African American Risk Research Articles

The key role of NLRP3 and STING in APOL1-associated podocytopathy.

Coding variants in apolipoprotein L1 (APOL1), termed G1 and G2, can explain most excess kidney disease risk in African Americans; however, the molecular pathways of APOL1-induced kidney dysfunction remain poorly understood. Here, we report that expression of G2 APOL1 in the podocytes of Nphs1rtTA/TRE-G2APOL1 (G2APOL1) mice leads to early activation of the cytosolic nucleotide sensor, stimulator of interferon genes (STING), and the NLR family pyrin domain-containing 3 (NLRP3) inflammasome. STING and NLRP3 expression was increased in podocytes from patients with high-risk APOL1 genotypes, and expression of APOL1 correlated with caspase-1 and gasdermin D (GSDMD) levels. To demonstrate the role of NLRP3 and STING in APOL1-associated kidney disease, we generated transgenic mice with the G2 APOL1 risk variant and genetic deletion of Nlrp3 (G2APOL1/Nlrp3 KO), Gsdmd (G2APOL1/Gsdmd KO), and STING (G2APOL1/STING KO). Knockout mice displayed marked reduction in albuminuria, azotemia, and kidney fibrosis compared with G2APOL1 mice. To evaluate the therapeutic potential of targeting NLRP3, GSDMD, and STING, we treated mice with MCC950, disulfiram, and C176, potent and selective inhibitors of NLRP3, GSDMD, and STING, respectively. G2APOL1 mice treated with MCC950, disulfiram, and C176 showed lower albuminuria and improved kidney function even when inhibitor treatment was initiated after the development of albuminuria.

S413 The Interaction Effect of Gender and Socio-Economic Status on the Incidence of COVID-19 in Patients With Gastroesophageal Reflux Disease: A Population-Based Study

Introduction: Reports on COVID-19 have shown gender and racial differences in health outcomes. Our aim was to examine the relationship between social determinants of health and risk of COVID-19 in patients with gastroesophageal reflux disease (GERD). Methods: We analyzed medical records from a large population database (Explorys, IBM) pooled from 26 major healthcare systems across US. Only adult patients with diagnosis of GERD from January 1999-May 2021 and COVID-19 from December 2019-May 2021 were included. Data on gender, race/ethnicity, insurance status and PPI use were collected. Univariable and multivariable analyses were used for statistical analysis. Model was stratified by gender. Effect modification by PPI use was examined. Results: We identified 6215670 GERD patients of which 4057825 (65%) used PPI, 2409175 (59%) were females and 1648650 (41%) were males. A total of 3605950 (58%) were uninsured. Cumulative incidence of COVID-19 among PPI users and non-users was 0.11% vs 0.04% (P< 0.001). In univariate analysis, odds (OR) of COVID-19 was highest among whites 3.35 [3.11-3.6, P< 0.05], African Americans OR 2.9 [2.7-3.12, P< 0.05] and Hispanics OR 2.8 [2.6-3.0, P< 0.05]. Risk of COVID-19 was modified across all races if they were PPI users: whites OR 2.83 [2.6-3.14, P< 0.001], African Americans OR 3.11 [2.8-3.5, P< 0.05] and Hispanics OR 1.9 [1.4-2.5, p< 0.05]. Lack of insurance was significantly associated with COVID-19 diagnosis OR 3.1 [2.9-3.3, P < 0.001]. In the multivariate model, after adjusting for covariates, African American race was the strongest independent risk factor for COVID-19 OR 4.8 [4.3-5.2], P< 0.001) followed by PPI use OR 2.9 [2.7-3.1, P< 0.001]. There was no clear association between Hispanic or white race and COVID-19 OR 0.99 [0.87-1.1, P=0.6] and OR 0.94 [0.86-1.0, P=0.2], respectively. When the model was stratified by gender, being female reduced the risk of COVID-19 in Hispanics OR 0.55 [0.2-0.7, P< 0.001]. Female gender did not modify COVID-19 risk in African Americans (OR 1.2 [1.0-1.4, P=0.53] or whites OR 1.2 [1.0-1.4, P=0.9]. Patients with GERD who had public insurance such as Medicare OR 0.3 [0.2-0.31, P < 0.001] or Medicaid OR 0.4 [0.4-0.48, P< 0.001] had reduced risk of COVID-19 diagnosis compared to the uninsured. Conclusion: In GERD patients, COVID-19 diagnosis was highest among African Americans and PPI users. Female Hispanics were least likely to be diagnosed with COVID-19. Insurance status may indirectly influence susceptibility to COVID-19.Figure 1.: Multivariable regression analysis. A forest plot of gender differences for odds of COVID-19 diagnosis in patients with gastroesophageal reflux disease (GERD) based on race/ethnicity and public insurance type. Abbreviation: PPI, proton pump inhibitors.Table 1.: Baseline Characteristics of Patients with Gastroesophageal Reflux Disease (GERD) Included in the Study. Abbreviations: PPI, proton pump inhibitors; CI, confidence interval.

Nutrition Intervention for Reduction of Cardiovascular Risk in African Americans Using the 2019 American College of Cardiology/American Heart Association Primary Prevention Guidelines.

Introduction: The 2019 American College of Cardiology/American Heart Association (ACC/AHA) Prevention Guidelines emphasize reduction in dietary sodium, cholesterol, refined carbohydrates, saturated fat and sweetened beverages. We hypothesized that implementing this dietary pattern could reduce cardiovascular risk in a cohort of volunteers in an urban African American (AA) community church, during a 5-week ACC/AHA-styled nutrition intervention, assessed by measuring risk markers and adherence, called HEART-LENS (Helping Everyone Assess Risk Today Lenten Nutrition Study). Methods: The study population consisted of 53 volunteers who committed to eat only home-delivered non-dairy vegetarian meals (average daily calories 1155, sodium 1285 mg, cholesterol 0 mg; 58% carbohydrate, 17% protein, 25% fat). Body mass index (BMI) and fasting serum markers of cardiometabolic and risk factors were measured, with collection of any dietary deviation. Results: Of 53 volunteers, 44 (mean age 60.2 years, 37 women) completed the trial (88%); 1 was intolerant of the meals, 1 completed both blood draws but did not eat delivered food, and 7 did not return for the tests. Adherence to the diet was reported at 93% in the remaining 44. Cardiometabolic risk factors improved significantly, highlighted by a marked reduction in serum insulin (−43%, p = 0.000), hemoglobin A1c (6.2% to 6.0%, p = 0.000), weight and BMI (−10.2 lbs, 33 to 31 kg/m2, p = 0.000), but with small reductions of fasting glucose (−6%, p = 0.405) and triglyceride levels (−4%, p = 0.408). Additionally, improved were trimethylamine-N-oxide (5.1 to 2.9 µmol/L, −43%, p = 0.001), small dense low-density lipoprotein cholesterol (LDL) (24.2 to 19.1 mg/dL, −21%, p = 0.000), LDL (121 to 104 mg/dL, −14%, p = 0.000), total cholesterol (TC) (190 to 168 mg/dL, −12%, p = 0.000), and lipoprotein (a) (LP(a)) (56 to 51 mg/dL, −11%, p = 0.000); high sensitivity C-reactive protein (hs-CRP) was widely variable but reduced by 16% (2.5 to 2.1 ng/mL, p = NS) in 40 subjects without inflammatory conditions. Soluble urokinase plasminogen activator (suPAR) levels were not significantly changed. The ACC/AHA pooled cohort atherosclerotic cardiovascular disease (ASCVD) risk scores were calculated for 41 and 36 volunteers, respectively, as the ASCVD risk could not be calculated for 3 subjects with low lipid fractions at baseline and 8 subjects after intervention (p = 0.184). In the remaining subjects, the mean 10-year risk was reduced from 10.8 to 8.7%, a 19.4% decrease (p = 0.006), primarily due to a 14% decrease in low-density lipoprotein cholesterol and a 10 mm Hg (6%) reduction in systolic blood pressure. Conclusions: In this prospective 5-week non-dairy vegetarian nutrition intervention with good adherence consistent with the 2019 ACC/AHA Guidelines in an at-risk AA population, markers of cardiovascular risk, cardiometabolism, and body weight were significantly reduced, including obesity, low-density lipoprotein cholesterol (LDLc) density, LP(a), inflammation, and ingestion of substrates mediating production of trimethylamine-N-oxide (TMAO). Albeit reduced, hs-CRP and suPAR, were not lowered consistently. This induced a significant decrease in the 10-year ASCVD risk in this AA cohort. If widely adopted, this could dramatically reduce and possibly eradicate, the racial disparity in ASCVD events and mortality, if 19% of the 21% increase is eliminated by this lifestyle change.

Association of oral microbiota with lung cancer risk in a low-income population in the Southeastern USA.

Oral microbiome plays an important role in oral health and systemic diseases, including cancer. We aimed to prospectively investigate the association of oral microbiome with lung cancer risk. We analyzed 156 incident lung cancer cases (73 European Americans and 83 African Americans) and 156 individually matched controls nested within the Southern Community Cohort Study. Oral microbiota were assessed using 16S rRNA gene sequencing in pre-diagnostic mouth rinse samples. Paired t test and the permutational multivariate analysis of variance test were used to evaluate lung cancer risk association with alpha diversity or beta diversity, respectively. Conditional logistic regression models were used to evaluate the association of individual bacterial abundance or prevalence with lung cancer risk. No significant differences were observed for alpha or beta diversity between lung cancer cases and controls. Abundance of families Lachnospiraceae_[XIV], Peptostreptococcaceae_[XI], and Erysipelotrichaceae and species Parvimonas micra was associated with decreased lung cancer risk, with odds ratios (ORs) and 95% confidence intervals (CIs) of 0.76 (0.59-0.98), 0.80 (0.66-0.97), 0.81 (0.67-0.99), and 0.83 (0.71-0.98), respectively (all p < 0.05). Prevalence of five pre-defined oral pathogens were not significantly associated with overall lung cancer risk. Prevalence of genus Bacteroidetes_[G-5] and species Alloprevotella sp._oral_taxon_912, Capnocytophaga sputigena, Lactococcus lactis, Peptoniphilaceae_[G-1] sp._oral_taxon_113, Leptotrichia sp._oral_taxon_225, and Fretibacterium fastidiosum was associated with decreased lung cancer risk, with ORs and 95% CIs of 0.55 (0.30-1.00), 0.36 (0.17-0.73), 0.53 (0.31-0.92), 0.43 (0.21-0.88), 0.43 (0.19-0.94), 0.57 (0.34-0.99), and 0.54 (0.31-0.94), respectively (all p < 0.05). Species L. sp._oral_taxon_225 was significantly associated with decreased lung cancer risk in African Americans (OR [95% CIs] 0.28 [0.12-0.66]; p = 0.00012). Results from this study suggest that oral microbiota may play a role in the development of lung cancer.

CEACAM Gene Family Mutations Associated With Inherited Breast Cancer Risk – A Comparative Oncology Approach to Discovery

IntroductionRecent studies comparing canine mammary tumors (CMTs) and human breast cancers have revealed remarkable tumor similarities, identifying shared expression profiles and acquired mutations. CMTs can also provide a model of inherited breast cancer susceptibility in humans; thus, we investigated breed-specific whole genome sequencing (WGS) data in search for novel CMT risk factors that could subsequently explain inherited breast cancer risk in humans.MethodsWGS was carried out on five CMT-affected Gold Retrievers from a large pedigree of 18 CMT-affected dogs. Protein truncating variants (PTVs) detected in all five samples (within human orthlogs) were validated and then genotyped in the 13 remaining CMT-affected Golden Retrievers. Allele frequencies were compared to canine controls. Subsequently, human blood-derived exomes from The Cancer Genome Atlas breast cancer cases were analyzed and allele frequencies were compared to Exome Variant Server ethnic-matched controls.ResultsCarcinoembryonic Antigen-related Cell Adhesion Molecule 24 (CEACAM24) c.247dupG;p.(Val83Glyfs∗48) was the only validated variant and had a frequency of 66.7% amongst the 18 Golden Retrievers with CMT. This was significant compared to the European Variation Archive (p-value 1.52 × 10–8) and non-Golden Retriever American Kennel Club breeds (p-value 2.48 × 10–5). With no direct ortholog of CEACAM24 in humans but high homology to all CEACAM gene family proteins, all human CEACAM genes were investigated for PTVs. A total of six and sixteen rare PTVs were identified in African and European American breast cancer cases, respectively. Single variant assessment revealed five PTVs associated with breast cancer risk. Gene-based aggregation analyses revealed that rare PTVs in CEACAM6, CEACAM7, and CEACAM8 are associated with European American breast cancer risk, and rare PTVs in CEACAM7 are associated with breast cancer risk in African Americans. Ultimately, rare PTVs in the entire CEACAM gene family are associated with breast cancer risk in both European and African Americans with respective p-values of 1.75 × 10–13 and 1.87 × 10–04.ConclusionThis study reports the first association of inherited CEACAM mutations and breast cancer risk, and potentially implicates the whole gene family in genetic risk. Precisely how these mutations contribute to breast cancer needs to be determined; especially considering our current knowledge on the role that the CEACAM gene family plays in tumor development, progression, and metastasis.

The Ratios of Triglycerides and C-reactive protein to High density-lipoprotein -cholesterol as valid biochemical markers of the Nascent Metabolic Syndrome

ABSTRACT Aims: Metabolic syndrome (MetS), a cardiometabolic cluster, is a major global problem. The ratio of triglycerides (TG) to high-density lipoprotein cholesterol (HDL-C) is a good biomarker of MetS in certain populations C-reactive protein (CRP) has also been also shown to be a biomarker of MetS. Since CRP captures inflammation, we compared the ratios of TG to HDL-C and CRP to HDL-C in patients with nascent MetS. Methods: Patients with MetS (n = 58) and matched controls (n = 44) were recruited. Fasting blood samples were obtained for routine laboratories, insulin, and adipokines. TG and CRP ratios to HDL-C were calculated. Data were analyzed statistically. Results: Both the TG to HDL-C and CRP to HDL-C ratios were significantly increased in MetS and both increased with increasing severity of MetS. Whilst both correlated with cardiometabolic features and insulin resistance, only the CRP to HDL-C ratio correlated significantly with adiponectin and leptin. Receiver operating characteristic curve analysis showed that both ratios showed excellent discrimination for MetS with no significant differences between ratios. Conclusions: Thus both the TG to HDL-C and CRP to HDL-C ratios are significantly increased in patients with nascent MetS and appear to be valid biomarkers of MetS. However, these preliminary findings with CRP: HDL-C need confirmation in large prospective studies and could have important implications for assessing cardiometabolic risk in African Americans, an under-served population.

Application of a Lifestyle-Based Score to Predict Cardiovascular Risk in African Americans: The Jackson Heart Study.

Cardiovascular disease (CVD) primordial prevention tools applicable to diverse populations are scarce. Our aim was to assess the performance of a lifestyle-based tool to estimate CVD risk in an African American population. The Jackson Heart Study is a prospective cohort including 5306 African American participants in Jackson, Mississippi (2000–2004), with a mean follow up of 12 years. The Healthy Heart Score is a lifestyle-based CVD risk prediction model based on nine components: body mass index (BMI), physical activity, smoking, and a 5-component diet score. Gender-specific beta coefficients from its derivation cohorts were used to assess the performance of the Healthy Heart Score. Model discrimination was assessed using Harrell’s C-Index for survival data and time dependent Area Under the Curve. Model calibration was evaluated through calibration plots. A total of 189 CVD events occurred. The Healthy Heart Score showed high-moderate discrimination for CVD events (C-statistic 0.75 [95% CI, 0.71–0.78]) but with little improvement over the age-only model. Both the age-only and Healthy Heart Score models had better performance in participants without diabetes at baseline and showed good calibration. In African Americans, the Healthy Heart Score does not improve prediction of mid-life CVD events beyond what is obtained by age alone.

A novel Mendelian randomization method with binary risk factor and outcome.

Mendelian randomization (MR) applies instrumental variable (IV) methods to observational data using a genetic variant as an IV. Several Monte-Carlo studies investigate the performance of MR methods with binary outcomes, but few consider them in conjunction with binary risk factors. To develop a novel MR estimator for scenarios with a binary risk factor and outcome; and compare to existing MR estimators via simulations and real data analysis. A bivariate Bernoulli distribution is adapted to the IV setting. Empirical bias and asymptotic coverage probabilities are estimated via simulations. The proposed method is compared to the Wald method, two-stage predictor substitution (2SPS), two-stage residual inclusion (2SRI), and the generalized method of moments (GMM). An analysis is performed using existing data from the CLEAR study to estimate the potential causal effect of smoking on rheumatoid arthritis risk in African Americans. Bias was low for the proposed method and comparable to 2SPS. The Wald method was often biased towards the null. Coverage was adequate for the proposed method, 2SPS, and 2SRI. Coverage for the Wald and GMM methods was poor in several scenarios. The causal effect of ever smoking on rheumatoid arthritis risk was not statistically significant using a variety of genetic instruments. Simulations suggest the proposed MR method is sound with binary risk factors and outcomes, and comparable to 2SPS and 2SRI in terms of bias. The proposed method also provides more natural framework for hypothesis testing compared to 2SPS or 2SRI, which require ad-hoc variance adjustments.

Invited Perspective: Air Pollution and Breast Cancer Risk: Current State of the Evidence and Next Steps.

Invited Perspective: Air Pollution and Breast Cancer Risk: Current State of the Evidence and Next Steps.

Associations of prenatal metabolomics profiles with early childhood growth trajectories and obesity risk in African Americans: the CANDLE study.

ObjectivePrenatal metabolomics profiles, providing measures of in utero nutritional and environmental exposures, may improve the prediction of childhood outcomes. We aimed to identify prenatal plasma metabolites associated with early childhood body mass index (BMI) trajectories and overweight/obesity risk in offspring.MethodsThis study included 450 African American mother-child pairs from the Conditions Affecting Neurocognitive Development and Learning in Early Childhood Study. An untargeted metabolomics analysis was performed on the mothers’ plasma samples collected during the second trimester. The children’s BMI-z-score trajectories from birth to age 4 [rising-high- (9.8%), moderate- (68.2%), and low-BMI (22.0%)] and overweight/obesity status at age 4 were the main outcomes. The least absolute shrinkage and selection operator (LASSO) was used to select the prenatal metabolites associated with childhood outcomes.ResultsThe mothers were 24.5 years old on average at recruitment, 76.4% having education less than 12 years and 80.0% with Medicaid or Medicare. In LASSO, seven and five prenatal metabolites were associated with the BMI-z-score trajectories and overweight/obese at age 4, respectively. These metabolites are mainly from/relevant to the pathways of steroid biosynthesis, amino acid metabolism, vitamin B complex, and xenobiotics metabolism (e.g., caffeine and nicotine). The odds ratios (95% CI) associated with a one SD increase in the prenatal metabolite risk scores (MRSs) constructed from the LASSO-selected metabolites were 2.97 (1.95–4.54) and 2.03 (1.54–2.67) for children being in the rising-high-BMI trajectory group and overweight/obesity at age 4, respectively. The MRSs significantly improved the risk prediction for childhood outcomes beyond traditional prenatal risk factors. The increase (95% CI) in the area under the receiver operating characteristic curves were 0.10 (0.03–0.18) and 0.07 (0.02–0.12) for the rising-high-BMI trajectory (P=0.005) and overweight/obesity at age 4 (P=0.007), respectively.ConclusionsPrenatal metabolomics profiles advanced prediction of early childhood growth trajectories and obesity risk in offspring.

Racial/ethnic differences in anthropometric and hormone-related factors and endometrial cancer risk: the Multiethnic Cohort Study.

Anthropometric and hormone-related factors are established endometrial cancer risk factors; however, little is known about the impact of these factors on endometrial cancer risk in non-White women. Among 110,712 women participating in the Multiethnic Cohort (MEC) Study, 1150 incident invasive endometrial cancers were diagnosed. Hazard ratios (HRs) and 95% confidence intervals (CIs) for associations with endometrial cancer risk for race/ethnicity and for risk factors across racial/ethnic groups were calculated. Having a higher body mass index (BMI) at baseline or age 21 years was strongly associated with increased risk (pint race/ethnicity ≥ 0.36). Parity (vs nulliparity) was inversely associated with risk in all the groups except African Americans (pint 0.006). Current use of postmenopausal hormones at baseline (PMH-E; vs never use) was associated with increased risk in Whites and Japanese Americans (pint 0.002). Relative to Whites, endometrial cancer risk was lower in Japanese Americans and Latinas and non-significantly higher in Native Hawaiians. Risk in African Americans did not differ from that in Whites. Racial/ethnic differences in endometrial cancer risk were not fully explained by anthropometric or hormone-related risk factors. Further studies are needed to identify reasons for the observed racial/ethnic differences in endometrial cancer risk.

Benign Prostatic Hyperplasia in African American Men Merits Greater Consideration in Academic Medicine

Benign Prostatic Hyperplasia (BPH) is a non-cancerous enlargement of the prostate gland, which is highly prevalent in aging men. This process of benign prostate enlargement is known to occur more rapidly in African American men, which has resulted in a disproportionately increased prevalence relative to the general population. In the United States, the cause of this disproportionately increased risk in African Americans is believed to be due to both genetic factors as well as a complex myriad of variables related to health disparities. Despite a robust increase in research related to prostate cancer in African American men, the issue of BPH/LUTS in the African American community deserves equally increased attention in academic medicine. The purpose of this article is to provide a brief review of the medical literature on BPH/LUTS in the African American community to highlight unknown components of the disease and to demonstrate the need for more equitable urologic healthcare.

Engulfment and cell motility 1 (ELMO1) and apolipoprotein A1 (APOA1) as candidate genes for sickle cell nephropathy.

Sickle cell disease (SCD) and apolipoprotein L1 (APOL1) G1/G2 variants increase chronic kidney disease (CKD) risk in African Americans by poorly understood mechanisms. We applied bioinformatics to identify new candidate genes associated with SCD-related CKD. An interaction network demonstrated APOA1 connecting haemoglobin subunit β (HBB) and APOL1 with 36 other candidate genes. Gene expression revealed upregulation of engulfment and cell motility 1 (ELMO1) and downregulation of APOA1 in the kidney cortex of SCD versus non-SCD mice. Analysis of candidate genes identified ELMO1 rs10951509 to be associated with albuminuria and APOA1 rs11216132 with haemoglobinuria in patients with SCD. A bioinformatic approach highlights ELMO1 and APOA1 as potentially associated with SCD nephropathy.

Coffee consumption and cancer risk in African Americans from the Southern Community Cohort Study

Coffee consumption has been associated with the risk of cancer at several anatomical sites, but the findings, mostly from studies of non-Hispanic whites and Asians, are inconsistent. The association between coffee consumption and the incidence of cancer has not been thoroughly examined in African Americans. We conducted a nested case–control study including 1801 cancer cases and 3337 controls among African Americans from the Southern Community Cohort Study (SCCS) to examine the association between coffee drinking, as assessed by a semi-quantitative food frequency questionnaire, and the risk of four common cancers (lung, prostate, breast, colorectal). We used logistic regression adjusted for age, sex and cancer-specific risk factors. Overall, only ≤ 9.5% of African American cases and controls from the SCCS drank regular or decaffeinated coffee ≥ 2 times/day. After adjustment for major cancer-specific risk factors, coffee consumption was not statistically significantly associated with the risk of lung, breast, colorectal, or prostate cancers (OR range 0.78–1.10; P ≥ 0.27 for ≥ 2 versus < 1 times/day) or overall cancer risk (OR 0.93; 95% CI 0.75–1.16; P = 0.52 for ≥ 2 versus < 1 times/day). Coffee consumption was not associated with the risk of cancer among African Americans in our study.

Two genetic variants explain the association of European ancestry with multiple sclerosis risk in African-Americans

Epidemiological studies have suggested differences in the rate of multiple sclerosis (MS) in individuals of European ancestry compared to African ancestry, motivating genetic scans to identify variants that could contribute to such patterns. In a whole-genome scan in 899 African-American cases and 1155 African-American controls, we confirm that African-Americans who inherit segments of the genome of European ancestry at a chromosome 1 locus are at increased risk for MS [logarithm of odds (LOD) = 9.8], although the signal weakens when adding an additional 406 cases, reflecting heterogeneity in the two sets of cases [logarithm of odds (LOD) = 2.7]. The association in the 899 individuals can be fully explained by two variants previously associated with MS in European ancestry individuals. These variants tag a MS susceptibility haplotype associated with decreased CD58 gene expression (odds ratio of 1.37; frequency of 84% in Europeans and 22% in West Africans for the tagging variant) as well as another haplotype near the FCRL3 gene (odds ratio of 1.07; frequency of 49% in Europeans and 8% in West Africans). Controlling for all other genetic and environmental factors, the two variants predict a 1.44-fold higher rate of MS in European-Americans compared to African-Americans.

Sensor‐measured physical activity is associated with decreased cardiovascular disease risk in African Americans

AbstractIntroductionFew studies have examined relationships between sensor‐measured physical activity (PA) and cardiovascular disease (CVD) risk among African Americans. This study described relationships between PA and CVD risk in NEW Soul study participants.MethodsParticipants completed a dual X‐ray absorptiometry scan and measures of blood pressure, waist and hip circumference, height, and weight. Actigraph GTM accelerometers measured moderate to vigorous physical activity (MVPA). We assessed relationships between minutes/day of MVPA and total body fat percent, total lean body mass, total fat mass, total bone mass, total fat distribution, body mass index (BMI), systolic and diastolic blood pressure, and waist‐to‐hip ratio, adjusting for age, sex, and education.ResultsParticipants (N = 159) were mostly women (79%), overweight/obese (99%), and had stage 1 or 2 hypertension (60%). Participants’ means ± SD for MVPA were 14.3 ± 12.5 min/day, total body fat percent 44.6% ± 7.5%, total lean body mass 54.7 ± 10.5 kg, systolic blood pressure 133.5 ± 16.7 mmHg, diastolic blood pressure 83.1 ± 9.6 mmHg, waist‐to‐hip ratio 0.9 ± 0.1, and BMI 36.9 ± 6.9 kg/m2. Every 10‐min increase in MVPA minutes per day was associated with a 1.2 kg kg/m2 decrease in BMI (t = –P = .02) and 2.0% decrease in total body fat percent (P ≤ .0001). MVPA also was negatively associated with total fat mass (P = .002) and total fat distribution (P = .003).ConclusionsFindings confirmed protective relationships between PA and CVD risk, suggesting the importance of increasing PA among African Americans.

Abstract 1169: Racial/ethnic differences in postmenopausal breast cancer incidence and risk factors: Results from the Multiethnic Cohort (MEC) Study

Abstract The impact of hormone-related factors on breast cancer risk has been well-studied; however, data on racial/ethnic minorities, especially Native Hawaiian women, remain relatively scarce. MEC participants completed a baseline questionnaire providing information on hormone-related factors. During a median follow-up of 20 years, 4,634 incident invasive breast cancer cases were identified among 81,511 postmenopausal women (20,003 White, 16,060 African American, 5,468 Native Hawaiian, 22,333 Japanese American, and 17,647 Latina). We used Cox proportional hazards regression models to estimate hazard ratios (HRs) and 95% confidence intervals (CIs) for associations of: (1) race/ethnicity with estrogen receptor positive (ER+) and negative (ER-) breast cancer risk and (2) hormone-related factors with ER+ and ER- breast cancer risk across race/ethnicity. Models were adjusted for baseline age and body mass index (BMI), parity, as well as ages at menarche, menopause, and first birth. Compared to Whites, age-adjusted ER+ breast cancer risk was higher in Native Hawaiians (HR 1.42 [CI 1.26-1.60]), lower in African Americans (0.72 [0.66-0.80]) and Latinas (0.54 [0.49-0.60]), and similar in Japanese Americans (0.97 [0.89-1.05]). Risk for ER- disease was higher in African Americans (1.41 [1.15-1.72]) than in Whites, but no difference was observed in Native Hawaiians, Latinas or Japanese Americans. These results were unchanged after adjustment for hormone-related factors. In the full population, parity and a later age at natural menopause were associated with a decreased ER+ breast cancer risk, and postmenopausal hormone (PMH) use and a higher BMI with an increased risk. There was no significant interaction of these factors with race/ethnicity (p-value for interaction [p-int] ≥0.10). In race/ethnicity specific analyses, parity (vs nulliparity) was associated with lower ER+ breast cancer risk in Whites (0.72 [0.59-0.87]), Japanese Americans (0.57 [0.44-0.74]), and Latinas (0.63 [0.46-0.86]). Age at menopause (≥55 vs &amp;lt;45 years) was inversely associated with ER+ disease risk in African Americans (0.69 [0.52-0.91]) and Japanese Americans (0.69 [0.57-0.84]). PMH use (ever vs never) increased ER+ breast cancer risk by 17-36% in all racial/ethnic groups except Native Hawaiians. BMI (≥30 vs &amp;lt;25 kg/m2) was associated with a 22-66% increased risk of ER+ disease in all racial/ethnic groups. For ER- breast cancer, ever use of oral contraceptives was the only factor associated with risk in the full population (p-int 0.45) and we observed an increased risk of ER- disease in Whites (1.52 [1.09-2.12]) and African Americans (1.80 [1.30-2.51]). Although we observed different associations across racial/ethnic groups for several hormone-related factors with risk of ER+ disease, these did not appear to explain the observed racial/ethnic differences in breast cancer incidence. Citation Format: Danja Sarink, Loic Le Marchand, Lenora W. Loo, Song-Yi Park, Kami K. White, V Wendy Setiawan, Anna H. Wu, Lynne R. Wilkens, Melissa A. Merritt. Racial/ethnic differences in postmenopausal breast cancer incidence and risk factors: Results from the Multiethnic Cohort (MEC) Study [abstract]. In: Proceedings of the Annual Meeting of the American Association for Cancer Research 2020; 2020 Apr 27-28 and Jun 22-24. Philadelphia (PA): AACR; Cancer Res 2020;80(16 Suppl):Abstract nr 1169.

Associations Between Reproductive and Hormone-Related Factors and Risk of Nonalcoholic Fatty Liver Disease in a Multiethnic Population

Despite apparent differences between men and women in the prevalence and incidence of nonalcoholic fatty liver disease (NAFLD), there are limited epidemiologic data regarding the associations of reproductive and hormone-related factors with NAFLD. We examined the associations of these factors and exogenous hormone use with NAFLD risk in African American, Japanese American, Latino, Native Hawaiian, and white women. We conducted a nested case-control study (1861 cases and 17,664 controls) in the Multiethnic Cohort Study. NAFLD cases were identified using Medicare claims data; controls were selected among participants without liver disease and individually matched to cases by birth year, ethnicity, and length of Medicare enrollment. Reproductive and hormone-related factors and covariates were obtained from the baseline questionnaire. Multivariable logistic regression was used to calculate odds ratios (ORs) and 95% CIs. Later age at menarche was associated inversely with NAFLD (Ptrend= .01). Parity, regardless of number of children or age at first birth, was associated with increased risk of NAFLD (OR, 1.25; 95% CI, 1.05-1.48). Oral contraceptive use also was linked to increased risk of NAFLD (OR, 1.14; 95% CI, 1.01-1.29; duration of use Ptrend= .04). Compared with women with natural menopause, those with oophorectomy (OR, 1.41; 95% CI, 1.18-1.68) or hysterectomy (OR, 1.33; 95% CI, 1.11-1.60) had an increased risk of NAFLD. A longer duration of menopause hormone therapy (only estrogen therapy) was linked with an increasing risk of NAFLD (OR per 5 years of use, 1.08, 95% CI, 1.01-1.15). Findings from a large multiethnic study support the concept that menstrual and reproductive factors, as well as the use of exogenous hormones, are associated with the risk of NAFLD.

COVID19 coagulopathy in Caucasian patients.

SummaryAlthough the pathophysiology underlying severe COVID19 remains poorly understood, accumulating data suggest that a lung‐centric coagulopathy may play an important role. Elevated D‐dimer levels which correlated inversely with overall survival were recently reported in Chinese cohort studies. Critically however, ethnicity has major effects on thrombotic risk, with a 3–4‐fold lower risk in Chinese compared to Caucasians and a significantly higher risk in African‐Americans. In this study, we investigated COVID19 coagulopathy in Caucasian patients. Our findings confirm that severe COVID19 infection is associated with a significant coagulopathy that correlates with disease severity. Importantly however, Caucasian COVID19 patients on low molecular weight heparin thromboprophylaxis rarely develop overt disseminated intravascular coagulation (DIC). In rare COVID19 cases where DIC does develop, it tends to be restricted to late‐stage disease. Collectively, these data suggest that the diffuse bilateral pulmonary inflammation observed in COVID19 is associated with a novel pulmonary‐specific vasculopathy termed pulmonary intravascular coagulopathy (PIC) as distinct to DIC. Given that thrombotic risk is significantly impacted by race, coupled with the accumulating evidence that coagulopathy is important in COVID19 pathogenesis, our findings raise the intriguing possibility that pulmonary vasculopathy may contribute to the unexplained differences that are beginning to emerge highlighting racial susceptibility to COVID19 mortality.

Stroke risk in African Americans with subclinical auditory dysfuntion evidenced by Distortion Product Otoacoustic Emissions: the Jackson heart study

Objective: Distortion product otoacoustic emissions (DPOAEs) are sensitive to early indices of cochlear pathology. Pathology to the cochlea is in part mediated by ischaemic related mechanisms. We propose that DPOAEs may provide an objective measure of cardiovascular risk. Design: Cross-sectional. Study sample: The relationships between stroke risk and DPOAEs of 1,107 individuals from the Jackson Heart Study (JHS), an all-African-American cohort, were assessed. Linear regression models were used for analysis among all participants and delimited to normal hearing, defined as either a pure-tone threshold average of 500, 1000, 2000, and 4000 Hz (PTA4) ≤ 25 dBHL or pure-tone thresholds for all individual tested frequencies for each ear (500, 1000, 2000, 4000, and 8000 Hz) ≤ 25 dBHL. Results: We observed a significant inverse relationship between DPOAE amplitudes and stroke risk scores in the pooled cohort and in the subgroups with normal hearing defined by pure tone thresholds. Participants in the high-risk group had significantly lower DPOAE amplitudes than those in the low stroke risk group. Conclusions: Our results indicate that auditory dysfunction as measured by DPOAEs are related to stroke risk. Further prospective studies are needed to determine if DPOAEs could be used as a predictive tool for cardiovascular disease.