Caucasian Research Articles

The association of disparities in neighborhood median household income and mortality in patients admitted to the hospital with atrial fibrillation

BackgroundLower neighborhood median household income (nMHI) is associated with increased adverse outcomes in patients with atrial fibrillation (AF). However, its effect on mortality is yet unknown. MethodsData from the regional United States (U.S.) electronic medical records database, Research Action for Health Network (REACHnet), was extracted for adult patients with AF at Tulane Medical Center over 10 years. Annual nMHI & neighborhood high school graduation (HSG) data was collected from the US Census bureau. Only African Americans (AA) and Caucasians (CC) who had socioeconomic data were included. Low nMHI and low HSG were defined as ≤$25,000 & <90% respectively. High nMHI and HSG were defined as >$50,000 & ≥90% respectively. Primary endpoints were all cause and cardiovascular (CV) mortality. Cox-proportional hazard ratios were used to evaluate the endpoints. ResultsWe included 4616 patients diagnosed with AF. During a median follow up of 4.6 years, 434 patients died of which 32.7% patients had CV mortality. There was a stepwise decrease in incidence of both all-cause and CV mortality as nMHI increased. Patients with low nMHI had the greatest risk of all-cause mortality (HR 1.9, C.I. 1.2–3.2, P 0.004). The association between low nMHI and all-cause mortality persisted after adjusting for age, sex, race, HSG and stroke risk factors using CHA2DS2VASC, delta CHA2DS2VASC scores and oral anticoagulant use. CV mortality followed a similar trend as all-cause mortality, however, this association was not significant after adjusting for the above variables. Apart from low nMHI, CHA2DS2VASC delta CHA2DS2VASC were statistically significant independent predictors of both all-cause and CV mortality. ConclusionLow nMHI is an independent risk factor for all cause and CV mortality in AF. Higher burden of co-morbidities is the driving force behind this disparity. Future studies should evaluate the role of educational and therapeutic intervention in these populations to reduce mortality.

Abstract 13725: The Dose Difference of Carvedilol for Heart Failure Management Between Asian-Americans and Japanese Could Show No Difference in the Improvement of Heart Function

Introduction: Carvedilol has improved cardiac mortality and morbidity for heart failure with reduced ejection fraction (HFrEF). The initial and target doses used in the Japanese randomized controlled trials (RCTs) were almost half of those in the USA leading to markedly lower recommended doses for HF management the in Japanese national guidelines compared to the USA. Hypothesis: Race may play a role in the optimal dose of carvedilol for HFrEF management. Methods: The international collaborative study was performed to compare the dose difference and the effect on heart functions, such as left ventricular EF (LVEF) and heart rate (HR), among Asian-Americans (AA), Caucasians (CA), and Japanese (JA) using real-world data. Each local ethics committee approved the study protocol at the University of California, San Diego (UCSD), the Osaka University Hospital (OUH), and the OU pharmaceutical sciences. The initial population at UCSD Health and OUH consisted of 1078 patients with HFrEF (≥ 20 years, EF&lt;40%) treated with carvedilol (668 AA and CA and 410 JA). After inclusion/exclusion criteria, the study population consisted of 26 AA, 36 CA, and 96 JA. Results: Initial carvedilol dose (mg/day) (AA, 14.5 ± 11.9; CA, 19.1 ± 18.7; JA, 4.3 ± 4.2) and the dose at one year (30.9 ± 22.4; 34.5 ± 21.4; 11.2 ± 6.5) were significantly lower for JA compared to AA or CA ( p &lt; 0.05 vs JA, respectively). AA had the highest frequency of carvedilol discontinuation (%; AA, 10.7; CA, 2.6; JA, 6.5) and dose reduction (18.4, 10.7, 2.2) ( p &lt; 0.05, chi-square test). Clinical measurements of LVEF (%) measured before carvedilol initiation and after one year (before; 28.9 ± 8.8, 26.5 ± 8.0, 28.8 ± 7.4, after; 42.9 ± 11.1, 37.5 ± 15.3, 41.2 ± 13.1) and HR (beats/min) (before; 81.9 ± 19.0, 77.7 ± 13.5, 74.7 ± 10.9, after; 77.8 ± 10.6, 74.0 ± 12.5, 69.4 ± 9.4) showed no significant difference among the three groups. There were also no significant differences in event-free survival and in changes from baseline to 1 year in LVEF and HR, LVDd, or LVDs. Conclusions: JA patients exhibited similar effectiveness compared to AA and CA despite markedly lower carvedilol doses. Doses in AA were more similar to CA vs JA. Dose-deescalation may be an option in Asian HFrEF patients intolerable to high doses of carvedilol.

LBMON114 Enrichment Of Rare Sequence Variants In Genes That Communicate Metabolic Signals To The GnRH System In Hypothalamic Amenorrhea

Abstract Introduction Functional hypothalamic amenorrhea (HA) is commonly associated with increased exercise or decreased caloric intake and often with stress. We have previously demonstrated an increased burden of rare sequence variants (RSVs) in genes involved in GnRH ontogeny and upstream regulation in women with HA, but the role of metabolic and stress signaling to the GnRH neuronal system is poorly defined in this population. Methods The study included 100 women with a confirmed diagnosis of HA. The control cohort consisted of 468 women (aged 45­­-65 years) drawn from the NIH ClinSeq® Project. Exome sequencing was performed on peripheral blood genomic DNA. A subset of 72 genes was analyzed that have been shown to: 1) link metabolic or stress with reproductive phenotypes or 2) integrate metabolic and stress pathways with control of GnRH secretion. Joint genotyping of case and control samples was performed using the GATK GenotypeGVCFs function, locus-filtering using the VariantRecalibrator function, and genotype refinement using CalculateGenotypePosteriors with computation of median depths. Median depth positions &amp;lt;10, positions failing GATK VQSR or GATK genotype quality scores &amp;lt;20 were excluded. RSVs were identified by &amp;lt; 1% frequency in any subpopulation in gnomeAD for all-subjects (AS) and &amp;lt; 1% frequency in non-Finnish Europeans for Caucasians (CS). Data were analyzed for AS and for CS using a one-sided Fisher exact test for metabolism genes and stress genes. An additional regression analysis was conducted on the number of RSVs in a given gene as a predictor of HA vs. control. Comparisons with a p-value of &amp;lt; 0.1 are reported. Results HA patients exhibited an increased burden of RSVs in metabolism genes vs. controls (AS p=0. 043; CS p=0.105). The total number of RSVs per gene highlighted differences between HA and controls for the following genes: ADAMTSL1, GRINA, GRIN1, HCRTR1, TENM3, and NOS1 (AS p&amp;lt;0. 001, p=0. 032, p=0. 057, p=0. 082, p=0. 091, p=0. 095; CS p=0. 024, p=0. 044, p=0. 044, p NS, p=0. 086, p NS). Interestingly, RSVs in NOS1 and TENM3 appeared to be protective for HA (odds ratio &amp;lt;1 for both). In contrast, candidate stress genes were not significant in either the AS or CS (p=0.788, p=0.910). Conclusions These data suggest that RSVs in genes involved in phenotypes or signaling pathways that link metabolism to GnRH secretion may predispose to development of HA in the setting of decreased energy balance, but not for stress-related genes. GRINA and GRIN1 are important components of glutamate signaling that facilitate both appetite and GnRH secretion either directly or through kisspeptin. HCRTR1 plays a similar role in linking appetite and GnRH secretion while NOS1, which facilitates kisspeptin signaling, may be protective. This work highlights the need for further studies to understand the potential roles of ADAMTSL1 and TENM3 as risk factors for HA. Presentation: Monday, June 13, 2022 12:30 p.m. - 2:30 p.m.

S74 Demographic Analysis of Pancreatic Cancer Incidence Rates by Race and Gender

Introduction: Pancreatic cancer (PC) is the third-leading cause of cancer related-deaths in the US as of 2020. In recent years, there has been an increasing focus on the disparities of PC incidence. African Americans have worse overall outcomes compared to other racial groups. The stage of PC at time of diagnosis may be utilized to address this disparity. Methods: This study analyzed the stage of PC at diagnosis in males by race/ethnicity from 2015-2019 using data extracted from the National Cancer Institute Surveillance, Epidemiology, and End Results Cancer (SEER) Statistics Explorer Network. Age-adjusted incidence rates per 100,000 are categorized into localized, regional, and distant stages of cancer diagnosis and stratified by race/ethnicity. Results: For female patients, the rate of diagnosis was significantly higher for African Americans (AA) compared to other races across all stages of PC. AA females had higher incidence rates of localized, regional, and distant disease at 2.29%, 4.11%, and 6.96%, respectively [Table, Figure 1a]. In comparison, Asian/Pacific Islander (API) females had the lowest incidence rate at 1.34%, 2.78%, and 4.15%, respectively. The incidence rate per 100,000 for localized and regional PC was not significantly different between AA and Caucasian (CN) males at 2.10 and 2.18, respectively, for localized PC, at 4.44 and 4.45, respectively for regional PC [Figure1b]. Hispanic (HP) and API males had significantly lower incidence compared to AA and CN males at 1.76 and 1.58, respectively, for localized disease, and 3.13 and 3.17, respectively, for regional. Distant PC at time of diagnosis was significantly greater among AA males at 9.23%, compared to rates of 7.59% in CN males, 6.36% in HP males, and 5.11% in API males. All results p< 0.01. Conclusion: The rate of incidence for AA females is greater across all stages of PC, suggesting a genetic or socioeconomic predisposition, although further investigation is necessary. In males with PC, there is a disproportionately greater incidence of stage IV PC. With well-established increased mortality rates among AA, it is important to consider the role of access to healthcare. While multifactorial in etiology, highlighting the racial disparity in stage of PC at diagnosis emphasizes the importance of clinical suspicion. Earlier recognition should be prioritized with interventions to improve outcomes of PC in AA males.Figure 1.: SEER Age-Adjusted Incidence Rates of PC, 2015-2019 by Stage at Diagnosis and Race/Ethnicity, Female (1a) and Male (1b) Table 1. - SEER Age-Adjusted Incidence Rates (with 95% CI) of PC, 2015-2019 By Stage at Diagnosis and Race/Ethnicity, Female and Male Localized Regional Distant Female Black 2.29 (2.16-2.43) 4.11 (3.93-4.29) 6.96 (6.73-7.20) White 1.76 (1.71-1.80) 3.35 (3.28-3.41) 5.34 (5.26-5.42) Hispanic (any race) 1.74 (1.64-1.84) 3.06 (2.93-3.20) 5.09 (4.92-5.27) Asian/Pacific Islander 1.34 (1.23-1.46) 2.78 (2.61-2.95) 4.15 (3.95-4.36) Male Black 2.10 (1.94-2.26) 4.45 (4.23-4.68) 9.23 (8.91-9.56) White 2.18 (2.12-2.24) 4.44 (4.36-4.52) 7.59 (7.48-7.70) Hispanic (any race) 1.76 (1.64-1.88) 3.13 (2.98-3.28) 6.36 (6.14-6.58) Asian/Pacific Islander 1.58 (1.44-1.73) 3.17 (2.97-3.37) 5.11 (4.86-5.37)

168. A comparative analysis of racial disparities in nationally derived hospital data and two prospective multicenter surgical databases of adult spinal deformity surgery

<h3>BACKGROUND CONTEXT</h3> While past research has shown racial disparities exist in the outcomes and utilization of spine surgery, those studies were often performed on nondisease-specific national databases, which may capture different patient populations and complication rates compared to prospective multicenter databases. <h3>PURPOSE</h3> Purpose: 1) Assess racial disparities for enrollment in two prospective multicenter databases (ASD-DB1 and ASD-DB2). 2) Assess racial disparities in demographics, outcomes, in three databases: ASD-DB1, ASD-DB2, and the National Surgical Quality Improvement Program (NSQIP). We hypothesize that race will not affect enrollment in prospective multicenter studies. Disparities in national databases will be different than those in prospective databases. <h3>STUDY DESIGN/SETTING</h3> Retrospective review. <h3>PATIENT SAMPLE</h3> ASD patients in ASD-DB1, ASD-DB2, and NSQIP. <h3>OUTCOME MEASURES</h3> Preoperative demographic and clinical characteristics, intraoperative surgical techniques utilized, postoperative complications, correction, and change in HRQOLs. <h3>METHODS</h3> ASD-DB1 (2-year follow-up) included ASD patients from 2008-2019. ASD-DB2 (6-week follow-up) included ASD patients from 2019-2021. NSQIP (30-day follow-up) included ASD patients from 2012-2018. Racial disparities were assessed in African Americans (AA), Asians (AN) and Hispanics (H), compared to Caucasians (CA). Enrollment racial disparities were evaluated in ASD-DB1 and ASD-DB2. <h3>RESULTS</h3> ASD-DB1: 1,356 patients. Compared to CA, AA and H were younger, AA had higher max Cobb and higher rates of diabetes, H had lower SRS Activity, Mental, and Total, and AN had higher SRS Pain (all p < 0.05). The counties that enrollment sites for ASD-DB1 were located in were overall 66% CA, 18% AA, 16% H, and 11% AN. ASD-DB1 was 91% CA, 5% AA, 0% H, 1% AN. ASD-DB2: 338 patients. Compared to CA, AAs were younger and more alone (p < 0.05 all). The counties that enrollment sites for ASD-DB2 were located in were 66% CA, 18% AA, 16% AA, and 11% AN. ASD-DB2 was 91% CA, 5% AA, 0% H, and 1% AN. On multivariable analysis (MVA), no disparity in complications, recovery in HRQOLs, surgical techniques, or correction were found in ASD-DB1 or ASD-DB2 (p GT 0.05 for all). NSQIP had 2,660 patients. AAs were younger and had higher rate of ASA Class 4, dependence and diabetes (all p< 0.05). On MVA, AAs more reoperation (OR 2.2; P=0.005), greater than 5 days length of stay (OR 1.63; P=0.010), septic shock (OR 10; P=0.000), renal failure (OR 6.5; P=0.022) and deep wound infection (OR 2.77;P=0.048) (all p<0.05). <h3>CONCLUSIONS</h3> All three databases found disparities in baseline patient presentation. Both prospective databases predominantly enrolled white patients compared to county demographics. Neither of the prospective databases found racial disparities in complications, HRQOLs, radiographic correction, or techniques utilized. The national database found racial disparities in 30-day postoperative outcomes. This suggests there exist differences in patient populations and data granularity between nationally collected and prospective databases. <h3>FDA DEVICE/DRUG STATUS</h3> This abstract does not discuss or include any applicable devices or drugs.

Different colour predictions of facial preference by Caucasian and Chinese observers

Facial colour characteristics convey vital personal information and influence social interactions and mate choices as contributing factors to perceived beauty, health, and age. How various colour characteristics affect facial preference and whether there are cultural differences are not fully understood. Here, we provide a useful and repeatable methodology for skin colour research based on a realistic skin model to investigate the effect of various facial colour characteristics on facial preference and compare the role of colour predictors in Caucasian (CA) and Chinese (CN) samples. Our results show that, although the average skin colour of facial areas plays a limited role, together with colour variation and contrast, there are stronger links between colour and facial preference than previously revealed. We also find large cultural differences in facial colour perceptions; Chinese observers tend to rely more heavily on colour and lightness cues to judge facial preference than Caucasian observers.

Abstract 5414: RNA sequencing reveals that CYP3A5 siRNA treatment induces cell cycle blockade and senescence in MDAPCa2b human prostate cancer cells

Abstract Background: Previously we have demonstrated that CYP3A5 inhibition blocks prostate cancer (PC) cell growth partly by attenuating androgen receptor (AR) activation and downstream signaling. We further investigated whether CYP3A5 inhibition blocks PC cell growth independently of AR signaling. Initially, most PCs respond to androgen deprivation therapy (ADT), but eventually PC becomes castration resistant and does not respond to ADT. With very limited options available for patients with castration resistant prostate cancer (CRPC), there is an urgent need for the development of novel targeted therapies for this subtype of PC. Additionally, understanding the role of CYP3A5 as promoter of PC growth in African Americans (AA) is very relevant as AAs preferentially carry wild type CYP3A5 gene, often present with aggressive disease, and have higher mortality rate versus Caucasian (CA) patients, who typically express the mutant CYP3A5. Method: We used MDAPCa2b PC cell line of AA origin carrying one copy of wild type CYP3A5 for our study. After inhibiting the CYP3A5 using siRNA pool of 3 siRNAs, we performed Illumina RNA sequencing. Differentially expressed genes (DEGs) between non-target and CYP3A5 siRNA triplicate samples were identified using DESeq2, at a false discovery rate of adjusted p &amp;lt; 0.05. Furthermore, KEGG pathway analysis was performed to identify the roles of the differentially expressed genes in regulating prostate cancer growth. Results: We identified 1814 DEGs after inhibiting CYP3A5 using siRNA pool in MDAPCa2b cells, 825 of which increased or decreased expression greater than two-fold. The differentially down-regulated genes associate with several growth regulatory pathways: cell cycle progression (39), cellular senescence (16) DNA replication (18) and base excision repair (9). Additionally, we identified that CYP3A5 siRNA downregulates several genes which are dysregulated (including oncogenes and tumor suppressors) in different cancer type including RAS, c-Met, ERBB2, FGFR2, cyclin E, p53, Myc, PTEN, RARβ and CDK2. The upregulated genes correspond to two pathways, retinol metabolism pathway (arrests proliferation) and steroid hormone biosynthesis. We also identified several unique genes which are down regulated with CYP3A5 siRNA treatment like Glo1, FoxM1 (often upregulated in several cancers) and Tk1 (marker for chemotherapy sensitivity). Conclusion: CYP3A5 siRNA inhibits several genes involved in cell growth and proliferation. Targeting CYP3A5 represents a potential novel therapeutic approach, especially for AAs expressing wild type CYP3A5. Citation Format: Richard L. Tillett, Shirley Shen, Edwin C. Oh, Oscar B. Goodman Jr., Ranjana Mitra. RNA sequencing reveals that CYP3A5 siRNA treatment induces cell cycle blockade and senescence in MDAPCa2b human prostate cancer cells [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 5414.

Macula Densa Intracellular Alkalinization Activates NOS1β but Suppresses NOS1α during Tubuloglomerular Feedback

Increased NaCl at the macula densa, the same stimulus of the tubuloglomerular feedback (TGF), also induces intracellular alkalinization (pH: from 7.4 to 7.8) and enhances nitric oxide (NO) generation. Neuronal NO synthase (NOS1) is the primary isoform of NOS expressed in the macula densa and its activity is strongly pH‐dependent. Nevertheless, the impact of pH on the catalytic capacity of NOS1 remains controversial with inconsistent observations. A potential explanation for this discrepancy may be due to the presence of different splice variants of NOS1 (NOS1α and NOS1β). Therefore, we hypothesized that the macula densa intracellular alkalinization during TGF activates NOS1β but suppresses NOS1α, which modulates the NO production and thus the TGF responsiveness. To test this hypothesis, we measured the NOS activity of purified NOS1α and NOS1β proteins in various pH environments using the Griess method. The pH‐dependent NO production curves of NOS1α and NOS1β were different. The optimal pH was ~6.5 for NOS1α, but ~8.5 for NOS1β. The maximum activities of NOS1α and NOS1β were similar at their optimal pH of 6.5 and 8.5, respectively. Then, we measured and compared the renal cortical NOS1 expression, macula densa NO generation, TGF response in vitro and in vivo, renal vascular resistance (RVR), and mean arterial pressure (MAP) in the Sprague Dawley (SD) rats and the spontaneously hypertensive rats (SHRs). While the total NOS1 expression was not significantly different between SD rats and SHRs, the alternative splicing patterns were contradictory. The ratio of NOS1α/NOS1β was greater in SHRs than SD rats (2.94±0.48 vs 0.36±0.07; n=6, p&lt;0.01 vs SD), which was associated with the reduced NO production (21.6±4.5 vs 38.3±5.6 units/min; n=8, p&lt;0.01 vs SD), enhanced TGF in vitro (4.9±0.4 vs 3.5±0.5 µm; n=10, p&lt;0.05 vs SD) and in vivo (12.8±2.1 vs 9.1±1.7 mmHg; n=9, p&lt;0.01 vs SD), increased RVR (23.9±1.3 vs 17.8±1.5 mmHg.ml‐1.min‐1.g kidney wt‐1; n=6, p&lt;0.05 vs SD), and elevated MAP (127.3±6.6 vs 101.7±4.2 mmHg; n=6, p&lt;0.05 vs SD). We also measured and compared the NOS1 expression in the renal biopsy (cortex) tissues of Caucasians (CAs) and African Americans (AAs). There was no significant difference in the total NOS1 expression between CAs and AAs, whereas the ratio of NOS1α/NOS1β was greater in AAs than CAs (3.53±1.64 vs 0.43±0.31; n=10‐11, p&lt;0.01 vs CAs), which was associated with the higher serum creatinine level (1.25±0.08 vs 1.03±0.12 mg/dl; n=10‐11, p&lt;0.05 vs CAs). Lastly, we determined the effects of pH on the macula densa NO generation as well as the TGF responsiveness in SD rats and SHRs. When the pH of the tubular perfusate was switched from 7.4 to 8.0, the macula densa NO production increased by 29.5±6.9% (from 39.7±4.5 to 51.4±5.7 units/min) in SD rats, whereas it decreased by 26.2±4.3% (from 22.5±3.4 to 16.6±4.2 units/min) in SHRs (n=7, p&lt;0.05 vs 7.4); the TGF response in vitro decreased by 24.3±5.4% (from 3.7±0.4 to 2.8±0.6 µm) in SD rats, while it increased by 19.1±3.9% (from 4.7±0.4 to 5.6±0.5 µm) in SHRs (n=7, p&lt;0.05 vs 7.4). In conclusion, the present study demonstrates that the macula densa intracellular alkalinization during TGF activates NOS1β but suppresses NOS1α, which regulates the NO generation, the TGF response and potentially the renal hemodynamics.

Abstract 141: African American Women With Cyp3a4/5 Polymorphisms Have Increased Statin Intolerance.

Background: Approximately 3 million Americans have ill managed lipidemia due to statin intolerance (SI) or statin-associated myopathy (SAM). Atorvastatin and simvastatin are the most prescribed statins which are transported into the liver by SLCO1B1 and metabolized by cytochrome P450 (CYP) 3A4 and 3A5. CYP3A4*22 and CYP3A5*3 are two polymorphisms known to decrease their activity; thus, increasing the systemic daily exposure (AUC) and serum concentration (C max ) of unmetabolized statin. In Caucasian (CAU) populations the prevalence [5-7% CYP3A4*22 and 90% CYP3A5*3] and effect of these polymorphisms is well characterized but not in African American (AA) populations. We hypothesize that the prevalence of SI and SAM are correlated with CYP3A4/5 polymorphisms in AA populations. Methods: After IRB approval, saliva samples were collected from patients currently prescribed atorvastatin or simvastatin at The Ohio State University Medical for genotyping. SLCO1B1 status was assessed to control for its confounding effect. Participants with polymorphic results were contacted to complete 8 blood draws over 13hrs for pharmacokinetic analysis. Electronic medical records were utilized to collect demographic information, medical histories, risk factors, and concomitant medications. Results: Preliminary analysis of 502 participants (395 AA, 104 CAU, and 3 others) shows racially different polymorphic prevalence. Reduced activity of CYP3A4 was present in 5.8% CAU vs 0.51% AA. Notably, CYP3A5*3 is inactive in 73% and reduced in 20.3% of CAU compared to 41.7% and 40.7% respectively in AA. A statistically significant increase in SI in AA women vs CAU women (p=0.0032) was observed. In combined analysis, atorvastatin has reduced odds of intolerance compared to simvastatin (OR=0.463; p &lt;0.05). However, the odds of SAM is higher in patients with no history of cardiovascular disease (OR=6.137; p &lt;0.01) and those with chronic kidney disease (OR=1.269; p &lt;0.05). Clinical significance: Considering, the CYP3A5 is fully active in 18.5% of the AA population compared to 6.8% CAU, the characterization of this metabolic enzyme is of clinical significance in minority populations to better manage lipidemia, assess the safety profile of current therapeutic doses, and reduce SAM.

EDITORIAL COMMENT

The authors test the hypothesis that African American (AA) race confers a lower success rate on urethral reconstruction for stricture using a retrospective case series design. Detailed preoperative stricture information show that Caucasian (CA) and AA patients have similar stricture length and undergo equivalent surgical reconstructions (eg anastomotic versus substitution urethroplasty). The ability to answer questions about disparate outcomes depends on a sufficient number of events (eg complications or stricture recurrences) and the authors are hampered by their own success.

Does One’s Socioeconomic Status Predispose to the Development of Stress-Induced Cardiomyopathy?

Introduction: Stress-induced cardiomyopathy (SIC) has a higher incidence in Caucasians (CAUCs) compared to African-Americans (AAs). Whether this is due to racial predisposition, selection bias, or environmental factors remains unclear. Hypothesis: We hypothesize that people from lower socioeconomic strata (SES) have a lower incidence of SIC. It is possible that the incidence of SIC could be similar among CAUCs and AAs at the same SES. Stress preconditioning maybe protective in preventing SIC. Methods: Data of patients with the discharge diagnosis of SIC were extracted from the Myocardial Infarction Data Acquisition System spanning the period from 2006 through 2015. The incidence of SIC among CAUCs and AAs was compared per 100,000 New Jersey population and examined across income brackets. CAUCs and AAs data were compared using two-sample proportion tests. Results: During the study period, CAUCs had an overall higher incidence of SIC compared to AAs, 0.017% versus 0.0084% per 100,000 population (p value <0.0001). This difference persisted after a logistic regression adjustment (p = 0.0064). CAUCs in the income brackets of 30–40k had lower incidence of SIC than those in the 60–80k income bracket (p = 0.0156). Those with an income of 60–80k had lower incidence of SIC compared to those with an income of 80–100k. AAs with income between 30 and 60k had a lower incidence of SIC than CAUCs (p = 0.0330). Conclusions: CAUCs exhibited a trend towards less SIC as a function of lower income. This was not observed among AAs. AAs had a lower incidence of SIC. Our study suggests that SES has a protective effect among CAUCs.

A network-based integration for understanding racial disparity in prostate cancer

Compared to Caucasians (CAs), African Americans (AAs) have a higher rate of incidence and mortality in prostate cancer and are prone to be diagnosed at later stages. To understand this racial disparity, molecular features of different types, including gene expression, DNA methylation and other genomic alterations, have been compared between tumor samples from the two races, but led to different disparity associated genes (DAGs). In this study, we applied a network-based algorithm to integrate a comprehensive set of genomic datasets and identified 130 core DAGs. Out of these genes, 78 were not identified by any individual dataset but prioritized and selected through network propagation. We found DAGs were highly enriched in several critical prostate cancer-related signaling transduction and cell cycle pathways and were more likely to be associated with patient prognosis in prostate cancer. Furthermore, DAGs were over-represented in prostate cancer risk genes identified from previous genome wide association studies. We also found DAGs were enriched in kinase and transcription factor encoding genes. Interestingly, for many of these prioritized kinases their association with racial disparity did not manifest from the original genomic/transcriptomic data but was reflected by their differential phosphorylation levels between AA and CA prostate tumor samples. Similarly, the disparity relevance of some transcription factors was not reflected at the mRNA or protein expression level, but at the activity level as demonstrated by their differential ability in regulating target gene expression. Our integrative analysis provided new candidate targets for improving prostate cancer treatment and addressing the racial disparity problem.

Racial and gender differences of cervical vertebral maturation staging between African Americans versus Caucasian patients of various age groups: A retrospective study

The primary purpose of this study was to compare CVM staging between African American (AA) and Caucasian (CC) subjects, grouped based on gender. The secondary objectives were to conduct a CVM comparison of (1) male vs. female subjects, grouped based on their race, and (2) AA vs. CC subjects, categorized based on their age group. All patients between 8-18 years of age (University of XXX), meeting the criteria, were included between the period of the year 2007 to 2020. Three blinded independent evaluators analysed the lateral cephalograms for a 6-stage CVM system (CS1 to CS6) as described by McNamara and Franchi. Samples were divided based on race, gender, and age to conduct the statistical analysis for racial and gender comparisons. Out of the initial 1,300 lateral cephalograms, 1,276 with the mean age: 12.7 years SD 2.5 years, and median CVM: 4 (IQR: 25% percentile- 2 and 75% percentile- 4) were included. Gender-specific racial age comparison showed no significant differences for male subjects for most of the CVM stages (P>0.05). Overall and race-specific gender comparison of age showed significant differences for almost all CVM stages (P<0.05). No significant difference of CVM was found on racial comparison for overall, females (P=0.6131) or males (P=0.0825) subjects. On age-specific racial comparison, AA girls (8-10 years) were skeletally more mature than CC girls (P=0.0143); over 14-year-old CC girls (P<0.0001) and over 16-year-old CC boys (P=0.0008), being skeletally more mature than AA boys of the same age. There was no significant difference between AA and CC subjects on gender-specific comparisons for most of the CVM stages. A significant difference of age was observed for most of the CVM stage between male and female subjects on race-specific comparisons. Female patients were ahead in skeletal maturity as compared to males for each CVM stage. The CVM for 8-12-year-old AA females was significantly higher than that of the CC females, whereas the CVM for>14-year-old CC females was significantly higher than AA females.

The Effect of Race and Shear Stress on CRP-Induced Responses in Endothelial Cells.

Background C-reactive protein (CRP) is an independent biomarker of systemic inflammation and a predictor of future cardiovascular disease (CVD). More than just a pure bystander, CRP directly interacts with endothelial cells to decrease endothelial nitric oxide synthase (eNOS) expression and bioactivity, decrease nitric oxide (NO) production, and increase the release of vasoconstrictors and adhesion molecules. Race is significantly associated with CRP levels and CVD risks. With aerobic exercise, the vessel wall is exposed to chronic high laminar shear stress (HiLSS) that shifts the endothelium phenotype towards an anti-inflammatory, antioxidant, antiapoptotic, and antiproliferative environment. Thus, the purpose of this study was to assess the racial differences concerning the CRP-induced effects in endothelial cells and the potential role of HiLSS in mitigating these differences. Methods Human umbilical vein endothelial cells (HUVECs) from four African American (AA) and four Caucasian (CA) donors were cultured and incubated under the following conditions: (1) static control, (2) CRP (10 μg/mL, 24 hours), (3) CRP receptor (FcγRIIB) inhibitor followed by CRP stimulation, (4) HiLSS (20 dyne/cm2, 24 hours), and (5) HiLSS followed by CRP stimulation. Results AA HUVECs had significantly higher FcγRIIB receptor expression under both basal and CRP incubation conditions. Blocking FcγRIIB receptor significantly attenuated the CRP-induced decrements in eNOS expression only in AA HUVECs. Finally, HiLSS significantly counteracted CRP-induced effects. Conclusion Understanding potential racial differences in endothelial function is important to improve CVD prevention. Our results shed light on FcγRIIB receptor as a potential contributor to racial differences in endothelial function in AA.

A Multicentre Study Comparing Cerebrovascular Disease Profiles in Pacific Islander and Caucasian Populations Presenting with Stroke and Transient Ischaemic Attack

Introduction: In a multicentre study, we contrasted cerebrovascular disease profiles in Pacific Island (PI)-born patients (Indigenous Polynesian [IP] or Indo-Fijian [IF]) presenting with transient ischaemic attack (TIA), ischaemic stroke (IS) or intracerebral haemorrhage (ICH) with those of Caucasians (CSs). Methods: Using a retrospective case-control design, we compared PI-born patients with age- and gender-matched CS controls. Consecutive patients were admitted to 3 centres in South Western Sydney (July 2013–June 2020). Demographic and clinical data studied included vascular risk factors, stroke subtypes, and imaging characteristics. Results: There were 340 CS, 183 (27%) IP, and 157 (23%) IF patients; mean age 65 years; and 302 (44.4%) female. Of these, 587 and patients presented with TIA/IS and 93 (13.6%) had ICH. Both IP and IF patients were significantly more likely to present >24 h from symptom onset (odds ratios [ORs] vs. CS 1.87 and 2.23). IP patients more commonly had body mass indexes >30 (OR 1.94). Current smoking and excess alcohol intake were higher in CS. Hypertension, diabetes, and chronic kidney disease were significantly higher in both IP and IF groups in comparison to CS. IP patients had higher rates of AF and those with known AF were more commonly undertreated than both IF and CS patients (OR 2.24, p = 0.007). ICH was more common in IP patients (OR 2.32, p = 0.005), while more IF patients had intracranial arterial disease (OR 5.10, p < 0.001). Discussion/Conclusion: Distinct cerebrovascular disease profiles are identifiable in PI-born patients who present with TIA or stroke symptoms in Australia. These may be used in the future to direct targeted approaches to stroke prevention and care in culturally and linguistically diverse populations.

Clinical features and outcomes between African American and Caucasian patients with Takotsubo Syndrome.

Takotsubo syndrome (TS) is an acute, reversible form of heart failure, often mimicking an acute coronary syndrome (ACS). Data regarding racial differences in TS are inconsistent. The aim is to assess clinical features associated with unfavorable in-hospital outcomes between African American (AA) and Caucasian (CAU) patients. A retrospective electronic health record query identified 44 AA patients and 110 CAU patients with a diagnosis of TS. Our primary outcome was a composite of death, stroke, and cardiogenic shock during hospitalization. Variables associated with an increased risk of the primary composite outcomes were included in a logistic regression model. Compared to CAU patients, AA patients were a more comorbid population, and presented a higher prevalence of history of illicit drug use (27.3% vs. 13.6% P=0.044). There were no significant differences regarding in-hospital complication rates between AA and CAU patients. In the logistic regression model, infection was associated with greater risk of developing the primary outcome in AA patients (OR=7.26 [95% CI 1.22-43.17], P=0.029), whereas angina was a protective factor (OR=0.11 [95% CI 0.02-0.65], P=0.015). In CAU patients, severely depressed ejection fraction and worse peak creatinine during hospitalization increased risk of developing the primary outcome (OR=5.88 95% CI [2.01-17.17], P<0.001 and OR=1.64 [95% CI 1.15-2.58], P=0.031, respectively). Meanwhile, emotional stressors were protective (OR=0.16 [95% CI 0.03-0.88], P=0.004). Despite experiencing the same rate of in-hospital complications, the clinical profiles of AA patients are distinct from CAU patients admitted for TS, and clinical variables correlated with worse in-hospital outcomes also differ by race.

Abstract 12141: Echocardiographic Characteristics and Outcomes Between African American and Caucasians in Acute Pulmonary Embolism

Introduction: Socio-economical differences and delayed medical care have been associated to a higher mortality in African American (AA) PE patients. Hypothesis: Peri-PE mortality is higher in AA than Caucasian (CC) patients in a single medical center. Methods: A 26 months retrospective review of AA and CC patients admitted with an acute PE. Results: A total of 303 AA and 343 CC were identified. African Americans were younger, had more females, diabetes, chronic kidney disease and smokers than CC. A history of recent surgery and trauma were more common in CC. (Table I) Both groups had similar clinical presentations, biomarkers, and radiologic characteristics (CTA); except for RV strain that was more common among AA. In the initial echocardiogram, LV function was similar in both groups, although, AA had more often an underfilled LV and an abnormal RV. (Table II) There was no difference in hospital mortality between AA (n=21[6.9%]) and CC (n=21[6.1%]), p=0.67. Among 107 (AA=54, CC=53) patients who received advanced therapies, the mortality was higher in AA (18.5% vs.3.8% p=0.01). In a logistic regression analysis, the risk of death was increased by age (OR 1.04; 95%CI 1.020-1.073) and the need of advanced therapies (OR 2.43; 95%CI 1.029-5.769). Although AA race (OR 1.77; 95%CI 0.862-3.647), BMI (OR 0.99; 95%CI 0.950-1.038), abnormal RV (OR 0.71; 95%CI 0.321-1.601) and abnormal LV function (OR 1.737; 95%CI 0.754-4.005) did not increase significantly the risk of death. Conclusion: Despite hemodynamic changes of the LV and RV appreciated in AA, there was no difference in overall mortality. The risk of death was increased by age and need for advanced therapies.

Long-term outcomes of primary cardiac malignant tumors: Difference between African American and Caucasian population.

BackgroundThe survival outcome for primary cardiac malignant tumors (PMCTs) based on race has yet to be fully elucidated in previously published literature. This study aimed to address the general long‐term outcome and survival rate differences in PMCTs among African Americans and Caucasian populations.MethodsThe 18 cancer registries database from the Surveillance, Epidemiology, and End Results (SEER) Program from 1975 to 2016 were utilized. Ninety‐four African American (AA) and 647 Caucasian (CAU) patients from the SEER registry were available for survival analysis. The log‐rank test was used to compare the difference in mortality between two populations and presented by the Kaplan–Meier curves. A multivariate Cox proportional hazards regression was used to determine the independent predictors of all‐cause mortality.ResultsThe overall 30‐day, 1‐year, and 5‐year survival rates were 74%, 44.3%, and 16.6%, respectively, with a median survival of 10 months. There was no significant difference in survival rate between the two races (p‐value = 0.55). The 1‐year survival rate improved significantly during the study timeline in the AA population (13.3% during 1975–1998, 40.9% during 1999–2004, 50% during 2005–2010, and 59.7% during 2011–2016, p‐value = 0.0064). Age of diagnosis, type of tumor, disease stage, and chemotherapy administration are the main factors that predict survival outcomes of PMCT patients. Interactive nomogram was developed based on significant predictors.ConclusionsPMCTs have remained one of the most lethal diseases with poor survival outcome. Survival rate improved during the timeline in AA patients, but in general, racial differences in survival outcome were not observed.

Two Individuals with Rare Blocked Antigen Phenomenon and Coinciding Warm Autoantibody Mimicking Alloanti-Jk3 Resolved with JK Analysis

Abstract Introduction/Objective Kidd antigens can bind complement (C3) as well as Kidd specific warm autoantibodies (WAAb). An 838G&amp;gt;A single nucleotide variant (SNV) defines JK*01 and JK*02 which codes the antithetical Jka and Jk b, respectively. Both alleles translate the high prevalence (&amp;gt;99%) Jk3 (JK3). The 130G&amp;gt;A is associated with weak Jka and weak Jkb expression. In vivo binding of non-agglutinating globulins can cause false-negative phenotypes by means of the blocked antigen phenomenon (BAP). Methods/Case Report Transfusions were requested for a 74-year-old Caucasian (CA) female with Evan’s Syndrome, and an 85-year-old African American (AA) female with metastatic uterine cancer. Both had a history of nonspecific WAAb. Direct antiglobulin testing (DAT) detected moderate in vivo sensitization of IgG and C3. They phenotyped Jk(a- b-) with untreated and EDTA glycine-acid (EGA) treated IgG DAT-negative cells. Their serum contained anti-Jk3 reactivity, while a panreactive WAAb in the eluate reacted with Jk3- donor and EGA treated DAT-negative autologous cells. Weak anti-Jka and anti-Jkb reactivity remained in the alloadsorbed serum of the antithetical adsorbing cells. Genetic testing of the CA revealed JK*01W.01(130A)/02 alleles, while cDNA confirmed the alleles would be transcribed into mRNA. Sequencing of the AA detected 130G/A, and 838G/A as well as other silent mutations predicting either a Jk(a+wb+) or Jk(a+b+w) phenotype. The CA received one compatible JK:-3 transfusion, and both individuals benefited from multiple least incompatible transfusions of Jk a+ and/or Jk b+ donors with expected hemoglobin increases (1 g/dL per transfusion). The CA serologically phenotyped Jk(a-b+) 132 days later following prolonged immunosuppressive therapy while a normocytic normochromic anemia and the WAAb persisted. No follow up evaluations of the AA are available. Results (if a Case Study enter NA) NA Conclusion Unexpected BAP can confound immunohematology testing and lead WAAbs mimicking alloanti-Jk3 to be mischaracterized as allogeneic. By predicting phenotypes, genetic analysis can aid serological techniques in antibody characterization and help circumvent complications searching for rare JK:-3 donors.

Small Extracellular Vesicle-Derived microRNAs Stratify Prostate Cancer Patients According to Gleason Score, Race and Associate with Survival of African American and Caucasian Men.

Simple SummaryNovel biomarkers are needed to guide prognosis and treatment of aggressive forms of prostate cancer (PCa). In this study, small extracellular vesicles (sEVs)-derived microRNAs (miRs) are used to predict aggressive phenotypes and ancestral background of PCa patients. Two cohorts was used to study the diagnostic and prognostic utility of sEV-associated miRs in predicting aggressive forms of PCa in African American (AA) and Caucasian (CA) men. In training cohort, miR profiling was performed and top-ranked sEV-associated miRs were then validated in two independent confirmatory cohorts comprising 150 plasma samples. Results revealed that sEV-associated miR-6068 and miR-1915-3p were enriched in PCa patients compared to healthy subjects. sEV-associated miR-6716-5p and miR-3692-3p distinguished AA from CA men and low from high Gleason score. However, miR-1915-3p was the only studied miR associated with longer recurrence-free survival as independent prognostic marker. The utility of small extracellular vesicles (sEVs)-derived microRNAs (miRs) to segregate prostate cancer (PCa) patients according to tumor aggressiveness and ancestral background has not been fully investigated. Thus, we aimed to determine the diagnostic and prognostic utility of sEV-associated miRs in identifying aggressive PCa in African American (AA) and Caucasian (CA) men. Using a training cohort, miR profiling was performed on sEVs isolated from plasma of PCa patients. Top-ranked sEV-associated miRs were then validated in 150 plasma samples (75 AA and 75 CA) collected from two independent cohorts; NIH (n = 90) and Washington University (n = 60) cohorts. Receiver operating characteristic (ROC) curve, Kaplan–Meier and Cox proportional hazards regression were used to assess these miRs as clinical biomarkers. Among nine top-ranked sEV-associated miRs, miR-6068 and miR-1915-3p were enriched in sEVs collected from PCa patients compared to healthy volunteers. Moreover, miR-6716-5p and miR-3692-3p segregated AA from CA men and low from high Gleason score (GS), respectively. Upregulation of sEV-associated miR-1915-3p, miR-3692-3p and miR-5001-5p was associated with improved survival time, and only miR-1915-3p was associated with longer recurrence-free survival (RFS) as an independent prognostic marker. Taken together, we identified novel sEV-associated miRs that can differentiate PCa patients from normal, AA from CA and high from low GS and predicts RFS.