Socioeconomic status and modification of atherosclerotic cardiovascular disease risk prediction: epidemiological analysis using data from the atherosclerosis risk in communities study.

OBJECTIVE: Examine whether the relationship between the pooled cohort equations (PCE) predicted 10-year risk for atherosclerotic cardiovascular disease (ASCVD) and absolute risk for ASCVD is modified by socioeconomic status (SES). DESIGN: Population-based longitudinal cohort study-Atherosclerosis Risk in Communities (ARIC)-investigating the development of cardiovascular disease across demographic subgroups. SETTING: Four communities in the USA-Forsyth County, North Carolina, Jackson, Mississippi, suburbs of Minneapolis, Minnesota and Washington County, Maryland. PARTICIPANTS: We identified 9782 ARIC men and women aged 54-73 without ASCVD at study visit 4 (1996-1998). PRIMARY OUTCOME MEASURES: Risk ratio (RR) differences in 10-year incident hospitalisations or death for ASCVD by SES and PCE predicted 10-year ASCVD risk categories to assess for risk modification. SES measures included educational attainment and census-tract neighbourhood deprivation using the Area Deprivation Index. PCE risk categories were 0%-5%, >5%-10%, >10%-15% and >15%. SES as a prognostic factor to estimate ASCVD absolute risk categories was further investigated as an interaction term with the PCE. RESULTS: ASCVD RRs for participants without a high school education (referent college educated) increased at higher PCE estimated risk categories and was consistently >1. Results indicate education is both a risk modifier and delineates populations at higher ASCVD risk independent of PCE. Neighbourhood deprivation did modify association but was less consistent in direction of effect. However, for participants residing in the most deprived neighbourhoods (referent least deprived neighbourhoods) with a PCE estimated risk >10%-15%, risk was significantly elevated (RR 1.65, 95% CI 1.05 to 2.59). Education and neighbourhood deprivation inclusion as an interaction term on the PCE risk score was statistically significant (likelihood ratio p≤0.0001). CONCLUSIONS: SES modifies the association between PCE estimated risk and absolute risk of ASCVD. SES added into ASCVD risk prediction models as an interaction term may improve our ability to predict absolute ASCVD risk among socially disadvantaged populations.

Optimal medical therapy with or without surgical revascularization and long-term outcomes in ischemic cardiomyopathy.

OBJECTIVES: Optimal medical therapy in patients with heart failure and coronary artery disease is associated with improved outcomes. However, whether this association is influenced by the performance of coronary artery bypass grafting is less well established. Thus, the aim of this study was to determine the possible relationship between coronary artery bypass grafting and optimal medical therapy and its effect on the outcomes of patients with ischemic cardiomyopathy. METHODS: The Surgical Treatment for Ischemic Heart Failure trial randomized 1212 patients with coronary artery disease and left ventricular ejection fraction 35% or less to coronary artery bypass grafting with medical therapy or medical therapy alone with a median follow-up over 9.8 years. For the purpose of this study, optimal medical therapy was collected at baseline and 4 months, and defined as the combination of 4 drugs: angiotensin-converting enzyme inhibitor or angiotensin receptor blocker, beta-blocker, statin, and 1 antiplatelet drug. RESULTS: At baseline and 4 months, 58.7% and 73.3% of patients were receiving optimal medical therapy, respectively. These patients had no differences in important parameters such as left ventricular ejection fraction and left ventricular volumes. In a multivariable Cox model, optimal medical therapy at baseline was associated with a lower all-cause mortality (hazard ratio, 0.78; 95% confidence interval, 0.66-0.91; P = .001). When landmarked at 4 months, optimal medical therapy was also associated with a lower all-cause mortality (hazard ratio, 0.82; 95% confidence interval, 0.62-0.99; P = .04). There was no interaction between the benefit of optimal medical therapy and treatment allocation. CONCLUSIONS: Optimal medical therapy was associated with improved long-term survival and lower cardiovascular mortality in patients with ischemic cardiomyopathy and should be strongly recommended.

Optimal medical therapy with or without surgical revascularization and long-term outcomes in ischemic cardiomyopathy

Objectives: Optimal medical therapy in patients with heart failure and coronary artery disease is associated with improved outcomes. However, whether this association is influenced by the performance of coronary artery bypass grafting is less well established. Thus, the aim of this study was to determine the possible relationship between coronary artery bypass grafting and optimal medical therapy and its effect on the outcomes of patients with ischemic cardiomyopathy. Methods: The Surgical Treatment for Ischemic Heart Failure trial randomized 1212 patients with coronary artery disease and left ventricular ejection fraction 35% or less to coronary artery bypass grafting with medical therapy or medical therapy alone with a median follow-up over 9.8 years. For the purpose of this study, optimal medical therapy was collected at baseline and 4 months, and defined as the combination of 4 drugs: angiotensin-converting enzyme inhibitor or angiotensin receptor blocker, beta-blocker, statin, and 1 antiplatelet drug. Results: At baseline and 4 months, 58.7% and 73.3% of patients were receiving optimal medical therapy, respectively. These patients had no differences in important parameters such as left ventricular ejection fraction and left ventricular volumes. In a multivariable Cox model, optimal medical therapy at baseline was associated with a lower all-cause mortality (hazard ratio, 0.78; 95% confidence interval, 0.66-0.91; P » .001). When landmarked at 4 months, optimal medical therapy was also associated with a lower all-cause mortality (hazard ratio, 0.82; 95% confidence interval, 0.62-0.99; P » .04). There was no interaction between the benefit of optimal medical therapy and treatment allocation. Conclusions: Optimal medical therapy was associated with improved long-term survival and lower cardiovascular mortality in patients with ischemic cardiomyopathy and should be strongly recommended.

CABG Improves Outcomes in Patients With Ischemic Cardiomyopathy: 10-Year Follow-Up of the STICH Trial.

OBJECTIVES: The authors investigated the impact of coronary artery bypass grafting (CABG) on first and recurrent hospitalization in this population. BACKGROUND: In the STICH (Surgical Treatment for Ischemic Heart Failure) trial, CABG reduced all-cause death and hospitalization in patients with and ischemic cardiomyopathy and left ventricular ejection fraction <35%. METHODS: A total of 1,212 patients were randomized (610 to CABG + optimal medical therapy [CABG] and 602 to optimal medical therapy alone [MED] alone) and followed for a median of 9.8 years. All-cause and cause-specific hospitalizations were analyzed as time-to-first-event and as recurrent event analysis. RESULTS: Of the 1,212 patients, 757 died (62.4%) and 732 (60.4%) were hospitalized at least once, for a total of 2,549 total all-cause hospitalizations. Most hospitalizations (66.2%) were for cardiovascular causes, of which approximately one-half (907 or 52.9%) were for heart failure. More than 70% of all hospitalizations (1,817 or 71.3%) were recurrent events. The CABG group experienced fewer all-cause hospitalizations in the time-to-first-event (349 CABG vs. 383 MED, adjusted hazard ratio [HR]: 0.85; 95% confidence interval [CI]: 0.74 to 0.98; p = 0.03) and in recurrent event analyses (1,199 CABG vs. 1,350 MED, HR: 0.78, 95% CI: 0.65 to 0.94; p < 0.001). This was driven by fewer total cardiovascular (CV) hospitalizations (744 vs. 968; p < 0.001, adjusted HR: 0.66, 95% CI: 0.55 to 0.81; p = 0.001), the majority of which were due to HF (395 vs. 512; p < 0.001, adjusted HR: 0.68, 95% CI: 0.52-0.89; p = 0.005). We did not observe a difference in non-CV events. CONCLUSIONS: CABG reduces all-cause, CV, and HF hospitalizations in time-to-first-event and recurrent event analyses. (Comparison of Surgical and Medical Treatment for Congestive Heart Failure and Coronary Artery Disease [STICH]; NCT00023595).

In-Hospital and Postdischarge Mortality Among Patients With Acute Decompensated Heart Failure Hospitalizations Ending on the Weekend Versus Weekday: The ARIC Study Community Surveillance.

Background Hospital staffing is usually reduced on weekends, potentially impacting inpatient care and postdischarge coordination of care for patients with acute decompensated heart failure (ADHF). However, investigations of in-hospital mortality on the weekend versus weekday, and post-hospital outcomes of weekend versus weekday discharge are scarce. Methods and Results Hospitalizations for ADHF were sampled by stratified design from 4 US areas by the Community Surveillance component of the ARIC (Atherosclerosis Risk in Communities) study. ADHF was classified by a standardized computer algorithm and physician review of the medical records. Discharges or deaths on Saturday, Sunday, or national holidays were considered to occur on the "weekend." In-hospital mortality was compared between hospitalizations ending on a weekend versus weekday. Post-hospital (28-day) mortality was compared among patients discharged alive on a weekend versus weekday. From 2005 to 2014, 39 699 weighted ADHF hospitalizations were identified (19% terminating on a weekend). Demographics, comorbidities, length of stay, and guideline-directed therapies were similar for patients with hospitalizations ending on a weekend versus weekday. In-hospital death doubled on the weekend compared with weekday (12% versus 6%) and was not attenuated by adjustment for potential confounders (odds ratio, 2.37; 95% CI, 1.93-2.91). There was no association between weekend discharge and 28-day mortality among patients discharged alive. Conclusions The risk of in-hospital death among patients admitted with ADHF appears to be doubled on the weekends when hospital staffing is usually reduced. However, among patients discharged alive, hospital discharge on a weekend is not adversely associated with mortality.

Burden of medical co-morbidities and benefit from surgical revascularization in patients with ischaemic cardiomyopathy.

AIMS: The landmark STICH trial found that surgical revascularization compared to medical therapy alone improved survival in patients with heart failure (HF) of ischaemic aetiology and an ejection fraction (EF) ≤ 35%. However, the interaction between the burden of medical co-morbidities and the benefit from surgical revascularization has not been previously described in patients with ischaemic cardiomyopathy. METHODS AND RESULTS: The STICH trial (ClinicalTrials.gov Identifier: NCT00023595) enrolled patients ≥ 18 years of age with coronary artery disease amenable to coronary artery bypass grafting (CABG) and an EF ≤ 35%. Eligible participants were randomly assigned 1:1 to receive medical therapy (MED) (n = 602) or MED/CABG (n = 610). A modified Charlson co-morbidity index (CCI) based on the availability of data and study definitions was calculated by summing the weighted points for all co-morbid conditions. Patients were divided into mild/moderate (CCI 1-4) and severe (CCI ≥ 5) co-morbidity. Cox proportional hazards models were used to evaluate the association between CCI and outcomes and the interaction between severity of co-morbidity and treatment effect. The study population included 349 patients (29%) with a mild/moderate CCI score and 863 patients (71%) with a severe CCI score. Patients with a severe CCI score had greater functional limitations based on 6-min walk test and impairments in health-related quality of life as assessed by the Kansas City Cardiomyopathy Questionnaire. A total of 161 patients (Kaplan-Meier rate = 50%) with a mild/moderate CCI score and 579 patients (Kaplan-Meier rate = 69%) with a severe CCI score died over a median follow-up of 9.8 years. After adjusting for baseline confounders, patients with a severe CCI score were at higher risk for all-cause mortality (hazard ratio 1.44, 95% confidence interval 1.19-1.74; P < 0.001). There was no interaction between CCI score and treatment effect on survival (P = 0.756). CONCLUSIONS: More than 70% of patients had a severe burden of medical co-morbidities at baseline, which was independently associated with increased risk of death. There was not a differential benefit of surgical revascularization with respect to survival based on severity of co-morbidity.

Heart Failure and Cognitive Impairment in the Atherosclerosis Risk in Communities (ARIC) Study.

BACKGROUND: Previous studies suggest that heart failure (HF) is an independent risk factor for cognitive decline. A better understanding of the relationship between HF, cognitive status, and cognitive decline in a community-based sample may help clinicians understand disease risk. OBJECTIVE: To examine whether persons with HF have a higher prevalence of cognitive impairment and whether persons developing HF have more rapid cognitive decline. DESIGN: This observational cohort study of American adults in the Atherosclerosis Risk in Communities (ARIC) study has two components: cross-sectional analysis examining the association between prevalent HF and cognition using multinomial logistic regression, and change over time analysis detailing the association between incident HF and change in cognition over 15 years. PARTICIPANTS: Among visit 5 (2011-2013) participants (median age 75 years), 6495 had neurocognitive information available for cross-sectional analysis. Change over time analysis examined the 5414 participants who had cognitive scores and no prevalent HF at visit 4 (1996-1998). MEASUREMENTS: The primary outcome was cognitive status, classified as normal, mild cognitive impairment [MCI], and dementia on the basis of standardized cognitive tests (delayed word recall, word fluency, and digit symbol substitution). Cognitive change was examined over a 15-year period. Control variables included socio-demographic, vascular, and smoking/drinking measures. RESULTS: At visit 5, participants with HF had a higher prevalence of dementia (adjusted relative risk ratio [RRR] = 1.60 [95% CI 1.13, 2.25]) and MCI (RRR = 1.36 [1.12, 1.64]) than those without HF. A decline in cognition between visits 4 and 5 was - 0.07 standard deviation units [- 0.13, - 0.01] greater among persons who developed HF compared to those who did not. Results did not differ by ejection fraction. CONCLUSION: HF is associated with neurocognitive dysfunction and decline independent of other co-morbid conditions. Further study is needed to determine the underlying pathophysiology.

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.

Guideline-Directed Medical Therapy and Survival Following Hospitalization in Patients with Heart Failure.

BACKGROUND: Modification of guideline-directed medical therapy (GDMT) in hospitalized patients with heart failure (HF) has not been extensively evaluated. METHODS: The community surveillance arm of the Atherosclerosis Risk in Communities Study identified 6959 HF hospitalizations from 2005-2011. Predictors of GDMT modification and survival were assessed using multivariable logistic regression and Cox proportional hazards models. RESULTS: For 5091 hospitalizations, patient mean age was 75 years, 53% were female, 69% were white, and 81% had acute decompensated heart failure (ADHF). Regarding ejection fraction (EF), 31% of patients had HF with reduced EF (HFrEF), 24% had HF with preserved EF (HFpEF), and 44% were missing EF values. At admission, 52% of patients received angiotensin-converting enzyme inhibitors/angiotensin receptor blockers (ACEIs/ARBs), 66% ß-blockers (BBs), 9% aldosterone-receptor antagonists, 16% digoxin, 10% hydralazine, and 29% nitrates. Modification of GDMT occurred in up to 23% of hospitalizations. Significant predictors of GDMT initiation included ADHF and HFrEF; discontinuation of medications was observed with select comorbidities. In HFrEF, initiation of any GDMT was associated with reduced 1-year all-cause mortality (adjusted hazard ratio [HR] 0.41, 95% confidence interval [CI] 0.23-0.71) as was initiation of ACEI/ARBs, BBs, and digoxin. Discontinuation of any therapy versus maintaining GDMT was associated with greater mortality (HR 1.30, 95% CI 1.02-1.66). Similar trends were observed in HFpEF. CONCLUSIONS: Our study suggests that GDMT initiation is associated with increased survival, and discontinuation of therapy is associated with reduced survival in hospitalized patients with HF. Future studies should be conducted to confirm the impact of GDMT therapy modification in this population.

Antihypertensive adherence and outcomes among community-dwelling Medicare beneficiaries: the Atherosclerosis Risk in Communities Study.

RATIONALE, AIMS, AND OBJECTIVES: Despite proven benefits for reducing incidence of major cardiac events, antihypertensive drug therapy remains underutilized in the United States. This analysis assesses antihypertensive drug adherence, utilization predictors, and associations between adherence and outcomes (a composite of cardiovascular events, Medicare inpatient payments, and inpatient days). METHODS: The sample consisted of Atherosclerosis Risk in Communities Study cohort participants reporting hypertension without prevalent cardiovascular disease during 2006 to 2007 annual follow-up calls. Atherosclerosis Risk in Communities records were linked to Medicare claims through 2012. Antihypertensive medication adherence was measured as more than 80% proportion days covered by using Medicare Part D claims. Standard and hierarchical regression models were used to evaluate adjusted associations between person characteristics and adherence and between adherence and outcomes. RESULTS: Among 1826 hypertensive participants with Part D coverage, 31.5% had no antihypertensive class with more than 80% proportion days covered in the 3 months preceding the report of hypertension in 2006 to 2007. After adjustment for confounders, positive predictors of use included female gender and diabetes; negative predictors were African-American race and current smoking. Adjusted association between receiving no therapy and a composite endpoint of cardiovascular outcomes through 2012 was not statistically significant (hazard ratio: 0.93; 95% confidence interval: 0.72, 1.22) nor was the adjusted association with Medicare inpatient days or payments (incremental difference at 48 months in payments: $1217; 95% CI: -$2030, $4463). CONCLUSIONS: Despite having medical and prescription coverage, nearly a third of hypertensive participants were not adherent to antihypertensive drug therapy. Differences in clinical outcomes associated with nonadherence, though not statistically significant, were consistent with results from randomized trials. The approach provides a model framework for rigorous assessment of detailed data that are increasingly available through emerging sources.

Predictors of Medication Adherence in the Elderly: The Role of Mental Health.

The aging population routinely has comorbid conditions requiring complicated medication regimens, yet nonadherence can preclude optimal outcomes. This study explored the association of adherence in the elderly with demographic, socioeconomic, and disease burden measures. Data were from the fifth visit (2011-2013) for 6,538 participants in the Atherosclerosis Risk in Communities Study, conducted in four communities. The Morisky-Green-Levine Scale measured self-reported adherence. Forty percent of respondents indicated some nonadherence, primarily due to poor memory. Logit regression showed, surprisingly, that persons with low reading ability were more likely to report being adherent. Better self-reported physical or mental health both predicted better adherence, but the magnitude of the association was greater for mental than for physical health. Compared with persons with normal or severely impaired cognition, mild cognitive impairment was associated with lower adherence. Attention to mental health measures in clinical settings could provide opportunities for improving medication adherence.

Contribution of medications and risk factors to QTc interval lengthening in the atherosclerosis risk in communities (ARIC) study.

RATIONALE, AIMS, AND OBJECTIVES: Prolongation of the corrected QT (QTc) interval is associated with increased morbidity and mortality. The association between QTc interval-prolonging medications (QTPMs) and risk factors with magnitude of QTc interval lengthening is unknown. We examined the contribution of risk factors alone and in combination with QTPMs to QTc interval lengthening. METHOD: The Atherosclerosis Risk in Communities study assessed 15 792 participants with a resting, standard 12-lead electrocardiogram and ≥1 measure of QTc interval over 4 examinations at 3-year intervals (1987-1998). From 54 638 person-visits, we excluded participants with QRS ≥ 120 milliseconds (n = 2333 person-visits). We corrected the QT interval using the Bazett and Framingham formulas. We examined QTc lengthening using linear regression for 36 602 person-visit observations for 14 160 cohort members controlling for age ≥ 65 years, female sex, left ventricular hypertrophy, QTc > 500 milliseconds at the prior visit, and CredibleMeds categorized QTPMs (Known, Possible, or Conditional risk). We corrected standard errors for repeat observations per person. RESULTS: Eighty percent of person-visits had at least one risk factor for QTc lengthening. Use of QTPMs increased over the 4 visits from 8% to 17%. Among persons not using QTPMs, history of prolonged QTc interval and female sex were associated with the greatest QTc lengthening, 39 and 12 milliseconds, respectively. In the absence of risk factors, Known QTPMs and ≥2 QTPMs were associated with modest but greater QTc lengthening than Possible or Conditional QTPMs. In the presence of risk factors, ≥2 QTPM further increased QTc lengthening. In combination with risk factors, the association of all QTPM categories with QTc lengthening was greater than QTPMs alone. CONCLUSION: Risk factors, particularly female sex and history of prolonged QTc interval, have stronger associations with QTc interval lengthening than any QTPM category alone. All QTPM categories augmented QTc interval lengthening associated with risk factors.

Sudden Cardiac Death in Patients With Ischemic Heart Failure Undergoing Coronary Artery Bypass Grafting: Results From the STICH Randomized Clinical Trial (Surgical Treatment for Ischemic Heart Failure).

BACKGROUND: The risk of sudden cardiac death (SCD) in patients with heart failure after coronary artery bypass graft surgery (CABG) has not been examined in a contemporary clinical trial of surgical revascularization. This analysis describes the incidence, timing, and clinical predictors of SCD after CABG. METHODS: Patients enrolled in the STICH trial (Surgical Treatment of Ischemic Heart Failure) who underwent CABG with or without surgical ventricular reconstruction were included. We excluded patients with prior implantable cardioverter-defibrillator and those randomized only to medical therapy. The primary outcome was SCD as adjudicated by a blinded committee. A Cox model was used to examine and identify predictors of SCD. The Fine and Gray method was used to estimate the incidence of SCD accounting for the competing risk of other deaths. RESULTS: Over a median follow-up of 46 months, 113 of 1411 patients who received CABG without (n = 934) or with (n = 477) surgical ventricular reconstruction had SCD; 311 died of other causes. The mean left ventricular ejection fraction at enrollment was 28±9%. The 5-year cumulative incidence of SCD was 8.5%. Patients who had SCD and those who did not die were younger and had fewer comorbid conditions than did those who died of causes other than SCD. In the first 30 days after CABG, SCD (n=5) accounted for 7% of all deaths. The numerically greatest monthly rate of SCD was in the 31- to 90-day time period. In a multivariable analysis including baseline demographics, risk factors, coronary anatomy, and left ventricular function, end-systolic volume index and B-type natriuretic peptide were most strongly associated with SCD. CONCLUSIONS: The monthly risk of SCD shortly after CABG among patients with a low left ventricular ejection fraction is highest between the first and third months, suggesting that risk stratification for SCD should occur early in the postoperative period, particularly in patients with increased preoperative end-systolic volume index or B-type natriuretic peptide. CLINICAL TRIAL REGISTRATION: URL: http://www.clinicaltrials.gov. Unique identifier: NCT0002359.

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.

Are Trends in Hospitalization Prior to Hospice Use Associated With Hospice Episode Characteristics?

This study expands current knowledge of factors associated with initiation of hospice care by examining prehospice patterns of medical care leading to Medicare hospice use and the relationships to hospice episode characteristics. Data from the Atherosclerosis Risk in Communities (ARIC) study cohort offer the ability to control for measures that are not available in Medicare claims data, including marital status, nursing home residency, and education. For 1248 ARIC participants who used hospice (2006-2012), participant level trends in the number of hospital days per 30-day period over the year prior to hospice initiation were generated using a fixed-effects model. Logistic regression was used to estimate the associations between increasing hospital use over the year prior to hospice enrollment with key patient characteristics (diagnosis, age, and comorbidity) and episode characteristics (short hospice stay ending in death, long hospice stay, and live discharge). Participants with severe comorbidity (measured as a Charlson comorbidity index score greater than 5) had higher odds of increasing hospital use prior to hospice (odds ratio [OR] = 3.28, confidence interval [CI] = 2.25-4.78). Increasing hospital use did not vary by diagnosis but was associated with reduced odds of a live hospice discharge (OR = 0.55, CI = 0.34-0.88) or long stay in hospice (OR = 0.44, CI = 0.24-0.79) and increased odds of a short stay in hospice (OR = 1.92, CI = 1.36-2.71). The evidence that care patterns prior to hospice use are associated with hospice outcomes could facilitate development of interventions to improve timely hospice referral.

Prognostic Importance of Dyspnea for Cardiovascular Outcomes and Mortality in Persons without Prevalent Cardiopulmonary Disease: The Atherosclerosis Risk in Communities Study.

BACKGROUND: The relationship between dyspnea and incident heart failure (HF) and myocardial infarction (MI) among patients without previously diagnosed cardiopulmonary disease is unclear. We studied the prognostic relevance of self-reported dyspnea for cardiovascular outcomes and all-cause mortality in persons without previously diagnosed cardiopulmonary disease. METHODS AND RESULTS: We studied 10 881 community-dwelling participants (mean age 57±6, 56% women, 25% black) who were free of prevalent cardiopulmonary disease from Atherosclerosis Risk in Communities Study. Dyspnea status at study entry using the modified Medical Research Council (mMRC) scale. The primary outcomes were time to HF, MI or all-cause death. Dyspnea prevalence was 22%, and was mild (mMRC grade 1 or 2) in 21% and moderate-to-severe (mMRC 3 or 4) in 1%. The main correlates of dyspnea were older age, female sex, higher BMI and active smoking. Over a follow-up of 19±5 years, greater self-reported dyspnea severity was associated with worse prognosis. Mild dyspnea was associated with significantly heightened risk of HF (adjusted Hazard Ratio, HR,1.30; 95% CI: 1.16-1.46), MI (adjusted HR 1.34; 95%CI: 1.20-1.50), and death (adjusted HR 1.16; 95%CI: 1.06-1.26), with moderate/severe dyspnea associated with an even greater risk (adjusted HR 2.14, 95%CI: 1.59-2.89; 1.93, 95%CI: 1.41-2.56; 1.96, 95%CI: 1.55-2.48, respectively). CONCLUSION: In community-dwelling persons free of previously diagnosed cardiopulmonary disease, self-reported dyspnea is common and, even when of mild intensity, it is independently associated with a greater risk of incident HF, MI, and death. Our data emphasize the prognostic importance of even mild self-reported dyspnea for cardiovascular outcomes.

Reactive hyperemia is associated with adverse clinical outcomes in heart failure.

INTRODUCTION: Impaired endothelial function, as assessed by brachial artery flow-mediated dilation (FMD), is an established risk factor for cardiovascular events. FMD is impaired in heart failure (HF) patients, but less is known about hyperemic brachial artery flow. We investigated the relationship between FMD and hyperemic flow with adverse clinical outcomes in HF patients. METHODS: Brachial artery FMD and hyperemic flow were assessed in 156 patients (70.5 % Male; 45.5% Caucasian; mean age (± SD) = 56.2 (±12.4) years) with HF and reduced left ventricular ejection fraction (LVEF). Cox proportional hazard models were used to assess the potential explanatory association of FMD and hyperemic flow with the composite outcome of death or cardiovascular hospitalization over a median 5-year follow-up period. RESULTS: Both FMD and hyperemic flow were negatively correlated with age, but unrelated to sex, race, body mass index, LVEF or N-terminal pro-B-Type natriuretic peptide (NT-ProBNP). Reduced hyperemic flow, but not FMD, was associated with an increased risk of death or cardiac hospitalization after controlling for traditional risk factors. CONCLUSION: The association of reduced hyperemic flow with increased risk of adverse clinical outcomes suggests that micro-vascular function may be an important prognostic marker in patients with HF.

Medication Adherence Based on Part D Claims for Patients With Heart Failure After Hospitalization (from the Atherosclerosis Risk in Communities Study).

Medication nonadherence is a common precipitant of heart failure (HF) hospitalization and is associated with poor outcomes. Recent analyses of national data focus on long-term medication adherence. Little is known about adherence of patients with HF immediately after hospitalization. Hospitalized patients with HF were identified from the Atherosclerosis Risk in Communities study. Atherosclerosis Risk in Communities data were linked to Medicare inpatient and part D claims from 2006 to 2009. Inclusion criteria were a chart-adjudicated diagnosis of acute decompensated or chronic HF; documentation of angiotensin-converting enzyme inhibitor/angiotensin receptor blocker (ACEI/ARB), ß blocker (BB), or diuretic prescription at discharge; and Medicare part D coverage. Proportion of ambulatory days covered was calculated for up to twelve 30-day periods after discharge. Adherence was defined as ≥80% proportion of ambulatory days covered. We identified 402 participants with Medicare part D: mean age 75, 30% men, and 41% black. Adherence at 1, 3, and 12 months was 70%, 61%, and 53% for ACEI/ARB; 76%, 66%, and 62% for BB; and 75%, 68%, and 59% for diuretic. Adherence to any single drug class was positively correlated with being adherent to other classes. Adherence varied by geographic site/race for ACEI/ARB and BB but not diuretics. In conclusion, despite having part D coverage, medication adherence after discharge for all 3 medication classes decreases over 2 to 4 months after discharge, followed by a plateau over the subsequent year. Interventions should focus on early and sustained adherence.

Effects of an accelerated intravenous iron regimen in hospitalized patients with advanced heart failure and iron deficiency.

STUDY OBJECTIVE: To assess the short-term efficacy and safety of an accelerated intravenous iron regimen in hospitalized patients with heart failure and iron deficiency. DESIGN: Prospective, single-arm, open-label study. SETTING: Large tertiary care medical center. PATIENTS: Thirteen patients with New York Heart Association class III-IV heart failure, anemia (hemoglobin level ≤ 12.0 g/dl), and iron deficiency (ferritin level < 100 ng/ml, or ferritin level of 100-300 ng/ml with transferrin saturation < 20%) hospitalized between April 2011 and December 2013. INTERVENTION: All patients received sodium ferric gluconate 250 mg in 100 ml of normal saline intravenously over 2 hours twice/day until the iron deficit was corrected or the patient was discharged. MEASUREMENTS AND MAIN RESULTS: Changes in hematologic parameters were assessed at 1-4 weeks after therapy. Patients received a mean ± standard deviation (SD) total iron dose of 1269 ± 207 mg over 3.4 ± 1.0 days. After a mean ± SD follow-up of 13.1 ± 5.6 days, intravenous iron increased hemoglobin level by 1.2 g/dl (95% confidence interval [CI] 0.45-1.9, p=0.005), ferritin level by 364.2 ng/ml (95% CI 129.7-598.7, p=0.007), and transferrin saturation by 10.5% (95% CI 6.5-14.6%, p<0.001). Changes in hemoglobin level did not correlate with volume status, as determined by differences in body weight. No significant changes in blood pressure or heart rate were observed. Adverse events were few and minor in severity (e.g., nausea, constipation, and abdominal discomfort). CONCLUSION: An accelerated intravenous iron regimen improved hematologic parameters and was well tolerated in hospitalized patients with advanced heart failure. A randomized multicenter trial comparing this regimen with placebo is warranted.