Older patients with acute decompensated heart failure (ADHF) have persistently poor outcomes including frequent rehospitalization despite guidelines-based therapy. We hypothesized that such patients ...have multiple, severe impairments in physical function, cognition, and mood that are not addressed by current care pathways. We prospectively examined frailty, physical function, cognition, mood, and quality of life in 27 consecutive older patients with ADHF at 3 medical centers and compared these with 197 participants in 3 age-matched cohorts: stable heart failure (HF) with preserved ejection fraction (n = 80), stable HF with reduced ejection fraction (n = 56), and healthy older adults (n = 61). Based on Fried criteria, frailty was present in 56% of patients with ADHF versus 0 for the age-matched chronic HF and health cohorts. Patients with ADHF had markedly reduced Short Physical Performance Battery score (5.3 ± 2.8) and 6-minute walk distance (178 ± 102 m) (p <0.001 vs other cohorts), with severe deficits in all domains of physical function: balance, mobility, strength, and endurance. In the patients with ADHF, cognitive impairment (78%) and depression (30%) were common, and quality of life was poor. In conclusion, older patients with ADHF are frequently frail with severe and widespread impairments in physical function, cognition, mood, and quality of life that may contribute to their persistently poor outcomes, are frequently unrecognized, are not addressed in current ADHF care paradigms, and are potentially modifiable with targeted interventions.
Exercise intolerance is the primary symptom in patients with heart failure and preserved ejection fraction (HFpEF), a major determinant of their decreased quality of life, and an important outcome in ...clinical trials. Although cardiopulmonary exercise testing (CPET) provides peak and submaximal diagnostic indexes, the reliability of peak treadmill CPET in patients >55 years of age with HFpEF has not been examined. Two CPETs were performed in 52 patients with HFpEF (70 ± 7 years old). The 2 tests were separated by an average of 23 ± 13 days (median 22) and performed under identical conditions, with no intervention or change in status between visits except for initiation of a placebo run-in. A multistep protocol for patient screening, education, and quality control was used. Mean peak oxygen consumption was similar on tests 1 and 2 (14.4 ± 2.4 vs 14.3 ± 2.3 ml/kg/min). Correlation coefficients and intraclass correlations from the testing days were determined (oxygen consumption, r = 0.85, p <0.001, intraclass correlation 0.855; ventilatory anaerobic threshold, r = 0.79, p <0.001, intraclass correlation 0.790; ventilation per carbon dioxide slope, r = 0.87, p <0.001, intraclass correlation 0.864; heart rate, r = 0.94, p <0.001, intraclass correlation 0.938). These results challenge conventional wisdom that serial baseline testing is required in clinical trials with exercise-capacity outcomes. In conclusion, in women and men with HFpEF and severe physical dysfunction, key submaximal and peak ET variables exhibited good reliability and were not significantly altered by a learning effect or placebo administration.
Objectives The purpose of this study was to determine the mechanisms responsible for reduced aerobic capacity (peak V o2 ) in patients with heart failure with preserved ejection fraction (HFPEF). ...Background HFPEF is the predominant form of heart failure in older persons. Exercise intolerance is the primary symptom among patients with HFPEF and a major determinant of reduced quality of life. In contrast to patients with heart failure and reduced ejection fraction, the mechanism of exercise intolerance in HFPEF is less well understood. Methods Left ventricular volumes (2-dimensional echocardiography), cardiac output, V o2 , and calculated arterial-venous oxygen content difference (A-V o2 Diff) were measured at rest and during incremental, exhaustive upright cycle exercise in 48 HFPEF patients (age 69 ± 6 years) and 25 healthy age-matched controls. Results In HFPEF patients compared with healthy controls, V o2 was reduced at peak exercise (14.3 ± 0.5 ml·kg·min−1 vs. 20.4 ± 0.6 ml·kg·min−1 ; p < 0.0001) and was associated with a reduced peak cardiac output (6.3 ± 0.2 l·min−1 vs. 7.6 ± 0.2 l·min−1 ; p < 0.0001) and A-V o2 Diff (17 ± 0.4 ml·dl−1 vs. 19 ± 0.4 ml·dl−1 , p < 0.0007). The strongest independent predictor of peak V o2 was the change in A-V o2 Diff from rest to peak exercise (A-V o2 Diff reserve) for both HFPEF patients (partial correlate, 0.58; standardized β coefficient, 0.66; p = 0.0002) and healthy controls (partial correlate, 0.61; standardized β coefficient, 0.41; p = 0.005). Conclusions Both reduced cardiac output and A-V o2 Diff contribute significantly to the severe exercise intolerance in elderly HFPEF patients. The finding that A-V o2 Diff reserve is an independent predictor of peak V o2 suggests that peripheral, noncardiac factors are important contributors to exercise intolerance in these patients.
Objectives The purpose of this study was to evaluate the mechanisms for improved exercise capacity after endurance exercise training (ET) in elderly patients with heart failure and preserved ejection ...fraction (HFPEF). Background Exercise intolerance, measured objectively by reduced peak oxygen consumption (VO2 ), is the primary chronic symptom in HFPEF and is improved by ET. However, the mechanisms are unknown. Methods Forty stable, compensated HFPEF outpatients (mean age 69 ± 6 years) were examined at baseline and after 4 months of ET (n = 22) or attention control (n = 18). The VO2 and its determinants were assessed during rest and peak upright cycle exercise. Results After ET, peak VO2 in those patients was higher than in control patients (16.3 ± 2.6 ml/kg/min vs. 13.1 ± 3.4 ml/kg/min; p = 0.002). That was associated with higher peak heart rate (139 ± 16 beats/min vs. 131 ± 20 beats/min; p = 0.03), but no difference in peak end-diastolic volume (77 ± 18 ml vs. 77 ± 17 ml; p = 0.51), stroke volume (48 ± 9 ml vs. 46 ± 9 ml; p = 0.83), or cardiac output (6.6 ± 1.3 l/min vs. 5.9 ± 1.5 l/min; p = 0.32). However, estimated peak arterial-venous oxygen difference was significantly higher in ET patients (19.8 ± 4.0 ml/dl vs. 17.3 ± 3.7 ml/dl; p = 0.03). The effect of ET on cardiac output was responsible for only 16% of the improvement in peak VO2. Conclusions In elderly stable compensated HFPEF patients, peak arterial-venous oxygen difference was higher after ET and was the primary contributor to improved peak VO2 . This finding suggests that peripheral mechanisms (improved microvascular and/or skeletal muscle function) contribute to the improved exercise capacity after ET in HFPEF. (Prospective Aerobic Reconditioning Intervention Study PARIS; NCT01113840 )
Abstract Objectives This study sought to determine whether a relatively low single dose or a week-long dosage of dietary inorganic nitrate could improve exercise tolerance in patients with heart ...failure with preserved ejection fraction (HFpEF). Background Exercise intolerance is the primary manifestation of HFpEF and is largely due to noncardiac factors that reduce oxygen delivery to active skeletal muscles. A recent study showed improved exercise capacity in patients with HFpEF after a single, acute dose of beetroot juice (BRJ) (12.9 mmol inorganic nitrate) while another recent study showed neutral and negative effects of an organic nitrate. Methods Twenty HFpEF patients (69 ± 7 years of age ) were enrolled in an initial cross-over design comparing a single, acute dose of BRJ (6.1 mmol nitrate) to a nitrate-depleted placebo BRJ. A second phase, 1 week of daily doses, used an all-treated design in which patients consumed BRJ for an average of 7 days. The primary outcome of the study was submaximal aerobic endurance, measured as cycling time to exhaustion at 75% of measured maximal power output. Results No adverse events were associated with the intervention. Submaximal aerobic endurance improved 24% after 1 week of daily BRJ dosing (p = 0.02) but was not affected by the single, acute dose of the BRJ compared to placebo. Consumption of BRJ significantly reduced resting systolic blood pressure and increased plasma nitrate and nitrite in both of the dosing schemes. Conclusions One week of daily dosing with BRJ (6.1 mmol inorganic nitrate) significantly improves submaximal aerobic endurance and blood pressure in elderly HFpEF patients.
Objective To examine the longitudinal associations between sex, diabetes self-care, and the health-related quality of life (HRQL) of children and adolescents with type 1 or type 2 diabetes. Study ...design The sample included 910 participants with type 1 and 241 participants with type 2, ages 10-22 years at baseline, from the SEARCH for Diabetes in Youth Study, a longitudinal observational study. The primary outcome measure was the Pediatric Quality of Life Inventory. Repeated measures, mixed-model regression analysis was conducted with the use of data from baseline and at least one follow-up assessment, spanning approximately 4 years. Results HRQL was greater among those with type 1 versus type 2 diabetes. Among participants with type 1, greater (better) Pediatric Quality of Life Inventory total scores over time were related to greater parent education ( P = .0007), lower glycated hemoglobin values ( P < .0001), and greater physical activity during the past 7 days ( P = .0001). There was a significant interaction between sex and age ( P < .0001); girls' HRQL remained stable or decreased over time, whereas males' HRQL increased. For participants with type 2 diabetes, there was no significant interaction by age and sex, but lower total HRQL was related to being female ( P = .011) and greater body mass index z-scores ( P = .014). Conclusions HRQL in this cohort varied by diabetes type. The interaction between sex and age for type 1 participants, coupled with poorer HRQL among female than male participants with type 2 diabetes, suggests the impacts of diabetes on HRQL differ by sex and should be considered in clinical management. Encouraging physical activity and weight control continue to be important in improving HRQL.
The Healthy Living Partnerships to Prevent Diabetes Study Katula, Jeffrey A., PhD, MA; Vitolins, Mara Z., DrPH; Morgan, Timothy M., PhD ...
American journal of preventive medicine,
April 2013, Letnik:
44, Številka:
4
Journal Article
Recenzirano
Odprti dostop
Background Since the Diabetes Prevention Project (DPP) demonstrated that lifestyle weight-loss interventions can reduce the incidence of diabetes by 58%, several studies have translated the DPP ...methods to public health−friendly contexts. Although these studies have demonstrated short-term effects, no study to date has examined the impact of a translated DPP intervention on blood glucose and adiposity beyond 12 months of follow-up. Purpose To examine the impact of a 24-month, community-based diabetes prevention program on fasting blood glucose, insulin, insulin resistance as well as body weight, waist circumference, and BMI in the second year of follow-up. Design An RCT comparing a 24-month lifestyle weight-loss program (LWL) to an enhanced usual care condition (UCC) in participants with prediabetes (fasting blood glucose=95−125 mg/dL). Data were collected in 2007−2011; analyses were conducted in 2011−2012. Setting/participants 301 participants with prediabetes were randomized; 261 completed the study. The intervention was held in community-based sites. Intervention The LWL program was led by community health workers and sought to induce 7% weight loss at 6 months that would be maintained over time through decreased caloric intake and increased physical activity. The UCC received two visits with a registered dietitian and a monthly newsletter. Main outcome measures The main measures were fasting blood glucose, insulin, insulin resistance, body weight, waist circumference, and BMI. Results Intent-to-treat analyses of between-group differences in the average of 18- and 24-month measures of outcomes (controlling for baseline values) revealed that the LWL participants experienced greater decreases in fasting glucose (−4.35 mg/dL); insulin (−3.01 μU/ml); insulin resistance (−0.97); body weight (−4.19 kg); waist circumference (−3.23 cm); and BMI (−1.40), all p -values <0.01. Conclusions A diabetes prevention program administered through an existing community-based system and delivered by community health workers is effective at inducing significant long-term reductions in metabolic indicators and adiposity. Trial registration This study is registered at Clinicaltrials.gov NCT00631345.
Background Specific immunotherapy (SIT) is the only treatment with proved long-term curative potential in patients with allergic disease. Allergen-specific IgE is the causative agent of allergic ...disease, and antibodies contribute to SIT, but the effects of SIT on aeroallergen-specific B-cell repertoires are not well understood. Objective We sought to characterize the IgE sequences expressed by allergen-specific B cells and track the fate of these B-cell clones during SIT. Methods We used high-throughput antibody gene sequencing and identification of allergen-specific IgE with combinatorial antibody fragment library technology to analyze immunoglobulin repertoires of blood and the nasal mucosa from aeroallergen-sensitized subjects before and during the first year of subcutaneous SIT. Results Of 52 distinct allergen-specific IgE heavy chains from 8 allergic donors, 37 were also detected by using high-throughput antibody gene sequencing of blood samples, nasal mucosal samples, or both. The allergen-specific clones had increased persistence, higher likelihood of belonging to clones expressing other switched isotypes, and possibly larger clone size than the rest of the IgE repertoire. Clone members in nasal tissue showed close mutational relationships. Conclusion In the future, combining functional binding studies, deep antibody repertoire sequencing, and information on clinical outcomes in larger studies might aid assessment of SIT mechanisms and efficacy.
Background Although numerous studies have translated the Diabetes Prevention Program lifestyle intervention into various settings, no study to date has reported a formal cost analysis. Purpose To ...describe costs associated with the Healthy Living Partnerships to Prevent Diabetes (HELP PD) trial. Design HELP PD was a 24-month RCT testing the impact of a lifestyle weight-loss intervention administered through a diabetes education program and delivered by community health workers (CHWs) on blood glucose and body weight among prediabetics. Setting/participants In all, 301 participants with prediabetes were randomized in Forsyth County NC. Data reported in these analyses were collected in 2007–2011 and analyzed in 2011–2012. Intervention The lifestyle weight-loss group had a 7% weight loss goal achieved and maintained by caloric restriction and increased physical activity. The usual care group received two visits with a registered dietitian and monthly newsletters. Main outcome measures Measures are direct medical costs, direct nonmedical costs, and indirect costs over the 2-year study period. Research costs are excluded. Results The direct medical cost (in 2010 dollars) to identify one participant was $16.85. Direct medical costs per capita for participants in the usual care group were $142 and $850 for lifestyle weight-loss participants. Per capita direct costs of care outside the study were $7454 for the usual care group and $5177 for the lifestyle weight-loss group. Per capita direct nonmedical costs were $12,881 for the usual care group and $13,836 for the lifestyle weight-loss group. The lifestyle weight-loss group in HELP PD cost $850 in direct medical costs for 2 years, compared to $2631 in direct medical costs for the first 2 years of DPP. Conclusions A community-based translation of the DPP can be delivered effectively and with reduced costs. Trial registration This study is registered at clinicaltrials.gov NCT00631345.
Atrial fibrillation (AF) is prevalent in patients with type 2 diabetes mellitus (DM) and is associated with markers of poor glycemic control; however, the impact of glycemic control on incident AF ...and outcomes is unknown. The aims of this study were to prospectively evaluate if intensive glycemic control in patients with DM affects incident AF and to evaluate morbidity and mortality in patients with DM and incident AF. A total of 10,082 patients with DM from the Action to Control Cardiovascular Risk in Diabetes (ACCORD) cohort were studied in a randomized, double-blind fashion. Participants were randomized to an intensive therapeutic strategy targeting a glycated hemoglobin level of <6.0% or a standard strategy targeting a glycated hemoglobin level of 7.0% to 7.9%. Incident AF occurred in 159 patients (1.58%) over the follow-up period, at a rate of 5.9 per 1,000 patient-years in the intensive-therapy group and a rate of 6.37 per 1,000 patient-years in the standard-therapy group (p = 0.52). In a multivariate model, predictors of incident AF were age, weight, diastolic blood pressure, heart rate, and heart failure history. Patients with DM and new-onset AF had a hazard ratio of 2.65 for all-cause mortality (95% confidence interval 1.8 to 3.86, p <0.0001), a hazard ratio of 2.1 for myocardial infarction (95% confidence interval 1.33 to 3.31, p = 0.0015), and a hazard ratio of 3.80 for the development of heart failure (95% confidence interval 2.48 to 5.84, p <0.0001). In conclusion, intensive glycemic control did not affect the rate of new-onset AF. Patients with DM and incident AF had an increased risk for morbidity and mortality compared with those without AF.
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