***TASK*** the task is to summarize an input biomedical literature in six sentences 
    ***INPUT*** the input is a biomedical literature 
    ***OUTPUT*** the output is the summary of an input biomedical literature in six sentences 
    ***DOCUMENTATION*** 
    ***EXAMPLES*** 
    Input: Background : Heart failure ( HF ) survival has improved , and nowadays , many patients with HF die of noncardiac causes , including cancer . Our aim was to investigate whether a causal relationship exists between HF and the development of cancer . Methods : HF was induced by inflicting large anterior myocardial infa rct ion in  APCmin mice , which are prone to developing precancerous intestinal tumors , and tumor growth was measured . In addition , to rule out hemodynamic impairment , a heterotopic heart transplantation model was used in which an infa rct ed or sham-operated heart was transplanted into a recipient mouse while the native heart was left in situ . After 6 weeks , tumor number , volume , and proliferation were quantified . C and i date secreted proteins were selected because they were previously associated both with ( colon ) tumor growth and with myocardial production in post – myocardial infa rct ion proteomic studies . Myocardial gene expression levels of these selected c and i date s were analyzed , as well as their proliferative effects on HT-29 ( colon cancer ) cells . We vali date d these c and i date s by measuring them in plasma of healthy subjects and patients with HF . Finally , we associated the relation between cardiac specific and inflammatory biomarkers and new-onset cancer in a large , prospect i ve general population cohort . Results : The presence of failing hearts , both native and heterotopically transplanted , result ed in significantly increased intestinal tumor load of 2.4-fold in APCmin mice ( all P<0.0001 ) . The severity of left ventricular dysfunction and fibrotic scar strongly correlated with tumor growth ( P=0.002 and P=0.016 , respectively ) . We identified several proteins ( including serpinA3 and A1 , fibronectin , ceruloplasmin , and paraoxonase 1 ) that were elevated in human patients with chronic HF ( n=101 ) compared with healthy subjects ( n=180 ; P<0.001 ) . Functionally , serpinA3 result ed in marked proliferation effects in human colon cancer ( HT-29 ) cells , associated with Akt-S6 phosphorylation . Finally , elevated cardiac and inflammation biomarkers in apparently healthy humans ( n=8319 ) were predictive of new-onset cancer ( n=1124 ) independently of risk factors for cancer ( age , smoking status , and body mass index ) . Conclusions : We demonstrate that the presence of HF is associated with enhanced tumor growth and that this is independent of hemodynamic impairment and could be caused by cardiac excreted factors . A diagnosis of HF may therefore be considered a risk factor for incident cancer INTRODUCTION From a prospect i ve multicentre multicountry clinical trial , we developed and vali date d risk models to predict prospect i ve all-cause mortality and hospitalizations because of heart failure ( HF ) in patients with HF . METHODS AND RESULTS BIOSTAT-CHF is a research programme design ed to develop and externally vali date risk models to predict all-cause mortality and HF hospitalizations . The index cohort consisted of 2516 patients with HF from 69 centres in 11 European countries . The external validation cohort consisted of 1738 comparable patients from six centres in Scotl and , UK . Patients from the index cohort had a mean age of 69 years , 27 % were female , 83 % were in New York Heart Association ( NYHA ) class II-III and the mean left ventricular ejection fraction ( LVEF ) was 31 % . The full prediction models for mortality , hospitalization owing to HF , and the combined outcome , yielded c-statistic values of 0.73 , 0.69 , and 0.71 , respectively . Predictors of mortality and hospitalization owing to HF were remarkably different . The five strongest predictors of mortality were more advanced age , higher blood urea nitrogen and N-terminal pro-B-type natriuretic peptide , lower haemoglobin , and failure to prescribe a beta-blocker . The five strongest predictors of hospitalization owing to HF were more advanced age , previous hospitalization owing to HF , presence of oedema , lower systolic blood pressure and lower estimated glomerular filtration rate .  Patients from the validation cohort were aged 74 years , 34 % were female , 85 % were in NYHA class II-III , and mean LVEF was 41 % ; c-statistic values for the full and compact model were comparable to the index cohort . CONCLUSION A small number of variables , which are usually readily available in the routine clinical setting , provide useful prognostic information for patients with HF . Predictors of mortality were remarkably different from predictors of hospitalization owing to HF BACKGROUND Several recent studies have suggested an increased cancer risk among patients with heart failure ( HF ) . However , these studies are constrained by limited size and follow-up , lack of comprehensive data on other health attributes , and adjudicated cancer outcomes . OBJECTIVES This study sought to determine whether HF is associated with cancer incidence and cancer-specific mortality . METHODS The study assembled a cohort from the Physicians ' Health Studies I and II , 2 r and omized controlled trials of aspirin and vitamin supplements conducted from 1982 to 1995 and from 1997 to 2011 , respectively , that included annual health evaluations and determination of cancer and HF diagnoses . In the primary analysis , the study excluded participants with cancer or HF at baseline and performed multivariable-adjusted Cox models to determine the relationship between HF and cancer , modeling HF as a time-varying exposure . In a complementary analysis , the study used the l and mark method and identified cancer-free participants at 70 years of age , distinguishing between those with and without HF , and likewise performed Cox regression . Sensitivity analyses were performed at 65 , 75 , and 80 years of age . RESULTS Among 28,341 Physicians ' Health Study participants , 1,420 developed HF . A total of 7,363 cancers developed during a median follow-up time of 19.9 years ( 25th to 75th percentile : 11.0 to 26.8 years ) . HF was not associated with cancer incidence in crude ( hazard ratio : 0.92 ; 95 % confidence interval : 0.80 to 1.08 ) or multivariable-adjusted analysis ( hazard ratio : 1.05 ; 95 % confidence interval : 0.86 to 1.29 ) . No association was found between HF and site-specific cancer incidence or cancer-specific mortality after multivariable adjustment . Results were similar when using the l and mark method at all l and mark ages . CONCLUSIONS HF is not associated with an increased risk of cancer among male physicians BACKGROUND Heart failure ( HF ) is associated with excess morbidity and mortality for which noncardiac causes are increasingly recognized . The authors previously described an increased risk of cancer among HF patients compared with community controls . OBJECTIVES This study examined whether HF was associated with an increased risk of subsequent cancer among a homogenous population of first myocardial infa rct ion ( MI ) survivors . METHODS A prospect i ve cohort study was conducted among Olmsted County , Minnesota , residents with incident MI from 2002 to 2010 . Patients with prior cancer or HF diagnoses were excluded . RESULTS A total of 1,081 participants ( mean age 64 ± 15 years ; 60 % male ) were followed for 5,327 person-years ( mean 4.9 ± 3.0 years ) . A total of 228 patients developed HF , and 98 patients developed cancer ( excluding nonmelanoma skin cancer ) . Incidence density rates for cancer diagnosis ( per 1,000 person-years ) were 33.7 for patients with HF and 15.6 for patients without HF ( p = 0.002 ) . The hazard ratio ( HR ) for cancer associated with HF was 2.16 ( 95 % confidence interval [ CI ] : 1.39 to 3.35 ) ; adjusted for age , sex , and Charlson comorbidity index ; HR : 1.71 ( 95 % CI : 1.07 to 2.73 ) . The HRs for mortality associated with cancer were 4.90 ( 95 % CI : 3.10 to 7.74 ) for HF-free and 3.91 ( 95 % CI : 1.88 to 8.12 ) for HF patients ( p for interaction = 0.76 ) . CONCLUSIONS Patients who develop HF after MI have an increased risk of cancer . This finding extends our previous report of an elevated cancer risk after HF compared with controls , and calls for a better underst and ing of shared risk factors and underlying mechanisms AIMS The prevalence of cardiovascular and non-cardiovascular co-morbidities and their relative importance for outcomes in heart failure with preserved ejection fraction ( HFPEF ) remain poorly characterized . This study aim ed to investigate this . METHODS AND RESULTS The Karolinska-Rennes ( KaRen ) Study was a multinational prospect i ve observational study design ed to characterize HFPEF . Inclusion required acute HF , defined by the Framingham criteria , LVEF ≥ 45 % , and NT-pro-BNP ≥ 300 ng/L or BNP ≥ 100 ng/L. Detailed clinical data were collected at baseline and patients were followed prospect ively for 18 months . Predictors of the primary ( HF hospitalization or all-cause mortality ) and secondary ( all-cause mortality ) outcomes were assessed with multivariable Cox regression . A total of 539 patients [ 56 % women ; median ( interquartile range ) age 79 ( 72 - 84 ) years ; NT-pro-BNP/BNP 2448 (1290 - 4790)/429 ( 229 - 805 ) ng/L ] were included .  Known history of HF was present in 40 % . Co-morbidities included hypertension ( 78 % ) , atrial fibrillation/flutter ( 65 % ) , anaemia ( 51 % ) , renal dysfunction ( 46 % ) , CAD ( 33 % ) , diabetes ( 30 % ) , lung disease ( 25 % ) , and cancer ( 16 % ) . The primary outcome occurred in 268 patients [ 50 % ; 106 deaths ( 20 % ) and 162 HF hospitalizations ( 30 % ) ] . Important independent predictors of the primary and /or secondary outcomes were age , history of non-cardiovascular syncope , valve disease , anaemia , lower sodium , and higher potassium , but no cardiovascular co-morbidities . Renin-angiotensin system antagonist and mineralocorticoid receptor antagonist use predicted improved prognosis . CONCLUSION HFPEF was associated with higher age , female gender , hypertension , atrial fibrillation/flutter , and numerous non-cardiovascular co-morbidities . Prognosis was determined by non-cardiovascular co-morbidities , but use of conventional heart failure medications may still be associated with improved outcomes 
    Output:
    
In this meta- analysis and systematic review , our results demonstrated that heart failure may increase the risk of incident cancer and that HF associated with cancer increases the risk of mortality