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: heart failure with preserved ejection fraction ( hfpef ) is associated with a decrease in cardiopulmonary reserve leading to significant maladaptive changes in peripheral arterial and muscular functions . cardiopulmonary reserve and oxygen uptake efficiency are both decreased in chronic heart failure with reduced ejection fraction ( hf - ref ) . other small studies have demonstrated that the oxygen uptake efficiency slope ( oues ) is decreased in chronic hf patients and in older patients with hfpef . hfpef is characterized by an increase in some biomarkers related to neurohumoral activation . previous investigations have reported significant differences between patients with hfpef versus hf patients with reduced ejection fraction such as lower n - terminal prohormone of brain natriuretic peptide ( nt - probnp ) in hfpef . the characterization of changes in biomarkers at rest and following peak exercise has not been fully addressed in this form of hf . similarly , disorders of endothelial function and peripheral arterial blood flow have been a matter of controversies in patients with hfpef . no investigations have studied the changes in biomarkers related to lv wall stress , subclinical inflammation , and oxidative stress concomitantly with the evaluation of cardiopulmonary reserve and peripheral arterial function in hfpef compared with healthy subjects . the primary objective of this study was to investigate the changes cardiopulmonary reserve and peripheral arterial function , and biomarkers related to neurohumoral activation , inflammation , and oxidative stress in patients with hfpef compared with healthy subjects . this study was a prospective nonrandomized investigation including both patients with hfpef and healthy subjects . patients were included in the hfpef group if they had new york heart association ( nyha ) classes ii and iii symptoms and if they had a left ventricle ejection fraction ( lvef ) 50 % measured by echocardiography within the 12 months prior to enrolment in the study . the diagnosis of hfpef was confirmed by the presence of at least one abnormality on the screening echocardiography consistent with this condition such as atrial dilatation , left ventricle ( lv ) concentric remodeling or hypertrophy , and / or evidence of diastolic dysfunction by doppler studies . lv volumes and filling rates were further assessed by radionuclide ventriculography at the beginning of the study . patients with symptomatic hypotension ( systolic blood pressure ( sbp ) 90 mmhg ) or poorly controlled hypertension ( sbp 160 and / or diastolic blood pressure 90 mmhg ) were excluded . similarly , patients with severe chronic pulmonary disease limiting exercise capacity , severe renal failure ( creatinine 250mol / l ) , or significant liver dysfunction ( transaminases 3-fold upper normal values ) were excluded . healthy subjects were included if they presented with no significant medical conditions and were on no medication at the time of assessment . subjects or patients presenting with acute or active chronic inflammatory conditions were excluded from this study . all patients and healthy subjects provided written informed consent before undergoing any study - related procedures . the study was approved by the montreal heart institute research scientific and ethics committees . gas exchange parameters were measured breath by breath during testing , and then averaged every 15 seconds for minute ventilation ( ve , l / min ) , o2 uptake ( vo2 , l / min ) , and co2 production ( vco2 , l / min ) using an automated gas analyzer system ( oxycon pro , hoechberg , germany ) . heart rate and manual brachial blood pressure were recorded before the test and at 2 - minute intervals during exercise and recovery . criteria for maximal effort were the attainment of the primary maximal criteria , a leveling off of oxygen uptake ( 150 ml / min ) despite increased intensity or one of the three secondary maximal criteria : ( 1 ) a respiratory exchange ratio 1.05 , ( 2 ) inability to maintain walking , and ( 3 ) patient exhaustion due to fatigue or other clinical symptoms ( dyspnea , ecg , and / or blood pressure abnormalities ) . the average value of the vo2 recorded during the last 15 seconds of exercise was considered as the peak oxygen uptake ( vo2 peak ) , and ve / vco2 slope was also determined . the oxygen uptake efficiency slope ( oues ) was calculated during exercise using the slope of the relation vo2 and the log of ventilation as previously reported . the heart rate recovery ( hrr ) was measured at 1 ( hrr 1 ) and 2 ( hrr 2 ) minutes following the termination of exercise . venous blood samples were taken after semisupine rest for at least 15 minutes from both experimental populations under fasting state in the morning . serum samples were centrifuged ( 1500 g , 15 min , 4c ) and immediately frozen at 80c . blood tests were performed in the resting state for all parameters and within 2 minutes following peak exercise for the brain natriuretic peptide ( bnp ) . these two biomarkers were measured by electrochemiluminescence immunoassay using the roche bnp and probnp assays ( roche diagnostics , mannheim , germany ) on the elecsys 2010 analyzer ( roche diagnostics ) . serum high - sensitivity c - reactive protein ( hscrp ) was measured using the dade behring cardiophase hscrp assay ( siemens healthcare diagnostics products , marburg , germany ) on the bn prospec nephelometer ( siemens healthcare diagnostics products ) . plasma level of thiobarbituric acid reactive substances ( tbars ) was measured colorimetrically as previously described . plasma levels of interleukin - 6 ( il - 6 ) and 8 - epi - prostaglandin f2 were analyzed by elisa using the r & d systems kits ( minneapolis , mn , usa ) . forearm basal arterial flow was assessed using the strain gauge plethysmography ( sgp ) methods as previously described . briefly , all subjects sat with their arms resting in a supine position on supports positioned above the level of the heart . venous cuffs were then connected to automatic pneumatic inflators ( hokanson , e-20 rapid cuff inflator ; bellevue , wa ) set to 50 mmhg and calibrated strain gauges were placed around both forearms and connected to a plethysmograph ( hokanson , model ec - 4 , bellevue , wa ) . arterial inflow was calculated by determining the upslope of strain gauge signals calculated using a linear regression model . continuous baseline characteristics are expressed as mean standard deviation and categorical variables as frequencies and percentages . the proportion of male was compared between groups with a chi - square test and continuous baseline characteristics were compared using a student 's t - test . all measurements including parameters of cardiopulmonary function , biomarkers , and arterial blood flow were analyzed using ancova or repeated measures ancova including age as a covariate to control for its potentially confounding effect . results are expressed as adjusted means standard errors or adjusted geometric means . to evaluate whether biomarkers influenced aerobic capacity , pearson 's correlations were performed . a total of 32 subjects were recruited for this study including 18 patients with hfpef and 14 healthy subjects . of the patients studied , 83 % were in nyha class ii symptoms at the time of admission . all hfpef patients exhibited a larger lv end - diastolic volume and a shorter peak filling rate ( pfr ) with a higher time to pfr compared with the healthy subjects confirming a significant diastolic dysfunction in our patients . the majority of patients ( 67 % ) were treated with an angiotensin ii receptor blocker ( arbs ) and 50 % received a beta - blocker . all patients and healthy subjects performed a maximal effort as evidenced by a respiratory exchange ratio 1.05 ( data not shown ) . exercise duration and peak mets achieved were significantly lower in patients with hfpef compared with healthy subjects . similarly , peak vo2 and the ve / vco2 slope were significantly decreased by 41 % and increased by 15 % , respectively . hrr at 1 and 2 min after the termination of exercise were significantly lower in patients compared with the healthy subjects . plasma levels of hscrp ( p 0.05 ) , tbars ( p 0.01 ) , and 8 - epi - prostaglandin f2 ( p 0.05 ) were significantly increased in patients with hfpef compared with healthy subjects . the patients exhibited a 4-fold increase in nt - probnp ( p 0.001 ) ( figure 1 ) and a 3-fold increase in bnp plasma concentrations ( p 0.01 ) in resting state ( figure 1 ) . the relationships between biomarkers with selected exercise and biochemistry parameters are presented in table 3 and figure 3 . significant relationships were observed between bnp , hscrp , il - 6 , and 8 - epi - prostaglandin f2 and peak vo2 and hrr 2 ( table 3 ) . there was also a modest but significant relationship between hscrp and il - 6 and between hscrp and exercise duration in the hfpef population ( figure 3 ) . peripheral arterial flows in resting state and following arterial occlusion are presented in figure 4 . basal peripheral arterial forearm blood flow was not statistically different in the study population as demonstrated by the area under the curve ( auc ) in hfpef patients compared with healthy subjects ( resp . , 52370 versus 38641 , ns ) ( figure 4 ( a ) ) . no difference in the hyperemic responsein this study we reported a significant reduction in aerobic capacity and oxygen uptake efficiency in ambulatory patients with hfpef . we also reported a significant increase in some biomarkers related to subclinical inflammation and oxidative stress . both bnp and nt - probnp were significantly elevated at rest with a similar magnitude of bnp increase at peak exercise in both patients and healthy subjects . in addition , we observed some significant relationship between peak aerobic capacity and hrr following exercise with bnp , il - 6 , and 8 - epi - prostaglandin f2 . we observed no significant differences in basal and posthyperemic blood flow in hfpef patients compared with healthy subjects . previous investigations have reported a significant reduction in functional and peak aerobic capacities in patients with hfpef . here we reported a decrease in peak vo2 of 37 % in patients with hfpef compared with controls . this magnitude of decrease is in agreement with the overall decrease of 40 % reported by other investigators . in addition , we observed a 30 % reduction in the oues in hfpef patients compared with healthy control subjects . these changes are consistent with previous reports showing significant decrease in cardiopulmonary reserve and abnormal ventilator function in these patients . previous investigations have shown an increase in selected biomarkers such as il - 6 and nt - probnp in patients with hfpef . our findings confirm our former observations and data from other investigators showing significant increases of the c - reactive protein and il - 6 and demonstrating a significant proinflammatory state in these patients . in addition to earlier studies , we reported a 3-fold increase in bnp at rest which was maintained at peak exercise in hfpef patients . the similar magnitude of bnp increase at peak exercise for both hf and health subjects patients suggests a preservation of wall stress during exercise in patients with hfpef . here we also reported a significant increase in biomarkers related to oxidative stress in patients with hfpef compared with healthy subjects . indeed , two biomarkers of oxidative stress including tbars and 8 - epi - prostaglandin f2 were both significantly increased , confirming a prooxidative state in these patients . previous investigations have reported a role of oxidative stress in the pathophysiology of hf . other observations have reported a detrimental effect of oxidative stress on the degradation of cardiac extracellular matrix degradation in humans and on the cardiac contractility in mice . the role of biomarker changes and specially those related to subclinical inflammation and oxidative stress on the pathophysiology of hfpef remain unknown . we further explored the relationships between selected clinical and functional parameters with some biomarkers in our study population . we reported a significant relationship between peak vo2 and hrr at 2 minutes with bnp , 8 - epi - prostaglandin f2 , hscrp , and il - 6 in the overall population . this suggests a significant relationship between inflammation and autonomic regulation with functional capacity in hfpef patients . these observations are in agreement with previous studies showing a relationship between sympathetic and parasympathetic tones and regulation of inflammation in chronic hf patients and in a canine pacing model of hf . , we reported no significant differences in basal and posthyperemic peripheral arterial blood flow in patients with hfpef compared with healthy subjects . abnormal endothelial function is associated with a decreased aerobic capacity in high risk patients and in patients with hf with decreased lvef . there has been little data regarding the changes in peripheral arterial blood flow at rest and following stress in patients with hfpef . a previous investigation reported a decrease in leg blood flow at rest and following exercise . in contrast , other clinical studies reported no difference in leg flow - mediated dilation or in brachial artery flow - mediated dilation following submaximal exercise compared with healthy subjects . in that same study , no significant relationship between the reduction in peak vo2 and brachial artery flow - mediated dilation has been reported beyond the effect of aging . the differences between a previous study and our data may be explained by some clinical differences in the patient population and methodological approaches . first , the etiology of hf was different with some patients presenting dyspnea because of bronchial asthma in the latter study . most importantly , the rate of use of angiotensin - ii modulating agents was 73 % in the current study as opposed to 40 % on average in previous publications . the high proportion of use of arbs ( i.e. , 67 % ) may have contributed to attenuate the changes in basal and posthyperemic blood flow in our patients . finally , we used sgp as opposed to magnetic resonance or brachial artery flow - mediated dilation methods . contrary to these techniques , we mechanically assessed the increase in forearm volume after the cuff deflation using calibrated strain gauges connected to a plethysmograph . this technique correlates well with the near - infrared spectroscopy for noninvasive assessment of arterial forearm flow . nevertheless sgp may not be sensitive enough to detect small changes in microvascular function in hfpef patients . however , to minimize the impact of age on our observations ancova analyses were computed using age as a covariate . also no investigations have reported any effect of age on biomarkers and functional parameters in patients with symptomatic hf caused by preserved ejection fraction . secondly , the sample size was small . despite this , our study population was fairly homogenous allowing small variance and significance in most of the parameters studied . thirdly chronic use of arbs may have significantly impacted our findings on forearm blood flow data . finally , we only measured plasma level of bnp at peak exercise . the inclusion of other biomarkers may have provided additional insights on the mechanisms involved with exercise limitations in these patients . in conclusion , this study demonstrates that ambulatory patients with hfpef exhibit a significant reduction in cardiopulmonary reserve and oxygen uptake efficiency concomitantly with an elevation in broad spectrum of biomarkers confirming a proinflammatory and a prooxidative status in these patients . the relationship between some biomarkers of inflammation and oxidative stress suggest a role of these processes on functional capacity in these patients . the role of biomarkers and the assessment of peripheral arterial function by multimodality techniques deserve further investigations .
output:

agent
background . changes in cardiopulmonary reserve and biomarkers related to wall stress , inflammation , and oxidative stress concomitantly with the evaluation of peripheral arterial blood flow have not been investigated in patients with heart failure with preserved ejection fraction ( hfpef ) compared with healthy subjects ( ctl ) . methods and results . eighteen hfpef patients and 14 ctl were recruited . plasma levels of inflammatory and oxidative stress biomarkers were measured at rest . brain natriuretic peptide ( bnp ) was measured at rest and peak exercise . cardiopulmonary reserve was assessed using an exercise protocol with gas exchange analyses . peripheral arterial blood flow was determined by strain gauge plethysmography . peak vo2 ( 12.0 0.4 versus 19.1 1.1 ml / min / kg , p < 0.001 ) and oxygen uptake efficiency slope ( 1.55 0.12 versus 2.06 0.14 , p < 0.05 ) were significantly decreased in hfpef patients compared with ctl . bnp at rest and following stress , c - reactive - protein , interleukin - 6 , and tbars were significantly elevated in hfpef . both basal and posthyperemic arterial blood flow were not significantly different between the hfpef patients and ctl . conclusions . hfpef exhibits a severe reduction in cardiopulmonary reserve and oxygen uptake efficiency concomitantly with an elevation in a broad spectrum of biomarkers confirming an inflammatory and prooxidative status in patients with hfpef .
***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: heart failure with preserved ejection fraction ( hfpef ) is associated with a decrease in cardiopulmonary reserve leading to significant maladaptive changes in peripheral arterial and muscular functions . cardiopulmonary reserve and oxygen uptake efficiency are both decreased in chronic heart failure with reduced ejection fraction ( hf - ref ) . other small studies have demonstrated that the oxygen uptake efficiency slope ( oues ) is decreased in chronic hf patients and in older patients with hfpef . hfpef is characterized by an increase in some biomarkers related to neurohumoral activation . previous investigations have reported significant differences between patients with hfpef versus hf patients with reduced ejection fraction such as lower n - terminal prohormone of brain natriuretic peptide ( nt - probnp ) in hfpef . the characterization of changes in biomarkers at rest and following peak exercise has not been fully addressed in this form of hf . similarly , disorders of endothelial function and peripheral arterial blood flow have been a matter of controversies in patients with hfpef . no investigations have studied the changes in biomarkers related to lv wall stress , subclinical inflammation , and oxidative stress concomitantly with the evaluation of cardiopulmonary reserve and peripheral arterial function in hfpef compared with healthy subjects . the primary objective of this study was to investigate the changes cardiopulmonary reserve and peripheral arterial function , and biomarkers related to neurohumoral activation , inflammation , and oxidative stress in patients with hfpef compared with healthy subjects . this study was a prospective nonrandomized investigation including both patients with hfpef and healthy subjects . patients were included in the hfpef group if they had new york heart association ( nyha ) classes ii and iii symptoms and if they had a left ventricle ejection fraction ( lvef ) 50 % measured by echocardiography within the 12 months prior to enrolment in the study . the diagnosis of hfpef was confirmed by the presence of at least one abnormality on the screening echocardiography consistent with this condition such as atrial dilatation , left ventricle ( lv ) concentric remodeling or hypertrophy , and / or evidence of diastolic dysfunction by doppler studies . lv volumes and filling rates were further assessed by radionuclide ventriculography at the beginning of the study . patients with symptomatic hypotension ( systolic blood pressure ( sbp ) 90 mmhg ) or poorly controlled hypertension ( sbp 160 and / or diastolic blood pressure 90 mmhg ) were excluded . similarly , patients with severe chronic pulmonary disease limiting exercise capacity , severe renal failure ( creatinine 250mol / l ) , or significant liver dysfunction ( transaminases 3-fold upper normal values ) were excluded . healthy subjects were included if they presented with no significant medical conditions and were on no medication at the time of assessment . subjects or patients presenting with acute or active chronic inflammatory conditions were excluded from this study . all patients and healthy subjects provided written informed consent before undergoing any study - related procedures . the study was approved by the montreal heart institute research scientific and ethics committees . gas exchange parameters were measured breath by breath during testing , and then averaged every 15 seconds for minute ventilation ( ve , l / min ) , o2 uptake ( vo2 , l / min ) , and co2 production ( vco2 , l / min ) using an automated gas analyzer system ( oxycon pro , hoechberg , germany ) . heart rate and manual brachial blood pressure were recorded before the test and at 2 - minute intervals during exercise and recovery . criteria for maximal effort were the attainment of the primary maximal criteria , a leveling off of oxygen uptake ( 150 ml / min ) despite increased intensity or one of the three secondary maximal criteria : ( 1 ) a respiratory exchange ratio 1.05 , ( 2 ) inability to maintain walking , and ( 3 ) patient exhaustion due to fatigue or other clinical symptoms ( dyspnea , ecg , and / or blood pressure abnormalities ) . the average value of the vo2 recorded during the last 15 seconds of exercise was considered as the peak oxygen uptake ( vo2 peak ) , and ve / vco2 slope was also determined . the oxygen uptake efficiency slope ( oues ) was calculated during exercise using the slope of the relation vo2 and the log of ventilation as previously reported . the heart rate recovery ( hrr ) was measured at 1 ( hrr 1 ) and 2 ( hrr 2 ) minutes following the termination of exercise . venous blood samples were taken after semisupine rest for at least 15 minutes from both experimental populations under fasting state in the morning . serum samples were centrifuged ( 1500 g , 15 min , 4c ) and immediately frozen at 80c . blood tests were performed in the resting state for all parameters and within 2 minutes following peak exercise for the brain natriuretic peptide ( bnp ) . these two biomarkers were measured by electrochemiluminescence immunoassay using the roche bnp and probnp assays ( roche diagnostics , mannheim , germany ) on the elecsys 2010 analyzer ( roche diagnostics ) . serum high - sensitivity c - reactive protein ( hscrp ) was measured using the dade behring cardiophase hscrp assay ( siemens healthcare diagnostics products , marburg , germany ) on the bn prospec nephelometer ( siemens healthcare diagnostics products ) . plasma level of thiobarbituric acid reactive substances ( tbars ) was measured colorimetrically as previously described . plasma levels of interleukin - 6 ( il - 6 ) and 8 - epi - prostaglandin f2 were analyzed by elisa using the r & d systems kits ( minneapolis , mn , usa ) . forearm basal arterial flow was assessed using the strain gauge plethysmography ( sgp ) methods as previously described . briefly , all subjects sat with their arms resting in a supine position on supports positioned above the level of the heart . venous cuffs were then connected to automatic pneumatic inflators ( hokanson , e-20 rapid cuff inflator ; bellevue , wa ) set to 50 mmhg and calibrated strain gauges were placed around both forearms and connected to a plethysmograph ( hokanson , model ec - 4 , bellevue , wa ) . arterial inflow was calculated by determining the upslope of strain gauge signals calculated using a linear regression model . continuous baseline characteristics are expressed as mean standard deviation and categorical variables as frequencies and percentages . the proportion of male was compared between groups with a chi - square test and continuous baseline characteristics were compared using a student 's t - test . all measurements including parameters of cardiopulmonary function , biomarkers , and arterial blood flow were analyzed using ancova or repeated measures ancova including age as a covariate to control for its potentially confounding effect . results are expressed as adjusted means standard errors or adjusted geometric means . to evaluate whether biomarkers influenced aerobic capacity , pearson 's correlations were performed . a total of 32 subjects were recruited for this study including 18 patients with hfpef and 14 healthy subjects . of the patients studied , 83 % were in nyha class ii symptoms at the time of admission . all hfpef patients exhibited a larger lv end - diastolic volume and a shorter peak filling rate ( pfr ) with a higher time to pfr compared with the healthy subjects confirming a significant diastolic dysfunction in our patients . the majority of patients ( 67 % ) were treated with an angiotensin ii receptor blocker ( arbs ) and 50 % received a beta - blocker . all patients and healthy subjects performed a maximal effort as evidenced by a respiratory exchange ratio 1.05 ( data not shown ) . exercise duration and peak mets achieved were significantly lower in patients with hfpef compared with healthy subjects . similarly , peak vo2 and the ve / vco2 slope were significantly decreased by 41 % and increased by 15 % , respectively . hrr at 1 and 2 min after the termination of exercise were significantly lower in patients compared with the healthy subjects . plasma levels of hscrp ( p 0.05 ) , tbars ( p 0.01 ) , and 8 - epi - prostaglandin f2 ( p 0.05 ) were significantly increased in patients with hfpef compared with healthy subjects . the patients exhibited a 4-fold increase in nt - probnp ( p 0.001 ) ( figure 1 ) and a 3-fold increase in bnp plasma concentrations ( p 0.01 ) in resting state ( figure 1 ) . the relationships between biomarkers with selected exercise and biochemistry parameters are presented in table 3 and figure 3 . significant relationships were observed between bnp , hscrp , il - 6 , and 8 - epi - prostaglandin f2 and peak vo2 and hrr 2 ( table 3 ) . there was also a modest but significant relationship between hscrp and il - 6 and between hscrp and exercise duration in the hfpef population ( figure 3 ) . peripheral arterial flows in resting state and following arterial occlusion are presented in figure 4 . basal peripheral arterial forearm blood flow was not statistically different in the study population as demonstrated by the area under the curve ( auc ) in hfpef patients compared with healthy subjects ( resp . , 52370 versus 38641 , ns ) ( figure 4 ( a ) ) . no difference in the hyperemic responsein this study we reported a significant reduction in aerobic capacity and oxygen uptake efficiency in ambulatory patients with hfpef . we also reported a significant increase in some biomarkers related to subclinical inflammation and oxidative stress . both bnp and nt - probnp were significantly elevated at rest with a similar magnitude of bnp increase at peak exercise in both patients and healthy subjects . in addition , we observed some significant relationship between peak aerobic capacity and hrr following exercise with bnp , il - 6 , and 8 - epi - prostaglandin f2 . we observed no significant differences in basal and posthyperemic blood flow in hfpef patients compared with healthy subjects . previous investigations have reported a significant reduction in functional and peak aerobic capacities in patients with hfpef . here we reported a decrease in peak vo2 of 37 % in patients with hfpef compared with controls . this magnitude of decrease is in agreement with the overall decrease of 40 % reported by other investigators . in addition , we observed a 30 % reduction in the oues in hfpef patients compared with healthy control subjects . these changes are consistent with previous reports showing significant decrease in cardiopulmonary reserve and abnormal ventilator function in these patients . previous investigations have shown an increase in selected biomarkers such as il - 6 and nt - probnp in patients with hfpef . our findings confirm our former observations and data from other investigators showing significant increases of the c - reactive protein and il - 6 and demonstrating a significant proinflammatory state in these patients . in addition to earlier studies , we reported a 3-fold increase in bnp at rest which was maintained at peak exercise in hfpef patients . the similar magnitude of bnp increase at peak exercise for both hf and health subjects patients suggests a preservation of wall stress during exercise in patients with hfpef . here we also reported a significant increase in biomarkers related to oxidative stress in patients with hfpef compared with healthy subjects . indeed , two biomarkers of oxidative stress including tbars and 8 - epi - prostaglandin f2 were both significantly increased , confirming a prooxidative state in these patients . previous investigations have reported a role of oxidative stress in the pathophysiology of hf . other observations have reported a detrimental effect of oxidative stress on the degradation of cardiac extracellular matrix degradation in humans and on the cardiac contractility in mice . the role of biomarker changes and specially those related to subclinical inflammation and oxidative stress on the pathophysiology of hfpef remain unknown . we further explored the relationships between selected clinical and functional parameters with some biomarkers in our study population . we reported a significant relationship between peak vo2 and hrr at 2 minutes with bnp , 8 - epi - prostaglandin f2 , hscrp , and il - 6 in the overall population . this suggests a significant relationship between inflammation and autonomic regulation with functional capacity in hfpef patients . these observations are in agreement with previous studies showing a relationship between sympathetic and parasympathetic tones and regulation of inflammation in chronic hf patients and in a canine pacing model of hf . , we reported no significant differences in basal and posthyperemic peripheral arterial blood flow in patients with hfpef compared with healthy subjects . abnormal endothelial function is associated with a decreased aerobic capacity in high risk patients and in patients with hf with decreased lvef . there has been little data regarding the changes in peripheral arterial blood flow at rest and following stress in patients with hfpef . a previous investigation reported a decrease in leg blood flow at rest and following exercise . in contrast , other clinical studies reported no difference in leg flow - mediated dilation or in brachial artery flow - mediated dilation following submaximal exercise compared with healthy subjects . in that same study , no significant relationship between the reduction in peak vo2 and brachial artery flow - mediated dilation has been reported beyond the effect of aging . the differences between a previous study and our data may be explained by some clinical differences in the patient population and methodological approaches . first , the etiology of hf was different with some patients presenting dyspnea because of bronchial asthma in the latter study . most importantly , the rate of use of angiotensin - ii modulating agents was 73 % in the current study as opposed to 40 % on average in previous publications . the high proportion of use of arbs ( i.e. , 67 % ) may have contributed to attenuate the changes in basal and posthyperemic blood flow in our patients . finally , we used sgp as opposed to magnetic resonance or brachial artery flow - mediated dilation methods . contrary to these techniques , we mechanically assessed the increase in forearm volume after the cuff deflation using calibrated strain gauges connected to a plethysmograph . this technique correlates well with the near - infrared spectroscopy for noninvasive assessment of arterial forearm flow . nevertheless sgp may not be sensitive enough to detect small changes in microvascular function in hfpef patients . however , to minimize the impact of age on our observations ancova analyses were computed using age as a covariate . also no investigations have reported any effect of age on biomarkers and functional parameters in patients with symptomatic hf caused by preserved ejection fraction . secondly , the sample size was small . despite this , our study population was fairly homogenous allowing small variance and significance in most of the parameters studied . thirdly chronic use of arbs may have significantly impacted our findings on forearm blood flow data . finally , we only measured plasma level of bnp at peak exercise . the inclusion of other biomarkers may have provided additional insights on the mechanisms involved with exercise limitations in these patients . in conclusion , this study demonstrates that ambulatory patients with hfpef exhibit a significant reduction in cardiopulmonary reserve and oxygen uptake efficiency concomitantly with an elevation in broad spectrum of biomarkers confirming a proinflammatory and a prooxidative status in these patients . the relationship between some biomarkers of inflammation and oxidative stress suggest a role of these processes on functional capacity in these patients . the role of biomarkers and the assessment of peripheral arterial function by multimodality techniques deserve further investigations .
output:
