Ignite Creation Date:
2024-05-06 @ 3:28 PM
Last Modification Date:
2024-10-26 @ 1:50 PM
Study NCT ID:
NCT04646252
Status:
RECRUITING
Last Update Posted:
2024-05-29
First Post:
2020-11-22
Brief Title:
The Role of Glycocalyx Integrity in the Primary Prevention of Major Cardiovascular Events
Sponsor:
University of Athens
Organization:
University of Athens
Study Overview
Official Title:
Impaired Endothelial Glycocalyx Predicts Adverse Outcome in Subjects Without Overt Cardiovascular Disease a 6 Year Follow up Study
Status:
RECRUITING
Status Verified Date:
2024-05
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
None
Brief Summary:
The researchers intend to recruit individuals who are referred for a routine screening in the primary prevention outpatient clinic of Attikon University hospital Athens According to institutional protocols a detailed medical history for atherosclerotic risk factors and current medication is recorded and a baseline clinical examination is performed Moreover fasting blood samples are drawn to diagnose the presence of diabetes mellitus and hyperlipidemia Glycocalyx examination is performed at the same visit The subjects are revaluated at one month and then followed up according to the attending physicians instructions Pulse wave velocity and the rest pulse wave analysis parameters were also calculated to determine the additive predictive value for cardiovascular events beyond SCORE2 All subjects are followed up for adverse events death stroke myocardial infarction hospitalization for heart failure for 6 years after enrollment via telephonic contact and planned appointment at the outpatient clinic
Detailed Description:
Blood pressure is measured in each subject with the aid of a digital oscillometric sphygmomanometer TensioMed Budapest Hungary Ltd Each subject rests in a quiet room at 25C for 30 minutes before the examination The cuff is placed in the right arm while the subject is seated The diagnosis of hypertension is made on the basis of1 systolic blood pressure 140 mmHgdiastolic blood pressure 90 mmHg after 3 consecutive measurements or 2 the participant is receiving antihypertensive treatment Moreover fasting blood samples are drawn to identify the presence of diabetes mellitus and hyperlipidemia in our sample Specifically DM is determined by either plasma glucose 126 mgdl measured by the enzymatic in vitro test Roche automatic chemistry clinical analyzer or treatment with antidiabetic agents Similarly hyperlipidemia was defined by either Total Cholesterol 230 mgdl andor LDL 160 mgdl and or TGs 200 mg dl measured by the colorimetric spectrophotometry Roche Diagnostics or the use of lipid lowering agents according to the running guidelines held during the initial examination Additionally smokers are considered only those participants who are actively smoking at the time of enrollment Also the presence of positive family history of coronary artery disease is defined as coronary disease in a first degree female relative before 65 years or a male relative before 55 years of age BMI is calculated as the ratio of weight kg to the square of height m2 Furthermore SCORE estimation system is used to calculate the 10-year cardiovascular risk for each participant
As far as ethnicity is concerned an individual is not considered Greek in case heshe was born abroad and also has at least a foreigner parent or heshe is born in Greece but both parents were foreigners Inversely a subject was considered Greek if they and simultaneously both parents were born in Greece
Exclusion criteria are the history of Coronary artery disease CAD Peripheral Arterial Disease PAD Heart failure HF Stroke hepatic or renal failure active neoplasia and poorly controlled DM defined as Hba1C7
ENDOTHELIAL GLYCOCALYX EVALUATION The researchers quantified the perfused boundary region PBR measured in μm of the sublingual microvasculature by using Sideview Darkfield Imaging Microscan Glycocheck Microvascular Health Solutions Inc Salt Lake City UT USA Briefly SDF camera utilizes green reflected light emitting diode LED light 540 nm from hemoglobin molecules to depict the radial displacements of RBCs within the microvessels The camera is inserted under the tongue and captures more than 3000 vascular segments of vessels with diameter ranging from 5 μm to 25 μm The images are obtained automatically by the Glycocheck software Afterwards the system checks the quality of the recordings and selects the valid frames contrast enhancement greater than 60 which are going to be further analyzed The RBC column width as well as the total perfused diameter of microvessels is estimated by the software with high accuracy Then PBR is calculated by the formula Perfused Diameter- RBC column width2The software also provides the PBR of vessels with diameter 5-9μm 10-19μm 20-25μm and the mean 5-25μm As a result PBR expresses the outer area of the vessels lumen that is vulnerable to RBC penetration and is consistent with the integrity of glycocalyx layer Thus high PBR values are considered as indicator of damaged endothelial glycocalyx with affected barrier properties which allows high spatio-temporal distribution of RBCs On the other hand Conversely low PBR values are associated with robust thick glycocalyx layer The whole procedure lasts for approximately 3 minutes does not require high expertise is operator independent has satisfactory reproducibility and thus is highly recommended as a validated technique for the assessment of endothelial glycocalyx function The PBR measurements are independent of red blood cell filling of the vessels segments hematocrit because the software only includes vessel segments that have a filling percentage of more than 50 Hence vessel segments are only selected when at least 11 of the 21-line markers have a positive signal for the presence of an erythrocyte Thus PBR values are independent of hematocrit reflecting a damaged glycocalyx that is more accessible for circulating erythrocytes
In the current study the evaluation of PBR takes place between 900 and 1100 after 8 hours fasting and abstinence from alcohol and smoking and temporary discontinuation of medications for 48 h before the examination as well
PULSE WAVE VELOCITY Pulse wave velocity carotid to femoral and Augmentation Index were estimated non-invasively using a dedicated technique Complior Alam Medical Vincennes France
FOLLOW UP A follow up assessment is performed 6 years after the recruitment via telephonic contact and planned appointment at the outpatient clinic Briefly at the reevaluation the participants or their legal representatives - in case of inability or death- are asked for the incidence of major cardiovascular events or death attributed to any cause The primary composite outcome of major adverse events consists of death myocardial infarction ICD-10 DI20-22 stroke ICD-10 DI60-68 DG45 and hospitalization for heart failure ICD-10 DI50-51 DI42 DI11 Each of the forenamed events is documented by hospital medical records or attending phycians letters and confirmed by the national security electronic records using the appropriate ICD10
STATISTICAL ANALYSIS
Statistical analysis is performed by SPSS version 25 IBM SPSS Statistics Inc Chicago IL and Stata version 16 StataCorp LP College Station TX Scale variables are presented as mean SD in case of normal distribution as determined by the normality tests Kolmogorov-Smirnov test and Shapiro-Wilk or as medians and interquartile ranges in case of non-normal distribution Nominal variables are expressed as frequencies and percentages Scale variables are compared using independent samples Students t tests or Mann-Whitney tests as indicated whereas categorical variables are compared using Chi-square tests or Fishers exact tests as appropriate In addition patients are dichotomized based on the mean values of PBR for the sublingual microvessel diameter 5-25μm 5-9 μm 10-19 μm and 20-25 μm Cox proportional hazard models are built for each variable to decide whether any of mean values of the above PBR categories can serve as an independent predictor of major cardiovascular events or death at a significance level of p value005 Cumulative event rates are calculated using the Kaplan-Meier survival analysis for subjects with lower vs higher mean PBR value The log-rank test for time-to-event data with respect to the total events is used for comparison of these two groups Cox proportional hazard models are built for each possible risk factor in relation to the study endpoints Estimated hazard ratios and their respective 95 confidence intervals are obtained P value005 are considered significant Multivariate analysis include factors with proven clinical value or p value 01 at univariate analysis Moreover chi-square values of multivariate models were comparedbefore and after adjusting for PBR Chi square change with p value005 is considered significant Furthermore the net reclassification index NRI and Harrells C were calculated to evaluate improvement in risk prediction by PBR and p value005 is considered significant
As far as ethnicity is concerned an individual is not considered Greek in case heshe was born abroad and also has at least a foreigner parent or heshe is born in Greece but both parents were foreigners Inversely a subject was considered Greek if they and simultaneously both parents were born in Greece
Exclusion criteria are the history of Coronary artery disease CAD Peripheral Arterial Disease PAD Heart failure HF Stroke hepatic or renal failure active neoplasia and poorly controlled DM defined as Hba1C7
ENDOTHELIAL GLYCOCALYX EVALUATION The researchers quantified the perfused boundary region PBR measured in μm of the sublingual microvasculature by using Sideview Darkfield Imaging Microscan Glycocheck Microvascular Health Solutions Inc Salt Lake City UT USA Briefly SDF camera utilizes green reflected light emitting diode LED light 540 nm from hemoglobin molecules to depict the radial displacements of RBCs within the microvessels The camera is inserted under the tongue and captures more than 3000 vascular segments of vessels with diameter ranging from 5 μm to 25 μm The images are obtained automatically by the Glycocheck software Afterwards the system checks the quality of the recordings and selects the valid frames contrast enhancement greater than 60 which are going to be further analyzed The RBC column width as well as the total perfused diameter of microvessels is estimated by the software with high accuracy Then PBR is calculated by the formula Perfused Diameter- RBC column width2The software also provides the PBR of vessels with diameter 5-9μm 10-19μm 20-25μm and the mean 5-25μm As a result PBR expresses the outer area of the vessels lumen that is vulnerable to RBC penetration and is consistent with the integrity of glycocalyx layer Thus high PBR values are considered as indicator of damaged endothelial glycocalyx with affected barrier properties which allows high spatio-temporal distribution of RBCs On the other hand Conversely low PBR values are associated with robust thick glycocalyx layer The whole procedure lasts for approximately 3 minutes does not require high expertise is operator independent has satisfactory reproducibility and thus is highly recommended as a validated technique for the assessment of endothelial glycocalyx function The PBR measurements are independent of red blood cell filling of the vessels segments hematocrit because the software only includes vessel segments that have a filling percentage of more than 50 Hence vessel segments are only selected when at least 11 of the 21-line markers have a positive signal for the presence of an erythrocyte Thus PBR values are independent of hematocrit reflecting a damaged glycocalyx that is more accessible for circulating erythrocytes
In the current study the evaluation of PBR takes place between 900 and 1100 after 8 hours fasting and abstinence from alcohol and smoking and temporary discontinuation of medications for 48 h before the examination as well
PULSE WAVE VELOCITY Pulse wave velocity carotid to femoral and Augmentation Index were estimated non-invasively using a dedicated technique Complior Alam Medical Vincennes France
FOLLOW UP A follow up assessment is performed 6 years after the recruitment via telephonic contact and planned appointment at the outpatient clinic Briefly at the reevaluation the participants or their legal representatives - in case of inability or death- are asked for the incidence of major cardiovascular events or death attributed to any cause The primary composite outcome of major adverse events consists of death myocardial infarction ICD-10 DI20-22 stroke ICD-10 DI60-68 DG45 and hospitalization for heart failure ICD-10 DI50-51 DI42 DI11 Each of the forenamed events is documented by hospital medical records or attending phycians letters and confirmed by the national security electronic records using the appropriate ICD10
STATISTICAL ANALYSIS
Statistical analysis is performed by SPSS version 25 IBM SPSS Statistics Inc Chicago IL and Stata version 16 StataCorp LP College Station TX Scale variables are presented as mean SD in case of normal distribution as determined by the normality tests Kolmogorov-Smirnov test and Shapiro-Wilk or as medians and interquartile ranges in case of non-normal distribution Nominal variables are expressed as frequencies and percentages Scale variables are compared using independent samples Students t tests or Mann-Whitney tests as indicated whereas categorical variables are compared using Chi-square tests or Fishers exact tests as appropriate In addition patients are dichotomized based on the mean values of PBR for the sublingual microvessel diameter 5-25μm 5-9 μm 10-19 μm and 20-25 μm Cox proportional hazard models are built for each variable to decide whether any of mean values of the above PBR categories can serve as an independent predictor of major cardiovascular events or death at a significance level of p value005 Cumulative event rates are calculated using the Kaplan-Meier survival analysis for subjects with lower vs higher mean PBR value The log-rank test for time-to-event data with respect to the total events is used for comparison of these two groups Cox proportional hazard models are built for each possible risk factor in relation to the study endpoints Estimated hazard ratios and their respective 95 confidence intervals are obtained P value005 are considered significant Multivariate analysis include factors with proven clinical value or p value 01 at univariate analysis Moreover chi-square values of multivariate models were comparedbefore and after adjusting for PBR Chi square change with p value005 is considered significant Furthermore the net reclassification index NRI and Harrells C were calculated to evaluate improvement in risk prediction by PBR and p value005 is considered significant
Study Oversight
Has Oversight DMC:
None
Is a FDA Regulated Drug?:
False
Is a FDA Regulated Device?:
False
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
None
Is an FDA AA801 Violation?:
None