Abstract Background Poor sleep quality is associated with increased cardiovascular risk, although its relationship with left ventricle (LV) structure is poorly understood and ethnic differences in the relationship between sleep and LV structure have not been studied. We investigated the association between poor sleep quality and LV structure in a tri-ethnic cohort. Methods A total of 1284 participants were analysed from the Southall and Brent Revisited (SABRE) study (age=49.9±6.2y; male 75.9%, Europeans (EU)=615, South Asians (SA)=457, African/African-Caribbean (AC)=212). A composite sleep quality score was calculated, and LV structure was measured using echocardiography. Associations between sleep quality and LV mass indexed to height 1 .7 (LVMi), relative wall thickness (RWT) and LV end-diastolic volume indexed to height 1 .7 (LVEDVi) were estimated using multivariable linear regression with adjustment for demographic and lifestyle factors across three models. Analyses were performed in the whole cohort and stratified by ethnicity. Results Compared with those who reported very good sleep quality, participants with poorer sleep quality had higher LVMi (4.8 (95% CI 1.4; 8.2)g/(m 1 .7 ⋅unit sleep score); p =0.006). When stratifying by ethnicity, the association between sleep quality and LVMi was unconvincing in EU (1.9(-3.5, 7.3)g/(m 1.7 ⋅unit sleep score); p =0.493), whereas poor sleep was associated with higher LVMi in AC and SA participants (9.1(1.3;16.8)g/(m 1.7 ⋅unit sleep score); p =0.023 and 5.8(0.5;11.0)g/(m 1.7 ⋅unit sleep score); p =0.031 respectively). Conclusions Poor sleep quality is associated with higher LVMi in older African/African-Caribbeans and South Asians, but not in Europeans. This may contribute to cardiovascular risk. Graphical Abstract

Abstract Background Cardiovascular disease (CVD) is a major global health challenge. Vascular ageing assessment can identify high-risk individuals for effective prevention, but the knowledge, awareness, perceptions, applications, and limitations of vascular ageing assessment in clinical and research settings are limited. This study assessed these aspects among researchers and clinicians. Methods A pilot-tested questionnaire from our previous study was distributed to clinicians and researchers. Participant’s characteristics and percentages for responses on various aspects of vascular ageing including knowledge, awareness, perceptions, applications, and limitations were reported. Results Two hundred seventy-six people completed the survey (aged 47 ± 15 years, 49.6% male, 67.0% researchers, response rate 75.4%). Findings indicated a consensus on the importance of vascular ageing in a research and clinical context. Approximately 75% acknowledged the association between vascular ageing and overall CVD risk. The group identified as most likely to benefit from vascular ageing assessment were individuals with positive family histories of CVD. There was a consensus on the potential for vascular ageing biomarkers to improve CVD risk evaluation and prevention. Over 90% believe that vascular ageing can be modified. However, less than 10% of clinicians currently measure vascular ageing in clinical settings, citing time constraints, cost and lack of guidelines as main barriers. Conclusions This study highlights the perceived value of vascular ageing measures in both research and clinical settings and identifies the challenges and limitations hindering widespread implementation. Addressing the identified challenges may facilitate the integration of vascular ageing assessments into routine clinical practice, potentially improving CVD risk stratification and patient outcomes.

BACKGROUND AND AIMS:Increasing evidence suggests that COVID-19 survivors experience long-term cardiovascular complications possibly through development of vascular damage. The study aimed to investigate whether accelerated vascular ageing occurs after COVID-19 infection, and if so, identify its determinants. METHODS:This prospective, multicentric, cohort study, included 34 centres in 16 countries worldwide, in 4 groups of participants-COVID-19-negative controls (ⅰ) and three groups of individuals with recent (6 ± 3 months) exposure to SARS-CoV-2: not hospitalized (ⅱ), hospitalized in general wards (ⅲ), and hospitalized in intensive care units (ⅳ). The main outcome was carotid-femoral pulse wave velocity (PWV), an established biomarker of large artery stiffness. RESULTS:2390 individuals (age 50 ± 15 years, 49.2% women) were recruited. After adjustment for confounders, all COVID-19-positive groups showed higher PWV (+0.41, +0.37, and +0.40 m/s for groups 2-4, P < .001, P = .001 and P = .003) vs. controls [PWV 7.53 (7.09; 7.97) m/s adjusted mean (95% CI)]. In sex-stratified analyses, PWV differences were significant in women [PWV (+0.55, +0.60, and +1.09 m/s for groups 2-4, P < .001 for all)], but not in men. Among COVID-19 positive women, persistent symptoms were associated with higher PWV, regardless of disease severity and cardiovascular confounders [adjusted PWV 7.52 (95% CI 7.09; 7.96) vs. 7.13 (95% CI 6.67; 7.59) m/s, P < .001]. A stable or improved PWV after 12 months was found in the COVID+ groups, whereas a progression was observed in the COVID- group. CONCLUSIONS:COVID-19 is associated with early vascular ageing in the long term, especially in women.

RationaleLung function in early adulthood is associated with subsequent adverse health outcomes.ObjectivesTo ascertain whether stable and reproducible lung function trajectories can be derived in different populations and investigate their association with objective measures of cardiovascular structure and function.MethodsUsing latent profile modelling, we studied three population-based birth cohorts with repeat spirometry data from childhood into early adulthood to identify trajectories of forced expiratory volume in 1 s (FEV1)/forced vital capacity (FVC). We used multinomial logistic regression models to investigate early-life predictors of the derived trajectories. We then ascertained the extent of the association between the derived FEV1/FVC trajectories and blood pressure and echocardiographic markers of increased cardiovascular risk and stroke in ~3200 participants at age 24 years in one of our cohorts.ResultsWe identified four FEV1/FVC trajectories with strikingly similar latent profiles across cohorts (pooled N=6377): above average (49.5%); average (38.3%); below average (10.6%); and persistently low (1.7%). Male sex, wheeze, asthma diagnosis/medication and allergic sensitisation were associated with trajectories with diminished lung function in all cohorts. We found evidence of an increase in cardiovascular risk markers ascertained by echocardiography (including left ventricular mass indexed to height and carotid intima-media thickness) with decreasing FEV1/FVC (with p values for the mean crude effects per-trajectory ranging from 0.10 to p<0.001). In this analysis, we considered trajectories as a pseudo-continuous variable; we confirmed the assumption of linearity in all the regression models.ConclusionsChildhood lung function trajectories may serve as predictors in the development of not only future lung disease, but also the cardiovascular disease and multimorbidity in adulthood.

Vascular ageing is the deterioration of arterial structure and function which occurs naturally with age, and which can be accelerated with disease. Measurements of vascular ageing are emerging as markers of cardiovascular risk, with potential applications in disease diagnosis and prognosis, and for guiding treatments. However, vascular ageing is not yet routinely assessed in clinical practice. A key step towards this is the development of technologies to assess vascular ageing. In this Roadmap, experts discuss several aspects of this process, including: measurement technologies; the development pipeline; clinical applications; and future research directions. The Roadmap summarises the state of the art, outlines the major challenges to overcome, and identifies potential future research directions to address these challenges.

Abstract Translating vascular aging research from bench to bedside presents both significant opportunities and challenges. This paper summarizes insights from a roundtable discussion at the Artery 23 conference, featuring perspectives from basic science, clinical trials, regulation, and industry. The main conclusions of the discussion are as follows: basic science research must align with clinical relevance, using appropriate animal models and standardized measurement techniques. Pragmatic and registry-based clinical trials offer viable alternatives to traditional randomized controlled trials, facilitating real-world applicability. The regulatory landscape, particularly for software medical devices, must evolve to keep pace with technological advancements like artificial intelligence. Industry efforts focus on developing devices or solutions for vascular aging assessment and treatment strategies, yet face hurdles in large-scale adoption and reimbursement. Despite significant progress, the development of pharmacological interventions to mitigate vascular aging remains a critical need. This discussion underscores the importance of interdisciplinary collaboration to overcome barriers and translate scientific discoveries into clinical practice effectively.

Objectives: Blood pressure (BP) is the leading global cause of mortality, and its prevalence is increasing in children and adolescents. Aortic BP is lower than brachial BP in adults. We aimed to assess the extent of this difference and its impact on the diagnosis of hypertension among adolescents. Methods: We used data from 3850 participants from a UK cohort of births in the early 1990s in the Southwest of England, who attended their ∼17-year follow-up and had valid measures of brachial and aortic BP at that clinic [mean (SD) age 17.8 (0.4) years, 66% female individuals]. Data are presented as mean differences [95% prediction intervals] for both sexes. Results: Aortic systolic BP (SBP) was lower than brachial SBP [male, −22.3 (−31.2, −13.3) mmHg; female, −17.8 (−25.5, −10.0) mmHg]. Differences between aortic and brachial diastolic BP (DBP) were minimal. Based on brachial BP measurements, 101 male individuals (6%) and 22 female individuals (1%) were classified as hypertensive. In contrast, only nine male individuals (<1%) and 14 female individuals (<1%) met the criteria for hypertension based on aortic BP, and the predictive value of brachial BP for aortic hypertension was poor (positive-predictive value = 13.8%). Participants with aortic hypertension had a higher left ventricular mass index than those with brachial hypertension. Conclusion: Brachial BP substantially overestimates aortic BP in adolescents because of marked aortic-to-brachial pulse pressure amplification. The use of brachial BP measurement may result in an overdiagnosis of hypertension during screening in adolescence.

VascAgeNet ("Network for Research in Vascular Ageing"; CA18216, www.vascagenet.eu) is a European COoperation in Science and Technology (COST) Action on vascular aging. It was launched in November 2019 to refine, harmonize, and promote the use of vascular aging biomarkers and to support the next generation of researchers and innovators in the field. By November 2023, VascAgeNet had more than 350 members with different backgrounds. Examples for initiatives are various in-person working group meetings, three successful training schools, three awareness-raising events to reach the public, a total of 46 grants for exchange and conference visits, three animations, several scientific publications and presentations, and a wide reach on social media. VascAgeNet has represented a unique opportunity for many members to learn and to propose and implement new ideas; thanks to this Action a strong, multidisciplinary, and active community has been built.

ObjectivesIn general, a terminology shared and agreed by different stakeholders is important to facilitate communication and cooperation. This holds true in the field of vascular ageing for the benefit of global cardiovascular health. The need to promote a common language and understanding across this area was recognised by VascAgeNet, a collaborative network with relevant and diverse expertise in the vascular ageing field, supported by the European Cooperation in Science and Technology. To contribute to the spread of unified terms in the vascular ageing field, a glossary was created by VascAgeNet and this paper describes the systematic process used for its development.MethodsAn initial list of terms and preliminary definitions were collated from the network. A dedicated team was created to design the glossary development process, to facilitate its implementation and to maximise outreach and dissemination. The key steps of the process were to determine: (1) the target audience; (2) a list of priority terms; (3) a template structure for definitions; (4) methods for collecting feedback and (5) the dissemination plan.ResultsAn implementation strategy was provided for each key step and shared within the network; main decisions were agreed by all members of the glossary team. Small groups of definitions were released on a regular basis within a pilot phase including 19 terms (status: 05.09.2023) that were published openly at https://vascagenet.eu/official-glossary.ConclusionsThe strategy for creating the first Vascular Ageing Glossary has been successfully designed and developed within VascAgeNet. A pilot phase covering the first publicly available terms was completed. The glossary is a living document, available to the scientific community, which aims to unify the vascular ageing language.

BACKGROUND:Regulation has a key role for medical devices throughout their lifecycle aiming to guarantee effectiveness and safety for users. Requirements of Regulation (EU) 2017/745 (MDR) have an impact on novel and previously approved systems. Identification of key stakeholders' needs can support effective implementation of MDR improving the translation to clinical practice of vascular ageing assessment. The aim of this work is to explore knowledge and perception of medical device regulatory framework in vascular ageing field.RESEARCH DESIGN AND METHODS:A survey was developed within VascAgeNet and distributed in the community by means of the EUSurvey platform.RESULTS:Results were derived from 94 participants (27% clinicians, 62% researchers, 11% companies) and evidenced mostly a fair knowledge of MDR (despite self-judged as poor by 51%). Safety (83%), validation (56%), risk management (50%) were considered relevant and associated with the regulatory process. Structured support and regulatory procedures connected with medical devices in daily practice at the institutional level are lacking (only 33% report availability of a regulatory department).CONCLUSIONS:Regulation was recognized relevant by the VascAgeNet community and specific support and training in medical device regulatory science was considered important. A direct link with the regulatory sector is not yet easily available.

Blood pressure and vascular ageing trajectories differ between men and women. These differences develop due to sex-related factors, attributable to sex chromosomes or sex hormones, and due to gender-related factors, mainly related to different sociocultural behaviors. The present review summarizes the relevant facts regarding gender-related differences in vascular function in hypertension. Among sex-related factors, endogenous 17ß-estradiol plays a key role in protecting pre-menopausal women from vascular ageing. However, as vascular ageing (preceding and inducing hypertension) has a steeper increase in women than in men starting already from the third decade, it is likely that gender-related factors play a prominent role, especially in the young. Among gender-related factors, psychological stress (including that one related to gender-based violence and discrimination), depression, some psychological traits, but also low socioeconomic status, are more common in women than men, and their impact on vascular ageing is likely to be greater in women. Men, on the contrary, are more exposed to the vascular adverse consequences of alcohol consumption, as well as of social deprivation, while "toxic masculinity" traits may result in lower adherence to lifestyle and preventive strategies. Unhealthy diet habits are more prevalent in men and smoking is equally prevalent in the two sexes, but have a disproportional negative effect on women's vascular health. In conclusion, given the major and complex role of gender-related factors in driving vascular alterations and blood pressure patterns, gender dimension should be systematically integrated into future research on vascular function and hypertension and to tailor cardiovascular prevention strategies.

Objectives Blood pressure is the leading global cause of mortality, and its prevalence is increasing in children and adolescents. Aortic blood pressure (BP) is lower than brachial BP in adults. We aimed to assess the extent of this difference and its impact on the diagnosis of hypertension among adolescents. Methods We used data from 3850 participants from a UK cohort of births in the early 1990s in the Southwest of England, who attended their ∼17 year follow-up and had valid measures of brachial and aortic BP at that clinic (mean(SD) age 17.8(0.4)y, 66% female). Data are presented as mean differences [95% prediction intervals] for both sexes. Results Aortic systolic BP was lower than brachial systolic BP (male, -22.3[-31.2, - 13.3]mmHg; female, -17.8[-25.5, -10.0]mmHg). Differences between aortic and brachial diastolic BP were minimal. Based on brachial BP measurements, 101 males (6%) and 22 females (1%) were classified as hypertensive. In contrast, only nine males (<1%) and 14 females (<1%) met the criteria for hypertension based on aortic BP, and the predictive value of brachial BP for aortic hypertension was poor (positive predictive value = 13.8%). Participants with aortic hypertension had a higher left ventricular mass index than those with brachial hypertension. Conclusions Brachial BP substantially overestimates aortic BP in adolescents due to marked aortic-to-brachial pulse pressure amplification. The use of brachial BP measurement may result in an overdiagnosis of hypertension during screening in adolescence.

This review critiques the literature supporting clinical assessment and management of cardiovascular disease and cardiovascular disease risk stratification with brachial-ankle pulse wave velocity (baPWV). First, we outline what baPWV actually measures-arterial stiffness of both large central elastic arteries and medium-sized muscular peripheral arteries of the lower limb. Second, we argue that baPWV is not a surrogate for carotid-femoral pulse wave velocity. While both measures are dependent on the properties of the aorta, baPWV is also strongly dependent on the muscular arteries of the lower extremities. Increased lower-extremity arterial stiffness amplifies and hastens wave reflections at the level of the aorta, widens pulse pressure, increases afterload, and reduces coronary perfusion. Third, we used an established evaluation framework to identify the value of baPWV as an independent vascular biomarker. There is sufficient evidence to support (1) proof of concept; (2) prospective validation; (3) incremental value; and (4) clinical utility. However, there is limited or no evidence to support (5) clinical outcomes; (6) cost-effectiveness; (8) methodological consensus; or (9) reference values. Fourth, we address future research requirements. The majority of the evaluation criteria, (1) proof of concept, (2) prospective validation, (3) incremental value, (4) clinical utility and (9) reference values, can be supported using existing cohort datasets, whereas the (5) clinical outcomes and (6) cost-effectiveness criteria require prospective investigation. The (8) methodological consensus criteria will require an expert consensus statement. Finally, we finish this review by providing an example of a future clinical practice model.

BACKGROUND:Vascular age (VA) is independent and chronological age for assessing cardiovascular disease (CVD) risk. However, tools for the implementation of VA are currently lacking. We aimed to develop a questionnaire to assess the current knowledge gaps related to VA and barriers to its implementation in routine practice.METHODS:Using a stepwise mixed-method approach, a quantitative questionnaire was constructed in four phases: (1) basic item generation and the development of a semi-qualitative questionnaire (SQQ); (2) dissemination to the VascAgeNet extended network and an analysis of the semi-qualitative questionnaire responses; (3) the development of a quantitative questionnaire (QQ); and (4) an assessment of the content and face validity and internal reliability in an additional sample.RESULTS:Based on six main topics initially identified through an expert panel, a SQQ was developed and disseminated. Finally, a 22-item QQ was developed, with questions grouped around three main themes: knowledge of VA and its risk factors; perceptions and beliefs regarding the importance and contribution of VA to risk classification; and the application of VA measurements in clinical and research practice and its potential limitations (Cronbach's alpha between 0.920 and 0.982 for all three categories).CONCLUSION:We report the development of a QQ on VA addressed to both clinicians and non-clinicians aiming to assess their knowledge, perceptions and application of VA measurements.

BACKGROUND: Left ventricular mass (LVM) is an important predictor of cardiovascular risk. In adolescence, LVM is commonly indexed to height 2.7 , although some evidence suggests that this may not fully account for sex differences. METHODS: We investigated appropriate allometric scaling of LVM to height, total lean mass, and body surface area, in a UK birth cohort of 2039 healthy adolescents (17±1 years). Allometric relationships were determined by linear regression stratified by sex, following log transformation of x and y variables [log(y)=a+b×log(x)], b is the allometric exponent. RESULTS: Log (LVM) showed linear relationships with log(height) and log(lean mass). Biased estimates of slope resulted when the sexes were pooled. The exponents were lower than the conventional estimate of 2.7 for males (mean [95% CI]=1.66 [1.30–2.03]) and females (1.58 [1.27–1.90]). When LVM was indexed to lean mass, the exponent was 1.16 (1.05–1.26) for males and 1.07 (0.97–1.16) for females. When LVM was indexed to estimated body surface area, the exponent was 1.53 (1.40–1.66) for males and 1.34 (1.24–1.45) for females. CONCLUSIONS: Allometric exponents derived from pooled data, including men and women without adjustment for sex were biased, possibly due to sex differences in body composition. We suggest that when assessing LVM, clinicians should consider body size, body composition, sex, and age. Our observations may also have implications for the identification of young individuals with cardiac hypertrophy.

3D-speckle tracking echocardiography(3D-STE) allows simultaneous assessment of ejection fraction(EF) and multidirectional strains, but its prognostic utility in the general population is unknown. We investigated if 3D-STE strains predicted a composite of major cardiac endpoints(MACE) beyond cardiovascular risk factors(CVDRF), and whether they were superior to 3D-EF. 529 participants in SABRE, a UK-based tri-ethnic general population cohort (69±6y; 76.6% male) with acceptable 3D-STE imaging were studied. Associations between 3D-EF or multidirectional myocardial strains and MACE(coronary heart disease(fatal/non-fatal), heart failure hospitalization, new-onset arrhythmia and cardiovascular mortality) were determined using Cox regression including adjustment for CVDRF and 2D-EF. Whether 3D-EF, global longitudinal strain(3D-GLS) and principle tangential strain(3D-PTS/3D-strain) improved cardiovascular risk stratification over CVDRF was investigated using a likelihood ratio test on a series of nested Cox proportional hazards models and Harrell's C statistics. During follow-up(median, 12y), there were 92 events. 3D-EF, 3D-GLS and 3D-PTS and 3D-RS were associated with MACE in unadjusted and models adjusted for CVDRF but not CVDRF+2D-EF. Compared to 3D-EF, both 3D-GLS and 3D-PTS slightly improved the predictive value over CVDRF for MACE, but the improvement was modest(C statistic increased from 0.698(0.647, 0.749) to 0.715(0.663, 0.766) comparing CVDRF with CVDRF +3D-GLS). 3D-STE-derived LV myocardial strains predicted MACE in a multi-ethnic general population sample of elderly individuals from the UK; however the added prognostic value of 3D-STE myocardial strains was small.