Ignite Creation Date:
2024-05-06 @ 11:58 AM
Last Modification Date:
2024-10-26 @ 12:52 PM
Study NCT ID:
NCT03646019
Status:
UNKNOWN
Last Update Posted:
2018-08-24
First Post:
2018-08-10
Brief Title:
Serum Oxidative Status as a Potential Predictor of Coronary Artery Disease
Sponsor:
Prof Tony hayek MD
Organization:
Rambam Health Care Campus
Study Overview
Official Title:
Serum Oxidative Status as a Potential Predictor of Coronary Artery Disease
Status:
UNKNOWN
Status Verified Date:
2018-08
Last Known Status:
NOT_YET_RECRUITING
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:
Coronary artery disease CAD is a major cause of death and disability in developed countriesHuman studies revealed a significant association between serum oxidative status using PON1 TBARS and thiol levels and the presence of CAD and its severity However these studies were addressing the severity of CAD depending on coronary angiography of patients presenting with ST elevation myocardial infarction Non ST elevation myocardial infarction unstable angina pectoris while part of them even had a history of CAD Others where admitted for an elective coronary angiography for suspected stable CAD while only few patients were assessed for atypical chest pain This study thus aims to assess the relationship between PON1 activity TBARS and thiol levels and the existence of CAD and its severity in patients with no previous history of CAD presenting to the emergency department ED with acute chest pain but with no evidence of acute myocardial infarction or acute ECG ischemic changes Assessment with a Cardiac CT scan instead of coronary angiography will allow the investigators to study the status of coronary atherosclerosis and calcium burden in all participants including those presenting with atypical chest pain that most probably will not be referred by physicians to a coronary angiography Further sub groups analysis will estimate this relationship particularly in low-intermediate risk groups depending on 3 different validated scoring systems - TIMI GRACE and HEART score
Detailed Description:
Oxidized low-density lipoprotein LDL has a pivotal role in the initiation as well as the progression of atherosclerosis High-density lipoprotein HDL exerts a protective effect on the cardiovascular system and serum HDL-cholesterol levels correlates inversely with atherosclerosis severity since it protects against oxidative damage It is believed that the anti oxidant activity of HDL is mainly determined by the HDL-associated enzyme paraoxanase 1 PON1 The direct role of PON1 in reducing oxidative stress was demonstrated in studies using the PON1 knock out mice model and the human PON1 transgenic mice model HDL particles isolated from PON1-deficient mice were unable to inhibit LDL oxidation in cultured arterial cells in contrast to the HDL isolated from control mice Moreover HDL isolated from PON1 transgenic mice that exhibited 3-fold increase in PON1 activity was more effective in protecting LDL against oxidation compared to control wild type mice PON1 was shown to inhibit cholesterol influx by reducing the formation of oxidized LDL increasing the breakdown of specific oxidized lipids in oxidized LDL and decreasing macrophage uptake of oxidized LDL PON1 also inhibits cholesterol biosynthesis and stimulates HDL-mediated cholesterol efflux from macrophages Human studies revealed a significant association between decreased PON1 activity and increased risk of CAD Mean PON1 activity levels were lower in patients with acute myocardial infarction AMI than stable CAD patients and highest level were observed in control patients In patients with AMI PON1 activity increased significantly within 6 weeks of the acute event even though it was still markedly lower as compared to the stable CAD patients Suggesting that sudden lowering of serum PON1 activity in a population which already has lower activity may be one of the risk factors for development of AMI Ayub et al has reported that serum PON1 activity was already decreased within 2 hours of the onset of symptoms of AMI and remained low subsequently suggesting that the decreased PON1 activity may have preceded the acute event A prospective study reported that low serum PON1 activity is a predictive risk factor for subsequent coronary events Moreover PON1 activity has presented a possible biochemical marker for CAD severity assessed by coronary angiography Thiobarbituric acid reactive substances TBARS is an increased lipid peroxidation indicator that was found to be increased in CAD A weak but significant correlation was also observed between levels of TBARS and angiographic progression of disease especially moderate coronary artery stenosis Elif Azarsiz et al propose that the elevation in TBARS levels might be a more marked indicator for the degree of atherosclerosis than the insufficiency in antioxidant enzymes such as PON1 Thiol -SH levels were found to be lower in the CAD group compared with the non CAD group and control group Decreased serum thiol levels were associated with the presence and severity of CAD
In this study first set of blood samples will be obtained at presentation to the ED and later on at the department of internal medicine Ein the Rambams Medical Health Center including CBC count creatinine electrolytes and two high sensitive troponin measurements A second set of blood samples will be obtained at the morning of the cardiac CT scan after 10-12-h over-night fast including serum level of HbA1C CRP kidney and liver function total cholesterol HDL cholesterol LDL cholesterol and triglycerides All parameters will be measured on fresh blood samples at the Rambams Medical Health Center biochemical and endocrine laboratories Serum oxidative status will be determined by collecting additional blood tube 5 ml of blood at the morning of the cardiac CT scan After centrifuging the clotted sample serum will be separated and stored at minus 40 celsius for further analysis of PON-1 aryl esterase activity measurement of protein thiol groups glutathione and measurement of serum level of thiobarbituric acid reactive substances TBARS measured as malondialdehyde MDA equivalents at Lipid Research Laboratory of the Rappaport Faculty of Medicine at the Technion Haifa - Israel
Patients not already on beta-blocking drugs will receive oral metoprolol 50-200 mg for heart rates over 65 beatsmin An additional intravenous metoprolol 5-10 mg will be administered to achieve a target heart rate 65 beatsmin 5-15 minutes before the test However no patient will be excluded because of a heart rate above this target
The cardiac CT scan images will be interpreted by a panel of experienced radiologists blinded to the study at Rambam Medical Health Center The degree of coronary obstruction will be measured in terms of the percent of stenosis Participant with stenosis less than or equal to 49 is considered to have a non significant CAD Participant with stenosis more than 49 is considered to have a significant CAD Calcium burden will be measured by the Agatston score Subjects with significant stenosis in the cardiac CT scan will undergo coronary angiography for a further assessment of the degree of stenosis Result of the coronary angiography will be assessed in relation to the measurement of serum oxidative status as well
In this study hypertension will be defined as a DBP 90 mmHg SBP 140 mmHg measured using a calibrated electronic blood pressure machine in both arms while sitting after at least 30 min of rest and the average of 3 recording will be used or self reported use of anti hypertensive drug Diabetes mellitus DM will be diagnosed if the HbA1C is 65 or if the patient is treated with insulin or oral hypoglycemic agents Body mass index BMI will be computed as weight height squared km2
In this study first set of blood samples will be obtained at presentation to the ED and later on at the department of internal medicine Ein the Rambams Medical Health Center including CBC count creatinine electrolytes and two high sensitive troponin measurements A second set of blood samples will be obtained at the morning of the cardiac CT scan after 10-12-h over-night fast including serum level of HbA1C CRP kidney and liver function total cholesterol HDL cholesterol LDL cholesterol and triglycerides All parameters will be measured on fresh blood samples at the Rambams Medical Health Center biochemical and endocrine laboratories Serum oxidative status will be determined by collecting additional blood tube 5 ml of blood at the morning of the cardiac CT scan After centrifuging the clotted sample serum will be separated and stored at minus 40 celsius for further analysis of PON-1 aryl esterase activity measurement of protein thiol groups glutathione and measurement of serum level of thiobarbituric acid reactive substances TBARS measured as malondialdehyde MDA equivalents at Lipid Research Laboratory of the Rappaport Faculty of Medicine at the Technion Haifa - Israel
Patients not already on beta-blocking drugs will receive oral metoprolol 50-200 mg for heart rates over 65 beatsmin An additional intravenous metoprolol 5-10 mg will be administered to achieve a target heart rate 65 beatsmin 5-15 minutes before the test However no patient will be excluded because of a heart rate above this target
The cardiac CT scan images will be interpreted by a panel of experienced radiologists blinded to the study at Rambam Medical Health Center The degree of coronary obstruction will be measured in terms of the percent of stenosis Participant with stenosis less than or equal to 49 is considered to have a non significant CAD Participant with stenosis more than 49 is considered to have a significant CAD Calcium burden will be measured by the Agatston score Subjects with significant stenosis in the cardiac CT scan will undergo coronary angiography for a further assessment of the degree of stenosis Result of the coronary angiography will be assessed in relation to the measurement of serum oxidative status as well
In this study hypertension will be defined as a DBP 90 mmHg SBP 140 mmHg measured using a calibrated electronic blood pressure machine in both arms while sitting after at least 30 min of rest and the average of 3 recording will be used or self reported use of anti hypertensive drug Diabetes mellitus DM will be diagnosed if the HbA1C is 65 or if the patient is treated with insulin or oral hypoglycemic agents Body mass index BMI will be computed as weight height squared km2
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