Renin-Angiotensin Inhibition and Outcomes in Nursing Home Residents With Heart Failure.

BACKGROUND: Angiotensin-converting enzyme inhibitors or angiotensin receptor blockers (ACEIs-ARBs) improve outcomes in heart failure (HF). Less is known about this association in nursing home (NH) residents. METHODS: Of the 8024 hospitalized HF patients, 542 were NH residents, of whom 250 received ACEIs-ARBs. We assembled a propensity score-matched cohort of 157 pairs of NH residents receiving and not receiving ACEIs-ARBs balanced on 29 baseline characteristics (mean age, 83 years, 74% women, 17% African American), in which we estimated hazard ratios (HRs) and 95% confidence intervals (CIs) for outcomes associated with ACEI-ARB use. We then checked for interaction in a matched cohort of 5130 patients (378 were NH residents) assembled from the 8024 patients. RESULTS: Among 314 matched NH residents, HRs (95% CIs) for 30-day all-cause readmission, HF readmission, and all-cause mortality were 0.78 (0.47-1.28), 0.68 (0.29-1.60), and 1.26 (0.70-2.27), respectively. Respective HRs (95% CIs) at 1 year were 0.76 (0.56-1.02), 0.68 (0.42-1.09), and 1.04 (0.78-1.38). Among 5130 matched patients, ACEI-ARB use was associated with a significantly lower risk of all outcomes at both times, with no significant interactions, except for 1-year mortality, which was only significant in the non-NH subgroup (P for interaction, 0.026). CONCLUSIONS: We found no evidence that the use of ACEIs or ARBs is associated with improved outcomes in patients with HF in the NH setting. However, we also found no evidence that this association is different in NH residents with HF versus non-NH patients with HF. Future larger studies are needed to demonstrate effectiveness of these drugs in the NH setting.

Characteristics and outcomes of patients with advanced chronic systolic heart failure receiving care at the Veterans Affairs versus other hospitals: insights from the Beta-blocker Evaluation of Survival Trial (BEST).

BACKGROUND: Characteristics and outcomes of patients with heart failure and reduced ejection fraction receiving care at Veterans Affairs (VA) versus non-VA hospitals have not been previously reported. METHODS AND RESULTS: In the randomized controlled Beta-blocker Evaluation of Survival Trial (BEST; 1995-1999), of the 2707 (bucindolol=1353; placebo=1354) patients with heart failure and left ventricular ejection fraction ≤35%, 918 received care at VA hospitals, of which 98% (n=898) were male. Of the 1789 receiving care at non-VA hospitals, 68% (n=1216) were male. Our analyses were restricted to these 2114 male patients. VA patients were older with higher symptom and comorbidity burdens. There was no significant between-group difference in unadjusted primary end point of 2-year all-cause mortality (35% VA versus 32% non-VA; hazard ratio associated with VA hospitals, 1.09; 95% confidence interval, 0.94-1.26), which remained unchanged after adjustment for age and race (hazard ratio, 1.00; 95% confidence interval, 0.86-1.16) or multivariable adjustment, including cardiovascular morbidities (hazard ratio, 0.94; 95% confidence interval, 0.80-1.10). There was no between-group difference in cause-specific mortalities or hospitalizations. Chronic kidney disease, pulmonary edema, left ventricular ejection fraction <20%, and peripheral arterial disease were significant predictors of mortality for both groups. African America race, New York Heart Association class IV symptoms, atrial fibrillation, and right ventricular ejection fraction <20% were associated with higher mortality among non-VA hospital patients only; however, these differences from VA patients were not significant. CONCLUSIONS: Patients with heart failure and reduced ejection fraction receiving care at VA hospitals were older and sicker; yet their risk of mortality and hospitalization was similar to younger and healthier patients receiving care at non-VA hospitals. CLINICAL TRIAL REGISTRATION URL: http://www.clinicaltrials.gov. Unique identifier: NCT00000560.

Medication management of chronic heart failure in older adults.

Heart failure (HF) is a common problem in older adults. Individuals aged 65 years or older are at a higher risk for developing HF, especially diastolic HF or HF with preserved ejection fraction (HFpEF). HF can be seen in up to 20 % of adults aged 85 years or older. In contrast to middle-aged (40-64 years) HF patients, multiple cardiac, non-cardiac and geriatric syndrome co-morbidities are seen in elderly HF patients. Additionally, age-related changes in pharmacokinetics and pharmacodynamics influence medication therapy. Hence, the management of older patients with HF is challenging and treatment should be modified in the light of the above-mentioned conditions. This article discusses the current evidence for medication management in both systolic HF or HF with reduced ejection fraction (HFrEF) and HFpEF, noting, however, the limited data for HFpEF and HFrEF in those 80 years of age or older. The objective of this article is to discuss evidence-based and outcomes-driven pharmacologic management strategies for chronic HF in the older adults for whom functional and other patient-centered outcomes might be more than or as important as clinical outcomes. Optimal management would be expected to help to reduce illness burden, reduce mortality and hospitalizations, and improve function and quality of life.

Update on diastolic heart failure or heart failure with preserved ejection fraction in the older adults.

Nearly half of all heart failure (HF) patients have diastolic HF (DHF) or clinical HF with normal or near-normal left ventricular ejection fraction (LVEF). Although the terminology has not been clearly defined, it is increasingly being referred to as HF with preserved ejection fraction (HFPEF). The prevalence of HFPEF increases with age, especially among older women. Identifying HFPEF is important because the etiology, pathogenesis, prognosis, and optimal management may differ from that for systolic HF (SHF) or HF with reduced ejection fraction. The clinical presentation of HF is similar for both SHF and HFPEF. As in SHF, HFPEF is a clinical diagnosis. Once a clinical diagnosis of HF has been made, the presence of HFPEF can be established by confirming a normal or near-normal LVEF, often by an echocardiogram. HFPEF is often associated with a history of hypertension, concentric left ventricular hypertrophy, vascular stiffness, and left ventricular diastolic dysfunction. As in SHF, HFPEF is also associated with poor outcomes. While therapies with angiotensin-converting enzyme inhibitors and beta-blockers improve outcomes in SHF, there is currently no such evidence of their benefits in older HFPEF patients. In this review recent advances in the diagnosis and management of HFPEF in older adults are discussed.

In-hospital cardiology consultation and evidence-based care for nursing home residents with heart failure.

OBJECTIVES: To determine the association between cardiology consultation and evidence-based care for nursing home (NH) residents with heart failure (HF). PARTICIPANTS: Hospitalized NH residents (n = 646) discharged from 106 Alabama hospitals with a primary discharge diagnosis of HF during 1998-2001. DESIGN: Observational. MEASUREMENTS OF EVIDENCE-BASED CARE: Preadmission estimation of left ventricular ejection fraction (LVEF) for patients with known HF (n = 494), in-hospital LVEF estimation for HF patients without known LVEF (n = 452), and discharge prescriptions of angiotensin-converting enzyme inhibitors or angiotensin receptor blockers (ACEIs or ARBs) to systolic HF (LVEF <45%) patients discharged alive who were eligible to receive those drugs (n = 83). Eligibility for ACEIs or ARBs was defined as lack of prior allergy or adverse effect, serum creatinine lower than 2.5 mg/dL, serum potassium lower than 5.5 mEq/L, and systolic blood pressure higher than 100 mm Hg. RESULTS: Preadmission LVEF was estimated in 38% and 12% of patients receiving and not receiving cardiology consultation, respectively (adjusted odds ratio [AOR], 3.49; 95% CI, 2.16-5.66; P < .001). In-hospital LVEF was estimated in 71% and 28% of patients receiving and not receiving cardiology consultation, respectively (AOR, 6.01; 95% CI, 3.69-9.79; P < .001). ACEIs or ARBs were prescribed to 62% and 82% of patients receiving and not receiving cardiology consultation, respectively (AOR, 0.24; 95% CI, 0.07-0.81; P = .022). CONCLUSION: In-hospital cardiology consultation was associated with significantly higher odds of LVEF estimation among NH residents with HF; however, it did not translate into higher odds of discharge prescriptions for ACEIs or ARBs to NH residents with systolic HF who were eligible for the receipt of these drugs.

Effect of warfarin on outcomes in septuagenarian patients with atrial fibrillation.

Anticoagulation has been shown to decrease ischemic stroke in atrial fibrillation (AF). However, concerns remain regarding their safety and efficacy in those ≥70 years of age who constitute most patients with AF. Of the 4,060 patients (mean age 65 years, range 49 to 80) in the Atrial Fibrillation Follow-up Investigation of Rhythm Management (AFFIRM) trial, 2,248 (55% of 4,060) were 70 to 80 years of age, 1,901 of whom were receiving warfarin. Propensity score for warfarin use, estimated for each of the 2,248 patients, was used to match 227 of the 347 patients not on warfarin (in 1:1, 1:2, or 1:3 sets) to 616 patients on warfarin who were balanced in 45 baseline characteristics. All-cause mortality occurred in 18% and 33% of matched patients receiving and not receiving warfarin, respectively, during up to 6 years (mean 3.4) of follow-up (hazard ratio [HR] when warfarin use was compared to its nonuse 0.58, 95% confidence interval [CI] 0.43 to 0.77, p <0.001). All-cause hospitalization occurred in 64% and 67% of matched patients receiving and not receiving warfarin, respectively (HR associated with warfarin use 0.93, 95% CI 0.77 to 1.12, p = 0.423). Ischemic stroke occurred in 4% and 8% of matched patients receiving and not receiving warfarin, respectively (HR associated with warfarin use 0.57, 95% CI 0.31 to 1.04, p = 0.068). Major bleeding occurred in 7% and 10% of matched patients receiving and not receiving warfarin, respectively (HR associated with warfarin use 0.73, 95% CI 0.44 to 1.22, p = 0.229). In conclusion, warfarin use was associated with decreased mortality in septuagenarian patients with AF but had no association with hospitalization or major bleeding.

Association between smoking and outcomes in older adults with atrial fibrillation.

Tobacco smoking is a risk factor for atrial fibrillation (AF), but little is known about the impact of smoking in patients with AF. Of the 4060 patients with recurrent AF in the Atrial Fibrillation Follow-up Investigation of Rhythm Management (AFFIRM) trial, 496 (12%) reported having smoked during the past two years. Propensity scores for smoking were estimated for each of the 4060 patients using a multivariable logistic regression model and were used to assemble a matched cohort of 487 pairs of smokers and nonsmokers, who were balanced on 46 baseline characteristics. Cox and logistic regression models were used to estimate the associations of smoking with all-cause mortality and all-cause hospitalization, respectively, during over 5 years of follow-up. Matched participants had a mean age of 70 ± 9 years (± S.D.), 39% were women, and 11% were non-white. All-cause mortality occurred in 21% and 16% of matched smokers and nonsmokers, respectively (when smokers were compared with nonsmokers, hazard ratio=HR=1.35; 95% confidence interval=95%CI=1.01-1.81; p=0.046). Unadjusted, multivariable-adjusted and propensity-adjusted HR (95% CI) for all-cause mortality associated with smoking in the pre-match cohort were: 1.40 (1.13-1.72; p=0.002), 1.45 (1.16-1.81; p=0.001), and 1.39 (1.12-1.74; p=0.003), respectively. Smoking had no association with all-cause hospitalization (when smokers were compared with nonsmokers, odds ratio=OR=1.21; 95%CI=0.94-1.57, p=0.146). Among patients with AF, a recent history of smoking was associated with an increased risk of all-cause mortality, but had no association with all-cause hospitalization.

Intrinsic association of widowhood with mortality in community-dwelling older women and men: findings from a prospective propensity-matched population study.

OBJECTIVES: Widowhood is associated with increased mortality. However, to what extent this association is independent of other risk factors remains unclear. In the current study, we used propensity score matching to design a study to examine the independent association of widowhood with outcomes in a balanced cohort of older adults in the United States. METHODS: We used public-use copies of the Cardiovascular Health Study data obtained from the National Heart, Lung, and Blood Institute. Of the 5,795 community-dwelling older men and women aged 65 years and older in Cardiovascular Health Study, 3,820 were married and 1,436 were widows or widowers. Propensity scores for widowhood, estimated for each of the 5,256 participants, were used to assemble a cohort of 819 pairs of widowed and married participants who were balanced on 74 baseline characteristics. The 1,638 matched participants had a mean (± standard deviation) age of 75 (± 6) years, 78% were women, and 16% African American. RESULTS: All-cause mortality occurred in 46% (374/819) and 51% (415/819) of matched married and widowed participants, respectively, during more than 11 years of median follow-up (hazard ratio associated with widowhood, 1.18; 95% confidence interval, 1.03-1.36; p = .018). Hazard ratios (95% confidence intervals) for cardiovascular and noncardiovascular mortalities were 1.07 (0.87-1.32; p = .517) and 1.28 (1.06-1.55; p = .011), respectively. Widowhood had no independent association with all-cause or heart failure hospitalization or incident cardiovascular events. CONCLUSIONS: Among community-dwelling older adults, widowhood was associated with increased mortality, which was independent of confounding by baseline characteristics and largely driven by an increased noncardiovascular mortality. Widowhood had no independent association with hospitalizations or incident cardiovascular events.

Understanding the reasons for the underuse of pneumococcal vaccination by community-dwelling older African Americans.

OBJECTIVES: To understand the potential roles of various patient and provider factors in the underuse of pneumococcal vaccination in Medicare-eligible older African Americans. DESIGN: The Cardiovascular Health Study. SETTING: Four U.S. states. PARTICIPANTS: Seven hundred ninety-five pairs of community-dwelling Medicare-eligible African-American and white adults aged 65 and older, balanced according to age and sex. MEASUREMENTS: Data on self-reported race, receipt of pneumococcal vaccination, and other important sociodemographic and clinical variables were collected at baseline. RESULTS: Participants had a mean age ± standard deviation of 73 ± 6; 63% were female. Pneumococcal vaccination rates were 22% for African Americans and 28% for whites (unadjusted odds ratios (OR) for African Americans=0.75; 95% confidence interval (CI)=0.60-0.94; P=.01). This association remained significant despite adjustment for sociodemographic and clinical confounders, including education, income, chronic obstructive pulmonary disease, and prior pneumonia (OR=0.74, 95% CI=0.56-0.97; P=.03), but the association was no longer significant after additional adjustment for the receipt of influenza vaccination (OR=0.79, 95% CI=0.59-1.06; P=.12). Receipt of influenza vaccination was associated with higher odds of receiving pneumococcal vaccination (unadjusted OR=6.43, 95% CI=5.00-8.28; P<.001), and the association between race and pneumococcal vaccination lost significance when adjusted for influenza vaccination alone (OR=0.81, 95% CI=0.63-1.03; P=.09). CONCLUSION: The strong association between receipt of influenza and pneumococcal vaccinations suggests that patient and provider attitudes toward vaccination, rather than traditional confounders such as education and income, may help explain the underuse of pneumococcal vaccination in older African Americans.

Lead exposure during development results in increased neurofilament phosphorylation, neuritic beading, and temporal processing deficits within the murine auditory brainstem.

Low-level lead (Pb) exposure is a risk factor for learning disabilities, attention deficit hyperactivity disorder (ADHD), and other neurological dysfunction. It is not known how Pb produces these behavioral deficits, but low-level exposure during development is associated with auditory temporal processing deficits in an avian model, while hearing thresholds remain normal. Similar auditory processing deficits are found in children with learning disabilities and ADHD. To identify cellular changes underlying this functional deficit, Pb-induced alterations of neurons and glia within the mammalian auditory brainstem nuclei were quantified in control and Pb-exposed mice at postnatal day 21 by using immunohistochemistry, Western blotting, and 2D gel electrophoresis. Pb-treated mice were exposed to either 0.1 mM (low) or 2 mM (high) Pb acetate throughout gestation and through 21 days postnatally. Pb exposure results in little change in glial proteins such as glial fibrillary acidic protein (GFAP), myelin basic protein (MBP), or F4/80 as determined by Western blot analysis and immunohistochemistry. In contrast, Pb exposure alters neuronal structural proteins by inducing increased phosphorylation of both the medium (NFM) and high-weight (NFH) forms of neurofilament within auditory brainstem nuclei. Axons immunolabeled for neurofilament protein show neuritic beading following Pb exposure both in vivo and in vitro, suggesting that Pb exposure also impairs axonal transport. Functional assessment shows no significant loss of peripheral function, but does reveal impairments in brainstem conduction time and temporal processing within the brainstem. These results provide evidence that Pb exposure during development alters axonal structure and function within brainstem auditory nuclei.

An Arabidopsis histidine kinase is essential for megagametogenesis.

Cytokinin-Independent 1 (CKI1) belongs to a group of putative plant histidine kinases whose members do not appear to act as ethylene receptors. The deduced protein structure, combined with the observation that Arabidopsis callus cultures overexpressing CKI1 exhibit a "cytokinin-independent" cell division and greening phenotype, led to the hypothesis that CKI1 is involved in cytokinin signaling, perhaps acting as a cytokinin receptor. To test the function of CKI1, we used a reverse-genetic approach to identify plants carrying T-DNA insertions in CKI1. Two independent alleles were identified, which produce the same developmental phenotype. Analyses of populations segregating for the cki1-5 or cki1-6 T-DNA insertion alleles failed to reveal any homozygous cki1 plants, indicating that the homozygous mutant condition was lethal. Based on segregation distortion, transmission studies, a microscopy-based examination of developing female gametophytes, and mRNA expression data, we suggest that CKI1 function is required for megagametophyte development. Our work with CKI1 mutants indicates that signal transduction by means of a HisAsp phosphorelay system may play an important and previously unsuspected role in female gametophyte development in Arabidopsis.

Mitochondrial GFA2 is required for synergid cell death in Arabidopsis.

Little is known about the molecular processes that govern female gametophyte (FG) development and function, and few FG-expressed genes have been identified. We report the identification and phenotypic analysis of 31 new FG mutants in Arabidopsis. These mutants have defects throughout development, indicating that FG-expressed genes govern essentially every step of FG development. To identify genes involved in cell death during FG development, we analyzed this mutant collection for lines with cell death defects. From this analysis, we identified one mutant, gfa2, with a defect in synergid cell death. Additionally, the gfa2 mutant has a defect in fusion of the polar nuclei. We isolated the GFA2 gene and show that it encodes a J-domain-containing protein. Of the J-domain-containing proteins in Saccharomyces cerevisiae (budding yeast), GFA2 is most similar to Mdj1p, which functions as a chaperone in the mitochondrial matrix. GFA2 is targeted to mitochondria in Arabidopsis and partially complements a yeast mdj1 mutant, suggesting that GFA2 is the Arabidopsis ortholog of yeast Mdj1p. These data suggest a role for mitochondria in cell death in plants.