***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: Phase I of the Trials of Hypertension Prevention ( TOHP ) was a r and omized , multicenter investigation that included double-blind , placebo-controlled testing of calcium and magnesium supplementation among 698 healthy adults ( 10.5 % blacks and 31 % women ) aged 30 to 54 years with high-normal diastolic blood pressure ( DBP ) ( 80 to 89 mm Hg ) . Very high compliance ( 94 to 96 % by pill counts ) with daily doses of 1 g of calcium ( carbonate ) , 360 mg of magnesium ( diglycine ) , or placebos was corroborated for the active supplements by significant net increases in all urine and serum compliance measures in white men and for urine compliance measures in white women . Overall , neither calcium nor magnesium produced significant changes in blood pressure at 3 and 6 months . Analyses stratified by baseline intakes of calcium , magnesium , sodium , or initial blood pressures also showed no effect of supplementation . These analyses suggested that calcium supplementation may have result ed in a DBP decrease in white women and that response modifiers in this subgroup might have included lower initial urinary calcium levels , urinary sodium levels , or lower body mass index . However , overall analyses indicated that calcium and magnesium supplements are unlikely to lower blood pressure in adults with high-normal DBP . The subgroup analyses , useful to formulate hypotheses , raise the possibility of a benefit to white women , which requires testing in future trials OBJECTIVE To test the effect of daily supplemental calcium on  serum total and high-density lipoprotein cholesterol ( HDL-C ) levels and blood pressure in adults . DESIGN R and omized , double-blind , placebo-controlled clinical trial ; adjunct study to a trial of calcium and colon cell proliferation in patients with sporadic adenoma . SETTING Outpatient clinic . PATIENTS A total of 193 men and women , aged 30 to 74 years . INTERVENTION Treatment with 1.0 and 2.0 g/d of elemental calcium vs placebo over a 4-month period for cholesterol determinations and 6 months for blood pressure . MAIN OUTCOME MEASURES Serum total cholesterol and HDL-C levels , systolic and diastolic blood pressure . RESULTS Because there were no apparent differences in responses between the 1.0-g and 2.0-g calcium groups , their data were combined and compared with those of the placebo group . Among all participants , the mean total cholesterol level dropped 0.07 mmol/L ( 2.9 mg/dL ) ( 1.3 % ) ( P = .43 ) more , and the mean HDL-C level dropped 0.01 mmol/L ( 0.4 mg/dL ) ( 1.1 % ) ( P = .71 ) less in the calcium group than in the placebo group . Among participants without a history of hypercholesterolemia , the mean total cholesterol level dropped 0.18 mmol/L ( 6.8 mg/dL ) ( 3.3 % ) ( P = .10 ) and the HDL-C level dropped 0.02 mmol/L ( 0.6 mg/dL ) ( 1.5 % ) ( P = .61 ) more in the calcium group than in the placebo group . Among all participants , there was no apparent change in blood pressure until 6 months , when the mean systolic blood pressure dropped 0.8 mm Hg ( 0.6 % ) ( P = .85 ) and the mean diastolic blood pressure dropped 0.4 mm Hg ( 0.5 % ) ( P = .80 ) more in the calcium group than in the placebo group . CONCLUSIONS There were no substantial or statistically significant effects of calcium supplementation on total cholesterol or HDL-C levels or on blood pressure . There was a suggestion ( not statistically significant ) of a 0.07 to 0.18 mmol/L ( 3 - 7 mg/dL ) or 2 % to 4 % drop in the total cholesterol level , a finding similar to that reported in other studies , which indicates the need for further study Evidence from animal and human studies indicate that calcium supplementation may ameliorate two risk factors for atherosclerotic cardiovascular disease , hypertension and hyperlipidemia . We sought to characterize dietary fat consumption and plasma lipid profiles in hypertensive and normotensive subjects and plasma lipid responses to supplemental calcium . A r and omized , double-blind , placebo-controlled , crossover protocol was used to assess blood pressure and lipid response to 8 wk of 1000 mg of elemental calcium in 43 hypertensive and 27 normotensive subjects .  Nutrient intakes and plasma lipids were measured repeatedly . Hypertensive female subjects consumed significantly less ( p less than 0.05 ) phosphorus , potassium , and magnesium and had significantly higher triglycerides ( p less than 0.04 ) and lower HDL-cholesterol ( p less than 0.02 ) than did normotensive subjects . There were no significant changes in dietary plasma lipids with calcium supplementation .  Mildly hyperlipidemic normotensive subjects had a significant decrease in total cholesterol ( p less than 0.05 ) . No significant changes in plasma lipids occurred with calcium supplementation in hypertensive subjects In a double-blind , placebo-controlled trial with 58 normotensive female students , the effect of oral-calcium supplementation ( 1500 mg Ca++/day for 6 wk ) on diastolic and systolic blood pressure was studied while students were consuming a low-calcium diet ( 500 mg Ca++/day  )  by restricting the intake of dairy products . Results show that , in both the calcium- and placebo-supplemented groups , blood pressure values decreased slightly and no effect of oral-calcium supplementation on blood pressure could be demonstrated . In addition , at baseline neither systolic nor diastolic blood pressure correlated with habitual calcium intake . Diastolic but not systolic blood pressure correlated significantly with body mass index ( r = 0.31 , p = 0.01 ) . It is concluded that oral-calcium supplementation for 6 wk does not influence blood pressure in young , healthy normotensive females consuming low-calcium diet Calcium has been shown to inhibit iron absorption . The consequences of chronic calcium supplementation on iron status are unclear , however . As part of a r and omized calcium-supplementation trial in lactating and nonlactating women in the postpartum period , we determined whether long-term calcium supplementation and lactation status affected iron stores as measured by serum ferritin concentrations . Subjects ( 95 lactating and 92 nonlactating ) were enrolled at approximately 6 mo postpartum and then r and omly assigned to receive either 500 mg Ca as calcium carbonate or a placebo twice daily with meals for 6 mo . Lactating women weaned their infants approximately 2 mo after enrollment ( ie , approximately 8 mo postpartum ) . Calcium supplementation had no effect on serum ferritin concentrations . At the end of the study , geometric mean serum ferritin concentrations were 28.4 microg/L in the calcium-supplemented group and 27.5 microg/L in the placebo group ( P > 0.5 ) . Lactation status was significantly related to serum ferritin concentrations . At baseline , serum ferritin concentrations were higher in lactating women than in nonlactating women ( 47.7 compared with 31.5 microg/L , P < 0.001 ) . In lactating women , serum ferritin concentrations decreased by a mean of 17 microg/L after weaning . By 12 mo postpartum , mean serum ferritin concentrations in women who were previously lactating were not significantly higher than those of nonlactating women ( 30.5 compared with 25.5 microg/L ) . These findings provide reassurance that long-term calcium supplementation does not impair iron stores . Furthermore , lactation status should be considered when assessing iron nutriture of women and determinants of iron status in population The effect of calcium supplement use on iron stores was examined in a r and omized controlled study in free-living , healthy , premenopausal women . Of 109 women who completed the study , 52 were in the control group  and 57 took two tablets containing 250 mg Ca as the carbonate with each of two meals daily for 12 wk . In all subjects at baseline , plasma ferritin concentrations were positively correlated with heme-iron intake ( r = 0.21 , P = 0.04 ) , serum iron concentration ( r = 0.19 , P = 0.04 ) , transferrin saturation ( r = 0.31 , P = 0.001 ) , and hemoglobin concentration ( r = 0.22 , P = 0.02 ) , and negatively correlated with total iron-binding capacity ( TIBC , r = -0.42 , P < 0.001 ) . No significant differences in absolute or percent changes in plasma ferritin concentrations , serum iron concentrations , TIBC , transferrin saturation , hemoglobin concentrations , or hematocrit were observed between the treatment and control groups . Thus , over a 12-wk period , use of 1000 mg Ca as the carbonate daily with meals does not appear to be detrimental to iron stores in healthy , free-living , premenopausal women Summary Background The associations of blood pressure with the different manifestations of incident cardiovascular disease in a contemporary population have not been compared . In this study , we aim ed to analyse the associations of blood pressure with 12 different presentations of cardiovascular disease . Methods We used  linked electronic health records from 1997 to 2010 in the CALIBER ( CArdiovascular research using LInked Bespoke studies and Electronic health Records ) programme to assemble a cohort of 1·25 million patients , 30 years of age or older and initially free from cardiovascular disease , a fifth of whom received blood pressure-lowering treatments . We studied the heterogeneity in the age-specific associations of clinical ly measured blood pressure with 12 acute and chronic cardiovascular diseases , and estimated the lifetime risks ( up to 95 years of age ) and cardiovascular disease-free life-years lost adjusted for other risk factors at index ages 30 , 60 , and 80 years . This study is registered at Clinical Trials.gov , number NCT01164371 . Findings During 5·2 years median follow-up , we recorded 83 098 initial cardiovascular disease presentations . In each age group , the lowest risk for cardiovascular disease was in people with systolic blood pressure of 90–114 mm Hg and diastolic blood pressure of 60–74 mm Hg , with no evidence of a J-shaped increased risk at lower blood pressures . The effect of high blood pressure varied by cardiovascular disease endpoint , from strongly positive to no effect . Associations with high systolic blood pressure were strongest for intracerebral haemorrhage ( hazard ratio 1·44 [ 95 % CI 1·32–1·58 ] ) , subarachnoid haemorrhage ( 1·43 [ 1·25–1·63 ] ) , and stable angina ( 1·41 [ 1·36–1·46 ] ) , and weakest for abdominal aortic aneurysm ( 1·08 [ 1·00–1·17 ] ) . Compared with diastolic blood pressure , raised systolic blood pressure had a greater effect on angina , myocardial infa rct ion , and peripheral arterial disease , whereas raised diastolic blood pressure had a greater effect on abdominal aortic aneurysm than did raised systolic pressure . Pulse pressure associations were inverse for abdominal aortic aneurysm ( HR per 10 mm Hg 0·91 [ 95 % CI 0·86–0·98 ] ) and strongest for peripheral arterial disease ( 1·23 [ 1·20–1·27 ] ) . People with  hypertension ( blood pressure ≥140/90 mm Hg or those receiving blood pressure-lowering drugs ) had a lifetime risk of overall cardiovascular disease at 30 years of age of 63·3 % ( 95 % CI 62·9–63·8 ) compared with 46·1 % ( 45·5–46·8 ) for those with normal blood pressure , and developed cardiovascular disease 5·0 years earlier ( 95 % CI 4·8–5·2 ) . Stable and unstable angina accounted for most ( 43 % ) of the cardiovascular disease-free years of life lost associated with hypertension from index age 30 years , whereas heart failure and stable angina accounted for the largest proportion ( 19 % each ) of years of life lost from index age 80 years . Interpretation The widely held assumptions that blood pressure has strong associations with the occurrence of all cardiovascular diseases across a wide age range , and that diastolic and systolic associations are concordant , are not supported by the findings of this high-resolution study . Despite modern treatments , the lifetime burden of hypertension is substantial . These findings emphasise the need for new  blood pressure-lowering strategies , and will help to inform the design of r and omised trials to assess them . Funding Medical Research Council , National Institute for Health Research , and Wellcome Trust The effects of growth , menstrual status , and calcium supplementation on iron status were studied over 4 y in 
    Output:
    
AUTHORS ' CONCLUSIONS An increase in calcium intake slightly reduces both  systolic and diastolic blood pressure in normotensive people , particularly in young people , suggesting a role in the prevention of hypertension .
These results should be interpreted with caution , since the proposed biological mechanism explaining the relationship between calcium and blood pressure has not been fully confirmed .
The effect across multiple prespecified subgroups and a possible dose response effect reinforce this conclusion .
Even small reductions in blood pressure could have important health implication s for reducing vascular disease .