Sleep Apnea, Coronary Atherosclerosis and Heart Failure in Diabetes Patients With Nephropathy

NCT04549324 | Completed DMC

• 1 other identifier: 1-10-72-122-20
• Study Type: observational
• Target: 74
• Locations: 1 country
• Sites: 1

Brief Summary

Background: Diabetes, and especially diabetic kidney disease is associated with the development of cardiovascular disease such as calcification in the coronary arteries and heart failure. Sleep apnea is frequent among patients with diabetes and diabetic kidney disease and sleep apnea itself is a solitary risk factor in the development of cardiovascular disease. Nonetheless, sleep apnea is underdiagnosed in diabetes patients because of a discrepancy between sleep apnea severity and actual oxygen deficiency symptoms which makes the diagnosis difficult. For that reason, many diabetics have undiagnosed sleep apnea together with cardiovascular disease. Early discovery of sleep apnea among high risk diabetic patients may therefore be considered crucial before cardiovascular complications develop. For this reason, sleep apnea screening of high-risk diabetics can possibly improve early diagnostics of cardiovascular disease. Aim: This study will seek to establish the association between obstructive sleep apnea (OSA) and coronary calcification and heart failure in patients with diabetic kidney disease. The basic hypothesis of the study is that patients with diabetic kidney disease and concurrent OSA have a higher prevalence and severity of coronary calcification and heart failure compared to patients without OSA. Methods: Diabetic adult patients with scheduled check-ups at Steno Diabetes Center Aarhus, or Department of Renal Medicine on Aarhus University Hospital will be included in the study. Firstly, all included patients are screened for sleep apnea with the devices SomnoTouch® and ApneaLink®. Based on the sleep apnea determination; 40 patients with moderate-severe sleep apnea are compared with 40 patients without sleep apnea. In both groups, the patients are examined for calcification in the coronary vessels using a CT-scan while the function of the heart is examined by ultrasound (echocardiography). The stiffness of aorta is measured and performed using radial artery tonometry (SphygmoCor®). Furthermore, range of blood- and urine samples will be performed The perspectives are that patients with diabetes should be regularly evaluated for sleep apnea and that patients with moderate/severe sleep apnea should undergo further examination for cardiovascular disease even though the patients don't display any symptoms of either cardiovascular disease or sleep apnea.

Conditions

Sleep Apnea; Diabetic Nephropathy Type 2; Coronary Atheroscleroses; Heart Insufficiency; Arterial Stiffness; Kidney Diseases; Vascular Diseases

Outcome Measures

Primary Outcomes (4)

• The association between sleep apnea and coronary atherosclerosis (Agatston Score) measured with cardiac CT-scan in patients with diabetic nephropathy.

  The degree of atherosclerosis in the coronary artery walls is evaluated by cardiac CT-scan and subsequent quantified by Agatston score. Patients with an estimated glomerular filtration rate (eGFR) ≤ 25 ml/min/1,73 m2 is scanned without contrast whereas patients with an eGFR 26-60 ml/min/1,73 m2 are screened with contrast. All Agatston scoring will be performed by a cardiologist blinded to information on patient biochemical characteristics and AHI. The only biochemical parameter which the cardiologist is not blinded to is eGFR.

  Cardiac CT-scan will be performed no later than 1 month after inclusion. All Agatston scores will be estimated straight after the cardiac CT-scan.

• The association between sleep apnea and systolic function in patients with diabetic nephropathy.

  All patients included in the study will undergo transthoracic echocardiography. Systolic function is evaluated by two-dimensional automated evaluation of ejection fraction (2-D auto-EF). The echocardiographic-clinician is blinded to AHI-status.

  Transthoracic echocardiography will be performed no later than 1 month after inclusion and prior to cardiac CT-scan

• The association between sleep apnea and diastolic heart failure in patients with diabetic nephropathy.

  All patients included in the study will undergo transthoracic echocardiography. Diastolic function is evaluated by E/e´. The echocardiographic-clinician is blinded to AHI-status.

  Transthoracic echocardiography will be performed no later than 1 month after inclusion and prior to cardiac CT-scan

• The association between sleep apnea and systolic function in patients with diabetic nephropathy.

  All patients included in the study will undergo transthoracic echocardiography. Systolic function is evaluated by Left Ventricular Global Longitudinal Strain (GLS). The echocardiographic-clinician is blinded to AHI-status.

  Transthoracic echocardiography will be performed no later than 1 month after inclusion and prior to cardiac CT-scan

Secondary Outcomes (30)

• The association between sleep apnea and coronary plaque volume in patients with diabetic nephropathy.

  Cardiac CT-scan will be performed no later than 1 month after inclusion.

• Association of sleep apnea and aortic stiffness (defined as Pulse Wave Velocity (PWV)) in patients with diabetic nephropathy.

  PWV is performed the same day as the patient is included.

• Association between Matrix Gla Protein (MGP) and coronary calcification in patients with sleep apnea and diabetic nephropathy.

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

• Association between Calcification propensity score (T50test) and coronary calcification in patients with sleep apnea and diabetic nephropathy.

  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 coronary calcification in patients with sleep apnea and diabetic nephropathy.

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

Study Arms (2)

Sleep Apnea (AHI ≥ 15 per hour)

Patients with moderate/severe sleep apnea (Apnea/hypopnea-index ≥ 15 per hour).

Non-Sleep Apnea (AHI < 5 per hour)

Patients without sleep apnea (Apnea/hypopnea-index \< 5 per hour).

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)
• Sampling Method: Non-Probability Sample

Study Population

Diabetic adult patients (Type 2) with scheduled check-ups at Steno Diabetes Center Aarhus, or Department of Renal Medicine on Aarhus University Hospital can be included in the study if they satisfy all eligible criteria. Additionally, patients from the GP and within the including area of Aarhus University Hospital were invited to participate in the study. The study cohort will consist of: Generel characteristics of both groups: \- Diabetes Mellitus Type 2 with an eGFR between 10-60 ml/min/1,73 m\^2 Sleep Apnea: 1. 40 patients with an apnea/hyponea-index above ≥ 15 per hour. Non-Sleep Apnea: 2. 40 patients with an apnea/hyponea-index below \< 5 per hour.

You may qualify if:

• ≥ 18 years.
• Diabetes Mellitus Type 2 with an eGFR between 10-60 ml/min/1,73 m\^2 (Equalling CKD-group 3, 4 and 5 non-dialysis).

You may not qualify if:

• Known sleep apnea in continuous positive airway pressure(CPAP) treatment.
• Known mild sleep apnea (AHI 5-14) after the sleep apnea measurement.
• Participants with central apnea (\> 50 % of central apnea episodes in the AHI ≥ 15 group.) or Cheyne Stokes after the sleep apnea measurement.
• \< 4 hours of recording (ApneaLink)
• Known coronary arterial disease with previous revascularization (PCI or CABG)

Sponsors & Collaborators

• University of Aarhus: lead

Study Sites (1)

Aarhus University Hospital

Aarhus, 8200, Denmark

Location

Biospecimen

Retention: SAMPLES WITH DNA

Whole Blood, Plasma, Urine

MeSH Terms

Conditions

Sleep Apnea Syndromes; Coronary Artery Disease; Heart Failure; Kidney Diseases; Vascular Diseases

Condition Hierarchy (Ancestors)

Apnea; Respiration Disorders; Respiratory Tract Diseases; Sleep Disorders, Intrinsic; Dyssomnias; Sleep Wake Disorders; Nervous System Diseases; Coronary Disease; Myocardial Ischemia; Heart Diseases; Cardiovascular Diseases; Arteriosclerosis; Arterial Occlusive Diseases; Urologic Diseases; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Male Urogenital Diseases

Study Officials

• Niels H. Buus, MD PhD DMSc

  Department of Renal diseases, Aarhus University Hospital

  STUDY CHAIR

• Sebastian Nielsen, MD student

  Department of Renal diseases, Aarhus University Hospital

  PRINCIPAL INVESTIGATOR

• Jakob T. Nyvad, MD

  The Clinic of Hypertension, Aarhus University Hospital

  STUDY CHAIR

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: CROSS SECTIONAL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 8, 2020
• First Posted: September 16, 2020
• Study Start: October 1, 2020
• Primary Completion: January 24, 2022
• Study Completion: January 24, 2022
• Last Updated: February 7, 2022

Record last verified: 2021-10

Data Sharing

• IPD Sharing: Will not share

Locations

DK (1)