Relationship Between LDL-Cholesterol, Small and Dense LDL Particles, and mRNA Expression in a Cohort of African Americans.

Understanding the characteristics and behavior of LDL particles provides insights into the atherogenic risk of high levels of LDL cholesterol (LDL-C) in hypercholesterolemia. Studying LDL particles helps identify specific LDL subtypes (e.g., small and dense LDL particles, sdLDL) that may be atherogenic and, consequently, potential targets for therapeutics. This study cohort consists of African Americans (AAs), a population disproportionately affected by hypercholesterolemia, thereby accentuating the importance of the investigation.Differential expression (DE) analysis was undertaken utilizing a dataset comprising 17,947 protein-coding mRNAs from the whole-blood transcriptomes of 416 samples to identify mRNAs associated with LDL-C and sdLDL. Subsequently, mediation analyses were used to investigate the mediating role of sdLDL particles on the relationship between LDL-C and mRNA expression. Finally, pathway enrichment analysis was conducted to identify pathways involving mRNAs whose relationship with LDL-C is mediated by sdLDL.DE analysis revealed 1048 and 284 mRNA transcripts differentially expressed by LDL-C and sdLDL, respectively. Mediation analysis revealed that the associations between LDL-C and 33 mRNAs were mediated by sdLDL. Pathway analysis showed the 33 mRNAs are involved in pathways associated with immune system, inflammatory response, metabolism, and cardiovascular disease (CVD) risk.Our study provides valuable insights into the complex interplay between LDL-C, sdLDL and mRNA expression in a large sample of AAs. The results underscore the importance of incorporating sdLDL measurement alongside LDL-C levels to improve the accuracy of managing hypercholesterolemia and effectively stratify the risk of CVD. This is essential as differences in sdLDL modulate atherogenic properties at the transcriptome level.

Cultivating Relationships as a Community-Based Recruitment Strategy in Transdisciplinary Aging Research: Lessons From an Academic-Community Partnership.

Participation of Black American older adults in community-engaged research remains challenging in health sciences. The objectives of this study were to describe the specific efforts, successes, and challenges in recruiting Black American older adults in research led by the Health and Wellness in Aging Across the Lifespan core, part of the Virginia Commonwealth University Institute for Inclusion, Inquiry, and Innovation (iCubed). We conducted a cross-case analysis of 6 community-engaged research projects using the community-engaged research continuum model. Successful recruitment strategies comprised a multifaceted approach to community-based collaboration, including a wellness program with a long standing relationship with the community, engaging key stakeholders and a community advisory board, and building a community-based coalition of stakeholders. Posting flyers and modest monetary compensation remain standard recruitment strategies. The cross-case analysis offered critical lessons on the community's nature and level of engagement in research. Relationship building based on trust and respect is essential to solving complex aging issues in the community.

Quality of life in older adults with opioid use disorder: A scoping review.

The increasing prevalence of Substance Use Disorder (SUD) and opioid use disorder (OUD) is part of a national health crisis and reflects an unfortunate trend among populations of older adults. Opioid Use Disorder and opioid-related mortalities are also rising among older adults following this trend. Compared to younger populations, the effect of SUD and OUD on quality of life (QOL) in older adults is complex and poorly understood. This scoping review explores how QOL has been evaluated in high-risk subpopulations of older adults with SUD, specifically OUD. The articles reviewed for this paper targeted studies measuring QOL in older adults with OUD. We uncovered a paucity of literature devoted to studying interventions to improve QOL in older adults with OUD. This review supports further research on clinical interventions targeting improving QOL for older adults with OUD.

Histone acetylation at the sulfotransferase 1a1 gene is associated with its hepatic expression in normal aging.

OBJECTIVES: Phase II drug metabolism is poorly studied in advanced age and older adults may exhibit significant variability in their expression of phase II enzymes. We hypothesized that age-related changes to epigenetic regulation of genes involved in phase II drug metabolism may contribute to these effects. METHODS: We examined published epigenome-wide studies of human blood and identified the SULT1A1 and UGT1A6 genes as the top loci showing epigenetic changes with age. To assess possible functional alterations with age in the liver, we assayed DNA methylation (5mC) and histone acetylation changes around the mouse homologs Sult1a1 and Ugt1a6 in liver tissue from mice aged 4-32 months. RESULTS: Our sample shows a significant loss of 5mC at Sult1a1 (ß = -1.08, 95% CI [-1.8, -0.2], SE = 0.38, P = 0.011), mirroring the loss of 5mC with age observed in human blood DNA at the same locus. We also detected increased histone 3 lysine 9 acetylation (H3K9ac) with age at Sult1a1 (ß = 0.11, 95% CI [0.002, 0.22], SE = 0.05, P = 0.04), but no change to histone 3 lysine 27 acetylation (H3K27ac). Sult1a1 gene expression is significantly positively associated with H3K9ac levels, accounting for 23% of the variation in expression. We did not detect any significant effects at Ugt1a6. CONCLUSIONS: Sult1a1 expression is under epigenetic influence in normal aging and this influence is more pronounced for H3K9ac than DNA methylation or H3K27ac in this study. More generally, our findings support the relevance of epigenetics in regulating key drug-metabolizing pathways. In the future, epigenetic biomarkers could prove useful to inform dosing in older adults.

The Healthy Meal Program: A food insecurity screening and referral program for urban dwelling older adults.

OBJECTIVE: To describe the Healthy Meal Program (HMP), a community-academic partnership that aims to address the food insecurity and social isolation in older adults living in an urban setting. PROGRAM IMPLEMENTATION: Low-income older adults were screened for food insecurity and social isolation. A partnership with the food bank and a farm-based organization helped provide a weekly congregate or home-delivered meal, pilot a cooking class, and offer a mobile market selling fresh vegetables at discounted prices. PROGRAM EVALUATION: Overall, 339 individuals agreed to participate in the screening process. Sixty-eight percent (n = 230) screened positive for food insecurity and 41% (n = 139) screened positive for social isolation. Among individuals who were food insecure, 159 were referred to a food commodity program, 31 to meals on wheels, 23 to Supplemental Nutrition Assistance Program benefits, and 28 to emergency food pantries. The mobile market served 75 participants weekly and 15 individuals took part in cooking classes. CONCLUSIONS: Screening for food insecurity and social isolation in the HMP helped to assess the prevalence of these social determinants of health in low-income older adults. Weekly congregate meals, home visits, and group cooking classes were initiatives taken to decrease the impact of food insecurity and social isolation in this vulnerable population.

Influence of physiological and psychological factors on cognitive dysfunction in heart failure patients.

AIM: Our study aimed to examine factors that contribute to cognitive dysfunction in patients with heart failure (HF). BACKGROUND: Although a majority of patients with HF have mild to moderate cognitive impairment, little is known about factors that influence progressive cognitive decline in this population. METHODS: We examined the influence of physiological factors (NYHA functional class II - IV, ejection fraction, co-morbidity burden, polypharmacy), psychosocial factors (anxiety, depression, evaluation for advanced therapy), and associated toxicities (anticholinergic drug burden), on cognitive dysfunction. Data were analyzed using mean (SE) for continuous variables and frequency and percent for categorical variables. Differences between NYHA functional classification (Class II vs. Class III/IV) were examined using Chi Square. Linear regression models were used to assess associations among model variables. RESULTS: Of the 113 participants with HF, Class III-IV HF were more cognitively impaired than those with NYHA Class II (p < 0.0001), had higher anxiety (p = 0.002), and depression (p = 0.003), and lower EF (p = 0.041). A majority of participants had a moderate anticholinergic drug burden, and NYHA Class III/IV participants had significantly higher medication counts than Class II participants (p = 0.034). Regression analysis found that NYHA Class III/IV, anxiety, depression and evaluation for advanced therapy significantly influenced cognitive dysfunction. CONCLUSIONS: Findings support a high prevalence of cognitive dysfunction, anxiety, and depression in NYHA class II-IV with a greater level of cognitive dysfunction in class III/IV patients.

Warfarin pharmacogenomics and African ancestry.

In this issue of Blood, Limdi and coauthors demonstrate that racially informed warfarin pharmacogenetic algorithms perform better than traditional algorithms, which previously excluded genetic variants that are unique to patients with African ancestry.

2018 American Society of Consultant Pharmacists Annual Meeting & Exhibition.

Poster abstracts are evaluated based on the following criteria: significance of the problem to healthy aging or medication management; innovativeness of ideas, methods, and/or approach; methodological rigor of methods and approach; presentation of finding; implications identified for future research, practice, and/or policy; and clarity of writing. Submissions are not evaluated through the peer-reviewed process used by The Consultant Pharmacist. Industry support is indicated, where applicable. Presenting author is in italics. The poster abstract presentation is supported by the ASCP Foundation.

Epigenetic regulation of drug metabolism in aging: utilizing epigenetics to optimize geriatric pharmacotherapy.

We explore the relationship between epigenetic aging and drug metabolism. We review current evidence for changes in drug metabolism in normal aging, followed by a description of how epigenetic modifications associated with age can regulate the expression and functionality of genes. In particular, we focus on the role of epigenome-wide studies of human and mouse liver in understanding these age-related processes with respect to xenobiotic processing. We highlight genes encoding drug metabolizing enzymes and transporters revealed to be affected by epigenetic aging in these studies. We conclude that substantial evidence exists for epigenetic aging impacting drug metabolism and transport genes, but more work is needed. We further highlight the promise of pharmacoepigenetics applied to enhancing drug safety in older adults.

Pharmacogenomics in Clinical Practice for Older People.

Older people are over-represented among individuals that experience adverse drug reactions (ADR) and adverse drug events (ADE). Furthermore, older people are over-represented among individuals that visit emergency departments and are hospitalized because of ADRs. Moreover, older people are overrepresented among those who suffer ADEs while hospitalized. Finally, older people are among those most likely to have an anaphylactic response to prescription medications. Therefore, older people are prime candidates for efforts aimed at optimizing pharmacotherapeutic outcomes. Pharmacogenomics is an approach of using genetic data to optimize pharmacotherapeutic outcomes. Over the last two decades, pharmacogenomics grew from research initiatives into the current environment of pharmacogenomics implementation. Specifically, implementing pharmacogenomics into clinical settings or within health care systems has proven beneficial in optimizing pharmacotherapeutic outcomes. Therefore, pharmacists focused on optimizing pharmacotherapeutic outcomes for older people should be aware of the approaches to and resources available for implementing pharmacogenomics. KEY WORDS: Drug labeling biomarkers, Genes, Older adults, Pharmacogenomics.

Genome-wide analysis of hepatic DNA methylation reveals impact of epigenetic aging on xenobiotic metabolism and transport genes in an aged mouse model.

Hepatic xenobiotic metabolism and transport decline with age, while intact xenobiotic metabolism is associated with longevity. However, few studies have examined the genome-wide impact of epigenetic aging on these processes. We used reduced representation bisulfite sequencing (RRBS) to map DNA methylation changes in liver DNA from mice ages 4 and 24 months. We identified several thousand age-associated differentially methylated sites (a-DMS), many of which overlapped genes encoding Phase I and Phase II drug metabolizing enzymes, in addition to ABC and SLC classes of transporters. Notable genes harboring a-DMS were Cyp1a2, Cyp2d9, and Abcc2 that encode orthologs of the human drug metabolizing enzymes CYP1A2 and CYP2D6, and the multidrug resistance protein 2 (MRP2) transporter. Cyp2d9 hypermethylation with age was significantly associated with reduced gene expression, while Abcc2 expression was unchanged with age. Cyp1a2 lost methylation with age while, counterintuitively, its expression also reduced with age. We hypothesized that age-related dysregulation of the hepatic transcriptional machinery caused down-regulation of genes despite age-related hypomethylation. Bioinformatic analysis of hypomethylated a-DMS in our sample found them to be highly enriched for hepatic nuclear factor 4 alpha (HNF4α) binding sites. HNF4α promotes Cyp1a2 expression and is downregulated with age, which could explain the reduction in Cyp1a2 expression. Overall, our study supports the broad impact of epigenetic aging on xenobiotic metabolism and transport. Future work should evaluate the interplay between hepatic nuclear receptor function and epigenetic aging. These results may have implications for studies of longevity and healthy aging.

Understanding the preference for receiving mental health and substance use support in African Americans 50 and older.

OBJECTIVE: This study aims to determine whether current tobacco and/or alcohol use is associated with setting preferences for seeking support for substance use (SU) and mental health (MH) services to African Americans ages 50 and older. METHODS: Data from 368 African American individuals (aged 50+) who participated in a community-based needs assessment survey were used. Preferences included community-based (e.g., health centers) and traditional settings (e.g., doctor's office). SU was measured as a categorical variable detailing past-month use of conventional cigarettes and alcohol graded by risk levels. Logistic regression models tested the associations between SU and setting preference before and after adjusting for the influence of self-reported MH diagnoses. RESULTS: Prior to adjustment for the influence of MH outcomes, high-risk use of tobacco and alcohol in the past month was associated with a lower odds of preferring MH/SU support in traditional settings (OR = 0.23, 95% CI = 0.06-0.85) compared to participants engaged in no-/low- risk substance use. This association was no longer significant after accounting for the influence of mental health symptoms and covariates. DISCUSSION: These results provide preliminary evidence that mental health outcomes mediate the association between substance use and setting preference for seeking MH/SU support in traditional settings. TRANSLATIONAL SIGNIFICANCE: This exploratory study encourages additional investigation of the association between substance use, setting preferences, and the likelihood of seeking treatment in community health centers using larger sample sizes. Additional opportunities to offer mental health/substance use support to African American older adults within clinical settings should be explored.

Low-Income Older Adults' Vulnerability to Anticholinergic Medication-Associated Frailty.

BACKGROUND: A growing body of research supports the negative impact of anticholinergic drug burden on physical frailty. However, prior research has been limited to homogeneous white European populations, and few studies have evaluated how anticholinergic burden tools compare in their measurement function and reliability with minority community-dwelling adult populations. This study investigated the association between anticholinergic drug exposure and frailty by conducting a sensitivity analysis using multiple anticholinergic burden tools in a diverse cohort. METHODS: A comprehensive psychometric approach was used to assess the performance of five clinical Anticholinergic Burden Tools: Anticholinergic Cognitive Burden Scale (ACB), Anticholinergic Drug Scale (ADS), average daily dose, total standardized daily doses (TSDD), and Cumulative Anticholinergic Burden scale (CAB). Spearman correlation matrix and intraclass correlation coefficients (ICC) were used to determine the association among the variables. Ordinal logistic regression is used to evaluate the anticholinergic burden measured by each scale to determine the prediction of frailty. Model performance is determined by the area under the curve (AUC). RESULTS: The cohort included 80 individuals (mean age 69 years; 55.7% female, 71% African American). All anticholinergic burden tools were highly correlated (p < 0.001), ICC3 0.66 (p < 0.001, 95% confidence interval (CI) 0.53-0.73). Among individuals prescribed anticholinergics, 33% were robust, 44% were prefrail, and 23% were frail. All five tools predicted prefrail and frail status (p < 0.05) with low model misclassification rates for frail individuals (AUC range 0.78-0.85). CONCLUSION: Anticholinergic burden tools evaluated in this cohort of low-income African American older adults were highly correlated and predicted prefrail and frail status. Findings indicate that clinicians can select the appropriate instrument for the clinic setting and research question while maintaining confidence that all five tools will produce reliable results. Future anticholinergic research is needed to unravel the association between interventions such as deprescribing on incident frailty in longitudinal data.

Creating structural community cohesion: Addressing racial equity in older adult homelessness.

Older adults and racial minorities are overrepresented in homeless populations. Shelter and housing options for homeless older adults who have complex health and social needs are necessary, but not readily available. Older homeless adults that require, but do not receive, health-sensitive, age-sensitive, and racial equity housing, remain vulnerable to poor outcomes and premature mortality. Accordingly, this study examines the development of a coalition to better address older adult homelessness within a racial equity framework. A community coalition was established to better address older adult homelessness within the lens of age-sensitivity and racial equity, due to a disconnect between healthcare and senior housing placement programs, creating unaddressed multifaceted health issues/complications. The community coalition development is described, including the coalition process, activities, and outcomes. Local rehoused older adults are also interviewed and described to better understand their central life circumstances.

Modulatory effect of fenofibrate on endothelial production of neutrophil chemokines IL-8 and ENA-78.

PURPOSE: The PPAR-alpha agonists (fibrates) are commonly used in the treatment of dyslipidemia. It has been hypothesized that the cardio-protective effects of fibrates are partially due to immunomodulatory effects. However, there is a paucity of data regarding the effect of fibrates on neutrophilic chemokines such as epithelial neutrophil activating protein (ENA-78) and interleukin (IL)-8. We investigated the influence of fenofibrate on IL-1ß-stimulated production of ENA-78 and IL-8 from human endothelial cells (HUVECs). METHODS: HUVECs were cultured in the presence or absence of IL-1ß and fenofibrate ranging from 1-50 uM. ENA-78 and IL-8 were measured and normalized to total protein content in cell culture supernates by multiplex immunofluorescence detection. Experimental samples were measured in triplicate. Significance was set at P < 0.05 by ANOVA with correction for multiple comparisons. RESULTS: Endothelial production of both ENA-78 and IL-8 was induced by the proinflammatory cytokine IL-1ß. ENA-78 concentrations increased by more than 160-fold over constitutively produced ENA-78 upon IL-1ß stimulation (mean ± SEM: 10,129 ± 1591 pg/mg vs. 61 ± 9.5 mg/mg; P < 0.0001). IL-8 concentrations increased by slightly over 5-fold (6145 ± 860 pg/mg vs. 1160 ± 201 pg/mg; P = 0.0003). ENA-78 protein and mRNA were significantly reduced by fenofibrate while no drug effects were observed on IL-8 production. CONCLUSIONS: Fenofibrate blunts IL-1ß-mediated ENA-78 production with no effect on IL-8. This represents a novel mechanism by which fenofibrate exerts anti-inflammatory effects and should be further explored.

Cardiometabolic genomics and pharmacogenomics investigations in Filipino Americans: Steps towards precision health and reducing health disparities.

Background: Filipino Americans (FAs) are the third-largest Asian American subgroup in the United States (US). Some studies showed that FAs experience more cardiometabolic diseases (CMDs) than other Asian subgroups and non-Hispanic Whites. The increased prevalence of CMD observed in FAs could be due to genetics and social/dietary lifestyles. While FAs are ascribed as an Asian group, they have higher burdens of CMD, and adverse social determinants of health compared to other Asian subgroups. Therefore, studies to elucidate how FAs might develop CMD and respond to medications used to manage CMD are warranted. The ultimate goals of this study are to identify potential mechanisms for reducing CMD burden in FAs and to optimize therapeutic drug selection. Collectively, these investigations could reduce the cardiovascular health disparities among FAs. Rationale and design: This is a cross-sectional epidemiological design to enroll 300 self-identified Filipino age 18 yrs. or older without a history of cancer and/or organ transplant from Virginia, Washington DC, and Maryland. Once consented, a health questionnaire and disease checklist are administered to participants, and anthropometric data and other vital signs are collected. When accessible, we collect blood samples to measure basic blood biochemistry, lipids, kidney, and liver functions. We also extract DNA from the blood or saliva for genetic and pharmacogenetic analyses. CMD prevalence in FAs will be compared to the US population. Finally, we will conduct multivariate analyses to ascertain the role of genetic and non-genetic factors in developing CMD in FAs. Virginia Commonwealth University IRB approved all study materials (Protocol HM20018500). Summary: This is the first community-based study to involve FAs in genomics research. The study is actively recruiting participants. Participant enrollment is ongoing. At the time of this publication, the study has enrolled 97 participants. This ongoing study is expected to inform future research to reduce cardiovascular health disparities among FAs.

Anticholinergic Medication Burden in Parkinson's Disease Outpatients.

BACKGROUND: Individuals with Parkinson's disease (PD) may be especially vulnerable to future cognitive decline from anticholinergic medications. OBJECTIVE: To characterize anticholinergic medication burden, determine the co-occurrence of anticholinergic and cholinesterase inhibitors, and to assess the correlations among anticholinergic burden scales in PD outpatients. METHODS: We studied 670 PD outpatients enrolled in a clinic registry between 2012 and 2020. Anticholinergic burden was measured with the Anticholinergic Cognitive Burden Scale (ACB), Anticholinergic Drug Scale (ADS), Anticholinergic Risk Scale (ARS), and Drug Burden Index-Anticholinergic component (DBI-Ach). Correlations between scales were assessed with weighted kappa coefficients. RESULTS: Between 31.5 to 46.3% of PD patients were taking medications with anticholinergic properties. Among the scales applied, the ACB produced the highest prevalence of medications with anticholinergic properties (46.3%). Considering only medications with definite anticholinergic activity (scores of 2 or 3 on ACB, ADS, or ARS), the most common anticholinergic drug classes were antiparkinsonian (8.2%), antipsychotic (6.4%), and urological (3.3%) medications. Cholinesterase inhibitors and medications with anticholinergic properties were co-prescribed to 5.4% of the total cohort. The most highly correlated scales were ACB and ADS (κ= 0.71), ACB and ARS (κ= 0.67), and ADS and ARS (κ= 0.55). CONCLUSION: A high proportion of PD patients (20%) were either taking antiparkinsonian, urological, or antipsychotic anticholinergic medications or were co-prescribed anticholinergic medications and cholinesterase inhibitors. By virtue of its detection of a high prevalence of anticholinergic medication usage and its high correlation with other scales, our data support use of the ACB scale to assess anticholinergic burden in PD patients.

Socioeconomic Effects on Psychosocial Factors Among Low-Income Older Adults.

OBJECTIVES: Older adults have been disproportionately affected by COVID-19. The primary goal of this study is to determine the socioeconomic effects on psychosocial factors among low-income independent-living older adults, in an urban setting, during the COVID-pandemic. METHODS: Participants were recruited through Virginia Commonwealth University's Richmond Health and Wellness Program. Telephone surveys (n=100) were conducted using the Epidemic - Pandemic Impacts Inventory Geriatric with the Racial/Ethnic Discrimination addendum. Responses were analyzed for income and education effects across seven domains: home life, social activities/isolation, economic, emotional health-wellbeing, physical health, COVID-infection history, and positive change behaviors/experiences. RESULTS: The sample population was between 51 and 87 years of age, 88% were Black, 57% reported incomes of $10,000/year or less, and 60% reported a high-school education or less. There were income effects for social activities/isolation (f = 3.69, p<.05) and positive change (f = 8.40, p<.01), and education effects for COVID History (f = 4.20, p <.04). DISCUSSION: Overall results highlight the social patterns for a diverse sample of low-income urban older adults; education and income are identified as risk factors for social losses, COVID-infection experiences, racial/ethnic discrimination during the COVID-pandemic, and positive change behaviors.

COVID in Context: The Lived Experience of Richmond's Low-Income Older Adults.

Taking a phenomenological approach, this qualitative study describes the lived experiences of low-income older adults during the COVID-19 pandemic. A socio-ecological model was used to organize the five identified themes describing the lived experience: socio-economic context, Black Lives Matter and the politics of race, COVID and polarized views of COVID, interpersonal context (social connections), and individual context (feelings, beliefs, and behaviors). Study findings illustrate the intersectionality of contextual influences on the experience of low-income older adults. Study participants demonstrated remarkable resilience and coping strategies developed in response to the challenges they experienced throughout their lifetime which benefited them when faced with the pandemic, social unrest, and political events that took place in 2020. This study highlights the importance of understanding the larger context of COVID-19 which has significant implications for policy makers and public health leaders.