Cigarette Smoking, Cessation, and Risk of Heart Failure With Preserved and Reduced Ejection Fraction

Background: Smoking is well-recognized as a risk factor for heart failure (HF). However, few studies have evaluated the prospective association of cigarette smoking and smoking cessation with heart failure with preserved ejection fraction (HFpEF) and heart failure with reduced ejection fraction (HFrEF) as distinct phenotypes. Objectives: The aim of this study was to quantify the association of cigarette smoking and smoking cessation with the incidence of HFpEF and HFrEF. Methods: In 9,345 ARIC (Atherosclerosis Risk In Communities) study White and Black participants without history of HF at baseline in 2005 (age range 61-81 years), we quantified the associations of several established cigarette smoking parameters (smoking status, pack-years, intensity, duration, and years since cessation) with physician-adjudicated incident acute decompensated HF using multivariable Cox models. Results: Over a median follow-up of 13.0 years, there were 1,215 incident HF cases. Compared with never smokers, current cigarette smoking was similarly associated with HFpEF and HFrEF, with adjusted HRs ∼2. There was a dose-response relationship for pack-years of smoking and HF. A more extended period of smoking cessation was associated with a lower risk of HF, but significantly elevated risk persisted up to a few decades for HFpEF and HFrEF. Conclusions: All cigarette smoking parameters consistently showed significant and similar associations with HFpEF and HFrEF. Smoking cessation significantly reduced the risk of HF, but excess HF risk persisted for a few decades. Our results strengthened the evidence that smoking is an important modifiable risk factor for HF and highlighted the importance of smoking prevention and cessation for the prevention of HF, including HFpEF

Recurrent Acute Decompensated Heart Failure Admissions for Patients With Reduced Versus Preserved Ejection Fraction (from the Atherosclerosis Risk in Communities Study)

Hospitals are required to report all-cause 30-day readmissions for patients discharged with heart failure. Same-cause readmissions have received less attention but may differ for heart failure with reduced ejection fraction (HFrEF) versus heart failure with preserved ejection fraction (HFpEF). The ARIC study began abstracting medical records for cohort members hospitalized with acute decompensated heart failure (ADHF) in 2005. ADHF was validated by physician review, with HFrEF defined by ejection fraction <50%. Recurrent admissions for ADHF were analyzed within 30 days, 90 days, 6 months, and 1 year of the index hospitalization using repeat-measures Cox regression models. All recurrent ADHF admissions per patient were counted rather than the more typical analysis of only the first occurring readmission. From 2005 to 2014, 1,133 cohort members survived at least 1 hospitalization for ADHF and had ejection fraction recorded. Half were classified as HFpEF. Patients with HFpEF were more often women and had more co-morbidities. The overall ADHF readmission rate was greatest within 30 days of discharge but was higher for patients with HFrEF (115 vs 88 readmissions per 100 person-years). After adjustments for demographics, year of admission, and co-morbidities, there was a trend for higher ADHF readmissions with HFrEF, relative to HFpEF, at 30 days (hazard ratio [HR] 1.41, 95% confidence interval [CI] 0.92 to 2.18), 90 days (HR 1.39, 95% CI 1.05 to 1.85), 6 months (HR 1.47, 95% CI, 1.18 to 1.84), and 1 year (HR 1.42, 95% CI 1.18 to 1.70) of follow-up. In conclusion, patients with HFrEF have a greater burden of short- and long-term readmissions for recurrent ADHF

Incident Heart Failure and Long-Term Risk for Venous Thromboembolism

Background: Heart failure (HF) hospitalization places patients at increased short-term risk for venous thromboembolism (VTE). Long-term risk for VTE associated with incident HF, HF subtypes, or structural heart disease is unknown. Objectives: In the ARIC (Atherosclerosis Risk In Communities) cohort, VTE risk associated with incident HF, HF subtypes, and abnormal echocardiographic measures in the absence of clinical HF was assessed. Methods: During follow-up, ARIC identified incident HF and subcategorized HF with preserved ejection fraction or reduced ejection fraction. At the fifth clinical examination, echocardiography was performed. Physicians adjudicated incident VTE using hospital records. Adjusted Cox proportional hazards models were used to evaluate the association between HF or echocardiographic exposures and VTE. Results: Over a mean of 22 years in 13,728 subjects, of whom 2,696 (20%) developed incident HF, 729 subsequent VTE events were identified. HF was associated with increased long-term risk for VTE (adjusted hazard ratio: 3.13; 95% confidence interval: 2.58 to 3.80). In 7,588 subjects followed for a mean of 10 years, the risk for VTE was similar for HF with preserved ejection fraction (adjusted hazard ratio: 4.71; 95% CI: 2.94 to 7.52) and HF with reduced ejection fraction (adjusted hazard ratio: 5.53; 95% confidence interval: 3.42 to 8.94). In 5,438 subjects without HF followed for a mean of 3.5 years, left ventricular relative wall thickness and mean left ventricular wall thickness were independent predictors of VTE. Conclusions: In this prospective population-based study, incident hospitalized HF (including both heart failure with preserved ejection fraction and reduced ejection fraction), as well as echocardiographic indicators of left ventricular remodeling, were associated with greatly increased risk for VTE, which persisted through long-term follow-up. Evidence-based strategies to prevent long-term VTE in patients with HF, beyond time of hospitalization, are needed

Temporal trends in prevalence and prognostic implications of comorbidities among patients with acute decompensated heart failure: The ARIC study community surveillance

Background: Patients with heart failure (HF) have multiple coexisting comorbidities. The temporal trends in the burden of comorbidities and associated risk of mortality among patients with HF with preserved ejection fraction (HFpEF) and HF with reduced ejection fraction (HFrEF) are not well established. Methods: HF-related hospitalizations were sampled by stratified design from 4 US areas in 2005 to 2014 by the community surveillance component of the ARIC study (Atherosclerosis Risk in Communities). Acute decompensated HF was classified by standardized physician review and a previously validated algorithm. An ejection fraction <50% was considered HFrEF. A total of 15 comorbidities were abstracted from the medical record. Mortality outcomes were ascertained for up to 1-year postadmission by linking hospital records with death files. Results: A total of 5460 hospitalizations (24 937 weighted hospitalizations) classified as acute decompensated HF had available ejection fraction data (53% female, 68% white, 53% HFrEF, 47% HFpEF). The average number of comorbidities was higher for patients with HFpEF versus HFrEF, both for women (5.53 versus 4.94; P<0.0001) and men (5.20 versus 4.82; P<0.0001). There was a significant temporal increase in the overall burden of comorbidities, both for patients with HFpEF (women: 5.17 in 2005-2009 to 5.87 in 2010-2013; men: 4.94 in 2005-2009 and 5.45 in 2010-2013) and HFrEF (women: 4.78 in 2005-2009 to 5.14 in 2010-2013; men: 4.62 in 2005-2009 and 5.06 in 2010-2013; P-trend<0.0001 for all). Higher comorbidity burden was significantly associated with higher adjusted risk of 1-year mortality, with a stronger association noted for HFpEF (hazard ratio [HR] per 1 higher comorbidity, 1.19 [95% CI, 1.14-1.25] versus HFrEF (HR, 1.10 [95% CI, 1.05-1.14]; P for interaction by HF type=0.02). The associated mortality risk per 1 higher comorbidity also increased significantly over time for patients with HFpEF and HFrEF, as well (P for interaction with time=0.002 and 0.02, respectively) Conclusions: The burden of comorbidities among hospitalized patients with acute decompensated HFpEF and HFrEF has increased over time, as has its associated mortality risk. Higher burden of comorbidities is associated with higher risk of mortality, with a stronger association noted among patients with HFpEF versus HFrEF

Racial Differences and Temporal Obesity Trends in Heart Failure with Preserved Ejection Fraction

BACKGROUND/OBJECTIVES: Obesity increases with age, is disproportionately prevalent in black populations, and is associated with heart failure with preserved ejection fraction (HFpEF). An “obesity paradox,” or improved survival with obesity, has been reported in patients with HFpEF. The aim of this study was to examine whether racial differences exist in the temporal trends and outcomes associated with obesity among older patients with HFpEF. DESIGN: Community surveillance of acute decompensated heart failure (ADHF) hospitalizations, sampled by stratified design from 2005 to 2014. SETTING: Atherosclerosis Risk in Communities Study (NC, MS, MD, MN). PARTICIPANTS: A total of 10,147 weighted hospitalizations for ADHF (64% female, 74% white, mean age 77 years), with ejection fraction ≥50%. MEASUREMENTS: ADHF classified by physician review, HFpEF defined by ejection fraction ≥50%. Body mass index (BMI) calculated from weight at hospital discharge. Obesity defined by BMI ≥30 kg/m2, class III obesity by BMI ≥40 kg/m2. RESULTS: When aggregated across 2005–2014, the mean BMI was higher for black compared to white patients (34 vs 30 kg/m2; P <.0001), as was prevalence of obesity (56% vs 43%; P <.0001) and class III obesity (24% vs 13%; P <.0001). Over time, the annual mean BMI and prevalence of class III obesity remained stable for black patients, but steadily increased for white patients, with annual rates statistically differing by race (P-interaction =.04 and P =.03, respectively). For both races, a U-shaped adjusted mortality risk was observed across BMI categories, with the highest risk among patients with a BMI ≥40 kg/m2. CONCLUSION: Black patients were disproportionately burdened by obesity in this decade-long community surveillance of older hospitalized patients with HFpEF. However, temporal increases in mean BMI and class III obesity prevalence among white patients narrowed the racial difference in recent years. For both races, the worst survival was observed with class III obesity. Effective strategies are needed to manage obesity in patients with HFpEF

Predicting Risk in Patients Hospitalized for Acute Decompensated Heart Failure and Preserved Ejection Fraction: The Atherosclerosis Risk in Communities Study Heart Failure Community Surveillance

Background Risk-prediction models specifically for hospitalized heart failure with preserved ejection fraction are lacking. Methods and Results We analyzed data from the ARIC (Atherosclerosis Risk in Communities) Study Heart Failure Community Surveillance to create and validate a risk score predicting mortality in patients ≥55 years of age admitted with acute decompensated heart failure with preserved ejection fraction (ejection fraction ≥50%). A modified version of the risk-prediction model for acute heart failure developed from patients in the EFFECT (Enhanced Feedback for Effective Cardiac Treatment) study was used as a composite predictor of 28-day and 1-year mortalities and evaluated together with other potential predictors in a stepwise logistic regression. The derivation sample consisted of 1852 hospitalizations from 2005 to 2011 (mean age, 77 years; 65% women; 74% white). Risk scores were created from the identified predictors and validated in hospitalizations from 2012 to 2013 (n=821). Mortality in the derivation and validation sample was 11% and 8% at 28 days and 34% and 31% at 1 year. The modified EFFECT score, including age, systolic blood pressure, blood urea nitrogen, sodium, cerebrovascular disease, chronic obstructive pulmonary disease, and hemoglobin, was a powerful predictor of mortality. Another important predictor for both 28-day and 1-year mortalities was hypoxia. The risk scores were well calibrated and had good discrimination in the derivation sample (area under the curve: 0.76 for 28-day and 0.72 for 1-year mortalities) and validation sample (area under the curve: 0.73 and 0.71, respectively). Conclusions Mortality after acute decompensation in patients with heart failure with preserved ejection fraction is high, with one third of patients dying within a year. A prediction tool may allow for greater discrimination of the highest risk patients. Clinical Trial Registration: URL: https://www.clinicaltrials.gov. Unique identifier: NCT00005131

Heart Failure Stages among Older Adults in the Community: The Atherosclerosis Risk in Communities Study

Background: Although heart failure (HF) disproportionately affects older adults, little data exist regarding the prevalence of American College of Cardiology/American Heart Association HF stages among older individuals in the community. Additionally, the role of contemporary measures of longitudinal strain and diastolic dysfunction in defining HF stages is unclear. Methods: HF stages were classified in 6118 participants in the Atherosclerosis Risk in Communities study (67-91 years of age) at the fifth study visit as follows: A (asymptomatic with HF risk factors but no cardiac structural or functional abnormalities), B (asymptomatic with structural abnormalities, defined as left ventricular hypertrophy, dilation or dysfunction, or significant valvular disease), C1 (clinical HF without prior hospitalization), and C2 (clinical HF with earlier hospitalization). Results: Using the traditional definitions of HF stages, only 5% of examined participants were free of HF risk factors or structural heart disease (Stage 0), 52% were categorized as Stage A, 30% Stage B, 7% Stage C1, and 6% Stage C2. Worse HF stage was associated with a greater risk of incident HF hospitalization or death at a median follow-up of 608 days. Left ventricular (LV) ejection fraction was preserved in 77% and 65% in Stages C1 and C2, respectively. Incorporation of longitudinal strain and diastolic dysfunction into the Stage B definition reclassified 14% of the sample from Stage A to B and improved the net reclassification index (P=0.028) and integrated discrimination index (P=0.016). Abnormal LV structure, systolic function (based on LV ejection fraction and longitudinal strain), and diastolic function (based on e', E/e', and left atrial volume index) were each independently and additively associated with risk of incident HF hospitalization or death in Stage A and B participants. Conclusions: The majority of older adults in the community are at risk for HF (Stages A or B), appreciably more compared with previous reports in younger community-based samples. LV ejection fraction is robustly preserved in at least two-thirds of older adults with prevalent HF (Stage C), highlighting the burden of HF with preserved LV ejection fraction in the elderly. LV diastolic function and longitudinal strain provide incremental prognostic value beyond conventional measures of LV structure and LV ejection fraction in identifying persons at risk for HF hospitalization or death

Predictors of mortality by sex and race in heart failure with preserved ejection fraction: Aric community surveillance study

BACKGROUND: Heart failure with preserved ejection fraction (HFpEF) accounts for half of heart failure hospitalizations, with limited data on predictors of mortality by sex and race. We evaluated for differences in predictors of all-cause mortality by sex and race among hospitalized patients with HFpEF in the ARIC (Atherosclerosis Risk in Communities) Community Surveillance Study. METHODS AND RESULTS: Adjudicated HFpEF hospitalization events from 2005 to 2013 were analyzed from the ARIC Community Surveillance Study, comprising 4 US communities. Comparisons between clinical characteristics and mortality at 1 year were made by sex and race. Of 4335 adjudicated acute decompensated heart failure cases, 1892 cases (weighted n=8987) were categorized as HFpEF. Men had an increased risk of 1-year mortality compared with women in adjusted analysis (hazard ratio [HR], 1.27; 95% CI, 1.06–1.52 [P=0.01]). Black participants had lower mortality compared with White participants in unadjusted and adjusted analyses (HR, 0.79; 95% CI, 0.64–0.97 [P=0.02]). Age, heart rate, worsening renal function, and low hemoglobin were associated with increased mortality in all subgroups. Higher body mass index was associated with improved survival in men, with borderline interaction by sex. Higher blood pressure was associated with improved survival among all groups, with significant interaction by race. CONCLUSIONS: In a diverse HFpEF population, men had worse survival compared with women, and Black participants had improved survival compared with White participants. Age, heart rate, and worsening renal function were associated with increased mortality across all subgroups; high blood pressure was associated with decreased mortality with interaction by race. These insights into sex-and race-based differences in predictors of mortality may help strategize targeted management of HFpEF

Measurement of νˉμ\bar{\nu}_{\mu} and νμ\nu_{\mu} charged current inclusive cross sections and their ratio with the T2K off-axis near detector

We report a measurement of cross section $\sigma(\nu_{\mu}+{\rm nucleus}\rightarrow\mu^{-}+X)$ and the first measurements of the cross section $\sigma(\bar{\nu}_{\mu}+{\rm nucleus}\rightarrow\mu^{+}+X)$ and their ratio $R(\frac{\sigma(\bar \nu)}{\sigma(\nu)})$ at (anti-)neutrino energies below 1.5 GeV. We determine the single momentum bin cross section measurements, averaged over the T2K $\bar{\nu}/\nu$-flux, for the detector target material (mainly Carbon, Oxygen, Hydrogen and Copper) with phase space restricted laboratory frame kinematics of $\theta_{\mu}$500 MeV/c. The results are $\sigma(\bar{\nu})=\left( 0.900\pm0.029{\rm (stat.)}\pm0.088{\rm (syst.)}\right)\times10^{-39}$ and $\sigma(\nu)=\left( 2.41\ \pm0.022{\rm{(stat.)}}\pm0.231{\rm (syst.)}\ \right)\times10^{-39}$in units of cm$^{2}$/nucleon and$R\left(\frac{\sigma(\bar{\nu})}{\sigma(\nu)}\right)= 0.373\pm0.012{\rm (stat.)}\pm0.015{\rm (syst.)}$.Comment: 18 pages, 8 figure