***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: Coronary endothelial function is impaired in hypertension ; however , the severity of this impairment varies among patients . We aim ed to identify the predictors of coronary endothelial dysfunction among clinical variables related to hypertension and atherosclerosis . Twenty-seven untreated , uncomplicated essential hypertensive patients and 10 age-matched healthy controls were studied prospect ively . Myocardial blood flow ( MBF ) was measured by using 15O-water positron emission tomography ( PET ) at rest and during a cold pressor test ( CPT ) .  Coronary vascular resistance ( CVR ) during CPT was used as a marker of coronary endothelial function . Serum low density lipoprotein ( LDL ) cholesterol , high density lipoprotein ( HDL ) cholesterol , triglycerides , malondialdehyde-LDL , homeostasis model assessment , high-sensitivity C-reactive protein ( hs-CRP ) , and plasma interleukin-6 ( IL-6 ) and tumor necrosis factor (TNF)-α were also measured . CVR during CPT  was significantly higher in hypertensive patients than in healthy controls ( 114±26 vs. 94±12 mmHg/[mL/g/min ] ; p<0.05 ) . By univariate analysis , CVR during CPT  was correlated with LDL cholesterol ( r=0.38 , p<0.05 ) , IL-6 ( r=0.46 , p<0.02 ) , and TNF-α ( r=0.39 , p<0.05 ) in hypertensive patients . By multivariate analysis , IL-6 and TNF-α were significant independent predictors of CVR during CPT . Elevated plasma IL-6 and TNF-α levels were independent predictors of coronary endothelial dysfunction in hypertensive patients . These results suggest that plasma IL-6 and TNF-α might be useful for identifying the high risk subgroup of hypertensive patients with coronary endothelial dysfunction and provide an important clue to link systemic inflammation to the development of coronary atherosclerosis Obesity is associated with vascular endothelial dysfunction , as indicated by impaired endothelium-dependent dilation . Presently there is no direct evidence that energy intake – restricted weight loss alone improves conduit or resistance artery endothelium-dependent dilation , the mechanisms involved , or whether improvements differ with patient age . A total of 40 overweight or obese ( body mass index : ≥25<40 kg/m2 ) nondiabetic men and women aged 21 to 69 years completed 12 weeks of  reduced energy intake ( n=26 ; 15 male ) or attention control ( n=14 ; 9 male ) and 4 weeks of weight maintenance ( r and omized trial ) . Energy intake restriction  reduced estimated total energy intake ( 33 % ) , body weight ( 10.5 % ) , total and abdominal body fat , plasma leptin , oxidized low-density lipoprotein , and improved several metabolic risk factors . Brachial artery flow-mediated dilation was increased by 30 % ( 6.0±0.7 % versus 7.9±0.7%&Dgr ; ; P=0.01 ; n=17 ) . Peak forearm blood flow during intrabrachial artery infusion of acetylcholine was increased by 26 % ( 16.8±1.4 versus 21.1±1.9 mL/100 mL per minute ; P<0.05 ; n=15 ) ; this was inversely related to the reduction in the abdominal visceral : subcutaneous fat ratio ( r=−0.46 ; P<0.05 ) and was abolished by inhibition of NO synthesis with NG-monomethyl-l-arginine . Improvements in endothelium-dependent dilation were not related to age : mean increases in subjects > 50 years of age were similar to or greater than those < 50 years of age . Energy intake – restricted weight loss alone is an effective intervention for improving peripheral conduit and resistance artery endothelial function in young and older overweight/obese adults . The improvements in resistance artery function are mediated by an increase in NO bioavailability and are related to reductions in abdominal visceral fat As a competitive inhibitor of endothelial nitric oxide synthase , asymmetric dimethylarginine ( ADMA ) has been related to atherosclerotic disease . Little is known about the prognostic impact of baseline ADMA determination . In a prospect i ve cohort of 1908 patients with coronary artery disease , we assessed baseline serum concentration of ADMA in 1874 consecutive patients with coronary artery disease . One hundred fourteen individuals developed the primary end point of death from cardiovascular causes or nonfatal myocardial infa rct ion during a mean follow-up of 2.6±1.2 years . Median concentrations of ADMA levels were higher among individuals who subsequently developed the primary end point than among those who did not ( 0.70 versus 0.63 & mgr;mol/L ; P<0.001 ) . The risk of future cardiovascular event was associated with increasing thirds of baseline ADMA ( P for trend , < 0.001 ) such that individuals in the highest third at entry had a hazard ratio 2.48 times higher than those in the lowest third ( 95 % confidence interval , 1.52 to 4.06 ; P<0.001 ) . This relationship remained nearly unchanged after adjustment for most potential confounders . Prediction models that simultaneously incorporated ADMA , B-type natriuretic peptide , C-reactive protein , and creatinine in addition to traditional risk factors revealed B-type natriuretic peptide ( hazard ratio , 1.96 ; 95 % confidence interval , 1.3 to 3.0 ; P=0.002 ) and ADMA ( hazard ratio , 1.90 ; 95 % confidence interval , 1.3 to 2.8 ; P=0.001 ) as the strongest risk predictors . High levels of baseline  ADMA independently predict future cardiovascular risk . ADMA has prognostic value beyond traditional risk factors and novel biomarkers and might guide therapeutic strategies OBJECTIVE Diabetic patients have a reduced endothelial response to phosphodiesterase-5 inhibitors . The aim of this study was to determine the effects of chronic therapy with sildenafil on endothelial function in patients with Type 2 diabetes mellitus ( DM2 ) . METHODS In a double-blind , placebo-controlled parallel design , 20 patients without erectile dysfunction r and omly received a loading dose of sildenafil ( 100 mg ) for 3 days , followed by either sildenafil 25 mg three times a day ( t.d.s . ) for 4 weeks or sildenafil 25 mg t.d.s . for 4 days followed by placebo t.d.s . for 3 weeks . RESULTS After 1 week , flow-mediated dilatation ( FMD ) improved significantly ( > 50 % compared with baseline ) in patients allocated to both sildenafil arms ( 62 and 64 % , respectively ) . In patients allocated to chronic sildenafil , a progressive increase in percentage of patients with FMD improvement was noted ( 78 , 86 and 94 % at 2 , 3 and 4 weeks , respectively ) while a progressive decrease in the placebo group occurred ( 45 , 18 and 6 % at 2 , 3 and 4 weeks , respectively ) . At the end of the study , a significant improvement in FMD compared with baseline was noted after chronic sildenafil ( FMD from 6.8 + /- 0.5 to 12.5 + /- 0.7 % , P = 0.01 vs. baseline ) . A decrease in endothelin-1 levels and an increase in nitrite/nitrate levels were found after chronic sildenafil ; significant changes from baseline in C-reactive protein , interleukin 6 , intercellular adhesion molecule and vascular adhesion molecule levels were also found . CONCLUSIONS In DM2 patients , daily sildenafil administration improves endothelial function and reduces markers of vascular inflammation , suggesting that the diabetes-induced impairment of endothelial function may be improved by prolonged phosphodiesterase-5 inhibition The preponderance of evidence states that , in adult men , estradiol ( E2 ) inhibits LH secretion by decreasing pulse amplitude and responsiveness to GnRH consistent with a pituitary site of action . However , this conclusion is based on studies that employed pharmacologic doses of sex steroids , used nonselective aromatase inhibitors , and /or were performed in normal ( NL ) men , a model in which endogenous counterregulatory adaptations to physiologic perturbations confound interpretation of the results . In addition , studies in which estrogen antagonists were administered to NL men demonstrated an increase in LH pulse frequency , suggesting a potential additional hypothalamic site of E2 feedback . To reconcile these conflicting data , we used a selective aromatase inhibitor , anastrozole , to examine the impact of E2 suppression on the hypothalamic-pituitary axis in the male . Parallel studies of NL men and men with idiopathic hypogonadotropic hypogonadism ( IHH ) , whose pituitary-gonadal axis had been normalized with long-term GnRH therapy , were performed to permit precise localization of the site of E2 feedback . In this so-called t and em model , a hypothalamic site of action of sex steroids can thus be inferred whenever there is a difference in the gonadotropin responses of NL and IHH men to alterations in their sex steroid milieu . A selective GnRH antagonist was also used to provide a semiquantitative estimate of endogenous GnRH secretion before and after E2 suppression . Fourteen NL men and seven IHH men were studied . In Exp 1 , nine NL and seven IHH men received anastrozole ( 10 mg/day po x 7 days ) . Blood sample s were drawn daily between 0800 and 1000 h in the NL men and immediately before a GnRH bolus dose in the IHH men . In Exp 2 , blood was drawn ( every 10 min x 12 h ) from nine NL men at baseline and on day 7 of anastrozole . In a subset of five NL men , 5 microg/kg of the Nal-Glu GnRH antagonist was administered on completion of frequent blood sampling , then sampling continued every 20 min for a further 8 h. Anastrozole  suppressed E2 equivalently in the NL ( 136 + /- 10 to 52 + /-2 pmol/L , P < 0.005 ) and IHH men ( 118 + /- 23 to 60 + /- 5 pmol/L , P < 0.005 ) . Testosterone levels rose significantly ( P < 0.005 ) , with a mean increase of 53 + /- 6 % in NL vs. 56 + /- 7 % in IHH men . Despite these similar changes in sex steroids , the increase in gonadotropins was greater in NL than in IHH men ( 100 + /- 9 vs. 58 + /- 6 % for LH , P = 0.07 ; and 85 + /- 6 vs. 41 + /- 4 % for FSH , P < 0.002 ) . Frequent sampling studies in the NL men demonstrated that this rise in mean LH levels , after aromatase blockade , reflected an increase in both LH pulse frequency ( 10.2 + /- 0.9 to 14.0 + /- 1.0 pulses/24 h , P < 0.05 ) and pulse amplitude ( 5.7 + /- 0.7 to 8.4 + /- 0.7 IU/L , P < 0.001 ) . Percent LH inhibition after acute GnRH receptor blockade was similar at baseline and after E2 suppression ( 69.2 + /- 2.4 vs. 70 + /- 1.9 % ) , suggesting that there was no change in the quantity of endogenous GnRH secreted . From these data , we conclude that in the human male , estrogen has dual sites of negative feedback , acting at the hypothalamus to decrease GnRH pulse frequency and at the pituitary to decrease responsiveness to GnRH OBJECTIVES We examined the predictive power of erectile dysfunction ( ED ) on coronary heart disease ( CHD ) events in Chinese men with type 2 diabetes . BACKGROUND Subjects with diabetes are prone to develop cardiovascular complications . Erectile dysfunction is strongly associated with CHD in cross-sectional studies , but prospect i ve data are lacking . METHODS A consecutive cohort of men with no clinical evidence of cardiovascular disease underwent comprehensive assessment s for diabetic complications .  Erectile dysfunction was defined according to the definition of the National Institutes of Health Consensus Conference 1992 . Coronary heart disease events were censored with central ized territory-wide hospital data bases in 2005 . RESULTS Of 2,306 subjects ( age : 54.2 + /- 12.7 years ; follow-up : 4.0 [ range 1.7 to 7.1 ] years ) , 26.7 % had ED at baseline . The incidence of CHD events was higher in men with ED than those without ( 19.7/1,000 person-years , 95 % confidence interval [ CI ] 14.3 to 25.2 person-years vs.  
    Output:
    
In addition to male hypogonadism and macrovascular disease , endothelial dysfunction is central to the connection between the metabolic syndrome and ED .
Conversely , improved glycemic control and weight loss have been found to improve erectile function .
CONCLUSION ED is very prevalent in men with DM and obesity .