Adult Age Research Articles

Higher Long-Term Visit-to-Visit Blood Pressure Variability Is Associated With Severe Cerebral Small Vessel Disease in the General Population.

Long-term visit-to-visit blood pressure (BP) variability is linked to various diseases, but its impact on cerebral small vessel disease (cSVD) burden, and its features remains uncertain. We analyzed 1284 participants from the Kailuan cohort (2006-2022). Visit-to-visit systolic BP (SBP), diastolic BP (DBP), and pulse pressure (PP) variability were categorized into tertiles (low, middle, high). Magnetic resonance imaging identified white matter hyperintensities (WMH), lacunae of presumed vascular origin (LA), cerebral microbleeds (CMBs), and visible perivascular spaces (PVS). Total cSVD burden was classified as none (0), mild (1), moderate (2), or severe (3-4) based on the presence of these features. Logistic regression estimated odds ratios (ORs) and 95% confidence intervals (CIs). High SBP variability was associated with moderate cSVD burden (OR = 1.89, 95% CI: 1.09-3.29) and PVS (OR = 1.62, 95% CI: 1.10-2.39). High DBP variability was associated with LA (OR = 1.74, 95% CI: 1.06-2.84). High PP variability showed a significant risk for severe cSVD burden (OR = 2.49, 95% CI: 1.34-4.63). These associations were modified by age and hypertension status. Among young adults (age < 60 years), high PP variability was associated with severe cSVD burden (OR = 3.33, 95% CI: 1.31-8.44), LA (OR = 3.02, 95% CI: 1.31-6.93), and PVS (OR = 1.86, 95% CI: 1.20-2.88). The risk effects of SBP and PP variability on cSVD burden were significant only in participants with hypertension. High long-term visit-to-visit BP variability (BPV), particularly in combination with hypertension, is a significant risk factor for total cSVD. Special attention should be given to PP variability in younger adults.

The Unique Challenge of Coronary Artery Disease in Adult Patients with Congenital Heart Disease

Advances in medical and surgical interventions have resulted in a steady increase in the number of patients with congenital heart disease (CHD) reaching adult age. Unfortunately, this ever-growing population faces an added challenge: an increased risk of acquiring coronary artery disease. This review provides insight into the complex interactions between coronary artery disease and CHD in adults. We describe the peculiar features of cardiac anatomy in these patients, the possible role cardiac sequelae may play in an increased risk of myocardial ischemia, and the diagnostic challenges in this patient group. Furthermore, this review outlines the risk factors and potential mechanisms of accelerated atherosclerosis in adults with CHD by pointing out areas where current knowledge is incomplete and highlighting areas for further research. The review concludes by examining potential management strategies for this particular population, emphasizing the necessity for a multidisciplinary approach. Understanding the unique coronary risks that adults with CHD experience can enhance patient care and improve long-term results.

Association between sleep duration and three obesity indicators among middle-aged and elderly adults: findings from the NHANES 2005–2014

ObjectiveObesity has emerged as a worldwide problem. In recent years, it has been verified that there is an association between sleep duration and obesity indicators. This provides a new approach to control obesity. In this study, the relationship between duration of sleep and body mass index (BMI), waist circumference (WC), and waist-to-height ratio (WHtR) among Americans ≥45 years old was investigated.MethodsData was collected from the National Health and Nutrition Examination Survey (NHANES) between 2005 and 2014. The link between sleep duration and obesity indicators was analysed using multiple regression models and weighted smoothed curve fitting. Subgroup analysis was conducted to assess the consistency of the connection between sleep duration and obesity indicators across various groups.ResultsThis study involved 7,118 males and 7,265 females, with an average age of 62.09. After total adjustment, sleep duration was negatively correlated with BMI (β = −0.19, 95%CI: −0.26, −0.12), WC (β = −0.36, 95%CI: −0.53, −0.19) and WHtR (β = −0.27, 95%CI: −0.38, −0.17). Subgroup analyses revealed more significant negative associations between sleep duration and BMI, WC, and WHtR among non-Hispanic White participants, and those without diabetes and hypertension.ConclusionSleep duration was significantly negatively associated with BMI, WC, and WHtR, suggesting that longer sleep duration may contribute to lower obesity indicators in middle-aged and elderly Americans. Subgroup analysis showed that their negative correlation differed between races, diabetes, or hypertension status. However, additional prospective studies are required to validate these findings and investigate potential causal relationships.

Impact of serum carotenoids on cardiovascular mortality risk in middle-aged and elderly adults with metabolic syndrome

BackgroundMetabolic syndrome (MetS), characterized by abdominal adiposity, hypertension, hyperglycemia, and dyslipidemia, is associated with dysregulated immune function, elevated oxidative stress, and chronic low-grade inflammation. Aging exacerbates insulin resistance and the prevalence of MetS. Dietary antioxidants, such as carotenoids, may play a role in preventing cardiovascular disease (CVD) mortality, but evidence remains mixed, particularly among middle-aged and elderly individuals with MetS.MethodsWe analyzed data from 6,601 participants aged 40 years and above with MetS from the National Health and Nutrition Examination Survey (NHANES) III (1988–1994) and NHANES 2001–2006 cycles. Serum concentrations of α-carotene, β-carotene, lycopene, β-cryptoxanthin, and combined lutein/zeaxanthin were quantified. Participants were followed for a median of 16.8 years. Cox proportional-hazards models were used to assess the association between serum carotenoid concentrations and CVD mortality risk, with adjustment for potential confounders.ResultsDuring the follow-up period, 1,237 CVD deaths were identified. Analysis revealed an inverse dose–response relationship between serum lycopene levels and cardiovascular mortality risk. Compared to the lowest quartile, the multivariable-adjusted hazard ratios (95% confidence intervals) for ascending quartiles of serum lycopene were 0.84 (0.71, 1.00), 0.87 (0.74, 1.03), and 0.77 (0.61, 0.97), with a significant trend (p = 0.039). No significant associations were observed for other carotenoids.ConclusionIn this prospective cohort study of 40-year-old and older individuals with MetS, we observed an inverse association between serum lycopene levels and CVD mortality risk.

Acquired and genetic drivers of C3 and C5 convertase dysregulation in C3 glomerulopathy and immunoglobulin-associated MPGN.

Dysregulation of the alternative pathway of complement plays a central role in the pathophysiology of C3 Glomerulopathy (C3G). Various autoimmune and genetic factors targeting the alternative pathway have been associated to both C3G and primary Immunoglobulin-associated Membranoproliferative Glomerulonephritis (Ig-MPGN), suggesting shared pathophysiological mechanisms. This review highlights the wide range of disease drivers identified that mainly target components or protein complexes of the alternative pathway, both in C3G and Ig-MPGN. Nephritic factors, which constitute a heterogeneous group of autoantibodies targeting the C3 or the C5 convertase, are the most common abnormalities. Monoclonal gammopathies are frequent in aging adults. They may promote complement activation and have in some cases also found to target alternative pathway regulatory proteins. Additionally, some patients with C3G and Ig-MPGN carry rare variants in genes encoding complement activating or regulating proteins of the alternative pathway. This review provides an informative overview of pathogenetic mechanisms associated with each abnormality, acting at different steps in the complement cascade. The diversity of targets involved in the C3G pathophysiology suggests the potential benefit of therapeutical approaches tailored to the underlying disease drivers, with a pivotal impact upstream or at the level of the C3 or C5 convertase activity.

Consumption of Sugar-Sweetened Beverages by Polish Young Adults: A Preliminary Study on the Importance of Sugar Tax Familiarity and Health Effects

Consumption of sugar-sweetened beverages (SSBs) contributes to the risk of developing overweight and obesity in children and adults. Thus, reducing free sugar is a globally recognized public health priority. The implementation of a sugar tax is one way of achieving this goal. This study aimed to investigate the relationship between familiarity with the sugar tax and its importance in reducing obesity, the perceived health consequences of SSBs, situations and reasons for consumption, and the frequency of SSB consumption. A cross-sectional study was conducted in May 2022 among 216 Polish adults (age 18–45). Hierarchical cluster analysis was used to identify three homogeneous clusters with regard to the perceived health consequences of consuming SSBs. A logistic regression model was used to verify the relationship between the frequency of SSB consumption (dependent variable) and other variables. Respondents with higher familiarity with the sugar tax (OR: 0.594; 95% CI: 0.42–0.85) and those in the “Unaware of disease” (OR: 0.437; 95% CI: 0.18–0.94) and “Disease-conscious” (OR: 0.484; 95% CI: 0.24–0.97) clusters were less likely to consume SSBs at least once per week than those in the “Moderately disease-conscious” cluster. Both the place of SSB consumption (i.e., restaurant—OR: 1.847; 95% CI: 1.14–3.64, work or university—OR: 3.217; 95% CI: 1.51–6.88, family home—OR: 2.877; 95% CI: 1.50–5.53) as well as a preference for their taste (OR: 4.54; 95% CI: 1.66–12.45) increased the chance of consuming SSBs at least once a week. In conclusion, it is necessary to continue educating the public about the health consequences of SSB consumption. The use of legislative measures (i.e., sugar tax) also contributes to reducing SSB consumption and can thus counteract the increasing obesity rate.

Comparison of inflammatory mediator cytokine responses to inactivated virus platform COVID-19 vaccines between elderly and young adult populations

The coronavirus disease 2019 (COVID-19) pandemic has encouraged global vaccine research, yet vaccine effectiveness in the elderly remains a concern due to immunosenescence. The aim of this study was to compare the cytokine response elicited by an inactivated virus-based COVID-19 vaccine between elderly and young adults, focusing on key cytokines involved in cellular and humoral immunity: tumor necrosis factor-alpha (TNF-α), interleukin (IL)-2, IL-6, IL-10, and interferon-gamma (IFN-γ). A cross-sectional study was conducted in the Jakarta-Bogor region of Indonesia from January 2023 to December 2023. The study population was divided into two age cohorts: elderly (60−85 years) and younger adults (30−40 years). Blood samples were collected twice, after the first booster dose and four weeks after the second booster dose. Serum cytokine concentrations were measured using Luminex assays with microparticles conjugated to monoclonal antibodies against TNF-α, IL-2, IL-6, IL-10, and IFN-γ. Comparisons of the cytokine levels were conducted using Student’s t-tests or Mann-Whitney U tests as appropriate. A total of 74 individuals were included, with 37 each in the elderly and young adult groups. The results showed significant differences in cytokine responses between the two age groups. After the first booster, the levels of IL-6 and IFN-γ were significantly higher in young adults compared to the elderly. After the second booster, the levels of IL-6 were still significantly higher in the young adult group compared to the elderly group (p=0.001). Data indicated that after the second booster dose, the levels of TNF-α increased significantly in the young adult group only (p=0.004), while the levels of IL-2 (p=0.040) and IFN-γ (p=0.006) increased in the elderly group only compared to after the first dose. IL-10 levels increased in both groups (both had p=0.020). This study highlights that young adults had stronger pro-inflammatory responses, while the elderly relied more on IL-2 and IFN-γ for T-cell immunity, suggesting the need for vaccination strategies for the elderly to optimize immune responses.

Abstract 4145877: Association of heat exposure with cardiovascular and all-cause hospitalizations among elderly adults in the United States

Background: Heat exposure is associated with an increase in cardiovascular mortality, particularly among older adults. Climate change has led to an increase in days with hot temperatures. The burden of hospitalizations associated with heat exposure is not well known. Methods: Data on all hospitalizations among Medicare beneficiaries 65 years of age and older in summer months (May through September) for 2016 to 2019 were obtained from Medicare Provider Analysis and Review (MEDPAR) files. Total daily cardiovascular and all-cause hospitalizations in each US county in the contiguous United States (US) were determined and daily county-level maximum heat index levels were obtained from the gridMET dataset. Counties with &lt;100 elderly residents were excluded. The association between daily heat index and hospitalizations was quantified using the distributive lag non-linear framework, with a generalized linear regression model – assuming a quasi-Poisson distribution. The model accounted for the lagged association, for up to 10 days, for daily heat index as well as covariates (ozone, particulate matter, and precipitation levels). Estimates from this model were used to determine the number and fraction of hospitalizations attributable to high temperatures on hot days. Hot days were defined as those with a heat index level in the 90 th percentile based on a county-specific historical period (1979-2015). Results: A total of 2085 counties (out of 3108) were included. The median threshold for hot days was 90.2°F (IQR 84.8°F to 95.5°F) [32.3°C (IQR 29.3°C to 35.3°C)]. Between 2016 and 2019, hot days were associated with 3044.0 (95% CI 2641.5 to 3380.9) or 0.067% (95% CI 0.058% to 0.074%) of all cardiovascular hospitalizations. Hot days were associated with 42132.2 (95% CI 41159.9 to 43082.1) or 0.22% (95% 0.21% to 0.225%) of all hospitalizations among Medicare beneficiaries. Conclusions: Between 2016 and 2019 days with high heat index levels were associated with higher levels of cardiovascular and all-cause hospitalizations among elderly Medicare beneficiaries across the contiguous US. As the number of hot days continues to increase due to climate change, the burden of heat related hospitalizations is likely to continue to increase.

Abstract 4138482: The burden of ischemic heart disease, hypertension, diabetes mellitus, and obesity among older Latino and Chinese adults with and without limited English proficiency

Background: An estimated 15% of Latinos and 34% of Chinese in the US have limited English proficiency (LEP). However, there is limited information on whether ischemic heart disease (IHD) and its risk factors (hypertension, HTN; diabetes mellitus, DM; and obesity) vary by LEP vs. non-LEP status in these ethnic groups. This information may be valuable for targeting healthcare interventions. METHODS: This cross-sectional study used data for Latino (79,588 men, 85,560 women), and Chinese (25,944 men, 32,586 women) adults aged 50-79 years who were members of a northern California health plan in 2018-2019. Age, sex, language preference, obesity (BMI ≥30 for Latino and ≥27.5 kg/m2 for Chinese), and IHD, HTN, and DM diagnoses were abstracted from electronic health records. LEP was defined as Spanish/Chinese vs. English (non-LEP) language preference. Prevalence was compared by LEP status within age-sex groups. Modified Poisson regression was used to estimate age-adjusted prevalence ratios. RESULTS: Among Latino men aged 50-64 (57,835, 39% LEP) and 65-79 (21,753, 30% LEP) and Chinese men aged 50-64 (14,751, 42% LEP) and 65-79 (11,193, 40.3% LEP) years, IHD prevalence was lower in LEP vs. non-LEP (Latino: 3.5% vs. 6.0% and 13.8% vs. 19.0%; Chinese: 3.6% vs. 5.8% and 11.9% vs. 14.5%). Similar trends were observed in women, but IHD prevalence was much lower. Among Latino and Chinese men, HTN and obesity prevalence was lower, but DM was similar. For women, HTN was similar, but DM was higher in LEP Latina (age 50-79) and Chinese adults (age 65-79), while obesity was lower in LEP Chinese but not Latina adults. Differences remained after adjusting for age (aPR). CONCLUSION: The burden of IHD, HTN, and obesity is similar or lower among LEP vs. non-LEP Latino and Chinese adults, while the burden of DM is higher for LEP vs. non-LEP Latina and Chinese women. These findings suggest that while DM prevalence is already high, acculturation is associated with higher risk of developing some chronic CVD conditions, underscoring the need for targeted healthcare interventions. Further research is needed to explore mechanisms driving these disparities and to develop culturally appropriate strategies to improve health outcomes.

Abstract 4137535: Gastrointestinal Bleeding Risk: Diltiazem versus Metoprolol in Patients on Rivaroxaban, Apixaban, or Dabigatran.

Introduction: A recent JAMA study by Ray et al., reported severe bleeding risk among older adults with atrial fibrillation (Afib) receiving apixaban or rivaroxaban along with diltiazem compared to metoprolol. Our investigation extended to evaluating the gastrointestinal (GI) bleeding risk associated with various Xa inhibitors and dabigatran when combined with either diltiazem, or metoprolol among all adults ages 18 and older. Method: We conducted a comparative retrospective cohort study using de-identified patient data obtained from the global network of the TriNetX platform, a comprehensive electronic health records system comprising 120 healthcare systems and more than 147 million patients worldwide. The cohorts were divided into patients treated with diltiazem vs. metoprolol while receiving apixaban or rivaroxaban (Cohort A), patients receiving metoprolol with apixaban vs. rivaroxaban treatment (Cohort B), patients treated with diltiazem with apixaban vs rivaroxaban (Cohort C), and patients treated with diltiazem vs metoprolol who received dabigatran (Cohort D). The risk of gastrointestinal hemorrhage among the cohorts was evaluated. Propensity score matching was employed to balance baseline characteristics between the cohorts, including age, sex, ethnicity, and comorbidities. Results: The risk of GI bleed in patients taking diltiazem with either apixaban or rivaroxaban was 6.3%, while the risk in patients taking metoprolol with either of these Xa inhibitors was 5.7 % (p&lt; 0.0001, 95%CI (1.074,1.111), RR 1.09. In patients taking metoprolol with apixaban, GI bleed risk was 5.4%, compared to 6.4% in those taking metoprolol with rivaroxaban (p&lt; 0.0001, 95% CI (0.838, 0.868), RR 0.85. For patients taking diltiazem with rivaroxaban, GI bleed risk was 7.3%, whereas it was 5.8% in those taking diltiazem with apixaban (p&lt; 0.0001, 95% CI (1.194, 1.265), RR 1.23. Risk of GI bleed in patients taking diltiazem with dabigatran was 7.4%% while it was 6.71% for patients treated with metoprolol and dabigatran (p&lt; 0.0011, CI 95% (1.038,1.16), RR 1.097) Discussion: Global patients’ data in this study suggested similar findings reported by Ray et al. Additionally, among all ages adults with Afib, treatment with metoprolol and apixaban was associated with the lower risk of GI bleed when compared with metoprolol and rivaroxaban. While the highest risk of GI bleed was associated with concurrent diltiazem and dabigatran use.

Abstract 4138698: Association of ALDH2*2 Variant with Increased HDL-Cholesterol Levels in East Asian Populations

Background: Mitochondrial aldehyde dehydrogenase 2 (ALDH2) is responsible for acetaldehyde metabolism with alcohol consumption. ALDH2 deficiency is a common enzymopathy – afflicting ~540 million East Asians. The ALDH2*2 variant, a missense mutation, significantly decreases enzyme activity. Recent studies suggest a potential link between ALDH2 deficiency and increased cardiovascular disease (CVD) risk. High-Density Lipoprotein cholesterol (HDL-C) is inversely associated with CVD and is known to increase with alcohol consumption. However, the impact of ALDH2*2 on HDL-C levels in East Asians remain unclear. Methods: Using the NIH All of Us cohort, we assessed HDL-C levels and reported alcohol consumption habits (never, &lt; once/week, &gt; once/week) at enrollment, as well as ALDH2 variant status among East Asian participants. Differences in HDL-C values were analyzed with Mann-Whitney U-tests. Results: Among 3,289 US Asian adults (age 46.8 ± 16.1 years; 58.8% female), median HDL-C was 54mg/dL [IQR 45, 67]. Of these, 2809 (85.4%) had wildtype ALDH2, and 480 (14.6%) had ALDH2*2 . Individuals with ALDH2*2 reported lower alcohol consumption (Figure A) but exhibited higher HDL-C levels (p=0.0002). The association was similar regardless of sex (Figure B). Conclusion: The ALDH2*2 variant is associated with higher HDL-C levels, despite lower alcohol consumption, indicating a possible independent influence on HDL-C levels. In the context of previous studies linking ALDH2 deficiency to adverse CVD outcomes, this suggests that ALDH2 may have a role independent of HDL-C levels, or it could affect HDL function rather than the HDL-C level itself.

Abstract 4140118: Identification of Obstructive and Non-Obstructive Hypertrophic Cardiomyopathy Patients Using Natural Language Processing in a Large Integrated Healthcare System

Introduction: Accurately identifying and characterizing patients with hypertrophic cardiomyopathy (HCM) is critical for population management and care optimization. Research Question: To develop natural language processing (NLP) algorithms to identify and characterize obstructive (oHCM) and non-obstructive (nHCM) HCM patients directly from echocardiograms, and to compare with the presence or absence of HCM-related diagnosis codes. Methods: We developed and validated NLP algorithms to identify HCM from all adult (age≥18yrs) echocardiograms performed from 2010-2019 in Kaiser Permanente Northern CA (KPNC), capturing measures of any HCM, HCM subtype, hypertrophy subtype, septal and posterior LV wall thickness, resting and stress/Valsalva LVOT gradients, and systolic anterior motion. We developed a rules-based algorithm (following AHA/ACC criteria) to classify patients as having HCM, including oHCM or nHCM subtypes, and possible HCM (defined as wall thickness ≥2cm without other criteria meeting an HCM definition). We evaluated the presence of HCM-related ICD-9/10 diagnosis codes among patients classified as HCM/non-HCM from echocardiograms using NLP, and linked baseline demographics and clinical parameters from our integrated electronic medical record. Results: Among 472,405 adults with echocardiograms, we identified 2,892 patients with HCM based upon NLP-derived measures (all NLP measures achieved &gt;95% positive predictive value and &gt;95% negative predictive value), including 1,585 (55%) with oHCM, 1,145 (40%) with nHCM, and 162 (6%) which could not be classified (Figure). Among those 2,892 patients, 1,283 did not have any associated HCM ICD-9/10 diagnosis codes (Table). Among 469,513 patients with no identified HCM from NLP-based algorithms, HCM ICD-9/10 diagnosis codes existed in 1,567 patients (Table). We also identified 4,593 patients with possible HCM by NLP, only 4.5% of whom had an associated HCM code. Among confirmed HCM patients by NLP, oHCM patients were slightly older (66 vs 61 yrs), more likely female (53% vs 43%), had similar mean septal wall thickness (1.7cm vs 1.7cm), but were more likely to have a septal hypertrophy subtype (46% vs 28%) compared to nHCM patients. Conclusions: Echocardiogram-based NLP methods can improve the identification of and care for HCM patients. Many patients with possible HCM may be underdiagnosed, representing an opportunity for quality improvement.

Abstract 4140198: Impact of Non-ST-segment elevation Myocardial Infarction on outcomes of Diabetic Ketoacidosis in Hospitalized Patients: A National Inpatient Sample Analysis

Introduction: Diabetes Mellitus (DM) has a broad spectrum of complications and is one of the leading 5 causes of hospital admissions in the US. Decompensated DM is associated with high mortality in hospitalized patients. Cardiac ischemia and related events are proposed to be increasingly prevalent in hospitalized patients with decompensated diabetes. Numerous studies and reports have suggested that elevation in troponin levels is associated with high mortality in such patients. Notably, there have only been a few studies that assessed the prevalence of NSTEMI (Non-ST segment elevation myocardial infarction) and its effect on outcomes in patients hospitalized with Diabetes ketoacidosis (DKA). Methods: We aimed to compare the outcomes of DKA in hospitalized adults (age &gt;18 years) with NSTMI with those without NSTEMI using the National Inpatient Sample (NIS) database from 2018 to 2020. NIS is the largest publicly available all-payer inpatient care database in the United States, containing data on more than seven million hospital stays. Results: There were a total of 1113295 hospitalizations identified with a diagnosis of DKA. Of these, 9860 (0.88%) patients had NSTEMI. The mean age of this subpopulation was 38.71 years. Among these patients, 48.59% were female, and 58.40% were male. We attempted to assess the impact of NSTEMI on the occurrence of complications such as cardiac arrest, acute renal failure (ARF), Acute liver failure (ALF), Acute heart failure (Acute HF), and acute respiratory failure in patients admitted with DKA. The results of this analysis are depicted in the table below. The cost of hospitalization for DKA with NSTEMI was $35878 higher and the length of stay was 50% longer compared to the patients with DKA without NSTEMI. The Odds ratio for mortality was 2.84 for patients with NSTEMI. Conclusions: Our analysis suggests that the occurrence of NSTEMI negatively impacts outcomes in DKA patients. The occurrence of primary outcomes assessed in this study (Cardiac arrest, ARF, ALF, Acute HF, and Acute respiratory failure) was significantly higher in DKA patients with concomitant diagnosis of NSTEMI. NSTEMI also increased the cost burden on hospitalizations for DKA.

Abstract 4131486: Cardiovascular Mortality in Children and Young Adults: Trends and Demographic Differences in the United States, 1999 to 2021

Background: Cardiovascular disease (CVD) mortality in the U.S. younger population is on the rise. However, limited data is available on CVD-related mortality trends in this population. Aim: This study aimed to assess the temporal trends and demographic differences in CVD-related mortality among the U.S. youth. Methods: The CDC WONDER dataset was analyzed from 1999-2021 for CVD-related mortality in children and young adults (age &lt;25 years). Socio-demographic data including gender, race/ethnicity, urbanization status and census region was acquired. Age adjusted mortality rates (AAMR) per 100,000 persons and annual percent changes (APCs) with 95% confidence interval (CIs) were calculated. Results: Between 1999-2021, a total 54,283 CVD-related deaths occurred among the youth in the U.S. The overall AAMR declined from 1999-2008 (APC, -1.15 [-3.4 to 0.53]), followed by sharp decrease from 2008-2012 (APC, -3.28 [-4.68 to 0.86]). The AAMR continued to decrease steadily from 2012 to 2019 (APC: -1.20, [-3.76 to -0.06]), followed by a sharp increase in from 2019 to 2021, (APC, 3.03 [-0.66 to 5.12]). Males consistently had higher AAMRs than females from 1999 (AAMR males: 2.99 vs females: 2.3) to 2021 (AAMR males: 2.39 vs females: 1.74). Non-Hispanic (NH) Black or African Americans had the highest AAMR in 2020 (3.68), followed by NH Whites (1.71), Hispanic or Latinos (1.59), and Asian and Pacific Islanders (1.2). AAMRs also showed significant variations across different regions (overall AAMR West 1.81; Northeast 1.93; Midwest 2.3; South 2.69). Metropolitan areas (2.23) consistently had lower mortality rates than nonmetropolitan areas (2.59). Conclusion: Our analysis revealed that CVD-related mortality in the youth declined from 1999-2019, followed by an increase in 2020 to 2021. Highest mortality rates were seen in males, Black or African Americans, Western region of the U.S, and nonmetropolitan areas. Tailored interventions are necessitated to decrease the burden of CVD-related mortality in these demographics among children and young adults in the United States.

Explaining deep learning models for age-related gait classification based on acceleration time series

BackgroundGait analysis holds significant importance in monitoring daily health, particularly among older adults. Advancements in sensor technology enable the capture of movement in real-life environments and generate big data. Machine learning, notably deep learning (DL), shows promise to use these big data in gait analysis. However, the inherent black-box nature of these models poses challenges for their clinical application. This study aims to enhance transparency in DL-based gait classification for aged-related gait patterns using Explainable Artificial Intelligence, such as SHapley Additive exPlanations (SHAP). MethodsIn this cross-sectional study, a total of 244 participants, comprising 129 adults and 115 older adults (age>65), were included. They performed a 3-min walking task while accelerometers were affixed to the lumbar segment L3. DL models, convolutional neural network (CNN) and gated recurrent unit (GRU), were trained using 1-stride and 8-stride accelerations, respectively, to classify adult and older adult groups. SHAP was employed to explain the models' predictions. ResultsCNN achieved a satisfactory performance with an accuracy of 81.4 % and an AUC of 0.89, and GRU demonstrated promising results with an accuracy of 84.5 % and an AUC of 0.94. SHAP analysis revealed that both CNN and GRU assigned higher SHAP values to the data from vertical and walking directions, particularly emphasizing data around heel contact, spanning from the terminal swing to loading response phases. Furthermore, SHAP values indicated that GRU did not treat every stride equally. ConclusionCNN accurately distinguished between adults and older adults based on the characteristics of a single stride's data. GRU achieved accurate classification by considering the relationships and subtle differences between strides. In both models, data around heel contact emerged as most critical, suggesting differences in acceleration and deceleration patterns during walking between different age groups.

Abstract 4117640: Thirty-Year Prevalence and Prognosis of the Cardiovascular-Kidney-Metabolic Syndrome in U.S. Females and Males

Background: The American Heart Association recently published guidelines on how to clinically identify and categorize individuals with cardiovascular-kidney-metabolic (CKM) syndrome. The extent to which CKM syndrome prevalence and prognosis differ by sex remain unknown. This study aimed to examine the impact of sex on trends in prevalence over 30 years and long-term prognosis of the CKM syndrome in the US. Methods: We analyzed nationally representative NHANES 1988-2018 data collected from 33,868 US adults (age ≥20 years) who were under surveillance for all-cause mortality through December 31, 2019. We examined sex-specific prevalence of CKM syndrome, and sex-specific CKM associations with all-cause mortality. Results: Of the 33,868 adults studied, the mean±SD age was 48.4±18.3 years with 52% female and 56% non-White. Overall prevalence of CKM syndrome increased steadily from 1988 to 2018 in both sexes, with a larger temporal rise in prevalent Stage 3 CKM seen for males (from 18.9% to 22.4%) compared to females (from 13.9% to 15.2%) ( Figure 1 ). Over a median follow-up of 13.3 years, there were 8745 deaths. In multivariable cox-regression analysis, worsening CKM severity was associated with all-cause mortality (P&lt;0.001 for both sexes), with greater magnitudes of risk seen in females (HR=1.24 to 3.33) compared to males (HR=0.85 to 2.60) across all stages (LRT χ 2 =19.0, P interaction &lt;0.001); results were similar for cardiovascular mortality (LRT χ 2 =22.3, P interaction &lt;0.001) ( Table 1 ). Conclusions: Females, compared with males, exhibited a lower prevalence of CKM stage 3 but experienced excess mortality risk across the spectrum of multi-system CKM dysfunction. These findings underscore the importance of identifying mechanisms underlying joint cardiovascular, renal, and metabolic systems pathophysiology to close a potentially widening sex disparities gap in multi-organ disease risk.

Abstract 4136996: Co-morbid Insomnia and Obstructive Sleep Apnea (COMISA) are Related to Incident Hypertension in a 20-Year Retrospective Cohort Study of 1.3 million Younger Men and Women Veterans: Associations by Sex

Introduction: Insomnia and obstructive sleep apnea (OSA) each increase risk for hypertension (HTN). Among older adults, there is a negative synergistic association of comorbid insomnia and OSA (i.e., COMISA) on incident cardiovascular disease (CVD) but it is unknown if this comorbidity is associated with HTN risk earlier in the lifespan. Research Questions: 1) Is COMISA associated with incident HTN among younger adults? 2) Do COMISA-HTN associations differ by sex? Hypotheses: We hypothesized that 1) COMISA would be associated with a greater risk of HTN than having no sleep disorder, 2) the hazard would be larger than for insomnia and OSA alone, and 3) distinct COMISA-HTN associations would be observed among men and women, respectively. Methods: Analyses included Veterans who enrolled in Veterans Health Administration (VA) care 2001-2021, a group selected because of its early adult age distribution. We merged administrative data, including outpatient and inpatient encounters, diagnoses, (ICD-9-CM/10 codes/dates) and pharmacy records. Veterans without demographic data, a history of other sleep disorders or CVD, or &lt;2 clinical encounters were excluded. Sleep disorders were defined by 1 inpatient or ≥2 outpatient encounters. HTN was defined by 1 inpatient or ≥2 outpatient encounters and/or ≥1 antihypertensive medication fill. Time-varying Cox proportional hazard models were adjusted for sociodemographic, behavioral/lifestyle, and clinical factors, and stratified analyses by sex. We used multiple imputation to address missing data. Results: Analyses included 1,293,165 Veterans (12% women; mean age 32.8) with an average follow-up of 7.6 years. Men with COMISA showed a 19% greater risk of HTN vs. no sleep diagnosis (95% CL: 1.17-1.20). Risks were slightly lower – but still significant – for men with only insomnia (HR:1.08 [95% CL: 1.06-1.09]) or only OSA (HR:1.15 [95% CL: 1.13-1.16]). Women with COMISA had a 21% greater risk of HTN vs. those without a sleep diagnosis (95% CL: 1.16-1.26), and those with insomnia (HR:1.15 [95% CL: 1.11-1.19]) or OSA (HR:1.13 [95% CL: 1.09-1.17]) showed a lower, though still significant risk. Conclusion: In this younger group, Veterans with COMISA had a 19-21% greater risk of HTN than without a disorder, and this risk was similar by sex and slightly higher than that attributable to insomnia or OSA alone. Increased identification of disordered sleep among younger adults should be a cardiovascular prevention priority.

Abstract 4137672: Prevalence, Clinical Characteristics, and Outcomes in Heart Failure with Improved Ejection Fraction by Sex

Background: Heart failure with improved ejection fraction (HFimpEF) is a growing clinical entity. While males are more likely to present with HFrEF, there remains little understanding of how sex relates to the epidemiology, predictors, and progression of HFimpEF. Research Question: What are the differences in epidemiology, clinical characteristics, medical management, and outcomes in patients (pts) with HFimpEF based on sex. Methods: We identified adults age ≥18 years with incident HFrEF (EF ≤40%) between January 2013 and December 2018 within Kaiser Permanente Northern California, an integrated health system serving &gt;4.5 million members. HFimpEF was defined as subsequent EF measurement &gt;40% within the following 12 months. Sex was based on self-report. Among pts with HFimpEF, we examined guideline-directed medical therapy (GDMT) use at time of incident HFimpEF, and at 6- and 12-months post-HFimpEF, stratified by sex. The incidence of worsening HF (WHF) events and all-cause death was assessed in a landmark analysis at 12 months post-HFrEF. We compared event rates between patients with HFimpEF and persistent HFrEF using Cox proportional hazards models adjusted for baseline age and EF. Results: Among 12,639 patients with incident HFrEF (female: 36%), 33% experienced HFimpEF. Females were more likely to experience HFimpEF in the 12 months following HFrEF than males (34% vs. 32%, p&lt;0.01). Among pts with HFimpEF, treatment with GDMT was similar among males and females and declined after incident HFimpEF in both sexes (Figure, Panel A). Females had similar rates of WHF or all-cause death compared to males (adjusted [a]HR: 1.10, 95% CI: 0.96, 1.26, P=0.17). Compared with those with persistent HFrEF, pts with HFimpEF had lower rates of WHF or all-cause death, a finding which was consistent by sex (male: aHR: 0.55, 95% CI: 0.50 to 0.61, female: aHR: 0.54, 95% CI: 0.48 to 0.62; Pinteraction by sex=0.78; Figure, Panel B). Conclusions: HFimpEF is more common among females compared to males, but prognosis is similar. Despite similar medical therapy, GDMT discontinuation after EF improvement is prevalent. Improvement in EF is similarly associated with improved outcomes across sex. Further data are needed to elucidate the differential etiologies of HF by sex.

Abstract 4137518: The implications of polygenic versus phenotypic characterization of obesity for cardiovascular-kidney-metabolic health

Introduction: The overall amount and the distribution of body fat, proxied by body-mass index (BMI) and waist-to-hip ratio (WHR), are two important measures of obesity and have significant polygenic heritability. We aimed to investigate whether polygenic scores (PGS) for these traits have additional predictive utility, beyond phenotypic characterization of obesity, for cardiovascular-kidney-metabolic (CKM) health. Methods: We derived PGS for BMI (PGS BMI ) and WHR adjusted for BMI (PGS WHRadjBMI ) using PRS-CS-auto on summary statistics from ~700k individuals of European ancestry (EA) in the GIANT consortium and selecting ~1M common variants for each score. We conducted association analyses in the Atherosclerosis Risk in Communities study, a prospective cohort including 8,631 EA individuals with ascertainment of incident diabetes, hypertension, chronic kidney disease, atrial fibrillation, coronary heart disease, ischemic stroke, and heart failure. We used nested Cox models to measure the added predictive utility of PGS to BMI and WHR for incident CKM phenotypes. Results: The study cohort (age 54.4±5.7 years, 52.4% women, follow-up 24.5±7.6 years) had a baseline BMI of 26.4 kg/m 2 (median [IQR]; 21.6-29.6) and WHR of 0.94 (0.88-0.98). PGS BMI and PGS WHRadjBMI were associated with their phenotypes (partial R 2 ; BMI 0.11 and WHR 0.04, p &lt;0.001), although with a large phenotypic variability across the distribution of PGS (IQR for 1 st and 10 th deciles of PGS; BMI 19.6-28.3 and 22.6-35.9, WHR 0.79-1.03 and 0.87-1.05). Anthropometric measures of obesity were associated with a wider gradient of risk compared to PGS for obesity–most notable for diabetes and cardiovascular phenotypes (Table 1a). Addition of PGS BMI and PGS WHRadjBMI to BMI and WHR resulted in limited improvement in risk discrimination across incident CKM phenotypes (Table 1b). Conclusions: Observed anthropometric measures of obesity are sufficient, and for certain conditions far superior, to capture the risk of incident CKM phenotypes. These findings suggest PGS for adiposity traits likely have limited clinical utility to refine risk stratification for CKM syndrome among middle aged adults.

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.