High cumulative incidence of cancer in patients with cardio‐renal‐anaemia syndrome

Schroten, Nicolas F.; Putten, Karien van der; Rutten, Frans H.; Diepenbroek, Adry; Mosterd, Arend; Gaillard, Carlo A. J. M.

doi:10.1093/eurjhf/hfq078

Cited by 8 publications

(10 citation statements)

References 33 publications

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“…Further, the risk of cancer tended to be greater in younger patients arguing against a major role of measured and unmeasured comorbidities as these increase in prevalence with age. Other hypothetical explanations include the possibility that stress from chronic illness (17) or mechanisms associated directly with the physiology of HF may also be operating in cancer such as inflammation, tissue hypoxia and hormonal (erythropoietin) activation (18). None of these are currently established.…”

Section: Discussionmentioning

confidence: 99%

Patients With Heart Failure Have an Increased Risk of Incident Cancer

Hasin

Gerber

McNallan

et al. 2013

Journal of the American College of Cardiology

204

156

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Objective To evaluate the risk of cancer in patients with heart failure (HF) compared to community controls and its impact on outcome. Background HF is associated with excess morbidity and mortality. Non-cardiac causes of adverse outcomes in HF are increasingly recognized but not fully characterized. Methods In a case-control study, we compared history of cancer among community subjects newly diagnosed with HF from 1979–2002 to age-, sex-, and date-matched community controls without HF (961 pairs). Individuals without cancer at index (596 pairs) were followed for cancer in a cohort design, and the survival of HF patients who developed cancer was assessed. Results Before index, 22% of HF cases and 23% of controls had a history of cancer (odds ratio 0.94; 95% CI 0.75–1.17). During 9,203 person-years of follow-up [mean (SD), 7.7 (6.4) years], 244 new cancer cases were identified; HF patients had a 68% higher risk of developing cancer [hazard ratio (HR) 1.68; 95% CI 1.13–2.50] adjusted for body mass index, smoking and comorbidities. The HRs were similar for men and women with a trend toward a stronger association among subjects ≤75 years (P=0.22) and during the most recent time period (P=0.075). Among HF cases, incident cancer increased the risk of death (HR 1.56; 95% CI 1.22–1.99) adjusted for age, sex, year and comorbidities. Conclusions HF patients are at increased risk of cancer, which appears to have increased over time. Cancer increases mortality in HF underscoring the importance of non-cardiac morbidity and of cancer surveillance in the management of HF patients.

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Section: Discussionmentioning

confidence: 99%

Patients With Heart Failure Have an Increased Risk of Incident Cancer

Hasin

Gerber

McNallan

et al. 2013

Journal of the American College of Cardiology

204

156

View full text Add to dashboard Cite

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“…Assessing the cause of death in this way can, in itself, be very difficult and unacceptably inaccurate, preventing a clinical investigator from assessing and controlling the quality of data 29. Of interest, a relationship between CRA syndrome and cancer has been suggested 30. Finally, we did not measure haematinic parameters.…”

Section: Discussionmentioning

confidence: 99%

The cardiorenal anaemia syndrome in systolic heart failure: prevalence, clinical correlates, and long‐term survival

Scrutinio¹,

Passantino²,

Santoro³

et al. 2011

European J of Heart Fail

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AimsWe sought to assess the prevalence and clinical correlates of cardiorenal anaemia (CRA) syndrome in systolic heart failure and the relationship between renal dysfunction and anaemia on hard clinical outcomes. Methods and resultsWe studied 951 patients with chronic heart failure (CHF) and systolic dysfunction. The primary outcome was allcause mortality and urgent heart transplantation (UHT). Cox's regression analyses were used to assess the relation of the variables to the primary outcome. Hazard ratios (HRs) with 95% confidence intervals (CI) were calculated.The prevalence of CRA syndrome was 21.1%. Age (P , 0.001), body mass index (P , 0.001), diabetes (P ¼, 0.001), ischaemic aetiology (P , 0.006), left ventricular ejection fraction (P ¼ 0.018), and treatment with renin-angiotensin system inhibitors (P , 0.001) were independently related to CRA syndrome. During a median follow-up of 3.7 years, the primary outcome occurred in 404 patients (42.5%). Compared with patients with preserved renal function and normal haemoglobin (Hb) levels, those with CRA syndrome had a significantly increased risk for the primary outcome; the univariate and multivariate-adjusted HRs were 4.04 (CI: 3.11-5.24; P , 0.0001) and 2.22 (CI: 1.64-2.98; P , 0.0001), respectively. Three-year UHT-free survival was 86 and 47%, respectively. Among patients with renal dysfunction, the adjusted HR for the primary outcome increased by 17% (CI: 8 -26; P ¼ 0.0001) for each 1 g/dL decrease below an Hb value of 13.0 g/dL. ConclusionHeart failure, renal dysfunction, and anaemia are a fatal combination. Despite a relatively low prevalence, the CRA syndrome contributes to considerable mortality due to CHF.--

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“…Notably, however, the lowest survival rates are seen in patients with concurrent anaemia and renal dysfunction ,. Moreover, it has been proposed that the combination of HF, chronic kidney disease, and anaemia—CRAS—may also be associated with an increased risk of cancer . The effect of erythropoiesis‐stimulating agents (ESAs) in this setting will be addressed conclusively by the ongoing RED‐HF trial in which ∼2600 anaemic patients with HF were randomized to darbepoetin alfa or placebo, with the primary endpoint being death from any cause or first hospitalization for worsening HF …”

Section: The Cardiorenal Anaemia Syndrome and Iron Deficiencymentioning

confidence: 99%

Beyond the cardiorenal anaemia syndrome: recognizing the role of iron deficiency

Macdougall

Canaud²,

Francisco

et al. 2012

European J of Heart Fail

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Growing awareness that heart failure, renal impairment, and anaemia are frequent co-morbidities which can exacerbate one another in a vicious circle of clinical deterioration has led to the concept of the cardiorenal anaemia syndrome (CRAS). The role of iron deficiency within this complex interplay has been less well examined. Scrutiny of data from the recent FAIR-HF trial raises a new hypothesis: is it time for ‘CRAS’ to be supplemented with new acronyms such as CRIDS (cardiorenal–iron deficiency syndrome) or even CRAIDS (cardiorenal–anaemia–iron deficiency syndrome)? Iron deficiency occurs frequently in heart failure patients with or without anaemia. It not only impairs oxygen transport through reduced erythropoiesis, but adversely affects oxidative metabolism, cellular energetics, and immune mechanisms, and the synthesis and degradation of complex molecules such as DNA. One large observational study in patients with heart failure found iron deficiency to be an independent predictor of death or urgent heart transplantation (hazard ratio 1.58, 95% confidence interval 1.14–2.17, P = 0.005). In the FAIR-HF trial, i.v. iron therapy was associated with significant improvements in physical functioning in iron-deficient patients with heart failure, even in non-anaemic patients in whom haemoglobin levels did not change following i.v. iron administration. Key questions regarding the use of i.v. iron supplementation in the setting of heart failure merit exploration and could readily be answered by appropriately designed clinical trials. It is to be hoped that these important clinical trials are conducted, to permit a more subtle characterization of the patient's pathological condition and interventional requirements.

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High cumulative incidence of cancer in patients with cardio‐renal‐anaemia syndrome

Cited by 8 publications

References 33 publications

Patients With Heart Failure Have an Increased Risk of Incident Cancer

Patients With Heart Failure Have an Increased Risk of Incident Cancer

The cardiorenal anaemia syndrome in systolic heart failure: prevalence, clinical correlates, and long‐term survival

Beyond the cardiorenal anaemia syndrome: recognizing the role of iron deficiency

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