SGLT2 inhibitors improved health status in Black and White patients with HF regardless of race.

SOURCE CITATION: Gupta K, Spertus JA, Birmingham M, et al. Racial differences in quality of life in patients with heart failure treated with sodium-glucose cotransporter 2 inhibitors: a patient-level meta-analysis of the CHIEF-HF, DEFINE-HF, and PRESERVED-HF trials. Circulation. 2023;148:220-228. 37191040.

Historical Redlining, Socioeconomic Distress, and Risk of Heart Failure Among Medicare Beneficiaries.

BACKGROUND: The association of historical redlining policies, a marker of structural racism, with contemporary heart failure (HF) risk among White and Black individuals is not well established. METHODS: We aimed to evaluate the association of redlining with the risk of HF among White and Black Medicare beneficiaries. Zip code-level redlining was determined by the proportion of historically redlined areas using the Mapping Inequality Project within each zip code. The association between higher zip code redlining proportion (quartile 4 versus quartiles 1-3) and HF risk were assessed separately among White and Black Medicare beneficiaries using generalized linear mixed models adjusted for potential confounders, including measures of the zip code-level Social Deprivation Index. RESULTS: A total of 2 388 955 Medicare beneficiaries (Black n=801 452; White n=1 587 503; mean age, 71 years; men, 44.6%) were included. Among Black beneficiaries, living in zip codes with higher redlining proportion (quartile 4 versus quartiles 1-3) was associated with increased risk of HF after adjusting for age, sex, and comorbidities (risk ratio, 1.08 [95% CI, 1.04-1.12]; P<0.001). This association remained significant after further adjustment for area-level Social Deprivation Index (risk ratio, 1.04 [95% CI, 1.002-1.08]; P=0.04). A significant interaction was observed between redlining proportion and Social Deprivation Index (Pinteraction<0.01) such that higher redlining proportion was significantly associated with HF risk only among socioeconomically distressed regions (above the median Social Deprivation Index). Among White beneficiaries, redlining was associated with a lower risk of HF after adjustment for age, sex, and comorbidities (risk ratio, 0.94 [95% CI, 0.89-0.99]; P=0.02). CONCLUSIONS: Historical redlining is associated with an increased risk of HF among Black patients. Contemporary zip code-level social determinants of health modify the relationship between redlining and HF risk, with the strongest relationship between redlining and HF observed in the most socioeconomically disadvantaged communities.

Race Associated With Increased Complication Rates After Total Knee Arthroplasty.

BACKGROUND: Racial and ethnic disparities have been suggested to be associated with poor outcomes after total knee arthroplasty (TKA). While socioeconomic disadvantage has been studied, analyses of race as the primary variable are lacking. Therefore, we examined the potential differences between Black and White TKA recipients. Specifically, we assessed 30-day and 90-day, as well as 1 year: (1) emergency department visits and readmissions; (2) total complications; (3) as well as risk factors for total complications. METHODS: A consecutive series of 1,641 primary TKAs from January 2015 to December 2021 at a tertiary health care system were reviewed. Patients were stratified according to race, Black (n = 1,003) and White (n = 638). Outcomes of interest were analyzed using bivariate Chi-square and multivariate regressions. Demographic variables such as sex, American Society of Anesthesiologists classification, diabetes, congestive heart failure, chronic pulmonary disease, and socioeconomic status based on Area Deprivation Index were controlled for across all patients. RESULTS: The unadjusted analyses found that Black patients had an increased likelihood of 30-day emergency department visits and readmissions (P < .001). However, in the adjusted analyses, Black race was demonstrated to be a risk factor for increased total complications at all-time points (P ≤ .0279). Area Deprivation Index was not a risk for cumulative complications at these time points (P ≥ .2455). CONCLUSION: Black patients undergoing TKA may be at increased risk for complications with more risk factors including higher body mass index, tobacco use, substance abuse, chronic obstructive pulmonary disease, congestive heart failure, hypertension, chronic kidney disease, and diabetes and were thus, "sicker" initially than the White cohort. Surgeons are often treating these patients at the later stages of their diseases when risk factors are less modifiable, which necessitates a shift to early, preventable public health measures. While higher socioeconomic disadvantage has been associated with higher rates of complications, the results of this study suggest that race may play a greater role than previously thought.

Clinical and social determinants of health features of SARS-CoV-2 infection among Black and Caribbean Hispanic patients with heart failure: The SCAN-MP Study.

Patients with heart failure (HF) often have multiple chronic conditions and are at increased risk for severe disease and mortality when infected by SARS-CoV-2, the virus that causes COVID-19. Furthermore, disparities in outcomes with COVID-19 have been associated with both racial/ethnic identity but also social determinants of health. Among older, urban-dwelling, minority patients with HF, we sought to characterize medical and non-medical factors associated with SARS-CoV-2 infection. Patients with HF living in Boston and New York City over 60 years of age participating in the Screening for Cardiac Amyloidosis with Nuclear Imaging (SCAN-MP) study between 12/1/2019 and 10/15/2021 (n = 180) were tested for nucleocapsid antibodies to SARS-CoV-2 and queried for symptomatic infection with PCR verification. Baseline testing included the Kansas City Cardiomyopathy Questionnaire (KCCQ), assessment of health literacy, biochemical, functional capacity, echocardiography, and a novel survey tool that determined living conditions, perceived risk of infection, and attitudes towards COVID-19 mitigation. The association of infection with prevalent socio-economic conditions was assessed by the area deprivation index (ADI). There were 50 overall cases of SARS-CoV-2 infection (28%) including 40 demonstrating antibodies to SARS-CoV-2 (indicative of prior infection) and 10 positive PCR tests. There was no overlap between these groups. The first documented case from New York City indicated infection prior to January 17, 2020. Among active smokers, none tested positive for prior SARS-CoV-2 infection (0 (0%) vs. 20 (15%), p = 0.004) vs. non-smokers. Cases were more likely to be taking ACE-inhibitors/ARBs compared to non-cases (78% vs 62%, p = 0.04). Over a mean follow-up of 9.6 months, there were 6 total deaths (3.3%) all unrelated to COVID-19. Death and hospitalizations (n = 84) were not associated with incident (PCR tested) or prior (antibody) SARS-CoV-2 infection. There was no difference in age, co-morbidities, living conditions, attitudes toward mitigation, health literacy, or ADI between those with and without infection. SARS-CoV-2 infection was common among older, minority patients with HF living in New York City and Boston, with evidence of infection documented in early January 2020. Health literacy and ADI were not associated with infection, and there was no increased mortality or hospitalizations among those infected with SARS-CoV-2.

Longitudinal HbA1c trajectory modelling reveals the association of HbA1c and risk of hospitalization for heart failure for patients with type 2 diabetes mellitus.

BACKGROUND: Inconsistent conclusions in past studies on the association between poor glycaemic control and the risk of hospitalization for heart failure (HHF) have been reported largely due to the analysis of non-trajectory-based HbA1c values. Trajectory analysis can incorporate the effects of HbA1c variability across time, which may better elucidate its association with macrovascular complications. Furthermore, studies analysing the relationship between HbA1c trajectories from diabetes diagnosis and the occurrence of HHF are scarce. METHODS: This is a prospective cohort study of the SingHealth Diabetes Registry (SDR). 17,389 patients diagnosed with type 2 diabetes mellitus (T2DM) from 2013 to 2016 with clinical records extending to the end of 2019 were included in the latent class growth analysis to extract longitudinal HbA1c trajectories. Association between HbA1c trajectories and risk of first known HHF is quantified with the Cox Proportional Hazards (PH) model. RESULTS: 5 distinct HbA1c trajectories were identified as 1. low stable (36.1%), 2. elevated stable (40.4%), 3. high decreasing (3.5%), 4. high with a sharp decline (10.8%), and 5. moderate decreasing (9.2%) over the study period of 7 years. Poorly controlled HbA1c trajectories (Classes 3, 4, and 5) are associated with a higher risk of HHF. Using the diabetes diagnosis time instead of a commonly used pre-defined study start time or time from recruitment has an impact on HbA1c clustering results. CONCLUSIONS: Findings suggest that tracking the evolution of HbA1c with time has its importance in assessing the HHF risk of T2DM patients, and T2DM diagnosis time as a baseline is strongly recommended in HbA1c trajectory modelling. To the authors' knowledge, this is the first study to identify an association between HbA1c trajectories and HHF occurrence from diabetes diagnosis time.

Diabetes Mellitus, Race, and Effects of Omega-3 Fatty Acids on Incidence of Heart Failure Hospitalization.

OBJECTIVES: The primary aim was to evaluate whether prevalent type 2 diabetes (T2D) modifies the effects of omega-3 supplementation on heart failure (HF) hospitalization. The secondary aim was to examine if race modifies the effects of omega-3 supplements on HF risk. BACKGROUND: It is unclear whether race and T2D modify the effects of omega-3 supplementation on the incidence of HF. METHODS: In this ancillary study of the parent VITAL (Vitamin D and Omega-3 Trial)-a completed randomized trial testing the efficacy of vitamin D and omega-3 fatty acids on cardiovascular diseases and cancer, we assessed the role of T2D and race on the effects of omega-3 supplements on the incidence of HF hospitalization (adjudicated by a review of medical records and supplemented with a query of Centers for Medicare and Medicaid Services data). RESULTS: When omega-3 supplements were compared with placebo, the HR for first HF hospitalization was 0.69 (95% CI: 0.50-0.95) in participants with prevalent T2D and 1.09 (95% CI: 0.88-1.34) in those without T2D (P for interaction = 0.019). Furthermore, prevalent T2D modified the effects of omega-3 fatty acids on the incidence of recurrent HF hospitalization (HR: 0.53; 95% CI: 0.41-0.69 in participants with prevalent T2D vs HR: 1.07; 95% CI: 0.89-1.28 in those without T2D; P interaction <0.0001). In our secondary analysis, omega-3 supplementation reduced recurrent HF hospitalization only in Black participants (P interaction race × omega-3 = 0.0497). CONCLUSIONS: Our data show beneficial effects of omega-3 fatty acid supplements on incidence of HF hospitalization in participants with T2D but not in those without T2D, and such benefit appeared to be stronger in Black participants with T2D. (Intervention With Vitamin D and Omega-3 Supplements and Incident Heart Failure; NCT02271230; Vitamin D and Omega-3 Trial [VITAL]; NCT01169259 [parent study]).

Association of Transthyretin Val122Ile Variant With Incident Heart Failure Among Black Individuals.

Importance: A genetic variant in the TTR gene (rs76992529; Val122Ile), present more commonly in individuals with African ancestry (population frequency: 3%-4%), causes misfolding of the tetrameric transthyretin protein complex that accumulates as extracellular amyloid fibrils and results in hereditary transthyretin amyloidosis. Objective: To estimate the association of the amyloidogenic Val122Ile TTR variant with the risk of heart failure and mortality in a large, geographically diverse cohort of Black individuals. Design, Setting, and Participants: Retrospective population-based cohort study of 7514 self-identified Black individuals living in the US participating in the REGARDS (Reasons for Geographic and Racial Differences in Stroke) study with genetic data available and without heart failure at baseline. The participants were enrolled at the baseline visit (2003-2007). The end of follow-up for the majority of outcomes was on December 31, 2018. All-cause mortality data were available through December 31, 2020. Exposures: TTR Val122Ile (rs76992529) genotype. Main Outcome and Measures: The primary outcome was incident heart failure (first hospitalization for heart failure or death due to heart failure). The secondary outcomes were heart failure mortality, cardiovascular mortality, and all-cause mortality. The multivariable Cox proportional hazards regression analyses were adjusted for genetic ancestry and demographic, clinical, and social factors. Results: Among 7514 Black participants (median age, 64 years [IQR, 57-70 years]; 61% women), the population frequency of the TTR Val122Ile variant was 3.1% (232 variant carriers and 7282 noncarriers). During a median follow-up of 11.1 years (IQR, 5.9-13.5 years), incident heart failure occurred in 535 individuals (34 variant carriers and 501 noncarriers) and the incidence of heart failure was 15.64 per 1000 person-years among variant carriers vs 7.16 per 1000 person-years among noncarriers (adjusted hazard ratio [HR], 2.43 [95% CI, 1.71-3.46]; P < .001). Deaths due to heart failure occurred in 141 individuals (13 variant carriers and 128 noncarriers) and the incidence of heart failure mortality was 6.11 per 1000 person-years among variant carriers vs 1.85 per 1000 person-years among noncarriers (adjusted HR, 4.19 [95% CI, 2.33-7.54]; P < .001). Deaths due to cardiovascular causes occurred in 793 individuals (34 variant carriers and 759 noncarriers) and the incidence of cardiovascular death was 15.18 per 1000 person-years among variant carriers vs 10.61 per 1000 person-years among noncarriers (adjusted HR, 1.69 [95% CI, 1.19-2.39]; P = .003). Deaths due to any cause occurred in 2715 individuals (100 variant carriers and 2615 noncarriers) and the incidence of all-cause mortality was 41.46 per 1000 person-years among variant carriers vs 33.94 per 1000 person-years among noncarriers (adjusted HR, 1.46 [95% CI, 1.19-1.78]; P < .001). There was no significant interaction between TTR variant carrier status and sex on incident heart failure and the secondary outcomes. Conclusions and Relevance: Among a cohort of Black individuals living in the US, being a carrier of the TTR Val122Ile variant was significantly associated with an increased risk of heart failure.

Development and Validation of a Long-Term Incident Heart Failure Risk Model.

BACKGROUND: Average lifetime risk for heart failure (HF) is high but differs significantly across and within sex-race groups. No models for estimating long-term risk for HF exist, which would allow for earlier identification and interventions in high-risk subsets. The authors aim to derive 30-year HF risk equations. METHODS: Adults between the ages of 20 to 59 years and free of cardiovascular disease at baseline from 5 population-based cohorts were included. Among 24 838 participants (55% women, 25% Black based on self-report), follow-up consisted of 599 551 person-years. Sex- and race-specific 30-year HF risk equations were derived and validated accounting for competing risk of non-HF death. HF was based on a clinical diagnosis. Model discrimination and calibration were assessed using 10-fold cross-validation. Finally, the model was applied to varying risk factor patterns for systematic examination. RESULTS: The rate of incident HF was 4.0 per 1000 person-years. Harrell C statistics were 0.82 (0.80-0.83) and 0.84 (0.82-0.85) in White and Black men and 0.84 (0.82-0.85) and 0.85 (0.83-0.87) in White and Black women, respectively. Hosmer-Lemeshow calibration was acceptable, with χ2 <30 in all subgroups. Risk estimation varied across sex-race groups: for example, in an average 40-year-old nonsmoker with an untreated systolic blood pressure of 140 mm Hg and body mass index of 30 kg/m2, risk was estimated to be 22.8% in a Black man, 13.7% in a White man, 13.0% in a Black woman, and 12.1% in a White woman. CONCLUSIONS: Sex- and race-specific equations for prediction of long-term risk of HF demonstrated high discrimination and adequate calibration.

Comparison of Cardiorespiratory Fitness in Black or African American Versus Caucasian Patients With Heart Failure.

PURPOSE: Cardiopulmonary exercise testing (CPX) is a well-established assessment with important insight into prognosis and therapeutic efficacy in patients with heart failure (HF). Prior studies have identified several clinical differences between Black or African American (B-AA) and Caucasian patients with HF. Differences in key CPX responses between these two groups require further investigation. METHODS: Using a database consisting of subjects with symptomatic HF who had undergone CPX for inclusion in various prospective randomized clinical trials, we identified 198 (n = 94 [47%] B-AA; n = 105 [53%] Caucasian) patients with a qualifying baseline CPX. Significant univariate predictors of peak oxygen uptake (V˙o2peak) were included in a multivariate linear regression model. RESULTS: When compared with Caucasian patients, B-AA were younger (mean ± SD = 54.8 ± 10.0 vs 57.9 ± 9.6 yr, P = .03), had higher C-reactive protein (CRP) (median [IQR] = 4.9 [2.3, 8.8] vs 1.9 [0.6, 5.5] mg/L, P < .0001), lower hemoglobin (13.0 ± 1.8 vs 13.8 ± 1.6 g/dL, P = .003), and lower left ventricular ejection fraction (LVEF) (40 [32, 51] vs 53 [43, 59]%, P < .00010). During CPX, B-AA patients also had lower V˙o2peak (14.6 ± 3.9 vs 17.6 ± 4.8 mL·kg-1·min-1, P < .0001). No differences were observed between B-AA and Caucasian in the minute ventilation/carbon dioxide production (V˙e/V˙co2) slope (P = .14). The difference in V˙o2peak between B-AA and Caucasian was largely attenuated after adjusting for age, body mass index, CRP, N-terminal pro-brain natriuretic peptide, hemoglobin, LVEF, and peak HR (14.1: 95% CI, 13.2-14.9 vs 15.6: 95% CI, 14.4-16.8 mL·kg-1·min-1, P = .053). CONCLUSIONS: Directly measured V˙o2peak was significantly lower in B-AA than in Caucasians with HF. This is largely explained by differences in clinical characteristics, whereas no significant differences were observed in the V˙e/V˙co2 slope.

Association between ethnicity and degree of improvement in cardiac function following initiation of sacubitril/valsartan.

AIMS: The aim of this study was to determine the degree of short-term improvement in left ventricular ejection fraction (LVEF), haemodynamics, NT-proBNP and quality of life following initiation of sacubitril/valsartan in black patients when compared with white patients. METHODS: This was a retrospective, observational, single-centre, hypothesis-generating study of patients with symptomatic heart failure and reduced ejection fraction (HFrEF) treated with guideline recommended therapy, who were transitioned from an ACE inhibitor (ACE-I) or angiotensin receptor blocker (ARB) to sacubitril/valsartan. RESULTS: Our analysis included 83 patients (mean age 57 years) with echocardiography performed before and after transition from ACE-I/ARB to sacubitril/valsartan, after excluding patients with concomitant Cardiac resynchronization therapy implantation. Overall, sacubitril/valsartan was associated with LVEF improvement from 28.8% ±â€Š0.7 to 32.0% ±â€Š1.1% (P = 0.0002), but no reverse remodelling was observed. The association with LVEF improvement was only observed in white patients (n = 46, P = 0.0006), but not in black patients (n = 37, P = 0.1728), and appeared to be associated with reduced blood pressure (baseline vs. 2-week blood pressure 116.5 ±â€Š13.9 vs. 109.4 ±â€Š14.3 mmHg, respectively, in white patients, P = 0.0449). Fifteen patients (18.1%) became ineligible for primary prevention Implantable cardioverter defibrillator implantation. CONCLUSION: Sacubitril/valsartan was associated with improved LVEF, NT-proBNP concentrations and quality of life in patients with symptomatic HFrEF on guideline recommended therapy. However, in our cohort, improvement of LVEF and quality of life might be attenuated in black patients, which warrants further investigation.

Race and Ethnicity in Heart Failure: JACC Focus Seminar 8/9.

Heart failure (HF) affects >6 million Americans, with variations in incidence, prevalence, and clinical outcomes by race/ethnicity. Black adults have the highest risk for HF, with earlier age of onset and the highest risk of death and hospitalizations. The risk of hospitalizations for Hispanic patients is higher than White patients. Data on HF in Asian individuals are more limited. However, the higher burden of traditional cardiovascular risk factors, particularly among South Asian adults, is associated with increased risk of HF. The role of environmental, socioeconomic, and other social determinants of health, more likely for Black and Hispanic patients, are increasingly recognized as independent risk factors for HF and worse outcomes. Structural racism and implicit bias are drivers of health care disparities in the United States. This paper will review the clinical, physiological, and social determinants of HF risk, unique for race/ethnic minorities, and offer solutions to address systems of inequality that need to be recognized and dismantled/eradicated.

Racial/Ethnic Differences in 30-Day Mortality for Heart Failure and Pneumonia in the Veterans Health Administration Using Claims-based, Clinical, and Social Risk-adjustment Variables.

BACKGROUND: Prior studies have identified lower mortality in Black Veterans compared with White Veterans after hospitalization for common medical conditions, but these studies adjusted for comorbid conditions identified in administrative claims. OBJECTIVES: The objectives of this study were to compare mortality for non-Hispanic White (hereafter, "White"), non-Hispanic Black (hereafter, "Black"), and Hispanic Veterans hospitalized for heart failure (HF) and pneumonia and determine whether observed mortality differences varied according to whether claims-based comorbid conditions and/or clinical variables were included in risk-adjustment models. RESEARCH DESIGN: This was an observational study. SUBJECTS: The study cohort included 143,520 admissions for HF and 127,782 admissions for pneumonia for Veterans hospitalized in 132 Veterans Health Administration (VA) Medical Centers between January 2009 and September 2015. MEASURES: The primary independent variable was racial/ethnic group (ie, Black, Hispanic, and non-Hispanic White), and the outcome was all-cause mortality 30 days following admission. To compare mortality by race/ethnicity, we used logistic regression models that included different combinations of claims-based, clinical, and sociodemographic variables. For each model, we estimated the average marginal effect (AME) for Black and Hispanic Veterans relative to White Veterans. RESULTS: Among the 143,520 (127,782) hospitalizations for HF (pneumonia), the average patient age was 71.6 (70.9) years and 98.4% (97.1%) were male. The unadjusted 30-day mortality rates for HF (pneumonia) were 7.2% (11.0%) for White, 4.1% (10.4%) for Black and 8.4% (16.9%) for Hispanic Veterans. Relative to White Veterans, when only claims-based variables were used for risk adjustment, the AME (95% confidence interval) for the HF [pneumonia] cohort was -2.17 (-2.45, -1.89) [0.08 (-0.41, 0.58)] for Black Veterans and 1.32 (0.49, 2.15) [4.51 (3.65, 5.38)] for Hispanic Veterans. When clinical variables were incorporated in addition to claims-based ones, the AME, relative to White Veterans, for the HF [pneumonia] cohort was -1.57 (-1.88, -1.27) [-0.83 (-1.31, -0.36)] for Black Veterans and 1.50 (0.71, 2.30) [3.30 (2.49, 4.11)] for Hispanic Veterans. CONCLUSIONS: Compared with White Veterans, Black Veterans had lower mortality, and Hispanic Veterans had higher mortality for HF and pneumonia. The inclusion of clinical variables into risk-adjustment models impacted the magnitude of racial/ethnic differences in mortality following hospitalization. Future studies examining racial/ethnic disparities should consider including clinical variables for risk adjustment.

Survival analysis of patients with heart failure in the Ecuadorian Andean population.

INTRODUCTION: In western countries, it is estimated that one to two people per 100 adults have heart failure. In Latin America, and particularly in Ecuador, few studies have assessed survival in this disease. For this reason, this study aimed to determine survival and prognostic factors based on clinical and socio-demographic characteristics. METHODS: We did a single-center study of survival analysis in 228 patients with heart failure between 2015 and 2019. Survival analysis was done by the actuarial method and a multivariate Cox regression analysis. RESULTS: Overall survival at the first year was 86% and at five years was 46%. Heart failure etiology (hazard ratio, 1.162: 95% confidence interval, 1.001 to 1.349; P = 0.049), ethnicity (1.415; 10.1 to 199; P = 0.043), age (1.035; 1.011 to 1.06; P = 0.04) and altered values of basal creatinine (1.21; 1.002 to 1.461; P = 0.048) were associated with worse prognosis. CONCLUSIONS: Global survival time was similar to other international studies. Etiology, ethnicity, creatinine values, and age were factors associated with a worse vital prognosis.

INTRODUCCIÓN: En los países occidentales, se estima que entre una a dos personas por cada 100 adultos tienen diagnóstico de insuficiencia cardíaca. En América Latina, y particularmente en Ecuador, existen pocos estudios que hayan evaluado la sobrevida respecto a esta enfermedad. Por este motivo, este estudio se realizó con el fin de determinar los factores relacionados con la supervivencia y el pronóstico, en función de las características clínicas y sociodemográficas de los pacientes con insuficiencia cardiaca. MÉTODOS: Hicimos un estudio unicéntrico de supervivencia efectuado en 228 pacientes con insuficiencia cardíaca entre los años 2015-2019. El análisis de supervivencia se realizó mediante el método actuarial y por el método de regresión multivariada de Cox. RESULTADOS: La supervivencia global al año fue del 86% y a los cinco años fue del 46%. Variables como la etiología de la insuficiencia cardíaca (hazard ratio 1,162; intervalo de confianza 95%, 1,001 a 1,349; P = 0,049); la etnia (1,415; 10,1 a 199; P = 0,043), la edad (1,035, 1,011 a 1,06; P = 0,04) y los valores alterados de creatinina basal (1,21; 1,002 a 1,461; P = 0,048) se asociaron como factores de peor pronóstico. CONCLUSIONES: El tiempo de supervivencia global fue similar al reportado en estudios internacionales. Por otro lado, la etiología, la etnia, los valores de creatinina y la edad fueron factores asociados a un peor pronóstico vital.

Regional Adiposity and Risk of Heart Failure and Mortality: The Jackson Heart Study.

Background Visceral adipose tissue (VAT) is associated with incident heart failure (HF) and HF with preserved ejection fraction, yet it is unknown how pericardial and abdominal adiposity affect HF and mortality risks in Black individuals. We examined the associations of pericardial adipose tissue (PAT), VAT, and subcutaneous adipose tissue (SAT) with incident HF hospitalization and all-cause mortality in a large community cohort of Black participants. Methods and Results Among the 2882 Jackson Heart Study Exam 2 participants without prevalent HF who underwent body computed tomography, we used Cox proportional hazards models to examine associations between computed tomography-derived regional adiposity and incident HF hospitalization and all-cause mortality. Fully adjusted models included demographics and cardiovascular disease risk factors. Median follow-up was 10.6 years among participants with available VAT (n=2844), SAT (n=2843), and PAT (n=1386). Fully adjusted hazard ratios (95% CIs) of distinct computed tomography-derived adiposity measures (PAT per 10 cm3, VAT or SAT per 100 cm3) were as follows: for incident HF, PAT 1.08 (95% CI, 1.02-1.14) and VAT 1.04 (95% CI, 1.01-1.08); for HF with preserved ejection fraction, PAT 1.13 (95% CI, 1.04-1.21) and VAT 1.07 (95% CI, 1.01-1.13); for mortality, PAT 1.07 (95% CI, 1.03-1.12) and VAT 1.01 (95% CI, 0.98-1.04). SAT was not associated with either outcome. Conclusions High PAT and VAT, but not SAT, were associated with incident HF and HF with preserved ejection fraction, and only PAT was associated with mortality in the fully adjusted models in a longitudinal community cohort of Black participants. Future studies may help understand whether changes in regional adiposity improves HF, particularly HF with preserved ejection fraction, risk predictions. Registration URL: https://www.clinicaltrials.gov; Unique identifier: NCT00005485.

Free fatty acids and heart failure in the Multi-Ethnic Study of Atherosclerosis (MESA).

BACKGROUND: Free fatty acids (FFAs) may be associated with heart failure (HF) risk, but prospective research is lacking. OBJECTIVE: This study investigated associations between fasting FFAs and HF incidence overall and by ejection fraction (EF) subtypes [HF with preserved EF (HFpEF) and HF with reduced EF (HFrEF)] to evaluate FFAs as a potential biomarker for HF risk prediction. METHODS: This study was conducted in the Multi-Ethnic Study of Atherosclerosis (MESA) prospective cohort among 6,667 participants with complete baseline (2000-2002) FFAs and HF follow-up (through 2015). Associations between FFAs and HF incidence were evaluated with Cox proportional hazards regression. Cross-sectional associations between FFAs and HF risk markers were also evaluated using linear regression [N-terminal pro-B-type natriuretic peptide (NT-proBNP), left ventricular (LV) mass index] and logistic regression [LV hypertrophy (LVH)]. Stratification and cross-product terms were utilized to evaluate differences by age, sex, race/ethnicity and diabetes. RESULTS: FFAs were not associated with HF overall or with HFrEF. FFAs were not associated with HFpEF in the overall population or among males, but were borderline positively associated with risk among females (fully-adjusted tertile 3 vs. 1 HR=2.17, 95% CI: 1.06, 4.42) (sex P-interaction=0.05). FFAs were not associated with NT-proBNP, but were inversely associated with LV mass index and LVH with stronger associations among females (P-interaction≥0.10). Associations did not differ by age, race/ethnicity or diabetes status. CONCLUSIONS: FFAs generally do not appear to be an independent predictor for HF risk. Additional research is needed to confirm findings particularly studies evaluating associations by sex and EF subtypes.

Association of the transthyretin variant V122I with polyneuropathy among individuals of African ancestry.

Hereditary transthyretin-mediated (hATTR) amyloidosis is an underdiagnosed, progressively debilitating disease caused by mutations in the transthyretin (TTR) gene. V122I, a common pathogenic TTR mutation, is found in 3-4% of individuals of African ancestry in the United States and has been associated with cardiomyopathy and heart failure. To better understand the phenotypic consequences of carrying V122I, we conducted a phenome-wide association study scanning 427 ICD diagnosis codes in UK Biobank participants of African ancestry (n = 6062). Significant associations were tested for replication in the Penn Medicine Biobank (n = 5737) and the Million Veteran Program (n = 82,382). V122I was significantly associated with polyneuropathy in the UK Biobank (odds ratio [OR] = 6.4, 95% confidence interval [CI] 2.6-15.6, p = 4.2 × 10-5), which was replicated in the Penn Medicine Biobank (OR = 1.6, 95% CI 1.2-2.4, p = 6.0 × 10-3) and Million Veteran Program (OR = 1.5, 95% CI 1.2-1.8, p = 1.8 × 10-4). Polyneuropathy prevalence among V122I carriers was 2.1%, 9.0%, and 4.8% in the UK Biobank, Penn Medicine Biobank, and Million Veteran Program, respectively. The cumulative incidence of common hATTR amyloidosis manifestations (carpal tunnel syndrome, polyneuropathy, cardiomyopathy, heart failure) was significantly enriched in V122I carriers compared with non-carriers (HR = 2.8, 95% CI 1.7-4.5, p = 2.6 × 10-5) in the UK Biobank, with 37.4% of V122I carriers having at least one of these manifestations by age 75. Our findings show that V122I carriers are at increased risk of polyneuropathy. These results also emphasize the underdiagnosis of disease in V122I carriers with a significant proportion of subjects showing phenotypic changes consistent with hATTR amyloidosis. Greater understanding of the manifestations associated with V122I is critical for earlier diagnosis and treatment.

Incidence, Determinants and Mortality of Heart Failure Associated With Medical-Surgical Procedures in Patients ≥ 65 Years of Age (from the Cardiovascular Health Study).

Heart failure (HF) and myocardial infarction are serious complications of major noncardiac surgery in older adults. Many factors can contribute to the development of HF during the postoperative period. The incidence of, and risk factors for, procedure-associated heart failure (PHF) occurring at the time of, or shortly after, medical procedures in a population-based sample ≥ 65 years of age have not been fully characterized, particularly in comparison with HF not proximate to medical procedures. This analysis comprises 5,121 men and women free of HF at baseline from the Cardiovascular Health Study who were followed up for 12.0 years (median). HF events were documented by self-report at semi-annual contacts and confirmed by a formal adjudication committee using a review of the participants' medical records and standardized criteria for HF. Incident HF events were additionally adjudicated as either being related or unrelated to a medical procedure (PHF and non-PHF, respectively). We estimated cause-specific hazards ratios for the association of covariates with PHF and non-PHF. There were 1,728 incident HF events in the primary analysis: 168 (10%) classified as PHF, 1,526 (88%) as non-PHF, and 34 unclassified (2%). For those 1,045 participants in whom LV ejection fraction was known at the time of the HF event, it was ≥45% in 89 of 118 participants (75%) with PHF, compared to 517 of 927 participants (55%) with non-PHF (p < 0.001). Increased age, male gender, diabetes, and angina at baseline were associated with both PHF and non-PHF (range of hazard ratios (HR): 1.04-2.05]. Being Black was inversely associated with PHF [HR: 0.46, 95% confidence interval: 0.25-0.86]. Participants with increased age, without baseline angina, and with baseline LVEF<55% were at a significantly lower risk for PHF compared to non-PHF. Among those with PHF, surgical procedures-including cardiac, orthopedic, gastrointestinal, vascular, and urologic-comprised 83.3%, while percutaneous procedures comprised 8.9% (including 6.5% represented by cardiac catheterizations and pacemaker placements). Another group composed of a variety of procedures commonly requiring large fluid volume administration comprised 7.7%. There was a lower all-cause 30-day mortality in the PHF versus the non-PHF group (2.2% vs 5.7%), with a nonsignificant odds ratio of 0.39 in a minimally adjusted model. When individuals with prior myocardial infarction (MI) were excluded in a sensitivity analysis, the proportion of incident HF with concurrent MI was greater for PHF (32.9%) than for non-PHF (19.8%). In conclusion, PHF in older adults is a common entity with relatively low 30-day mortality. Baseline angina, lower age, and LVEF ≥ 55% were associated with a higher risk of PHF compared to non-PHF. Being Black was associated with a lower risk of PHF and PHF as a proportion of HF was lower in Black than in non-Black participants. Compared to non-PHF, PHF more frequently presented with concurrent MI and with preserved LV ejection fraction.

A retrospective analysis of high sensitivity cardiac troponin-T ranges in non-myocardial infarction emergency department visits.

INTRODUCTION: Current evidence suggests that high sensitivity cardiac troponin-T (hs-cTnT) values differ based on sex, race, age, and kidney function. However, most studies examining the relationship of hs-cTnT and these individual factors are in healthy participants, leading to difficulty in interpreting hs-cTnT values in the Emergency Department (ED) setting. We seek to examine the relationship between hs-cTnT values and sex, race, age, and kidney function in a contemporary, urban academic setting. METHODS: ED visits from June 2018 through April 2019 with at least 1 hs-cTnT and no diagnosis of acute myocardial infarction (AMI) at an academic medical center in the south side of Chicago were retrospectively analyzed. Median hs-cTnT values were stratified by sex (male or female), race (African American or Caucasian), age, estimated glomerular filtration rate (eGFR), and stage of chronic kidney disease. RESULTS: 9679 encounters, representing 7989 distinct patients, were included for analysis (age 58 ± 18 years, 59% female, 85% black). Males had significantly higher median hs-cTnT values than females (16 [8-34] vs. 9 [6-22] ng/L, p < 0.001), African Americans had a significantly lower median value than Caucasians (10 [6-24] vs. 15 [6-29] ng/L, p < 0.001), and those with atrial fibrillation (27 [16-48] vs. 9 [6-19] ng/L, p < 0.001) and heart failure (28 [14-48] vs. 8 [6-15] ng/L, p < 0.001) had higher median values than those without. Median hs-cTnT values increased significantly with increased age and decreased eGFR. All relationships continued to be significant even after multivariable regression of sex, age, race, eGFR, presence of atrial fibrillation, and presence of heart failure (p < 0.01). CONCLUSIONS: Analysis of hs-cTnT in non-AMI patients during ED encounters showed that males have higher values than females, African Americans have lower values than Caucasians, those with atrial fibrillation and heart failure have higher values than those without, and that older age and lower eGFR were associated with higher median values.