) and clinically significant bleeding. We also examined associations in the aspirin and placebo arms of the trial separately.

Results: During a median 4.7 years (IQR: 3.6-5.7 years) of follow-up, 435 MACE occurred, with an interaction observed between rs3798220-C and aspirin allocation (P = 0.049). rs3798220-C carrier status was associated with increased MACE risk in the placebo group (HR: 1.90; 95% CI: 1.11-3.24) but not in the aspirin group (HR: 0.54; 95% CI: 0.17-1.70). High LPA-GRS (vs low) was associated with increased MACE risk in the placebo group (HR: 1.70; 95% CI: 1.14-2.55), with risk attenuated in the aspirin group (HR: 1.41; 95% CI: 0.90-2.23), but the interaction was not statistically significant. In all participants, aspirin reduced MACE by 1.7 events per 1,000 person-years and increased clinically significant bleeding by 1.7 events per 1,000 person-years. However, in the rs3798220-C and high LPA-GRS subgroups, aspirin reduced MACE by 11.4 and 3.3 events per 1,000 person-years respectively, without significantly increased bleeding risk.

Conclusions: Aspirin may benefit older individuals with elevated lipoprotein(a) genotypes in primary prevention.

Background
While evidence links UPF to various chronic diseases, its association with sleep-related disorders, particularly obstructive sleep apnoea (OSA), remains unexplored. This study investigates the relationship between UPF intake and OSA using data from the National Health and Nutrition Examination Survey (NHANES).
Methods
A total of 13,953 participants aged 20 years and older were included. UPF consumption was quantified as a percentage of total grams per day (%gm/day) and a percentage of total energy intake (%kcal/day). OSA was assessed using standardised tools, along with reported snoring and excessive daytime sleepiness (EDS). Multivariable-adjusted logistic regression models with inverse probability treatment weighting were used to estimate associations between UPF intake and OSA outcomes.
Results
The prevalence of OSA was 26%. Compared with participants in the lowest quartile, those in the highest quartile of UPF consumption (%gm/day) had increased odds of OSA (OR = 1.23; 95% CI: 1.04, 1.46), snoring (OR = 1.19; 95% CI: 1.02, 1.38), and EDS (OR = 1.10; 95% CI: 0.93, 1.29). A linear relationship was observed between a 10% increase in UPF intake and OSA risk. However, no associations were found between UPF intake as a percentage of total energy intake (%kcal/day) and OSA (OR = 0.87; 95% CI: 0.72, 1.04), snoring (OR = 0.92; 95% CI: 0.79, 1.08), and EDS (OR = 1.00; 95% CI: 0.86, 1.17).
Conclusion
Higher UPF consumption (%gm/day) is associated with an increased risk of OSA and related symptoms. However, when UPF consumption was measured in terms of its contribution to total energy intake (%kcal/day), associations were not found, suggesting that factors beyond calorie content play a critical role in this relationship. Given the global rise in UPF intake, further research is needed to understand its impact on sleep health and to inform dietary recommendations.

Background: Central obesity is an important predictor of metabolic syndrome (MetS), but few studies have investigated the effect of life-course central obesity trajectories on risk of MetS. Thus, we examined the association between waist circumference (WC) trajectories from childhood to adulthood and risk of MetS in adulthood.
Methods: We used data from the Childhood Determinants of Adult Health with WC measured at three timepoints in 1985 (baseline), 2004-06 (follow-up 1), and 2014-19 (follow-up 2). Age- and sex-specific WC z-scores were calculated at each timepoint, and latent class growth mixture modelling was used to model WC trajectories. MetS was defined as having two or more out of elevated blood pressure, hypertriglyceridemia, low HDL-cholesterol, and hyperglycaemia, which were assessed using laboratory results and self-reported medical history at follow-up 2. Log binomial regression was used to examine the association, adjusting for baseline age, sex, lifestyle behaviours, socio-economic status, self-reported health status and follow-up duration.
Results: We included 1,156 children (mean baseline age 11.1 [2.6] years, male 49.6%, mean follow-up 32.4 [1.4] years). Five WC trajectories were identified: persistently low (80.4%), improving from high (3.1%), average rise to peak and return to average (2.2%), progressing to high (11.5%), and persistently high (2.8%). Prevalence of MetS was 15.5%. Compared to the persistently low, non-favourable trajectories were associated with increased risks of MetS: persistently high RR 6.53, 95%CI: 4.82-8.84; progressing to high RR 4.08, 95%CI: 2.99-5.57; average rise to peak and return to average RR 4.59, 95%CI: 2.77-7.60. In contrast, the improving from high trajectory had comparable risk of MetS to the persistently low (RR: 1.57, 95%CI: 0.69-3.60).
Conclusion: Non-favourable WC trajectories from childhood to adulthood are associated with elevated risks of MetS in adulthood. Preventive strategies targeting central obesity should be implemented early in life and maintained throughout the life course to reduce CVD risk.

Background: Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2), the virus responsible for COVID-19, has been associated with significant cardiovascular complications. Emerging evidence suggests individuals with prolonged symptoms following COVID-19, often referred to as Post-Acute Sequelae of SARS-CoV-2 infection (PASC), may experience similar cardiovascular effects. However, a clear consensus on these effects in COVID-19 survivors with PASC remains lacking, underscoring the need for further investigation.
Objective: This study aims to comprehensively examine and synthesize existing research on cardiac structure and function in individuals with PASC, focusing on identifying and characterizing specific cardiovascular effects unique to this population.
Method: Seven electronic databases (Medline, PubMed, Embase, Web of Science, CINAHL, Scopus, PsycINFO) were searched for studies on cardiac structure or function in individuals with PASC. Random effects meta-analyses using the restricted maximum likelihood method were used. Multivariable and univariable meta-regressions examined sources of heterogeneity. Two individual participant data (IPD) datasets were incorporated into a hybrid IPD meta-analysis. Publication bias was assessed using funnel plot, Egger’s test, and the trim-and-fill method. Evidence quality was evaluated with the GRADE tool.
Results: Sixteen studies included 1,629 COVID-19 survivors with PASC and 1,690 controls, with mean ages ranging from 51 to 60 years. Meta-analysis revealed significant reductions in left ventricular ejection fraction (mean difference (MD) = −1.47%), left ventricular end-diastolic volume (MD = −4.87ml), and global longitudinal strain for left ventricular function (MD = 1.16%). Tricuspid annular plane systolic excursion showed a slight reduction (MD = −0.90). Meta-regression and IPD analysis showed diabetes and older age were key risk factors for cardiac impairments.
Conclusion: This review confirms PASC is associated with negative effects on cardiac function, with diabetes and older age identified as key risk factors. Although findings show statistically significant impairment in cardiac function among individuals with PASC, the clinical significance requires further study.

Background: Recommendations for paediatric lipid screening exist in the US, although public attitudes towards them are unknown. This study aimed to understand US public attitudes towards paediatric lipid screening, and factors associated with them.

Methods: A cross-sectional online survey of 1940 US adults (≥18 years) recruited via Prolific Academic. Quota sampling recruited a representative sample by age, sex, and ethnicity. Attitudes towards paediatric lipid screening were measured using a five-point Likert scale (collapsed to oppose, neutral, support). Associations between prior knowledge of cardiovascular disease progression and dyslipidaemia screening/management and support for paediatric lipid screening was examined using multivariable ordinal logistic regression, adjusting for demographics and personal and family history of cardiovascular disease.

Results: 83% supported paediatric lipid screening; 4% opposed. 84% knew lifelong risk reduction lowers future cardiovascular event risk. 39-59% knew symptoms start after age 40, disease processes begin early, and pharmacological interventions are more effective than dietary changes. 89% were unaware of current US guidelines for universal lipid screening in children aged 9-11. Knowing disease processes begin early (odds ratio = 1.72, 95% confidence interval [CI] = 1.32, 2.26) and US guidelines (odds ratio = 2.16, CI = 1.21, 3.84) were associated with higher odds of supporting paediatric lipid screening. Older age, having a child under age 15 and longer time since having lipids checked were associated with lower odds of support. 56% supported paediatric lipid screening more after reading relevant facts (34% of opposers, 62% of neutral); 5% supported it less (5% of supporters, 3% of neutral). 89% indicated child lipid screening should be higher than the current US prevalence of 10%.

Conclusion: Public knowledge about paediatric lipid screening and management is limited, despite the US having guidelines since 2011. High public support for paediatric lipid screening could be leveraged to enhance screening rates among US children.