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 (Ts), wave reflection index (WRI) and the ratio of backward to forward pressure (Pb/Pf) were calculated.ResultsAIx did not correlate with log WRI or Pb/Pf. 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 Pb/Pf were closely correlated (r = 0.66; p<0.001). There was no correlation between the Ts and the timing of Pb or the reflected wave identified by wave intensity analysis. Wave intensity analysis showed that the morphology of type C waveforms (negative AIx) was principally due to a forward travelling (re-reflected) decompression wave in mid-systole. AIx correlated positively with age, inversely with height and was higher in women. In contrast log WRI and Pb/Pf showed negative associations with age, were unrelated to height and did not differ significantly by gender.ConclusionsAIx 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.

Abstract-Cardiometabolic risk is elevated in South Asians and African Caribbeans compared with Europeans, yet whether this is associated with ethnic differences in left-ventricular structure is unclear. Conventional M-mode or 2-dimensional echocardiography may be misleading, because they calculate left-ventricular mass and remodeling using geometric assumptions. Left-ventricular structure was compared in a triethnic population-based cohort using conventional and

BackgroundSubclinical left ventricular (LV) dysfunction has been inconsistently associated with early cognitive impairment, and mechanistic pathways have been poorly considered. We investigated the cross‐sectional relationship between LV dysfunction and structural/functional measures of the brain and explored the role of potential mechanisms.Method and ResultsA total of 1338 individuals (69±6 years) from the Southall and Brent Revisited study underwent echocardiography for systolic (tissue Doppler imaging peak systolic wave) and diastolic (left atrial diameter) assessment. Cognitive function was assessed and total and hippocampal brain volumes were measured by magnetic resonance imaging. Global LV function was assessed by circulating N‐terminal pro–brain natriuretic peptide. The role of potential mechanistic pathways of arterial stiffness, atherosclerosis, microvascular disease, and inflammation were explored. After adjusting for age, sex, and ethnicity, lower systolic function was associated with lower total brain (beta±standard error, 14.9±3.2 cm3; P<0.0001) and hippocampal volumes (0.05±0.02 cm3, P=0.01). Reduced diastolic function was associated with poorer working memory (−0.21±0.07, P=0.004) and fluency scores (−0.18±0.08, P=0.02). Reduced global LV function was associated with smaller hippocampal volume (−0.10±0.03 cm3, P=0.004) and adverse visual memory (−0.076±0.03, P=0.02) and processing speed (0.063±0.02, P=0.006) scores. Separate adjustment for concomitant cardiovascular risk factors attenuated associations with hippocampal volume and fluency only. Further adjustment for the alternative pathways of microvascular disease or arterial stiffness attenuated the relationship between global LV function and visual memory.ConclusionsIn a community‐based sample of older people, measures of LV function were associated with structural/functional measures of the brain. These associations were not wholly explained by concomitant risk factors or potential mechanistic pathways.

Purpose Left ventricular (LV) mechanics by speckle-tracking echocardiography (STE) is prognostic in patients with cardiovascular diseases, but evidence related to community-dwelling individuals is uncertain. We therefore performed a systematic review and meta-analysis of STE as a predictor of adverse outcomes in the general population. Methods PRISMA guidelines were followed and MEDLINE and EMBASE were searched to identify eligible studies. Primary outcome was all-cause mortality and secondary outcomes were composite cardiac and cardiovascular end-point. Random effects meta-analysis was performed, and a modified Newcastle-Ottawa Assessment Scale was used for quality assessment. Results Eight papers matched the predefined criteria (total number of individuals studied=11,744). All publications assessed global longitudinal strain (GLS) by two-dimensional speckle-tracking echocardiography (2D-STE), one assessed circumferential, radial and transverse strains, and one assessed GLS-derived post-systolic shortening. None assessed LV rotational measures in association with outcomes. Two studies reported associations between GLS and all-cause mortality and composite cardiovascular end-point. Six papers reported an association between GLS and composite cardiac end-point, three of which were from the same study. Four papers were suitable for meta-analysis. GLS predicted all-cause mortality (pooled minimally adjusted HR per unit strain (%)=1.07 [95% CI 1.03–1.11], p =0.001), and composite cardiovascular (pooled maximally adjusted HR=1.18 [1.09–1.28], p <0.0001) and cardiac (HR=1.08 [1.02–1.14], p =0.006) end-points. GLS also predicted coronary heart disease (HR=1.15 [1.03–1.29], p =0.017) and heart failure (HR=1.07 [1.02–1.13], p =0.012). The quality of all studies was good. Conclusions This study provides some evidence that STE may have utility as a measure of cardiac function and risk in the general population. 2D-STE-based GLS predicts total mortality, major adverse cardiac and cardiovascular end-points in community-dwelling individuals in a limited number of studies. Despite this, this systematic review also highlights important knowledge gaps in the current literature and further evidence is needed regarding the prognostic value of LV mechanics in unselected older populations. Registration number: CRD42018090302.

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.

OBJECTIVEDiabetes is associated with left ventricular (LV) diastolic and systolic dysfunction. South Asians may be at particular risk of developing LV dysfunction owing to a high prevalence of diabetes. We investigated the role of diabetes and hyperglycemia in LV dysfunction in a community-based cohort of older South Asians and white Europeans. RESEARCH DESIGN AND METHODSConventional and Doppler echocardiography was performed in 999 participants (542 Europeans and 457 South Asians aged 58-86 years) in a population-based study. Anthropometry, fasting bloods, coronary artery calcification scoring, blood pressure, and renal function were measured. RESULTSDiabetes and hyperglycemia across the spectrum of HbA 1c had a greater adverse effect on LV function in South Asians than Europeans (N-terminal-probrain natriuretic peptide b 6 SE 0.09 6 0.04, P = 0.01, vs. 20.04 6 0.05, P = 0.4, P for HbA 1c /ethnicity interaction 0.02), diastolic function (E/e9 0.69 6 0.12, P < 0.0001, vs. 0.09 6 0.2, P = 0.6, P for interaction 0.005), and systolic function (s9 20.11 6 0.06, P = 0.04, vs. 0.14 6 0.09, P = 0.1, P for interaction 0.2). Multivariable adjustment for hypertension, microvascular disease, LV mass, coronary disease, and dyslipidemia only partially accounted for the ethnic differences. Adverse LV function in diabetic South Asians could not be accounted for by poorer glycemic control or longer diabetes duration. CONCLUSIONSDiabetes and hyperglycemia have a greater adverse effect on LV function in South Asians than Europeans, incompletely explained by adverse risk factors. South Asians may require earlier and more aggressive treatment of their cardiometabolic risk factors to reduce risks of LV dysfunction.

Extensive evidence shows that risk factors for cardiovascular disease (CVD) begin to develop early in life. Childhood obesity and elevated blood pressure (BP) have become overwhelmingly challenging, with 57% of today's children predicted to be obese by the age of 35 years, and global rates of hypertension in children and adolescents increasing by 75% from 2000 to 2015. Thus, there is an urgent need for tools that can assess early CVD risk in youth, which may lead to better risk stratification, preventative intervention, and personalised medicine. Vascular ageing (the deterioration in vascular structure and function) is a pivotal progenitor of health degeneration associated with elevated BP. Exposure to adverse environmental and genetic factors from fetal life promotes the development and accumulation of subclinical vascular changes that direct an individual towards a trajectory of early vascular ageing (EVA)-an independent predictor of target organ damage in the heart, brain, and kidneys. Therefore, characterising vascular ageing from youth may provide a window into cardiovascular risk later in life. However, vascular ageing measurements only have value when techniques are accurate/validated and when reliable thresholds are available for defining normal ranges and ranges that signal increased risk of disease. The aim of this paper is to summarise current evidence on the importance of vascular ageing assessment in youth and the impact of interventions to prevent or delay EVA, to highlight the need for standardisation and validation of measurement techniques in children and adolescents, and the importance of establishing reference values for vascular ageing measures in this population.

Sex and gender are important modifiers of cardiovascular system physiology, pathophysiology, and disease development. The atherosclerosis process, together with the progressive loss of arterial elasticity with age, is a major factor influencing the development of overt cardiovascular, renal, and cerebrovascular disease. While differences between women and men in epidemiology and pathophysiology of vascular ageing are increasingly reported, sex-disaggregated data are still scarcely available for prospective studies. A better knowledge of sex differences in physiological ageing as well as in disease-related changes in vascular ageing trajectories is crucial to avoid misdiagnosis and mistreatment. This review presents key concepts and knowledge gaps identified in vascular ageing due to gonadal function, vascular physiology, pathophysiology, psychosocial factors, pregnancy, and prognostic relevance. Gender roles determine the effectiveness of any cardiovascular preventive strategy and acceptance for non-invasive or invasive diagnostics and therapeutics. Gender differences in health behaviour, also due to sociocultural norms conditioned by society, contribute to behaviours that may lead to premature arterial vascular ageing. These include differences in risk behaviours like smoking, diet, exercise, and in stress, but also conditions such as housing, noise pollution, poverty, disability, and any kind of stigmatisation. The VascAgeNet Gender Expert Group aims to advance the use of non-invasive vascular ageing measures in routine clinical settings by providing facts to fill in the gaps concerning sex and gender differences at each step of this process, and to search for solutions.