| 1. |
- Pocock, S. J., et al.
(författare)
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Weight loss and mortality risk in patients with chronic heart failure in the candesartan in heart failure: assessment of reduction in mortality and morbidity (CHARM) programme
- 2008
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Ingår i: European Heart Journal. - : Oxford University Press (OUP). - 1522-9645 .- 0195-668X. ; 29:21, s. 2641-50
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Tidskriftsartikel (refereegranskat)abstract
- AIMS: The curiosity that leanness is associated with poor survival in patients with chronic heart failure (CHF) needs further insight by investigating the impact of weight loss on prognosis in a large sample of patients across a broad spectrum of both reduced and preserved left ventricular (LV) systolic function. METHODS AND RESULTS: We investigated the change in weight over 6 months in 6933 patients in the Candesartan in Heart failure: Reduction in Mortality and morbidity (CHARM) programme, and its association with subsequent mortality (1435 deaths) over a median 32.9 months follow-up using Cox proportional hazard models to account for the impact of body mass index and other risk predictors. We then used time-updated Cox models to relate each patient's ongoing data on annual weight change to their mortality hazard. The percentage weight loss over 6 months had a highly significant monotonically increasing association with excess mortality, both for cardiovascular and for other causes of death. Patients with 5% or greater weight loss in 6 months had over a 50% increase in hazard compared with those with stable weight. Weight loss carried a particularly high risk in patients who were already lean at study entry. Findings were similar in the presence of dependent oedema, preserved or reduced LV ejection fraction, and treatment with candesartan, although weight loss was significantly less common on candesartan. The time-updated analyses revealed an even stronger link between weight loss and short-term risk of dying, i.e. risk increased more than four-fold for patients whose last recorded annual weight loss exceeded 10%. Weight gain had a more modestly increased short-term mortality risk. Weight loss accelerates in the year prior to death. CONCLUSIONS: Weight loss and leanness are important predictors of poor prognosis in CHF. Being lean and losing weight is particularly bad. The detection of weight change, and particularly weight loss, should be considered as an adverse sign prompting further evaluation.
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| 2. |
- O'Meara, E., et al.
(författare)
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Clinical correlates and consequences of anemia in a broad spectrum of patients with heart failure: results of the Candesartan in Heart Failure: Assessment of Reduction in Mortality and Morbidity (CHARM) Program
- 2006
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Ingår i: Circulation. - 1524-4539. ; 113:7, s. 986-94
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: We wished to determine the prevalence of, potential mechanistic associations of, and clinical outcomes related to anemia in patients with heart failure and a broad spectrum of left ventricular ejection fraction (LVEF). METHODS AND RESULTS: In multivariable analyses, we examined the associations between hemoglobin and baseline characteristics, laboratory variables, and outcomes in 2653 patients randomized in the CHARM Program in the United States and Canada. Anemia was equally common in patients with preserved (27%) and reduced (25%) LVEF but was more common in black and older patients. Anemia was associated with ethnicity, diabetes, low body mass index, higher systolic and lower diastolic blood pressure, and recent heart failure hospitalization. More than 50% of anemic patients had a glomerular filtration rate <60 mL.min(-1).1.73 m(-2) compared with <30% of nonanemic patients. Despite an inverse relationship between hemoglobin and LVEF, anemia was associated with an increased risk of death and hospitalization, a relationship observed in patients with both reduced and preserved LVEF. There were 133 versus 69 deaths and 527 versus 352 hospitalizations per 1000 patient-years of follow-up in anemic versus nonanemic patients (both P<0.001). The effect of candesartan in reducing outcomes was independent of hemoglobin. CONCLUSIONS: Anemia was common in heart failure, regardless of LVEF. Lower hemoglobin was associated with higher LVEF yet was an independent predictor of adverse mortality and morbidity outcomes. In heart failure, the causes of anemia and the associations between anemia and outcomes are probably multiple and complex.
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| 3. |
- Hillege, H. L., et al.
(författare)
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Renal function as a predictor of outcome in a broad spectrum of patients with heart failure
- 2006
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Ingår i: Circulation. - 1524-4539 .- 0009-7322. ; 113:5, s. 671-8
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Decreased renal function has been found to be an independent risk factor for cardiovascular outcomes in patients with chronic heart failure (CHF) with markedly reduced left ventricular ejection fraction (LVEF). The aim of this analysis was to evaluate the prognostic importance of renal function in a broader spectrum of patients with CHF. METHODS AND RESULTS: The Candesartan in Heart Failure:Assessment of Reduction in Mortality and Morbidity (CHARM) program consisted of three component trials that enrolled patients with symptomatic CHF, based on use of ACE inhibitors and reduced (< or =40%) or preserved LVEF (>40%). Entry baseline creatinine was required to be below 3.0 mg/dL (265 micromol/L). Routine baseline serum creatinine assessments were done in 2680 North American patients. An analysis of the estimated glomerular filtration rate (eGFR), using the Modification of Diet in Renal Disease equation and LVEF on risk of cardiovascular death or hospitalization for heart failure, as well as on all-cause mortality, was conducted on these 2680 patients. The proportion of patients with eGFR <60 mL/min per 1.73 m2 was 36.0%; 42.6% for CHARM-Alternative, 33.0% for CHARM-Added, and 34.7% for CHARM-Preserved. During the median follow-up of 34.4 months (total 6493 person-years), the primary outcome of cardiovascular death or hospital admission for worsening CHF occurred in 950 of 2680 subjects. Both reduced eGFR and lower LVEF were found to be significant independent predictors of worse outcome after adjustment for major confounding baseline clinical characteristics. The risk for cardiovascular death or hospitalization for worsening CHF as well as the risk for all-cause mortality increased significantly below an eGFR of 60 mL/min per 1.73 m2 (adjusted hazard ratio, 1.54 for 45 to 60 mL/min per 1.73 m2 and 1.86 for <45 mL/min per 1.73 m2 for the primary outcome, both P<0.001, and hazard ratio of 1.50, P=0.006, and 1.91, P=0.001, respectively, for all-cause mortality). The prognostic value of eGFR was not significantly different among the three component trials. There was no significant interaction between renal function, the effect of candesartan, and clinical outcome. CONCLUSIONS: Impaired renal function is independently associated with heightened risk for death, cardiovascular death, and hospitalization for heart failure in patients with CHF with both preserved as well as reduced LVEF. There was no evidence that the beneficial effect of candesartan was modified by baseline eGFR.
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| 4. |
- Kenchaiah, S., et al.
(författare)
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Body mass index and prognosis in patients with chronic heart failure: insights from the Candesartan in Heart failure: Assessment of Reduction in Mortality and morbidity (CHARM) program
- 2007
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Ingår i: Circulation. - 1524-4539. ; 116:6, s. 627-36
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: In individuals without known cardiovascular disease, elevated body mass index (BMI) (weight/height2) is associated with an increased risk of death. However, in patients with certain specific chronic diseases, including heart failure, low BMI has been associated with increased mortality. METHODS AND RESULTS: We examined the influence of BMI on prognosis using Cox proportional hazards models in 7599 patients (mean age, 65 years; 35% women) with symptomatic heart failure (New York Heart Association class II to IV) and a broad spectrum of left ventricular ejection fractions (mean, 39%) in the Candesartan in Heart failure: Assessment of Reduction in Mortality and morbidity (CHARM) program. During a median follow-up of 37.7 months, 1831 patients died. After adjustment for potential confounders, compared with patients with BMI between 30 and 34.9, patients in lower BMI categories had a graded increase in the risk of death. The hazard ratios (95% confidence intervals) were 1.22 (1.06 to 1.41), 1.46 (1.24 to 1.71), and 1.69 (1.43 to 2.01) among those with BMI of 25 to 29.9, 22.5 to 24.9, and < 22.5, respectively. The increase in risk of death among patients with BMI > or = 35 was not statistically significant (hazard ratio, 1.17; 95% confidence interval, 0.95 to 1.43). The association between BMI and mortality was not altered by age, smoking status, or left ventricular ejection fraction (P for interaction >0.20). However, lower BMI was associated with a greater risk of all-cause death in patients without edema but not in patients with edema (P for interaction <0.0001). Lower BMI was associated with a greater risk of cardiovascular death and noncardiovascular death. Baseline BMI did not influence the risk of hospitalization for worsening heart failure or due to all causes. CONCLUSIONS: In patients with symptomatic heart failure and either reduced or preserved left ventricular systolic function, underweight or low BMI was associated with increased mortality, primarily in patients without evidence of fluid overload (edema).
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| 5. |
- Pocock, S. J., et al.
(författare)
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Predictors of mortality and morbidity in patients with chronic heart failure
- 2006
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Ingår i: Eur Heart J. - 0195-668X .- 0195-668X. ; 27:1, s. 65-75
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Tidskriftsartikel (refereegranskat)abstract
- AIMS: We aimed to develop prognostic models for patients with chronic heart failure (CHF). METHODS AND RESULTS: We evaluated data from 7599 patients in the CHARM programme with CHF with and without left ventricular systolic dysfunction. Multi-variable Cox regression models were developed using baseline candidate variables to predict all-cause mortality (n=1831 deaths) and the composite of cardiovascular (CV) death and heart failure (HF) hospitalization (n=2460 patients with events). Final models included 21 predictor variables for CV death/HF hospitalization and for death. The three most powerful predictors were older age (beginning >60 years), diabetes, and lower left ventricular ejection fraction (EF) (beginning <45%). Other independent predictors that increased risk included higher NYHA class, cardiomegaly, prior HF hospitalization, male sex, lower body mass index, and lower diastolic blood pressure. The model accurately stratified actual 2-year mortality from 2.5 to 44% for the lowest to highest deciles of predicted risk. CONCLUSION: In a large contemporary CHF population, including patients with preserved and decreased left ventricular systolic function, routine clinical variables can discriminate risk regardless of EF. Diabetes was found to be a surprisingly strong independent predictor. These models can stratify risk and help define how patient characteristics relate to clinical course.
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| 6. |
- Solomon, S. D., et al.
(författare)
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Influence of nonfatal hospitalization for heart failure on subsequent mortality in patients with chronic heart failure
- 2007
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Ingår i: Circulation. - 1524-4539. ; 116:13, s. 1482-7
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Patients with chronic heart failure (HF) are at increased risk of both fatal and nonfatal major adverse cardiovascular events. We used data from the Candesartan in Heart failure: Assessment of Reduction in Mortality and morbidity (CHARM) trials to assess the influence of nonfatal hospitalizations for HF on subsequent mortality rates in a broad spectrum of HF patients. METHODS AND RESULTS: In the present study, 7599 patients with New York Heart Association class II to IV HF and reduced or preserved left ventricular ejection fraction were randomized to placebo or candesartan. We assessed the risk of death after discharge from a first hospitalization for HF using time-updated Cox proportional-hazards models on 7572 patients for whom discharge data were available. Of 7572 patients, 1455 (19%) had at least 1 HF hospitalization, and 586 of 1819 deaths occurred after discharge from an HF hospitalization. The mortality rate was increased after HF hospitalizations, even after adjustment for baseline predictors of death (hazard ratio, 3.15; 95% confidence interval, 2.83 to 3.50). Longer duration of HF hospitalization enhanced the risk of dying, as did repeat HF hospitalizations. Moreover, risk of death was highest within a month of discharge and then declined progressively over time, particularly for death resulting from HF progression and for sudden cardiac death. We observed a similar pattern of risk associated with all-cause hospitalization, although the magnitude was less than that with HF hospitalization. CONCLUSIONS: In patients with chronic HF, the risk of death is greatest in the early period after discharge after a hospitalization for HF and is directly related to the duration and frequency of HF hospitalizations. These findings suggest a role for increased surveillance in the early postdischarge period of greatest vulnerability after an HF admission.
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| 7. |
- Abrahamsson, Putte, 1965, et al.
(författare)
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Impact of hospitalization for acute coronary events on subsequent mortality in patients with chronic heart failure
- 2009
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Ingår i: Eur Heart J. - 1522-9645. ; 30:3, s. 338-45
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Tidskriftsartikel (refereegranskat)abstract
- AIMS: We explored the impact of having a hospital admission for an acute coronary syndrome (ACS) on the subsequent prognosis among patients with chronic heart failure (CHF). METHODS AND RESULTS: A total of 7599 patients with CHF, New York Heart Association Classes II-IV, were randomly assigned to candesartan or placebo. We assessed the risk of death after a first ACS using time-updated Cox proportional hazard models adjusted for baseline predictors. During a mean follow-up of 3.3 years, 1174 patients experienced at least one ACS. Myocardial infarction (MI) was the first ACS in 442 subjects and unstable angina (UA) in 732. After these events, 219 (49.5%) and 167 (22.8%) patients died during follow-up. The early risk of death was more pronounced after MI: 30.2% died within 30 days compared with 3.6% after UA. After an ACS event, the risk of death declined steadily over time, although 18 months after an MI the risk was still twice that of patients without an ACS. CONCLUSION: Patients with CHF, who develop an ACS, have markedly increased subsequent mortality, particularly in the early phase after an MI.
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| 8. |
- Hawkins, N. M., et al.
(författare)
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Prevalence and prognostic impact of bundle branch block in patients with heart failure: Evidence from the CHARM programme
- 2007
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Ingår i: European journal of heart failure. - : Wiley. - 1388-9842. ; 9:5, s. 510-7
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Bundle branch block (BBB) is a powerful independent predictor of cardiovascular mortality in patients with heart failure (HF) and reduced left ventricular ejection fraction (LVEF). The prognostic implications in HF with preserved systolic function (HF-PSF) are less well understood. METHODS: The Candesartan in Heart failure: Assessment of Reduction in Mortality and morbidity (CHARM) programme randomised 7599 patients with symptomatic HF to receive candesartan or placebo. The primary outcome comprised cardiovascular death or HF hospitalisation. The relative risk conveyed by BBB relative to a normal electrocardiogram was examined. RESULTS: The prevalence of BBB was significantly lower in patients with preserved compared with reduced systolic function (CHARM-Preserved 14.4%, Alternative 29.6%, Added 30.5%), p<0.0001. Overall, the adjusted hazard ratio for the primary outcome was 1.48 (95% confidence interval 1.22-1.78), p<0.0001, reflecting increased risk in patients with reduced LVEF (1.72 [1.28-2.31], p=0.0003). The apparently more modest risk among patients with HF-PSF was significant in unadjusted (1.80 [1.37-2.37], p<0.0001) but not adjusted analysis (1.16 [0.88-1.54], p=0.2897). However, no formal statistical difference was observed between the two cohorts, and interpretation is limited by the unknown prevalence of left and right BBB morphologies in each. Comparing BBB presence with absence yielded qualitatively similar results. CONCLUSION: The simple clinical finding of BBB is a powerful independent predictor of worse clinical outcomes in patients with HF and reduced LVEF. It is less frequent, with a more modest predictive effect, in patients with preserved systolic function.
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| 9. |
- Hawkins, N. M., et al.
(författare)
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Prevalence and prognostic implications of electrocardiographic left ventricular hypertrophy in heart failure: evidence from the CHARM programme
- 2007
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Ingår i: Heart. - : BMJ. - 1468-201X .- 1355-6037. ; 93:1, s. 59-64
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Electrocardiographic left ventricular hypertrophy (ECG LVH) is a powerful independent predictor of cardiovascular morbidity and mortality in hypertension. OBJECTIVE: To determine the contemporary prevalence and prognostic implications of ECG LVH in a broad spectrum of patients with heart failure with and without reduced left ventricular ejection fraction (LVEF). METHODS AND OUTCOME: The Candesartan in Heart failure: Assessment of Reduction in Mortality and morbidity (CHARM) programme randomised 7599 patients with symptomatic heart failure to receive candesartan or placebo. The primary outcome comprised cardiovascular death or hospital admission for worsening heart failure. The relative risk (RR) conveyed by ECG LVH compared with a normal ECG was examined in a Cox model, adjusting for as many as 31 covariates of prognostic importance. RESULTS: The prevalence of ECG LVH was similar in all three CHARM trials (Alternative, 15.4%; Added, 17.1%; Preserved, 14.7%; Overall, 15.7%) despite a more frequent history of hypertension in CHARM-Preserved. ECG LVH was an independent predictor of worse prognosis in CHARM-Overall. RR for the primary outcome was 1.27 (95% confidence interval (CI) 1.04 to 1.55, p = 0.018). The risk of secondary end points was also increased: cardiovascular death, 1.50 (95% CI 1.13 to 1.99, p = 0.005); hospitalisation due to heart failure, 1.19 (95% CI 0.94 to 1.50, p = 0.148); and composite major cardiovascular events, 1.35 (95% CI 1.12 to 1.62, p = 0.002). CONCLUSION: ECG LVH is similarly prevalent in patients with symptomatic heart failure regardless of LVEF. The simple clinical finding of ECG LVH was an independent predictor of a worse clinical outcome in a broad spectrum of patients with heart failure receiving extensive contemporary treatment. Candesartan had similar benefits in patients with and without ECG LVH.
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| 10. |
- O'Meara, E., et al.
(författare)
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Sex differences in clinical characteristics and prognosis in a broad spectrum of patients with heart failure: results of the Candesartan in Heart failure: Assessment of Reduction in Mortality and morbidity (CHARM) program
- 2007
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Ingår i: Circulation. - 1524-4539. ; 115:24, s. 3111-20
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: We wished to test previous hypotheses that sex-related differences in mortality and morbidity may be due to differences in the cause of heart failure or in left ventricular ejection fraction (LVEF) by comparing fatal and nonfatal outcomes in women and men with heart failure and a broad spectrum of left ventricular ejection fraction. METHODS AND RESULTS: We compared outcomes in 2400 women and 5199 men randomized in the Candesartan in Heart failure: Assessment of Reduction in Mortality and morbidity (CHARM) program using multivariable regression analyses. A total of 1188 women (50%) had a low LVEF (< or = 0.40), and 1212 had a preserved LVEF (> 0.40). Among the men, 3388 (65%) had a low LVEF, and 1811 had a preserved LVEF. A total of 1216 women (51%) and 3465 men (67%) had an ischemic cause of their heart failure. All-cause mortality was 21.5% in women and 25.3% in men (adjusted hazard ratio [HR], 0.77; 95% CI, 0.69 to 0.86; P<0.001). Fewer women (30.4%) than men (33.3%) experienced cardiovascular death or heart failure hospitalization (adjusted HR, 0.83; 95% CI, 0.76 to 0.91; P<0.001). The risks of sudden death (HR, 0.70; 95% CI, 0.58 to 0.85) and death due to worsening heart failure (HR, 0.72; 95% CI, 0.58 to 0.89) were reduced to a comparable extent. The adjusted risk of cardiovascular hospitalization was also lower in women (HR, 0.88; 95% CI, 0.82 to 0.95), mainly because of a reduced risk of heart failure hospitalization (HR, 0.87; 95% CI, 0.78 to 0.97). Women had a lower risk of death irrespective of cause of heart failure or LVEF. CONCLUSIONS: Among patients with heart failure, women have lower risks of most fatal and nonfatal outcomes that are not explained, as previously suggested, by LVEF or origin of the heart failure.
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