Adverse childhood experience, adopting a healthy lifestyle in adulthood, and risk of cardiovascular diseases.

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.

Cardiovascular Risk Factors in Childhood and Adulthood and Cardiovascular Disease in Middle Age.

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.

Pediatric Blood Pressure and Cardiovascular Health in Adulthood.

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.

Trends in Cardiovascular Health Among US Adolescents Aged 12-19 Years Using the New "Life's Essential 8" Metrics, 2007-2018.

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.

Utility of waist-to-height ratio, waist circumference and body mass index in predicting clustered cardiometabolic risk factors and subclinical vascular phenotypes in children and adolescents: A pooled analysis of individual data from 14 countries.

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.

Tracking of serum lipid levels from childhood to adulthood: Systematic review and meta-analysis.

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.

Subclinical atherosclerosis in young adults predicting cardiovascular disease: The Cardiovascular Risk in Young Finns Study.

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.

Non-High-Density Lipoprotein Cholesterol Levels From Childhood to Adulthood and Cardiovascular Disease Events.

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.

Influence of Repeated Plaque Visualization on Cardiovascular Risk Reduction after 3 years; a randomized controlled trial.

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.

This trial sought to determine whether visualization of coronary artery calcium (CAC) images influences behaviour change and cardiovascular risk reduction within a structured nurse-led program versus standard care. Intervention participants visualized their personalized CAC images within the first three months and commenced statin therapy. Control participants were blinded to their CAC images and were not provided statin therapy. Intervention participants had a greater absolute reduction in the Framingham Risk Score (Difference in differences: -3.4% [95% CI: -4.4% to -2.4%], p=<0.001) compared to controls. Those with sustained recollection of their CAC images within the intervention group also had greater reductions in systolic blood pressure and waist circumference.

Association of tobacco smoke exposure with metabolic profile from childhood to early adulthood: the Special Turku Coronary Risk Factor Intervention Project.

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 [ß = 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 [ß = 0.28 SD, (0.12-0.45), P = 0.001] and inversely associated with HDL particle size {ß = -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.

A substantial proportion of children are affected by tobacco smoke exposure worldwide, and early life exposure to passive tobacco smoke may be even more harmful than active smoking in terms of cardiovascular disease risk. Our study suggests the following: Passive tobacco smoke exposure during childhood is associated with metabolic measures indicative of increased cardio-metabolic risk and that the association profile is similar with active daily smoking during adolescence.Reducing both active and passive tobacco smoke exposures during childhood and adolescence could reduce the risk of future cardio-metabolic disease.

Blood Pressure at Different Life Stages Over the Early Life Course and Intima-Media Thickness.

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.

Tracking of apolipoprotein B levels measured in childhood and adolescence: systematic review and meta-analysis.

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; I2 = 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.

Childhood Non-HDL Cholesterol and LDL Cholesterol and Adult Atherosclerotic Cardiovascular Events.

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.

Modelling the replacement of red and processed meat with plant-based alternatives and the estimated effect on insulin sensitivity in a cohort of Australian adults.

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: 2004­2006, 2009­2011 and 2017­2019. We calculated the average daily intake of each food group in standard serves. Insulin sensitivity was estimated from fasting glucose and insulin concentrations in 2017­2019 (aged 39­49 years) using homoeostasis model assessment. Replacing red meat with a combination of plant-based alternatives was associated with higher insulin sensitivity (ß = 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.

Association of number of siblings with preclinical markers of cardiovascular disease. The cardiovascular risk in Young Finns study.

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.

The Influence of Dietary Counseling Over 20 Years on Tracking of Non-High-Density Lipoprotein Cholesterol from Infancy to Young Adulthood.

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.

Tracking of Cardiorespiratory Fitness from Childhood to Mid-adulthood.

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.

Association between secondhand smoke exposure across the life course and depressive symptoms among Chinese older adults.

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.

Establishing international optimal cut-offs of waist-to-height ratio for predicting cardiometabolic risk in children and adolescents aged 6-18 years.

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 75th to 95th 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.