Faculty Bibliography

BACKGROUND:Abdominal computed tomography (CT) is commonly performed in adults. Abdominal aortic calcification (AAC) can be visualized and quantified using artificial intelligence (AI) on CTs performed for other clinical purposes (opportunistic CT). We sought to investigate the value of AI-enabled AAC quantification as a predictor of coronary artery disease and its association with cardiovascular events. METHODS:A fully automated AI algorithm to quantify AAC from the diaphragm to aortic bifurcation using the Agatston score was retrospectively applied to a cohort of patient that underwent both non-contrast abdominal CT for routine clinical care and cardiac CT for coronary artery calcification (CAC) assessment. Subjects were followed for a median of 36 months for major adverse cardiovascular events (MACE, composite of death, myocardial infarction [MI], ischemic stroke, coronary revascularization) and major coronary events (MCE, MI or coronary revascularization). RESULTS:Our cohort included 3599 patients (median age 60 years, 62% male, 74% white) with an evaluable abdominal and cardiac CT. There was a positive correlation between presence and severity of AAC and CAC (r=0.56, P<0.001). AAC showed excellent discriminatory power for detecting or ruling out any CAC (AUC for PREVENT risk score 0.701 [0.683 to 0.718]; AUC for PREVENT plus AAC 0.782 [0.767 to 0.797]; P<0.001). There were 324 MACE, of which 246 were MCE. Following adjustment for the 10-year cardiovascular disease PREVENT score, the presence of AAC was associated with a significant risk of MACE (adjHR 2.26, 95% CI 1.67-3.07, P<0.001) and MCE (adjHR 2.58, 95% CI 1.80-3.71, P<0.001). A doubling of the AAC score resulted in an 11% increase in the risk of MACE and a 13% increase in the risk of MCE. CONCLUSIONS:Using opportunistic abdominal CTs, assessment of AAC using a fully automated AI algorithm, predicted CAC and was independently associated with cardiovascular events. These data support the use of opportunistic imaging for cardiovascular risk assessment. Future studies should investigate whether opportunistic imaging can help guide appropriate cardiovascular prevention strategies.

Although healthcare workers may be aware of the risks of physical inactivity, their levels of physical activity (PA) are similar to those of all US adults, with less than half engaging in sufficient PA. The purpose of this health promotion was to encourage daily PA among employees in a large academic healthcare system. We also tested whether individualized progress updates further influenced PA. This 10-week program was available to all employees of NYU Langone Health. Employees could sync their phone or accelerometer via app or web browser to count.it - the vendor chosen to monitor and manage step counts. Participants were asked to voluntarily provide basic information (age, sex, job role, work location) and complete the Physical Activity Vital Sign (minutes/week and intensity of PA) at enrollment and 10 weeks. For 10 weeks, participants were sent a message through their employee 'MyChart' portal with a link to information on the benefits of PA, and a reminder of that week's step-count challenge. Those meeting criteria for weekly challenges were included in gift card raffles. Participants were randomized 1:1 to receive the standard message ± additional emails detailing their progress. 3528 employees registered to participate (8% of all employees) although active users diminished over time (1225 at week 10). Average daily steps remained stable throughout (7319 + 4540 in week 1, 7229 + 5010 in week 10). Although there was no difference in any individual week, receipt of personalized feedback was associated with significantly higher average step counts throughout the 10-wk intervention as a whole (P = 0.01). Age and an urban work location were positively associated with steps, while female sex and a clerical job role were negatively associated with steps counts (all P < 0.005). Our findings provide important insight for workplace interventions to promote PA. They further suggest specific groups that may benefit from targeted efforts.

OBJECTIVES/OBJECTIVE:To describe the implementation of a workplace health promotion to address low levels of physical activity (PA). METHODS:Using the Exploration, Preparation, Implementation, Sustainment (EPIS) framework we implemented and evaluated a 10-week workplace step-count challenge to promote PA. All health system employees invited to participate. Data were collected on the exploration, preparation and implementation phases. RESULTS:During exploration, we recognized inadequate PA among employees. Meetings with key personnel were held to determine details of the health promotion and obtain support. We pursued a step-count PA intervention, capitalizing on employee ownership of smartphones with accelerometers. Vendors to host the intervention were evaluated. All employees were invited to participate. Participants received weekly messages about improving PA and notifications of weekly challenges. Exit interviews provided feedback and suggestions. CONCLUSION/CONCLUSIONS:A workplace health promotion focused on employee PA is feasible using EPIS.

BACKGROUND/UNASSIGNED:Elevated perceived stress is associated with adverse outcomes following myocardial infarction (MI) and may account for poorer recovery among women vs men. OBJECTIVES/UNASSIGNED:This randomized controlled trial tested effects of a mindfulness-based intervention on stress levels among women with MI. METHODS/UNASSIGNED:Women with elevated stress (Perceived Stress Scale [PSS-4]≥6) at least 2 months after MI were enrolled from 12 hospitals in the United States and Canada and via community advertising. Participants were randomized to a remotely delivered mindfulness intervention (MBCT-Brief) or heart disease education, both 8 weeks long. Follow-up was 6 months. Changes in stress (PSS-10; primary outcome) and secondary outcomes (depressive symptoms, anxiety, quality of life, disease-specific health status, actigraphy-assessed sleep) were compared between groups. RESULTS/UNASSIGNED: = 0.036). CONCLUSIONS/UNASSIGNED:MBCT-Brief was associated with greater 6-month reductions in stress than an active control among adherent participants. More frequent mindfulness practice was associated with greater improvements in psychological outcomes. Strategies to engage women with MI in mindfulness training and support regular home practice may enhance these effects.

BACKGROUND:Lipoprotein(a) [Lp(a)] is a driver of residual cardiovascular risk. Proprotein convertase subtilisin/kexin type 9 inhibitors (PCSK9i) decrease Lp(a) with significant heterogeneity in response. We investigated contributors to the heterogeneous response. METHODS:CHOlesterol Reduction and Residual Risk in Diabetes (CHORD) was a prospective study examining lipid lowering in participants with a low-density lipoprotein cholesterol (LDL-C) >100 mg/dL with and without diabetes (DM) on lipid lowering therapy (LLT) for 30-days with evolocumab 140 mg every 14 days combined with either atorvastatin 80 mg or ezetimibe 10 mg daily. Lp(a) level was measured by immunoturbidometry, and the apolipoprotein (a) [apo(a)] isoform size was measured by denaturing agarose gel electrophoresis and western blotting. We examined the change in Lp(a) levels from baseline to 30 days. RESULTS:Among 150 participants (mean age 50 years, 58% female, 50% non-White, 17% Hispanic, 50% DM), median (interquartile range) Lp(a) was 27.5 (8-75) mg/dL at baseline and 23 (3-68) mg/dL at 30 days, leading to a 10% (0-36) median reduction (P < 0.001). Among 73 (49%) participants with Lp(a) ≥30 mg/dL at baseline, there was a 15% (3-25) median reduction in Lp(a) (P < 0.001). While baseline Lp(a) level was not correlated with change in Lp(a) (r = 0.04, P = 0.59), apo(a) size directly correlated with Lp(a) reduction (P < 0.001). After adjustment for age, sex, race/ethnicity, DM, and type of LLT, apo(a) size remained positively associated with a reduction in Lp(a) (Beta 0.95, 95% confidence interval, 0.93-0.97, P < 0.001). CONCLUSION/CONCLUSIONS:Our data demonstrate variation in Lp(a) reduction with potent LLT. Change in Lp(a) was strongly associated with apo(a) isoform size.

OBJECTIVES/OBJECTIVE:We introduce a widely applicable model-based approach for estimating individual-level Social Determinants of Health (SDoH) and evaluate its effectiveness using the All of Us Research Program. MATERIALS AND METHODS/METHODS:Our approach utilizes aggregated SDoH datasets to estimate individual-level SDoH, demonstrated with examples of no high school diploma (NOHSDP) and no health insurance (UNINSUR) variables. Models are estimated using American Community Survey data and applied to derive individual-level estimates for All of Us participants. We assess concordance between model-based SDoH estimates and self-reported SDoHs in All of Us and examine associations with undiagnosed hypertension and diabetes. RESULTS:Compared to self-reported SDoHs, the area under the curve for NOHSDP is 0.727 (95% CI, 0.724-0.730) and for UNINSUR is 0.730 (95% CI, 0.727-0.733) among the 329 074 All of Us participants, both significantly higher than aggregated SDoHs. The association between model-based NOHSDP and undiagnosed hypertension is concordant with those estimated using self-reported NOHSDP, with a correlation coefficient of 0.649. Similarly, the association between model-based NOHSDP and undiagnosed diabetes is concordant with those estimated using self-reported NOHSDP, with a correlation coefficient of 0.900. DISCUSSION AND CONCLUSION/CONCLUSIONS:The model-based SDoH estimation method offers a scalable and easily standardized approach for estimating individual-level SDoHs. Using the All of Us dataset, we demonstrate reasonable concordance between model-based SDoH estimates and self-reported SDoHs, along with consistent associations with health outcomes. Our findings also underscore the critical role of geographic contexts in SDoH estimation and in evaluating the association between SDoHs and health outcomes.

IMPORTANCE/UNASSIGNED:While the association between cross-sectional measures of social isolation and adverse health outcomes is well established, less is known about the association between changes in social isolation and health outcomes. OBJECTIVE/UNASSIGNED:To assess changes of social isolation and mortality, physical function, cognitive function, cardiovascular disease (CVD), and stroke. DESIGN, SETTING, AND PARTICIPANTS/UNASSIGNED:In a cohort design, social isolation changes in 4 years and subsequent risk of mortality and other outcomes were assessed using the 13 649 eligible Health and Retirement Study (HRS) respondents from the 2006 to 2020 waves. Data were analyzed from October 11, 2023, to April 26, 2024. EXPOSURE/UNASSIGNED:The main exposure was the change in social isolation measured by the Steptoe 5-item Social Isolation Index from the initial assessment to a second assessment conducted 4 years later. Participants were classified into decreased isolation, stable, or increased isolation groups, stratified by their baseline isolation status. MAIN OUTCOMES AND MEASURES/UNASSIGNED:The primary outcomes were mortality, self-reported dependencies in activities of daily living, Alzheimer disease and Alzheimer disease-related dementia, CVD, and stroke. Dementia, CVD, and stroke were assessed using HRS-linked Medicare records. Incidence rates (IRs) of each group were estimated and a Cox proportional hazards regression model was used, with inverse-probability treatment weighting to adjust for confounders. RESULTS/UNASSIGNED:Among 13 649 participants (mean [SD] age at baseline, 65.3 [9.5] years; 8011 [58.7%] women) isolated at baseline, those with increased isolation had higher mortality (n = 693; IR = 68.19; 95% CI, 60.89-76.36 per 1000 person-years) than those who were stable (n = 1796; IR = 44.02; 95% CI, 40.47-47.88 person-years) or had decreased isolation (n = 2067; IR = 37.77; 95% CI, 34.73-41.09 person-years) isolation. Increased isolation was associated with higher risks of mortality (adjusted hazard ratio [AHR], 1.29; 95% CI, 1.09-1.51), disability (AHR, 1.35; 95% CI, 1.09-1.67), and dementia (AHR, 1.40; 95% CI, 1.02-1.93) compared with stable isolation. Similar findings were observed among socially nonisolated participants at baseline. CONCLUSIONS AND RELEVANCE/UNASSIGNED:In this cohort study, increased isolation was associated with elevated risks of mortality, disability, and dementia, irrespective of baseline isolation status. These results underscore the importance of interventions targeting the prevention of increased isolation among older adults to mitigate its adverse effects on mortality, as well as physical and cognitive function decline.

Electronic health records (EHRs) contain rich clinical information for millions of patients and are increasingly used for public health research. However, non-random inclusion of subjects in EHRs can result in selection bias, with factors such as demographics, socioeconomic status, healthcare referral patterns, and underlying health status playing a role. While this issue has been well documented, little work has been done to develop or apply bias-correction methods, often due to the fact that most of these factors are unavailable in EHRs. To address this gap, we propose a series of Heckman type bias correction methods by incorporating social determinants of health selection covariates to model the EHR non-random sampling probability. Through simulations under various settings, we demonstrate the effectiveness of our proposed method in correcting biases in both the association coefficient and the outcome mean. Our method augments the utility of EHRs for public health inferences, as we show by estimating the prevalence of cardiovascular disease and its correlation with risk factors in the New York City network of EHRs.

INTRODUCTION/UNASSIGNED:Quantitative, multiplexed imaging is revealing complex spatial relationships between phenotypically diverse tumor infiltrating leukocyte populations and their prognostic implications. The underlying mechanisms and tissue structures that determine leukocyte distribution within and around tumor nests, however, remain poorly understood. While presumed players in metastatic dissemination, new preclinical data demonstrates that blood and lymphatic vessels (lymphovasculature) also dictate leukocyte trafficking within tumor microenvironments and thereby impact anti-tumor immunity. Here we interrogate these relationships in primary human cutaneous melanoma. METHODS/UNASSIGNED:We established a quantitative, multiplexed imaging platform to simultaneously detect immune infiltrates and tumor-associated vessels in formalin-fixed paraffin embedded patient samples. We performed a discovery, retrospective analysis of 28 treatment-naïve, primary cutaneous melanomas. RESULTS/UNASSIGNED:Here we find that the lymphvasculature and immune infiltrate is heterogenous across patients in treatment naïve, primary melanoma. We categorized five lymphovascular subtypes that differ by functionality and morphology and mapped their localization in and around primary tumors. Interestingly, the localization of specific vessel subtypes, but not overall vessel density, significantly associated with the presence of lymphoid aggregates, regional progression, and intratumoral T cell infiltrates. DISCUSSION/UNASSIGNED:We describe a quantitative platform to enable simultaneous lymphovascular and immune infiltrate analysis and map their spatial relationships in primary melanoma. Our data indicate that tumor-associated vessels exist in different states and that their localization may determine potential for metastasis or immune infiltration. This platform will support future efforts to map tumor-associated lymphovascular evolution across stage, assess its prognostic value, and stratify patients for adjuvant therapy.

BACKGROUND:We previously reported a higher incidence of a pathogenic germline variant in the kinase insert domain receptor (KDR) in melanoma patients compared to the general population. Here, we dissect the impact of this genotype on melanoma tumor growth kinetics, tumor phenotype, and response to treatment with immune checkpoint inhibitors (ICIs) or targeted therapy. METHODS:The KDR genotype was determined and the associations between the KDR Q472H variant (KDR-Var), angiogenesis, tumor immunophenotype, and response to MAPK inhibition or ICI treatment were examined. Melanoma B16 cell lines were transfected with KDR-Var or KDR wild type (KDR-WT), and the differences in tumor kinetics were evaluated. We also examined the impact of KDR-Var on the response of melanoma cells to a combination of VEGFR inhibition with MAPKi. RESULTS:= 0.0159), and KDR-Var cells showed synergistic cytotoxicity to the combination of dabrafenib and lenvatinib. CONCLUSIONS:Our data demonstrate a role of germline KDR-Var in modulating melanoma behavior, including response to treatment. Our data also suggest that anti-angiogenic therapy might be beneficial in patients harboring this genotype, which needs to be tested in clinical trials.