Dataset Information

Predictors of development of diabetes in patients with chronic heart failure in the Candesartan in Heart Failure Assessment of Reduction in Mortality and Morbidity (CHARM) program.

ABSTRACT: The purpose of this study was to identify predictors of incident diabetes during follow-up of nondiabetic patients with chronic heart failure (CHF) in the Candesartan in Heart Failure Assessment of Reduction in Mortality and Morbidity (CHARM) program.A total of 1,620 nondiabetic patients had full baseline datasets. We compared baseline demographic, medication, and laboratory data for patients who did or did not develop diabetes and conducted logistic regression and receiver operator characteristic curve analyses.Over a median period of 2.8 years, 126 of the 1,620 patients (7.8%) developed diabetes. In multiple logistic regression analysis, the following baseline characteristics were independently associated with incident diabetes in decreasing order of significance by stepwise selection: higher A1C (odds ratio [OR] 1.78 per 1 SD increase; P < 0.0001), higher BMI (OR 1.64 per 1 SD increase; P < 0.0001), lipid-lowering therapy (OR 2.05; P = 0.0005), lower serum creatinine concentration (OR 0.68 per 1 SD increase; P = 0.0018), diuretic therapy (OR 4.81; P = 0.003), digoxin therapy (OR 1.65; P = 0.022), higher serum alanine aminotransferase concentration (OR 1.15 per 1 SD increase; P = 0.027), and lower age (OR 0.81 per 1 SD increase; P = 0.048). Using receiver operating characteristic curve analysis, A1C and BMI yielded areas under the curve of 0.723 and 0.712, respectively, increasing to 0.788 when combined. Addition of other variables independently associated with diabetes risk minimally improved prediction of diabetes.In nondiabetic patients with CHF in CHARM, A1C and BMI were the strongest predictors of the development of diabetes. Other minor predictors in part reflected CHF severity or drug-associated diabetes risk. Identifying patients with CHF at risk of diabetes through simple criteria appears possible and could enable targeted preventative measures.

SUBMITTER: Preiss D

PROVIDER: S-EPMC2671104 | biostudies-literature | 2009 May

REPOSITORIES: biostudies-literature

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Predictors of development of diabetes in patients with chronic heart failure in the Candesartan in Heart Failure Assessment of Reduction in Mortality and Morbidity (CHARM) program.

Preiss David D Zetterstrand Sofia S McMurray John J V JJ Ostergren Jan J Michelson Eric L EL Granger Christopher B CB Yusuf Salim S Swedberg Karl K Pfeffer Marc A MA Gerstein Hertzel C HC Sattar Naveed N

Diabetes care 20090205 5

<h4>Objective</h4>The purpose of this study was to identify predictors of incident diabetes during follow-up of nondiabetic patients with chronic heart failure (CHF) in the Candesartan in Heart Failure Assessment of Reduction in Mortality and Morbidity (CHARM) program.<h4>Research design and methods</h4>A total of 1,620 nondiabetic patients had full baseline datasets. We compared baseline demographic, medication, and laboratory data for patients who did or did not develop diabetes and conducted ...[more]

PMID: 19196892

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Project description:AimsThe Candesartan in Heart failure Assessment of Reduction in Mortality and morbidity (CHARM) programme consisted of three parallel, randomized, double-blind clinical trials comparing candesartan with placebo in patients with heart failure (HF) categorized according to left ventricular ejection fraction and tolerability to an angiotensin-converting enzyme inhibitor. We conducted a pharmacogenomic study of the CHARM trials with the objective of identifying genetic predictors of HF progression and of the efficacy and safety of treatment with candesartan.MethodsWe performed genome-wide association studies in 2727 patients of European ancestry from CHARM-Overall and stratified by CHARM study according to preserved and reduced ejection fraction and according to assignment to the interventional treatment with candesartan. We tested genetic association with the composite endpoint of cardiovascular death or hospitalization for heart failure for drug efficacy in candesartan-treated patients and for HF progression using patients from both candesartan and placebo arms. The safety endpoints for response to candesartan were hyperkalaemia, renal dysfunction, hypotension, and change in systolic blood pressure between baseline and 6 weeks of treatment. To support our observations, we conducted a genome-wide gene-level collapsing analysis from whole-exome sequencing data with the composite cardiovascular endpoint.ResultsWe found that the A allele (14% allele frequency) of the genetic variant rs66886237 at 8p21.3 near the gene GFRA2 was associated with the composite cardiovascular endpoint in 1029 HF patients with preserved ejection fraction from the CHARM-Preserved study (hazard ratio: 1.91, 95% confidence interval: 1.55-2.35; P = 1.7 × 10-9 ). The association was independent of candesartan treatment, and the genetic variant was not associated with the cardiovascular endpoint in patients with reduced ejection fraction. None of the genome-wide association studies for candesartan safety or efficacy conducted in patients treated with candesartan passed the significance threshold. We found no significant association from the gene-level collapsing analysis.ConclusionsWe have identified a candidate genetic variant potentially predictive of the progression of heart failure in patients with preserved ejection fraction. The findings require further replication, and we cannot exclude the possibility that the results may be chance findings.

Project description:ImportancePublic reporting of hospitals' 30-day risk-standardized readmission rates following heart failure hospitalization and the financial penalization of hospitals with higher rates have been associated with a reduction in 30-day readmissions but have raised concerns regarding the potential for unintended consequences.ObjectiveTo examine the association of the Hospital Readmissions Reduction Program (HRRP) with readmission and mortality outcomes among patients hospitalized with heart failure within a prospective clinical registry that allows for detailed risk adjustment.Design, setting, and participantsInterrupted time-series and survival analyses of index heart failure hospitalizations were conducted from January 1, 2006, to December 31, 2014. This study included 115 245 fee-for-service Medicare beneficiaries across 416 US hospital sites participating in the American Heart Association Get With The Guidelines-Heart Failure registry. Data analysis took place from January 1, 2017, to June 8, 2017.ExposuresTime intervals related to the HRRP were before the HRRP implementation (January 1, 2006, to March 31, 2010), during the HRRP implementation (April 1, 2010, to September 30, 2012), and after the HRRP penalties went into effect (October 1, 2012, to December 31, 2014).Main outcomes and measuresRisk-adjusted 30-day and 1-year all-cause readmission and mortality rates.ResultsThe mean (SD) age of the study population (n = 115 245) was 80.5 (8.4) years, 62 927 (54.6%) were women, and 91 996 (81.3%) were white and 11 037 (9.7%) were black. The 30-day risk-adjusted readmission rate declined from 20.0% before the HRRP implementation to 18.4% in the HRRP penalties phase (hazard ratio (HR) after vs before the HRRP implementation, 0.91; 95% CI, 0.87-0.95; P < .001). In contrast, the 30-day risk-adjusted mortality rate increased from 7.2% before the HRRP implementation to 8.6% in the HRRP penalties phase (HR after vs before the HRRP implementation, 1.18; 95% CI, 1.10-1.27; P < .001). The 1-year risk-adjusted readmission and mortality rates followed a similar pattern as the 30-day outcomes. The 1-year risk-adjusted readmission rate declined from 57.2% to 56.3% (HR, 0.92; 95% CI, 0.89-0.96; P < .001), and the 1-year risk-adjusted mortality rate increased from 31.3% to 36.3% (HR, 1.10; 95% CI, 1.06-1.14; P < .001) after vs before the HRRP implementation.Conclusions and relevanceAmong fee-for-service Medicare beneficiaries discharged after heart failure hospitalizations, implementation of the HRRP was temporally associated with a reduction in 30-day and 1-year readmissions but an increase in 30-day and 1-year mortality. If confirmed, this finding may require reconsideration of the HRRP in heart failure.

Project description:ImportanceThe US Hospital Readmissions Reduction Program (HRRP) was associated with reduced readmissions among Medicare beneficiaries hospitalized for acute myocardial infarction (AMI), heart failure (HF), and pneumonia. It is important to assess whether there has been a signal for concomitant harm with an increase in mortality.ObjectiveTo evaluate whether the announcement or the implementation of HRRP was associated with an increase in either in-hospital or 30-day postdischarge mortality following hospitalization for AMI, HF, or pneumonia.Design, setting, and participantsIn this cohort study, using Medicare data, all hospitalizations for AMI, HF, and pneumonia were identified among fee-for-service Medicare beneficiaries aged 65 years and older from January 1, 2006, to December 31, 2014. These were assessed for changes in trends for risk-adjusted rates of in-hospital and 30-day postdischarge mortality after announcement and implementation of the HRRP using an interrupted time series framework. Analyses were done in November 2017 and December 2017.ExposuresAnnouncement of the HRRP in March 2010, and implementation of its penalties in October 2012.Main outcomes and measuresMonthly risk-adjusted rates of in-hospital and 30-day postdischarge mortality.ResultsThe sample included 1.7 million AMI, 4 million HF, and 3.5 million pneumonia hospitalizations. Between 2006 and 2014, in-hospital mortality decreased for the 3 conditions (AMI, from 10.4% to 9.7%; HF, from 4.3% to 3.5%; pneumonia, from 5.3% to 4.0%) while 30-day postdischarge mortality decreased from 7.4% to 7.0% for AMI (P for trend < .001), but increased from 7.4% to 9.2% for HF (P for trend < .001) and from 7.6% to 8.6% for pneumonia (P for trend < .001). Before the HRRP announcement, monthly postdischarge mortality was stable for AMI (slope for monthly change, 0.002%; 95% CI, -0.001% to 0.006% per month), and increased by 0.004% (95% CI, 0.000% to 0.007%) per month for HF and by 0.005% (95% CI, 0.002% to 0.008%) per month for pneumonia. There were no inflections in slope around HRRP announcement or implementation (P > .05 for all). In contrast, there were significant negative deflections in slopes for readmission rates at HRRP announcement for all conditions.Conclusions and relevanceAmong Medicare beneficiaries, there was no evidence for an increase in in-hospital or postdischarge mortality associated with HRRP announcement or implementation-a period with substantial reductions in readmissions. The improvement in readmission was therefore not associated with any increase in in-hospital or 30-day postdischarge mortality.

Project description:ImportanceThe Hospital Readmissions Reduction Program (HRRP) has been associated with a reduction in readmission rates for heart failure (HF), acute myocardial infarction (AMI), and pneumonia. It is unclear whether the HRRP has been associated with change in patient mortality.ObjectiveTo determine whether the HRRP was associated with a change in patient mortality.Design, setting, and participantsRetrospective cohort study of hospitalizations for HF, AMI, and pneumonia among Medicare fee-for-service beneficiaries aged at least 65 years across 4 periods from April 1, 2005, to March 31, 2015. Period 1 and period 2 occurred before the HRRP to establish baseline trends (April 2005-September 2007 and October 2007-March 2010). Period 3 and period 4 were after HRRP announcement (April 2010 to September 2012) and HRRP implementation (October 2012 to March 2015).ExposuresAnnouncement and implementation of the HRRP.Main outcomes and measuresInverse probability-weighted mortality within 30 days of discharge following hospitalization for HF, AMI, and pneumonia, and stratified by whether there was an associated readmission. An additional end point was mortality within 45 days of initial hospital admission for target conditions.ResultsThe study cohort included 8.3 million hospitalizations for HF, AMI, and pneumonia, among which 7.9 million (mean age, 79.6 [8.7] years; 53.4% women) were alive at discharge. There were 3.2 million hospitalizations for HF, 1.8 million for AMI, and 3.0 million for pneumonia. There were 270 517 deaths within 30 days of discharge for HF, 128 088 for AMI, and 246 154 for pneumonia. Among patients with HF, 30-day postdischarge mortality increased before the announcement of the HRRP (0.27% increase from period 1 to period 2). Compared with this baseline trend, HRRP announcement (0.49% increase from period 2 to period 3; difference in change, 0.22%, P = .01) and implementation (0.52% increase from period 3 to period 4; difference in change, 0.25%, P = .001) were significantly associated with an increase in postdischarge mortality. Among patients with AMI, HRRP announcement was associated with a decline in postdischarge mortality (0.18% pre-HRRP increase vs 0.08% post-HRRP announcement decrease; difference in change, -0.26%; P = .01) and did not significantly change after HRRP implementation. Among patients with pneumonia, postdischarge mortality was stable before HRRP (0.04% increase from period 1 to period 2), but significantly increased after HRRP announcement (0.26% post-HRRP announcement increase; difference in change, 0.22%, P = .01) and implementation (0.44% post-HPPR implementation increase; difference in change, 0.40%, P < .001). The overall increase in mortality among patients with HF and pneumonia was mainly related to outcomes among patients who were not readmitted but died within 30 days of discharge. For all 3 conditions, HRRP implementation was not significantly associated with an increase in mortality within 45 days of admission, relative to pre-HRRP trends.Conclusions and relevanceAmong Medicare beneficiaries, the HRRP was significantly associated with an increase in 30-day postdischarge mortality after hospitalization for HF and pneumonia, but not for AMI. Given the study design and the lack of significant association of the HRRP with mortality within 45 days of admission, further research is needed to understand whether the increase in 30-day postdischarge mortality is a result of the policy.

Dataset Information

Predictors of development of diabetes in patients with chronic heart failure in the Candesartan in Heart Failure Assessment of Reduction in Mortality and Morbidity (CHARM) program.

Publications

Predictors of development of diabetes in patients with chronic heart failure in the Candesartan in Heart Failure Assessment of Reduction in Mortality and Morbidity (CHARM) program.

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