Aim and background: This study will seek to identify physiological and biochemical factors explaining and predicting a higher than expected central (aortic) blood pressure (BP) in patients with chronic kidney disease (CKD). The basic hypothesis of the study is that the degree of aortic calcification is an important component of elevated central BP, which, in turn, is important for the organ-damage and increased risk of cardiovascular disease associated with CKD. Methods: Adult patients with varying degrees of CKD undergoing scheduled coronary angiography (CAG) at Aarhus University Hospital will be included in this study. During the CAG procedure, systolic and diastolic BP is determined in the ascending part of aorta by a calibrated pressure transducer connected to the fluid-filled CAG catheter. Simultaneous with the registration of invasive aortic BP, estimation of central BP is performed using radial artery tonometry (SphygmoCor®), while a corresponding brachial BP is also measured. Prior to the CAG, a non-contrast CT scan of aorta in its entirety will be performed to enable blinded quantification of calcification in the wall of aorta and coronary arteries. Furthermore, echocardiography, resting BP measurement and a range of blood- and urine samples will be performed.
Study Type
OBSERVATIONAL
Enrollment
185
Aarhus University Hospital
Aarhus, Denmark
The difference between directly measured and estimated aortic (central) systolic blood pressure and the corresponding brachial systolic blood pressure
Systolic arterial pressure will be determined in the ascending part of aorta using a calibrated pressure transducer connected to the CAG catheter. Simultaneous measurement with af Oscillometric BP-device (Microlife A2 Basic) will be conducted. The difference in mmHg will be calculated.
Time frame: During the CAG-procedure
The degree of aortic calcification
The degree of calcification in the wall of the ascending, arcus, descending and abdominal aorta will be measured with a non-contrast CT scan. Agatston-scoring will be applied on the CT images 2 cm after the aortic valve to the aortic bifurcation to ensure that aortic valve calcification is not included in the score. All Agatston scoring will be performed by a radiologist blinded to information on patient biochemical characteristics.
Time frame: CT-scan will be performed prior to CAG if logistically possible and no later than 3 weeks after CAG. All Agatston scoring will be completed when all patients have been included in the study during the summer of 2021.
The difference between directly measured and estimated aortic (central) diastolic blood pressure and the corresponding brachial diastolic blood pressure.
Diastolic arterial pressure will be determined in the ascending part of aorta using a calibrated pressure transducer connected to the CAG catheter. Simultaneous measurement with af Oscillometric BP-device (Microlife A2 Basic) will be conducted. The difference in mmHg will be calculated.
Time frame: During the CAG procedure
Association between Matrix Gla Protein (MGP) and aortic calcification
To establish a deeper understanding of the pathogenesis of central arterial calcification in CKD, MGP, a novel biochemical marker of arterial calcification, will be collected and analysed in all patients.
Time frame: Analysis will be performed as batch-analysis at the end of inclusion of patients summer 2021
Association between Calcification propensity score (T50test) and aortic calcification
To establish a deeper understanding of the pathogenesis of central arterial calcification in CKD Calcification propensity score (T50test) will be collected and analysed in all patients.
Time frame: Analysis will be performed as batch-analysis at the end of inclusion of patients summer 2021
Association between sRANKL (soluble receptor activator of nuclear factor kappa-B ligand) and aortic calcification
To establish a deeper understanding of the pathogenesis of central arterial calcification in CKD sRANKL (soluble receptor activator of nuclear factor kappa-B ligand) will be collected and analysed in all patients.
Time frame: Analysis will be performed as batch-analysis at the end of inclusion of patients summer 2021
Association between 25-OH-Vitamin D(D3+D2) and aortic calcification
To establish a deeper understanding of the pathogenesis of central arterial calcification in CKD 25-OH-Vitamin D(D3+D2) will be collected and analysed in all patients.
Time frame: Analysis will be performed as batch-analysis at the end of inclusion of patients summer 2021
Association between Fetuin-A(alfa-2-Heremans Schmid glycoprotein; AHSG) and aortic calcification
To establish a deeper understanding of the pathogenesis of central arterial calcification in CKD Fetuin-A(alfa-2-Heremans Schmid glycoprotein; AHSG) will be collected and analysed in all patients.
Time frame: Analysis will be performed as batch-analysis at the end of inclusion of patients summer 2021.
Association between Sclerostin and aortic calcification
To establish a deeper understanding of the pathogenesis of central arterial calcification in CKD, Sclerostin will be collected and analysed in all patients.
Time frame: Analysis will be performed as batch-analysis at the end of inclusion of patients summer 2021
Association between osteoprotegerin and aortic calcification
To establish a deeper understanding of the pathogenesis of central arterial calcification in CKD, osteoprotegerin will be collected and analysed in all patients.
Time frame: Analysis will be performed as batch-analysis at the end of inclusion of patients summer 2021
Association between BsAP (bone-specific alkaline phosphatase) and aortic calcification
To establish a deeper understanding of the pathogenesis of central arterial calcification in CKD, BsAP (bone-specific alkaline phosphatase) will be collected and analysed in all patients.
Time frame: Analysis will be performed as batch-analysis at the end of inclusion of patients summer 2021
Association between TRAP5B (tartrate-resistant acid phosphatase 5b) and aortic calcification
To establish a deeper understanding of the pathogenesis of central arterial calcification in CKD, TRAP5B (tartrate-resistant acid phosphatase 5b) will be collected and analysed in all patients.
Time frame: Analysis will be performed as batch-analysis at the end of inclusion of patients summer 2021
Association between P1NP (procollagen type 1 N propeptide) and aortic calcification
To establish a deeper understanding of the pathogenesis of central arterial calcification in CKD, P1NP (procollagen type 1 N propeptide) will be collected and analysed in all patients.
Time frame: Analysis will be performed as batch-analysis at the end of inclusion of patients summer 2021
Association between aortic calcification and Left Ventricular Global Longitudinal Strain (GLS) as determined during echocardiography.
All patients included in this study will undergo echocardiography. In particular systolic and diastolic function will be in focus. As scans will be supervised and reanalysed by a cardiologist blinded to patient CKD-stage.
Time frame: No later than 1 month after central BP measurements
Association between aortic calcification and LVDd (Left ventricular diameter in diastole) as determined during echocardiography.
All patients included in this study will undergo echocardiography. In particular systolic and diastolic function will be in focus. As scans will be supervised and reanalysed by a cardiologist blinded to patient CKD-stage.
Time frame: No later than 1 month after central BP measurements
Association between aortic calcification and IVS (Interventricular septum thickness) as determined during echocardiography.
All patients included in this study will undergo echocardiography. In particular systolic and diastolic function will be in focus. As scans will be supervised and reanalysed by a cardiologist blinded to patient CKD-stage.
Time frame: No later than 1 month after central BP measurements
Association between aortic calcification and Two-dimensional automated evaluation of ejection fraction (2-D auto-EF) as determined during echocardiography.
All patients included in this study will undergo echocardiography. In particular systolic and diastolic function will be in focus. As scans will be supervised and reanalysed by a cardiologist blinded to patient CKD-stage.
Time frame: No later than 1 month after central BP measurements
Association between aortic calcification and Aorta (sinus) diameter as determined during echocardiography.
All patients included in this study will undergo echocardiography. In particular systolic and diastolic function will be in focus. As scans will be supervised and reanalysed by a cardiologist blinded to patient CKD-stage.
Time frame: No later than 1 month after central BP measurements
Association between aortic calcification and Early mitral inflow velocity (E) as determined during echocardiography.
All patients included in this study will undergo echocardiography. In particular systolic and diastolic function will be in focus. As scans will be supervised and reanalysed by a cardiologist blinded to patient CKD-stage.
Time frame: No later than 1 month after central BP measurements
Association between aortic calcification and Duration of Pulmonal Vein Reversal as determined during echocardiography.
All patients included in this study will undergo echocardiography. In particular systolic and diastolic function will be in focus. As scans will be supervised and reanalysed by a cardiologist blinded to patient CKD-stage.
Time frame: No later than 1 month after central BP measurements
Association between aortic calcification and Late mitral inflow velocity (A) as determined during echocardiography.
All patients included in this study will undergo echocardiography. In particular systolic and diastolic function will be in focus. As scans will be supervised and reanalysed by a cardiologist blinded to patient CKD-stage.
Time frame: No later than 1 month after central BP measurements
Association between aortic calcification and Early diastolic mitral annulus velocity (E') as determined during echocardiography.
All patients included in this study will undergo echocardiography. In particular systolic and diastolic function will be in focus. As scans will be supervised and reanalysed by a cardiologist blinded to patient CKD-stage.
Time frame: No later than 1 month after central BP measurements
Association between aortic calcification and PW (Posterior wall thickness) as determined during echocardiography.
All patients included in this study will undergo echocardiography. In particular systolic and diastolic function will be in focus. As scans will be supervised and reanalysed by a cardiologist blinded to patient CKD-stage.
Time frame: No later than 1 month after central BP measurements
Association between aortic calcification and Aorta (ascendens) diameter as determined during echocardiography.
All patients included in this study will undergo echocardiography. In particular systolic and diastolic function will be in focus. As scans will be supervised and reanalysed by a cardiologist blinded to patient CKD-stage.
Time frame: No later than 1 month after central BP measurements
Association between aortic calcification and RVDd (Right ventricular diameter in diastole) as determined during echocardiography.
All patients included in this study will undergo echocardiography. In particular systolic and diastolic function will be in focus. As scans will be supervised and reanalysed by a cardiologist blinded to patient CKD-stage.
Time frame: No later than 1 month after central BP measurements
Association between aortic calcification and LAD (Left atrial diameter) as determined during echocardiography.
All patients included in this study will undergo echocardiography. In particular systolic and diastolic function will be in focus. As scans will be supervised and reanalysed by a cardiologist blinded to patient CKD-stage.
Time frame: No later than 1 month after central BP measurements
Association between aortic calcification and LAV (Left atrial volume) as determined during echocardiography.
All patients included in this study will undergo echocardiography. In particular systolic and diastolic function will be in focus. As scans will be supervised and reanalysed by a cardiologist blinded to patient CKD-stage.
Time frame: No later than 1 month after central BP measurements
Association between aortic calcification and TEI-Index as determined during echocardiography.
All patients included in this study will undergo echocardiography. In particular systolic and diastolic function will be in focus. As scans will be supervised and reanalysed by a cardiologist blinded to patient CKD-stage.
Time frame: No later than 1 month after central BP measurements
Association between aortic calcification and Tricuspid annular plane systolic excursion (TAPSE) as determined during echocardiography.
All patients included in this study will undergo echocardiography. In particular systolic and diastolic function will be in focus. As scans will be supervised and reanalysed by a cardiologist blinded to patient CKD-stage.
Time frame: No later than 1 month after central BP measurements
Association of arterial stiffness (defined as Pulse Wave Velocity (PWV)) and aortic calcification
To get a non-invasive estimate of arterial stiffness, measurement of Pulse Wave Velocity (PWV) (carotid-femoral and carotid-radial) will be performed. PWV will be recorded with the Sphygmocor® device according to regular protocol. Calibration of the device will be performed using an oscillometric device after 5 minutes of rest. Only measurements with an estimated standard deviation of +/- 1.0 m/s will be accepted and included in the study. If possible, two acceptable measurements will be conducted for each included patient. Calculation of PWV will be performed automatically by the device using a previously published formula.
Time frame: No later than 1 month after Central BP.
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