***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 
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    ***EXAMPLES*** 
    Input: OBJECTIVES This study investigated the effects of walking training ( WT ) on cardiovascular function and autonomic regulation in patents with intermittent claudication ( IC ) . DESIGN R and omized controlled trial . METHODS Forty-two male patients with IC ( ≥50years ) were r and omly allocated into two groups : control ( CG , n=20 , 30min of stretching exercises ) and WT ( WTG , n=22 , 15 bouts of 2min of walking interpolated by 2min of upright rest-walking intensity was set at the heart rate of pain threshold ) . Both interventions were performed twice/week for 12 weeks . Walking capacity ( maximal treadmill test ) , blood pressure ( auscultatory ) , cardiac output ( CO2 rebreathing ) , heart rate ( ECG ) , stroke volume , systemic vascular resistance , forearm and calf vascular resistance ( plethysmography ) , and low ( LF ) and high frequency ( HF ) components of heart rate variability and spontaneous baroreflex sensitivity were measured at baseline and after 12 weeks of the study . RESULTS WT increased total walking distance ( + 302±85 m , p=0.001 ) and spontaneous baroreflex sensitivity ( + 2.13±1.07ms/mmHg , p=0.02 ) . Additionally , at rest , WT decreased systolic and mean blood pressures ( -10±3 and -5±2mmHg , p=0.001 and p=0.01 , respectively ) , cardiac output ( -0.37±0.24l/min , p=0.03 ) , heart rate ( -4±2bpm , p=0.001 ) , forearm vascular resistance ( -8.5±2.8U , p=0.02 ) and LF/HF ( -1.24±0.99 , p=0.001 ) . No change was observed in the CG . CONCLUSIONS In addition to increasing walking capacity , WT improved cardiovascular function and autonomic regulation in patients with IC Objective —Peripheral artery disease ( PAD ) is characterized by impaired blood flow to the lower extremities , causing claudication and exercise intolerance . The mechanism(s ) by which exercise training improves functional capacity is not understood . This study tested the hypothesis that in PAD patients who undergo supervised exercise training  , increases in capillary density ( CD ) in calf muscle take place before improvements in peak oxygen uptake ( VO2 ) . Methods and Results —Thirty-five PAD patients were r and omly assigned to 12 weeks of directly supervised or home-based exercise training .  Peak VO2 testing and gastrocnemius muscle biopsies were performed at baseline and after training . CD ( endothelial cells/mm2 ) was measured using immunofluorescence staining . After 3 weeks of directly supervised training , patients had an increase in CD ( 216±66 versus 284±77 , P<0.01 ) but no increase in peak VO2 . However , after 12 weeks , peak VO2 increased ( 15.3±2.8 versus 16.8±3.8 , P<0.01 ) , whereas in muscle , CD remained increased over baseline , but there were no changes in markers of oxidative capacity . Within subjects , CD was related to peak VO2 before and after directly supervised training . Conclusion —Changes in CD in ischemic muscle with training may modulate the response to training , and those changes precede the increase in VO2 BACKGROUND Serum markers of inflammation and platelet activation are related to cardiovascular risk . Cardiovascular risk reduction is a major treatment goal in patients with peripheral arterial disease ( PAD ) . Although current guidelines recommend supervised exercise training ( SET ) for PAD patients with intermittent claudication , its contribution to risk reduction remains unclear . Aim of the present study was to assess the impact of SET on inflammation and platelet activation as surrogates for cardiovascular risk . METHODS Fifty-three patients with intermittent claudication were r and omly assigned to SET on top of best medical treatment ( BMT ) for 6 months ( SET-group ) or to BMT only ( BMT-group ) . High sensitivity C-reactive protein ( hs-CRP ) , interleukin-6 ( IL-6 ) and fibrinogen as well as soluble P-selectin ( sP-sel ) , prothrombin fragment 1 + 2 ( F1.2 ) and monocyte-platelet aggregates ( MPA ) were determined at study entry , after 3 , 6 and 12 months . RESULTS While clinical improvement , reflected by an increase of walking capacity , was observed upon SET , no lasting changes of markers of inflammation and platelet activation were found within the SET-group during the training period . Compared to the BMT-group no improvements of these markers were observed in response to training at any time point ( all p > 0.05 ) . CONCLUSION Regular SET added no further anti-inflammatory effect and had no effect on platelet activation when provided on top of BMT in PAD patients with intermittent claudication Flaws in the design , conduct , analysis , and reporting of r and omised trials can cause the effect of an intervention to be underestimated or overestimated . The Cochrane Collaboration ’s tool for assessing risk of bias aims to make the process clearer and more Background It is unclear how much of the reduction in cardiac mortality in coronary heart disease ( CHD ) patients with exercise training  is the result of direct effects on the heart and coronary vasculature , or to indirect effects , via primary risk factors . Objective The aim of this article was to quantify the cardiac mortality benefits of exercise-based rehabilitation attributable to risk factor reductions versus the direct effects on the heart and vasculature . Methods The IMPACT coronary heart disease model was used to examine the reduction in cardiac mortality attributable to changes in risk factors from a meta- analysis of cardiac rehabilitation r and omized , controlled trials . Patients were receiving rehabilitation following an acute myocardial infa rct ion , angina pectoris or revascularization . Outcomes considered were primary risk factors ( total cholesterol , systolic blood pressure and smoking behaviour ) and cardiac mortality . Results Nineteen exercise-only cardiac rehabilitation trials ( including 2984 patients ) were identified . Across these trials , exercise training reduced pooled cardiac mortality by 28 % ( relative risk , 0.72 , 95 % confidence interval 0.55–0.95 ) , with 30 fewer deaths than in the control group . Applying the CHD model , approximately 17 ( 58 % ) of these 30 fewer deaths were attributable to reductions in major cardiovascular risk factors : 7.1 deaths ( minimum estimate 6.2 , maximum estimate 9.5 ) attributable to an 18 % reduction in smoking prevalence ; 5.9 deaths ( minimum −0.6 , maximum 12.6 ) to a 0.11 mmol/l reduction in cholesterol , and 4.4 deaths ( −1.0 minimum , 6.7 maximum ) to a 2.0 mmHg reduction in systolic blood pressure . Conclusions Approximately half of the 28 % reduction in cardiac mortality achieved with exercise-based cardiac rehabilitation may be attributed to reductions in major risk factors , particularly smoking . Eur J Cardiovasc Prev Rehabil 13:369–374 © 2006 The European Society of Background Inflammation is the driving force in atherosclerosis . One central strategy in the treatment of peripheral arterial disease ( PAD ) is the promotion of angiogenesis . Here , proangiogenic Tie-2 expressing monocytes ( TEM ) and circulating angiogenic cells ( CAC ) play a crucial role . Exercise training ( ET ) is recommended in PAD patients at Fontaine stage II to promote angiogenesis . Methods 40 patients with intermittend claudication ( IC ) [ 2 groups : supervised ET ( SET ) vs. non-supervised ET ( nSET ) , each n = 20 ] and 20 healthy controls were included in the study .  Analysis of TEM and CAC was performed from whole blood by flow-cytometry . TEM were identified via CD45 , CD86 , CD14 , CD16 and analysed for the expression of Tie-2 . CAC were identified via their expression of CD45 ( CD45dim ) , CD34 and VEGF-R2 ( CD309/KDR ) . Follow up was performed after mean of 7.65 ± 1.62 months . Results In comparison to healthy controls , we found increased proportions of CAC ( p < 0.0001 ) and similar TEM numbers in both ET groups . At follow-up ( FU ) TEM poroportions increased ( p < 0.001 ) and CAC proportions decreased ( p < 0.01 ) , but both more significantly in SET ( p < 0.001 ) than nSET ( p = 0.01 ) . Only in SET fibrinogen levels decreased and VEGF-A increased ( both p < 0.05 ) . Finally , we found in both ET groups a significant increase in absolute walking distance but with a higher individual increase in SET ( p < 0.01 ) . TEM and CAC proportions correlated inversely with the absolute walking distance ( CAC : r = −0.296 , p = 0.02 ; TEM : r = −0.270 , p = 0.04 ) as well as with ABI ( CAC : r = −0.394 , p < 0.01 ; TEM : r = −0.382 , p < 0.01 ) . Conclusions ET  influences the distribution of CAC and TEM proportions . nSET , although still effective in regard to an improved walking distance , is less effective in the influence of proangiogenic cells and inflammatory burden than SET . Our results indicate SET to be a more preferential exercise form , supporting the necessity to establish more SET programs In 1997 , the World Health Organization published a l and mark document recognizing obesity as a worldwide disease that poses a serious threat to public health ( 1 ) . Persons who are overweight or obese have substantially increased risk for morbidity from numerous chronic disorders , such as diabetes ( 2 , 3 ) , hypertension ( 4 , 5 ) , and cardiovascular disease ( 6 , 7 ) . Obesity-related health risk is greater when excess fat is deposited in the abdomen region because this phenotype is a stronger predictor of cardiovascular disease and type 2 diabetes mellitus than general obesity is ( 8 - 11 ) . This may be partially explained by excess accumulation of visceral fat , an independent correlate of insulin resistance ( 9 - 11 ) and dyslipidemia ( 8 , 9 ) . These observations highlight the need to identify appropriate treatment strategies to prevent and reduce obesity and suggest that the effectiveness of these treatments would be enhanced if abdominal obesity , particularly visceral fat , was substantially reduced . Diet restriction remains the most common method of obesity reduction ( 12 ) . Despite the observation that low levels of physical activity are a major cause of obesity ( 13 ) , increased physical activity alone is not thought to be a useful strategy for obesity reduction . Some reports have suggested that physical activity in obese adults results in only modest weight loss ( approximately 1 to 2 kg ) independent of the effects of diet restriction ( 14 ) . However , these conclusions are drawn from studies in which individual energy intake and expenditure were not rigorously controlled or accurately measured ( 15 - 17 ) . Moreover , in most studies , the negative energy balance induced by exercise was modest enough that substantial weight loss was not expected ( 15 - 17 ) . Currently , no compelling evidence supports the observation that exercise alone is not a useful method for reducing total or abdominal obesity . It is well known that a single exercise session is associated with a significant improvement in insulin-stimulated glucose uptake ( 18 , 19 ) . It is also clear that weight loss is associated with an improvement in insulin action ( 20 - 24 ) . It is unclear , however , whether regular exercise improves glucose metabolism after the short-term effects of exercise and changes in body fat distribution are considered . Segal and colleagues ( 25 ) controlled for the confounding effect of the last exercise session and body composition changes and found that exercise had no independent effect on insulin sensitivity ( 25 ) . Given the established importance of insulin resistance as an antecedent to both cardiovascular disease and type 2 diabetes mellitus ( 26 ) , it is important to clarify whether exercise improves insulin action independent of fat loss . We performed a r and omized , controlled trial to determine the independent effect of diet-induced or exercise-induced weight loss on obesity and insulin resistance in moderately obese men . We also evaluated whether exercise without weight loss was associated with reductions in abdominal obesity and insulin resistance . Methods Participants Participants were recruited from Kingston , Ontario , Canada , a typical suburban region , through the general media . We selected men with a body mass index greater than 27 kg/m2 and a waist circumference greater than 100 cm whose weight had been stable ( 2 kg ) for 6 months before study entry . Participants were nonsmokers who consumed an average of fewer than two alcoholic beverages per day , had a sedentary lifestyle , and took no medications known to affect the principal outcome measures . All participants had a preparticipation medical examination that included screening for normal glucose tolerance and plasma lipid profile . A computer program was used to r and omly assign eligible men to one of the following four groups : control , diet-induced weight loss , exercise-induced weight loss , and exercise without weight loss ( Figure 1 ) . Of the 101 participants who were r and omly assigned to groups , 34 chose not to participate because they were diss 
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Conclusions This systematic review and meta‐ analysis shows favorable effects of SET on modifiable cardiovascular risk factors , specifically blood pressure and cholesterol levels .
Despite the moderate quality , small trial sample sizes , and study heterogeneity , these findings support the prescription of SET programs not only to increase walking distances but also for risk factor modification .