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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 Long-term sickness absence from employment has negative consequences for the economy and can lead to widened health inequalities. Sick notes (also called ‘fit notes’) are issued by general practitioners when a person cannot work for health reasons for more than 7 days. We quantified the sick note rate in people with evidence of COVID-19 in 2020, 2021 and 2022, as an indication of the burden for people recovering from COVID-19.Design Cohort study.Setting With National Health Service (NHS) England approval, we used routine clinical data (primary care, hospital and COVID-19 testing records) within the OpenSAFELY-TPP database.Participants People 18–64 years with a recorded positive test or diagnosis of COVID-19 in 2020 (n=365 421), 2021 (n=1 206 555) or 2022 (n=1 321 313); general population matched in age, sex and region in 2019 (n=3 140 326), 2020 (n=3 439 534), 2021 (n=4 571 469) and 2022 (n=4 818 870); people hospitalised with pneumonia in 2019 (n=29 673).Primary outcome measure Receipt of a sick note in primary care.Results Among people with a positive SARS-CoV-2 test or COVID-19 diagnosis, the sick note rate was 4.88 per 100 person-months (95% CI 4.83 to 4.93) in 2020, 2.66 (95% CI 2.64 to 2.67) in 2021 and 1.73 (95% CI 1.72 to 1.73) in 2022. Compared with the age, sex and region-matched general population, the adjusted HR for receipt of a sick note over the entire follow-up period (up to 10 months) was 4.07 (95% CI 4.02 to 4.12) in 2020 decreasing to 1.57 (95% CI 1.56 to 1.58) in 2022. The HR was highest in the first 30 days postdiagnosis in all years. Among people hospitalised with COVID-19, after adjustment, the sick note rate was lower than in people hospitalised with pneumonia.Conclusions Given the under-recording of postacute COVID-19-related symptoms, these findings contribute a valuable perspective on the long-term effects of COVID-19. Despite likely underestimation of the sick note rate, sick notes were issued more frequently to people with COVID-19 compared with those without, even in an era when most people are vaccinated. Most sick notes occurred in the first 30 days postdiagnosis, but the increased risk several months postdiagnosis may provide further evidence of the long-term impact.

Abstract Objectives In 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. Methods An 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. Results An 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 . Conclusions The 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.

Summary: Background: The COVID-19 pandemic disrupted healthcare and may have impacted ethnic inequalities in healthcare. We aimed to describe the impact of pandemic-related disruption on ethnic differences in clinical monitoring and hospital admissions for non-COVID conditions in England. Methods: In this population-based, observational cohort study we used primary care electronic health record data with linkage to hospital episode statistics data and mortality data within OpenSAFELY, a data analytics platform created, with approval of NHS England, to address urgent COVID-19 research questions. We included adults aged 18 years and over registered with a TPP practice between March 1, 2018, and April 30, 2022. We excluded those with missing age, sex, geographic region, or Index of Multiple Deprivation. We grouped ethnicity (exposure), into five categories: White, Asian, Black, Other, and Mixed. We used interrupted time-series regression to estimate ethnic differences in clinical monitoring frequency (blood pressure and Hba1c measurements, chronic obstructive pulmonary disease and asthma annual reviews) before and after March 23, 2020. We used multivariable Cox regression to quantify ethnic differences in hospitalisations related to diabetes, cardiovascular disease, respiratory disease, and mental health before and after March 23, 2020. Findings: Of 33,510,937 registered with a GP as of 1st January 2020, 19,064,019 were adults, alive and registered for at least 3 months, 3,010,751 met the exclusion criteria and 1,122,912 were missing ethnicity. This resulted in 14,930,356 adults with known ethnicity (92% of sample): 86.6% were White, 7.3% Asian, 2.6% Black, 1.4% Mixed ethnicity, and 2.2% Other ethnicities. Clinical monitoring did not return to pre-pandemic levels for any ethnic group. Ethnic differences were apparent pre-pandemic, except for diabetes monitoring, and remained unchanged, except for blood pressure monitoring in those with mental health conditions where differences narrowed during the pandemic. For those of Black ethnicity, there were seven additional admissions for diabetic ketoacidosis per month during the pandemic, and relative ethnic differences narrowed during the pandemic compared to the White ethnic group (Pre-pandemic hazard ratio (HR): 0.50, 95% confidence interval (CI) 0.41, 0.60, Pandemic HR: 0.75, 95% CI: 0.65, 0.87). There was increased admissions for heart failure during the pandemic for all ethnic groups, though highest in those of White ethnicity (heart failure risk difference: 5.4). Relatively, ethnic differences narrowed for heart failure admission in those of Asian (Pre-pandemic HR 1.56, 95% CI 1.49, 1.64, Pandemic HR 1.24, 95% CI 1.19, 1.29) and Black ethnicity (Pre-pandemic HR 1.41, 95% CI: 1.30, 1.53, Pandemic HR: 1.16, 95% CI 1.09, 1.25) compared with White ethnicity. For other outcomes the pandemic had minimal impact on ethnic differences. Interpretation: Our study suggests that ethnic differences in clinical monitoring and hospitalisations remained largely unchanged during the pandemic for most conditions. Key exceptions were hospitalisations for diabetic ketoacidosis and heart failure, which warrant further investigation to understand the causes. Funding: LSHTM COVID-19 Response Grant (DONAT15912).

BackgroundThree-dimensional echocardiography (3DE) measures of the left ventricle (LV) predict outcomes in high risk individuals, but their prognostic value in the general population is unknown. We aimed to establish whether 3DE was associated with mortality and morbidity in a multi-ethnic community-based sample, if associations differed by sex, and explored potential mechanisms explaining sex differences.Methods922 individuals (69.7 ± 6.2 years; 717 men) from the SABRE study underwent a health examination including echocardiography. Associations between 3DE LV measures (ejection fraction (EF), end-diastolic volume (EDV), end-systolic volume (ESV), LV remodeling index (LVRI) and LV sphericity index (LVSI), and all-cause mortality and a composite cardiovascular endpoint [comprising new onset (non)fatal coronary heart disease, heart failure hospitalization, new-onset arrhythmias and cardiovascular mortality] were determined using multivariable Cox regression over a median follow-up of 8 years (all-cause mortality) and 7 years (composite cardiovascular endpoint).ResultsThere were 123 deaths and 151 composite cardiovascular endpoints. Lower EF, higher LV volumes and LVSI were associated with increased all-cause mortality, and higher LV volumes were associated with the composite cardiovascular endpoint independent of potential confounders. Associations between LV volumes, LVRI, LVSI, and mortality differed by sex (p interaction

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.

Abstract Background Whether earlier onset of puberty is associated with higher cardiovascular risk in early adulthood is not well understood. Our objective was to examine the association between puberty timing and markers of cardiovascular structure and function at age 25 years. Methods We conducted a prospective birth cohort study using data from the Avon Longitudinal Study of Parents and Children (ALSPAC). Participants were born between April 1, 1991, and December 31, 1992. Exposure of interest was age at peak height velocity (aPHV), an objective and validated growth-based measure of puberty onset. Outcome measures included cardiovascular structure and function at age 25 years: carotid intima-media thickness (CIMT), left ventricular mass index (LVMI) and relative wall thickness (RWT), pulse wave velocity (PWV) and systolic blood pressure (SBP). Multiple imputation was used to impute missing data on covariates and outcomes. Linear regression was used to examine the association between aPHV and each measure of cardiac structure and function, adjusting for maternal age, gestational age, household social class, maternal education, mother’s partner’s education, breastfeeding, parity, birthweight, maternal body mass index, maternal marital status, maternal prenatal smoking status and height and fat mass at age 9. All analyses were stratified by sex. Results A total of 2752–4571 participants were included in the imputed analyses. A 1-year older aPHV was not strongly associated with markers of cardiac structure and function in males and females at 25 years and most results spanned the null value. In adjusted analyses, a 1-year older aPHV was associated with 0.003 mm (95% confidence interval (CI) 0.00001, 0.006) and 0.0008 mm (95% CI − 0.002, 0.003) higher CIMT; 0.02 m/s (95% CI − 0.05, 0.09) and 0.02 m/s (95% CI − 0.04, 0.09) higher PWV; and 0.003 mmHg (95% CI − 0.60, 0.60) and 0.13 mmHg (95% CI − 0.44, 0.70) higher SBP, among males and females, respectively. A 1-year older aPHV was associated with − 0.55 g/m2.7 (95% CI − 0.03, − 1.08) and − 0.89 g/m2.7 (95% CI − 0.45, − 1.34) lower LVMI and − 0.001 (95% CI − 0.006, 0.002) and − 0.002 (95% CI − 0.006, 0.002) lower RWT among males and females. Conclusions Earlier puberty is unlikely to have a major impact on pre-clinical cardiovascular risk in early adulthood.

Children with obesity typically have larger left ventricular heart dimensions during adulthood. However, whether this is due to a persistent effect of adiposity extending into adulthood is challenging to disentangle due to confounding factors throughout the lifecourse. We conducted a multivariable mendelian randomization (MR) study to separate the independent effects of childhood and adult body size on 4 magnetic resonance imaging (MRI) measures of heart structure and function in the UK Biobank (UKB) study. Strong evidence of a genetically predicted effect of childhood body size on all measures of adulthood heart structure was identified, which remained robust upon accounting for adult body size using a multivariable MR framework (e.g., left ventricular end-diastolic volume (LVEDV), Beta = 0.33, 95% confidence interval (CI) = 0.23 to 0.43, P = 4.6 × 10-10). Sensitivity analyses did not suggest that other lifecourse measures of body composition were responsible for these effects. Conversely, evidence of a genetically predicted effect of childhood body size on various other MRI-based measures, such as fat percentage in the liver (Beta = 0.14, 95% CI = 0.05 to 0.23, P = 0.002) and pancreas (Beta = 0.21, 95% CI = 0.10 to 0.33, P = 3.9 × 10-4), attenuated upon accounting for adult body size. Our findings suggest that childhood body size has a long-term (and potentially immutable) influence on heart structure in later life. In contrast, effects of childhood body size on other measures of adulthood organ size and fat percentage evaluated in this study are likely explained by the long-term consequence of remaining overweight throughout the lifecourse.

Background Image‐quality (IQ) compromises left ventricle assessment by 3‐dimensional echocardiography (3DE). Sicker/frailer patients often have suboptimal IQ, and therefore observed associations may be biased by IQ. We investigated its effect in an observational study of older people and when IQ was modified experimentally in healthy volunteers. Methods and Results 3DE feasibility by IQ was assessed in 1294 individuals who attended the second wave of the Southall and Brent Revisited study and was compared with 2‐dimensional (2D)‐echocardiography feasibility in 147 individuals. Upon successful analysis, means of ejection fraction (3D‐EF) and global longitudinal strain (3D‐GLS) (plus 2D‐EF) were compared in individuals with poor versus good IQ. In 2 studies of healthy participants, 3DE‐IQ was impaired by (1) intentionally poor echocardiographic technique, and (2) use of a sheet of ultrasound‐attenuating material (neoprene rubber; 2–4 mm). The feasibility was 41% (529/1294) for 3DE versus 61% (89/147) for 2D‐EF, P

Background Low‐grade inflammation in the young may contribute to the early development of cardiovascular disease. We assessed whether circulating levels of glycoprotein acetyls (GlycA) were better able to predict the development of adverse cardiovascular disease risk profiles compared with the more commonly used biomarker high‐sensitivity CRP (C‐reactive protein). Methods and Results A total of 3306 adolescents and young adults from the Avon Longitudinal Study of Parents and Children (mean age, 15.4±0.3; n=1750) and Cardiovascular Risk in Young Finns Study (mean age, 32.1±5.0; n=1556) were included. Baseline associations between inflammatory biomarkers, body composition, cardiovascular risk factors, and subclinical measures of vascular dysfunction were assessed cross‐sectionally in both cohorts. Prospective risk of developing hypertension and metabolic syndrome during 9‐to‐10‐year follow‐up were also assessed as surrogate markers for future cardiovascular risk. GlycA showed greater within‐subject correlation over 9‐to‐10‐year follow‐up in both cohorts compared with CRP, particularly in the younger adolescent group (r=0.36 versus 0.07). In multivariable analyses, GlycA was found to associate with multiple lifestyle‐related cardiovascular disease risk factors, cardiometabolic risk factor burden, and vascular dysfunction (eg, mean difference in flow‐mediated dilation=−1.2 [−1.8, −0.7]% per z‐score increase). In contrast, CRP levels appeared predominantly driven by body mass index and showed little relationship to any measured cardiovascular risk factors or phenotypes. In both cohorts, only GlycA predicted future risk of both hypertension (risk ratio [RR], ≈1.1 per z‐score increase for both cohorts) and metabolic syndrome (RR, ≈1.2–1.3 per z‐score increase for both cohorts) in 9‐to‐10‐year follow‐up. Conclusions Low‐grade inflammation captured by the novel biomarker GlycA is associated with adverse cardiovascular risk profiles from as early as adolescence and predicts future risk of hypertension and metabolic syndrome in up to 10‐year follow‐up. GlycA is a stable inflammatory biomarker which may capture distinct sources of inflammation in the young and may provide a more sensitive measure than CRP for detecting early cardiovascular risk.

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.

Purpose: To define and compare cardiovascular (CV) health scores (CHS) from adolescence (17 yrs) to emerging adulthood (24 yrs) using longitudinal data from a large British birth cohort. Methods: 3142 participants from the Avon Longitudinal Study of Parents and Children (ALSPAC) study attended clinical investigations at 17.8 ± 0.4 yrs and 24.0 ± 0.8 yrs (38% male). CV health was assessed using smoking status, body mass index (BMI), plasma glucose, cholesterol, sitting brachial blood pressure, left ventricle (LV) hypertrophy, arterial stiffness (carotid-to-femoral pulse wave velocity) and atherosclerosis (carotid intima-media thickness) metrics. Prevalence was stratified into poor (0_points), intermediate (1_point) and ideal (2_points) health categories and a composite, individual-level CHS for all 8 metrics was calculated (total range, 0–16 points). Prevalence of ideal health was assessed using ANOVA and linear mixed modelling assessed age##sex modifications. Results: Overall CHS was high at 17 yrs but from 17–24 yrs the proportion of ideal scores decreased for all metrics, in both sexes (Table). The average overall CHS decreased from 14.97 ± 1.1 to 13.99 ± 1.4 in males (p < 0.0001) and 14.82 ± 1.2 to 14.28 ± 1.4 in females (p < 0.0001, age##sex p = 0.0001). Significant sex differences were observed in the proportion of individuals with ideal health at both ages, with males having a higher CHS than females at 17 yrs but a lower CHS at 24 yrs. Male Female Sex differences Age 17 yrs 24 yrs 17 yrs 24 yrs 17 24 Age##sex Score 0 1 2 0 1 2 p 0 1 2 0 1 2 p p p p Smoking 22.6 19.3 58.1 27.8 35.6 36.6

Background: People of South Asian and African Caribbean ethnicities living in UK have a high risk of cardiometabolic disease. Limited data exist regarding detailed cardiometabolic phenotyping in this population. Methods enabling this are widely available, but the practical aspects of undertaking such studies in large and diverse samples are seldom reported.Methods: The Southall and Brent Revisited (SABRE) study is the UK's largest tri-ethnic longitudinal cohort. Over 1,400 surviving participants (58–85 years) attended the 2nd study visit (2008–2011); during which, comprehensive cardiovascular phenotyping, including 3D-echocardiography [3D-speckle-tracking (3D-STE)], computed tomography, coronary artery calcium scoring, pulse wave velocity, central blood pressure, carotid artery ultrasound, and retinal imaging, were performed. We describe the methods used with the aim of providing a guide to their feasibility and reproducibility in a large tri-ethnic population-based study of older people.Results: Conventional echocardiography and all vascular measurements showed high feasibility (>90% analyzable of clinic attendees), but 3D-echocardiography (3DE) and 3D-STE were less feasible (71% 3DE acquisition feasibility and 38% 3D-STE feasibility of clinic attendees). 3D-STE feasibility differed by ethnicity, being lowest in South Asian participants and highest in African Caribbean participants (p < 0.0001). Similar trends were observed in men (P < 0.0001) and women (P = 0.005); however, in South Asians, there were more women with unreadable 3D-images compared to men (67 vs. 58%). Intra- and inter-observer variabilities were excellent for most of conventional and advanced echocardiographic measures. The test-retest reproducibility was good-excellent and fair-good for conventional and advanced echocardiographic measures, respectively, but lower than when re-reading the same images. All vascular measures demonstrated excellent or fair-good reproducibility.Conclusions: We describe the feasibility and reproducibility of detailed cardiovascular phenotyping in an ethnically diverse population. The data collected will lead to a better understanding of why people of South Asian and African Caribbean ancestry are at elevated risk of cardiometabolic diseases.

BackgroundWave intensity analysis provides valuable information on ventriculo-arterial function, hemodynamics, and energy transfer in the arterial circulation. Widespread use of wave intensity analysis is limited by the need for concurrent measurement of pressure and flow waveforms. We describe a method that can estimate wave intensity patterns using only non-invasive pressure waveforms (pWIA).MethodsRadial artery pressure and left ventricular outflow tract (LVOT) flow velocity waveforms were recorded in 12 participants in the Southall and Brent Revisited (SABRE) study. Pressure waveforms were analyzed using custom-written software to derive the excess pressure (Pxs) which was scaled to peak LVOT velocity and used to calculate wave intensity. These data were compared with wave intensity calculated using the measured LVOT flow velocity waveform. In a separate study, repeat measures of pWIA were performed on 34 individuals who attended two clinic visits at an interval of ≈1 month to assess reproducibility and reliability of the method.ResultsPxs waveforms were similar in shape to aortic flow velocity waveforms and the time of peak Pxs and peak aortic velocity agreed closely. Wave intensity estimated using pWIA showed acceptable agreement with estimates using LVOT velocity tracings and estimates of wave intensity were similar to values reported previously in the literature. The method showed fair to good reproducibility for most parameters.ConclusionThe Pxs is a surrogate of LVOT flow velocity which, when appropriately scaled, allows estimation of aortic wave intensity with acceptable reproducibility. This may enable wider application of wave intensity analysis to large studies.

Background: We have previously shown that 3D echocardiography-derived (3DE) indices of left ventricular (LV) structure predict all-cause mortality differently in men and women [1]. However, the mechanism behind these sex differences remains unknown. We therefore examined the role of macro- and micro-vascular disease in explaining these sex differences. Methods: 910 individuals (age, 69.7 ± 6.2 years; 77.7% male) from the SABRE study, a UK-largest tri-ethnic longitudinal cohort, underwent a health examination. Associations between 3DE-derived LV measures (end-diastolic volume (EDV), end-systolic volume (ESV) and LV remodeling index (LVRI)) and all-cause mortality were determined using multivariable Cox regression. Total arterial compliance (TAC), augmentation index (AI), eGFR and microalbuminuria were added to these models. Results: 103 (14.5%) men and 17 (8.4%) women died over median follow-up of 8 years. After multivariable adjustment, lower LVRI, and higher volumes were independently associated with increased risk of mortality in men; however, associations were reversed in women (Table 1; p (interaction: LVRI = 0.034, EDV = 0.051, and ESV = 0.009)). TAC was lower in women (0.73 ± 0.24 vs 0.83 ± 0.27, p < 0.0001) and AI higher (156.1 ± 22.3 vs 145.4 ± 21, p < 0.0001; adjustment for TAC and AI attenuated the associations in women, but not in men (Table 1), resulting in smaller sex differences in associations. Adjustment for measures of microvascular disease had negligible effect on associations in men or women. Table 1Associations between 3DE-derived indices of LV structure and all-cause mortality Men, HR (95% CI), p Women, HR (95% CI), p 3D LVRI† (N = 689; 99 deaths, SD = 0.37 g/ml) (N = 190; 16 deaths, SD = 0.34 g/ml) Model 1 0.77 (0.63, 0.94), 0.012 1.5 (0.95, 2.5), 0.082 + TAC 0.82 (0.66, 1.0), 0.071 1.25 (0.72, 2.1), 0.426 + Central AI 0.82 (0.67, 1.0), 0.072 (N = 629; 89 deaths) 1.23 (0.67, 2.2), 0.504 (N = 170; 13 deaths) + TAC + Central AI 0.87 (0.70, 1.1), 0.260 (N = 629; 89 deaths) 1.1 (0.58, 2.0), 0.801 (N = 170; 13 deaths) + eGFR 0.79 (0.64, 0.96), 0.021 1.5 (0.95, 2.4), 0.083 + Microalbuminuria 0.78 (0.64, 0.95), 0.015 1.6 (0.99, 2.8), 0.053 + eGFR + Microalbuminuria 0.79 (0.65, 0.97), 0.023 1.6 (0.98, 2.7), 0.061 3D EDV (N = 707; 103 deaths, SD = 9.9 ml/m2) (N = 203; 17 deaths, SD = 7.3 ml/m2) Model 1 1.26 (1.1, 1.5), 0.007 0.51 (0.25, 1.1), 0.076 + TAC 1.23 (0.99, 1.5), 0.060 0.78 (0.29, 2.0), 0.613 + Central AI 1.25 (1.04, 1.5), 0.013 (N = 646; 92 deaths) 0.75 (0.31, 1.8), 0.519 (N = 183; 14 deaths) + TAC + Central AI 1.22 (0.98, 1.5), 0.078 (N = 646; 92 deaths) 1.0 (0.38, 3.1), 0.871 (N = 183; 14 deaths) + eGFR 1.23(1.0, 1.45), 0.014 0.51 (0.25, 1.0), 0.071 + Microalbuminuria 1.25 (1.0, 1.5), 0.010 0.60 (0.28, 1.3), 0.189 + eGFR + Microalbuminuria 1.23 (1.0, 1.45), 0.016 0.57 (0.27, 1.2), 0.144 3D ESV (N = 707; 103 deaths, SD = 6.1 ml/m2) (N = 203; 17 deaths, SD = 3.7 ml/m2) Model 1 1.37 (1.14, 1.66), 0.001 0.56 (0.31, 1.0), 0.048 + TAC 1.34 (1.1, 1.6), 0.004 0.68 (0.36, 1.3), 0.221 + Central AI 1.38 (1.13, 1.7), 0.001 (N = 646; 92 deaths) 0.72 (0.36, 1.4), 0.347 (N = 183; 14 deaths) + TAC + Central AI 1.35 (1.1, 1.7), 0.004 (N = 646; 92 deaths) 0.82 (0.40, 1.7), 0.598 (N = 183; 14 deaths) 3D ESV (N = 707; 103 deaths, SD = 6.1 ml/m2) (N = 203; 17 deaths, SD = 3.7 ml/m2) + eGFR 1.34 (1.1, 1.6), 0.002 0.58 (0.32,1.0), 0.059 + Microalbuminuria 1.37 (1.1, 1.6), 0.001 0.58 (0.31, 1.1), 0.079 + eGFR + Microalbuminuria 1.33 (1.1, 1.6), 0.002 0.61 (0.33, 1.1), 0.104 Model 1: adjusted for age, ethnicity, SBP, antihypertensive medication, cholesterol: HDL ratio, BMI, DM, smoking. †LV remodelling index (LVRI) defined as LV mass to end-diastolic volumes (EDV) ratio (the lower numbers for LVRI due to lower available numbers of LV mass (N= 879)). 3D ESV is log transformed. AI, augmentation index (%); EDV, end-diastolic volumes (ml/m2); eGFR, estimated glomerular filtration rate (ml/min/1.73 m2); ESV, end-systolic volumes (ml/m2); HR, hazard ratio; LVRI, left ventricular remodelling index (g/ml); TAC, total arterial compliance (ml/mmHg); SD, standard deviation. Conclusion: In a large tri-ethnic sample of the UK general population, sex differences in associations between 3DE LV structural measures and mortality seem to be partially explained by arterial stiffness and wave reflection.

Background: Measurement of wave intensity (WI) requires simultaneous or quasi-simultaneous measurement of pressure and flow limiting its use. Previous work in dogs [1] and humans [2] has shown that the excess pressure waveforms calculated using reservoir analysis correspond closely with aortic flow waveforms. This offers a potential method to estimate WI using only pressure waveforms (pWI). We investigated the feasibility of this approach and agreement with established methods. Methods: 262 participants (68.3 (SD = 5.5); 74% male) without aortic stenosis or heart failure were recruited from a UK-based longitudinal study, Southall and Brent Revisited. Central pressure waveforms, aortic flow velocity and carotid WI were measured using tonometry (Sphygmocor, AtCor), echocardiography (iE33, Philips) and ultrasonography (SSD-5500, Aloka) respectively. Reservoir analysis was performed as previously described [2] and excess pressure waveforms were calibrated to flow velocity assuming a peak velocity of 1 m/s. Method agreement was assessed as mean difference (MD), limits of agreement (LOA) and concordance coefficient (CC). Results: Analysis failed in 9 individuals; results for those with analysable data are shown in Table 1. Aortic pWI was higher than aortic WI but showed good concordance (logW1: MD(LOA) = −0.41(−0.73, −0.09) CC = 0.7; logW2: MD(LOA) = −0.41 (−0.73, −0.09); CC = 0.7). Agreement of pWI with carotid WI showed no bias and concordance was fair to poor (logW1: MD (LOA) = −0.16 (−1.30, 0.99) CC = 0.3; logW2: MD (LOA) = −0.02 (−1.23, 1.2); CC = 0.1). Table 1Results Variables N Median/(%) p25 p75 Age, y 207 67.9 63.6 71.9 BMI, kg/m2 207 26.6 24.1 30.1 Systolic BP, mmHg 207 139 126 148 Diastolic BP, mmHg 207 76 70 82 Heart rate, bpm 207 66 59 74.5 Male sex, % 150 72.5 Ethnicity European 88 (42.5%) South Asian 75 (36.2%) African Caribbean 44 (21.3%) Current smoker 18 (8.8%) Diabetes 65 (31.4%) Hypertension 130 (62.8%) Aorta W1, mmHg.m.s−3 207 7103 5041 9910 W2, mmHg.m.s−3 207 1637 1147 2518 pW1, mmHg.m.s−3 207 10,526 7677 14,336 pW2, mmHg.m.s−3 207 2491 1779 3560 time W1 to W2, s 207 0.25 0.23 0.27 Peak velocity, m/s 207 1.34 1.2 1.46 Carotid artery W1, mmHg.m.s-3 207 8714 6550 12,883 W2, mmHg.m.s-3 207 2327 1471 3227 time W1 to W2, s 207 0.29 0.27 0.31 Peak velocity, m/s 207 1.10 0.92 1.30 BMI, body mass index; BP, blood pressure; p25, 25th centile; p75, 75th centile; pW1, peak intensity of initial forward compression wave (W1) estimated using pressure only; pW2, peak intensity of initial forward compression wave (W2) estimated using pressure only; W1, peak intensity of initial forward compression wave (W1) calculated using aortic velocity; W2, peak intensity of initial forward compression wave (W2) calculated using aortic velocity. Conclusion: Estimation of aortic WI from pressure waveforms using reservoir analysis is feasible.

Introduction: Left ventricular mass (LVM) predicts cardiovascular risk. In early life, LVM is conventionally indexed to height 2.7 [1], although this may not account for sex differences in growth. We investigated allometric scaling of LVM to height, lean mass (LM) and body surface area (BSA) in a UK birth cohort. Methods: 861 individuals underwent echocardiography to assess LVM at age 17.7 (SD 0.3) years and 24.0 (SD 0.6) years. LM was quantified using dual-energy X-ray absorptiometry. Group and sex-specific allometric relationships were determined by linear regression, following log transformation of x and y variables (log(y) = a + b * log(x)) (b = scaling exponent). Results: LVM showed a linear relationship with LM and log(height), although the intercepts differed by sex. At age 17, the exponent relating LVM to height in males and females combined was 2.67 (95% CI: 2.41, 2.91), very close to the suggestion of height 2.7. Sex-specific estimates for height were lower and close to the estimate of 1.7 [2], at 1.77 (1.17, 2.37) and 1.83 (1.35, 2.31), for males and females, respectively. The female exponent at age 24 remained close to 1.7, while the male exponent increased to 2.14 (1.54, 2.73). Exponents for LM and BSA remained similar between ages 17 and 24 (see Table 1 for detail). Conclusion: A universal approach for allometric indexing of LVM may be inappropriate in early adulthood, and indexation may need to be both age- and gender-specific. It remains unclear which indexing method is superior at these ages, although height may be unsuitable. These observations may have important implications for identifying young individuals with cardiac hypertrophy. Table 1 Height Lean BSA n Coefficient (+ 95% CI) p n Coefficient (+ 95% CI) p n Coefficient (+ 95% CI) p Age 17 Group 861 2.67 (2.41, 2.91)

Introduction: Adult obesity is associated with greater arterial stiffness however in youth the relationship is unclear. We investigated associations between arterial stiffness and adiposity and explored the contribution of blood pressure from adolescence to emerging adulthood (17–24 yrs). Methods: 3885 individuals (2152 female) had measurements of carotid-femoral pulse wave velocity (PWV), DXA total fat mass (TFM) and mean arterial pressure (MAP). Measurements were repeated aged 24 yrs (n = 1659). Linear regression and mixed models assessed sex—stratified associations between PWV, TFM and MAP, and age interactions. Results: From 17–24 yrs PWV, TFM and MAP increased (Table 1). TFM showed a weak negative association with PWV in males at 17 yrs and 24 yrs. A positive association was observed in females at 17 yrs which was stronger at 24 yrs (pinteraction = 0.03). After adjustment for MAP the negative association was stronger in males and a negative association emerged in females aged 17 yrs; at 24 yrs the association remained positive in females. Adjustment for smoking, socioeconomic status and education attenuated associations in females aged 24, but otherwise had minimal effects. MAP was positively associated with PWV in both males and females at 17 yrs and 24 yrs; however, the association was weaker at 24 yrs, especially in males (pinteraction < 0.0001). Conclusion: The association between adiposity and arterial stiffness differs by sex, is modified by age and influenced by blood pressure. In emerging adolescence, a positive association is seen between adiposity and PWV in women, suggesting that this may be an important time to control adiposity to provide long term cardiovascular benefits. Table 1 17 years 24 years Male Female Male Female Male Female mean ± SD mean ± SD mean ± SD mean ± SD Mean difference ± SD PWV (m/s) 6.1 ± 0.7 5.5 ± 0.6 6.7 ± 1.2 6.1 ± 0.7 0.65 ± 0.1** 0.55 ± 0.9** TFM (kg) 13.0 ± 8.8 20.9 ± 8.5 20.3 ± 9.3 24.5 ± 10.3 7.3 ± 6.5** 3.7 ± 6.5** MAP (mmHg) 83.0 ± 6.5 80.8 ± 6.5 85.5 ± 7.7 81.3 ± 7.7 2.5 ± 7.4** 0.5 ± 7.4* Regression Analysis PWV and TFM β (95% CI) β (95% CI) β (95% CI) β (95% CI) TFM##age p-value Age −0.004 (−0.10, 0.03) 0.083 (0.004, 0.0)** −0.072 (−0.18, 0.04) 0.17 (0.10, 0.23)** 0.3 0.03 + MAP −0.13 (−0.20, −0.06)** −0.020 (−0.07, 0.03) −0.12 (−0.24, −0.001)* 0.10 (0.03, 0.17)** 0.16 0.05 + SES education and smoking −0.13 (−0.2, −0.06)** −0.025 (−0.08, 0.03) −0.13 (−0.26, 0.0007)* 0.05 (−0.025, 0.12) 0.4 0.7 PWV and MAP MAP##age p-value Age 0.16 (0.10, 0.22)** 0.24 (0.20, 0.28)** 0.06 (−0.04, 0.15) 0.20 (0.13, 0.26)**

Objective: Exaggerated exercise blood pressure (BP) is associated with cardiovascular risk factors in adolescence. Aerobic fitness and adiposity (fat mass or ‘fatness’) are important independent contributors to cardiovascular risk in adolescence, but their interrelated associations with exercise BP are unknown. The aim of this study was to determine the respective relationship between fitness, fatness and exercise BP in a large birth cohort of adolescents. Methods: 2356 adolescents from the Avon Longitudinal Study of Parents and Children (aged 17.8 ± 0.4 years, 38.5% male) completed a submaximal exercise step-test that allowed fitness (VO2max) to be determined from workload and heart rate using a validated equation. Exercise BP was measured immediately on test cessation and fatness calculated as the ratio of total fat mass to total body mass measured by DXA. Results: Exercise systolic BP decreased stepwise with each tertile of fitness (146 [144, 147]; 142 [141, 144]; 141 [139, 142] mmHg), but increased with each tertile of fatness (137 [135, 138]; 143 [142, 144]; 148 [147, 149] mmHg). In separate models, fitness and fatness were independently associated with exercise systolic BP after adjustment for sex, age, height, smoking and socioeconomic status (standardised β: −1.97, 95% CI: −2.90, − 1.04 mmHg/SD and 5.69, 95% CI: 4.61, 6.77 mmHg/SD respectively). However, when fitness and fatness were included in the same model, only fatness remained independently associated with exercise BP (6.15, 95% CI: 4.88, 7.41 mmHg/SD). Conclusion: Both fitness and fatness are associated with exercise BP in adolescence. However, the fitness-exercise BP association was not independent of fatness, suggesting fatness accounts for the association with exercise BP.

Introduction: In adults, aging is associated with a rise in blood pressure (BP) and a disproportionate increase in central systolic blood pressure (cSBP) relative to brachial SBP (bSBP) (i.e. reduced aortic to radial pulse pressure amplification (PPamp)). But changes in brachial and central BP have not been studied in the transition from adolescence to early adulthood when PPamp is greatest. We therefore investigated changes in BP over this age period in a large population-based birth cohort. Methods: 1835 participants (1099 female) in the Avon Longitudinal Study of Parents and Children (ALSPAC) underwent repeat clinic examination, including measurements of brachial and central BP, aged 17 yrs and 24 yrs. Measures at 17 to 24 yrs were compared with paired t-tests. Results: Aged 17 yrs the difference between bSBP and cSBP was 19.7 ± 4.7 mmHg, while at 24yrs the difference was 18.2 ± 4.6 mmHg (age interaction p < 0.001). From 17 to 24 yrs diastolic BP increased, bSBP decreased and cSBP increased, PPamp decreased while augmentation index (AIx) increased (Table 1). Table 1 Variables Mean ± SD at 17 Mean ± SD at 24 Difference (95% CI) p bSBP (mmHg) 116.2 ± 11.5 115.3 ± 11.0 −0.93 (−1.4, −0.47) 0.001 cSBP (mmHg) 96.5 ± 0.2 97.1 ± 0.2 0.58 (0.17, 0.99) 0.006 DBP (mmHg) 64.5 ± 0.2 66.6 ± 0.2 2.1 (1.7, 2.5)

Background: 3D speckle-tracking echocardiography (3D-STE) is a novel method to quantify left ventricular (LV) mechanical dyssynchrony. 3D-STE is influenced by image quality, but studies on the magnitude of its effect on 3D-STE derived LV systolic dyssynchrony indices (SDIs) and their test-retest reproducibility are limited.Methods: 3D-STE was performed in two groups, each comprising 18 healthy volunteers with good echocardiographic windows. In study 1, optimal and inferior-quality images, by intentionally poor echocardiographic technique, were acquired. In study 2, sub-optimal quality images were acquired by impairing ultrasound propagation using neoprene rubber sheets (thickness 2, 3, and 4 mm) mimicking mildly, moderately, and severely impaired images, respectively. Measures (normalized to cardiac cycle duration) were volume- and strain-based SDIs defined as the standard deviation of time to minimum segmental values, and volume- and strain-derived dispersion indices. For both studies test-retest reproducibility was assessed.Results: Test-retest reproducibility was better for most indices when restricting the analysis to good quality images; nevertheless, only volume-, circumferential strain-, and principal tangential strain-derived LV dyssynchrony indices achieved fair to good reliability. There was no evidence of systematic bias due to sub-optimal quality image. Volume-, circumferential strain-, and principal tangential strain-derived SDIs correlated closely. Radial strain- and longitudinal strain-SDI correlated moderately or weakly with volume-SDI, respectively.Conclusions: Sub-optimal image quality compromised the reliability of 3D-STE derived dyssynchrony indices but did not introduce systematic bias in healthy individuals. Even with optimal quality images, only 3D-STE indices based on volume, circumferential strain and principal tangential strain showed acceptable test-retest reliability.

Introduction: Increased adiposity is associated with poorer left ventricular (LV) function but the mediating role of blood pressure (BP) and other cardiovascular measures is unknown. We investigated the roles of potential mediators in adolescents in a UK birth cohort, the Avon Longitudinal Study of Parents and Children. Methods: Fat and lean mass were assessed by dual energy X-ray absorptiometry (DXA) in 2,068 individuals (age 17.7(SD 0.32) years; 45% male; weight 67(SD 13) kg). BP was measured and echocardiography performed. Tissue Doppler systolic (s’), early diastolic longitudinal function (e’) and transmitral E/A were used as measures of LV systolic and diastolic function respectively. Mediation was estimated using structural equation modelling; height, sex, socioeconomic position, lean mass and smoking were included as potential confounders in all models. Results: Table 1 shows the total and direct (total – indirect (mediated)) effects (standardized β) for each potential mediator, alongside %mediation. No convincing associations were found between fat mass and s’ or e’. Conclusions: MAP, HR and EDV, an indicator of preload, are important mediators of the effect of adiposity on diastolic function in adolescence, while TPR appears to account for none of the effect. Absence of mediation by PP, in combination with the mediation by TAC, suggests that stroke volume contributes some mediative effect. These findings emphasise the importance of adiposity and risk factor control in adolescence.

Objective: Exaggerated exercise blood pressure (BP) is associated with higher left-ventricular mass index (LVMI). Paradoxically, exercise BP and LVMI may be higher with greater fitness, but underlying factors are poorly understood. This study aimed to determine the influence of fitness on exercise BP and its relationship with LVMI in adolescents. Methods: 4835 adolescents from the Avon Longitudinal Study of Parents and Children, aged 15.4(0.3) years, 49% male completed a submaximal cycle test. Exercise BP was measured immediately on test cessation and fitness calculated as physical work capacity 170 adjusted for lean body-mass. LVMI (n = 1589), cardiac output (CO, n = 1628) and total peripheral resistance (TPR, n = 1628) were measured by echocardiography 2.4 (0.4) years later. Results: Each unit of fitness was associated with a 6.46 mmHg increase (95% CI: 5.83, 7.09) in exercise systolic BP. Exercise systolic BP increased step-wise by third of fitness (difference 6.06 mmHg, 95% CI:4.99, 7.13 first vs. middle; 11.13 mmHg, 10.05, 12.20 middle vs. highest). Each 5 mmHg increase in exercise systolic BP was associated with 0.25 g/m2. 7 (0.16–0.35) greater LVMI, attenuated with adjustment for fitness. There was evidence of an interaction between fitness and exercise BP on LVMI, more-marked in the middle fitness third (difference -0.27g/m2.7, -0.51,0.04 vs. first third), but similar in lowest and highest fitness thirds. CO increased (difference 0.06 L/min, -0.05,0.17; 0.23 L/min, 0.12,0.34), TPR decreased (difference -0.13AU, -0.84,0.59; -1.08AU, -0.1.80,-0.35 with fitness. Conclusion: Fitness may modify associations between exercise BP and LVMI in adolescence. Higher CO, but lower TPR suggests a physiological exercise BP-LVMI relationship with higher fitness, rather than pathological elevations in exercise BP and LVMI.

Background: Oscillometric mean arterial pressure (MAP) agrees closely with invasive MAP, [1] but most devices do not report MAP and it is usually estimated by a form factor (FF). However, blood pressure (BP) measurement errors will affect FF, its correlations with exposures, and introduce errors into MAP estimated from the BP waveform. Methods: Brachial BP was measured using a Pulsecor device in 1,112 participants in the Southall and Brent Revisited study (68.8 ± 6.1 y; 78.2% male; 47.4% White-European; 38.3% South-Asian; 14.3% African-Caribbean). Form factors (FFosc and FFwave) were calculated as (MAP-diastolic BP)/(systolic BP-diastolic BP) by oscillometry (MAPosc) or from the BP waveform (MAPwave). Results: FFosc and FFwave differed (0.28 (SD = 0.02) vs. 0.36 (SD = 0.04); p

Background: Mean arterial pressure (MAP) is required for many hemodynamic calculations. Most automated devices do not report MAP and a form factor (FF) is used to estimate it from systolic and diastolic blood pressure (BP). The appropriate choice of FF in the brachial artery is controversial: 0.33 is the traditional value, but invasive measurements report a value of 0.4. [1] Non-invasive studies have provided some support for FF = 0.4 but have usually not measured MAP directly, nor used brachial blood pressure waveforms, or accounted for BP measurement errors. We addressed these issues in a sample of white Europeans drawn from the Southall and Brent Revisited study. Methods: BP was measured using a Pulsecor device (USCOM). Form factors (FFosc and FFwave) were calculated as (MAP-diastolic BP)/(systolic BP-diastolic BP) using MAPosc calculated by oscillometry and MAPwave calculated as the waveform mean respectively. Results: Data are mean ± SD of 527 observations (Table 1). FFosc was lower than FFwave and use of FF = 0.4 (MAP0.4) overestimated MAPosc. Allowing for measurement errors based on [2–3] gave estimates of MAPwave that were more similar to MAPosc. Conclusions: Measurement errors confound estimation of MAP using FF. Measurement errors vary substantially between devices [4] precluding a single FF for all studies. Non-invasive MAP should be estimated by oscillometric methods.

Background: It has been proposed that high blood pressure (BP) in young people is due to high cardiac output (CO) with normal total peripheral resistance (TPR) – a hyperkinetic/hyperdynamic circulation. We investigated this in a large, population- based cohort of adolescents. Methods: The study was conducted on 2091 participants in the Avon Longitudinal Study of Parents and Children (ALSPAC), a prospective population-based birth cohort study, aged 17. BP measurement and echocardiography was performed and heart rate (HR), stroke volume (SV) and TPR calculated. Data are means (SD). Results: Table 1 shows selected characteristics of the sample. Higher quintiles of systolic BP were associated with higher SV, higher HR and higher TPR. However, the proportional contribution made by SV, HR and TPR to mean arterial pressure differed little by systolic BP quintile (stroke volume (32–34%) heart rate (25–29%) and TPR (39–41%)). Variable Males (n = 939) Females (n = 1152) All (n = 2091) y (0.3) (0.3) (0.3) kg/m2 (3.7) (4.2) (4.0) mmHg 11)/64(8) 9)/65(7) 11)/65(8) bpm 0 0 0 L/min 1.0) 0.8) 0.9) ml 3 1 3 mmHg ml/min (5.9) (6.0) (6.0) Conclusions: Higher blood pressure is attributable to a combination of higher cardiac output (i.e. SV×HR) and higher TPR in a population-based sample of adolescents. There is no evidence of a disproportionate contribution from CO at higher BP levels.

Background: Hypertension has adverse effects on microvascular function but there are limited methods that permit non-invasive assessment of the microcirculation in man in vivo. We used Near Infrared Spectroscopy (NIRS) to assess microvascular reactive hyperaemia in skeletal muscle following a short period of ischemia. We tested if differences between normotensive and hypertensive individuals could be detected. Methods: Older adults enrolled in a population-based cohort study underwent measurements of oxy-Hb changes during a 30-second arterial occlusion and hyperaemic response using NIRS (Portamon, Artinis). Time-to-peak hyperaemic response was calculated. Hypertension diagnosis was determined by questionnaire and clinic blood pressure (BP) (diastolic BP > 90 mmHg or systolic BP > 140 mmHg). Diabetes diagnosis and information about medication were determined by questionnaire. Data are mean (SD) or adjusted mean±SEM. Multivariable linear regression was used. Associations with hypertension were adjusted for age, gender, ethnicity and presence of diabetes. Results: 129 participants (99 = male, 72(6) years old, 74(57%) hypertensive participated). Time-to-peak hyperaemic response was significantly longer in hypertensive than normotensive participants after adjustment for age and gender (12.5±0.49 versus 10.5±0.57seconds, p = 0.06). This association persisted after adjustment for ethnicity and the presence of diabetes (12.6±0.50 versus 10.5±0.57, p = 0.03). Conclusion: Hypertension is associated with impairment of post-ischemic reactive hyperaemia in skeletal muscle microvasculature. Differences between hypertensive and normotensive older adults can be detected non-invasively using NIRS.

Introduction: Increased arterial stiffness (AS) in adults causes increased left ventricular (LV) afterload, putting additional strain on the heart. Long-term, this can lead to an adverse cardiovascular phenotype and AS has been found to be a determinant of CVD, independent of traditional cardiovascular risk factors. However, limited evidence exists for this association in children and adolescents. Methods: 1625 young adults (age 17y; 46% male) from the Avon Longitudinal Study of Parents and Children (ALSPAC), a UK based birth cohort, underwent echocardiography and carotid-to-femoral pulse wave velocity (PWV) measures. Linear regression was used to investigate associations between PWV and LV structure and function, including LV mass, relative wall thickness (RWT), left atrial diameter (LAD), mitral inflow (E:A), midwall fractional shortening (MFS) and tissue Doppler peak systolic velocity (s′). Results: Elevated PWV was associated with increased LV mass and RWT and inversely associated with E:A and MFS (Table 1). Adjustment for age and sex attenuated the association with LV mass. Further adjustment for body mass index (BMI), systolic blood pressure (SBP), alcohol, smoking and socioeconomic status (SES) attenuated the association with RWT, whilst the associations with E:A and MFS remained. Unadjusted Age and sex adjusted Age, sex, BMI, SBP, alcohol, smoking, SES adjusted Coefficient±SE P value Coefficient±SE P value Coefficient±SE P value LV mass2.7 (g/m2.7) 0.55±0.21 0.009 −0.066±0.225 0.768 −0.123±0.225 0.584 RWT 0.007±0.002

Objectives: Masked hypertension (MH) is associated with hypertension-related markers of organ damage, but is undetectable by clinic (resting) BP. Exaggerated systolic BP response to submaximal exercise reveals MH in adults, but it is unknown whether this is the case during adolescence. We aimed to determine if exercise BP was raised in adolescents with MH, and associations with markers of organ damage. Methods: 585 adolescents (aged 17.7 ± 0.3 years; 41.9% male) from the Avon longitudinal study of parents and children (ALSPAC), completed a step-exercise test with post-exercise BP, resting (clinic) BP and 24-hour ambulatory BP (ABP). MH was defined on the basis of guideline adult thresholds as clinic BP ≤ 140/90 mmHg and 24 h ABP ≥ 130/80 mmHg, or paediatric thresholds (age, sex and height percentiles). Assessment of markers of organ damage including left-ventricular mass (LVM) and carotid-femoral pulse wave velocity (PWV) was also undertaken. Results: 45 (7.7%) participants were classified with MH. Resting and post-exercise SBP were higher in those with MH vs. normotensives (126.1 ± 7.3 mmHg vs. 114.7 ± 10.0 mmHg, p < 0.001; 152.2 ± 17.3 vs 141.1 ± 15.1 mmHg, p = 0.001). A post-exercise SBP threshold of 150 mmHg revealed MH (AUC = 0.69, 95% CI: 0.61–0.76, p < 0.001) and was associated with greater LVM index (30.2 ± 6.5 vs. 27.6 ± 5.8 g/m2.7, p < 0.001) and PWV (5.9 ± 0.6 vs. 5.7 ± 0.7 m/s, p = 0.01). Conclusions: This is the first study within adolescents demonstrating post-exercise SBP can reveal MH and an association with markers of organ damage. Exaggerated exercise BP might be a warning signal of underlying high BP and increased cardiovascular risk undetected by clinic BP.

Background: High blood pressure (BP) is a major risk factor for elevated LV mass (LVM) in adults. Evidence suggests that BP tracks from childhood into adolescence and adulthood, however findings on the association between childhood BP and LVM are inconsistent and the temporal relationship between BP in childhood and elevated LVM in adolescence is unknown. Methods: Echocardiography and sitting brachial systolic BP (SBP) measurements were performed on 2065 17yr olds. 1377 participants (742 females, 635 males) had complete BP data measured at age 7yrs, 9yrs, 11yrs and 15yrs. LVM was calculated and indexed to height2.7 (LVMI). Linear regression was used to investigate associations. Results: Elevated LVMI at 17yrs was associated with increased SBP at all ages in females and in males at 9yrs, 11yrs, 15yrs and 17yrs (Table 1). Adjustment for cardiometabolic risk factors at age 17 (age, free-fat mass, height, height2 and smoking (Model 1)) did not substantially attenuate all LVMI and BP associations and associations at earlier ages remained significant after further adjustment for SBP at age 17. Age (yrs) Unadjusted Model 1 Model 1+ SBP at 17yrs Male Female Male Female Male Female 7 0.01±0.03 0.09±0.02** 0.02±0.03 0.06±0.02** −0.02±0.03 0.07±0.02** 9 0.06±0.03* 0.06±0.02* 0.02±0.02 −0.007±0.02 0.02±0.02 −0.006±0.8 11 0.15±0.03** 0.06±0.02** 0.09±0.03** 0.008±0.02 0.09±0.03** 0.009±0.02 15 0.05±0.02* 0.06±0.02** 0.02±0.02 0.04±0.02* 0.02±0.02 0.03±0.02* 17 0.16±0.03** 0.14±0.02** 0.13±0.03** 0.09±0.02** Data are β±SE(g/m 2.7) *= p

Background: Vascular risk factors have been associated with brain aging. We aimed to determine the associations between blood pressure (BP), atherosclerosis, arterial stiffness and microvascular damage with both structural and functional measures of the brain. Methods: A community-based sample of 1287 individuals (69 ± 6 yrs) underwent cognitive function testing and MRI to measure hippocampal brain volumes. Brachial and central systolic BP (SBP, cSBP) and pulse pressure (PP, cPP), diastolic BP (DBP), arterial stiffness (cfPWV), atherosclerosis (cIMT) and microvascular disease (composite from retinopathy, ACR and eGFR measures) were measured. Results: After adjusting for age, sex and ethnicity hippocampal volume was significantly associated with SBP (β ± SE: −0.004 ± 0.002; p = 0.01), PP (β ± SE: −0.008 ± 0.002; p < 0.0001), cPP(β ± SE: −0.01 ± 0.003; p < 0.0001) and cfPWV (β ± SE: −0.02 ± 0.01; p = 0.04). Cognitive function (z-score) was significantly associated with PP (β ± SE: −0.004 ± 0.002; p = 0.003) and cPP (β ± SE: −0.005 ± 0.002; p = 0.02). After further adjustment for concomitant risk factors (heart-rate, diabetes, hypertension, previous stroke, coronary artery disease, waist-to-hip ratio, years of education and smoking) only the associations with PP (Hippocampal volume β ± SE: −0.005 ± 0.002; p = 0.02, cognitive function β ± SE: −0.004 ± 0.001; p = 0.01) and cPP (Hippocampal volume β ± SE: −0.008 ± 0.003; p = 0.004, cognitive function β ± SE: −0.004 ± 0.002; p = 0.048) remained significant. Conclusion: In this community based sample brachial and central PP were significantly associated with measures of brain structure and function, not explained by concomitant risk factors.

Background: Mid-life cardiovascular risk factors may be detrimental to cognitive function in later life; however results are inconsistent. We investigated the impact of mid-life blood pressure, glucose, cholesterol and obesity on cognitive function. Methods: In a community based sample aged 49.6±6years: waist-to-hip ratio (WHR), fasting blood glucose, HDL cholesterol and blood pressure were measured. 20 years later 1284 of these individuals underwent cognitive function testing to assess global function, executive function, memory and attention. Data are β±SE, *p

ObjectivesAugmentation index (AIx) is widely used as a measure of wave reflection. We compared the relationship between AIx and age, height and sex with 'gold standard' measures of wave reflection derived from measurements of pressure and flow to establish how well AIx measures wave reflection.Materials and methodsMeasurements of carotid pressure and flow velocity were made in the carotid artery of 65 healthy normotensive individuals (age 21-78 yr; 43 male) and pulse wave analysis, wave intensity analysis and wave separation was performed; waveforms were classified into type A, B or C. AIx, the time of the first shoulder (T(s)), wave reflection index (WRI) and the ratio of backward to forward pressure (P(b)/P(f)) were calculated.ResultsAIx did not correlate with log WRI or P(b)/P(f). When AIx was restricted to positive values AIx and log WRI were positively correlated (r = 0.33; p = 0.04). In contrast log WRI and P(b)/P(f) were closely correlated (r = 0.66; pConclusionsAIx has serious limitations as a measure of wave reflection. Negative AIx values derived from Type C waves should not be used as estimates of wave reflection magnitude.

People of South Asian descent have an increased risk of cardiovascular disease (CVD) and diabetes, but little is known about the microcirculation in South Asian people despite evidence that this plays an important role in the aetiology of CVD. We compared the retinal microcirculation in a population-based sample of 287 middle-aged adults (144 European 143 South Asian) matched for age and sex. Retinal photographs were taken and analysed using a validated semi-automated program and microvascular measures were compared. Blood pressure, anthropometry and fasting bloods were also measured. South Asians had significantly fewer arteriolar and venular vessels and bifurcations. Arterioles and venules were longer and venules were also more tortuous in South Asians. These differences were not explained by adjustment for traditional risk factors including blood pressure, body mass index, diabetes or measures of insulin resistance. People of South Asian descent have rarefaction of the retinal microcirculation compared to age-sex matched individuals of European descent. Reduced microvascular density could contribute to the elevated risk of CVD and impaired glucose tolerance in South Asian people.