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

NCT04114695 | Completed

• 1 other identifier: VEK-nr 66842
• Study Type: observational
• Target: 185
• Locations: 1 country
• Sites: 1

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.

Conditions

Arterial Calcification; Kidney Diseases; Coronary Artery Disease; Aortic Calcification; Stroke; Vascular Diseases; Vascular Calcification

Outcome Measures

Primary Outcomes (3)

• 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 Outcomes (27)

• Association between Matrix Gla Protein (MGP) and aortic calcification

  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

  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

  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

  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

  Analysis will be performed as batch-analysis at the end of inclusion of patients summer 2021.

Study Arms (5)

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.

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)
• 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.

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Central Jutland Regional Hospital: lead

Study Sites (1)

Aarhus University Hospital

Aarhus, 8200, Denmark

Location

Related Publications (2)

• Nyvad J, Christensen KL, Andersen G, Reinhard M, Norgaard BL, Madsen JS, Nielsen S, Thomsen MB, Jensen JM, Peters CD, Buus NH. PIVKA-II but not dp-ucMGP is associated with aortic calcification in chronic kidney disease. BMC Nephrol. 2024 Nov 27;25(1):426. doi: 10.1186/s12882-024-03876-5.

  PMID: 39604863 DERIVED

• Nyvad J, Christensen KL, Andersen G, Reinhard M, Maeng M, Nielsen S, Thomsen MB, Jensen JM, Norgaard BL, Buus NH. Aortic Calcification is Associated With the Difference Between Invasive Central and Cuff-Measured Brachial Blood Pressure in Chronic Kidney Disease. Am J Hypertens. 2024 Jun 14;37(7):455-464. doi: 10.1093/ajh/hpae029.

  PMID: 38477704 DERIVED

Biospecimen

Retention: SAMPLES WITH DNA

Whole Blood, Plasma, Urine

MeSH Terms

Conditions

Kidney Diseases; Coronary Artery Disease; Stroke; Vascular Diseases; Vascular Calcification

Condition Hierarchy (Ancestors)

Urologic Diseases; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Male Urogenital Diseases; Coronary Disease; Myocardial Ischemia; Heart Diseases; Cardiovascular Diseases; Arteriosclerosis; Arterial Occlusive Diseases; Cerebrovascular Disorders; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Calcinosis; Calcium Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases

Study Officials

• Niels H Buus, MD PhD DMSc

  Department of Renal diseases, Aarhus University Hospital

  STUDY CHAIR

• Jakob T Nyvad, M.D.

  The Clinic of Hypertension, Aarhus University Hospital

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: CROSS SECTIONAL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: M.D., PhD-student

Study Record Dates

• First Submitted: August 14, 2019
• First Posted: October 3, 2019
• Study Start: October 15, 2019
• Primary Completion: January 1, 2022
• Study Completion: January 1, 2022
• Last Updated: March 31, 2022

Record last verified: 2022-03

Locations

DK (1)