Heart Failure In African Americans Research Articles

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.

Cardiorenal Complications in Young-Onset Type 2 Diabetes Compared Between White Americans and African Americans.

To explore risks and associated mediation effects of developing chronic kidney disease (CKD) and heart failure (HF) in young- and usual-onset type 2 diabetes (T2D) between White Americans (WAs) and African Americans (AAs). From U.S. medical records, 1,491,672 WAs and 31,133 AAs were identified and stratified by T2D age of onset (18-39, 40-49, 50-59, 60-70 years). Risks, mediation effects, and time to CKD and HF were evaluated, adjusting for time-varying confounders. In the 18-39, 40-49, 50-59, 60-70 age-groups, the hazard ratios (of developing CKD and HF in AAs versus WAs were 1.21 (95% CI 1.17-1.26) and 2.21 (1.98-2.45), 1.25 (1.22-1.28) and 1.86 (1.75-1.97), 1.21 (1.19-1.24) and 1.54 (1.48-1.60), and 1.10 (1.08-1.12) and 1.11 (1.07-1.15), respectively. In AAs and WAs aged 18-39 years, time in years to CKD (8.7 [95% CI 8.2-9.1] and 9.7 [9.2-10.2]) and HF (10.3 [9.3-11.2] and 12.1 [10.6-13.5]) were, on average, 3.6 and 4.0 and 3.1 and 4.1 years longer compared with those diagnosed at age 60-70 years. Compared with females, AA males aged <60 years had an 11-49% higher CKD risk, while WA males aged <40 years had a 23% higher and those aged ≥50 years a 7-14% lower CKD risk, respectively. The mediation effects of CKD on the HF risk difference between ethnicities across age-groups (range 54-91%) were higher compared with those of HF on CKD risk difference between ethnicities across age-groups (13-39%). Developing cardiorenal complications within an average of 10 years of young-onset T2DM and high mediation effects of CKD on HF call for revisiting guidelines on early diagnosis and proactive treatment strategies for effective management of cardiometabolic risk.

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 033: Epigenetic Clocks And Incident Heart Failure: The Atherosclerosis Risk In Communities (aric)

Background: DNA methylation (DNAm)-based measures of aging, termed epigenetic clocks (EC), are associated with aging-related outcomes including cardiovascular disease (CVD) and all-cause mortality. Associations of ECs with heart failure (HF) are unclear. We tested whether ECs were positively associated with risk of incident HF in the Atherosclerosis Risk in Communities (ARIC) study and evaluated whether adding ECs to Pooled Cohort Equation (PCE) variables improved risk prediction. Methods: We measured DNAm in peripheral blood leukocytes in 2,263 African American (mean age=56.3 years) and 925 European American (mean age=59.5 years) participants using the Illumina HM450K and calculated 7 ECs: Horvath, Hannum, extrinsic (EEAA) and intrinsic (IEAA) epigenetic age acceleration, Hannum, PhenoAge, and GrimAge. HF was ascertained by ICD- 9 code 428 and adjudication by an expert panel. We carried out race stratified proportional hazards regression to test associations ECs with incident HF, adjusting for PCE variables: age, sex, smoking, total cholesterol, HDL, systolic blood pressure (SBP), antihypertensive medication use, and diabetes. We calculated area under the curve (AUC) and integrated discrimination index (IDI) to evaluate improvement in risk prediction when adding the ECs to PCE variables. Results: The number of incident HF events and mean follow-up time in African Americans and European Americans were 640 (189 in the first 10 years) and 19.3 years, and 191 and 21.7 years, respectively. All 7 ECs were positively associated with HF in both African Americans and European Americans. In African Americans with follow-up restricted to the first 10 years, the HR for a one SD increment in GrimAge (5.64 years) was 1.57 (95% CI=1.31, 1.88), comparable to that for a one-SD (5.82 years) increment in age (HR=1.58, 95% CI=1.36, 1.83) and greater than that for a one-SD (20.2mmHg) increment in SBP (HR=1.33, 95% CI=1.18, 1.51). In European Americans across the entire follow-up period, the HR for a one-SD increment in GrimAge (6.13 years) was 1.22 (95% CI=1.06, 1.41), smaller than that for a one-SD (5.50 years) increment in age (HR=1.93, 95% CI=1.63, 2.29) and larger than that for a one-SD (17.9 mmHG) increment in SBP (HR=1.13, 95% CI=0.98, 1.30). In African Americans with follow-up restricted to the first 10 years, adding GrimAge to PCE variables increased AUC by 0.019 (95% CI=0.003, 0.035) and the IDI was 0.010 (95% CI=0.002, 0.019). In European Americans, adding GrimAge did not change AUC appreciably (0.004, 95% CI=-0.006, 0.014) and the IDI was 0.002 (95% CI=0.000, 0.005). Conclusion: ECs are positively associated with HF in African American and European American participants independent of traditional CVD risk factors. GrimAge modestly improved heart failure risk prediction in African Americans. HF-specific DNAm-based measures should be developed and evaluated for improvement in risk prediction.

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&gt;0.05). However, increases in hsCRP levels on follow-up were associated with a significantly increased risk of incident HF hospitalization (Table, p&lt;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.

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

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

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 &lt; 0.05,

A Smartphone App for Self-Management of Heart Failure in Older African Americans: Feasibility and Usability Study.

BackgroundMobile health (mHealth) apps are dramatically changing how patients and providers manage and monitor chronic health conditions, especially in the area of self-monitoring. African Americans have higher mortality rates from heart failure than other racial groups in the United States. Therefore, self-management of heart failure may improve health outcomes for African American patients.ObjectiveThe aim of the present study was to determine the feasibility of using an mHealth app, and explore the outcomes of quality of life, including self-care maintenance, management, and confidence, among African American patients managing their condition after discharge with a diagnosis of heart failure.MethodsPrior to development of the app, we conducted qualitative interviews with 7 African American patients diagnosed with heart failure, 3 African American patients diagnosed with cardiovascular disease, and 6 health care providers (cardiologists, nurse practitioners, and a geriatrician) who worked with heart failure patients. In addition, we asked 6 hospital chaplains to provide positive spiritual messages for the patients, since spirituality is an important coping method for many African Americans. These formative data were then used for creating a prototype of the app, named Healthy Heart. Specifically, the Healthy Heart app incorporated the following evidence-based features to promote self-management: one-way messages, journaling (ie, weight and symptoms), graphical display of data, and customized feedback (ie, clinical decision support) based on daily or weekly weight. The educational messages about heart failure self-management were derived from the teaching materials provided to the patients diagnosed with heart failure, and included information on diet, sleep, stress, and medication adherence. The information was condensed and simplified to be appropriate for text messages and to meet health literacy standards. Other messages were derived from interviews conducted during the formative stage of app development, including interviews with African American chaplains. Usability testing was conducted over a series of meetings between nurses, social workers, and computer engineers. A pilot one-group pretest-posttest design was employed with participants using the mHealth app for 4 weeks. Descriptive statistics were computed for each of the demographic variables, overall and subscales for Health Related Quality of Life Scale 14 (HQOL14) and subscales for the Self-Care of Heart Failure Index (SCHFI) Version 6 using frequencies for categorical measures and means with standard deviations for continuous measures. Baseline and postintervention comparisons were computed using the Fisher exact test for overall health and paired t tests for HQOL14 and SCHFI questionnaire subscales.ResultsA total of 12 African American participants (7 men, 5 women; aged 51-69 years) diagnosed with heart failure were recruited for the study. There was no significant increase in quality of life (P=.15), but clinically relevant changes in self-care maintenance, management, and confidence were observed.ConclusionsAn mHealth app to assist with the self-management of heart failure is feasible in patients with low literacy, low health literacy, and limited smartphone experience. Based on the clinically relevant changes observed in this feasibility study of the Healthy Heart app, further research should explore effectiveness in this vulnerable population.

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.

Abstract 24: Amyloidogenic V122I Transthyretin Variant is Associated With Progression of Adverse Cardiac Mechanics in Middle-aged African American Adults: The Coronary Artery Risk Development in Young Adults (CARDIA) Study

Introduction: Direct-to-consumer testing (e.g. 23andme) reports now include common pathogenic variants in the transthyretin (TTR) gene, such as V122I. TTR cardiac amyloidosis due to V122I is an autosomal dominant disease known to be of variable penetrance in elderly African Americans. However, the association of carrier status for V122I with echocardiographic measures of cardiac mechanics in middle-age African Americans is not known. Hypothesis: Presence of V122I TTR mutation is associated with adverse cardiac mechanics in middle-aged African Americans. Methods: All African Americans from the CARDIA study with imputed genetic data (R 2 = 0.98) and echocardiography at year 25 (Y25) were included. Echo parameters at Y25 and change from Y25 to Y30 were compared between V122I heterozygote carriers and controls using linear regression models. The analysis was adjusted for age, sex, and top 3 principal components of ancestry. Analysis for change from Y25 to Y30 was adjusted for baseline Y25 echo parameters. Results: Of 874 included participants, mean age was 50.2 (3.6) years at Y25. There were 843 controls and 31 carriers for the V122I genotype (3.5% prevalence). There was no difference in age, sex, or clinical characteristics. Carriers of the V122I variant had worse diastolic function as measured by early diastolic tissue Doppler velocity (e’) at Y25 (9.2 [2.1] vs. 10.2 [2.4], p=0.048). From Y25 to Y30, V122I carriers had greater progression of left ventricular (LV) volume and mass as well as greater decline in subclinical LV systolic function as measured by circumferential strain (Table). Conclusions: Prevalence of the carrier status of the V122I genotype in CARDIA is relatively high and consistent with prior studies. Our findings suggest that the V122I mutation may be a unique risk enhancer for heart failure in middle-aged African Americans. Further data are needed for clarity on risk associated with carrier status of V122I and implications for cascade screening given emerging therapies for TTR cardiac amyloidosis.

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 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.

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.

Loss-of-function variants influence the human serum metabolome.

The metabolome is a collection of small molecules resulting from multiple cellular and biological processes that can act as biomarkers of disease, and African-Americans exhibit high levels of genetic diversity. Exome sequencing of a sample of deeply phenotyped African-Americans allowed us to analyze the effects of annotated loss-of-function (LoF) mutations on 308 serum metabolites measured by untargeted liquid and gas chromatography coupled with mass spectrometry. In an independent sample, we identified and replicated four genes harboring six LoF mutations that significantly affected five metabolites. These sites were related to a 19 to 45% difference in geometric mean metabolite levels, with an average effect size of 25%. We show that some of the affected metabolites are risk predictors or diagnostic biomarkers of disease and, using the principle of Mendelian randomization, are in the causal pathway of disease. For example, LoF mutations in SLCO1B1 elevate the levels of hexadecanedioate, a fatty acid significantly associated with increased blood pressure levels and risk of incident heart failure in both African-Americans and an independent sample of European-Americans. We show that SLCO1B1 LoF mutations significantly increase the risk of incident heart failure, thus implicating the metabolite in the causal pathway of disease. These results reveal new avenues into gene function and the understanding of disease etiology by integrating -omic technologies into a deeply phenotyped population study.

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.

CALL ME SENILE NO MORE: AN UNUSUAL CASE OF HEART FAILURE SECONDARY TO CARDIOPULMONARY AMYLOIDOSIS

Amyloidosis causing heart failure in elderly African Americans is often assumed to be senile systemic amyloidosis. A 78-year-old African-American male non-smoker presented with a 1 year history of reduced exercise capacity and 2 months of lower extremity swelling. His medical history included