***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: Importance Defining what represents a macronutritionally balanced diet remains an open question and a high priority in nutrition research . Although the amount of protein may have specific effects , from a broader dietary perspective , the choice of protein sources will inevitably influence other components of diet and may be a critical determinant for the health outcome . Objective To examine the associations of animal and plant protein intake with the risk for mortality . Design , Setting , and Participants This prospect i ve cohort study of US health care professionals included 131 342 participants from the Nurses ' Health Study ( 1980 to end of follow-up on June 1 , 2012 ) and Health Professionals Follow-up Study ( 1986 to end of follow-up on January 31 , 2012 ) .  Animal and plant protein intake was assessed by regularly up date d vali date d food frequency question naires . Data were analyzed from June 20 , 2014 , to January 18 , 2016 . Main Outcomes and Measures Hazard ratios ( HRs ) for all-cause and cause-specific mortality . Results Of the 131 342 participants , 85 013 were women ( 64.7 % ) and 46 329 were men ( 35.3 % ) ( mean [ SD ] age , 49 [ 9 ] years ) .  The median protein intake , as assessed by percentage of energy , was 14 % for animal protein ( 5th-95th percentile , 9%-22 % ) and 4 % for plant protein ( 5th-95th percentile , 2%-6 % ) . After adjusting for major lifestyle and dietary risk factors , animal protein intake was not associated with all-cause mortality ( HR , 1.02 per 10 % energy increment ; 95 % CI , 0.98 - 1.05 ; P for trend = .33 ) but was associated with higher cardiovascular mortality ( HR , 1.08 per 10 % energy increment ; 95 % CI , 1.01 - 1.16 ; P for trend = .04 ) . Plant protein was associated with lower all-cause mortality ( HR , 0.90 per 3 % energy increment ; 95 % CI , 0.86 - 0.95 ; P for trend < .001 ) and cardiovascular mortality ( HR , 0.88 per 3 % energy increment ; 95 % CI , 0.80 - 0.97 ; P for trend = .007 ) . These associations were confined to participants with at least 1 unhealthy lifestyle factor based on smoking , heavy alcohol intake , overweight or obesity , and physical inactivity , but not evident among those without any of these risk factors . Replacing animal protein of various origins with plant protein was associated with lower mortality . In particular , the HRs for all-cause mortality were 0.66 ( 95 % CI , 0.59 - 0.75 ) when 3 % of energy from plant protein was substituted for an equivalent amount of protein from processed red meat , 0.88 ( 95 % CI , 0.84 - 0.92 ) from unprocessed red meat , and 0.81 ( 95 % CI , 0.75 - 0.88 ) from egg . Conclusions and Relevance High animal protein intake was positively associated with cardiovascular mortality and high plant protein intake was inversely associated with all-cause and cardiovascular mortality  , especially among individuals with at least 1 lifestyle risk factor . Substitution of plant protein for animal protein , especially that from processed red meat , was associated with lower mortality , suggesting the importance of protein source BACKGROUND Statin intolerance limits many patients from achieving optimal low-density lipoprotein cholesterol ( LDL-C ) concentrations . Current options for such patients include using a lower but tolerated dose of a statin and adding or switching to ezetimibe or other non-statin therapies . METHODS ODYSSEY ALTERNATIVE ( NCT01709513 ) compared alirocumab with ezetimibe in patients at moderate to high cardiovascular risk with statin intolerance ( unable to tolerate ≥2 statins , including one at the lowest approved starting dose ) due to muscle symptoms . A placebo run-in and statin rechallenge arm were included in an attempt to confirm intolerance . Patients ( n = 361 ) received single-blind subcutaneous ( SC ) and oral placebo for 4 weeks during placebo run-in . Patients reporting muscle-related symptoms during the run-in were to be withdrawn . Continuing patients were r and omized ( 2:2:1 ) to double-blind alirocumab 75 mg SC every 2 weeks ( Q2W ; plus oral placebo ) , ezetimibe 10 mg/d ( plus SC placebo Q2W ) , or atorvastatin 20 mg/d ( rechallenge ; plus SC placebo Q2W ) for 24 weeks . Alirocumab dose was increased to 150 mg Q2W at week 12 depending on week 8 LDL-C values . Primary end point was percent change in LDL-C from baseline to week 24 ( intent-to-treat ) for alirocumab vs ezetimibe . RESULTS Baseline mean ( st and ard deviation ) LDL-C was 191.3 ( 69.3 ) mg/dL ( 5.0 [ 1.8 ] mmol/L ) . Alirocumab reduced mean ( st and ard error ) LDL-C by 45.0 % ( 2.2 % ) vs 14.6 % ( 2.2 % ) with ezetimibe ( mean difference 30.4 % [ 3.1 % ] , P < .0001 ) . Skeletal muscle-related events were less frequent with alirocumab vs atorvastatin ( hazard ratio 0.61 , 95 % confidence interval 0.38 - 0.99 , P = .042 ) . CONCLUSIONS Alirocumab produced greater LDL-C reductions than ezetimibe in statin-intolerant patients , with fewer skeletal-muscle adverse events vs atorvastatin Background : A continuous relationship between reductions in low-density lipoprotein cholesterol ( LDL-C ) and major adverse cardiovascular events ( MACE ) has been observed in statin and ezetimibe outcomes trials down to achieved levels of 54 mg/dL. However , it is uncertain whether this relationship extends to LDL-C levels < 50 mg/dL. We assessed the relationship between additional LDL-C , non – high-density lipoprotein cholesterol , and apolipoprotein B100 reductions and MACE among patients within the ODYSSEY trials that compared alirocumab with controls ( placebo/ezetimibe )  , mainly as add-on therapy to maximally tolerated statin . Methods : Data were pooled from 10 double-blind trials ( 6699 patient-years of follow-up ) . R and omization was to alirocumab 75/150 mg every 2 weeks or control for 24 to 104 weeks , added to background statin therapy in 8 trials . This analysis included 4974 patients ( 3182 taking alirocumab , 1174 taking placebo , 618 taking ezetimibe ) . In a post hoc analysis , the relationship between average on-treatment lipid levels and percent reductions in lipids from baseline were correlated with MACE ( coronary heart disease death , nonfatal myocardial infa rct ion , ischemic stroke , or unstable angina requiring hospitalization ) in multivariable analyses . Results : Overall , 33.1 % of the pooled cohort achieved average LDL-C < 50 mg/dL ( 44.7%–52.6 % allocated to alirocumab , 6.5 % allocated to ezetimibe , and 0 % allocated to placebo ) . In total , 104 patients experienced MACE ( median time to event , 36 weeks ) . For every 39 mg/dL lower achieved LDL-C , the risk of MACE appeared to be 24 % lower ( adjusted hazard ratio , 0.76 ; 95 % confidence interval , 0.63–0.91 ; P=0.0025 ) . Percent reductions in LDL-C from baseline were inversely correlated with MACE rates ( hazard ratio , 0.71 ; 95 % confidence interval , 0.57–0.89 per additional 50 % reduction from baseline ; P=0.003 ) . Strengths of association material ly similar to those described for LDL-C were observed with achieved non – high-density lipoprotein cholesterol and apolipoprotein B100 levels or percentage reductions . Conclusions : In a post hoc analysis from 10 ODYSSEY trials , greater percentage reductions in LDL-C and lower on-treatment LDL-C were associated with a lower incidence of MACE , including very low levels of LDL-C ( < 50 mg/dL ) . These findings require further validation in the ongoing prospect i ve ODYSSEY OUTCOMES trial . Clinical Trial Registration : URL : https://www . clinical trials.gov . Unique identifiers : NCT01507831 , NCT01623115 , NCT01709500 , NCT01617655 , NCT01644175 , NCT01644188 , NCT01644474 , NCT01730040 , NCT01730053 , and NCT01709513 BACKGROUND Diabetes confers an increased risk of adverse cardiovascular and renal events . In the EMPA-REG OUTCOME trial , empagliflozin , a sodium-glucose cotransporter 2 inhibitor , reduced the risk of major adverse cardiovascular events in patients with type 2 diabetes at high risk for cardiovascular events . We wanted to determine the long-term renal effects of empagliflozin , an analysis that was a prespecified component of the secondary microvascular outcome of that trial . METHODS We r and omly assigned patients with type 2 diabetes and an estimated glomerular filtration rate of at least 30 ml per minute per 1.73 m(2 ) of body-surface area to receive either empagliflozin ( at a dose of 10 mg or 25 mg ) or placebo once daily . Prespecified renal outcomes included incident or worsening nephropathy ( progression to macroalbuminuria , doubling of the serum creatinine level , initiation of renal-replacement therapy , or death from renal disease ) and incident albuminuria . RESULTS Incident or worsening nephropathy occurred in 525 of 4124 patients ( 12.7 % ) in the empagliflozin group and in 388 of 2061 ( 18.8 % ) in the placebo group ( hazard ratio in the empagliflozin group , 0.61 ; 95 % confidence interval , 0.53 to 0.70 ; P<0.001 ) . Doubling of the serum creatinine level occurred in 70 of 4645 patients ( 1.5 % ) in the empagliflozin group and in 60 of 2323 ( 2.6 % ) in the placebo group , a significant relative risk reduction of 44 % . Renal-replacement therapy was initiated in 13 of 4687 patients ( 0.3 % ) in the empagliflozin group and in 14 of 2333 patients ( 0.6 % ) in the placebo group , representing a 55 % lower relative risk in the empagliflozin group . There was no significant between-group difference in the rate of incident albuminuria . The adverse-event profile of empagliflozin in patients with impaired kidney function at baseline was similar to that reported in the overall trial population . CONCLUSIONS In patients with type 2 diabetes at high cardiovascular risk , empagliflozin was associated with slower progression of kidney disease and lower rates of clinical ly relevant renal events than was placebo when added to st and ard care . ( Funded by the Boehringer Ingelheim and Eli Lilly and Company Diabetes Alliance ; EMPA-REG OUTCOME Clinical Trials.gov number , NCT01131676 . ) BACKGROUND Previous trials have shown that the use of statins to lower cholesterol reduces the risk of cardiovascular events among persons without cardiovascular disease . Those trials have involved persons with elevated lipid levels or inflammatory markers and involved mainly white persons . It is unclear whether the benefits of statins can be extended to an intermediate-risk , ethnically diverse population without cardiovascular disease . METHODS In one comparison from a 2-by-2 factorial trial , we r and omly assigned 12,705 participants in 21 countries who did not have cardiovascular disease and were at intermediate risk to receive rosuvastatin at a dose of 10 mg per day or placebo . The first co primary outcome was the composite of death from cardiovascular causes , nonfatal myocardial infa rct ion , or nonfatal stroke , and the second co primary outcome additionally included revascularization , heart failure , and resuscitated cardiac arrest . The median follow-up was 5.6 years . RESULTS The overall mean low-density lipoprotein cholester 
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Some good news comes from a systematic review and meta- analysis which has documented that about 60–75 min per day of vigorous intensity physical activity ( > 35.5METs-h/week ) seems to reduce the increased risk of death associated with high sitting time .