Adult Outcomes Research Articles

Life's Essential 8 and Poor Brain Health Outcomes in Middle-Aged Adults.

Mounting evidence points to a strong connection between cardiovascular risk during middle age and brain health later in life. The American Heart Association's Life's Essential 8 (LE8) constitutes a research and public health construct capturing key determinants of cardiovascular health. However, the overall effect of the LE8 on global, clinically relevant metrics of brain health is still unknown. We tested the hypothesis that worse LE8 profiles are associated with higher composite risk of the most important clinical endpoints related to poor brain health. We conducted a two-stage (discovery and replication) prospective study using data from the UK Biobank (UKB) and All of Us (AoU), 2 large population studies in the United Kingdom and the United States, respectively. The primary exposure was the LE8 score, a validated tool that captures 8 modifiable cardiovascular risk factors (blood pressure, glucose, cholesterol, body mass index, smoking, physical activity, diet, and sleep duration), organized in 3 categories (optimal, intermediate, and poor). The primary outcome was a composite of stroke, dementia, or late-life depression. We evaluated associations using multivariable Cox proportional hazard models. The discovery stage included 316,127 UKB participants (mean age 56, 52% female). Over a mean (SD) follow-up time of 4.9 (0.4) years, the unadjusted risk of the composite outcome was 0.7% (95% CI 0.61-0.74), 1.2% (95% CI 1.11-1.22), and 1.8% (95% CI 1.70-1.91) in participants with optimal, intermediate, and poor cardiovascular health, respectively (p < 0.001). This association remained significant in multivariable Cox models (intermediate vs optimal cardiovascular health hazard ratio [HR], 1.37; 95% CI 1.24-1.52, and poor vs optimal cardiovascular health HR, 2.11; 95% CI 1.88-2.36, p trend <0.001). The replication stage included 68,407 AoU participants (mean age 56, 60% female). Over a mean (SD) follow-up time of 2.9 (1.41) years, the unadjusted risk of the composite outcome was 2.8% (95% CI 2.49-3.05), 6% (95% CI 5.76-6.22), and 9.7% (95% CI 9.24-10.24) in participants with optimal, intermediate, and poor cardiovascular health, respectively (p < 0.001). This association remained significant in multivariable Cox models (intermediate vs optimal cardiovascular health, HR 1.35; 95% CI 1.21-1.51, and poor vs optimal cardiovascular health, HR 1.94; 95% CI 1.72-2.18; p trend <0.001). Among middle-aged adults enrolled in 2 large population studies, poor cardiovascular health profiles were associated with two-fold higher risk of developing a composite outcome that captures the most important diseases related to poor brain health. Because the evaluated risk factors are all modifiable, our findings highlight the potential brain health benefits of using the Life's Essential 8 to guide cardiovascular health optimization.

Does 24/7 care result in better outcomes for adults with eating disorders? A comparison of inpatient/residential care to partial hospitalization/intensive outpatient care for patients at low BMIs

Does 24/7 care result in better outcomes for adults with eating disorders? A comparison of inpatient/residential care to partial hospitalization/intensive outpatient care for patients at low BMIs

Real-World Effectiveness of Upadacitinib in Moderate‑to‑Severe Atopic Dermatitis (AD): Results From Longitudinal Analyses of the CorEvitas AD Registry

Introduction: Clinical trials demonstrated that upadacitinib is efficacious in treating atopic dermatitis (AD). Its real-world effectiveness is less understood. In this study, we investigated the longitudinal real-world outcomes of upadacitinib-treated adults in the CorEvitas AD Registry. Methods: The CorEvitas AD Registry is a prospective, non-interventional registry of adults diagnosed with AD in the United States and Canada. We evaluated participants enrolled through April 30, 2024 with data available prior to upadacitinib exposure (baseline) and at the six-month follow-up visit, and were receiving upadacitinib at the follow-up visit. Outcomes evaluated include the achievement of: Validated Investigators Global Assessment Scale for Atopic Dermatitis (vIGA-ADTM) of “clear” or “almost clear” among participants rated “mild” or worse at baseline (vIGA-AD 0/1); Eczema Area and Severity Index improvement of ≥75%/≥90%/100% from baseline (EASI 75/90/100); Peak Pruritus Numeric Rating Scale (PP-NRS) improvement ≥4 among participants with a score ≥4 at baseline (∆PP-NRS≥4); PP-NRS score of 0 or 1 among participants with a score &gt;1 at baseline (PP-NRS 0/1); Dermatology Life Quality Index (DLQI) score improvement ≥4 among participants with a score ≥4 at baseline (∆DLQI≥4); and DLQI score of 0 or 1 among participants with a score &gt;1 at baseline (DLQI 0/1). Simultaneous achievement of both EASI 90 &amp; PP-NRS 0/1 was also assessed. Data were analyzed as observed with no imputation. Safety events were not assessed in this analysis. Results: The longitudinal analysis included 192 participants (mean age 46.2 years; 57.8% female; 69.8% White; 43.8% prior exposure to dupilumab or tralokinumab; 64.4% receiving 15 mg dose at follow-up visit; mean upadacitinib treatment duration of 6.0 months). More than half achieved clear/almost clear skin (66.1% vIGA-AD 0/1), EASI 75 (69.3%), and EASI 90 (59.2%); 45.3% achieved complete skin clearance (EASI 100). More than 40% reported little-to-no itch (44.4% PP-NRS 0/1) and no impact of AD on quality of life (43.3% DLQI 0/1), and more than half reported meaningful improvements in itch (58.6% ∆PP-NRS≥4) and quality of life (76.0% ∆DLQI≥4). Simultaneous attainment of both EASI 90 &amp; PP-NRS 0/1 was achieved in 46.6% of participants at 6 months. Conclusions: In the real-world setting, the majority of adults treated and remained on upadacitinib achieved clinically meaningful outcomes in skin lesions, itch, and quality of life, with many achieving complete skin clearance, little-to-no itch, and experiencing no impact of AD on their quality of life. These findings underscore upadacitinib's potential to offer multidimensional relief to patients with AD in everyday clinical practice.

Glycaemic control and adult height: a nationwide Swedish cohort study on childhood type 1 diabetes

Abstract Aims To assess adult height outcomes across levels of glycaemic control in children and adolescents with type 1 diabetes, as well as to investigate the impact of sex, age at disease onset, and timing of glycaemic control in relation to puberty. Methods In this population-based Swedish cohort study, we collected data on glycaemic control and height from specialist healthcare visits of all individuals with childhood-onset type 1 diabetes in the National Diabetes Register. Using linear and logistic regression, we compared suboptimal (HbA1c 53–75 mmol/mol [7.0–9.0%]) and poor (HbA1c &amp;gt;75 mmol/mol [&amp;gt;9.0%]) to optimal (HbA1c &amp;lt;53 mmol/mol [&amp;lt;7.0%]) glycaemic control in relation to final adult height and the risk of short stature. Results Poor glycaemic control was associated with lower final adult height (-2.91 cm [95% CI - 3.48, -2.33] for males, -1.83 cm [-2.42, -1.23] for females) as well as a higher risk of short stature in males (odds ratio 1.90 [1.07, 3.35]) but not in females (0.73 [0.36, 1.51]). For females, adult height was only lower among those with type 1 diabetes since before puberty and if the poor glycaemic control occurred before puberty. For males, adult height was lower irrespective of their age at diabetes onset, but only if they had poor glycaemic control during or after puberty. Conclusions Poor glycaemic control after the onset of type 1 diabetes, compared to optimal control, is associated with lower adult height in males and females. The prepubertal period seems to be more critical for females than males.

Metabolic and bariatric surgery for adolescents with severe obesity: Benefits, risks, and specific considerations

International and national guidelines recommend metabolic and bariatric surgery (MBS) as a treatment option for adolescents with severe obesity, but few countries offer MBS to adolescents in routine clinical care. This narrative review summarizes existing adolescent MBS guidelines and the available underpinning evidence. Two randomized trials and additional prospective studies have demonstrated efficacy and safety in adolescent MBS, and the health benefits appear to be similar or superior to outcomes in adults. However, there are specific challenges regarding the intervention during adolescence related to decision-making capacity and a peak in risk-taking behavior. Adolescents with severe obesity have—as a group—a mental health vulnerability, and specific nutritional concerns need to be addressed in relation to MBS. This review also describes how study findings can be translated into clinical care. We use Sweden as an example, where the National Board of Health and Welfare recommends MBS for selected adolescents with severe obesity aged 15 years or older. We present practical advice for implementing and integrating MBS in adolescents in the framework of multidisciplinary pediatric and adolescent care for obesity.

Successful aging and older adults’ health outcomes through outdoor-based interventions like adventure therapy: A scoping review

AbstractOutdoor-based interventions, like adventure therapy, have numerous positive benefits, yet current literature is inconclusive on this topic regarding older adult participants. Therefore, the purpose of this study is to explore health outcomes for older adults engaging in outdoor-based interventions, including adventure therapy. A scoping review was conducted using 20 databases and specific journals, and a staged blinded review. The resulting data was synthesized into three groups that align with the components of successful aging: Prevention of disease/disability, retaining good physical/cognitive functioning, and active engagement. From these findings, implications for allied health professionals and experiential educators are discussed, and future research directions are recommended.

Direct Oral Anticoagulants Versus Warfarin in Patients With Isolated Heparin-Induced Thrombocytopenia or Heparin-Induced Thrombocytopenia With Thrombosis.

No existing studies compare oral anticoagulants to treat heparin-induced thrombocytopenia with or without thrombosis (HIT/HITT). This retrospective study evaluated thrombotic and bleeding outcomes in adults treated for HIT/HITT with a direct oral anticoagulant (DOAC) or warfarin between 2012 and 2023 within the Ochsner Health System. Patients with mechanical heart valves, valvular atrial fibrillation, antiphospholipid syndrome, active malignancy, or venous thromboembolism (VTE) within the previous 6 months were excluded. The primary outcome was a composite of new or progressive VTE or arterial thromboembolism. Secondary outcomes included major and clinically relevant non-major bleeding, duration of hospitalization, time to platelet recovery, and incidence of skin necrosis, gangrene, and amputation. Forty-nine patients receiving a DOAC and 30 patients receiving warfarin were included. Baseline characteristics were similar between cohorts. There were non-statistically significant increased rates of both the primary outcome (8.9% vs. 4.3%, p = 0.65) and the composite bleeding outcome (32.7% vs. 23.3%, p = 0.37) in the DOAC cohort. Larger, prospective studies are needed to confirm these findings.

The contribution of attention-deficit/hyperactivity disorder polygenic load to metabolic and cardiovascular health outcomes: a large-scale population and sibling study.

Emerging evidence suggests that ADHD is associated with increased risk for metabolic and cardiovascular (cardiometabolic) diseases. However, an understanding of the mechanisms underlying these associations is still limited. In this study we estimated the associations of polygenic scores (PGS) for ADHD with several cardiometabolic diseases and biomarkers. Furthermore, we investigated to what extent the PGS effect was influenced by direct and indirect genetic effects (i.e., shared familial effects). We derived ADHD-PGS in 50,768 individuals aged 18-90 years from the Dutch Lifelines Cohort study. Using generalised estimating equations, we estimated the association of PGS with cardiometabolic diseases, derived from self-report and several biomarkers measured during a physical examination. We additionally ran within-sibling PGS analyses, using fixed effects models, to disentangle direct effects of individuals' own ADHD genetic risk from confounding due to indirect genetic effects of relatives, as well as population stratification. We found that higher ADHD-PGS were statistically significantly associated with several cardiometabolic diseases (R-squared [R2] range = 0.03-0.50%) and biomarkers (related to inflammation, blood pressure, lipid metabolism, amongst others) (R2 range = 0.01-0.16%) (P < 0.05). Adjustment for shared familial factors attenuated the associations between ADHD-PGS and cardiometabolic outcomes (on average 56% effect size reduction), and significant associations only remained for metabolic disease. Overall our findings suggest that increased genetic liability for ADHD confers a small but significant risk increase for cardiometabolic health outcomes in adulthood. These associations were observable in the general population, even in individuals without ADHD diagnosis, and were partly explained by familial factors shared among siblings.

Young adults' circulating FGF23 and α-klotho and their relationship with habitual dietary acid load and phosphorus intake during growth.

The bone-derived hormone FGF23, primarily secreted by osteocytes, is a major player in the regulation of phosphate homeostasis. It becomes upregulated by increased circulating phosphate concentration, e.g. due to elevations in phosphorus intake (P-In) or alterations in habitual dietary acid load. The present study aimed to investigate whether long-term endogenous acid production or a habitual high phosphorus intake during childhood and adolescence may be prospectively related with altered adult levels of FGF23 and the FGF23-related metabolite α-klotho. Urinary phosphate excretion (PO4-Ex), net acid excretion (NAE), and potential renal acid load (uPRAL) were analyzed in 24-h urine samples (n = 3369) collected from 343 healthy 3-17 years old participants of the DONALD Study (Dortmund, Germany) to assess, biomarker-based, P-In and habitual dietary acid load. Circulating FGF23, α-klotho, and further blood parameters were additionally examined in young adulthood. Individual means of standard-deviation-scores were calculated for 24-h urinary biomarker excretions and anthropometrics longitudinally determined between ages 3-17 years. Multivariable linear regression was used to analyze the prospective relations of pre-adulthood PO4-Ex, NAE, and uPRAL with the adulthood outcomes FGF23 and α-klotho. After adjusting for growth period-related covariates and adulthood confounders only for P-In during growth, i.e., PO4-Ex, but not for NAE and uPRAL, a significant positive association (p = 0.03) with FGF23 and an inverse trend (p = 0.10) with the FGF23-α-klotho ratio were observed. Neither PO4-Ex, nor NAE or uPRAL were associated with soluble α-klotho levels in adulthood. The prospective relationships of long-term assessed 24-h phosphaturia and habitual dietary acid load during growth with adult circulating, phosphate-adjusted FGF23 strongly suggest that children´s habitually higher P-In does unfavorably affect adult FGF23-α-klotho axis.

Abstract 4117397: SGLT2i And Cardio-Renal Outcomes In Type 2 Diabetes Mellitus: A Systematic Review And Meta Analysis.

Background: Diabetes Mellitus (DM) significantly impacts global health through cardiovascular and renal complications. SGLT2 inhibitors (SGLT2i) have emerged as beneficial for cardiovascular outcomes in Type 2 Diabetes Mellitus (T2DM). However, only few studies report outcomes related to renal function. Aim: This study aims to analyse the efficacy of SGLT2i on cardiorenal outcomes in adults with T2DM. Methods: A systematic review and meta-analysis, following PRISMA-2020 guidelines was conducted. We evaluated the efficacy of SGLT2i on cardiorenal outcomes in adults with T2DM. We included randomized controlled trials(RCT) and post hoc analyses that compared SGLT2i with placebo, focusing on cardiovascular mortality, nonfatal myocardial infarction, nonfatal stroke, heart failure hospitalizations, and renal outcomes such as the progression of albuminuria and the decline of eGFR. Dichotomous outcomes were calculated using relative risk (RR) with 95% confidence interval (CI). Results: We identified 2753 studies, registered in PubMed(=788), Embase(n=538), WoS(n=369), Scopus(n=908), and Cochrane(n=150). We included 11 studies 6 RCT and 7 Post Hoc Analysis, sample size of 50.653 patients. Meta-analysis showed that SGLT2i improve cardiovascular outcomes such as reduced cardiovascular mortality (RR 0.84 [95% CI 0.73–0.97] p=0.02), heart failure hospitalizations (RR 0.65 [95%CI 0.54–0.77]p&lt;0.00001), and their composites outcomes. Furthermore, renal outcomes with SGLT2i significantly improve Urinary Albumin-to-Creatinine Ratio (RR1.10 [95%CI 1.03–1.18]p=0.004), Improvement of the decline of the eGFR (RR1.08 [95%CI 1.04–1.11] p&lt;0.00001) and progression of albuminuria (RR 0.69[95%CI 0.66–0.72]p&lt;0.00001). Slower Doubling of serum creatinine (RR 0.71 [95% CI 0.61–0.82] p&lt;0.00001), end-stage kidney disease (RR 0.66 [95% CI 0.53–0.83] p=0.0003). Reduced Acute Kidney Injury (RR 0.72 [95% CI 0.58–0.89] p=0.002) and renal impairment (RR 0.57 [95% CI 0.34–0.95] p=0.03). Regarding death from renal causes, we identified a 46% relative reduction in the risk in SGLT2i group, although was not statistically significant (RR 0.54 [95% CI: 0.23, 1.27] p=0.16). The observed heterogeneity across studies calls for careful application of these results to individual patients. Conclusion: SGLT2i confers notable advantages in managing cardiorenal complications in T2DM, demonstrating a reduction in cardiovascular mortality and heart failure hospitalizations and offering a nephroprotective effect.

Rocatinlimab Improves Patient-Reported Outcomes in Adults with Moderate-to-Severe Atopic Dermatitis: Results from a Double-Blind Placebo-Controlled Phase2b Study.

In adults with moderate-to-severe atopic dermatitis (AD), rocatinlimab demonstrated significant and progressive improvement in clinical measures of disease severity compared with placebo. This post hoc analysis of a phase2b study was undertaken to understand the disease burden and to assess the impact of rocatinlimab on patient-reported outcomes (PROs). This analysis used baseline data from a multicenter, randomized, double-blind study of adults with moderate-to-severe AD, who completed a Worst Pruritus numerical rating scale (NRS), Sleep Disturbance NRS, and the Dermatology Life Quality Index (DLQI). A mixed model for repeated measures was used to estimate changes in PRO scores from baseline; scores were also compared with clinically meaningful change benchmarks. The analysis included 267 subjects, mean (SD) age 37.9 (14.7) years, 40.8% female; 55.1% grade3 and 44.9% grade4 Investigator Global Assessment for AD. Mean (SD) scores were: Worst Pruritus NRS 7.5 (1.9), Sleep Disturbance NRS 5.5 (2.9), DLQI total score 12.6 (7.1). Worst Pruritus and Sleep NRS scores had low positive correlations with SCORing AD (SCORAD) score (r = 0.44, r = 0.45 respectively) and negligible correlations with Eczema Area and Severity Index (EASI) score and area affected (r < 0.30). DLQI score varied by sex, study country, race, age, longer disease duration, disease severity (EASI and SCORAD), presence of asthma, and Worst Pruritus NRS, Sleep disturbance NRS, and DLQI scores. Rocatinlimab showed benefit on all three PROs, with significant improvements from baseline at the end of the double-blind period (week18) and active treatment extension (week36). Benefits were maintained over 20weeks' post-treatment follow-up. The benefit of rocatinlimab treatment on PROs is rapid and maintained for at least 20weeks following treatment completion. This analysis demonstrates the importance of characterizing the burden of moderate-to-severe AD from the patient's perspective, alongside clinical disease measures, to develop a fuller picture of treatment benefit. ClinicalTrials.gov identifier, NCT03703102.

Abstract 4138672: Blood Pressure and Cardiovascular Outcomes in Adults with Diabetes and Chronic Kidney Disease

Background: Most international guidelines recommend intensive blood pressure (BP) targets (e.g., &lt;130/80 mm Hg) for patients with chronic kidney disease (CKD). However, the data supporting these recommendations are limited, particularly for those with concomitant diabetes. Hypothesis: Systolic BP (SBP) &lt;130 mm Hg and diastolic BP (DBP) &lt;80 mm Hg are associated with a reduced risk of cardiovascular disease (CVD) in adults with diabetes and CKD. Aims: To determine the association of BP with incident CVD risk among adults with diabetes and CKD. Methods: From a Korean nationwide health screening database, we identified 373,966 adults aged 20-79 with both diabetes and CKD who: (1) underwent baseline health examinations in 2009-2013; (2) had ≥3 BP measurements; and (3) did not have CVD at baseline. The associations of baseline average SBP and DBP with CVD risk were assessed using multivariable-adjusted cause-specific Cox models. The primary outcome was CVD event, defined as a composite of myocardial infarction, stroke, heart failure, or death from CVD. Results: The median (Q1-Q3) age of the participants was 62 (53-70) years; 40.8% were female. Over a median follow-up of 10.2 years, a total of 40,781 incident CVD events occurred. Compared with SBP 130 to &lt;140 mm Hg as the referent group, the multivariable-adjusted HRs (95% CIs) for CVD event in the SBP ≥150 mm Hg, 140 to &lt;150 mm Hg, 120 to &lt;130 mm Hg, and &lt;120 mm Hg groups were 1.34 (1.29-1.39), 1.11 (1.08-1.14), 0.89 (0.87-0.91), and 0.77 (0.74-0.80), respectively. Compared with DBP 80 to &lt;90 mm Hg as the referent group, the HRs (95% CIs) in the DBP ≥100 mm Hg, 90 to &lt;100 mm Hg, 70 to &lt;80 mm Hg, and &lt;70 mm Hg groups were 1.70 (1.56-1.85), 1.19 (1.15-1.24), 0.88 (0.86-0.90), and 0.83 (0.80-0.87), respectively (Figure A). SBP &lt;130 mm Hg and DBP &lt;80 mm Hg were each associated with a reduced CVD risk in a log-linear manner (Figure B, Figure C). The findings were consistent when examining kidney instead of cardiovascular outcomes. Conclusion: Among patients with diabetes and CKD, SBP below 130 mm Hg and DBP below 80 mm Hg were associated with a reduced risk of CVD.

Clinical and Biochemical Outcomes in Transgender Individuals Undergoing Hormone Therapy: Protocol for a Systematic Review.

Monitoring of various clinical outcomes and parameters, such as lipid levels, is recommended in transgender individuals undergoing hormone therapies. However, comprehensive data to inform these recommendations is scarce. This study aims to conduct a systematic review and meta-analysis to synthesize evidence from existing literature on the effect of exogenous hormone therapy on clinical and biochemical outcomes for transgender adolescents and adults. We will search multiple electronic databases and will include prospective and retrospective observational studies with and without a control group. The study population will include transgender individuals undergoing hormone therapy with testosterone or estrogen. Comparisons will include age-matched, cisgender individuals and changes from baseline. Primary outcomes include changes in or the development of abnormal lipid parameters. Secondary outcomes include BMI, weight, height, and blood pressure for age, serum testosterone or estrogen levels, and development of disease including hypertension, diabetes, fatty liver disease, obesity, adverse cardiac events, as well as all-cause mortality. The meta-analysis will pool the studies where applicable, and meta-regressions will be conducted to evaluate effect modifiers. The GRADE (Grading of Recommendations Assessment, Development, and Evaluation) approach will be used to evaluate the overall certainty of evidence. We will summarize the selection of the eligible studies using a PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) flowchart. The results will be presented in a table summarizing the evidence. Data collection is ongoing, and the paper is expected to be published in Spring 2025. This systematic review will summarize and evaluate the evidence of the clinical and biochemical outcomes associated with hormone therapies for transgender individuals. PROSPERO CRD42024483138; https://tinyurl.com/yc4sfvnb. PRR1-10.2196/57931.

Abstract 4126650: Prognostic Value of Femoral-Ankle Pulse Wave Velocity for Cardiovascular Outcomes in Older Adults: The Atherosclerosis Risk in Communities (ARIC) study

Background: Carotid-femoral pulse wave velocity (cfPWV) is a representative measure of central arterial stiffness and an independent predictor of cardiovascular disease (CVD). Femoral-ankle PWV (faPWV) represents peripheral arterial stiffness, but its association with CVD has not been specifically studied. Aim: To compare faPWV and cfPWV regarding their associations with CVD outcomes. Methods: We analyzed 3,402 ARIC participants without prior heart failure (HF), coronary heart disease (CHD), or stroke at visit 5 (2011-13) (mean age 74.8 [SD 4.9] years, 36.1% male, and 78.0% White). faPWV and cfPWV were measured by Omron VP-1000 Plus. The outcomes of interest were composite and individual outcomes of CVD (HF, CHD, and stroke). We ran unadjusted and multivariable Cox proportional hazards models. Results: During a median follow-up of 9.0 years, there were 607 CVD events. Overall, faPWV showed an inverse association with CVD (Table). P-for-trend reached statistical significance in Models 1 and 2 and was borderline significant in Model 3 (p=0.077). In contrast, as anticipated, cfPWV was positively associated with CVD in all Models, although the association was somewhat attenuated in Model 3 (p-for-trend=0.045 and hazard ratio [HR] for top vs. bottom quartile 1.22 [95%CI 0.95-1.56]). Given their opposite patterns, we explored the ratio of cfPWV and faPWV (“cf/fa ratio”) and found that its association with CVD appeared stronger (p-for-trend=0.004 and HR for top vs. bottom quartile 1.37 [1.08-1.74]) than cfPWV. When each CVD subtype was examined separately, HF showed most consistent associations with our stiffness measures, and only the cf/fa ratio remained significant for HF up to Model 3 (p-for-trend=0.010 and HR for top vs. bottom quartile 1.40 [1.03-1.90]). Conclusions: faPWV was inversely associated with CVD, and cf/fa ratio appeared more strongly associated with CVD compared to cfPWV. Our findings indicate distinct prognostic implications of central vs. peripheral arterial stiffness and suggest cf/fa ratio as a new stiffness measure predicting CVD.

Abstract Su804: Use of Machine Learning Models to Predict Neurologically Intact Survival for Advanced Age Adults Following Out-of-hospital Cardiac Arrest

Background: We recently published a multivariable logistic regression model that successfully predicted neurologic outcomes in advanced age adults (≥ 65 years old) who achieve return of spontaneous circulation following out-of-hospital cardiac arrest (OHCA). Prior to externally validating this model, we sought to compare the predictive performance of our logistic regression model against common machine learning (ML) algorithms using the same dataset. Methods: We performed a retrospective observational analysis of the Cardiac Arrest Registry to Enhance Survival database from 2013-2021. All non-traumatic OHCA occurring in adults (≥65 years) who survived to hospital admission were included. The primary outcome measure was neurologically intact survival defined as a cerebral performance category (CPC) score of 1 or 2 at hospital discharge. Our original logistic regression model was compared to Boosted Trees and Decision Tree ML algorithms and assessed using accuracy, Area Under the Receiver Operating Characteristic Curve (AUC-ROC) and Area Under the Precision-Recall Curve (AUC-PR). The model variables included age, gender, race/ethnicity, location, witnessed status, who initiated cardiopulmonary resuscitation, whether an automated external defibrillator was applied prior to emergency medical services arrival, and first monitored rhythm. Results: A total of 83,561 OHCA were included. Median age was 75 years (IQR 69-82), 58.9% were male, 53% were White, 67% experienced an OHCA at home, 52% were witnessed by a bystander, 44% received bystander CPR, and 34% were found in shockable rhythm. Neurologically intact survival (CPC 1 or 2) occurred in 23% of patients. The logistic regression model had an accuracy of 79.6%, AUC-PR 0.542, and AUC-ROC of 0.774. The Boosted Trees model had an accuracy of 79.2%, AUC-PR 0.555, and AUC-ROC of 0.774. The Decision Tree Model had an accuracy of 79.3%, AUC-PR 0.490, and AUC-ROC of 0.717. Conclusion: Boosted Trees and Decision Tree ML models performed comparably to the logistic regression model in predicting favorable versus unfavorable neurological outcomes following successful resuscitation from OHCA in advanced-age adults. Given their similar performance, logistic regression may be preferred for its simplicity and interpretability over alternative ML models. Future efforts to improve and ultimately externally validate the model are warranted.

Abstract 4137620: Serum Acylcarnitines Predict Longitudinal Deteriorations in Cardiac Function and Adverse Outcomes in Older Adults

Background: Circulating acylcarnitines (ACs), biomarkers of mitochondrial β-oxidative function, are linked to cardiovascular diseases (CVD) yet the extent to which ACs relate to prospective cardiac aging remains uncertain. We investigate the longitudinal associations between ACs, cardiac function, and clinical outcomes. Methods: A population-based sample of community older adults without CVD underwent baseline serum metabolomic profiling and interval echocardiography at five years. Incident hospitalizations were prospectively tracked from 2014 to 2021. Multiple linear regression adjusted for significant clinical variables. Results: Of 202 participants (baseline 65±11.9 years, 49.3% women), we observed interval increases in risk factors (hypertension 39% vs 52.2% p&lt;0.001; dyslipidemia 39% vs 50% p=0.034; diabetes 11.7% vs 18.8% p=0.035; smoking 13.2% vs 24.7% p=0.003; waist circumference 81±10.1 vs 86±9.9cm p&lt;0.001) during follow-up (4.9±0.4 years). These changes paralleled E/e’ increases (8.9±2.6 vs 11.1±3.3 p&lt;0.001) and E/A decreases (1.09±0.4 vs 1.0±0.4 p&lt;0.001). Baseline C8:1 (β=0.182 p=0.011), C22:3 (β=0.148 p=0.047), C22:5 (β=0.210 p=0.003), C5:1 (β=-0.142 p=0.048), and C16-OH (β=-0.156 p=0.028) levels were associated with E/e’ change over time while C6 (β=0.163 adj. p=0.019), C8:1 (β=0.137 adj. p=0.047), C10:2 (β=0.153 adj. p=0.035), C14:3 (β=0.147 adj. p=0.031), and C16:1-OH/C14:1-DC (β=0.158 adj. p=0.022) were associated with E/A change. At follow-up, baseline C8:1 (β=0.178 adj. p=0.006) and C10:3 (β=0.145 adj. p=0.024) were associated with E/e’ while C4-DC/C6-OH (β=-0.004 adj. p=0.034) was associated with E/A. Baseline C22:2 predicted incident hospitalizations (HR=1.20 95%CI 1.03-1.39, adj. p=0.018). Conclusion: Circulating ACs independently predicted declining cardiac function and adverse outcomes over five years among older adults without CVD. The prognostic effect of ACs should be translated to strategies targeting mitochondrial health in cardiac aging prevention.

Artificial intelligence driven clustering of blood pressure profiles reveals frailty in orthostatic hypertension.

Gravity, an invisible but constant force , challenges the regulation of blood pressure when transitioning between postures. As physiological reserve diminishes with age, individuals grow more susceptible to such stressors over time, risking inadequate haemodynamic control observed in orthostatic hypotension. This prevalent condition is characterized by drops in blood pressure upon standing; however, the contrary phenomenon of blood pressure rises has recently piqued interest. Expanding on the currently undefined orthostatic hypertension, our study uses continuous non-invasive cardiovascular data to explore the full spectrum of blood pressure profiles and their associated frailty outcomes in community-dwelling older adults. Given the richness of non-invasive beat-to-beat data, artificial intelligence (AI) offers a solution to detect the subtle patterns within it. Applying machine learning to an existing dataset of community-based adults undergoing postural assessment, we identified three distinct clusters (iOHYPO, OHYPO and OHYPER) akin to initial and classic orthostatic hypotension and orthostatic hypertension, respectively. Notably, individuals in our OHYPER cluster exhibited indicators of frailty and sarcopenia, including slower gait speed and impaired balance. In contrast, the iOHYPO cluster, despite transient drops in blood pressure, reported fewer fallers and superior cognitive performance. Surprisingly, those with sustained blood pressure deficits outperformed those with sustained rises, showing greater independence and higher Fried frailty scores. Working towards more refined definitions, our research indicates that AI approaches can yield meaningful blood pressure morphologies from beat-to-beat data. Furthermore, our findings support orthostatic hypertension as a distinct clinical entity, with frailty implications suggesting that it is worthy of further investigation.

Personality trait change during adolescence as a predictor of later substance use, depressive symptoms, and perceived maturity

Adolescence is considered a critical period for understanding how individuals develop their self-concepts and personality dispositions, with the assumption that these changes presage important life outcomes. However, this tenet has been infrequently tested; few studies have included rigorous, frequent assessment of personality traits during adolescence, particularly from multiple rater perspectives. The current study utilizes data from the Oregon Youth Substance Use Project (OYSUP; N = 951), which followed students throughout their school years into early adulthood. Student- and teacher-reports of the Big Five personality traits were assessed yearly from grades 7 to 10, as well as drug use, well-being, and maturity outcomes later in emerging adulthood. Using latent growth curve models and true intraindividual change score models, results indicated that youth exhibited relative stability but significant trait changes on multiple domains during adolescence. Moreover, individual differences in these changes predicted likelihood for drug use and depressive symptoms later, as well as the students’ perceptions of their status as being developed adults, even when accounting for initial trait levels. Findings differed somewhat between youth- and teacher-reports of personality, with both demonstrating value for predicting young adult outcomes, indicating multiple perspectives of personality development are important.

What will my life be like when I am 25? How do children's social class contexts predict their imagined and actual futures?

AbstractChildren use school as a way to imagine and strive toward their futures. We analyzed thousands of essays written by children in Britain in the late 1960s about what their lives would be like as adults. We used a bottom‐up approach to explore naturally occurring topics in these essays and tested how these topics varied with children's social class context and their adult outcomes. Higher education was the most prevalent topic in these children's essays; children whose fathers—and maternal grandfathers—had higher‐status occupations were especially likely to write about this, as well as about interests in teaching, medicine, and the military. Children in lower class contexts were especially likely to write about making money, but also about family and daily responsibilities. We further found that—controlling for family background—children who wrote more about higher education and less about money‐making tended to achieve education, status, and income.

Stress tests and biomarkers of resilience: Proceedings of the second state of resilience science conference.

The "Stress Tests and Biomarkers of Resilience" conference, hosted by the American Geriatrics Society and the National Institute on Aging, marks the second in a series aimed at advancing the field of resilience science. Held on March 4-5, 2024, in Bethesda, Maryland, this conference built upon the foundational work from the first conference, which focused on defining resilience across various domains-physical, cognitive, and psychosocial. This year's gathering centered around three factors: the biology that underlies resilient outcomes; the social, environmental, genetic, and psychosocial factors that impact that resilience biology; and the biomarker testing and imaging that predicts resilient outcomes for older adults. The presentations and discussions around these topics were underscored by considerations around the many impacts of social determinants of health on resiliency interventions, and by advances in the modern training and research methodologies that influence data collection and experiment design.