Clinical trial NCT04114695: Aortic Calcification and Central Blood Pressure in Patients With Chronic Kidney Disease
Official title: Aortic Calcification and Central Blood Pressure in Patients With Chronic Kidney Disease
Study type: OBSERVATIONAL
Overall status: COMPLETED
Conditions: Arterial Calcification
Kidney Diseases
Coronary Artery Disease
Aortic Calcification
Stroke
Vascular Diseases
Vascular Calcification
Lead sponsor: Central Jutland Regional Hospital
Sponsor class: OTHER
First posted: 2019-10-03
Enrollment: 185
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: CROSS_SECTIONAL
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.

Brief summary: 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.


Eligibility criteria: 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.

Primary outcomes:
measure: The difference between directly measured and estimated aortic (central) systolic blood pressure and the corresponding brachial systolic blood pressure
timeFrame: During the CAG-procedure
measure: The degree of aortic calcification
timeFrame: 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.
measure: The difference between directly measured and estimated aortic (central) diastolic blood pressure and the corresponding brachial diastolic blood pressure.
timeFrame: During the CAG procedure
Secondary outcomes:
measure: Association between Matrix Gla Protein (MGP) and aortic calcification
timeFrame: Analysis will be performed as batch-analysis at the end of inclusion of patients summer 2021
measure: Association between Calcification propensity score (T50test) and aortic calcification
timeFrame: Analysis will be performed as batch-analysis at the end of inclusion of patients summer 2021
measure: Association between sRANKL (soluble receptor activator of nuclear factor kappa-B ligand) and aortic calcification
timeFrame: Analysis will be performed as batch-analysis at the end of inclusion of patients summer 2021
measure: Association between 25-OH-Vitamin D(D3+D2) and aortic calcification
timeFrame: Analysis will be performed as batch-analysis at the end of inclusion of patients summer 2021
measure: Association between Fetuin-A(alfa-2-Heremans Schmid glycoprotein; AHSG) and aortic calcification
timeFrame: Analysis will be performed as batch-analysis at the end of inclusion of patients summer 2021.
measure: Association between Sclerostin and aortic calcification
timeFrame: Analysis will be performed as batch-analysis at the end of inclusion of patients summer 2021
measure: Association between osteoprotegerin and aortic calcification
timeFrame: Analysis will be performed as batch-analysis at the end of inclusion of patients summer 2021
measure: Association between BsAP (bone-specific alkaline phosphatase) and aortic calcification
timeFrame: Analysis will be performed as batch-analysis at the end of inclusion of patients summer 2021
measure: Association between TRAP5B (tartrate-resistant acid phosphatase 5b) and aortic calcification
timeFrame: Analysis will be performed as batch-analysis at the end of inclusion of patients summer 2021
measure: Association between P1NP (procollagen type 1 N propeptide) and aortic calcification
timeFrame: Analysis will be performed as batch-analysis at the end of inclusion of patients summer 2021
measure: Association between aortic calcification and Left Ventricular Global Longitudinal Strain (GLS) as determined during echocardiography.
timeFrame: No later than 1 month after central BP measurements
measure: Association between aortic calcification and LVDd (Left ventricular diameter in diastole) as determined during echocardiography.
timeFrame: No later than 1 month after central BP measurements
measure: Association between aortic calcification and IVS (Interventricular septum thickness) as determined during echocardiography.
timeFrame: No later than 1 month after central BP measurements
measure: Association between aortic calcification and Two-dimensional automated evaluation of ejection fraction (2-D auto-EF) as determined during echocardiography.
timeFrame: No later than 1 month after central BP measurements
measure: Association between aortic calcification and Aorta (sinus) diameter as determined during echocardiography.
timeFrame: No later than 1 month after central BP measurements
measure: Association between aortic calcification and Early mitral inflow velocity (E) as determined during echocardiography.
timeFrame: No later than 1 month after central BP measurements
measure: Association between aortic calcification and Duration of Pulmonal Vein Reversal as determined during echocardiography.
timeFrame: No later than 1 month after central BP measurements
measure: Association between aortic calcification and Late mitral inflow velocity (A) as determined during echocardiography.
timeFrame: No later than 1 month after central BP measurements
measure: Association between aortic calcification and Early diastolic mitral annulus velocity (E') as determined during echocardiography.
timeFrame: No later than 1 month after central BP measurements
measure: Association between aortic calcification and PW (Posterior wall thickness) as determined during echocardiography.
timeFrame: No later than 1 month after central BP measurements
measure: Association between aortic calcification and Aorta (ascendens) diameter as determined during echocardiography.
timeFrame: No later than 1 month after central BP measurements
measure: Association between aortic calcification and RVDd (Right ventricular diameter in diastole) as determined during echocardiography.
timeFrame: No later than 1 month after central BP measurements
measure: Association between aortic calcification and LAD (Left atrial diameter) as determined during echocardiography.
timeFrame: No later than 1 month after central BP measurements
measure: Association between aortic calcification and LAV (Left atrial volume) as determined during echocardiography.
timeFrame: No later than 1 month after central BP measurements
measure: Association between aortic calcification and TEI-Index as determined during echocardiography.
timeFrame: No later than 1 month after central BP measurements
measure: Association between aortic calcification and Tricuspid annular plane systolic excursion (TAPSE) as determined during echocardiography.
timeFrame: No later than 1 month after central BP measurements
measure: Association of arterial stiffness (defined as Pulse Wave Velocity (PWV)) and aortic calcification
timeFrame: No later than 1 month after Central BP.
Other outcomes:
Locations:
city: Aarhus
country: Denmark
facility: Aarhus University Hospital
Study officials:
affiliation: Department of Renal diseases, Aarhus University Hospital
name: Niels H Buus, MD PhD DMSc
role: STUDY_CHAIR
affiliation: The Clinic of Hypertension, Aarhus University Hospital
name: Jakob T Nyvad, M.D.
role: PRINCIPAL_INVESTIGATOR
References: