African-American Failure Research Articles

TCT-793 Unraveling the Connection: Central Obesity, Atherosclerosis, and Heart Failure in African Americans: Focusing on the Mediating Role of Atherosclerosis

TCT-793 Unraveling the Connection: Central Obesity, Atherosclerosis, and Heart Failure in African Americans: Focusing on the Mediating Role of Atherosclerosis

Hypertension is associated with more advanced heart failure in african americans with suspected cardiac amyloidosis

Abstract Background Prior studies have shown worse clinical outcomes for African Americans with transthyretin and light chain cardiac amyloidosis as compared to Caucasians. Hypertensive heart disease is common among African Americans, and a known echocardiographic mimic of cardiac amyloidosis. The association between hypertension and heart failure severity in patients with suspected cardiac amyloidosis has not been well characterized. Purpose We sought to identify phenotypic differences between African American and Caucasian patients with suspected cardiac amyloidosis with and without hypertension. Methods We retrospectively identified consecutive patients who underwent cardiac biopsy for evaluation of cardiac amyloidosis at our institution between 2000–2018. Clinical and demographic data were obtained from the medical record. Electrocardiograms and echocardiograms performed at the time of cardiac biopsy were interpreted by study personnel. Results Among 230 patients with suspected cardiac amyloidosis, 144 (58%) had a prior diagnosis of hypertension. Hypertension was more common among African Americans (71 of 91, 78%) than among Caucasians (73 of 139, 52%). Among African Americans with suspected cardiac amyloidosis, those with hypertension had higher left ventricular mass index (156 versus 119 g/m2), lower left ventricular ejection fraction (47% versus 56%), worse global longitudinal strain (−9.0% versus −11.7%), and higher creatine (1.95 versus 1.43 mg/dL) than those without hypertension (p<0.05 for all). There were no differences in these parameters among Caucasians with and without hypertension. Conclusions Among African Americans with suspected cardiac amyloidosis, those with hypertension had worse systolic function and more advanced heart failure than those without hypertension. Targeted screening and/or surveillance strategies are needed to improve early diagnosis of cardiac amyloidosis in African American patients with hypertension. Funding Acknowledgement Type of funding sources: None.

APOL1 Genetic Testing in Patients With Recent African Ancestry and Hypertension: A Pilot Study of Attitudes and Perceptions

The incidence of kidney failure in African Americans is 2-3 times higher than that in White Americans. A portion of the increased kidney risk appears to be because of polymorphisms in the gene encoding apolipoprotein L1 (APOL1). The precise mechanism of how APOL1 renal-risk variants accelerate kidney disease progression is a matter of intense research, and currently there are no proven treatments for APOL1-related kidney disease. Currently, there are large National Institutes of Health-funded national studies (APOL1 Long-term Kidney Transplantation Outcomes Network [“APOLLO”] and Living Donor Extended Time Study [“LETO”]) underway to help define the role of APOL1 genotyping in the context of kidney donation and transplantation.

Vericiguat, organic nitrates, and heart failure in African Americans

African Americans (AA) have a higher prevalence of heart failure (HF) when compared with White Americans (3% vs 2%), respectively and HF comes on at an earlier age and is more severe in AA. The A-HEFT trial with the combination of hydralazine and isosorbide dinitrate (ISDNHYD) for self-described AA with NYHA class III–IV heart failure with reduced ejection fraction (HFrEF) showed reduction in mortality and HF hospitalizations with a class I level of evidence A recommendation in the ACC/AHA guidelines. Vericiguat is an oral soluble guanylate cyclase stimulator that enhances the cyclic guanosine monophosphate (GMP) pathway. A randomized, double-blind, placebo-controlled trial in patients with higher risk HFrEF in which AA were underrepresented found that vericiguat reduced the composite primary outcome of cardiovascular death or first HF hospitalization. In the new era of guideline directed medical therapies of quadruple therapy – hydralazine and isosorbide dinitrate should be preferred over vericiguat in AA with HFrEF.

Abstract 14450: Association of Trajectory of High Sensitivity C-reactive Protein and Incident Heart Failure in African Americans: The Jackson Heart Study

Introduction: Elevation in the inflammatory marker high sensitivity C-reactive protein (hsCRP) is associated with worse outcomes in patients with heart failure (HF). We aimed to determine if baseline or trajectory of hsCRP levels over time predict incident HF hospitalization. Methods: Jackson Heart Study (JHS) participants’ (n=4203 African Americans) hsCRP levels were measured over 3 visits (visit 1: 2000 to 2004; visit 2: 2005 to 2008; visit 3: 2009 to 2013). We assessed the association of a single hsCRP level measurement at baseline (visit 1) with incident HF hospitalization using Cox proportional hazard models. Furthermore, we assessed the association of trajectory of hsCRP over repeated measurements (visit 1-3) with incident HF using a joint model, which incorporates estimated hsCRP from a linear mixed effects model into a Cox hazards model to predict incident HF hospitalization while incorporating trajectory of hsCRP over visits. All hazard ratios (HR) are presented as an increase in hsCRP by 1 standard deviation on a Log 2 scale. Results: At baseline, mean age of participants was 55±13 years, 63.4% were women, and mean hsCRP level was 0.5±0.7 mg/dl. Over a median follow-up of 12 years, 353 (8.4%) participants were hospitalized with incident HF. After adjustment for covariates, baseline hsCRP was not associated with increased risk of incident HF hospitalization (Table, p>0.05). However, increases in hsCRP levels on follow-up were associated with a significantly increased risk of incident HF hospitalization (Table, p<0.05). Conclusions: While an elevated hsCRP level at one time point may not be associated with incident HF, the increasing trajectory of change in hsCRP over time is predictive of increased risk for incident HF hospitalization in African Americans. These data support the role of increased inflammatory status in the development of heart failure.

Association of plasma adiponectin with pulmonary hypertension, mortality and heart failure in African Americans: Jackson Heart Study.

BackgroundAdiponectin is a polypeptide hormone related to obesity, and a known modulator of pulmonary vascular remodeling. Association between plasma adiponectin levels and pulmonary hypertension (PH) has not been studied in African Americans (AAs) who are disproportionately affected by obesity. The relationship between adiponectin and heart failure (HF) and mortality, outcomes associated with PH, is unclear.MethodsWe performed cross-sectional and longitudinal analysis to examine if there is an association between plasma adiponectin and PH and associated clinical outcomes, in participants of Jackson Heart Study (JHS). JHS is a prospective observational cohort study of heart disease in AAs from Jackson, Mississippi.ResultsOf the 3161 participants included in the study, mean age (SD) was 56.38 (12.61) years, 1028 were men (32.5%), and mean (SD) BMI was 31.42 (7.05) kg/m2. Median (IQR) adiponectin was 4516.82 (2799.32–7065.85) ng/mL. After adjusting for potential confounders including BMI, higher adiponectin levels were associated with increased odds of PH (adjusted odds ratio per log increment in adiponectin, (1.81; 95% CI, 1.41–2.32). High adiponectin levels were also associated with associated HF admissions (adjusted hazard ratio [HR] per log increment in adiponectin, 1.63, 95% CI, 1.24–2.14) and mortality (adjusted HR per log increment in adiponectin, 1.20; 95% CI 1.02–1.41).ConclusionsElevated plasma adiponectin levels are associated with PH, HF admissions and mortality risk in AAs. High adiponectin levels may help identify an at-risk population that could be evaluated for targeted prevention and management strategies in future studies

Abstract 511: Transcriptomic Analysis of End-stage Human Heart Failure Highlights Strong Interaction Effect Between Race and Diabetes

African Americans (AA) have an elevated risk for cardiovascular diseases compared to Caucasian Americans (CA), including heart failure (HF). Type 2 diabetes (T2D) is a major risk factor for HF that also disproportionately affects AA. These health disparities and others reduce life expectancy ~3.5 y for AA compared to CA. While prior studies have explored the connection between diabetes and heart failure, the current understanding of HF pathogenesis is based almost exclusively from studies of CA, whereas those considering race have been either epidemiologic or narrow in focus. The purpose of this study was to examine things from a different angle through the use of genome-wide RNA-sequencing to uncover how diabetes differentially or similarly affects end-stage heart failure in AA vs CA. To accomplish this, human biopsy samples were obtained from 32 age and diabetes status (T2D or non-diabetic (ND)) matched male patients undergoing left ventricle assist device surgeries (n = 8: CA-ND, CA-T2D, AA-ND, AA-T2D). Differential expression analysis was then performed using generalized linear modeling to control for clinical covariates including hypertension and coronary artery disease. Results of T2D vs ND in AA patients showed a greater number of differentially expressed genes (DEGs, P < 0.05,

Association of Cardiac Injury and Malignant Left Ventricular Hypertrophy With Risk of Heart Failure in African Americans

African Americans have a higher burden of heart failure (HF) risk factors and clinical HF than other racial/ethnic groups. However, the factors underlying the transition from at-risk to clinical HF in African Americans are not well understood. To evaluate the contributions of left ventricular hypertrophy (LVH) and subclinical myocardial injury as determined by abnormal high-sensitivity cardiac troponin-I (hs-cTnI) measurements toward HF risk among African Americans. This prospective, community-based cohort study was conducted between July 2016 and September 2018 and included African American participants from Jackson, Mississippi enrolled in the Jackson Heart Study without prevalent HF who had hs-cTnI measurements and an echocardiographic examination at baseline. Participants were stratified into categories based on the presence or absence of LVH and subclinical myocardial injury (category 1: hs-cTnI <4 ng/L in women and <6 ng/L in men; category 2: 4-10 ng/L in women and 6-12 ng/L in men; category 3: >10 ng/L in women and >12 ng/L in men). Adjusted associations between LVH, subclinical myocardial injury, and the risk of incident HF hospitalization were assessed using Cox proportional hazards models. The study included 3987 participants (2552 women [64%]; 240 (6.0%) with LVH; 1003 (25.1%) with myocardial injury) with 285 incident HF events over a median follow-up of 9.8 years (interquartile range, 8.9-10.6 years). In adjusted analyses, higher LV mass and subclinical myocardial injury were independently associated with the risk of HF with a significant interaction between the 2 (Pint < 0.001). The highest risk of HF was noted among individuals with both LVH and myocardial injury (absolute incidence, 35%; adjusted hazard ratio [aHR; vs no LVH and no myocardial injury], 5.35; 95% CI, 3.66-7.83). A significant interaction by sex was also observed. Men with LVH and subclinical myocardial injury had an almost 15-fold higher risk of HF (aHR, 14.62; 95% CI, 7.61-28.10) vs those with neither LVH nor injuries. By contrast, women with this phenotype had a nearly 4-fold higher risk of HF (aHR, 3.81; 95% CI, 2.40-6.85). The combination of LVH and subclinical myocardial injury identifies a malignant, preclinical HF phenotype in African Americans with a very high risk of HF, particularly among men. This finding could have implications for future screening strategies that are designed to prevent HF in the population.

Restrictive Spirometry Pattern, Cardiac Structure and Function, and Incident Heart Failure in African Americans. The Jackson Heart Study.

Although chronic obstructive pulmonary disease has been related to heart failure, the relationship between the restrictive spirometry pattern (forced vital capacity [FVC] < 80% predicted with preserved forced expiratory volume in 1 second [FEV1]/FVC ratio) and heart failure is poorly understood. To determine whether having a restrictive spirometry pattern is associated with incident heart failure hospitalization. Community-dwelling African Americans from the Jackson Heart Study (total n = 5,306; analyzed n = 4,210 with spirometry and heart failure outcome data) were grouped by restrictive spirometry (FEV1/FVC ≥ 0.70, FVC < 80%; n = 840), airflow obstruction (FEV1/FVC < 0.70; n = 341), and normal spirometry (FEV1/FVC ≥ 0.70, FVC ≥ 80%; n = 3,029) at the time of baseline examination in 2000-2004. We assessed relationships of echocardiographic parameters and biomarkers with spirometry patterns using regression models. Incident heart failure was defined as an adjudicated hospitalization for heart failure after January 1, 2005 in subjects with no self-reported heart failure history. We used multivariable-adjusted Poisson regression models and Cox proportional hazards models, with death treated as a competing risk in the Cox models, to test associations between spirometry patterns and incident heart failure. We also modeled the association of FVC% predicted with heart failure hospitalization risk using a restricted cubic spline after excluding subjects with airflow obstruction. At the time of baseline spirometry, participants with restrictive spirometry had a median age of 57.2 years (interquartile range, 47.8-64.1); 38.1% were male. Compared with normal spirometry, restrictive spirometry was associated with a higher transmitral early (E) wave velocity to atrial (A) wave velocity ratio, higher pulmonary artery systolic pressure, and higher endothelin levels. After a median follow-up time of 8.0 years, 8.0% of subjects with restrictive spirometry (n = 67) had developed incident heart failure, compared with 3.8% of those with normal spirometry (n = 115) and 10.6% of those with airflow obstruction (n = 36). After risk adjustment, both a restrictive pattern (hazard ratio [HR], 1.5; 95% confidence interval [CI], 1.1-2.0) and airflow obstruction (HR, 1.7; 95% CI, 1.1-2.5) were associated with increased rates of incident heart failure hospitalization compared with normal spirometry. Using flexible modeling, the lowest hazards of heart failure hospitalization were observed around FVC 90-100%, with lower FVC% values associated with an increased incidence of heart failure. Both a restrictive pattern on spirometry and airflow obstruction identify African Americans with impaired lung health at risk for heart failure.

Whole exome analyses to examine the impact of rare variants on left ventricular traits in African American participants from the HyperGEN and GENOA studies.

Left ventricular (LV) hypertrophy, highest in prevalence among African Americans, is an established risk factor heart failure. Several genome wide association studies have identified common variants associated with LV-related quantitative-traits in African Americans. To date, however, the effect of rare variants on these traits has not been extensively studied, especially in minority groups. We therefore investigated the association between rare variants and LV traits among 1,934 African Americans using exome chip data from the Hypertension Genetic Epidemiology Network (HyperGEN) study, with replication in 1,090 African American from the Genetic Epidemiology Network of Arteriopathy (GENOA) study. We used single-variant analyses and gene-based tests to investigate the association between 86,927 variants and six structural and functional LV traits including LV mass, LV internal dimension-diastole, relative wall thickness, left atrial dimension (LAD), fractional shortening (FS), and the ratio of LV early-to-late transmitral velocity (E/A ratio). Only rare variants (MAF <1% and <5%) were considered in gene-based analyses. In gene-based analyses, we found a statistically significant association between potassium voltage-gated channel subfamily H member 4 (KCNH4) and E/A ratio (P=8.7*10-8 using a burden test). Endonuclease G (ENDOG) was associated with LAD using the Madsen Browning weighted burden (MB) test (P=1.4*10-7). Neither gene result was replicated in GENOA, but the direction of effect of single variants in common was comparable. G protein-coupled receptor 55 (GPR55) was marginally associated with LAD in HyperGEN (P=3.2*10-5 using the MB test) and E/A ratio in GENOA, but with opposing directions of association for variants in common (P=0.03 for the MB test). No single variant was statistically significantly associated with any trait after correcting for multiple testing. The findings in this study highlight the potential cumulative contributions of rare variants to LV traits which, if validated, could improve our understanding of heart failure in African Americans.

Diastolic wall strain is associated with incident heart failure in African Americans: Insights from the atherosclerosis risk in communities study

BackgroundIncreased left ventricular (LV) myocardial stiffness may be associated with impaired LV hemodynamics and incident heart failure (HF). However, an indicator that estimates LV myocardial stiffness easily and non-invasively is lacking. The purpose of this study was to determine whether diastolic wall strain (DWS), an echocardiographic estimator of LV myocardial stiffness, is associated with incident HF in a middle-aged community-based cohort of African Americans. Methods and resultsWe investigated associations between DWS and incident HF among 1528 African Americans (mean age 58.5 years, 66% women) with preserved LV ejection fraction (EF ≥50%) and without a history of cardiovascular disease in the Atherosclerosis Risk in Communities Study. Participants with the smallest DWS quintile (more LV myocardial stiffness) had a higher LV mass index, higher relative wall thickness, and lower arterial compliance than those in the larger four DWS quintiles (p<0.01 for all). Over a mean follow-up of 15.6 years, there were 251 incident HF events (incidence rate: 10.9 per 1000 person-years). After adjustment for traditional risk factors and incident coronary artery disease, both continuous and categorical DWS were independently associated with incident HF (HR 1.21, 95%CI 1.04–1.41 for 0.1 decrease in continuous DWS, p=0.014, HR 1.40, 95%CI 1.05–1.87 for the smallest DWS quintile vs other combined quintiles, p=0.022). ConclusionsDWS was independently associated with an increased risk of incident HF in a community-based cohort of African Americans. DWS could be used as a qualitative estimator of LV myocardial stiffness.

Abstract 12230: Increased Left Ventricular Myocardial Stiffness is Associated With Incident Heart Failure in African Americans: The Atherosclerosis Risk in Communities (ARIC) Study

Background: Increased left ventricular (LV) myocardial stiffness may be associated with future deterioration of LV hemodynamics and incident heart failure (HF). Diastolic wall strain (DWS) is a recently developed echocardiographic indicator of LV myocardial stiffness. We hypothesized that increased LV myocardial stiffness evaluated by DWS is associated with incident HF in a community-based African American cohort in the ARIC. Methods and Results: We investigated the association between LV myocardial stiffness and incident HF among 1553 African American participants (mean age 58.5 years, 66% women) without a history of cardiovascular diseases or LV wall motion abnormalities in the ARIC Study. Echocardiography was performed at Visit 3 in the African American cohort in Jackson, MS. DWS was calculated as (posterior wall thickness at end-systole - posterior wall thickness at end-diastole) / posterior wall thickness at end-systole. DWS quartiles were generated and used to make the Kaplan-Meier survival curves for incident HF with log-rank test. Cox proportional hazards models were used to evaluate the association between baseline DWS and incident HF. Over a median follow-up of 15.6 years, there were 251 HF events (incidence rate: 10.9 per 1,000 person-years). Participants with lower DWS (increased LV diastolic stiffness) had a higher incidence of HF than those with higher DWS (unadjusted hazard ratio 1.86, 95%CI 1.28-2.71 in 1 st quartile vs 4 th quartile, p=0.001). After adjustment for traditional risk factors and incident coronary heart disease during the course, DWS was independently associated with incident HF (hazard ratio 1.62, 95%CI 1.10-2.38 in 1 st quartile vs 4 th quartile, p=0.015). Conclusions: Increased LV myocardial stiffness evaluated by DWS was associated with an increased risk of HF in a community-based African American cohort in the ARIC. Increased LV myocardial stiffness may lead to future deterioration of LV hemodynamics and incident HF.

Abstract 11315: Ideal Cardiovascular Health, Cardiometabolic Remodeling, and Heart Failure in African-Americans: The Jackson Heart Study

Background: Though African-Americans are at disproportionately high risk for heart failure (HF) and cardiometabolic disease, few studies have evaluated the association between ideal cardiovascular health metrics and cardiometabolic diseases or incident HF in African-Americans. Hypothesis: Ideal cardiovascular health is associated with adverse cardiometabolic phenotypes and incident HF. Methods: A total of 4195 African-American participants without prevalent coronary heart disease with 7 ideal cardiovascular health (ICVH) metrics measured at baseline (2000-2004) underwent evaluation by cardiac magnetic resonance (CMR; n=1188) and/or abdominal computed tomography (CT; n=2352). 3661 (87%) participants were followed for incident HF. Results: Mean age at baseline was 54.4 years (65% women). A lower composite score of ICVH at baseline was associated with greater LV hypertrophy, greater LV concentric remodeling, worse LV strain, and greater visceral and subcutaneous adipose tissue in follow-up (all P &lt;0.0001). Ideal BMI, absence of smoking, controlled blood pressure and normoglycemia were associated with improved cardiac and adiposity phenotypes. Relative to individuals with 0-2 ideal ICVH factors, African-Americans with 3 factors had 48% lower incident HF risk (HR 0.52, 95% CI 0.35-0.75, P=0.0006) and those with ≥ 4 factors had 58% lower HF risk (HR 0.42, 95% CI 0.24-0.76, P=0.004). Of the 7 components of ICVH, non-ideal physical activity, smoking, and impaired glucose control were associated with incident HF risk. Conclusions: In African-Americans, lower ideal cardiovascular health in mid-life is associated with later adverse cardiometabolic remodeling and incident HF. Lack of physical activity, smoking and impaired glucose control are associated with incident HF risk and represent potential targets for prevention of cardiometabolic disease and HF in African-Americans.

Introducing Genetic Tests With Uncertain Implications in Living Donor Kidney Transplantation: ApoL1 as a Case Study.

Genetic mutations in apolipoprotein L1 (ApoL1) are associated with kidney disease. Apolipoprotein L1 mutations are common in African Americans (∼39% and 12% have 1 and 2 high-risk alleles, respectively). Carrying 2 ApoL1 risk alleles may explain much of the excess rate of kidney failure in African Americans compared to European Americans. Apolipoprotein L1 also has implications for kidney transplantation. Kidney grafts from deceased donors with 2 ApoL1 risk alleles have worse graft survival, but outcomes appear unaffected by recipient ApoL1 status. Unknown is whether donation increases the risk of kidney failure in living donors with 2 ApoL1 risk alleles and whether their donated kidneys have worse graft survival. There are 4 options to consider: (1) remain silent about ApoL1 risk alleles and renal failure and wait for more data; (2) counsel about race, ApoL1, and subsequent renal failure abstractly but remain agnostic about donor testing until more data are available; (3) provide counseling and encourage genotyping of prospective living donors of African ancestry as part of the living donor workup; or (4) mandate testing of all prospective living donors. We support option 3, and recommend, with donor permission, to discuss the results with potential recipients to promote informed decision-making. We also argue for a voluntary donor registry that collects long-term follow-up information. We provide ethical arguments to support these recommendations.

Markers of kidney disease and risk of subclinical and clinical heart failure in African Americans: the Jackson Heart Study.

African Americans and patients with chronic kidney disease (CKD) are at high risk for clinical heart failure (HF). In this study, we aimed to determine the association of markers of kidney disease with subclinical HF (by echocardiogram) and risk of clinical HF among a large, well-characterized community-based cohort of African American patients. We also examined whether the association of markers of kidney disease with HF was attenuated with adjustment for echocardiographic measures. We studied participants in the Jackson Heart Study, a large community-based cohort of African Americans. Estimated glomerular filtration rate (eGFR) and urine albumin:creatinine ratio (ACR) were measured at baseline. We tested the association of eGFR and urine ACR with left ventricular mass (LVM), left ventricular ejection fraction (LVEF) and physician-adjudicated incident HF. Among the 3332 participants in the study, 166 (5%) had eGFR <60 mL/min/1.73 m2 and 405 (12%) had urine ACR ≥30 mg/g. In models adjusted for demographics, comorbidity and the alternative measure of kidney disease, lower eGFR and higher urine ACR were associated with higher LVM {β-coefficient 1.54 [95% confidence interval (CI) 0.78-2.31] per 10 mL/min/1.73 m2 decrease in eGFR and 2.87 (95% CI 1.85-3.88) per doubling of urine ACR}. There was no association of eGFR and urine ACR with LVEF [β-coefficient -0.12 (95% CI -0.28-0.04) and -0.11 (95% CI -0.35-0.12), respectively]. There was no association of eGFR with the risk of incident HF [HR 1.02 (95% CI 0.91-1.14) per 10 mL/min/1.73 m2 decrease], while there was a significant association of urine ACR [HR 2.22 (95% CI 1.29-3.84) per doubling of urine ACR]. This association was only modestly attenuated with adjustment for LVM [HR 1.95 (95% CI 1.09-3.49)]. Among a community-based cohort of African Americans, lower eGFR and higher ACR were associated with higher LVM. Furthermore, higher urine ACR was associated with incident HF, which was not entirely explained by the presence of left ventricular disease.

Markers of endothelial dysfunction and inflammation predict progression of diabetic nephropathy in African Americans with type 1 diabetes

African Americans with early onset type 1 diabetes mellitus are at a high risk for severe diabetic nephropathy and end-stage renal disease. In order to determine whether baseline plasma levels of inflammatory markers predict incidence of overt proteinuria or renal failure in African Americans with type 1 diabetes mellitus we reexamined data of 356 participants in our observational follow-up study of 725 New Jersey African-Americans with Type 1 diabetes. At baseline and 6-year follow-up, a detailed structured clinical interview was conducted to document medical history including kidney dialysis or transplant, other diabetic complications, and renal-specific mortality. Plasma levels of 28 inflammatory biomarkers were measured using a multiplex bead analysis system. After adjusting for baseline age, glycohemoglobin and other confounders, the baseline plasma levels of intercellular adhesion molecule-1(s-ICAM-1) in the upper two quartiles were respectively associated with a 3 to 5-fold increases in the risk of progression from none or microalbuminuria to overt proteinuria. Baseline plasma levels of the chemokine eotaxin in the upper quartile were significantly associated with a 7-fold increase in risk of incident renal failure. These associations were independent of traditional risk factors for progression of diabetic nephropathy. Thus, in type 1 diabetic African Americans, s-ICAM-1 predicted progression to overt proteinuria and eotaxin predicted progression to renal failure.

G-Protein Beta-3 Subunit Genotype Predicts Enhanced Benefit of Fixed-Dose Isosorbide Dinitrate and Hydralazine: Results of A-HeFT

ObjectivesThe purpose of this study was to evaluate the influence of the guanine nucleotide-binding proteins (G-proteins), beta-3 subunit (GNB3) genotype on the effectiveness of a fixed-dose combination of isosorbide dinitrate and hydralazine (FDC I/H) in A-HeFT (African American Heart Failure Trial). BackgroundGNB3 plays a role in alpha2-adrenergic signaling. A polymorphism (C825T) exists, and the T allele is linked to enhanced alpha-adrenergic tone and is more prevalent in African Americans. MethodsA total of 350 subjects enrolled in the genetic substudy (GRAHF [Genetic Risk Assessment of Heart Failure in African Americans]) were genotyped for the C825T polymorphism. The impact of FDC I/H on a composite score (CS) that incorporated death, hospital stay for heart failure, and change in quality of life (QoL) and on event-free survival were assessed in GNB3 genotype subsets. ResultsThe GRAHF cohort was 60% male, 25% ischemic, 97% New York Heart Association functional class III, age 57 ± 13 years, with a mean qualifying left ventricular ejection fraction of 0.24 ± 0.06. For GNB3 genotype, 184 subjects were TT (53%), 137 (39%) CT, and 29 (8%) were CC. In GNB3 TT subjects, FDC I/H improved the CS (FDC I/H = 0.50 ± 1.6; placebo = −0.11 ± 1.8, p = 0.02), QoL (FDC I/H = 0.69 ± 1.4; placebo = 0.24 ± 1.5, p = 0.04), and event-free survival (hazard ratio: 0.51, p = 0.047), but not in subjects with the C allele (for CS, FDC I/H = −0.05 ± 1.7; placebo = −0.09 ± 1.7, p = 0.87; for QoL, FDC I/H = 0.28 ± 1.5; placebo = 0.14 ± 1.5, p = 0.56; and for event-free survival, p = 0.35). ConclusionsThe GNB3 TT genotype was associated with greater therapeutic effect of FDC I/H in A-HeFT. The role of the GNB3 genotype for targeting therapy with FDC I/H deserves further study.

Abstract 315: Anemia predicts 30-Day Hospital Readmission for Heart Failure in African Americans

Background: Anemia is a frequently encountered comorbidity that affects both death and hospitalization in patients with heart failure (HF). The effect of anemia on 30-day hospital readmission in African Americans (AA) with HF has not been studied. Methods: We retrospectively enrolled all 243 (61% female) self-reported AA adults admitted to the University of Illinois at Chicago hospital with the diagnosis of HF from January 2011 to December 2012. Extensive medical chart reviews were performed. Results: The prevalence of anemia with hemoglobin (Hb) &lt;12g/dl was 64.6%. After adjusting for factors known to affect readmission (table), lower Hb (&lt;12g/dl) levels were associated with increased 30-day readmission rates (OR 0.814, 95% CI 1.6-20.7, p=0.008) in a Cox proportional hazard logistic regression model. Conclusion: Lower Hb levels are associated with higher 30-day readmission rates in hospitalized AA patients with HF. Interventions towards appropriate treatment and prevention of anemia in AA with HF might reduce their readmission rates and improve their outcome.

Heart failure in African Americans: disparities can be overcome.

African Americans are disproportionately affected by heart failure, with a high prevalence at an early age. Hypertension, diabetes, obesity, and chronic kidney disease are all common in African Americans and all predispose to heart failure. Neurohormonal imbalances, endothelial dysfunction, genetic polymorphisms, and socioeconomic factors also contribute. In general, the same evidence-based treatment guidelines that apply to white patients with heart failure also apply to African Americans. However, the combination of hydralazine and isosorbide dinitrate is advised specifically for African Americans.

Health outcomes among non-Caucasian living kidney donors: knowns and unknowns

The growth in living kidney donation has been accompanied by greater racial diversity. Most information on post-donation health comes from single-center studies of dominantly Caucasian cohorts. Recent linkage of U.S. donor registration data with death records demonstrated higher mortality risks among African American donors, but importantly, no differences in death compared with demographically matched, healthy controls. Within the donor population, some recent studies have also identified higher likelihoods of post-donation hypertension, diabetes mellitus and kidney failure in African American and Hispanic donors. Thus, based on concerns for higher risks of long-term end-organ damage, it may be reasonable to consider race within the living donor selection process, such as use of more stringent exclusion criteria among non-Caucasian living donors with baseline elevated blood pressure. Recently identified associations of coding variants in the apolipoprotein L1 (APOL1) gene with nondiabetic renal failure in African Americans raise promise of APOL1 genotyping as a novel tool for risk stratifying African American potential donors, but more data are needed to understand implications for post-donation outcomes. To tailor counseling and informed consent, focused attention to long-term medical outcomes among non-Caucasian living donors is needed, and should include assembly of healthy non-donor controls for assessment of attributable risks of donation.