African American Cohort Research Articles

Long-Term Air Pollution and Blood Pressure in an African American Cohort: the Jackson Heart Study

African Americans are disproportionately affected by high blood pressure, which may be associated with exposure to air pollutants, such as fine particulate matter and ozone. Among African American Jackson Heart Study participants, this study examined associations between 1-year and 3-year mean fine particulate matter and ozone concentrations with prevalent and incident hypertension at Visits 1 (2000-2004, n=5,191) and 2 (2005-2008, n=4,105) using log binomial regression. Investigators examined associations with systolic blood pressure, diastolic blood pressure, pulse pressure, and mean arterial pressure using linear regression and hierarchical linear models, adjusting for sociodemographic, behavioral, and clinical characteristics. Analyses were conducted in 2017-2019. No associations were observed between fine particulate matter or ozone concentration and prevalent or incident hypertension. In linear models, an IQR increase in 1-year ozone concentration was associated with 0.67 mmHg higher systolic blood pressure (95% CI=0.27, 1.06), 0.42 mmHg higher diastolic blood pressure (95% CI=0.20, 0.63), and 0.50 mmHg higher mean arterial pressure (95% CI=0.26, 0.74). In hierarchical models, fine particulate matter was inversely associated with systolic blood pressure (-0.72, 95% CI= -1.31, -0.13), diastolic blood pressure (-0.69, 95% CI= -1.02, -0.36), and mean arterial pressure (-0.71, 95% CI= -1.08, -0.33). Attenuated associations were observed with 1-year concentrations and at Visit 1. Positive associations were observed between ozone and systolic blood pressure, diastolic blood pressure, and mean arterial pressure, and inverse associations between fine particulate matter and systolic blood pressure, diastolic blood pressure, and mean arterial pressure in an African American population with high (56%) prevalence of hypertension. Effect sizes were small and may not be clinically relevant.

Characteristics and resolution of hypertension in obese African American bariatric cohort

Weight reduction continues to be first-line therapy in the treatment of hypertension (HTN). However, the long-term effect of bariatric malabsorptive surgical techniques such as Roux-en-Y Gastric Bypass (RYGB) surgery in the management of hypertension (HTN) is less clear. African Americans (AA) are disproportionately affected by obesity and hypertension and have inconsistent outcomes after bariatric surgery (BS). Despite a plethora of bariatric literature, data about characteristics of a predominantly AA bariatric hypertensive cohort including hypertension in obese (HIO) are scarce and underreported. The aims of this study were, (1) to describe the preoperative clinical characteristics of HIO with respect to HTN status and age, and (2) to identify predictors of HTN resolution one year after RYGB surgery in an AA bariatric cohort enrolled at the Howard University Center for Wellness and Weight Loss Surgery (HUCWWS). In the review of 169 AA bariatric patients, the average BMI was 48.50 kg/m2 and the average age was 43.86 years. Obese hypertensive patients were older (46 years vs. 37.89 years; p < .0001); had higher prevalence of diabetes mellitus (DM, 43.09% vs. 10.87%; p < .0001) and dyslipidemia (38.2% vs. 13.04%; p 0.002). Hypertensive AA who were taking ≥ 2 antihypertensive medications prior to RYGB were 18 times less likely to experience HTN resolution compared to hypertensive AA taking 0–1 medications, who showed full or partial response. Also, HIO was less likely to resolve after RYGB surgery in patients who needed ≥ 2 antihypertensive medications prior to surgical intervention.

The gut microbiome of COVID-19 recovered patients returns to uninfected status in a minority-dominated United States cohort

ABSTRACT To investigate the relationship between intestinal microbiota and SARS-CoV-2-mediated pathogenicity in a United States, majority African American cohort. We prospectively collected fecal samples from 50 SARS-CoV-2 infected patients, 9 SARS-CoV-2 recovered patients, and 34 uninfected subjects seen by the hospital with unrelated respiratory medical conditions (controls). 16S rRNA sequencing and qPCR analysis was performed on fecal DNA/RNA. The fecal microbial composition was found to be significantly different between SARS-CoV-2 patients and controls (PERMANOVA FDR-P = .004), independent of antibiotic exposure. Peptoniphilus, Corynebacterium and Campylobacter were identified as the three most significantly enriched genera in COVID-19 patients compared to controls. Actively infected patients were also found to have a different gut microbiota than recovered patients (PERMANOVA FDR-P = .003), and the most enriched genus in infected patients was Campylobacter, with Agathobacter and Faecalibacterium being enriched in the recovered patients. No difference in microbial community structure between recovered patients and uninfected controls was observed, nor a difference in alpha diversity between the three groups. 24 of the 50 COVID-19 patients (48%) tested positive via RT-qPCR for fecal SARS-CoV-2 RNA. A significant difference in gut microbial composition between SARS-CoV-2 positive and negative samples was observed, with Klebsiella and Agathobacter being enriched in the positive cohort. No significant associations between microbiome composition and disease severity was found. The intestinal microbiota is sensitive to the presence of SARS-CoV-2, with increased relative abundance of genera (Campylobacter, Klebsiella) associated with gastrointestinal (GI) disease. Further studies are needed to investigate the functional impact of SARS-CoV-2 on GI health.

Plasma adipokines and glycaemic progression among African Americans: Findings from the Jackson Heart Study.

To evaluate the association between plasma biomarkers including leptin, adiponectin, adiponectin-to-leptin ratio and high-sensitivity C-reactive protein (hsCRP) with risk of glycaemic progression and incident dysglycaemia (pre-diabetes or diabetes) in a community-based sample of African American (AAs). We analysed data from 3223 participants without type 2 diabetes at baseline (2000-2004) who attended ≥1 follow-up visit. Poisson regression was used to generate risk ratios (RRs) for glycaemic progression and incident dysglycaemia. Over a median of 7 years, 46.4% developed glycaemic progression (n=1495). After adjusting for demographic and lifestyle variables, the RRs (95% CI) for glycaemic progression comparing highest (Q4) to lowest (Q1) quartiles were 1.30 (1.10-1.54), 0.74 (0.65-0.84), 0.70 (0.62-0.80) and 1.22 (1.07-1.38) for leptin, adiponectin, adiponectin-leptin ratio and hsCRP, respectively. Upon additional adjustment for BMI, the corresponding RRs (95% CIs) were 1.15 (0.94-1.42), 0.76 (0.67-0.86), 0.72 (0.62-0.84) and 1.14 (0.99-1.31) respectively. Among participants with normal glycaemia, the RRs (95% CIs) for incident pre-diabetes in Q4 vs Q1 were 1.37 (1.13-1.67), 0.73 (0.63-0.85), 0.70 (0.59-0.82) and 1.28 (1.10-1.48) for leptin, adiponectin, adiponectin-leptin ratio and hsCRP, respectively; equivalent RRs for incident diabetes were 5.15 (2.63-10.10), 0.36 (0.20-0.68), 0.21 (0.12-0.38) and 3.04 (1.70-5.44), respectively. In this large community-based cohort of AAs, our results suggest that high plasma leptin and hsCRP, as well as low adiponectin and adiponectin-to-leptin ratio, are associated with higher risks of glycaemic progression. The findings point to the potential utility of these biomarkers in predicting and preventing glycaemic progression in this high-risk population.

Common and Rare Variant Prediction and Penetrance of IBD in a Large, Multi-ethnic, Health System-based Biobank Cohort

Polygenic risk scores (PRS) may soon be used to predict inflammatory bowel disease (IBD) risk in prevention efforts. We leveraged exome-sequence and single nucleotide polymorphism (SNP) array data from 29,358 individuals in the multiethnic, randomly ascertained health system-based BioMe biobank to define effects of common and rare IBD variants on disease prediction and pathophysiology. PRS were calculated from European, African American, and Ashkenazi Jewish (AJ) reference case-control studies, and a meta-GWAS run using all three association datasets. PRS were then combined using regression to assess which combination of scores best predicted IBD status in European, AJ, Hispanic, and African American cohorts in BioMe. Additionally, rare variants were assessed in genes associated with very early-onset IBD (VEO-IBD), by estimating genetic penetrance in each BioMe population. Combining risk scores based on association data from distinct ancestral populations improved IBD prediction for every population in BioMe and significantly improved prediction among European ancestry UK Biobank individuals. Lower predictive power for non-Europeans was observed, reflecting in part substantially lower African IBD case-control reference sizes. We replicated associations for two VEO-IBD genes, ADAM17 and LRBA, with high dominant model penetrance in BioMe. Autosomal recessive LRBA risk alleles are associated with severe, early-onset autoimmunity; we show that heterozygous carriage of an African-predominant LRBA protein-altering allele is associated with significantly decreased LRBA and CTLA-4 expression with T-cell activation. Greater genetic diversity in African populations improves prediction across populations, and generalizes some VEO-IBD genes. Increasing African American IBD case-collections should be prioritized to reduce health disparities and enhance pathophysiological insight.

Incidence and progression of ankle osteoarthritis: The johnston county osteoarthritis project

ObjectiveTo determine the incidence and progression of ankle osteoarthritis (OA) and associated risk factors in a community-based cohort of African Americans and whites. MethodsData were from 541 participants who had standardized lateral and mortise radiography of the ankles in weight bearing at baseline (2013–2015) and follow-up (2017–2018). Incident radiographic ankle OA (rAOA) was defined as a Kellgren-Lawrence grade (KLG) ≥ 1 at follow-up among ankles with baseline KLG < 1; progressive rAOA was a ≥ 1 KLG increase at follow-up among ankles with KLG ≥ 1 at baseline. Symptoms were assessed using self-reported pain, aching, and stiffness (PAS) on most days and the Foot and Ankle Outcome Score (FAOS) symptoms subscale. Ankle-level logistic regression models were used to assess associations of ankle outcomes with covariates (age, sex, race, body mass index [BMI], smoking, number of symptomatic joints, comorbidities, prior ankle injury, and knee or foot OA). ResultsAmong ankles without rAOA at baseline, 28% developed incident rAOA, 37% had worsening FAOS symptoms, and 7% had worsening PAS. Incident rAOA and worsening ankle symptoms were associated with higher BMI and symptoms in other joints. Among ankles with baseline rAOA, 4% had progressive rAOA, 35% had worsening of FAOS symptoms, and 9% had worsening PAS. rAOA progression was associated with ankle injury and concomitant knee or foot OA; worsening of symptoms was associated with higher BMI and other symptomatic joints. ConclusionsNot all ankle OA is post-traumatic. Smoking prevention/cessation, a healthy weight, and injury prevention may be methods for reducing the incidence and progression of rAOA.

Association between goal-striving stress and rapid kidney function decline among African Americans: the Jackson Heart Study

African Americans (AAs) are disproportionately affected by kidney disease and also report higher psychosocial stressors than other racial groups. Goal-striving stress (GSS) is an understudied psychosocial stressor related to attempting...

Goals-of-Care Consult and Future Costs, Acute Care and Hospice Use in Matched Cohorts of African Americans and Whites

African Americans receive less hospice care and more aggressive end-of-life care than Whites. Little is known about how palliative care consultation to discuss goals-of-care (“PCC”) is associated with future acute care utilization and costs, or hospice use, by race. To compare future acute care costs and utilization and discharge to hospice between propensity-matched cohorts of African Americans with and without PCC, and Whites with and without PCC, we conducted a secondary analysis of 35,154 seriously-ill African American and White adults who had PCC at a high-acuity hospital and were discharged 2014-2016. We found no significant difference between African Americans with or without PCC in mean future acute care costs ($11,651 vs. $15,050, P=0.09), 30-day readmissions (P=0.58), future hospital days (P=0.34), future ICU admission (P=0.25), or future ICU days (P=0.30), but found greater discharge to hospice among African Americans with PCC (36.5% vs. 2.4%, P<0.0001). We found significant differences between Whites with PCC vs. without PCC in mean future acute care costs ($8,095 vs. $16,799, P<0.001), 30-day readmissions (10.2% vs. 16.7%, P<0.0001), future days hospitalized (3.7 vs. 6.3 days, P<0.0001), and discharge to hospice (42.7% vs. 3.0%, P<0.0001). Results suggest PCC decreases future acute care costs and utilization in Whites and, directionally but not significantly, in African Americans; and increases discharge to hospice in both races (15-fold in African Americans, 14-fold in Whites). Research is needed to understand how PCC supports end-of-life decision-making and hospice use across races and how systems and policies can enable effective goals-of-care consultations across settings.

Glutamate-Serine-Glycine Index: A Novel Potential Biomarker in Pediatric Non-Alcoholic Fatty Liver Disease.

Preliminary evidence suggests that the glutamate–serine–glycine (GSG) index, which combines three amino acids involved in glutathione synthesis, may be used as a potential biomarker of non-alcoholic fatty liver disease (NAFLD). We investigated whether the GSG index is associated with NAFLD in youth, independent of other risk factors. Intrahepatic fat content (HFF%) and abdominal fat distribution were measured by magnetic resonance imaging (MRI) in a multiethnic cohort of obese adolescents, including Caucasians, African Americans, and Hispanics. NAFLD was defined as HFF% ≥ 5.5%. Plasma amino acids were measured by mass spectrometry. The GSG index was calculated as glutamate/(serine + glycine). The GSG index was higher in NAFLD patients (p = 0.03) and positively correlated with HFF% (r = 0.26, p = 0.02), alanine aminotransferase (r = 0.39, p = 0.0006), and aspartate aminotransferase (r = 0.26, p = 0.03). Adolescents with a high GSG index had a twofold higher prevalence of NAFLD than those with a low GSG index, despite similar adiposity, abdominal fat distribution, and liver insulin resistance. NAFLD prevalence remained significantly different between groups after adjustment for age, sex, race/ethnicity, and body mass index (OR 3.07, 95% confidence interval 1.09–8.61, p = 0.03). This study demonstrates the ability of the GSG index to detect NAFLD in at-risk pediatric populations with different genetically determined susceptibilities to intrahepatic fat accumulation, independent of traditional risk factors.

Timing of school desegregation experience and late‐life cognition in the Study of Healthy Aging in African Americans (STAR) cohort

AbstractBackgroundPrior studies suggest segregated school experiences are associated with poorer late‐life cognition among African Americans. However, less is known about how the timing of school desegregation in the individual’s lifecourse or historically is associated with cognition for younger cohorts.MethodThe Study of Healthy Aging in African Americans (STAR) is a cohort of community‐dwelling Kaiser Permanente members residing in the San Francisco Bay area and Sacramento valley. The study has enrolled 722 African Americans (half ages 50‐64, half 65+) and aims to understand lifecourse processes that contribute to cognitive aging disparities. Experiences of segregation were self‐reported and modeled three ways: 1) having attended only segregated schools vs. only integrated; 2) by life stage when first transitioned to a desegregated school (i.e. 1st‐6th, 7th‐9th or 10th‐12th grades); and 3) the historical timing of school desegregation relative to the 1954 Brown vs. Board of Education decision mandating school integration (many districts were reluctant to integrate in a timely manner). Executive function, semantic memory and verbal memory measured with the Spanish and English Neuropsychological Assessment Scales (SENAS) were z‐standardized and averaged for overall cognition. Linear regression was used for analysis; models controlled for age, gender, and education.ResultParticipant mean age was 68 (8.7) and 69% were female. Compared with participants who only attended integrated schools (ref.; n=438), those who only attended segregated schools (n=145) had significantly lower overall cognition, executive function and semantic memory (see table). Those who transitioned from segregated to integrated schools between 7th and 9th grade (n=51) had worse executive function and semantic memory than those who only attended integrated schools; we did not observe significant associations for those who transitioned to integrated schools in 1st‐6th grades (n=44), or 10th‐12th grades (n=43). We observed no differences in cognition by historical timing of desegregation.ConclusionOlder African Americans who attended only segregated schools or experienced desegregation in 7th‐9th grades had worse later‐life cognitive test scores than those who attended racially integrated schools. Our findings suggest that only attending segregated schools and the timing of school desegregation in the lifecourse may have implications for understanding cognitive aging among African Americans.

Abstract 13716: Racial Differences in Patients With Cryptogenic Stroke With Insertable Cardiac Monitors

Introduction: African American (AA) patients have a higher incidence of stroke but lower prevalence of atrial fibrillation (AF). Studies involving long term monitoring with implantable cardiac monitors (ICM) for AF after cryptogenic stroke are limited by the under-representation of the AA population. Objective: We sought to assess racial differences in the diagnosis of AF by implantable cardiac monitors in patients with cryptogenic stroke. Methods: We performed a retrospective chart review study at Methodist University Hospital, University of Tennessee Health Science Center, Memphis TN. We included patients with cryptogenic stroke who received an ICM from September 2014 to June 2019 to assess for AF. Race and additional demographic characteristics were obtained from the electronic medical records. Interrogation reports from the ICMs were obtained by remote monitoring as well as clinic visits. Fisher exact and student t test were used to compare demographic data as well as the incidence of AF in these patients. Results: A total of 219 patients with cryptogenic stroke who underwent ICM implantation were included, of which 129 (58.9%) were AA. In the AA cohort, the patients were significantly younger than (62.3 versus 65.8 years; p =0.04) and had a significantly higher prevalence of hypertension (92.2% versus 68.5%; p &lt;0.01) and diabetes mellitus (40.3% versus 27.3%; p =0.04). Upon a mean follow up of 10.6 months, a total of 39 patients (17.8%) were diagnosed with AF on ICM monitoring. The mean time to the incidence of AF was 7.4 months. There was no significant difference in the incidence of AF in the AA population (17.8%) as compared to the rest of the population (17.8%) ( p =1.00). Conclusion: In this single center study of patients with cryptogenic stroke who underwent long term monitoring with ICM, there was no significant difference in the incidence of AF between AA and the rest of the population. We conclude that ICM’s have an equally important role in AF detection in AA patients as in the general population with cryptogenic stroke.

Abstract 13641: Serum Vitamin D3 Levels, Left Ventricular Structure and Incident Hospitalization for Heart Failure With Preserved Ejection Fraction in African Americans: The Jackson Heart Study

Background: Lower serum vitamin D3 (VitD3) concentration has been associated with cardiovascular disease. However, the associations between serum VitD3 levels and left ventricular (LV) structure and function and heart failure with preserved ejection fraction (HFpEF) have not been well-characterized community. The prevalence of VitD3 deficiency is higher among African Americans than in other race/ethnicity groups. We hypothesized that serum VitD3 levels are associated with LV concentric remodeling and incident heart failure (HF) in African Americans. Methods and Results: Among 4872 African Americans in the Jackson Heart Study cohort, we investigated the relationships between serum VitD3 levels and LV structure and function, evaluated with echocardiography, and incident HF hospitalization, categorized either HF with reduced EF (HFrEF: EF&lt;50%) or HFpEF (EF≥50%). The median and interquartile serum VitD3 levels were 12.0 (8.6-16.7) ng/mL. After adjustment for age, sex, body mass index, systolic blood pressure, anti-hypertensive medication use, current smoking status, and estimated glomerular filtration rate, lower VitD3 levels were associated with greater septal and posterior wall thickness and plasma brain natriuretic peptide (BNP) levels, but not with LV mass index or LVEF (Table). Over a median follow-up period of 11 (10.3~11) years, 313 participants developed incident HF (7.79 cases per 1,000 person-years), including 128 (41%) HFrEF and 185 (59%) HFpEF cases. After adjustment, lower serum VitD3 levels were associated with higher incidence of HF overall and levels seemed to be mostly related to HFpEF (Table). Conclusion: In this community-based African American cohort, lower serum VitD3 levels were associated with LV concentric remodeling and incident HF, mainly HFpEF. Further investigation is required to examine whether the supplementation of VitD3 can prevent LV concentric remodeling and incident HFpEF in African Americans.

Abstract 16967: Predictors for Recovery of Ejection Fraction in Urban Cohort of Patients With Heart Failure

Introduction: Despite the clinical and economic impact of heart failure with reduced ejection fraction (HFrEF), understanding surrounding factors associated with resolution of ejection fraction (EF) as well as its prognostic value, remains elusive. Hypothesis: Predictors for Recovery of EF may differ in African Americans compared to the general population. Methods: We conducted a single center retrospective chart review on patients following up in the adult heart failure clinic at our inner city hospital located in Central Brooklyn. Chart review of 312 patients was performed and data including, demographics, comorbidities, medications and echocardiographic parameters. Patients not on an ACE inhibitor or angiotensin receptor blocker (ARB) were excluded as were those with a diagnosis of heart failure with preserved ejection fraction. Results: Of 312 patients identified, 158 (50.6%) were male and 289 (92.6%) identified as African in ancestry. Mean time since diagnosis was 86.2 months (SEM 4.9). There were 113 (36.2%) patients who had recovery of ejection fraction to greater than 50%. There were 59 patients on Angiotensin Receptor-Neprilysin Inhibitor (ARNI) therapy. Patients on ARNI were less likely to have ventricular recovery with an Odds Ratio (OR) of 0.484. The duration of heart failure in the patients with ARNI was significantly less than those on ACE/ARB therapy, 29.15 months versus 99.49 months respectively (2 tailed P value for difference of means &lt;0.0001). Beta blocker use and Aldosterone antagonism were also associated with a reduced likelihood of recovery in ejection fraction (OR 0.177 and 0.294) respectively. Other classes of medication as well as comorbidities including an ischemic etiology had no statistically significant impact. Conclusion: In our predominantly African American cohort of patients, key GDMT medication including ARNI, Beta blockers and aldosterone antagonists reduced the odds of EF recovery.

Correction of Point-of-Care International Normalized Ratio (INR) Values in Patients with Sickle Cell Disease

Background: With a narrow therapeutic range, warfarin use needs to be closely monitored to minimize the risk of bleeding or thrombosis. Point-of-care (POC) International Normalized Ratio (INR) tests using finger stick blood samples provide instantaneous results and improve testing efficiency; however, the test accuracy of POC-INR may be affected by various factors such as anemia (1, 2). Thrombosis and warfarin use are prevalent in patients with sickle cell disease (SCD) (3), but evidence on the accuracy or correction of POC-INR in this patient population is lacking. This study evaluates correlation of POC-INR to clinical laboratory INR (CL-INR) in patients with SCD. Methods: POC-INR and CL-INR values measured within 12 hours of each other in patients with SCD treated at the UI-Health from 2015-2017 were collected. A total of 28 INR pairs were used to form a discovery cohort. A cohort of non-SCD African American (AA) patients with POC-INR and CL-INR values measured within 12 hours who were treated at UIC-Health during the same period were utilized as a control group. Patient demographic and clinical characteristics were recorded to calculate a correction factor. Additional 28 POC- and CL-INR pairs in patients with SCD were used to form a validation cohort. Descriptive statistics, Kruskal-Wallis test, Chi-square test, and linear regression were used for data analysis. The study was approved by the UIC Institutional Review Board (protocol #2020-0191). Results: In the discovery cohort with 100% AA patients, POC-INR in an acceptable range of the CL-INR, defined as an INR difference within ±0.5 INR of CL-INR when POC-INR &amp;lt; 2 or ±30% of CL-INR when POC-INR ≥ 2 (4), was present in 6 of 7 (86%) of patients when INR &amp;lt; 4 compared to 5 of 21 (24%) when INR ≥ 4. For POC-INR ≥ 4, a correction factor of 0.7 was derived using a linear regression model (95%CI: 0.685-0.752, P&amp;lt;0.001, R square: 0.991), which significantly improved the in-range POC-INR from 24% to 100% in the discovery cohort (P&amp;lt;0.001). In the validation cohort, the in-range POC-INR increased from 19% to 95% (P&amp;lt;0.001) after applying the correction factor of 0.7 (Figure 1). When compared to the non-SCD AA cohort, the patients with SCD were younger (38 vs 59 years, P&amp;lt;0.001) and more anemic (HCT 27% vs 37%, P&amp;lt;0.001). However, there was no significant difference in the in-range POC-INR percentage (37% vs 42%, P = 0.547) (Table 1). The correction factor for POC-INR ≥ 4 in the non-SCD AA cohort was the same as the SCD cohort as 0.7. Summary: POC-INR over-estimates a simultaneous CL-INR when POC-INR ≥ 4 in patients with SCD, and a correction factor significantly improved the agreement with CL-INR. Despite the difference in anemia, the accuracy of POC-INR and correction factor were similar between SCD patients and non-SCD AA patients. An institution-specific correction factor for POC-INR ≥ 4 should be applied similarly to both SCD and non-SCD patients. Reference: 1. R. W. Hoel et al., Correlation of point-of-care International Normalized Ratio to laboratory International Normalized Ratio in hemodialysis patients taking warfarin. Clin J Am Soc Nephrol4, 99-104 (2009). 2. C. E. DeRemer, B. McMichael, H. N. Young, Warfarin Patients With Anemia Show Trend of Out-of-Range International Normalized Ratio Frequency With Point-of-Care Testing in an Anticoagulation Clinic. J Pharm Pract32, 499-502 (2019) 3. A. Srisuwananukorn et al., Clinical, laboratory, and genetic risk factors for thrombosis in sickle cell disease. Blood Adv4, 1978-1986 (2020). 4. W. Plesch et al., Results of the performance verification of the CoaguChek XS system. Thromb Res123, 381-389 (2008). Disclosures Gordeuk: CSL Behring: Consultancy, Research Funding; Global Blood Therapeutics: Consultancy, Research Funding; Imara: Research Funding; Ironwood: Research Funding; Novartis: Consultancy. Saraf:Novartis, Global Blood Therapeutics: Membership on an entity's Board of Directors or advisory committees; Global Blood Therapeutics: Membership on an entity's Board of Directors or advisory committees, Other: Advisory Boards, Speakers Bureau; Pfizer, Global Blood Therapeutics, Novartis: Research Funding.

Candidate Gene Analysis Reveals Strong Association of CETP Variants With High Density Lipoprotein Cholesterol and PCSK9 Variants With Low Density Lipoprotein Cholesterol in Ghanaian Adults: An AWI-Gen Sub-Study.

Variations in lipid levels are attributed partly to genetic factors. Genome-wide association studies (GWASs) mainly performed in European, African American and Asian cohorts have identified variants associated with LDL-C, HDL-C, total cholesterol (TC) and triglycerides (TG), but few studies have been performed in sub-Saharan Africans. This study evaluated the effect of single nucleotide variants (SNVs) in eight candidate loci (ABCA1, LCAT, LPL, PON1, CETP, PCSK9, MVK, and MMAB) on lipid levels among 1855 Ghanaian adults. All lipid levels were measured directly using an automated analyser. DNA was extracted and genotyped using the H3Africa SNV array. Linear regression models were used to test the association between SNVs and log-transformed lipid levels, adjusting for sex, age and waist circumference. In addition Bonferroni correction was performed to account for multiple testing. Several variants of CETP, LCAT, PCSK9, and PON1 (MAF > 0.05) were associated with HDL-C, LDL-C and TC levels at p < 0.05. The lead variants for association with HDL-C were rs17231520 in CETP (β = 0.139, p < 0.0001) and rs1109166 in LCAT (β = −0.044, p = 0.028). Lower LDL-C levels were associated with an intronic variant in PCSK9 (rs11806638 [β = −0.055, p = 0.027]) and increased TC was associated with a variant in PON1 (rs854558 [β = 0.040, p = 0.020]). In silico functional analyses indicated that these variants likely influence gene function through their effect on gene transcription. We replicated a strong association between CETP variants and HDL-C and between PCSK9 variant and LDL-C in West Africans, with two potentially functional variants and identified three novel variants in linkage disequilibrium in PON1 which were associated with increasing TC levels in Ghanaians.

Estimation of covariate effects in proportional cross-ratio model of bivariate time-to-event outcomes

Medical studies often collect bivariate survival data including time to the same type of disease in twins or time to two different diseases from the same individuals. Cross-ratio, defined as the ratio of conditional hazard functions for one event given the other, is often used as a measure of dependency between the two survival outcomes. Statistical methods have also been proposed to estimate the effect of covariates on cross-ratio in order to identify common factors influencing both survival outcomes. There are currently three estimation approaches for cross-ratio, namely, a parametric approach using the Clayton copula, a semi-parametric two-stage approach proposed by Shih and Louis, and a nonparametric pseudo-partial likelihood approach proposed by Hu et al. In this paper, we compare the three estimation approaches on estimating covariates’ effect on the cross-ratio in simulation studies. We found that the nonparametric pseudo-partial likelihood estimation approach performed well and that the method was also robust under various model assumptions. Data from a longitudinal cohort of elderly African Americans were used to illustrate the three estimation approaches.

Metabolic Perturbation Associated with Per- and Polyfluoroalkyl Substances (PFAS) in an African American Pregnancy Cohort

Background. Per- and polyfluoroalkyl substances (PFASs) are suspected developmental toxicants that are ubiquitous and persistent in the environment. Exposures to PFASs during the prenatal period have been linked to adverse pregnancy and birth outcomes. Notably, communities of color and those affected by socioeconomic disadvantage, particularly African American (AA) pregnant women, disproportionately experience high levels of PFAS exposure and adverse health outcomes. Mechanisms underlying these relationships are complex and largely unknown. Methods. We used metabolomics, a high-throughput analytical method involving the identification and quantification of thousands of metabolic features associated with exogenous exposure and endogenous processes, to address these knowledge gaps. We measured serum levels of 12 PFAS and conducted high-resolution metabolic profiling on 320 maternal serum samples collected during the first trimester of pregnancy from Atlanta African American Maternal-Child cohort participants. We conducted untargeted Metabolome Wide Association Study (MWAS) to detect metabolic perturbations associated with PFAS exposures and explore underlying molecular mechanisms. Results. The average serum levels of perfluorooctanoic acid (PFOA) and perfluorooctanesulfonic acid (PFOS) were 0.94±0.57 and 3.28±1.67 ng/mL, respectively. In total, 29,524 metabolic features have been reliably extracted from two technical columns. Using multivariate linear regression models, we found 125 metabolic features were significantly associated with one or more PFAS, when controlling for covariates and false positive discovery rate. Pathway analysis indicated several oxidative stress and inflammatory pathways associated with PFAS exposures, including aspartate, arginine, and glycosphingolipid metabolism. We validated five metabolites using authentic chemical reference standards, including aspartate and arginine, which are both significantly associated with PFOA, PFOS, and perfluorononanoic acid (PFNA). Conclusions. Using untargeted MWAS, we identified and verified several pathways and metabolites associated with PFAS exposures among AA pregnant women, which offer promising initial evidence to examine the underlying molecular mechanisms and provide opportunities for interventions to improve outcomes in exposed mothers and children.

Acute Kidney Injury in a Predominantly African American Cohort of Kidney Transplant Recipients With COVID-19 Infection.

Renal involvement in severe or critical acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection is frequent. Acute kidney injury (AKI) in African American (AA) kidney transplant recipients (KTRs) with COVID-19 is not well described. We report our experience with a predominantly AA cohort (79%) of KTRs with COVID-19 infections in the Detroit Metropolitan area. In this retrospective, single-center study, we identified 39 KTRs who tested positive for SARS-CoV-2 between March 16 and April 25, 2020. Data from electronic medical records were retrieved and compared between KTRs without AKI and KTRs with AKI. One patient was excluded due to delayed graft function. Final analysis of AKI in KTRs with proven COVID-19 was done on 38 patients of which 30 were AA (79%). AKI occurred in 71.1% of COVID-19 KTRs (n = 27), of whom 6 (22.2%) patients required HD. The incidence of AKI in our cohort was 71% (27/38). AKI rate among AA was 76.7% versus 50% in non-AA cohort (P = 0.195). In a univariate logistic regression analysis, AA race was not significantly associated with AKI odds ratio (3.4; CI, 0.68-17.4; P = 0.14). After risk adjustment by race, patients with diabetes showed a significantly higher risk of AKI (adjusted odds ratio, 19.85; CI, 1.65-58.66; P = 0.012). KTRs with AKI had more preexisting renin angiotensin aldosterone system inhibitor use than KTRs without AKI (P = 0.03). KTRs infected with SARS-CoV-2 have a high incidence of AKI, with associated increased morbidity and mortality. Although no racial differences in mortality were noted in our KTRs with AKI, we await data from registries to help elucidate this difference.

Examining the Potential Impact of Race Multiplier Utilization in Estimated Glomerular Filtration Rate Calculation on African-American Care Outcomes.

Advancing health equity entails reducing disparities in care. African-American patients with chronic kidney disease (CKD) have poorer outcomes, including dialysis access placement and transplantation. Estimated glomerular filtration rate (eGFR) equations, which assign higher eGFR values to African-American patients, may be a mechanism for inequitable outcomes. Electronic health record-based registries enable population-based examination of care across racial groups. To examine the impact of the race multiplier for African-Americans in the CKD-EPI eGFR equation on CKD classification and care delivery. Cross-sectional study SETTING: Two large academic medical centers and affiliated community primary care and specialty practices. A total of 56,845 patients in the Partners HealthCare System CKD registry in June 2019, among whom 2225 (3.9%) were African-American. Exposures included race, age, sex, comorbidities, and eGFR. Outcomes were transplant referral and dialysis access placement. Of 2225 African-American patients, 743 (33.4%) would hypothetically be reclassified to a more severe CKD stage if the race multiplier were removed from the CKD-EPI equation. Similarly, 167 of 687 (24.3%) would be reclassified from stage 3B to stage 4. Finally, 64 of 2069 patients (3.1%) would be reassigned from eGFR > 20ml/min/1.73m2 to eGFR ≤ 20ml/min/1.73m2, meeting the criterion for accumulating kidney transplant priority. Zero of 64 African-American patients with an eGFR ≤ 20ml/min/1.73m2 after the race multiplier was removed were referred, evaluated, or waitlisted for kidney transplant, compared to 19.2% of African-American patients with eGFR ≤ 20ml/min/1.73m2 with the default CKD-EPI equation. Single healthcare system in the Northeastern United States and relatively small African-American patient cohort may limit generalizability. Our study reveals a meaningful impact of race-adjusted eGFR on the care provided to the African-American CKD patient population.

GABAergic polygenic risk for cocaine use disorder is negatively correlated with precuneus activity during cognitive control in African American individuals

Impaired cognitive control has been implicated in cocaine use disorder (CUD). GABAergic treatments have been proposed for CUD. Here we examined relationships between GABAergic genes and neural correlates of cognitive control in CUD. We analyzed two independent African American cohorts: one of >3000 genomewide-genotyped subjects with substance dependence and another of 40 CUD and 22 healthy control (HC) subjects who were exome-array genotyped and completed an fMRI Stroop task. We used five association thresholds to select variants of GABAergic genes in the reference cohort, yielding five polygenic risk scores (i.e., CUD-GABA-PRSs) for the fMRI cohort. At p < 0.005, the CUD-GABA-PRSs, which aggregated relative risks of CUD from 89 variants harboring in 16 genes, differed between CUD and HC individuals in the fMRI sample (p = 0.013). This CUD-GABA-PRS correlated inversely with Stroop-related activity in the left precuneus in CUD (r = −80.58, pFWE < 0.05) but not HC participants. Post-hoc seed-based connectivity analysis of the left precuneus identified reduced functional connectivity to the posterior cingulate cortex (PCC) in CUD compared to HC subjects (p = 0.0062) and the degree of connectivity correlated with CUD-GABA-PRSs in CUD individuals (r = 0.287, p = 0.036). Our findings suggest that the GABAergic genetic risk of CUD in African Americans relates to precuneus/PCC functional connectivity during cognitive control. Identification of these GABAergic processes may be relevant targets in CUD treatment. The novel identification of 16 GABAergic genes may be investigated further to inform treatment development efforts for this condition that currently has no medication with a formal indication for its treatment.