Racial/ethnic And Sociodemographic Disparities In Lipid Screening And Risk Factor Awareness Among Pregnant Women Receiving Prenatal Care

BACKGROUND: Atherosclerotic cardiovascular disease (ASCVD) remains a leading cause of morbidity and mortality with younger women being disproportionately affected by traditional risk factors including dyslipidemia. Despite recommendations for lipid screening in early adulthood, many younger women currently do not undergo screening. Prenatal and early pregnancy care represent underutilized opportunities for lipid screening and ASCVD risk assessment. We aimed to assess the prevalence and variations in pregnant women reporting a prior lipid screening and an awareness of high cholesterol as a risk factor for ASCVD. METHODS: We administered a survey to 234 pregnant women receiving prenatal care at one of the three clinics affiliated with the University of Pennsylvania Health System to assess self-reported demographic and clinical variables, prior lipid screening characteristics, and risk factor awareness. Participants’ responses were augmented by screening data and previous lipid profile results from their electronic medical records (EMR). RESULTS: A total of 200 pregnant women (86% response rate) completed the survey. Overall, 59% of pregnant women self-reported a previous lipid screening and 79% of women were aware of high cholesterol as an ASCVD risk factor. Stratified by racial/ethnic subgroups non-Hispanic (NH) Black women were less likely to report a prior screening (43% vs. 67%, p=0.022) and had lower levels of risk factor awareness (66% vs. 92%, p CONCLUSIONS: Significant racial/ethnic and sociodemographic disparities persist in both the presence of a prior lipid screening and awareness of high cholesterol as an ASCVD risk factor. Prenatal and early pregnancy care are underutilized opportunities to enhance lipid screening among younger women and reduce variations in access to preventive care

Age- and sex-based heterogeneity in coronary artery plaque presence and burden in familial hypercholesterolemia:A multi-national study

Objectives: Individuals with familial hypercholesterolemia (FH) are at an increased risk for coronary artery disease (CAD). While prior research has shown variability in coronary artery calcification (CAC) among those with FH, studies with small sample sizes and single-center recruitment have been limited in their ability to characterize CAC and plaque burden in subgroups based on age and sex. Understanding the spectrum of atherosclerosis may result in personalized risk assessment and tailored allocation of costly add-on, non-statin lipid-lowering therapies. We aimed to characterize the presence and burden of CAC and coronary plaque on computed tomography angiography (CTA) across age- and sex-stratified subgroups of individuals with FH who were without CAD at baseline. Methods: We pooled 1,011 patients from six cohorts across Brazil, France, the Netherlands, Spain, and Australia. Our main measures of subclinical atherosclerosis included CAC ranges (i.e., 0, 1–100, 101–400, &gt;400) and CTA-derived plaque burden (i.e., no plaque, non-obstructive CAD, obstructive CAD). Results: Ninety-five percent of individuals with FH (mean age: 48 years; 54% female; treated LDL-C: 154 mg/dL) had a molecular diagnosis and 899 (89%) were on statin therapy. Overall, 423 (42%) had CAC=0, 329 (33%) had CAC 1–100, 160 (16%) had CAC 101–400, and 99 (10%) had CAC &gt;400. Compared to males, female patients were more likely to have CAC=0 (48% [n = 262] vs 35% [n = 161]) and no plaque on CTA (39% [n = 215] vs 26% [n = 120]). Among patients with CAC=0, 85 (20%) had non-obstructive CAD. Females also had a lower prevalence of obstructive CAD in CAC 1–100 (8% [n = 15] vs 18% [n = 26]), CAC 101–400 (32% [n = 22] vs 40% [n = 36]), and CAC &gt;400 (52% [n = 16] vs 65% [n = 44]). Female patients aged 50–59 years were less likely to have obstructive CAD in CAC &gt;400 (55% [n = 6] vs 70% [n = 19]). Conclusion: In this large, multi-national study, we found substantial age- and sex-based heterogeneity in CAC and plaque burden in a cohort of predominantly statin-treated individuals with FH, with evidence for a less pronounced increase in atherosclerosis among female patients. Future studies should examine the predictors of resilience to and long-term implications of the differential burden of subclinical coronary atherosclerosis in this higher risk population.</p

Catalytic Enantioselective Allylation of Imines and Trifluoroketones Using New and Underutilized Organoboron Reagents

Thesis advisor: Amir H. HoveydaA general method for the catalytic enantioselective addition of silylallenes to phosphinoyl aldimines has been developed. Reactions are promoted in the presence of 5.0 mol% of an N–heterocyclic carbene–copper complex and a silyl-protected propargyl boron reagent. The reaction is efficient, requiring only 10 minutes, highly group selective, enantioselective and products can be further functionalized. Utility is highlighted in the total synthesis of marine alkaloid (S)-(–)-cyclooroidin using our product as a key intermediate in the total synthesis. The catalytic enantioselective addition of a 1,3-butadiene has been developed using a homoallenylboron reagent. These transformations are promoted by a C1-symmetric N–heterocyclic carbene–copper complex within 4 hours. Products can be obtained with gamma selectivity to afford the diene containing product. Efforts have been expanded towards the application of our product as a key intermediate towards the total synthesis of (+)-homochelidonine. Key transformations include a highly selective 1,2-protoboration of the 1,3-diene product followed by a Pd-catalyzed intramolecular sp2-sp3 Suzuki cross coupling. The development of a general catalytic enantioselective method for the propargyl addition to trifluoroketones has been studied. Reactions are complete within 15 minutes, broadly applied to alkyl-, alkenyl, alkynyl, aryl, and heteroaryl-substituted trifluoroketones, highly enantioselective and group selective. Key findings include use of an aminophenol containing an electron-withdrawing to improve reactivity and enantioselectivities. The method can be carried out on gram scale and has been applied to a substrate which can be elaborated towards glucocorticoid agonist BI 653048.Thesis (PhD) — Boston College, 2017.Submitted to: Boston College. Graduate School of Arts and Sciences.Discipline: Chemistry

Association of cardiovascular risk factor profile and financial hardship from medical bills among non-elderly adults in the United States

Background: While optimal cardiovascular risk factor (CRF) profile is associated with lower mortality, morbidity, and healthcare expenditures among individuals with atherosclerotic cardiovascular disease (ASCVD), less is known regarding its impact on financial hardship from medical bills. Therefore, we assessed whether an optimal CRF profile is associated with a lower burden of financial hardship from medical bills and a reduction in cost-related barriers to health.Methods: We used a nationally representative sample of adults between 18 and 64 years from the National Health Interview Survey between 2013 and 2017. We assessed ASCVD status and the number of risk factors to categorize the study population into 4 mutually exclusive categories: ASCVD (irrespective of CRF profile) and non-ASCVD with poor, average, and optimal CRF profile. Adjusted logistic regression model was used to determine the association of ASCVD/CRF profile with financial hardship from medical bills and cost-related barriers to health (cost-related medication non-adherence (CRN), foregone/delayed care, and high financial distress).Results: We included 119,388 non-elderly adults, representing 189 million individuals annually across the United States. Non-ASCVD/optimal CRF profile individuals had a lower prevalence of financial hardship and an inability paying medical bills when compared with individuals with ASCVD (24% vs 45% and 6% vs 19%, respectively). Among individuals without ASCVD and an optimal CRF profile, the prevalence of each cost-related barrier to health was \u3c50% compared with individuals with ASCVD. Poor/low income and uninsured individuals within non-ASCVD/average CRF profile strata had a lower prevalence of financial hardship and an inability paying medical bills when compared with middle/high income and insured individuals with ASCVD. Non-ASCVD individuals with optimal CRF profile had the lowest odds of all barriers to health.Conclusion: Optimal CRF profile is associated with a lower prevalence of financial hardship from medical bills and cost-related barriers to health despite lower income and lack of insurance

Current and Emerging Therapies for Atherosclerotic Cardiovascular Disease Risk Reduction in Hypertriglyceridemia

Hypertriglyceridemia (HTG) is a prevalent medical condition in patients with cardiometabolic risk factors and is associated with an increased risk of atherosclerotic cardiovascular disease (ASCVD), if left undiagnosed and undertreated. Current guidelines identify HTG as a risk-enhancing factor and, as a result, recommend clinical evaluation and lifestyle-based interventions to address potential secondary causes of elevated triglyceride (TG) levels. For individuals with mild to moderate HTG at risk of ASCVD, statin therapy alone or in combination with other lipid-lowering medications known to decrease ASCVD risk are guideline-endorsed. In addition to lifestyle modifications, patients with severe HTG at risk of acute pancreatitis may benefit from fibrates, mixed formulation omega-3 fatty acids, and niacin; however, evidence does not support their use for ASCVD risk reduction in the contemporary statin era. Novel therapeutics including those that target apoC-III and ANGPTL3 have shown to be safe, well-tolerated, and effective for lowering TG levels. Given the growing burden of cardiometabolic disease and risk factors, public health and health policy strategies are urgently needed to enhance access to effective pharmacotherapies, affordable and nutritious food options, and timely health care services

NHC–Cu-Catalyzed Addition of Propargyl­boron Reagents to Phos­phinoyl­imines. Enantioselective Synthesis of Tri­methyl­silyl-Substituted Homo­allenyl­amides and Application to the Synthesis of <i>S</i>‑(−)-Cyclooroidin

A catalytic method for the efficient and enantioselective addition of a 1-tri­methyl­silyl-substituted allene moiety to phos­phinoyl­imines is presented. Transformations are promoted by 5.0 mol % of a copper complex of an N-heterocyclic carbene in the presence of a propargylboron reagent that can be readily prepared in multigram quantities. Within 10 min of reaction, products are obtained in up to 91% yield, 98% allene (vs propargyl) selectivity, and 98:2 enantiomeric ratio. An assortment of aldimines serve as suitable substrates. The phosphinoyl and silyl groups can be removed efficiently and orthogonally. The silylallene moiety may be transformed to versatile derivatives that are difficult to access via nonsilylated allenes. The special features and utility of the approach are highlighted through a succinct enantioselective synthesis of marine alkaloid <i>S</i>-(−)-cyclooroidin