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Rebecca K Kelly,1 Costan G Magnussen,1,2 Matthew A Sabin,3 Michael Cheung,3 Markus Juonala3–5 1Menzies Institute for Medical Research, University of Tasmania, Hobart, Australia; 2Research Centre of Applied and Preventive Cardiovascular Medicine, University of Turku, Turku, Finland; 3Murdoch Childrens Research Institute, Royal Children's Hospital and University of Melbourne, Parkville, Australia; 4Department of Medicine, University of Turku, 5Division of Medicine, Turku University Hospital, Turku, Finland Abstract: The upward trend in adolescent hypertension is widely attributed to the adolescent obesity epidemic. Secular trends in adolescent prehypertension and hypertension have risen in congruence with increasing trends in the prevalence of overweight and obesity. The correlation between body mass index and blood pressure in adolescence is moderate to strong in most studies and strongest in those classified as overweight or obese. The mechanisms relating to the development of hypertension in overweight adolescents are unclear; however, a number of nonmodifiable and modifiable factors have been implicated. Importantly, certain clinical and biochemical markers in overweight adolescents are indicative of high risk for hypertension, including family history of hypertension and hyperinsulinemia. These characteristics may prove useful in stratifying overweight adolescents as high or low risk of comorbid hypertension. The treatment of overweight and obesity related hypertension in this population focuses on two key modalities: lifestyle change and pharmacotherapy. These approaches focus almost exclusively on weight reduction; however, a number of emerging strategies target hypertension more specifically. Among adolescents with overt hypertension there are also several factors that indicate higher risk of concurrent subclinical disease, persistent adult hypertension, and adult cardiovascular disease. This group may benefit substantially from more aggressive pharmacological treatments. Limitations in the literature relate to the paucity of studies reporting specific effects for the adolescent age group of overweight and obese individuals. Nonetheless, intervention for adiposity-related hypertension in adolescence may partially mitigate some of the cardiovascular risk in adulthood. Keywords: blood pressure, obesity, prevention, risk factors, childhood

Objective: Our aim was to study the associations of childhood lifestyle factors (the frequency of consumption of vegetables, fruit, fish, and meat, butter use on bread, and physical activity) with the metabolic syndrome (MetS) in adulthood.Research Design and Methods: The study cohort consisted of 2,128 individuals, 3-18 years of age at the baseline, with a follow-up time of 27 years. We used the average of lifestyle factor measurements taken in 1980, 1983, and 1986 in the analyses. Childhood dietary factors and physical activity were assessed by self-reported questionnaires, and a harmonized definition of MetS was used as the adult outcome.Results: Childhood vegetable consumption frequency was inversely associated with adult MetS (odds ratio [OR] 0.86 [95% CI 0.77-0.97], P = 0.02) in a multivariable analysis adjusted with age, sex, childhood metabolic risk factors (lipids, systolic blood pressure, insulin, BMI, and C-reactive protein), family history of type 2 diabetes and hypertension, and socioeconomic status. The association remained even after adjustment for adulthood vegetable consumption. Associations with the other childhood lifestyle factors were not found. Of the individual components of MetS, decreased frequency of childhood vegetable consumption predicted high blood pressure (0.88 [0.80-0.98], P = 0.01) and a high triglyceride value (0.88 [0.79-0.99], P = 0.03) after adjustment for the above-mentioned risk factors.Conclusions: Childhood vegetable consumption frequency is inversely associated with MetS in adulthood. Our findings suggest that a higher intake of vegetables in childhood may have a protective effect on MetS in adulthood. [ABSTRACT FROM AUTHOR]

Objectives: This study was designed to determine which of the National Cholesterol Education Program or National Health and Nutrition Examination Survey low- and high-density lipoprotein cholesterol classifications of dyslipidemia status in adolescents is most effective at predicting high common carotid artery intima-media thickness (IMT) in adulthood.Background: Two classifications of pediatric dyslipidemia status have been proposed. No study has assessed which of these is most effective for predicting adolescents who will develop preclinical atherosclerosis in adulthood.Methods: Three population-based, prospective cohort studies collected lipoprotein measurements on 1,711 adolescents age 12 to 18 years who were remeasured as young adults age 29 to 39 years. Lipoproteins in adolescence were classified according to National Cholesterol Education Program and National Health and Nutrition Examination Survey cut points, and high IMT in adulthood was defined as those at or above the age-, sex-, race-, and cohort-specific 90th percentile of IMT.Results: Independent of the classification employed, adolescents with dyslipidemia were at significantly increased risk of having high IMT in adulthood (relative risks from 1.6 to 2.5). Differences in predictive capacity between both classifications were minimal. Overweight or obese adolescents with dyslipidemia had increased carotid IMT (males: 0.11 mm; females: 0.08 mm) in adulthood compared with those who did not have both risk factors. Adolescent dyslipidemia status was more strongly associated with high IMT in adulthood than change in dyslipidemia status.Conclusions: Pediatric dyslipidemia classifications perform equally in the prediction of adolescents who are at increased risk of high IMT in young adulthood. Our data suggest that dyslipidemia screening could be limited to overweight or obese adolescents. [ABSTRACT FROM AUTHOR]

Objective: Child and adult body mass index (BMI) associates with adult carotid artery intima-media thickness (cIMT). However, the relative contribution of BMI at different life-periods on adult cIMT has not been quantified. This study aimed to determine the life-course model that best explains the relative contribution of BMI at different life-periods (childhood, adolescence, and young-adulthood) on cIMT in adulthood., Methods: BMI was calculated from direct measurements of height and weight at up to seven time-points from childhood to adulthood (1973-2007) among 2485 participants of the Cardiovascular Risk in Young Finns Study (YFS) and 1271 participants in the Bogalusa Heart Study (BHS). BMI measures at three ages representative of childhood (9-years), adolescence (18 years) and young-adulthood (30 years) life-periods were used. B-mode ultrasound was used to measure common cIMT in adulthood (>30 years). Associations were evaluated using the Bayesian relative life-course exposure model., Results: In both cohorts, cumulative exposure to higher levels of BMI across the life-course was associated with greater cIMT. Of the examined life-periods, BMI in young-adulthood provided the greatest relative contribution towards the development of adult cIMT for YFS (49.9 %, 95 % CrI = 34-68 %) and white BHS participants (48.6 %, 95 % CrI = 9-86 %), whereas BMI in childhood had the greatest relative contribution for black BHS participants (54.0 %, 95 % CrI = 8-89 %)., Conclusion: Although our data suggest sensitive periods in the life-course where prevention and intervention aimed at reducing BMI might provide most benefit in limiting the effects of BMI on cIMT, maintaining lower BMI across the life-course appears to be optimal., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Hyperlipidaemia is a major risk factor of atherosclerotic cardiovascular disease (ASCVD). Risk of cardiovascular events depends on cumulative lifetime exposure to low-density lipoprotein cholesterol (LDL-C) and, independently, on the time course of exposure to LDL-C, with early exposure being associated with a higher risk 1 . Furthermore, LDL-C fluctuations are associated with ASCVD outcomes 2-4 . However, the precise mechanisms behind this increased ASCVD risk are not understood. Here, we make the unexpected observation that early intermittent feeding of mice with a high-cholesterol Western-type diet (WD) accelerates atherosclerosis compared with late continuous exposure to WD, despite similar cumulative circulating LDL-C levels. We find that early intermittent hyperlipidaemia alters the number and homeostatic phenotype of resident-like arterial macrophages. Macrophage genes with altered expression are enriched for genes linked to human ASCVD in genome-wide association studies. We show that LYVE1 + resident macrophages are atheroprotective, and identify new biological pathways, related to actin filament organisation, whose alteration accelerates atherosclerosis. Using the Young Finns Study, we show that exposure to cholesterol early in life is significantly associated with the incidence and size of carotid atherosclerotic plaques in mid-adulthood. In summary, our results identify early intermittent exposure to cholesterol as a strong determinant of accelerated atherosclerosis, highlighting the importance of optimal control of hyperlipidaemia early in life, and providing insight into the underlying biological mechanisms. This knowledge will be essential to designing effective therapeutic strategies to combat atherosclerotic cardiovascular disease., (© 2024. The Author(s), under exclusive licence to Springer Nature Limited.)

Aim: To investigate the association between metabolically healthy obesity (MHO) and left ventricular geometric remodelling in Chinese children., Materials and Methods: This cross-sectional study used data from two population-based samples in China, including 2871 children aged 6-11 years. Weight status was defined based on body mass index according to the World Health Organization growth chart. Metabolic status was defined based on the 2018 consensus-based criteria proposed by Damanhoury et al. Obes Rev 2018;19:1476-1491 (blood pressure, lipids and glucose). Left ventricular geometric remodelling was determined as concentric remodelling, eccentric hypertrophy, and concentric hypertrophy. Multinomial logistic regression analysis was used to determine odds ratios (ORs) and 95% confidence intervals (CIs) for the association between categories of weight and metabolic status and left ventricular geometric remodelling., Results: Compared with children with metabolically healthy normal weight, those with MHO had higher odds of left ventricular geometric remodelling, with adjusted ORs (95% CIs) of 2.01 (1.23-3.28) for concentric remodelling, 6.36 (4.03-10.04) for eccentric hypertrophy, and 17.07 (7.97-36.58) for concentric hypertrophy. Corresponding ORs (95% CIs) were 2.35 (1.47-3.75), 10.85 (7.11-16.55), and 18.56 (8.63-39.94), respectively, for children with metabolically unhealthy obesity. In contrast, metabolically unhealthy normal weight was not associated with higher odds of left ventricular geometric remodelling. Findings were consistent in sensitivity analyses that used different definitions of weight and metabolic status and left ventricular geometric remodelling., Conclusions: Children with MHO had higher odds of left ventricular geometric remodelling than their metabolically healthy normal weight counterparts. Our findings suggest MHO may not be a benign condition for cardiac health in children., (© 2024 John Wiley & Sons Ltd.)

Purpose: The American Heart Association recently issued a substantial update to the definition and scoring of cardiovascular health (CVH), now called "Life's Essential 8" (LE8). We aimed to assess the trends in overall and individual LE8 CVH metrics among adolescents in the United States., Methods: A total of 6,999 United States adolescents aged 12-19 years from six cycles of the National Health and Nutrition Examination Survey from 2007-2008 to 2017-2018 were included in this study. The individual LE8 metrics included diet, physical activity, nicotine exposure, sleep health, body mass index (BMI), blood lipids, blood glucose, and blood pressure (BP). A higher CVH score indicates better CVH health., Results: The mean score of overall CVH significantly increased from 72.8 (95% confidence interval: 71.2-74.3) in 2007-2008 to 77.3 (76.1-78.5) in 2017-2018 in US adolescents (p-trend < .001). From 2007-2008 to 2017-2018, the mean scores increased from 75.5 (72.0-79.1) to 90.0 (88.0-91.9) for nicotine exposure, from 65.2 (61.6-68.8) to 73.3 (69.9-76.8) for sleep health, from 69.9 (67.1-72.8) to 73.0 (69.1-76.9) for blood lipids, and from 94.4 (93.0-95.9) to 96.2 (95.2-97.3) for BP (all p-trend < .05). However, the mean scores for diet, physical activity, and blood glucose did not significantly change (all p-trend > .05), whereas the mean score decreased from 81.4 (78.9-84.0) to 78.6 (76.4-80.8) for BMI (p-trend = .023)., Discussion: In United States adolescents, the overall CVH and four components (nicotine exposure, sleep health, blood lipids, and BP) significantly improved over time, diet, physical activity, and blood glucose remained unchanged, whereas BMI worsened., (Copyright © 2024 Society for Adolescent Health and Medicine. Published by Elsevier Inc. All rights reserved.)

Background: Both adverse childhood experiences (ACEs) and lifestyle factors have been associated with risk of cardiovascular diseases (CVDs) in later life, but whether and to what extent adherence to a healthy lifestyle in adulthood can offset the increased cardiovascular risk associated with ACEs is unclear. We aimed to determine whether and to what extent adopting to a healthy lifestyle in adulthood can offset the risk of CVDs in individuals according to their ACEs., Methods: A prospective cohort study included 143,869 participants aged 38-72 years, free of CVDs at baseline from the UK Biobank. The history of ACEs was assessed using the Childhood Trauma Screener. Participants were divided into three risk groups based on ACEs: low (no ACEs), intermediate (one or two ACEs), and high (three or more ACEs). A healthy lifestyle score in adulthood was constructed as the sum of four modifiable lifestyle factors (no smoking, adequate physical activity, healthy diet, no obesity), and participants were then categorized into three groups based on this score (unfavorable [0-1 point], intermediate [2-3 points], favorable [4 points]). Cox proportional hazard models were conducted to investigate the association between ACEs, healthy lifestyle, and incident CVDs., Results: During a median follow-up of 12.49 years, 13,373 incident cases of overall CVDs were identified. This included 7521 cases of coronary heart disease (CHD), 6175 cases of atrial fibrillation (AF) and 1813 cases of stroke. Individuals with high ACEs had a greater risk of incident overall CVDs (hazard ratio [HR] = 1.39, [95%CI = 1.29 to 1.50]), CHD (1.50 [1.36 to 1.65]) and AF (1.18 [1.05 to 1.33]) compared to those with low ACEs. The risk of CVDs decreased moving from unfavorable to favorable lifestyle categories (P for trend<0.001), with the lowest risk observed among individuals with a favorable lifestyle (0.70 [0.66 to 0.74] for overall CVDs, 0.69 [0.64 to 0.75] for CHD, and 0.71 [0.65 to 0.78] for AF). Participants with high ACEs and a favorable lifestyle had a 39 %, 40 % and 47 % lower risk of developing overall CVDs (0.61 [0.48 to 0.76]), CHD (0.60 [0.44 to 0.81], and AF (0.53 [0.36 to 0.77]) than those with high ACEs and an unfavorable lifestyle., Conclusions: Having a healthy lifestyle in adulthood could substantially attenuate the increased risk of overall CVDs, CHD, and AF conferred by ACEs., Competing Interests: Declaration of competing interest There were no potential conflicts of interests., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Purpose of Review: This review summarizes current knowledge on blood pressure in children and adolescents (youth), with a focus on primary hypertension-the most common form of elevated blood pressure in this demographic. We examine its etiology, progression, and long-term cardiovascular implications. The review covers definitions and recommendations of blood pressure classifications, recent developments in measurement, epidemiological trends, findings from observational and clinical studies, and prevention and treatment, while identifying gaps in understanding and suggesting future research directions., Recent Findings: Youth hypertension is an escalating global issue, with regional and national variations in prevalence. While the principles of blood pressure measurement have remained largely consistent, challenges in this age group include a scarcity of automated devices that have passed independent validation for accuracy and a generally limited tolerance for ambulatory blood pressure monitoring. A multifaceted interplay of factors contributes to youth hypertension, impacting long-term cardiovascular health. Recent studies, including meta-analysis and sophisticated life-course modelling, reveal an adverse link between youth and life-course blood pressure and subclinical cardiovascular outcomes later in life. New evidence now provides the strongest evidence yet linking youth blood pressure with clinical cardiovascular events in adulthood. Some clinical trials have expanded our understanding of the safety and efficacy of antihypertensive medications in youth, but this remains an area that requires additional attention, particularly regarding varied screening approaches. This review outlines the potential role of preventing and managing blood pressure in youth to reduce future cardiovascular risk. A global perspective is necessary in formulating blood pressure definitions and strategies, considering the specific needs and circumstances in low- and middle-income countries compared to high-income countries., (© 2024. The Author(s).)

Importance: Elevated non-high-density lipoprotein cholesterol (non-HDL-C; a recommended measure of lipid-related cardiovascular risk) is common in children and increases risk of adult cardiovascular disease (CVD). Whether resolution of elevated childhood non-HDL-C levels by adulthood is associated with reduced risk of clinical CVD events is unknown., Objective: To examine the associations of non-HDL-C status between childhood and adulthood with incident CVD events., Design, Setting, and Participants: Individual participant data from 6 prospective cohorts of children (mean age at baseline, 10.7 years) in the US and Finland. Recruitment took place between 1970 and 1996, with a final follow-up in 2019., Exposures: Child (age 3-19 years) and adult (age 20-40 years) non-HDL-C age- and sex-specific z scores and categories according to clinical guideline-recommended cutoffs for dyslipidemia., Main Outcomes and Measures: Incident fatal and nonfatal CVD events adjudicated by medical records., Results: Over a mean length of follow-up of 8.9 years after age 40 years, 147 CVD events occurred among 5121 participants (60% women; 15% Black). Both childhood and adult non-HDL-C levels were associated with increased risk of CVD events (hazard ratio [HR], 1.42 [95% CI, 1.18-1.70] and HR, 1.50 [95% CI, 1.26-1.78] for a 1-unit increase in z score, respectively), but the association for childhood non-HDL-C was reduced when adjusted for adult levels (HR, 1.12 [95% CI, 0.89-1.41]). A complementary analysis showed that both childhood non-HDL-C levels and the change between childhood and adulthood were independently associated with the outcome, suggesting that from a preventive perspective, both childhood non-HDL-C levels and the change into adulthood are informative. Compared with those whose non-HDL-C levels remained within the guideline-recommended range in childhood and adulthood, participants who had incident non-HDL-C dyslipidemia from childhood to adulthood and those with persistent dyslipidemia had increased risks of CVD events (HR, 2.17 [95% CI, 1.00-4.69] and HR, 5.17 [95% CI, 2.80-9.56], respectively). Individuals who had dyslipidemic non-HDL-C in childhood but whose non-HDL-C levels were within the guideline-recommended range in adulthood did not have a significantly increased risk (HR, 1.13 [95% CI, 0.50-2.56])., Conclusions and Relevance: Individuals with persistent non-HDL-C dyslipidemia from childhood to adulthood had an increased risk of CVD events, but those in whom dyslipidemic non-HDL-C levels resolve by adulthood have similar risk to individuals who were never dyslipidemic. These findings suggest that interventions to prevent and reduce elevated childhood non-HDL-C levels may help prevent premature CVD.

Importance: Recent evidence suggests that childhood levels of serum lipids, blood pressure, body mass index (BMI), and smoking contribute to adult risk of cardiovascular disease (CVD). Evidence is lacking on whether this is independent of adult risk levels., Objective: To quantify direct and indirect effects of childhood risk factors on adult CVD via adulthood risk factors using mediation analysis, and to quantify their relative importance during different life-course stages using a life-course approach., Design, Setting, and Participants: This prospective cohort study followed participants from the US, Finland, and Australia from childhood (1970s-1990s) until 2019, with data on CVD risk factors in childhood and adulthood. Longitudinal childhood and adulthood risk factors were summarized to describe BMI, lipids, and blood pressure cumulatively. Childhood and adulthood smoking were assessed with questionnaires. Data analysis was performed May 2022 to August 2023., Main Outcomes and Measures: The primary outcomes were fatal and nonfatal cardiovascular events in adulthood. Mediation analysis was used to estimate the direct and indirect effects of the childhood risk factors with CVD events, reported as incidence rate ratios (RRs) and 95% CIs., Results: A total of 10 634 participants (4506 male participants [42.4%]; mean [SD] age at childhood visit, 13.3 [3.0] years; mean [SD] age at adulthood visit, 32.3 [6.0] years) were included in the cohort. The mean (SD) age at CVD event or censoring was 49.2 (7.0) years. The median (IQR) follow-up time was 23.6 (18.7-30.2) years. Childhood risk factors, (low-density lipoprotein cholesterol [LDL-C], total cholesterol [TC], triglycerides, systolic blood pressure [SBP], smoking, BMI, and a combined score of these) were associated with CVD. BMI (direct effect for incidence RR per 1 SD unit, 1.18; 95% CI, 1.05-1.34) and LDL-C (direct effect incidence RR, 1.16; 95% CI, 1.01-1.34) in particular were found to play an important role via direct pathways, whereas the indirect effects were larger for TC, triglycerides, SBP, and the combined score. Childhood smoking only affected CVD via adulthood smoking. Life-course models confirmed that for the risk of CVD, childhood BMI plays nearly as important role as adulthood BMI, whereas for the other risk factors and the combined score, adulthood was the more important period., Conclusions and Relevance: In this cohort study of 10 634 participants, childhood risk factors were found to be associated both directly and indirectly to adult CVD, with the largest direct effect seen for BMI and LDL-C. These findings suggest that intervention for childhood risk factors, in particular BMI, is warranted to reduce incidence of adult CVD as it cannot be fully mitigated by risk factor management in adulthood.

Background and Aims: Atherosclerosis is accompanied by pre-clinical vascular changes that can be detected using ultrasound imaging. We examined the value of such pre-clinical features in identifying young adults who are at risk of developing atherosclerotic cardiovascular disease (ASCVD)., Methods: A total of 2641 individuals free of ASCVD were examined at the mean age of 32 years (range 24-45 years) for carotid artery intima-media thickness (IMT) and carotid plaques, carotid artery elasticity, and brachial artery flow-mediated endothelium-dependent vasodilation (FMD). The average follow-up time to event/censoring was 16 years (range 1-17 years)., Results: Sixty-seven individuals developed ASCVD (incidence 2.5%). The lowest incidence (1.1%) was observed among those who were estimated of having low risk according to the SCORE2 risk algorithm (<2.5% 10-year risk) and who did not have plaque or high IMT (upper decile). The highest incidence (11.0%) was among those who were estimated of having a high risk (≥2.5% 10-year risk) and had positive ultrasound scan for carotid plaque and/or high IMT (upper decile). Carotid plaque and high IMT remained independently associated with higher risk in multivariate models. The distributions of carotid elasticity indices and brachial FMD did not differ between cases and non-cases., Conclusions: Screening for carotid plaque and high IMT in young adults may help identify individuals at high risk for future ASCVD., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)

Aims: The clinical utility of waist-to-height ratio (WHtR) in predicting cardiometabolic risk factors (CMRFs) and subclinical markers of cardiovascular disease remains controversial. We aimed to compare the utility of WHtR with waist circumference (WC) and body mass index (BMI) in identifying children and adolescents (youths) at risk for cardiometabolic outcomes, including clustered CMRFs, high carotid intima-media thickness (cIMT), and arterial stiffness (assessed as high pulse wave velocity, PWV)., Methods: We analyzed data from 34,224 youths (51.0 % boys, aged 6-18 years) with CMRFs, 5004 (49.5 % boys, aged 6-18 years) with cIMT measurement, and 3100 (56.4 % boys, aged 6-17 years) with PWV measurement from 20 pediatric samples across 14 countries., Results: WHtR, WC, and BMI z-scores had similar performance in discriminating youths with ≥3 CMRFs, with the area under the curve (AUC) (95 % confidence interval, CI)) ranging from 0.77 (0.75-0.78) to 0.78 (0.76-0.80) using the modified National Cholesterol Education Program (NCEP) definition, and from 0.77 (0.74-0.79) to 0.77 (0.74-0.80) using the International Diabetes Federation (IDF) definition. Similarly, all three measures showed similar performance in discriminating youths with subclinical vascular outcomes, with AUC (95 % CI) ranging from 0.67 (0.64-0.71) to 0.70 (0.66-0.73) for high cIMT (≥P95 values) and from 0.60 (0.58-0.66) to 0.62 (0.58-0.66) for high PWV (≥P95 values)., Conclusions: Our findings suggest that WHtR, WC, and BMI are equally effective in identifying at-risk youths across diverse pediatric populations worldwide. Given its simplicity and ease of use, WHtR could be a preferable option for quickly screening youths with increased cardiometabolic risk in clinical settings., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests:Bo Xi reports financial support was provided by National Natural Science Foundation of China. None reports a relationship with None that includes: None has patent None pending to None. None If there are other authors, they declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024. Published by Elsevier Ltd.)

Background and Aims: The utility of lipid screening in pediatric settings for preventing adult atherosclerotic cardiovascular diseases partly depends on the lifelong tracking of lipid levels. This systematic review aimed to quantify the tracking of lipid levels from childhood and adolescence to adulthood., Methods: We systematically searched MEDLINE, Embase, Web of Science, and Google Scholar in March 2022. The protocol was registered with the International Prospective Register of Systematic Reviews (PROSPERO; ID: CRD42020208859). We included cohort studies that measured tracking of lipids from childhood or adolescence (<18 years) to adulthood (≥18) with correlation or tracking coefficients. We estimated pooled correlation and tracking coefficients using random-effects meta-analysis. Risk of bias was assessed with a review-specific tool., Results: Thirty-three studies of 19 cohorts (11,020 participants) were included. The degree of tracking from childhood and adolescence to adulthood differed among lipids. Tracking was observed for low-density lipoprotein cholesterol (pooled r = 0.55-0.65), total cholesterol (pooled r = 0.51-0.65), high-density lipoprotein cholesterol (pooled r = 0.46-0.57), and triglycerides (pooled r = 0.32-0.40). Only one study included tracking of non-high-density lipoprotein cholesterol (r = 0.42-0.59). Substantial heterogeneity was observed. Study risk of bias was moderate, mostly due to insufficient reporting and singular measurements at baseline and follow-up., Conclusions: Early-life lipid measurements are important for predicting adult levels. However, further research is needed to understand the tracking of non-high-density lipoprotein cholesterol and the stability of risk classification over time, which may further inform pediatric lipid screening and assessment strategies., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)

Dietary guidelines are increasingly promoting mostly plant-based diets, limits on red meat consumption, and plant-based sources of protein for health and environmental reasons. It is unclear how the resulting food substitutions associate with insulin resistance, a risk factor for type 2 diabetes. We modelled the replacement of red and processed meat with plant-based alternatives and the estimated effect on insulin sensitivity. We included 783 participants (55 % female) from the Childhood Determinants of Adult Health study, a population-based cohort of Australians. In adulthood, diet was assessed at three time points using FFQ: 2004–2006, 2009–2011 and 2017–2019. We calculated the average daily intake of each food group in standard serves. Insulin sensitivity was estimated from fasting glucose and insulin concentrations in 2017–2019 (aged 39–49 years) using homoeostasis model assessment. Replacing red meat with a combination of plant-based alternatives was associated with higher insulin sensitivity ( β = 10·5 percentage points, 95 % CI (4·1, 17·4)). Adjustment for waist circumference attenuated this association by 61·7 %. Replacing red meat with either legumes, nuts/seeds or wholegrains was likewise associated with higher insulin sensitivity. Point estimates were similar but less precise when replacing processed meat with plant-based alternatives. Our modelling suggests that regularly replacing red meat, and possibly processed meat, with plant-based alternatives may associate with higher insulin sensitivity. Further, abdominal adiposity may be an important mediator in this relationship. Our findings support advice to prioritise plant-based sources of protein at the expense of red meat consumption.

Background and Aims: The relationship between childhood tobacco smoke exposure and cardiac structure and function in midlife is unclear. We investigated the association between parental smoking with cardiac structure and function in adulthood., Methods: 1250 participants (56.5% female) from the Cardiovascular Risk in Young Finns Study who had data on parental smoking and/or serum cotinine, a biomarker of exposure to tobacco smoke, at baseline 1980 (age 3-18 years) and echocardiography performed in 2011. Parental smoking hygiene (i.e., smoking in the vicinity of children) was categorized by parental smoking and serum cotinine levels in offspring. Dimensions of the left ventricle, diastolic and systolic function, and cardiac remodeling were used as outcomes. Analyses were adjusted for sex, age, and covariates (blood pressure (BP), serum lipids, body mass index, socioeconomic status, smoking (only in adulthood)) in childhood and adulthood., Results: Parental smoking was not associated with systolic or diastolic function in adulthood. Participants exposed to parental smoking (odds ratio (OR) 1.90, 95%CI 1.23-2.92), hygienic parental smoking (OR 1.74, 95%CI 1.12-2.71), and non-hygienic parental smoking (OR 1.88, 95%CI 1.02-3.45) had higher odds of concentric remodeling (relative wall thickness >85th sex-specific percentile without left ventricular hypertrophy). These associations were attenuated after adjustment for child and adult covariates in the non-hygienic parental smoking group., Conclusions: Exposure to parental smoking in childhood was associated with a higher likelihood of concentric remodeling and thicker left ventricular and interventricular septal walls in midlife, which was not improved by parents who smoked hygienically. Parental smoking was not related to systolic or diastolic function in this relatively young population., Competing Interests: Declaration of conflicting interestsThe authors declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Importance: Although cardiovascular disease (CVD) begins in early life, the extent to which blood pressure (BP) at different life stages contributes to CVD is unclear., Objective: To determine the relative contribution of BP at different life stages across the early-life course from infancy to young adulthood with carotid intima-media thickness (IMT)., Design, Setting, and Participants: The analyses were performed in 2022 using data gathered from July 1989 through January 2018 within the Special Turku Coronary Risk Factor Intervention Project, a randomized, infancy-onset cohort of 534 participants coupled with annual BP (from age 7 months to 20 years), biennial IMT measurements (from ages 13 to 19 years), who were followed up with again at age 26 years., Exposures: BP measured from infancy (aged 7 to 13 months), preschool (2 to 5 years), childhood (6 to 12 years), adolescence (13 to 17 years), and young adulthood (18 to 26 years)., Main Outcomes and Measures: Primary outcomes were carotid IMT measured in young adulthood at age 26 years. Bayesian relevant life-course exposure models assessed the relative contribution of BP at each life stage., Results: Systolic BP at each life stage contributed to the association with young adulthood carotid IMT (infancy: relative weight, 25.3%; 95% credible interval [CrI], 3.6-45.8; preschool childhood: relative weight, 27.0%; 95% CrI, 3.3-57.1; childhood: relative weight, 18.0%; 95% CrI, 0.5-40.0; adolescence: relative weight, 13.5%; 95% CrI, 0.4-37.1; and young adulthood: relative weight, 16.2%; 95% CrI, 1.6-46.1). A 1-SD (at single life-stage) higher systolic BP accumulated across the life course was associated with a higher carotid IMT (0.02 mm; 95% CrI, 0.01-0.03). The findings for carotid IMT were replicated in the Cardiovascular Risk in Young Finns Study that assessed systolic BP from childhood and carotid IMT in adulthood (33 to 45 years)., Conclusion and Relevance: In this cohort study, a life-course approach indicated that accumulation of risk exposure to BP levels at all life stages contributed to adulthood carotid IMT. Of those, the contribution attributed to each observed life stage was approximately equal. These results support prevention efforts that achieve and maintain normal BP levels across the life course, starting in infancy.

Background: There are limited data on the association between secondhand smoke (SHS) exposure across the life course and depressive symptoms among older adults. We aimed to investigate the association of childhood household SHS exposure, adulthood household SHS exposure, lifetime social SHS exposure, and their coexistence with depressive symptoms in older adults., Methods: Data were from the 2011-2012 and 2014 waves of the Chinese Longitudinal Healthy Longevity Survey. About 4000 participants (aged 60 years or older) were recruited in a randomly selected half of the counties and cities in China. Data on SHS exposure, past-year depressive symptoms, and covariates were collected using a questionnaire. The chi-square test (for categorical variables) and t-test (for continuous variables) were used to assess differences in the participant characteristics across groups of SHS exposures. We estimated the odds ratios (ORs) and 95 % confidence intervals (CIs) of depressive symptom according to different types of SHS exposure., Results: Childhood household SHS exposure (OR = 1.42, 95%CI = 1.22-1.66), adulthood household SHS exposure (OR = 1.41, 95%CI = 1.21-1.63) and lifetime social SHS exposure (OR = 1.35, 95%CI = 1.14-1.58) were associated with higher odds of depressive symptoms. Additionally, those with a higher SHS exposure score had higher odds of depressive symptoms (1 point: OR = 1.56, 95%CI = 1.22-2.00; 2 points: OR = 1.77, 95%CI = 1.39-2.25; 3 points: OR = 1.83, 95%CI = 1.45-2.31). The results were similar when stratified by lifetime nonsmoking, former smoking, and current smoking., Limitations: Retrospective design may introduce recall bias., Conclusions: SHS exposure was associated with higher odds of depressive symptoms in older adults, with the effect seeming to be addictive., Competing Interests: Declaration of competing interest All authors disclosed no relevant relationships., (Copyright © 2023 Elsevier B.V. All rights reserved.)

To quantify the tracking of apolipoprotein B (apoB) levels from childhood and adolescence and compare the tracking of apoB with low-density lipoprotein (LDL) cholesterol, a systematic search of MEDLINE, Embase, Web of Science, and Google Scholar was performed in October 2023 (PROSPERO protocol: CRD42022298663). Cohort studies that measured tracking of apoB from childhood/adolescence (< 19 years) with a minimum follow-up of 1 year, using tracking estimates such as correlation coefficients or tracking coefficients, were eligible. Pooled correlations were estimated using random-effects meta-analysis. Risk of bias was assessed with a review-specific tool. Ten studies of eight unique cohorts involving 4677 participants met the inclusion criteria. Tracking of apoB was observed (pooled r = 0.63; 95% confidence interval [CI] = 0.53-0.71; I 2  = 96%) with no significant sources of heterogeneity identified. Data from five cohorts with tracking data for both lipids showed the degree of tracking was similar for apoB (pooled r = 0.59; 95% CI = 0.55-0.63) and LDL cholesterol (pooled r = 0.58; 95% CI = 0.47-0.68). Study risk of bias was moderate, mostly due to attrition and insufficient reporting., Conclusion: ApoB levels track strongly from childhood, but do not surpass LDL cholesterol in this regard. While there is strong evidence that apoB is more effective at predicting ASCVD risk than LDL cholesterol in adults, there is currently insufficient evidence to support its increased utility in pediatric settings. This also applies to tracking data, where more comprehensive data are required., What Is Known: • Apolipoprotein B is a known cause of atherosclerotic cardiovascular disease. • Apolipoprotein B levels are not typically measured in pediatric settings, where low-density lipoprotein cholesterol remains the primary lipid screening measure., What Is New: • This meta-analysis of 10 studies showed apolipoprotein B levels tracked strongly from childhood but did not exceed low-density lipoprotein cholesterol in this regard. • More comprehensive tracking data are needed to provide sufficient evidence for increased utility of apolipoprotein B in pediatric settings., (© 2023. The Author(s).)

Aims: Helping people to understand their cardiovascular (CV) risk can influence the choices they make for risk reduction, including medication adherence and lifestyle modification. This study sought whether repeated visualization of coronary artery calcium (CAC) images was effective in sustaining long-term risk control in primary prevention, independent of a risk reduction program., Methods: Asymptomatic, statin-naïve participants, 40-70 years, with a family history of premature coronary artery disease and a CAC score from 1-400 were randomised to a nurse-led CV risk reduction program or standard care with bi-annual reviews. Only the intervention group (220 of 449 participants) visualised their CAC image (with repeat exposure in the first 3 months) and were initiated on statin therapy. The primary outcome was change in Framingham Risk Score (FRS) at 36 months, and the impact of CAC image recall on CV risk was assessed., Results: The reduction in FRS (difference in differences (DID): -3.4% [95%CI: -4.4% to -2.4%], p=<0.001 and low-density-lipoprotein-cholesterol -1.2mmol/L [95%CI: -1.4 to -1.0], p=<0.001)) over 36 months was greater in the intervention than the control group. Within the intervention group, sustained recall of CAC images at 24 months was associated with lower systolic blood pressure (DID -4.3mmHg [95%CI: -7.7 to-0.9], p=0.01) and waist circumference (DID -2.0cm [95% CI: -3.9 to -0.1], p=0.03) at 36 months compared to unsustained recall., Conclusion: A nurse-led program, combining personalized patient visualization of CAC imaging with statin therapy, is beneficial for improving CV risk. Recalling the presentation of CAC images through repeated visual exposure may influence risk reduction., (© The Author(s) 2024. Published by Oxford University Press on behalf of the European Society of Cardiology.)

Background: Although low-density lipoprotein cholesterol (LDL-C) remains the primary cholesterol target in clinical practice in children and adults, non-high-density lipoprotein cholesterol (non-HDL-C) has been suggested as a more accurate measure of atherosclerotic cardiovascular disease (ASCVD) risk. We examined the associations of childhood non-HDL-C and LDL-C levels with adult ASCVD events and determined whether non-HDL-C has better utility than LDL-C in predicting adult ASCVD events., Methods: This prospective cohort study included 21 126 participants from the i3C Consortium (International Childhood Cardiovascular Cohorts). Proportional hazards regressions were used to estimate the risk for incident fatal and fatal/nonfatal ASCVD events associated with childhood non-HDL-C and LDL-C levels (age- and sex-specific z scores; concordant/discordant categories defined by guideline-recommended cutoffs), adjusted for sex, Black race, cohort, age at and calendar year of child measurement, body mass index, and systolic blood pressure. Predictive utility was determined by the C index., Results: After an average follow-up of 35 years, 153 fatal ASCVD events occurred in 21 126 participants (mean age at childhood visits, 11.9 years), and 352 fatal/nonfatal ASCVD events occurred in a subset of 11 296 participants who could be evaluated for this outcome. Childhood non-HDL-C and LDL-C levels were each associated with higher risk of fatal and fatal/nonfatal ASCVD events (hazard ratio ranged from 1.27 [95% CI, 1.14-1.41] to 1.35 [95% CI, 1.13-1.60] per unit increase in the risk factor z score). Non-HDL-C had better discriminative utility than LDL-C (difference in C index, 0.0054 [95% CI, 0.0006-0.0102] and 0.0038 [95% CI, 0.0008-0.0068] for fatal and fatal/nonfatal events, respectively). The discordant group with elevated non-HDL-C and normal LDL-C had a higher risk of ASCVD events compared with the concordant group with normal non-HDL-C and LDL-C (fatal events: hazard ratio, 1.90 [95% CI, 0.98-3.70]; fatal/nonfatal events: hazard ratio, 1.94 [95% CI, 1.23-3.06])., Conclusions: Childhood non-HDL-C and LDL-C levels are associated with ASCVD events in midlife. Non-HDL-C is better than LDL-C in predicting adult ASCVD events, particularly among individuals who had normal LDL-C but elevated non-HDL-C. These findings suggest that both non-HDL-C and LDL-C are useful in identifying children at higher risk of ASCVD events, but non-HDL-C may provide added prognostic information when it is discordantly higher than the corresponding LDL-C and has the practical advantage of being determined without a fasting sample., Competing Interests: Disclosures None.

Aims: To investigate the associations between passive tobacco smoke exposure and daily smoking with a comprehensive metabolic profile, measured repeatedly from childhood to adulthood., Methods and Results: Study cohort was derived from the Special Turku Coronary Risk Factor Intervention Project (STRIP). Smoking status was obtained by questionnaire, while serum cotinine concentrations were measured using gas chromatography. Metabolic measures were quantified by nuclear magnetic resonance metabolomics at 9 (n = 539), 11 (n = 536), 13 (n = 525), 15 (n = 488), 17 (n = 455), and 19 (n = 409) years. Association of passive tobacco smoke exposure with metabolic profile compared participants who reported less-than-weekly smoking and had serum cotinine concentration <1 ng/mL (no exposure) with those whose cotinine concentration was ≥10 ng/mL (passive tobacco smoke exposure). Associations of daily smoking with metabolic profile in adolescence were analysed by comparing participants reporting daily smoking with those reporting no tobacco use and having serum cotinine concentrations <1 ng/mL. Passive tobacco smoke exposure was directly associated with the serum ratio of monounsaturated fatty acids to total fatty acids [β = 0.34 standard deviation (SD), (0.17-0.51), P < 0.0001] and inversely associated with the serum ratios of polyunsaturated fatty acids. Exposure to passive tobacco smoke was directly associated with very-low-density lipoprotein particle size [β = 0.28 SD, (0.12-0.45), P = 0.001] and inversely associated with HDL particle size {β = -0.21 SD, [-0.34 to -0.07], P = 0.003}. Daily smokers exhibited a similar metabolic profile to those exposed to passive tobacco smoke. These results persisted after adjusting for body mass index, STRIP study group allocation, dietary target score, pubertal status, and parental socio-economic status., Conclusion: Both passive and active tobacco smoke exposures during childhood and adolescence are detrimentally associated with circulating metabolic measures indicative of increased cardio-metabolic risk., Competing Interests: Conflict of interest: None declared., (© The Author(s) 2023. Published by Oxford University Press on behalf of the European Society of Cardiology.)

This 26-year study found that non-high-density lipoprotein cholesterol (non-HDL-C) levels tracked from infancy to young adulthood suggesting early-life non-HDL-C could predict future levels. However, infancy-onset dietary counseling reduced the odds of maintaining at-risk non-HDL-C, highlighting the potential importance of early interventions in preventing cardiovascular risk associated with high pediatric non-HDL-C., Competing Interests: Declaration of Competing Interest This work was financially supported by the Academy of Finland (grants 206374, 294834, 251360, 275595, 307996, and 322112), the Juho Vainio Foundation, the Finnish Foundation for Cardiovascular Research, the Finnish Ministry of Education and Culture, the Finnish Cultural Foundation, the Sigrid Juselius Foundation, special governmental grants for Health Sciences Research (Turku University Hospital), the Yrjö Jahnsson Foundation, the Finnish Medical Foundation, and the Turku University Foundation. K.P. is funded by an Academy of Finland research fellowship (no. 322112). C.M. is supported by a National Health and Medical Research Council (NHMRC) investigator grant (APP1176494). The contents of the published material are solely the responsibility of the individual authors and do not reflect the views of the NHMRC. The authors declare no conflicts of interest disclose., (Copyright © 2023 The Author(s). Published by Elsevier Inc. All rights reserved.)

High cardiorespiratory fitness (CRF) in adulthood is important for survival from major chronic diseases and preserving good health. We examined how childhood CRF tracks, or persists, into adulthood. Among a cohort of 748 school children followed over 34 years, we found child CRF correlated with young- (r = 0.30) and mid-adulthood (r = 0.16) CRF., Competing Interests: Declaration of Competing Interest The Childhood Determinants of Adult Health Study was supported by Grants and fellowships from the Commonwealth Departments of Sport, Recreation and Tourism, and Health, the Commonwealth Schools Commission, the National Heart Foundation (GOOH 0578), the National Health and Medical Research Council (211316, 1128373, 1098369), Veolia Environmental Services and the Mostyn Family Foundation. The authors declare no conflict of interest., (Copyright © 2023 The Author(s). Published by Elsevier Inc. All rights reserved.)

To investigate the association of number of siblings with preclinical cardiovascular disease (CVD) markers in adulthood. The sample comprised 2776 participants (54 % female) from the Cardiovascular Risk in Young Finns Study who had CVD risk factor data measured in childhood in 1980 (aged 3-18 years) and markers of preclinical CVD measured in adulthood. Echocardiography was performed in 2011, and carotid intima-media thickness, carotid distensibility, brachial flow-mediated dilatation, and arterial pulse wave velocity were measured in 2001 or 2007. The association between the number of siblings and preclinical CVD was assessed using generalized linear and logistic regression models. Analyses were stratified by sex as associations differed between sexes. Women with 1 sibling had lower E/e'-ratio (4.9, [95%CI 4.8-5.0]) in echocardiography compared with those without siblings (5.1[4.9-5.2]) and those with ≥2 more siblings (5.1[5.0-5.2]) (P for trend 0.01). Men without siblings had the lowest E/A-ratio (1.4[1.3-1.5]) compared with those with 1 sibling (1.5[1.5-1.5]), or ≥2 siblings (1.5[1.5-1.5]) (P for trend 0.01). Women without siblings had highest left ventricular ejection fraction (59.2 %[58.6-59.7 %]) compared with those with 1 sibling (59.1 %[58.8-59.4 %]), or ≥2 siblings (58.4 %[58.1-58.8 %])(P for trend 0.01). In women, brachial flow-mediated dilatation, a measure of endothelial function, was the lowest among participants with ≥2 siblings (9.4 %[9.0-9.8 %]) compared with those with 1 sibling (10.0 %[9.6-10.3 %]) and those without siblings (10.4 %[9.7-11.0 %])(P for trend 0.03). We observed that number of siblings may be associated with increased risk of heart failure in women. As the associations were somewhat inconsistent in males and females, further research is warranted., Competing Interests: The authors declared they do not have anything to disclose regarding no conflict of interest with respect to this manuscript., (© 2023 The Authors.)

Objective: Exaggerated exercise blood pressure (BP) is independently associated with cardiovascular disease (CVD) outcomes. However, it is unknown how individual CVD risk factors may interact with one another to influence exercise BP. The aim of this study was to quantify direct and indirect associations between CVD risk factors and exercise BP, to determine what CVD risk factor/s most-strongly relate to exercise BP., Methods: In a cross-sectional design, 660 participants (44 ± 2.6 years, 54% male) from the population-based Childhood Determinants of Adult Health Study had BP measured during low-intensity fixed-workload cycling. CVD risk factors were measured, including body composition, clinic (rest) BP, blood biomarkers, and cardiorespiratory fitness. Associations between CVD risk factors and exercise BP were assessed using linear regression, with direct and indirect pathways of association assessed via structural equation model., Results: Sex, waist-to-hip ratio, fitness, and clinic BP were independently associated with exercise systolic BP (SBP), and along with age, had direct associations with exercise SBP (p < 0.05 all). Most CVD risk factors were indirectly associated with exercise SBP via a relation with clinic BP (p < 0.05 all). Clinic BP, waist-to-hip ratio, and fitness were most-strongly associated (direct and indirect association) with exercise SBP (β[95% CI]: 9.35 [8.04, 10.67], 4.91 [2.56, 7.26], and -2.88 [-4.25, -1.51] mm Hg/SD, respectively)., Conclusion: Many CVD risk factors are associated with exercise BP, mostly with indirect effects via clinic BP. Clinic BP, body composition, and fitness were most-strongly associated with exercise BP. These results may elucidate how lifestyle modification could be a primary strategy to decrease exaggerated exercise BP-related CVD risk., (© 2023 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Background: Waist-to-height ratio (WHtR) has been proposed as a simple and effective screening tool for assessing central obesity and cardiometabolic risk in both adult and pediatric populations. However, evidence suggests that the use of a uniform WHtR cut-off of 0.50 may not be universally optimal for pediatric populations globally. We aimed to determine the optimal cut-offs of WHtR in children and adolescents with increased cardiometabolic risk across different countries worldwide., Methods: We used ten population-based cross-sectional data on 24,605 children and adolescents aged 6-18 years from Brazil, China, Greece, Iran, Italy, Korea, South Africa, Spain, the UK, and the USA for establishing optimal WHtR cut-offs. We performed an external independent test (9,619 children and adolescents aged 6-18 years who came from other six countries) to validate the optimal WHtR cut-offs based on the predicting performance for at least two or three cardiometabolic risk factors., Results: Based on receiver operator characteristic curve analyses of various WHtR cut-offs to discriminate those with ≥ 2 cardiometabolic risk factors, the relatively optimal percentile cut-offs of WHtR in the normal weight subsample population in each country did not always coincide with a single fixed percentile, but varied from the 75 th to 95 th percentiles across the ten countries. However, these relatively optimal percentile values tended to cluster irrespective of sex, metabolic syndrome (MetS) criteria used, and WC measurement position. In general, using ≥ 2 cardiometabolic risk factors as the predictive outcome, the relatively optimal WHtR cut-off was around 0.50 in European and the US youths but was lower, around 0.46, in Asian, African, and South American youths. Secondary analyses that directly tested WHtR values ranging from 0.42 to 0.56 at 0.01 increments largely confirmed the results of the main analyses. In addition, the proposed cut-offs of 0.50 and 0.46 for two specific pediatric populations, respectively, showed a good performance in predicting ≥ 2 or ≥ 3 cardiometabolic risk factors in external independent test populations from six countries (Brazil, China, Germany, Italy, Korea, and the USA)., Conclusions: The proposed international WHtR cut-offs are easy and useful to identify central obesity and cardiometabolic risk in children and adolescents globally, thus allowing international comparison across populations., (© 2023. The Author(s).)

Aim: Determine if asymmetric handgrip strength exists in childhood and adulthood and quantify the degree of tracking of handgrip strength asymmetry over time., Methods: Participants from the Childhood Determinants of Adult Health Study had their right and left handgrip strength measured using handgrip dynamometry in childhood (1985: 9-15 y), young adulthood (2004-06: 26-36 y) and/or mid-adulthood (2014-19: 36-49 y). Handgrip strength asymmetry was calculated as: strongest handgrip strength/strongest handgrip strength on the other hand. Participants were categorised based on the degree of their asymmetry (0.0%-10.0%, 10.1%-20.0%, 20.1%-30.0%, >30.0%). Tracking was quantified using Spearman's correlations and log binomial regression., Results: Handgrip strength asymmetry was present in childhood and adulthood (>30.0% asymmetry: childhood = 6%, young adulthood = 3%, mid-adulthood = 4%). Handgrip strength asymmetry did not track between childhood and young- (r = 0.06, 95% CI = -0.02, 0.12) and mid-adulthood (r = 0.01, 95% CI = -0.09, 0.10). Tracking was more apparent between young- and mid-adulthood (r = 0.16, 95% CI = 0.09, 0.22). Participants with >30.0% asymmetry were at greater risk to maintain this status between childhood and young- (RR = 3.53, 95% CI = 1.15, 10.87) and mid-adulthood (RR = 2.14, 95% CI = 0.45, 10.20)., Conclusion: Although handgrip strength asymmetry tracked relatively poorly, asymmetric handgrip strength was apparent in children and adults. Handgrip strength asymmetry does not exclusively affect older adults and should be considered in protocols to better understand its role across the life course., (© 2023 The Authors. Acta Paediatrica published by John Wiley & Sons Ltd on behalf of Foundation Acta Paediatrica.)

Objectives: Diet plays an important role in cognitive health, but the long-term association of diet early in life with cognitive function in adulthood has not, to our knowledge, been rigorously studied. The aim of this study was to examine the association of youth, adulthood, and long-term dietary patterns from youth to adulthood with cognitive function in midlife., Methods: This was a population-based cohort study that assessed dietary intake in 1980 (baseline, participants 3-18 y of age), 1986, 2001, 2007, and 2011 and cognitive function in 2011. Six dietary patterns were derived from 48-h food recall or food frequency questionnaires using factor analysis. The dietary patterns were traditional Finnish, high-carbohydrate, vegetables and dairy products, traditional Finnish and high-carbohydrate, red meat, and healthy. Scores of long-term dietary patterns were calculated as the average between youth and adulthood. Cognitive function outcomes assessed included episodic memory and associative learning, short-term working memory and problem solving, reaction and movement time, and visual processing and sustained attention. Standardized z-scores of exposures and outcomes were used for analyses., Results: Participants (n = 790, mean age 11.2 y) were followed up for 31 y. Multivariable models showed that both youth and long-term vegetable and dairy products and healthy patterns were positively associated with episodic memory and associative learning scores (β = 0.080-0.111, P < 0.05 for all). Both youth and long-term traditional Finnish patterns were negatively associated with spatial working memory and problem solving (β = -0.085 and -0.097, respectively; P < 0.05 for both). Long-term high-carbohydrate and traditional Finnish and high-carbohydrate patterns were inversely associated with visual processing and sustained attention, whereas the vegetable and dairy products pattern was positively associated with this cognitive domain (β = -0.117 to 0.073, P < 0.05 for all). Adulthood high-carbohydrate and traditional Finnish and high-carbohydrate patterns were inversely associated with all cognitive domains except for reaction and movement time (β = -0.072 to -0.161, P < 0.05 for all). Both long-term and adulthood red meat pattern were positively associated with visual processing and sustained attention (β = 0.079 and 0.104, respectively; P < 0.05 for both). These effect sizes correspond to approximately 1.6 to 16.1 y of cognitive aging on these cognitive domains., Conclusions: Higher adherence to traditional Finnish, high-carbohydrate, and traditional Finnish and high-carbohydrate patterns across the early life course was associated with poorer cognitive function in midlife, whereas higher adherence to healthy and vegetable and dairy product patterns was associated with better cognitive function. The findings, if causative, highlight the importance of maintaining a healthy dietary pattern from early life to adulthood in an attempt to promote cognitive health., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Background: It is unclear whether detection and patient visualization of cardiovascular (CV) images using computed tomography to assess coronary artery calcium or carotid ultrasound (CU) to identify plaque and intima-medial thickness merely prompts prescription of lipid-lowering therapy or whether it motivates lifestyle change among patients., Objectives: This systematic review and meta-analysis sought to investigate whether patient visualization of CV images (computed tomography or CU) has a beneficial impact on improving overall absolute CV risk as well as lipid and nonlipid CV risk factors in asymptomatic individuals., Methods: The key words "CV imaging," "CV risk," "asymptomatic persons," "no known or diagnosed CV disease," and "atherosclerotic plaque" were searched in PubMed, Cochrane, and Embase in November 2021. Randomized trials that assessed the role of CV imaging in reducing CV risk in asymptomatic persons with no known CV disease were eligible for study inclusion. The primary outcome was a change in 10-year Framingham risk score from the trial commencement to the end of the follow-up following patient visualization of CV images., Results: Six randomized controlled trials (7,083 participants) were included; 4 studies used coronary artery calcium and 2 used CU to detect subclinical atherosclerosis. All studies used image visualization in the intervention group to communicate CV risk. Imaging-guidance was associated with a 0.91% improvement in 10-year Framingham risk score (95% CI: 0.24%-1.58%; P = 0.01). Significant reductions in low-density-lipoprotein, total cholesterol, and systolic blood pressure were observed (all P < 0.05)., Conclusions: Patient visualization of CV imaging is associated with overall CV risk reduction and improvement of individual risk factors: cholesterol and systolic blood pressure., Competing Interests: Funding Support and Author Disclosures Supported in part by a grant from the Ernst Heine Foundation, Sydney, Australia. The authors have reported that they have no relationships relevant to the contents of this paper to disclose., (Copyright © 2023 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

Background: Obesity-associated chronic inflammation mediates the development of adverse cardiometabolic outcomes. There are sparse data on associations between severe obesity and inflammatory biomarkers in adolescence; most are cross-sectional and limited to acute phase reactants. Here, we investigate associations between adiposity measures and inflammatory biomarkers in children and adolescents with severe obesity both cross-sectionally and longitudinally., Methods: From the Childhood Overweight Biorepository of Australia (COBRA) study, a total of n = 262 participants, mean age 11.5 years (SD 3.5) with obesity had measures of adiposity (body mass index, BMI; % above the 95th BMI-centile, %>95th BMI-centile; waist circumference, WC; waist/height ratio, WtH; % total body fat, %BF; % truncal body fat, %TF) and inflammation biomarkers (glycoprotein acetyls, GlycA; high-sensitivity C-Reactive Protein, hsCRP; white blood cell count, WBC; and neutrophil/lymphocyte ratio, NLR) assessed at baseline. Ninety-eight individuals at mean age of 15.9 years (3.7) participated in a follow-up study 5.6 (2.1) years later. Sixty-two individuals had longitudinal data. Linear regression models, adjusted for age and sex for cross-sectional analyses were applied. To estimate longitudinal associations between change in adiposity measures with inflammation biomarkers, models were adjusted for baseline measures of adiposity and inflammation., Results: All adiposity measures were cross-sectionally associated with GlycA, hsCRP and WBC at both time points. Change in BMI, %>95th BMI-centile, WC, WtH and %TF were associated with concomitant change in GlycA and WBC, but not in hsCRP and NLR., Conclusion: GlycA and WBC but not hsCRP and NLR may be useful in assessing adiposity-related severity of chronic inflammation over time., Competing Interests: Declaration of Competing Interest The authors declare no conflict of interest., (Copyright © 2023 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Background: Understanding the temporal trends in the burden of overall and type-specific cardiovascular diseases (CVDs) in youths and young adults and its attributable risk factors is important for effective and targeted prevention strategies and measures. We aimed to provide a standardized and comprehensive estimation of the prevalence, incidence, disability-adjusted life years (DALY), and mortality rate of CVDs and its associated risk factors in youths and young adults aged 15-39 years at global, regional, and national levels., Methods: We applied Global Burden of Disease, Injuries, and Risk Factors Study (GBD) 2019 analytical tools to calculate the age-standardized incidence, prevalence, DALY, and mortality rate of overall and type-specific CVDs (i.e., rheumatic heart disease, ischemic heart disease, stroke, hypertensive heart disease, non-rheumatic valvular heart disease, cardiomyopathy and myocarditis, atrial fibrillation and flutter, aortic aneurysm, and endocarditis) among youths and young adults aged 15-39 years by age, sex, region, sociodemographic index and across 204 countries/territories from 1990 to 2019, and proportional DALY of CVDs attributable to associated risk factors., Results: The global age-standardized DALY (per 100,000 population) for CVDs in youths and young adults significantly decreased from 1257.51 (95% confidence interval 1257.03, 1257.99) in 1990 to 990.64 (990.28, 990.99) in 2019 with an average annual percent change (AAPC) of - 0.81% (- 1.04%, - 0.58%, P < 0.001), and the age-standardized mortality rate also significantly decreased from 19.83 (19.77, 19.89) to 15.12 (15.08, 15.16) with an AAPC of - 0.93% (- 1.21%, - 0.66%, P < 0.001). However, the global age-standardized incidence rate (per 100,000 population) moderately increased from 126.80 (126.65, 126.95) in 1990 to 129.85 (129.72, 129.98) in 2019 with an AAPC of 0.08% (0.00%, 0.16%, P = 0.040), and the age-standardized prevalence rate significantly increased from 1477.54 (1477.03, 1478.06) to 1645.32 (1644.86, 1645.78) with an AAPC of 0.38% (0.35%, 0.40%, P < 0.001). In terms of type-specific CVDs, the age-standardized incidence and prevalence rate in rheumatic heart disease, prevalence rate in ischemic heart disease, and incidence rate in endocarditis increased from 1990 to 2019 (all P < 0.001). When stratified by sociodemographic index (SDI), the countries/territories with low and low-middle SDI had a higher burden of CVDs than the countries/territories with high and high-middle SDI. Women had a higher prevalence rate of CVDs than men, whereas men had a higher DALY and mortality rate than women. High systolic blood pressure, high body mass index, and low-density lipoprotein cholesterol were the main attributable risk factors for DALY of CVDs for all included countries and territories. Household air pollution from solid fuels was an additional attributable risk factor for DALY of CVDs in low and low-middle SDI countries compared with middle, high-middle, and high SDI countries. Compared with women, DALY for CVDs in men was more likely to be affected by almost all risk factors, especially for smoking., Conclusions: There is a substantial global burden of CVDs in youths and young adults in 2019. The burden of overall and type-specific CVDs varied by age, sex, SDI, region, and country. CVDs in young people are largely preventable, which deserve more attention in the targeted implementation of effective primary prevention strategies and expansion of young-people's responsive healthcare systems., (© 2023. The Author(s).)

Background/objectives: The strong regulation of protein intake can lead to overconsumption of total energy on diets with a low proportion of energy from protein, a process referred to as protein leverage. The protein leverage hypothesis posits that protein leverage explains variation in energy intake and potentially obesity in ecological settings. Here, we tested for protein leverage and the protein leverage hypothesis in children and adolescents., Subjects/methods: A population sample of children, mean (SD) age 7.6 (0.4) years (n = 422), followed up at age 9.8 (0.4) years (n = 387) and at age 15.8 (0.4) years (n = 229), participating for the Physical Activity and Nutrition in Children (PANIC) study., Exposures: 4-day food records-related proportional energy intake of proteins, fats, and carbohydrates., Outcomes: energy intake, body mass index (BMI) z-score and dual-energy X-ray absorptiometry-related energy expenditure., Results: Proportional energy intake of proteins was inversely associated with energy intake following power functions at all 3 ages (mean [95%CI] strength of leverage of L = -0.36 [-0.47 to -0.25]; L = -0.26 [-0.37 to -0.15]; L = -0.25 [-0.38 to -0.13]; all P < 0.001). Mixture analysis indicated that variance in energy intake was associated primarily with the proportional intake of energy from proteins, not with either fats or carbohydrates. At all 3 ages, energy intake was not associated with BMI z-score but positively associated with energy expenditure (all P < 0.001)., Conclusions: This study provides evidence consistent with protein leverage in a population sample of children and adolescents. Increased energy intake on diets with lower protein content was counterbalanced by increased energy expenditure and therefore did not translate into increased adiposity., (© 2023. The Author(s).)

Objective: The aim of this study was to determine the impact of proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitor use on incident sepsis and other severe infections., Methods: We searched PubMed, EMBASE, CENTRAL, and ClinicalTrial.gov up to September 14, 2021, for double-blind, placebo-controlled randomized trials of alirocumab, evolocumab, or inclisiran with >100 participants in each arm and report of serious adverse events related to infection. Data were synthesized with the fixed-effect Mantel-Haenszel model to generate risk ratios (RRs) with 95% confidence intervals (CIs) of each outcome for PCSK9 inhibitor versus placebo. Main outcome was sepsis. Other outcomes were total severe infections, severe bacterial and viral infections, and severe organ system-specific infections including respiratory tract, gastrointestinal, and genitourinary tract infections., Results: A total of 20 studies of 64,984 participants were included (alirocumab: n = 7; evolocumab: n = 9; inclisiran: n = 4). Sepsis was reported in 292 (0.51%) participants from 11 trials (PCSK9 inhibitor 0.47%; placebo 0.56%). PCSK9 inhibitor use was not associated with risk of sepsis compared with placebo (Summary RR: 0.85, 95% CI: 0.67-1.07, P = .16); nor was it associated with any severe infection (0.96, 95% CI: 0.89-1.03), severe bacterial (0.96, 95% CI: 0.81-1.14) and viral infections (1.01, 95% CI: 0.77-1.33); nor with any severe organ system-specific infection (all P values >.05). The between-study heterogeneity in all analyses was small., Conclusion: There was neither a beneficial nor a harmful association between PCSK9 inhibitors and risk of sepsis or severe infections. These findings provide reassurance regarding the safety of PCSK9 inhibitors in patients who are concerned about potential drug side effects related to infections., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Background: A healthful plant-based eating pattern is associated with lower type 2 diabetes risk; however, the association with its preceding state, impaired insulin sensitivity, is less well established, particularly in younger populations with repeated measures of diet over time., Objective: We aimed to examine the longitudinal relationship between a healthful plant-based eating pattern and insulin sensitivity in young to middle-aged adults., Methods: We included 667 participants from the Childhood Determinants of Adult Health (CDAH) study, a population-based cohort in Australia. Healthful plant-based diet index (hPDI) scores were derived from food frequency questionnaire data. Plant foods considered "healthful" were scored positively (e.g., whole grains, fruit, vegetables), with all remaining foods scored reversely (e.g., refined grains, soft drinks, meat). Updated homeostatic model assessment (HOMA2) estimated insulin sensitivity from fasting insulin and glucose concentrations. We used linear mixed-effects regression to analyze data from 2 time points: CDAH-1 (2004-2006, 26-36 y of age) and CDAH-3 (2017-2019, 36-49 y of age). hPDI scores were modeled as between- and within-person effects (i.e., a participant's overall mean and their deviation from said mean at each time point, respectively)., Results: The median follow-up duration was 13 y. In our primary analysis, each 10-unit difference in hPDI score was associated with higher log-HOMA2 insulin sensitivity [95% confidence interval], with between-person (β = 0.11 [0.05, 0.17], P < 0.001) and within-person effects (β = 0.10 [0.04, 0.16], P = 0.001). The within-person effect persisted despite accounting for compliance with dietary guidelines. Adjustment for waist circumference attenuated the between-person effect by 70% (P = 0.26) and the within-person effect by 40% (P = 0.04)., Conclusions: In young to middle-aged Australian adults, a healthful plant-based eating pattern (determined using hPDI scores) was longitudinally associated with higher insulin sensitivity, and therefore, potentially lower type 2 diabetes risk later in life., (Copyright © 2023 American Society for Nutrition. Published by Elsevier Inc. All rights reserved.)