Aortic Calcification and Central Blood Pressure in Patients With Chronic Kidney Disease (ACCEPT)

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 Overview

• Status: Completed
• Conditions: Vascular Diseases; Coronary Artery Disease; Stroke; Kidney Diseases; Vascular Calcification; Arterial Calcification; Aortic Calcification

• Study Type: Observational
• Enrollment (Actual): 185

Contacts and Locations

Study Locations

• Denmark
  • Aarhus, Denmark, 8200
    • Aarhus University Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

• Sampling Method: Non-Probability Sample

Study Population

Patients scheduled for CAG can be included in the study if they satisfy all inclusion criteria and do not meet any exclusion criteria.

The study cohort will consist of:

1. 160 patients with CKD at various stages based on estimated glomerular filtration rate (eGFR): 40 patients in stage 3a (eGFR 45-59 ml/min/1,73 m2), 40 patients in stage 3b (30-44 ml/min/1,73 m2), 40 patients in stage 4 (15-29 ml/min/1,73 m2) and 40 in stage 5 (<15 ml/min/1,73 m2). The stage 5 patients will be distributed between non-dialysis and dialysis patients.
2. 40 patients with renal function considered normal for age (eGFR ≥60 ml/min/1.73 m2) without proteinuria or structural kidney disease.

Description

Inclusion Criteria:

• Age >18 years
• Patient referred for planned CAG at the Department of Cardiology, Aarhus University Hospital (AUH)
• eGFR constantly either >60 ml/min or <60 ml/min in at least 2 separate blood-sample measurements over at least 3 months.
• Signed informed consent-form.

Exclusion Criteria:

• Antihypertensive treatment changed within the last two weeks prior to the CAG.
• Severe aortic valve stenosis (<1 cm) as central hemodynamics may be altered
• Maximum number of patients in CKD-group already reached.
• Atrial fibrillation or other cardiac arrhythmia making radial Pulse Wave Analysis (PWA) estimations impossible.
• Known significant stenosis of a. subclavia or a. brachialis
• Bilateral arteriovenous-fistula (even if one or both of these have been surgically removed) as this may significantly affect the pulse-wave form.

Study Plan

How is the study designed?

Number of groups / cohorts

5

Cohorts and Interventions

Group / Cohort
Non-CKD (eGFR >60 ml/min/1.73 m2); Patients with renal function considered normal for age (eGFR >60 ml/min/1.73 m2) without proteinuria or structural kidney disease.
CKD stage 3a (eGFR 45-59 ml/min/1,73 m2); Patients with CKD stage 3a (eGFR 45-59 ml/min/1,73 m2)
CKD stage 3b (eGFR 30-44 ml/min/1,73 m2); Patients with CKD stage 3b (eGFR 30-44 ml/min/1,73 m2)
CKD stage 4 (eGFR 15-29 ml/min/1,73 m2); Patients with CKD stage 4 (eGFR 15-29 ml/min/1,73 m2)
CKD stage 5 (eGFR <15 ml/min/1,73 m2); Patients with CKD stage 5 (eGFR <15 ml/min/1,73 m2). 50% of these patients will be in dialysis, while the other 50% will be pre-dialysis patients.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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.	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.	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.	During the CAG procedure

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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.	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.	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.	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.	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.	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.	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.	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.	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.	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.	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.	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.	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.	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.	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.	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.	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.	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.	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.	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.	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.	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.	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.	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.	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.	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.	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.	No later than 1 month after Central BP.

Collaborators and Investigators

• Sponsor: Central Jutland Regional Hospital
• Investigators: Study Chair: Niels H Buus, MD PhD DMSc, Department of Renal diseases, Aarhus University Hospital; Principal Investigator: Jakob T Nyvad, M.D., The Clinic of Hypertension, Aarhus University Hospital

Study record dates

Study Major Dates

• Study Start (ACTUAL): October 15, 2019
• Primary Completion (ACTUAL): January 1, 2022
• Study Completion (ACTUAL): January 1, 2022

Study Registration Dates

• First Submitted: August 14, 2019
• First Submitted That Met QC Criteria: October 1, 2019
• First Posted (ACTUAL): October 3, 2019

Study Record Updates

• Last Update Posted (ACTUAL): March 31, 2022
• Last Update Submitted That Met QC Criteria: March 28, 2022
• Last Verified: March 1, 2022

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Myocardial Ischemia; Heart Diseases; Cardiovascular Diseases; Metabolic Diseases; Arteriosclerosis; Arterial Occlusive Diseases; Urologic Diseases; Renal Insufficiency; Coronary Disease; Calcium Metabolism Disorders; Coronary Artery Disease; Kidney Diseases; Renal Insufficiency, Chronic; Vascular Diseases; Calcinosis; Vascular Calcification
• Other Study ID Numbers: VEK-nr 66842

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No