***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 — Epidemiological studies aim ed at correlating coronary heart disease ( CHD ) with serum ferritin levels have thus far yielded inconsistent results . We hypothesized that a labile iron component associated with non – transferrin-bound iron ( NTBI ) that appears in individuals with overt or cryptic iron overload might be more suitable for establishing correlations with CHD . Methods and Results — We investigated the relation of NTBI , serum iron , transferrin saturation , and serum ferritin with risk of CHD and acute myocardial infa rct ion ( AMI ) . The cohort used comprised a population -based sample of 11 471 postmenopausal women aged 49 to 70 years at enrollment in 1993 to 1997 . During a median follow-up of 4.3 years ( quartile limits Q1 to Q3 : 3.3 to 5.4 ) , 185 CHD events were identified , including 66 AMI events . We conducted a case-cohort study using all CHD cases and a r and om sample from the baseline cohort ( n=1134 ) . A weighted Cox proportional hazards model was used to estimate hazard ratios for tertiles of iron variables in relation to CHD and AMI . Adjusted hazard ratios of women in the highest NTBI tertile ( range 0.38 to 3.51 ) compared with the lowest ( range −2.06 to −0.32 ) were 0.84 ( 95 % confidence interval 0.61 to 1.16 ) for CHD and 0.47 ( 95 % confidence interval 0.31 to 0.71 ) for AMI . The results were similar for serum iron , transferrin saturation , and serum ferritin . Conclusions — Our results show no excess risk of CHD or AMI within the highest NTBI tertile compared with the lowest but rather seem to demonstrate a decreased risk . Additional studies are warranted to confirm our findings BACKGROUND Iron deficiency may impair aerobic performance . This study aim ed to determine whether treatment with intravenous iron ( ferric carboxymaltose ) would improve symptoms in patients who had heart failure , reduced left ventricular ejection fraction , and iron deficiency , either with or without anemia . METHODS We enrolled 459 patients with chronic heart failure of New York Heart Association ( NYHA ) functional class II or III , a left ventricular ejection fraction of 40 % or less ( for patients with NYHA class II ) or 45 % or less ( for NYHA class III ) , iron deficiency ( ferritin level < 100 microg per liter or between 100 and 299 microg per liter , if the transferrin saturation was < 20 % ) , and a hemoglobin level of 95 to 135 g per liter . Patients were r and omly assigned , in a 2:1 ratio , to receive 200 mg of intravenous iron ( ferric carboxymaltose ) or saline ( placebo ) . The primary end points were the self-reported Patient Global Assessment and NYHA functional class , both at week 24 . Secondary end points included the distance walked in 6 minutes and the health-related quality of life . RESULTS Among the patients receiving ferric carboxymaltose , 50 % reported being much or moderately improved , as compared with 28 % of patients receiving placebo , according to the Patient Global Assessment ( odds ratio for improvement , 2.51 ; 95 % confidence interval [ CI ] , 1.75 to 3.61 ) . Among the patients assigned to ferric carboxymaltose , 47 % had an NYHA functional class I or II at week 24 , as compared with 30 % of patients assigned to placebo ( odds ratio for improvement by one class , 2.40 ; 95 % CI , 1.55 to 3.71 ) . Results were similar in patients with anemia and those without anemia . Significant improvements were seen with ferric carboxymaltose in the distance on the 6-minute walk test and quality -of-life assessment s. The rates of death , adverse events , and serious adverse events were similar in the two study groups . CONCLUSIONS Treatment with intravenous ferric carboxymaltose in patients with chronic heart failure and iron deficiency , with or without anemia , improves symptoms , functional capacity , and quality of life ; the side-effect profile is acceptable . ( Clinical Trials.gov number , NCT00520780 ) The ' iron hypothesis ' cl aims that Fe depletion protects against IHD . The objective of the present study was to investigate the associations between serum ferritin levels and the risk of CVD and IHD  in a population -based sample . A total of 2874 subjects with serum ferritin levels between 15 and 300 microg/l from the Danish part of the ' Monitoring of Trends and Determinants in Cardiovascular Disease ' ( DAN-MONICA ) I study and the 1914 Cohort survey were followed for 10 years . Information on behavioural and socio-demographic characteristics were collected and serum ferritin levels measured . Non-fatal and fatal CVD and IHD were identified by the International Classification of Diseases diagnoses numbers . Multivariable Cox proportional hazard regression models with restricted cubic splines were performed . During the follow-up period , 310 subjects ( 201 men ; 109 women ) and 161 subjects ( 117 men ; forty-four women ) experienced CVD and IHD , respectively . Our analyses revealed no statistically significant associations between serum ferritin levels and the risk of CVD or IHD in both sexes . However , in women , the results argue for a U-shaped relationship between serum ferritin levels and CVD as well as IHD . In concordance with former prospect i ve studies , the present results do not support the hypothesis that normal body Fe stores should play a significant role in the development of CVD BACKGROUND In a recent Finnish study , ferritin was suggested to be an independent risk factor for acute myocardial infa rct ion . This study suggested that high levels of iron stores might thus be atherogenic and possibly explain partly the sex difference in the incidence of ischemic heart disease . METHODS AND RESULTS A r and omly selected group ( n = 2036 ) , men and women aged 25 to 74 years , were examined between June and September 1983 . All classic risk factors for coronary artery disease were measured as well as basic hematologic parameters and the parameters of iron metabolism , ie , iron , total iron-binding capacity ( TIBC ) , and ferritin . During the follow-up for 8.5 years , 81 subjects experienced acute myocardial infa rct ion ( 63 men and 18 women ) . The differences in the iron parameters between men and women were almost exclusively seen in ferritin values ( 198 micrograms/L in men and 91 micrograms/L in women ) , whereas small differences were seen in TIBC . The Cox proportional hazards model was used to estimate the contribution of independent variables to the risk of myocardial infa rct ion . TIBC was found to be a strong independent negative risk factor in men ( RR = 0.95 ; 95 % CI , 0.92 to 0.98 ) , whereas ferritin ( RR = 0.999 ; 95 % CI , 0.997 to 1.001 ) or other iron parameters had no significant predictive power . Each increase in TIBC of 1 mumol/L was associated with a 5.1 % decrease in the risk of myocardial infa rct ion . The classic major risk factors , ie , blood pressure , smoking , total cholesterol , and high-density lipoprotein , had significant independent correlation with myocardial infa rct ion . When Cox multivariate analysis was carried out on both sexes combined , TIBC was still an independent negative risk factor , and the logarithmic transform of ferritin had a weak negative correlation but was not statistically significant . Sex was in this group still a very strong risk factor after taking into account all classic risk factors as well as the parameters of iron metabolism . CONCLUSIONS This study suggests that transferrin , measured as TIBC , is an independent negative risk factor for myocardial infa rct ion . Other parameters of iron metabolism , including ferritin , were not found to contribute to the risk The positive association between body iron stores and  risk  of  coronary heart disease ( CHD ) initially observed among a Finnish male population has not been corroborated by studies conducted in other population s. The soluble transferrin receptor  (sTfR):ferritin ratio has been suggested to be a better index than ferritin to measure body iron stores . Because sTfR is sensitive to iron deficiency , this ratio can distinguish individuals with similar ferritin levels with respect to their iron status . To evaluate this novel index in relation to CHD risk , we prospect ively identified and confirmed 242 incident CHD cases and r and omly selected 483 controls matched for age , smoking , and fasting status among women that provided blood sample s in the Nurses ' Health Study during 9 y of follow-up . In both crude and multivariate analyses , neither the sTfR : ferritin ratio nor ferritin was significantly associated with an elevated risk of CHD . After multivariate adjustment for established and potential CHD risk factors , compared with women in the lowest quartile of the sTfR : ferritin ratio , women in the 2nd to 4th quartiles had relative risks ( RR ) ( 95 % CI ) of 1.39 ( 0.82 , 2.36 ) , 1.12 ( 0.66 , 1.91 ) , and 1.13 ( 0.65 , 1.97 ; P-trend = 0.61 ) , respectively . The multivariate RR ( 95 % CI ) for ferritin were 1.05 ( 0.62 , 1.77 ) , 1.19 ( 0.69 , 2.03 ) , and 1.05 ( 0.60 , 1.85 ; P-trend = 0.90 ) across quartiles . Our data do not support the hypothesis that excessive body iron stores are associated with risk of CHD OBJECTIVE Our specific aim in the prospect i ve , longitudinal assessment of 8,251 subjects in the National Health and Nutrition Examination Survey , NHANES I , followup study was to assess the important roles of modifiable dietary and behavioral characteristics in the causation and prevention of coronary heart disease ( CHD ) . METHODS Using NHANES I prospect i ve 10 year followup data , we studied 8,251 subjects ; 492 with cardiovascular events and 7,759 without events during the followup period ( 1971 - 75 to 1982 - 84 ) . Using general linear models and logistic regression , we assessed the relationships of CHD risk factors to CHD morbidity and mortality . RESULTS By logistic regression , the following factors were independently , significantly , and inversely associated with coronary heart and vascular disease deaths and hospitalizations : alcohol intake , dietary riboflavin , dietary iron , serum magnesium , leisure time exercise , habitual physical activity , and female gender . Positive significant independent determinants of CHD events included cigarette smoking , sedimentation rate , Quetelet index , maximum body weight , and age . CONCLUSIONS These associations emphasize the important role of modifiable dietary and behavioral characteristics in the causation and prevention of CHD BACKGROUND Iron has been suggested to play a role in the development of cardiovascular disease ( CVD ) through its pro-oxidant properties . However , epidemiological studies on iron status and the risk of CVD have yielded conflicting results . We therefore carried out a prospect i ve study to evaluate the relationship between iron status and CVD in a middle-aged French population . METHODS In total , 9917 subjects ( 3223 men aged 45 - 60 years and 6694 women aged 35 - 60 years ) included in the SU.VI.MAX ( SUpplementation en VItamines et Minéraux AntioXydants ) cohort were followed prospect ively for 7.5 years . All cases of ischaemic heart disease ( IHD ) were identified and vali date d. CVD risk factors , haemoglobin and serum ferritin concentrations were measured at baseline . FINDINGS Of men 4.3 % , and of women 37.8 % , presented at baseline a serum ferritin concentration < 30 microg l(-1 ) . During the follow-up , 187 subjects ( 148 men , 39 women ) developed IHD . Serum ferritin was positively associated with total cholesterol , serum triglycerides , systolic and diastolic blood pressure , body mass index and haemoglobin . No linear association was found between serum ferritin and IHD risk in men or in women . CONCLUSION Our data do not support a major role of iron status in the development of IHD in a healthy general population BACKGROUND We prospect ively studied iron intake in relation to the incidence of coronary disease in a 4-year follow-up of 44,933 men ( with no previous history of cardiovascular disease ) aged 40 to 75 years in 1986 who completed a food frequency question naire at baseline . METHODS AND RESULTS We documented 844 incident cases of coronary disease ( 249 nonfatal myocardial infa rct ions , 137 coronary disease fatalities , and 458 bypass operations or angioplasties ) . After adjustment for established risk factors , there was no significant association between total iron intake and risk of coronary heart disease . Men in the highest quintile of total intake ( median , 37 mg/d ) had a relative risk ( RR ) of fatal coronary disease or nonfatal myocardial infa rct ion of 0.73 ( 9 
    Output:
    
The most likely scenario that emerges from the available studies is that , in the reference range , iron status has a neutral effect .
Extreme conditions of iron deficiency , as well as of iron overload , are associated with modestly increased CVD risk , although with different proposed mechanisms