| 1. |
- O'Meara, E., et al.
(author)
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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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In: Circulation. - 1524-4539. ; 113:7, s. 986-94
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Journal article (peer-reviewed)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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| 2. |
- Desai, A. S., et al.
(author)
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Incidence and predictors of hyperkalemia in patients with heart failure: an analysis of the CHARM Program
- 2007
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In: J Am Coll Cardiol. - 1558-3597. ; 50:20, s. 1959-66
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Journal article (peer-reviewed)abstract
- OBJECTIVES: We explored the incidence and predictors of hyperkalemia in a broad population of heart failure patients. BACKGROUND: When used in optimal doses to treat patients with heart failure, renin-angiotensin-aldosterone system (RAAS) inhibitors improve clinical outcomes but can cause hyperkalemia. METHODS: Participants in the CHARM (Candesartan in Heart Failure-Assessment of Reduction in Mortality and Morbidity) (n = 7,599) Program were randomized to standard heart failure therapy plus candesartan or placebo, titrated as tolerated to a target of 32 mg once daily with recommended monitoring of serum potassium and creatinine. We assessed the incidence and predictors of hyperkalemia associated with dose reduction, study drug discontinuation, hospitalization, or death over the median 3.2 years of follow-up. RESULTS: Independent of treatment assignment, the risk of hyperkalemia increased with age > or =75 years, male gender, diabetes, creatinine > or =2.0 mg/dl, K+ > or =5.0 mmol/l, and background use of angiotensin-converting enzyme inhibitors or spironolactone. Candesartan increased the rate of aggregate hyperkalemia from 1.8% to 5.2% (difference 3.4%, p < 0.0001) and serious hyperkalemia (associated with death or hospitalization) from 1.1% to 1.8% (difference 0.7%, p < 0.001), with hyperkalemia associated with death reported in 2 (0.05%) candesartan patients and 1 (0.03%) placebo patient. The benefit of candesartan in reducing cardiovascular death or heart failure hospitalization (relative risk reduction 16%, p < 0.0001) was uniform in these subgroups, as was the incremental risk of hyperkalemia. CONCLUSIONS: The risk of hyperkalemia is increased in symptomatic heart failure patients with advanced age, male gender, baseline hyperkalemia, renal failure, diabetes, or combined RAAS blockade. Although these groups derive incremental clinical benefit from candesartan, careful surveillance of serum potassium and creatinine is particularly important.
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| 3. |
- Amundadottir, Laufey, et al.
(author)
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Genome-wide association study identifies variants in the ABO locus associated with susceptibility to pancreatic cancer.
- 2009
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In: Nature Genetics. - : Springer Science and Business Media LLC. - 1061-4036 .- 1546-1718. ; 41, s. 986-990
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Journal article (peer-reviewed)abstract
- We conducted a two-stage genome-wide association study of pancreatic cancer, a cancer with one of the lowest survival rates worldwide. We genotyped 558,542 SNPs in 1,896 individuals with pancreatic cancer and 1,939 controls drawn from 12 prospective cohorts plus one hospital-based case-control study. We conducted a combined analysis of these groups plus an additional 2,457 affected individuals and 2,654 controls from eight case-control studies, adjusting for study, sex, ancestry and five principal components. We identified an association between a locus on 9q34 and pancreatic cancer marked by the SNP rs505922 (combined P = 5.37 x 10(-8); multiplicative per-allele odds ratio 1.20; 95% confidence interval 1.12-1.28). This SNP maps to the first intron of the ABO blood group gene. Our results are consistent with earlier epidemiologic evidence suggesting that people with blood group O may have a lower risk of pancreatic cancer than those with groups A or B.
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| 4. |
- Jackson, C. E., et al.
(author)
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Albuminuria in chronic heart failure: prevalence and prognostic importance
- 2009
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In: Lancet. - 1474-547X. ; 374:9689, s. 543-50
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Journal article (peer-reviewed)abstract
- BACKGROUND: Increased excretion of albumin in urine might be a marker of the various pathophysiological changes that arise in patients with heart failure. Therefore our aim was to assess the prevalence and prognostic value of a spot urinary albumin to creatinine ratio (UACR) in patients with heart failure. METHODS: UACR was measured at baseline and during follow-up of 2310 patients in the Candesartan in Heart failure: Assessment of Reduction in Mortality and morbidity (CHARM) Programme. The prevalence of microalbuminuria and macroalbuminuria, and the predictive value of UACR for the primary composite outcome of each CHARM study--ie, death from cardiovascular causes or admission to hospital with worsening heart failure--and death from any cause were assessed. FINDINGS: 1349 (58%) patients had a normal UACR, 704 (30%) had microalbuminuria, and 257 (11%) had macroalbuminuria. The prevalence of increased UACR was similar in patients with reduced and preserved left ventricular ejection fractions. Patients with an increased UACR were older, had more cardiovascular comorbidity, worse renal function, and a higher prevalence of diabetes mellitus than did those with normoalbuminuria. However, a high prevalence of increased UACR was still noted among patients without diabetes, hypertension, or renal dysfunction. Elevated UACR was associated with increased risk of the composite outcome and death even after adjustment for other prognostic variables including renal function, diabetes, and haemoglobin A1c. The adjusted hazard ratio (HR) for the composite outcome in patients with microalbuminuria versus normoalbuminuria was 1.43 (95% CI 1.21-1.69; p<0.0001) and for macroalbuminuria versus normoalbuminuria was 1.75 (1.39-2.20; p<0.0001). The adjusted values for death were 1.62 (1.32-1.99; p<0.0001) for microalbuminuria versus normoalbuminuria, and 1.76 (1.32-2.35; p=0.0001) for macroalbuminuria versus normoalbuminuria. Treatment with candesartan did not reduce or prevent the development of excessive excretion of urinary albumin. INTERPRETATION: Increased UACR is a powerful and independent predictor of prognosis in heart failure. FUNDING: AstraZeneca.
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| 5. |
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| 6. |
- Meredith, P. A., et al.
(author)
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Clinical outcomes according to baseline blood pressure in patients with a low ejection fraction in the CHARM (Candesartan in Heart Failure: Assessment of Reduction in Mortality and Morbidity) Program
- 2008
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In: Journal of the American College of Cardiology. - : Elsevier BV. - 1558-3597 .- 0735-1097. ; 52:24, s. 2000-7
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Journal article (peer-reviewed)abstract
- OBJECTIVES: This study sought to investigate the efficacy and tolerability of candesartan, according to baseline blood pressure (BP), in the 4,576 patients with a low ejection fraction (EF) (or=141 mm Hg) and 4 DBP categories (or=81 mm Hg). RESULTS: Low SBP and DBP were associated with worse clinical outcomes. Baseline BP did not modify the effects of candesartan on clinical outcomes: the interaction p value between SBP category and treatment was 0.38 (0.22 for DBP category). For both placebo and candesartan, study drug discontinuation for adverse effects (especially hypotension) was highest in patients in the lowest baseline BP categories. However, the relative risk of discontinuation for hypotension, renal dysfunction, and hyperkalemia in the candesartan compared with placebo group was not increased in patients with a low baseline BP. CONCLUSIONS: In patients with low EF heart failure, the relative risks and benefits of candesartan treatment were similar in patients with a low BP compared to those with a higher BP.
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| 7. |
- O'Meara, E., et al.
(author)
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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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In: Circulation. - 1524-4539. ; 115:24, s. 3111-20
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Journal article (peer-reviewed)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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| 8. |
- Solomon, S. D., et al.
(author)
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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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In: Circulation. - 1524-4539. ; 116:13, s. 1482-7
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Journal article (peer-reviewed)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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| 9. |
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| 10. |
- Abrahamsson, Putte, 1965, et al.
(author)
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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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In: Eur Heart J. - 1522-9645. ; 30:3, s. 338-45
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Journal article (peer-reviewed)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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