Author + information
- Received December 21, 2016
- Revision received February 10, 2017
- Accepted February 16, 2017
- Published online June 26, 2017.
- Boback Ziaeian, MD, PhDa,b,
- Paul A. Heidenreich, MD, MSc,
- Haolin Xu, MSd,
- Adam D. DeVore, MD, MHSd,e,
- Roland A. Matsouaka, PhDd,f,
- Adrian F. Hernandez, MD, MHSd,e,
- Deepak L. Bhatt, MD, MPHg,
- Clyde W. Yancy, MDh and
- Gregg C. Fonarow, MDi,∗ ()
- aDivision of Cardiology, David Geffen School of Medicine at the University of California, Los Angeles, Los Angeles, California
- bDivision of Cardiology, Veteran Affairs Greater Los Angeles Healthcare System, Los Angeles, California
- cDivision of Cardiology, Veterans Affairs Palo Alto Healthcare System, Palo Alto, California
- dDuke Clinical Research Institute, Durham, North Carolina
- eDivision of Cardiology, Duke University Medical Center, Durham, North Carolina
- fDepartment of Biostatistics and Bioinformatics, Duke University, Durham, North Carolina
- gBrigham and Women’s Hospital Heart & Vascular Center, Harvard Medical School, Boston, Massachusetts
- hDivision of Cardiology, Northwestern University, Chicago, Illinois
- iAhmanson–UCLA Cardiomyopathy Center, University of California, Los Angeles Medical Center, Los Angeles, California
- ↵∗Address for correspondence:
Dr. Gregg C. Fonarow, Ahmanson–UCLA Cardiomyopathy Center, Ronald Reagan UCLA Medical Center, 10833 LeConte Avenue, Room A2-237 CHS, Los Angeles, California 90095-1679.
Objectives This study analyzed HFpEF patient characteristics and clinical outcomes according to race/ethnicity and adjusted for patient and hospital characteristics along with socioeconomic status (SES).
Background The proportion of hospitalizations for heart failure with preserved ejection fraction (HFpEF) has increased over the last decade. Whether the short- and long-term outcomes differ between racial/ethnic groups is not well described.
Methods The Get With The Guidelines–Heart Failure registry was linked to Medicare administrative data to identify hospitalized patients with HFpEF ≥65 years of age with left ventricular ejection fraction ≥50% between 2006 and 2014. Cox proportional hazards models were used to report hazard ratios (HRs) for 30-day and 1-year readmission and mortality rates with sequential adjustments for patient characteristics, hospital characteristics, and SES.
Results The final cohort included 53,065 patients with HFpEF. Overall 30-day mortality was 5.87%; at 1 year, it was 33.1%. The 30-day all-cause readmission rate was 22.2%, and it was 67.0% at 1 year. After adjusting for patient characteristics, hospital characteristics, and SES, 30-day mortality was lower for black patients (HR: 0.84; 95% confidence interval [CI]: 0.71 to 0.98; p = 0.031) and Hispanic patients (HR: 0.78; 95% CI: 0.64 to 0.96; p = 0.017) compared with white patients. One-year mortality was lower for black patients (HR: 0.93; 95% CI: 0.87 to 0.99; p = 0.031), Hispanic patients (HR: 0.83; 95% CI: 0.75 to 0.91; p < 0.001), and Asian patients (HR: 0.76; 95% CI: 0.66 to 0.88; p < 0.001) compared with white patients. Black patients had a higher risk of readmission at 30 days (HR: 1.09; 95% CI: 1.02 to 1.16; p = 0.012) and 1 year (HR: 1.14; 95% CI: 1.09 to 1.20; p < 0.001) compared with white patients.
Conclusions Black, Hispanic, and Asian patients had a lower mortality risk after a hospitalization for HFpEF compared with white patients; black patients had higher readmission rates. These differences in mortality and readmission risk according to race/ethnicity persisted after adjusting for patient characteristics, SES, and hospital factors.
- diastolic heart failure
- heart failure with preserved ejection fraction
Heart failure (HF) is an increasing public health burden in the United States, with an estimated 5.7 million adults self-reporting the condition in 2012 (1). By 2030, the prevalence of HF is expected to increase 46% to >8 million people secondary to an aging national demographic (2). Although reductions in ischemic heart disease have lowered the age-standardized rates of heart failure with reduced ejection fraction (HFrEF), the proportion of patients with heart failure with preserved ejection fraction (HFpEF) has increased over the last decade (3,4).
Previous research on the epidemiology and outcomes among patients with HFpEF is limited. Hypertension is the strongest known risk factor for HFpEF, along with age, obesity, and diabetes mellitus (5,6). Among hospitalized Medicare patients with HF, those with HFpEF have an observed lower mortality but higher readmission rate compared with those with HFrEF (7). Although adequate control of hypertension and volume status are critical to managing symptoms, effective therapies regrettably are not shown to alter the natural history of disease or improve survival for patients with HFpEF (8).
The quality of cardiovascular care for racial and ethnic minorities is known to vary (9). The rate of preventable hospitalizations for conditions that include HF is highest for black and Hispanic subjects compared with white subjects (10). Black and Hispanic subjects hospitalized with HFrEF exacerbations have higher 30-day and 1-year readmission rates and lower 30-day and 1-year mortality rates compared with white subjects (11). To the best of our knowledge, no comparable studies have assessed outcomes in hospitalized patients with HFpEF according to race/ethnicity.
The present study reports on the differences in patient characteristics and clinical outcomes for hospitalized patients with HFpEF according to racial/ethnic groups by using the Get With The Guidelines–Heart Failure (GWTG-HF) registry linked to the Centers for Medicare & Medicaid Services (CMS) administrative data.
Patients discharged from the GWTG-HF registry between January 1, 2006, and December 1, 2014, were screened. All patients included in the GWTG-HF registry have been identified by medical providers based on clinically diagnosed HF. Inclusion in the final cohort required age ≥65 years, eligible for Medicare Part A and B fee-for-service benefit during the discharge month, and left ventricular ejection fraction (LVEF) ≥50% on quantitative assessment; if quantitative LVEF was not available, qualitative assessment of normal or mild dysfunction was included. LVEF criteria were consistent with recent society guideline definitions (8,12). Patients were excluded if they were transferred to a hospice facility, left against medical advice, discharge disposition was unknown, or regional socioeconomic status (SES) was not available for linkage. The GWTG-HF registry was linked to CMS administrative data providing utilization of services, expenditures, and 30-day and 1-year outcomes data.
Baseline patient and hospital characteristics were described according to racial/ethnic groups. Patient factors included age, sex, medical history, vital signs, body mass index, laboratory tests (blood urea nitrogen, serum creatinine, serum sodium, hemoglobin, hemoglobin A1c, and lipid panel). Hospital characteristics included region, rural location, teaching status, and size. Percentages and median interquartile ranges were reported for categorical and continuous variables, respectively. The Pearson chi-square test was used to compare categorical variables, and the Wilcoxon rank sum tests were used to compare ordinal categorical variables or continuous variables. Standardized differences were provided between groups.
SES was linked by using patient zip code geocoding to the 2015 Area Health Resources File provided through the Health Resources & Services Administration. SES variables included median household income, median home value, percentage with high school diploma, and percentage with ≥4 years of college (13).
The primary outcomes included 30-day and 1-year mortality and readmission rates according to cause. Kaplan-Meier estimates of 30-day/1-year mortality outcomes were reported across race groups and compared by using log-rank tests. The cumulative incidence function of readmission outcomes at 30 days/1 year were reported across race groups and compared by using Gray’s test, which determines if the cumulative incidence functions are equal across treatment groups. A Cox proportional hazards model was used for 30-day and 1-year outcomes, and ties were handled by using the Efron method. The models were adjusted sequentially for patient and hospital characteristics followed by patient SES according to ZIP code (Online Tables 1 to 3). Control variables were selected based on a literature review and prior established models used in GWTG-HF (7,11,13).
Patient covariates with missing data were imputed for the Cox model (Online Table 4). Missing medical histories were imputed to not present. Multiple imputations with 25 datasets were used to impute other patient covariates. Hospital characteristics were not imputed. Patients’ SES variables were assigned values from census data of the year closest to the patient’s year of admission. Any dollar values of previous years were adjusted to 2015 U.S. dollars based on the Consumer Price Index.
The final cohort included 53,065 patients (Online Tables 5 to 8). The median age of hospitalization was 83 years for white patients, 77 years for black patients, 79 years for Hispanic patients, and 81 years for Asian patients (Table 1). Black and Hispanic patients had a notably younger age distribution. The proportion of female patients was higher among black subjects comparted with other ethnic groups. Black and Hispanic patients had lower rates of atrial fibrillation compared with the other ethnic groups. Black and Hispanic patients had higher rates of diabetes, hypertension, and median body mass index. Among black, Hispanic, and Asian patients, rates of chronic renal disease and dialysis were significantly higher. Systolic blood pressure on presentation was highest among black patients, followed by Hispanic and Asian patients. LVEF did differ considerably between the racial/ethnic groups. A larger proportion of black patients underwent treatment in teaching hospitals.
With respect to inpatient procedures, minority patients had higher rates of dialysis (Table 2). On discharge, black patients had generally higher rates of antihypertensive and diabetic medication prescription. Inpatient mortality was highest among Asian (3.44%) and white (3.01%) patients and lowest among black (1.70%) and Hispanic (2.30%) patients. Mortality at 30 days and 1 year were 5.87% and 33.10%, respectively, for the overall cohort, with lower rates among minority patients compared with white patients (Table 3, Figure 1). The 30-day and 1-year all-cause readmission rates were 22.16% and 66.95% for the overall cohort, with higher rates among black and Hispanic patients compared with white patients. Black patients had the highest readmission rate for cardiovascular and HF-related primary diagnoses at 1 year.
When controlling for hospital and patient factors, black and Hispanic ethnicities were associated with lower 30-day mortality compared with white race (Table 4, Online Table 9). Mortality at 1 year was lower as well for black, Hispanic, and Asian patients. The lower mortality rates persisted when adjusting for patient SES for black and Hispanic patients. All-cause 30-day and 1-year readmissions were higher among black patients compared with white patients when controlling for patient, hospital, and SES variables. Although Hispanic patients had a similar HR for all-cause readmissions at 30 days, this finding did not meet statistical significance across all models. Hispanic patients did have a higher risk of cardiovascular and HF-related readmissions compared with white patients that was statistically significant when controlling for patient characteristics, hospital characteristics, and regional SES. Black patients had a 12% higher HR for the composite endpoint of 1-year mortality and readmission compared with white patients in the fully adjusted model.
This study reports the differences in HFpEF patient characteristics (both short- and long-term outcomes) after an acute HF hospitalization using a large observational cohort from the GWTG-HF registry linked to CMS administrative data. HFpEF accounts for an increasing portion of HF hospitalizations and is a growing national burden. An HFpEF admission portends considerable risk of future hospitalization and mortality. This study found that minorities generally had lower 30-day and 1-year mortality rates and higher readmission rates compared with white patients, with significant differences in comorbidity burden.
Black and Hispanic patients with HFpEF had higher systolic blood pressure and body mass index. With respect to comorbidities, black and Hispanic patients had higher rates of diabetes, hypertension, and renal insufficiency. These findings suggest that the known risk factors for HFpEF are more prevalent among minority patients (5,6). These differences in comorbidities according to race/ethnicity among patients with HFpEF is consistent with the observed trends in cardiovascular risk factors among minorities nationally, in which the prevalence of obesity, poorly controlled hypertension, and diabetes has increased (10). Obesity is a strong risk factor for incident HFpEF among women (and especially black women) (14). Therefore, much of the current HFpEF burden would be prevented through primary prevention and improvements in the medical management of known cardiovascular risk factors that predispose to left ventricular diastolic dysfunction and the HFpEF syndrome.
Although post-discharge mortality is observed to be lower for black patients, the age-adjusted prevalence of HFpEF is significantly higher, and the per capita death rate for HFpEF may still be higher for black and Hispanic patients with HFpEF compared with white patients (15). The lower short- and long-term mortality among minorities might indicate differences with regard to HFpEF stage. Hospitalized minority patients may include a larger proportion of new or recent-onset disease with lower rates of 30-day and 1-year mortality. Within this Medicare cohort, black patients with HFpEF were 5 years younger, at index admission than white patients. Life expectancy is observed to be significantly lower among black patients with cardiovascular conditions compared with white patients (16). From the perspective of a patient’s life course, we would expect minorities to have a greater risk for incident HFpEF and a shorter life expectancy secondary to the condition.
Much of the mortality hazard was reduced when adjusting for patient-level factors, suggesting that objective vital signs, laboratory data, and comorbidities contribute to the differences in risk according to race/ethnicity. Differences in outcomes persisted when adjusting for hospital and SES among black patients. This finding suggests that the adjustments for regional SES did not contribute to the observed differences in hazard between racial/ethnic groups. The persistence of measured differences according to race/ethnicity despite the given adjustments suggests additional factors outside of the model should be considered. Lower quality transitional and outpatient care, neighborhood deprivation, and unmeasured provider bias may better explain the higher readmission risk for black patients (17). Minority patients in low-income communities face significant barriers in receiving access to quality cardiovascular care. Despite this entire cohort having access to Medicare insurance benefits, the ability to afford copayments for follow-up appointments and prescription medications may still contribute to observed disparities. Clinics in deprived neighborhoods may not have the payer mix necessary to support additional support staff, providers, and specialists required for early and frequent follow-up visits post-hospitalization.
The higher short- and long-term mortality rates among white patients with HFpEF are a competing risk that potentially confounds the higher observed readmission rates for black and Hispanic patients. However, the composite endpoint of readmission and mortality remained significantly higher among black patients compared with white patients in the fully adjusted model. Hispanic patients, like black patients, seemed to have a similarly elevated hazard for readmission risk relative to white patients, but statistical significance was not reached across all models. The smaller cohort size for Hispanic patients and number of events may have limited the statistical power to detect differences in the readmission hazard. Among Asian patients, there was a suggestion that the composite endpoint was lower compared with white patients.
Previous studies reported that patients with HFpEF have lower mortality rates and higher all-cause readmission rates compared with patients with HFrEF (7). A prior GWTG-HF registry study reporting outcomes post-hospitalization for all HF syndromes noted similarly lower mortality rates and higher readmission rates among black and Hispanic patients with HF when controlling for patient factors consistent with these findings (11). The Irbestartan in Heart Failure with Preserved Ejection Fraction Trial reported that approximately 40% of readmissions were for recurrent HF exacerbations (18). Biomarkers such as N-terminal pro–B-type natriuretic peptide are associated with a higher risk of hospitalization and mortality among patients with HFpEF (19). Given the high rates of readmission, future studies should consider risk stratifying patients for post-hospitalization interventions, which may reduce the HFpEF readmission burden. Identifying additional evidenced medical therapies to reduce the HF hospitalization and mortality are also needed (20).
The diagnosis of HFpEF was made according to assessment of LVEF and the clinical presentation of HF. The definition for HFpEF was based on the most recent society guidelines; previous studies have defined HFpEF with an LVEF as low as 40% (21). Although some guidelines recommend analyzing abnormal levels of natriuretic peptides and assessing diastolic dysfunction or relevant structural heart disease, additional echocardiographic data are not available in the registry (8,12). However, the proportion of patients with B-type natriuretic peptide levels >100 pg/ml or N-terminal pro–B-type natriuretic peptide levels >300 pg/ml was 94.0% and comparable to earlier reports of the false-negative rate for natriuretic peptide in patients with clinically diagnosed HF (22–24). The uniform assessment of LVEF in this registry is also lacking because different imaging modalities, including echocardiography (two-dimensional, three-dimensional, and contrast), cardiac magnetic resonance imaging, and angiography, may have been used to determine cardiac systolic function. Although this approach potentially limits standardized HFpEF definitions, the patient population may be more reflective of real-world clinical diagnosis.
The study was also limited to hospitals participating in the GWTG-HF registry and patients with Medicare benefits. Patients are generally older and may not be entirely representative of the general HFpEF population. The specific cause of death was not available to be able to determine contributing factors. Hospitals participating in the GWTG-HF registry may not be representative of hospitals nationally. Patient race/ethnicity is self-designated as recorded by administrative staff or medical providers and may be less accurate than direct patient reporting. The SES variables were limited to geocoding based on a patient’s ZIP code and may be insufficient to measure differences in SES between patients. The smaller sample size for Asian patients with HFpEF limited the statistical strength of observations in the Cox proportional hazards models. Lower observed mortality rates for black and Hispanic patients in this analysis does not account for a potentially higher rate of mortality before index admission.
Patients with HFpEF are an increasing proportion of acute HF admissions. Black and Hispanic patients with HFpEF had lower rates of short- and long-term mortality compared with white patients when controlling for patient and hospital risk factors. Black and Hispanic patients with HFpEF had a higher rate of hospital utilization after an index admission when controlling for patient and hospital factors. Minority patients thus have a higher prevalence of preventable comorbidities that complicate the management of HFpEF. More research is needed to help improve outcomes, narrow disparities, and reduce acute hospital utilization for patients with HFpEF.
COMPETENCY IN MEDICAL KNOWLEDGE: HFpEF is an increasing proportion of acute HF hospitalizations. Variations in outcomes according to race/ethnicity persist when accounting for patient risk factors and regional SEC.
TRANSLATIONAL OUTLOOK: Future studies are needed to improve survival for all patients with HFpEF and reduce the hospitalization burden. Targeted interventions may be needed to improve transitions after hospitalization for minority patients at high risk for readmission.
For supplemental tables, please see the online version of this article.
This research was supported by the American Heart Association–2015 Young Investigator Database Research Seed Grant. The Get With The Guidelines–Heart Failure (GWTG-HF) program is provided by the American Heart Association. GWTG-HF is sponsored, in part, by Amgen Cardiovascular and has been funded in the past through support from Medtronic, GlaxoSmithKline, Ortho-McNeil, and the American Heart Association Pharmaceutical Roundtable. Dr. DeVore has received research support from the American Heart Association, Amgen, and Novartis; and consulting support from Novartis. Dr. Hernandez has received research support from AstraZeneca, Bristol-Myers Squibb, GlaxoSmithKline, Luitpold Pharmaceuticals, Merck, and Novartis; and honoraria from Bayer, Boston Scientific, and Novartis. Dr. Bhatt has served as a member of advisory boards for Cardax, Elsevier Practice Update Cardiology, Medscape Cardiology, and Regado Biosciences; member of the Board of Directors of the Boston VA Research Institute and the Society of Cardiovascular Patient Care; Chair of the American Heart Association Quality Oversight Committee; member of Data Monitoring Committees for Duke Clinical Research Institute, Harvard Clinical Research Institute, Mayo Clinic, and Population Health Research Institute; has received honoraria from the American College of Cardiology (Senior Associate Editor, Clinical Trials and News, ACC.org), Belvoir Publications (Editor-in-Chief, Harvard Heart Letter), Duke Clinical Research Institute (clinical trial steering committees), Harvard Clinical Research Institute (clinical trial steering committee), HMP Communications (Editor-in-Chief, Journal of Invasive Cardiology), Journal of the American College of Cardiology (Guest Editor; Associate Editor), Population Health Research Institute (clinical trial steering committee), Slack Publications (Chief Medical Editor, Cardiology Today’s Intervention), Society of Cardiovascular Patient Care (Secretary/Treasurer), and WebMD (CME steering committees); has served as Deputy Editor for Clinical Cardiology; Chair for NCDR-ACTION Registry Steering Committee; Chair for VA CART Research and Publications Committee; has received research funding from Amarin, Amgen, AstraZeneca, Bristol-Myers Squibb, Eisai, Ethicon, Forest Laboratories, Ischemix, Lilly, Medtronic, Pfizer, Roche, Sanofi, and The Medicines Company; royalties from Elsevier (Editor, Cardiovascular Intervention: A Companion to Braunwald’s Heart Disease); served as site co-investigator for Biotronik, Boston Scientific, and St. Jude Medical; a trustee for the American College of Cardiology; and has performed unfunded research for FlowCo, PLx Pharma, and Takeda. Dr. Fonarow has received research support from the National Institutes of Health; and consulting support from Amgen, Janssen, Medtronic, Novartis, and St. Jude Medical. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose.
- Abbreviations and Acronyms
- Centers for Medicare & Medicaid Services
- Get With The Guidelines–Heart Failure
- heart failure
- heart failure with preserved ejection fraction
- heart failure with reduced ejection fraction
- hazard ratio
- left ventricular ejection fraction
- socioeconomic status
- Received December 21, 2016.
- Revision received February 10, 2017.
- Accepted February 16, 2017.
- 2017 American College of Cardiology Foundation
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