Cardiovascular Disease In African Americans Research Articles

Acute inflammation elicits decreased blood pressure but similar arterial stiffness in young African American adults.

African Americans (AA) have a higher risk for cardiovascular disease (CVD) as compared to their White (W) counterparts. CVD is characterized by increased blood pressure (BP), arterial stiffness and systemic inflammation. An acute inflammatory stimulus may explain physiological manifestations responsible for amplified CVD in AA that are not apparent at rest. The purpose of this study was to evaluate central and peripheral BP, central and local arterial stiffness, and indices of pulse wave morphology in young healthy AA and W participants in response to acute inflammation. Concentrations of the inflammatory cytokine interleukin-6 (IL-6) and measures of central and peripheral BP, central arterial stiffness (carotid-femoral pulse wave velocity (cfPWV)), local carotid arterial stiffness (β-stiffness, elastic modulus (Ep)), and indices of pulse wave morphology were assessed in 28 participants (21±2years, AA: n = 11) at baseline (BL), 24h and 48h post-inflammation. Changes in IL-6 concentrations (ΔIL-6) were significantly greater at 24h as compared to 48h post-inflammation (0.652±0.644 vs. -0.146±0.532pg/μl, P≤0.0001). Among AA participants, central and peripheral diastolic BP were significantly decreased at 24h post-inflammation as compared to BL (aortic diastolic BP: -4±4mmHg, P=0.016; brachial diastolic BP: -4±4mmHg, P=0.014). AA participants also experienced a significant decrease in central and peripheral mean arterial BP at 48h post-inflammation as compared to BL (aortic mean arterial pressure: -4±4mmHg, P=0.009; brachial mean arterial pressure: -4±4mmHg, P=0.012). Despite haemodynamic changes, there were no differences in central or local carotid arterial stiffness or indices of pulse wave morphology.

Abstract 10212: Exposure to Volatile Organic Compounds - Acrolein, Crotonaldehyde, and Styrene - is Associated with Blood Pressure in the Jackson Heart Study

Introduction: Cardiovascular disease (CVD) is the leading cause of death from environmental exposures. Although exposure to particulate matter ≤2.5μm (PM 2.5 ) is an established risk factor for CVD, the contribution of other hazardous pollutant exposure to CVD risk is less clear. Hypothesis: We assessed the hypothesis that volatile organic compounds (VOCs) are associated with blood pressure in 778 nonsmokers from the Jackson Heart Study (JHS), a large, community based observational study of CVD in African Americans from the tri-county Jackson, MS area. Methods: We measured urinary metabolites of 17 parent VOCs in spot urine samples collected at baseline using UPLC/MS. We tested the association between VOC metabolites and blood pressure in nonsmokers using generalized linear models adjusted for age, sex, body mass index (BMI), estimated glomerular filtration rate, cholesterol to high-density lipoprotein ratio, triglycerides, blood pressure medications, diabetes, and PM 2.5 . Two measurements of systolic and diastolic blood pressure (SBP, DBP) in the resting state were averaged using a Hawksley random zero sphygmomanometer. Results: Included participants had a BMI of 31.3 ± 7.1 kg/m 2 (mean ± SD), had triglycerides of 99.9 ± 57.9 mg/dL, and a less than 10% prevalence of CVD events. More than one-third were affluent (37.8%) and almost half used blood pressure medications (46%). We found that metabolites of acrolein (CEMA) and crotonaldehyde (HPMMA) were associated with a 1.5mmHg (CI: 0.5, 2.7; p=0.01), and a 1.1mmHg higher (CI: 0.1, 2.0; p=0.02) SBP per interquartile range (IQR) of VOC metabolite, respectively. Additionally, we found a 0.5mmHg higher (CI: 0.1, 0.8; p= 0.01) DBP per IQR of styrene metabolite, MA. In subgroup analysis, the association between CEMA and MA and blood pressure persisted only in men. Conclusions: In conclusion, these findings suggest that exposure to VOCs (acrolein, crotonaldehyde, and styrene) may be a significant contributor to risk of hypertension among African American nonsmokers.

Common genetic variation in circadian clock genes are associated with cardiovascular risk factors in an African American and Hispanic/Latino cohort.

Misalignment of the internal circadian time with external physical time due to environmental factors or due to genetic variantion in circadian clock genes has been associated with increased incidence of cardiovascular risk factors. Common genetic variation in circadian genes in the United States have been identified predominantly in European ancestry individuals. We therefore examined the association between circadian clock single nucleotide polymorphisms (SNPs) in Clock, Cry1, Cry2, Bmal1 and Per3 genes and cardiovascular risk factors in African Americans and Hispanic/Latinos. We analyzed 17 candidate circadian SNPs in 1,166 subjects who self-identified as African-American or Hispanic/Latino and were enrolled in the UIC Cohort of Patients, Family and Friends. We found significant differences in the minor allele frequencies between African American and Hispanic/Latino subjects. Our analyses also established ethnic-specific SNPs that are associated with cardiovascular risk factors. In Hispanic/Latinos, the rs6850524 in Clock was associated with increased risk for hypertension, meanwhile rs12649507, rs4864546, and rs4864548 reduced the risk, also rs8192440 (Cry1) reduced the risk for type 2 diabetes. In African Americans, the Clock rs1801260 and rs6850524 were negatively associated with the presence of obesity; Bmal1 rs11022775 reduced the risk for dyslipidemia; and the Cry2 rs2292912 increased the risk for dyslipidemia and diabetes. Genetic variations in candidate circadian-clock genes are associated with risk factors for cardiovascular disease in African-Americans and Hispanic/Latinos. Our findings may help to improve cardiovascular risk assessment as well as better understand how circadian misalignment impacts cardiovascular risk in diverse populations.

COVID‐19 Comorbidities predisposes participants from the Jackson Heart Study to disparate Health Outcomes

Coronavirus disease 2019 (COVID‐19) is a pandemic that is affecting people in all communities. Currently, over 13 million individuals around the world have contracted the disease and over 573,000 individuals have died as a result of the disease. If individuals contract COVID‐19, comorbidities such as hypertension, cardiovascular disease (CVD), diabetes, and obesity make individuals more susceptible to severe illnesses or even death. Nationally, the death rate of COVID‐19 in African Americans is more than twice that of Whites and Latinos. To better understand the devastating effects of COVID‐19 on the African American community, our goal is to examine data from the Jackson Heart Study, which currently investigates risk factors associated with CVD in African Americans, a comorbidity of COVID‐19. The prevalence of hypertension, type 2 diabetes, overweight and obesity in participants of the Jackson Heart Study is 62.9%, 18.8%, 32.2%, and 53.3%, respectively. African Americans account for approximately 37.8% of the population in MS; however, they account for approximately 50% of the cases and 51% of the deaths related to COVID‐19. In the Jackson, MS area, African Americans account for 72%, 56%, and 45% of COVID‐19 related deaths in Hinds, Madison and Rankin counties, respectively. In summary, the prevalence of COVID‐19 comorbidities in the participants of the Jackson Heart Study should alert and equip residents and health care workers to help reduce the disparate outcomes of the pandemic in this community. Future studies are needed to determine the physiological, immunological and social interactions.

Electrocardiogram machine learning for detection of cardiovascular disease in African Americans: the Jackson Heart Study.

AimsAlmost half of African American (AA) men and women have cardiovascular disease (CVD). Detection of prevalent CVD in community settings would facilitate secondary prevention of CVD. We sought to develop a tool for automated CVD detection.Methods and resultsParticipants from the Jackson Heart Study (JHS) with analysable electrocardiograms (ECGs) (n=3679; age, 6212 years; 36% men) were included. Vectorcardiographic (VCG) metrics QRS, T, and spatial ventricular gradient vectors magnitude and direction, and traditional ECG metrics were measured on 12-lead ECG. Random forests, convolutional neural network (CNN), lasso, adaptive lasso, plugin lasso, elastic net, ridge, and logistic regression models were developed in 80% and validated in 20% samples. We compared models with demographic, clinical, and VCG input (43 predictors) and those after the addition of ECG metrics (695 predictors). Prevalent CVD was diagnosed in 411 out of 3679 participants (11.2%). Machine learning models detected CVD with the area under the receiver operator curve (ROC AUC) 0.690.74. There was no difference in CVD detection accuracy between models with VCG and VCG + ECG input. Models with VCG input were better calibrated than models with ECG input. Plugin-based lasso model consisting of only two predictors (age and peak QRS-T angle) detected CVD with AUC 0.687 [95% confidence interval (CI) 0.6250.749], which was similar (P=0.394) to the CNN (0.660; 95% CI 0.5970.722) and better (P<0.0001) than random forests (0.512; 95% CI 0.4930.530).ConclusionsSimple model (age and QRS-T angle) can be used for prevalent CVD detection in limited-resources community settings, which opens an avenue for secondary prevention of CVD in underserved communities.

Renin--angiotensin system blockers and the risk of critical or fatal coronavirus disease 2019 in African Americans.

Renin--angiotensin system blockers and the risk of critical or fatal coronavirus disease 2019 in African Americans.

Interferon gamma-induced protein 10 (IP-10) and cardiovascular disease in African Americans.

Biomarkers of chronic inflammation (such as C-reactive protein) have long been associated with cardiovascular disease and mortality; however, biomarkers involved in antiviral cytokine induction and adaptive immune system activation remain largely unexamined. We hypothesized the cytokine interferon gamma inducible protein 10 (IP-10) would be associated with clinical and subclinical cardiovascular disease and all-cause mortality in African Americans. We assessed these associations in the Jackson Heart Study (JHS) cohort and the REasons for Geographic and Racial Differences in Stroke (REGARDS) study. There was a modest association of IP-10 with higher odds of left ventricular hypertrophy (OR = 1.20 (95% confidence interval (CI) 1.03, 1.41) per standard deviation (SD) higher natural log-transformed IP-10 in JHS). We did not observe associations with ankle brachial index, intima-media thickness, or arterial calcification. Each SD higher increment of ln-transformed IP-10 concentration was associated with incident heart failure (hazard ratio (HR) 1.26; 95% CI 1.11, 1.42, p = 4x10-4) in JHS, and with overall mortality in both JHS (HR 1.12 per SD, 95% CI 1.03, 1.21, p = 7.5x10-3) and REGARDS (HR 1.31 per SD, 95% CI 1.10, 1.55, p = 2.0 x 10−3), adjusting for cardiovascular risk factors and C-reactive protein. However, we found no association between IP-10 and stroke or coronary heart disease. These results suggest a role of IP-10 in heart failure and mortality risk independent of C-reactive protein. Further research is needed to investigate how the body’s response to chronic viral infection may mediate heart failure and overall mortality risk in African Americans.

The Association of Life's Simple 7 with Aldosterone among African Americans in the Jackson Heart Study.

Background: Among African Americans (AAs), attaining higher levels of American Heart Association (AHA) ideal cardiovascular health (Life’s Simple 7 [LS7]) is associated with lower risk of diabetes and cardiovascular disease (CVD). We previously showed that aldosterone is associated with higher risk of diabetes and CVD in AAs. Thus, we investigated the association of LS7 metrics with aldosterone in the Jackson Heart Study (JHS). Methods: Ideal metrics were defined by AHA 2020 goals for health behaviors (smoking, dietary intake, physical activity, and body mass index) and health factors (total cholesterol, blood pressure, and fasting glucose). The number of ideal LS7 metrics attained at baseline were summed into a continuous score (0–7) and categorical groups (Poor: 0–1, Intermediate: 2–3, and Ideal: ≥4 ideal LS7 metrics). Multivariable linear regression was used. Results: Among 4,095 JHS participants (mean age 55 ± 13 years, 65% female), median serum aldosterone was 4.90, 4.30, and 3.70 ng/dL in the poor (n = 1132), intermediate (n = 2288) and ideal (n = 675) categories respectively. Aldosterone was 15% [0.85 (0.80, 0.90)] and 33% [0.67 (0.61, 0.75)] lower in the intermediate and ideal LS7 categories compared to the poor LS7 category. Each additional LS7 metric attained on continuous LS7 score (0–7) was associated with an 11% [0.89 (0.86, 0.91)] lower aldosterone level with variation by sex with women having a 15% lower aldosterone vs. 5% in men. Conclusions: Higher attainment of ideal LS7 metrics was associated with lower serum aldosterone among AAs with a greater magnitude of association among women compared to men.

Developing Lay Summaries as a Bidirectional Learning Opportunity for Authors and Undergraduate Scholars: The Jackson Heart Study

In keeping with the use of “Plain Language” to reach all Americans with health information, the Jackson Heart Study (JHS), the largest single-site epidemiological study investigating predictors of cardiovascular disease in African Americans, requires JHS investigators to submit lay summaries with final manuscripts. We developed the Lay Summary Pilot Project as a bidirectional learning opportunity for JHS scholars and investigators. Results suggested that lay summaries increase the value of sharing research with scientific and nonscientific audiences and publishing lay summaries benefits communities by translating scientific research into useful health information.

RiSE to Prevent Cardiovascular Disease in African Americans

RiSE to Prevent Cardiovascular Disease in African Americans

Abstract P301: Obesity and Mortality: the Jackson Heart Study

Background: Mortality has been reported to be lower among individuals classified as overweight/obese (based on body mass index (BMI, kg/m 2 )) when compared with their normal weight counterparts (“obesity paradox”). One possible reason for this apparent paradox is that BMI includes the weight of lean muscle and fat mass, both of which vary with age, sex, and race/ethnicity, and variations in these individual mass measures may not be reflected by the BMI. We compared associations between all-cause mortality and BMI and other obesity measures that may better reflect central adiposity, including waist circumference (WC, cm), waist-to-height ratio (WHtR) and waist-to-hip ratio (WHR) in the Jackson Heart Study (JHS), a prospective cohort study of cardiovascular disease in African Americans. Methods: Data from 3,976 JHS participants (441 deaths) who attended Exam 2 (2005-2008) where various measures of obesity were collected, were analyzed. Cox regression models were used to evaluate the associations between obesity and all-cause mortality. “Time 0” for the survival analysis was the date of Exam 2 and the administrative censoring date was 12/31/2015. Obesity measures were analyzed as categories based on standard cut-points defining obesity and as quintiles. Covariates include age, sex and smoking. The predictive abilities of these obesity measures were assessed using c-index. Results: The age-sex-smoking adjusted mortality rates were the lowest among participants who were overweight (BMI 25-&lt;30) or with class I obesity (BMI 30-&lt;35). However, compared to normal weight participants (BMI 18.5-&lt;25), only participants with class III obesity (BMI ≥40) had a significantly higher mortality (adjusted HR [aHR] 1.92 [95% CI 1.34-2.75]). In addition, higher mortality was associated with obesity defined by WC (&gt;102 in men/&gt;88 in women vs. ≤102 in men/≤88 in women; aHR 1.45 [1.16-1.82]) and by WHR (≥0.9 in men/≥0.85 in women vs. &lt;0.9 in men/&lt;0.85 in women; aHR 1.54 [1.21-1.95]); but not by BMI (≥30 vs. &lt;25; aHR 1.04 [0.79-1.37]) or WHtR (≥0.5 vs. &lt;0.5; aHR 1.03 [0.72-1.49]). Sex-stratified analyses suggest the stronger predictor for mortality was WC-defined obesity in men and WHR-defined obesity in women; however, test for interactions were not statistically significant. The associations were not found to vary by age (&gt;65 vs. ≤65 years). Analyses using quintiles showed that the 5 th quintiles were associated with a significant increase in mortality compared with the 1 st quintiles for all obesity measures. The c-indexes were comparable for all obesity measures. Conclusions: The “obesity paradox” was suggested in the JHS based on BMI. However, only morbidly obese participants had a significantly higher mortality than normal weight participants. The recommended cut-points for defining obesity based on WC and WHR were significantly associated with increased mortality in this large cohort of African Americans.

Cardiovascular Diseases in African Americans: Fostering Community Partnerships to Stem the Tide

In 2002, the Institute of Medicine highlighted community partnerships as important in strategies for ensuring the public's health in the 21st century. Whether defined narrowly as the neighborhood or more broadly as the entire nation, communities represent settings in which health is supported and protected by healthy social connections and environments or risked and damaged by detrimental social, environmental, and policy determinants, as well as adverse behavioral and lifestyle choices. In this article, cardiovascular disease in African Americans is used as an example to highlight the successes achieved during the last half-century in reducing mortality rates, the persisting challenge of suboptimal adoption of evidence-based practices to promote community health and prevent disease, and the still widespread and pervasive health disparities. The article concludes with a call for the scientific community to embrace implementation research in strategic partnership with community stakeholders to stem the tide of cardiovascular disease and reduce related cardiovascular health disparities.

Cardiovascular Disease in African Americans: Innovative Community Engagement for Research Recruitment and Impact

Historical events and the illumination of unequal treatment of cardiovascular and other diseases among African Americans and their white counterparts have suppressed African Americans' participation in research. Approaches that bring scientific professionals into actual partnership with affected communities show promise for overcoming this reluctance. Two examples are the Jackson Heart Study (JHS) and the emerging Moyo Health Network (MOYO). JHS uses layers of community engagement, including a pioneering effort to develop future health scientists and practitioners, the JHS Undergraduate Training and Education Center (UTEC). JHS-UTEC focuses on preparing young adults and teenagers (mostly African Americans) for rigorous higher-level learning and careers in health research and practice. MOYO is a mobile platform for health research to examine factors contributing to the development of disparities in the young while creating channels to disseminate interventions. Community trust in MOYO is substantially enhanced through its education and training program, which offers engaging ideation events along with app development and coding training opportunities to young people. Participants impart their cultural insights while using newly acquired technology skills to help with the community-focused design and launch of the network. The JHS and MOYO provide models for addressing cardiovascular health disparities by fostering community partnerships.

Abstract P311: Individual Characteristics of Resilience Are Associated With Lower-Than-Expected Neighborhood Rates of Cardiovascular Disease in African-Americans: Results From the Morehouse-Emory Cardiovascular (MECA) Center for Health Equity Study

Background: Excess rates of cardiovascular (CV) disease in African-Americans, relative to Whites, have been well-documented. However, factors promoting CV health in the face of high risk, i.e. CV resilience, are unknown and may identify novel areas for intervention in reducing racial health disparities. Methods: Using data obtained from the Georgia Hospital Association, we identified age-, sex-, and income-matched neighborhoods (census tracts) in Atlanta, GA, with higher-than-expected (“high risk") or lower-than-expected (“low risk") rates of CV morbidity and mortality for African-Americans from 2010-2014. African-Americans from low risk (N = 742) and high risk (N = 753) neighborhoods were surveyed. Several domains of psychosocial well-being and neighborhood quality were assessed as features of resilience, in addition to individual demographic, socioeconomic and medical history variables. Ordinal logistic regression was used to determine odds of resilient characteristics among individuals living in neighborhoods at low versus high risk. Results: After adjustment for age, sex, household income, education, marital status and occupation, African-Americans living in low compared to high risk neighborhoods reported better overall neighborhood quality (odds ratio [OR] 1.25; 95% confidence interval [CI] 1.01, 1.57), driven by better aesthetic quality (OR 1.42; CI 1.17, 1.73), more safety (OR 1.34; CI 1.10, 1.62), absence of violence (OR 1.42; CI 1.10, 1.83) and better access to healthy foods (OR 1.50; CI 1.24, 1.82). Additionally, individuals from low compared to high risk neighborhoods reported greater environmental mastery (OR 1.33; CI 1.03, 1.71), purpose in life (OR 1.22, CI 1.01, 1.48), optimism (OR 1.28; CI 1.05, 1.55) and resilient coping (OR 1.33; CI 1.04, 1.70), while also reporting less depressive symptoms (OR 0.78; CI 0.63, 0.98). There were no reported differences in CV risk factors or disease, religious practices, spirituality or experiences of discrimination between low and high risk neighborhoods. Conclusions: African-Americans living in neighborhoods at lower risk for CVD morbidity and mortality reported better neighborhood quality and psychosocial well-being than individuals from neighborhoods at higher risk. Neighborhood and personal psychosocial determinants of health may confer resilience to CVD in African-American individuals and communities.

Abstract 005: Cumulative Stress Exposure is Associated With Incident Hypertension in African Americans: Findings From the Jackson Heart Study

Introduction and Hypothesis: Chronic stress has been associated with incident hypertension but evidence is mixed, particularly in African Americans. We tested the hypothesis that higher cumulative exposure to stress would be associated with increased risk of developing hypertension in the Jackson Heart Study (JHS), a prospective study of cardiovascular disease in African Americans. Methods: Analyses included 1,442 JHS participants free of hypertension at baseline (2000-2004) who completed at least 3 annual follow-up telephone interviews. Incident hypertension was defined as systolic blood pressure (SBP) ≥140 mm Hg or diastolic BP (DBP) ≥90 mm Hg or use of antihypertensive medications at Exam 2 (2005-2008) or Exam 3 (2009-2013). A single-item measure of stress (“How much stress have you experienced over the past year?”) was completed during annual interviews, and the percentage of assessments in each measurement interval (i.e., between Exams 1 and 2, between Exams 2 and 3) in which high stress was reported was categorized as No Chronic Stress (0%), Low Chronic Stress (1-33.3%) or High Chronic Stress (&gt;33.3%). Chronic stress exposure in each interval was used to predict incident hypertension at the following exam among participants free of hypertension at the start of the interval using repeated measures Poisson regression models with progressive adjustment for age, sex, years between exams and other relevant risk factors (education, marital status, parental history of hypertension, baseline SBP and DBP, body mass index, diabetes, chronic kidney disease). Results: The 1,442 participants in this analysis contributed data to 1,987 measurement intervals. The mean age was 49±0.26 years and 41% were male. During follow-up (median, 8 years), 44.0% of participants developed hypertension. The percentage of intervals with No, Low and High chronic stress was 62.3%, 9.2% and 28.6%, respectively. Multivariable-adjusted risk ratios (95% confidence interval) for incident hypertension associated with Low (vs. No) and High (vs. No) chronic stress were 1.11 (0.90-1.37) and 1.21 (1.06-1.38), respectively ( P trend=0.005). This association remained statistically significant after further adjustment for baseline stress ( P trend=0.014) and potential behavioral mediators (smoking, alcohol use, physical activity, diet; P trend=0.03). In stratified analyses, the association was present in women ( P trend=0.002), younger participants (&lt;50 years old; P trend=0.007) and those with normal BP at baseline ( P trend=0.001). Conclusion: We found that African Americans reporting higher chronic stress over time are at increased risk of developing hypertension, independent of baseline stress levels and cardiovascular and behavioral risk factors. Future studies should evaluate the use of stress management interventions to support primary prevention of hypertension in this high risk population.

Metabolite Profiles of Healthy Aging Index Are Associated With Cardiovascular Disease in African Americans: The Health, Aging, and Body Composition Study.

Metabolic dysfunction is a hallmark of differential aging, specifically in African Americans. Investigation of systemic metabolic state, multiorgan aging, and long-term cardiovascular outcome in African Americans has not been reported. We studied 291 African American males in the Health, Aging, and Body Composition (Health ABC) study to identify circulating metabolites related to the Newman healthy aging index (HAI; a multiparametric score comprised of blood pressure, blood glucose, neurocognitive function, creatinine, and forced vital capacity). We examined the relationship of selected metabolites differential abundant at the extremes of HAI with long-term survival from cardiovascular mortality. The median age was 73 years. We identified 19 metabolites differentially expressed in blood in 86 study participants at the extremes of HAI (HAI 0-3: N = 30 vs 8-10: N = 56). At a median follow-up of 10 years, 78 participants (27 per cent) died from cardiovascular causes. After adjustment for age, body mass index, presence of prevalent cardiovascular disease, creatinine, and HAI, six of these 19 metabolites were associated with long-term cardiovascular mortality. Although several metabolites had been previously reported in Caucasians (eg, isocitrate), we identified several metabolites with unreported association with cardiac disease. Metabolites associated with HAI and cardiac death in African Americans specified pathways relevant to nitric oxide, oxidative stress, mitochondrial function, urea cycle, and gut microbial metabolism. Metabolite profiling in African Americans identified known and novel metabolic pathways linked to HAI and cardiovascular death. Further investigation in larger patient cohorts is required to uncover race-based signatures of cardiovascular disease with aging.

167 - Glucose-6-phosphate Dehydrogenase Deficiency and Endothelial Dysfunction: Its Role in Excess CVD in African Americans

African Americans have high incidences of both cardiovascular disease (CVD) and glucose-6-phosphate dehydrogenase (G6PD) deficiency. Clinical studies demonstrate oxidative stress (OS) and lower blood GSH levels correlate with biomarkers of early atherosclerosis such as carotid intima media thickness and blood pressure. G6PD-deficient cells are susceptible to OS, which can lead to exhaustion/deficiency of GSH. We examined the hypothesis that G6PD-deficiency decreases GSH and Nitric oxide (NO), and upregulates cell adhesion molecules (CAMs) which can lead to excess endothelial dysfunction (ED) and atherosclerosis risk. G6PD deficiency in HUVEC and U937 monocytes was induced by using siRNA or by its pharmacological inhibitor (6-AN). G6PD-deficiency exhibited a dose-dependent increase in CAMs (ICAM-1 & VCAM-1), NADPH Oxidase 4, iNOS, MCP-1 and ROS, and reduction in GSH, eNOS and NO levels (p

Leukocyte telomere length and cardiovascular disease in African Americans: The Jackson Heart Study

Background and aimsIn European descent populations, shorter leukocyte telomere length (LTL) has been associated with subclinical atherosclerosis, cardiovascular disease (CVD), and mortality, while longer LTL has been associated with greater left ventricular hypertrophy. We evaluated the relationship of LTL with subclinical cardiovascular disease indices and incident clinical events and mortality in African Americans (AAs). MethodsAnalyses were restricted to 2518 participants of the Jackson Heart Study (JHS) with LTL measured by Southern blot in baseline blood samples. ResultsAdjusting for established CVD risk factors, longer LTL was significantly associated with lower prevalence of coronary artery calcification (CAC) (odds ratio (OR) = 0.810) per 1 kb increase in LTL; (95% confidence interval [CI] 0.656, 0.9998), p=0.0498). Longer LTL was also associated with higher ankle brachial index (ABI) (β = 0.023; (95% CI 0.004, 0.042), p=0.017) when comparing the highest to the lowest LTL quartile. There were no significant associations between LTL and abdominal aortic calcification, carotid intima-media thickness, or left ventricular mass. After a median follow-up of 9 years, longer LTL was associated with lower risk of incident ischemic stroke (hazard ratio (HR) 0.69 (95% CI 0.48, 0.99), p=0.044) and total mortality (HR 0.81 (95% CI 0.67, 0.97), p=0.026) in age and sex adjusted models, but these associations were no longer significant in fully adjusted models. ConclusionsAmong a community-based cohort of AAs, longer LTL was nominally associated with lower odds of CAC and increased ABI, indicative of decreased prevalence of subclinical atherosclerosis and peripheral arterial disease. These findings do not offer strong support for LTL as an independent biomarker of CVD risk in AAs.

Abstract MP022: Cost-effectiveness of the Non-laboratory Based Framingham Algorithm in Primary Prevention of Cardiovascular Disease: a Simulated Analysis of a Cohort of African American Adults

Background: The non-laboratory based (non-LB) Framingham algorithm, which substitutes body mass index for lipids, has been validated for screening cardiovascular disease (CVD) risk among African Americans (AA). However, its marginal cost and benefit tradeoffs have not been contrasted with the established laboratory based (LB) Framingham algorithm. This study examines the incremental cost-effectiveness ratio (ICER) of a simulated CVD prevention program guided by the non-LB versus LB Framingham algorithm. Methods: We simulated the World Health Organization CVD prevention guidelines on AA participants of the Atherosclerosis Risk in Communities (ARIC) cohort. Treatment intensity was tailored according to absolute CVD risk scores calculated by non-LB and LB Framingham algorithms. Costs were estimated using Medicare fee schedules (diagnostic tests, drugs and visits), Bureau of Labor Statistics (RN wages), and Chapman’s estimates for initial and follow-up costs of managing incident CVD events. Outcomes were assumed to be true positive cases detected at the treatment threshold. ICER was calculated using Drummond’s framework. Results: Among 2690 AA (mean age 53.3 ± 5.8 yrs, 59% female) the simulation under the non-LB vs LB Framingham algorithm had an ICER of -$46,240 per true positive case detected. The average 12-year discounted costs under the LB Framingham algorithm were 18.3% higher ($29,991 vs $25,357) and identified 6.5% fewer cases (309 vs 329) compared to the non-LB Framingham algorithm. Conclusion: The approach guided by the non-LB Framingham algorithm dominated the LB Framingham strategy with respect to both costs and predictive ability. Consequently, the non-LB Framingham algorithm could potentially provide a lower cost but a highly effective tool to address the high burden of CVD in AA and other resource constrained settings.

Abstract P077: Validation of the Pooled Cohort Equations for CVD Risk Assessment in African Americans: The Jackson Heart Study

Background: Cardiovascular disease (CVD) risk assessment tools such as the Framingham Risk Score are useful to identify population high risk subgroups for targeted intervention. However, no CVD risk score specific for African Americans (AAs) were available until the Pooled Cohort Equations (PCE) was introduced in 2013 for calculating sex- and race-specific10-year predicted risk of atherosclerotic cardiovascular disease (ASCVD). This study evaluated the performance of PCE in the Jackson Heart Study (JHS), a prospective cohort study of CVD in AAs. Methods: The analytic sample included 2,191 JHS participants who were 40-79 years old without a history of CVD or CVD procedures at baseline (2000-2004) and who were not a shared participant in the Atherosclerosis Risk in Communities (ARIC) Study. ASCVD events (CHD and stroke) were ascertained by active surveillance with medical records abstraction. Because all participants were followed at least 8 years through 2012, validation of the PCE was based on 8-year observed and predicted risks of ASCVD. The PCE was evaluated for discrimination and calibration properties using c-index and Hosmer-Lemeshow (HL) x 2 statistic, respectively. Overall and subgroup analysis among participants (no diabetes, LDL between 70 and 189 mg/dL and not taking statins) for whom CVD risk assessment may be applied to guide treatment for high blood cholesterol were performed. Stratified analyses evaluating the performance of PCE by baseline characteristics, including sex, age (&lt;50/≥50 years), income (affluent*/not affluent), education (&lt;high school/≥high school), BMI (&lt;30/≥30), diabetes status (yes/no), self-reported use of hypertension medications (yes/no), self-reported use of statins (yes/no) and current smoking status (yes/no) were also performed. Results: There were a total of 63 incident ASCVD events (29 CHD; 34 stroke). The PCE predicted total number of event was 130, with a c-index=0.78 (95% CI 0.54-0.96) and a HL x 2 =38.2 (p&lt;0.001). The PCE showed a similar discrimination but better calibration property in the subset of participants for whom CVD risk assessment may be applied to guide treatment for high blood cholesterol (n=1,576, c-index=0.78, 95% CI 0.43-1; HL x 2 =21.9, p=0.005). In stratified analyses, PCE had better calibration in participants who were younger (n=831, HL x 2 =10.5, p=0.23), not affluent (n=1,120, HL x 2 =12.6, p=0.12), less educated (n=186, HL x 2 =6.6, p=0.58), those with lower BMI (n=833, HL x 2 =8.5, p=0.39), those with diabetes (n=287, HL x 2 =11.1, p=0.20), and statin users (n=159, HL x 2 =10.8, p=0.21). Conclusions: Overall, the PCE showed good discrimination but did not calibrate well and overestimated the risk of ASCVD. In the subset of participants for whom CVD risk assessment may be applied to guide treatment for high blood cholesterol, the PCE showed improved calibration but still overestimated risk. *Defined as 3 times above poverty level.