human
***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: Purpose To assess the effects of short-acting nitrates on  exercise stress test ( EST ) results and the relation between EST results and coronary blood flow ( CBF ) response to nitrates in patients with microvascular angina ( MVA ) . Methods We completed 2 symptom/sign limited ESTs on 2 separate days , in a r and om sequence and in pharmacological washout , in 29 MVA patients and in 24 patients with obstructive coronary artery disease ( CAD ) : one EST was performed without any intervention ( control EST , C-EST ) , and the other after sublingual isosorbide dinitrate , 5 mg ( nitrate EST , N-EST ) . CBF response to nitroglycerin  ( 25 μg ) was assessed in the left anterior descending coronary artery by transthoracic Doppler-echocardiography . Results At C-EST . ST-segment depression ≥1 mm ( STD ) was induced in 26 ( 90 % ) and 23 ( 96 % ) MVA and CAD patients , respectively ( p = 0.42 ) , whereas at N-EST , STD was induced in 25 ( 86 % ) and 14 ( 56 % ) MVA and CAD patients , respectively ( p = 0.01 ) . Time and rate pressure product at 1 mm STD increased during N-EST , compared to C-EST , in CAD patients ( 475 ± 115 vs. 365 ± 146 s , p < 0.001 ; and 23511 ± 4352 vs. 20583 ± 6234 bpm⋅mmHg , respectively , p = 0.01 ) , but not in MVA patients ( 308 ± 160 vs. 284 ± 136 s ; p = 0.19 ; and 21290 ± 5438 vs. 20818 ± 4286 bpm⋅mmHg , respectively , p = 0.35 ) . In MVA patients , a significant correlation was found between heart rate at STD during N-EST and CBF response to nitroglycerin ( r = 0.40 , p = 0.04 ) . Conclusions Short-acting nitrates improve EST results in CAD , but not in MVA patients . In MVA patients a lower nitrate-dependent coronary microvascular dilation may contribute to the lack of effects of nitrates on EST results AIMS Chronic ischaemic cardiovascular disease ( CICD ) is a major cause of mortality and morbidity worldwide . The primary objective of the CICD-Pilot registry was to describe the clinical characteristics and management modalities across Europe in a broad spectrum of patients with CICD . METHODS AND RESULTS The CICD-Pilot registry is an international prospect i ve observational longitudinal registry , conducted in 100 centres from 10 countries selected to reflect the diversity of health systems and care attitudes across Europe . From April 2013 to December 2014 , 2420 consecutive CICD patients with non-ST-elevation acute coronary syndrome ( n = 755 ) and chronic stable coronary artery disease ( n = 1464 ) , of whom 933 ( 63.7 % ) were planned for elective coronary intervention , or with peripheral artery disease ( PAD ) ( n = 201 ) , were enrolled ( 30.5 % female patients ) . Mean age was 66.6 ± 10.9 years . The following risk factors were reported : smoking 54.6 % , diabetes mellitus 29.2 % , hypertension 82.6 % , and hypercholesterolaemia 74.1 % . Assessment of cardiac function was made in 69.5 % and an exercise stress test in 21.2 % during/within 1 year preceding admission . New stress imaging modalities were applied in a minority of patients . A marked increase was observed at discharge in the rate of prescription of angiotensin-converting enzyme-inhibitors/angiotensin receptor blockers  ( 82.8 % ) , beta-blockers  ( 80.2 % ) , statins  ( 92.7 % ) , aspirin  ( 90.3 % ) , and clopidogrel ( 66.8 % ) . Marked differences in clinical profile and treatment modalities were observed across the four cohorts . CONCLUSION The CICD-Pilot registry suggests that implementation of guideline -recommended therapies has improved since the previous surveys but that important heterogeneity exists in the clinical profile and treatment modalities in the different cohorts of patients enrolled with a broad spectrum of CICDs AIMS The Euro Heart Survey of Stable Angina set out to prospect ively study the presentation and management of patients with stable angina as first seen by a cardiologist in Europe , with particular reference to adherence to existing guidelines and regional variability in patient presentation and initial assessment . METHODS AND RESULTS Consecutive out patients with a clinical diagnosis by a cardiologist of stable angina were enrolled in the study and 3779 patients were included in the analysis . The average age was 61 years and 58 % were male . The majority of patients ( 88 % ) had mild to moderate angina , CCS class I or II . Despite a high prevalence of recognized risk factors , 27 % did not have cholesterol and 33 % did not have glucose measured within 4 weeks of assessment . The resting ECG was abnormal in 41 % of patients . An  exercise ECG  was performed or planned as part of initial investigation in 76 % of patients and 18 % had a stress imaging test such as perfusion scanning or stress echo . A coronary angiogram was performed or planned in 41 % , and 64 % had an echo . The time from assessment to investigation varied widely , particularly for angiography . One in 10 patients had neither any form of stress test nor angiography , with marked regional variation . Availability of invasive facilities increased the likelihood of both non-invasive and invasive investigations . Those with more severe symptoms or longer duration of symptoms or a positive non-invasive test were more likely to have  angiography . In multivariable analysis , a positive stress test was the strongest predictor of the use of angiography , associated with a six-fold increase in the likelihood of invasive investigation . However , gender and availability of facilities were also predictive . CONCLUSION Considerable variation in features at presentation and use of investigations has been identified in the stable angina population in Europe . The evaluation of biochemical cardiovascular risk factors was suboptimal . Overall rates of non-invasive investigation for angina and the clinical appropriateness of factors predictive of the use of invasive investigation were broadly in line with guidelines . However , the influence of access to facilities , and marked international variation in rates and timing of investigation suggest that factors unrelated to clinical need are also influential in the management of patients with stable angina IMPORTANCE In the era of widespread revascularization and effective antianginals , the prevalence and prognostic effect of anginal symptoms and myocardial ischemia among patients with stable coronary artery disease ( CAD ) are unknown . OBJECTIVE To describe the current clinical patterns among patients with stable CAD and the association of anginal symptoms or myocardial ischemia with clinical outcomes . DESIGN , SETTING , AND PARTICIPANTS The Prospect i ve Observational Longitudinal Registry of Patients With Stable Coronary Artery Disease ( CLARIFY ) registry enrolled out patients in 45 countries with stable CAD in 2009 to 2010 with 2-year follow-up ( median , 24.1 months ; range , 1 day to 3 years ) . Enrollees included 32 105 out patients with prior myocardial infa rct ion , chest pain , and evidence of myocardial ischemia , evidence of CAD on angiography , or prior revascularization . Of these , 20 291 ( 63.2 % ) had undergone a noninvasive test for myocardial ischemia within 12 months of enrollment and were categorized into one of the following 4 groups : no angina or ischemia ( n = 13 207 [ 65.1 % ] ) ; evidence of myocardial ischemia without angina ( silent ischemia ) ( n = 3028 [ 14.9 % ] ) ; anginal symptoms alone ( n = 1842 [ 9.1 % ] ) ; and angina and ischemia ( n = 2214 [ 10.9 % ] ) . EXPOSURES Stable CAD . MAIN OUTCOME AND MEASURE The composite of cardiovascular (CV)-related death or nonfatal myocardial infa rct ion . RESULTS Overall , 4056 patients ( 20.0 % ) had anginal symptoms and 5242 ( 25.8 % ) had evidence of myocardial ischemia on results of noninvasive testing . Of 469 CV-related deaths or myocardial infa rct ions , 58.2 % occurred in patients without angina or ischemia , 12.4 % in patients with ischemia alone , 12.2 % in patients with angina alone , and 17.3 % in patients with both . The hazard ratios for the primary outcome relative to patients without angina or ischemia and adjusted for age , sex , geographic region , smoking status , hypertension , diabetes mellitus , and dyslipidemia were 0.90 ( 95 % CI , 0.68 - 1.20 ; P = .47 ) for ischemia alone , 1.45 ( 95 % CI , 1.08 - 1.95 ; P = .01 ) for angina alone , and 1.75 ( 95 % CI , 1.34 - 2.29 ; P < .001 ) for both . Similar findings were observed for CV-related death and for fatal or nonfatal myocardial infa rct ion . CONCLUSIONS AND RELEVANCE In out patients with stable CAD , anginal symptoms ( with or without ischemia on noninvasive testing ) but not silent ischemia appear to be associated with an increased risk for adverse CV outcomes . Most CV events occurred in patients without angina or ischemia . TRIAL REGISTRATION is rct n.org Identifier : IS RCT N43070564 
    Output:
    
agent
***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: Purpose To assess the effects of short-acting nitrates on  exercise stress test ( EST ) results and the relation between EST results and coronary blood flow ( CBF ) response to nitrates in patients with microvascular angina ( MVA ) . Methods We completed 2 symptom/sign limited ESTs on 2 separate days , in a r and om sequence and in pharmacological washout , in 29 MVA patients and in 24 patients with obstructive coronary artery disease ( CAD ) : one EST was performed without any intervention ( control EST , C-EST ) , and the other after sublingual isosorbide dinitrate , 5 mg ( nitrate EST , N-EST ) . CBF response to nitroglycerin  ( 25 μg ) was assessed in the left anterior descending coronary artery by transthoracic Doppler-echocardiography . Results At C-EST . ST-segment depression ≥1 mm ( STD ) was induced in 26 ( 90 % ) and 23 ( 96 % ) MVA and CAD patients , respectively ( p = 0.42 ) , whereas at N-EST , STD was induced in 25 ( 86 % ) and 14 ( 56 % ) MVA and CAD patients , respectively ( p = 0.01 ) . Time and rate pressure product at 1 mm STD increased during N-EST , compared to C-EST , in CAD patients ( 475 ± 115 vs. 365 ± 146 s , p < 0.001 ; and 23511 ± 4352 vs. 20583 ± 6234 bpm⋅mmHg , respectively , p = 0.01 ) , but not in MVA patients ( 308 ± 160 vs. 284 ± 136 s ; p = 0.19 ; and 21290 ± 5438 vs. 20818 ± 4286 bpm⋅mmHg , respectively , p = 0.35 ) . In MVA patients , a significant correlation was found between heart rate at STD during N-EST and CBF response to nitroglycerin ( r = 0.40 , p = 0.04 ) . Conclusions Short-acting nitrates improve EST results in CAD , but not in MVA patients . In MVA patients a lower nitrate-dependent coronary microvascular dilation may contribute to the lack of effects of nitrates on EST results AIMS Chronic ischaemic cardiovascular disease ( CICD ) is a major cause of mortality and morbidity worldwide . The primary objective of the CICD-Pilot registry was to describe the clinical characteristics and management modalities across Europe in a broad spectrum of patients with CICD . METHODS AND RESULTS The CICD-Pilot registry is an international prospect i ve observational longitudinal registry , conducted in 100 centres from 10 countries selected to reflect the diversity of health systems and care attitudes across Europe . From April 2013 to December 2014 , 2420 consecutive CICD patients with non-ST-elevation acute coronary syndrome ( n = 755 ) and chronic stable coronary artery disease ( n = 1464 ) , of whom 933 ( 63.7 % ) were planned for elective coronary intervention , or with peripheral artery disease ( PAD ) ( n = 201 ) , were enrolled ( 30.5 % female patients ) . Mean age was 66.6 ± 10.9 years . The following risk factors were reported : smoking 54.6 % , diabetes mellitus 29.2 % , hypertension 82.6 % , and hypercholesterolaemia 74.1 % . Assessment of cardiac function was made in 69.5 % and an exercise stress test in 21.2 % during/within 1 year preceding admission . New stress imaging modalities were applied in a minority of patients . A marked increase was observed at discharge in the rate of prescription of angiotensin-converting enzyme-inhibitors/angiotensin receptor blockers  ( 82.8 % ) , beta-blockers  ( 80.2 % ) , statins  ( 92.7 % ) , aspirin  ( 90.3 % ) , and clopidogrel ( 66.8 % ) . Marked differences in clinical profile and treatment modalities were observed across the four cohorts . CONCLUSION The CICD-Pilot registry suggests that implementation of guideline -recommended therapies has improved since the previous surveys but that important heterogeneity exists in the clinical profile and treatment modalities in the different cohorts of patients enrolled with a broad spectrum of CICDs AIMS The Euro Heart Survey of Stable Angina set out to prospect ively study the presentation and management of patients with stable angina as first seen by a cardiologist in Europe , with particular reference to adherence to existing guidelines and regional variability in patient presentation and initial assessment . METHODS AND RESULTS Consecutive out patients with a clinical diagnosis by a cardiologist of stable angina were enrolled in the study and 3779 patients were included in the analysis . The average age was 61 years and 58 % were male . The majority of patients ( 88 % ) had mild to moderate angina , CCS class I or II . Despite a high prevalence of recognized risk factors , 27 % did not have cholesterol and 33 % did not have glucose measured within 4 weeks of assessment . The resting ECG was abnormal in 41 % of patients . An  exercise ECG  was performed or planned as part of initial investigation in 76 % of patients and 18 % had a stress imaging test such as perfusion scanning or stress echo . A coronary angiogram was performed or planned in 41 % , and 64 % had an echo . The time from assessment to investigation varied widely , particularly for angiography . One in 10 patients had neither any form of stress test nor angiography , with marked regional variation . Availability of invasive facilities increased the likelihood of both non-invasive and invasive investigations . Those with more severe symptoms or longer duration of symptoms or a positive non-invasive test were more likely to have  angiography . In multivariable analysis , a positive stress test was the strongest predictor of the use of angiography , associated with a six-fold increase in the likelihood of invasive investigation . However , gender and availability of facilities were also predictive . CONCLUSION Considerable variation in features at presentation and use of investigations has been identified in the stable angina population in Europe . The evaluation of biochemical cardiovascular risk factors was suboptimal . Overall rates of non-invasive investigation for angina and the clinical appropriateness of factors predictive of the use of invasive investigation were broadly in line with guidelines . However , the influence of access to facilities , and marked international variation in rates and timing of investigation suggest that factors unrelated to clinical need are also influential in the management of patients with stable angina IMPORTANCE In the era of widespread revascularization and effective antianginals , the prevalence and prognostic effect of anginal symptoms and myocardial ischemia among patients with stable coronary artery disease ( CAD ) are unknown . OBJECTIVE To describe the current clinical patterns among patients with stable CAD and the association of anginal symptoms or myocardial ischemia with clinical outcomes . DESIGN , SETTING , AND PARTICIPANTS The Prospect i ve Observational Longitudinal Registry of Patients With Stable Coronary Artery Disease ( CLARIFY ) registry enrolled out patients in 45 countries with stable CAD in 2009 to 2010 with 2-year follow-up ( median , 24.1 months ; range , 1 day to 3 years ) . Enrollees included 32 105 out patients with prior myocardial infa rct ion , chest pain , and evidence of myocardial ischemia , evidence of CAD on angiography , or prior revascularization . Of these , 20 291 ( 63.2 % ) had undergone a noninvasive test for myocardial ischemia within 12 months of enrollment and were categorized into one of the following 4 groups : no angina or ischemia ( n = 13 207 [ 65.1 % ] ) ; evidence of myocardial ischemia without angina ( silent ischemia ) ( n = 3028 [ 14.9 % ] ) ; anginal symptoms alone ( n = 1842 [ 9.1 % ] ) ; and angina and ischemia ( n = 2214 [ 10.9 % ] ) . EXPOSURES Stable CAD . MAIN OUTCOME AND MEASURE The composite of cardiovascular (CV)-related death or nonfatal myocardial infa rct ion . RESULTS Overall , 4056 patients ( 20.0 % ) had anginal symptoms and 5242 ( 25.8 % ) had evidence of myocardial ischemia on results of noninvasive testing . Of 469 CV-related deaths or myocardial infa rct ions , 58.2 % occurred in patients without angina or ischemia , 12.4 % in patients with ischemia alone , 12.2 % in patients with angina alone , and 17.3 % in patients with both . The hazard ratios for the primary outcome relative to patients without angina or ischemia and adjusted for age , sex , geographic region , smoking status , hypertension , diabetes mellitus , and dyslipidemia were 0.90 ( 95 % CI , 0.68 - 1.20 ; P = .47 ) for ischemia alone , 1.45 ( 95 % CI , 1.08 - 1.95 ; P = .01 ) for angina alone , and 1.75 ( 95 % CI , 1.34 - 2.29 ; P < .001 ) for both . Similar findings were observed for CV-related death and for fatal or nonfatal myocardial infa rct ion . CONCLUSIONS AND RELEVANCE In out patients with stable CAD , anginal symptoms ( with or without ischemia on noninvasive testing ) but not silent ischemia appear to be associated with an increased risk for adverse CV outcomes . Most CV events occurred in patients without angina or ischemia . TRIAL REGISTRATION is rct n.org Identifier : IS RCT N43070564 
    Output:
    