The Effect of Lipoprotein (a) on Arterial Stiffness, Endothelial Function and Left Atrial and Left Ventricular Deformation - An Observational Study.
Trial Snapshot
- Phase
- Not Applicable
- Status
- Recruiting
- Sponsor
- Enrollment
- 300
- Locations
- 2
- Primary Endpoint
- Comparison of endothelial glycocalyx thickness difference between groups
Study Overview
Brief Summary
- Introduction Lipoprotein(a), or Lp(a), is a type of lipoprotein that is structurally similar to LDL (low-density lipoprotein) but carries an additional protein called apolipoprotein (a).
- Purpose of the Study
The primary purpose of this study is to investigate the effect of Lp(a) levels on arterial stiffness, endothelial function, and left atrial (LA) and left ventricular (LV) deformation over a 12-month follow-up period.
Secondarily, the study will investigate:
- a) The incidence of major adverse cardiovascular events (MACE), including cardiovascular death, acute myocardial infarction, and acute stroke.
- b) The correlation between MACE incidence and parameters of arterial stiffness, endothelial function, and LA/LV deformation.
- c) The levels of oxidative load markers.
- Materials and Methods This observational study will include adults aged 18-75 years (regardless of gender) who visit the outpatient clinics of the 2nd University Cardiology Clinic at "Attikon" General Hospital. All participants will sign a consent form. A full medical history, clinical examination, and blood collection will be performed to determine levels of Total Cholesterol, LDL-C, HDL-C, triglycerides, and Lp(a) at each visit..
Participants will be divided into three groups:
- Group A: Lp(a) ≥50 mg/dL with Total Cholesterol<200 mg/dl
- Group B : Lp(a) <50 mg/dL. with Total Cholesterol>200 mg/dl
- Group C (Control): Lp(a) <50 mg/dL. with Total Cholesterol<200 mg/dl At each group n ≥ 100 participants are anticipated.
Measurements at baseline, at 6 and at 12 months:
- Arterial Stiffness: Determination of carotid-femoral pulse wave velocity (cf-PWV) using the Complior SP device and 24-hour pulse wave analysis with the Mobil-O-Graph device.
- Endothelial Function: Measurement of the endothelial glycocalyx thickness of sublingual capillaries using a Sidestream Dark Field (SDF) camera (GlycoCheck). This is expressed through the perfused boundary region (PBR) index.
- Cardiac Deformation: Use of two-dimensional strain (speckle tracking) to calculate the Global Longitudinal Strain (GLS) of the LV and LA strain.
- Oxidative Load: Determination of malondialdehyde (MDA) and protein carbonyls (PCs) levels as markers of oxidative stress using spectrophotometric kits.
Statistical Analysis: Comparisons regarding the changes in these markers over 6 and 12 months will be conducted between the three groups.
Detailed Description
- Introduction Lipoprotein(a), or Lp(a), is a type of lipoprotein that is structurally similar to LDL (low-density lipoprotein) but carries an additional protein called apolipoprotein (a). Recent data establishes Lp(a) as a predisposing risk factor for cardiovascular diseases, such as coronary artery disease, stroke, and aortic valve stenosis. Elevated levels of Lp(a) contribute to these conditions by promoting atherosclerosis. Its levels are primarily determined genetically, with minimal influence from diet and lifestyle. This makes it a significant factor for assessing cardiovascular risk, particularly in individuals with a family history of coronary artery disease or patients who experience early cardiovascular problems despite having normal lipid levels.
While Lp(a) levels can vary greatly, the generally accepted threshold for increased cardiovascular risk is 50 mg/dL (or 125 nmol/L). Individuals with levels above this limit are at a higher risk for cardiovascular events. It is estimated that 20-30% of the general population has elevated Lp(a) levels, making it a common risk factor. Currently, there are no widely available treatments specifically targeting Lp(a) levels, though PCSK9 inhibitors and inclisiran have shown promising results in clinical trials. 2. Purpose of the Study There is currently insufficient bibliographic documentation regarding the effect of Lp(a) on arterial stiffness, endothelial function, and the deformation of the left atrium and left ventricle.
The primary purpose of this study is to investigate the effect of Lp(a) levels on arterial stiffness, endothelial function, and left atrial (LA) and left ventricular (LV) deformation over a 6-month follow-up period.
Secondarily, the study will investigate:
- a) The incidence of major adverse cardiovascular events (MACE), including cardiovascular death, acute myocardial infarction, and acute stroke.
- b) The correlation between MACE incidence and parameters of arterial stiffness, endothelial function, and LA/LV deformation.
- c) The levels of oxidative load markers.
- Materials and Methods
This observational study will include adults aged 18-75 years (regardless of gender) who visit the outpatient clinics of the 2nd University Cardiology Clinic at "Attikon" General Hospital. All participants will sign a consent form. A full medical history, clinical examination, and blood collection will be performed to determine levels of Total Cholesterol, LDL-C, HDL-C, triglycerides, and Lp(a) at each visit. Participants will be divided into three groups:
Study Design
- Study Type
- Observational
- Observational Model
- Cohort
- Time Perspective
- Prospective
Eligibility Criteria
- Ages
- 18 Years to 75 Years (Adult, Older Adult)
- Sex
- All
- Accepts Healthy Volunteers
- Yes
Inclusion Criteria
- •Adults participants 18-75 years old
- •Willing to sign the informed consent and paerticipate in the study
Exclusion Criteria
- •History of autoimmune/autoinflammatory disease,
- •Severe valvular heart disease,
- •severe chronic kidney disease(eGFR<60 ml/min/1.73 m2),
- •Active Pregnancy
- •Severe hepatic impairment.
Arms & Interventions
Participants with normal lipids levels
Group C: PArticipants with Lp(a) (Lp(a) <50 mg/dL) and TotalCholesterol levels (Cholesterol ≥200 mg/dl) within reference range.
All participants (n≥100) will undergo assessment of arterial stiffness by measing PWV, evaluation of thickness of endothelial glycocalyx bymeasuring PBR, assessment of myocardial deformation by measuring LA strain and LV GLS and quantification of oxidative stress burden by measuring MDa and PCs at baseline, at 6 months and at 12 months.
Participants with elevated Lipoprotein a
Group A: PArticipants with elevated Lp(a) (Lp(a) ≥50 mg/dL) with normal Total Cholesterol levels (Cholesterol<200 mg/dl). All participants (n≥100) will undergo assessment of arterial stiffness by measing PWV, evaluation of thickness of endothelial glycocalyx bymeasuring PBR, assessment of myocardial deformation by measuring LA strain and LV GLS and quantification of oxidative stress burden by measuring MDa and PCs at baseline, at 6 months and at 12 months.
Participants with elevated Total Cholesterol
Group B: PArticipants with normal Lp(a) (Lp(a) <50 mg/dL) with elevated Total Cholesterol levels (Cholesterol ≥200 mg/dl).
All participants (n≥100) will undergo assessment of arterial stiffness by measing PWV, evaluation of thickness of endothelial glycocalyx bymeasuring PBR, assessment of myocardial deformation by measuring LA strain and LV GLS and quantification of oxidative stress burden by measuring MDa and PCs at baseline, at 6 months and at 12 months.
Outcomes
Primary Outcomes
Comparison of endothelial glycocalyx thickness difference between groups
Time Frame: 12 months
Comparison of Perfused Boundary Region (PBR) difference of sublingual vessels between groups
Comparison of arterial stiffness difference between groups
Time Frame: 12 months
Comparison of carotid-to-femoral Pulse Wave Velocity (PWV) difference between groups
Comparison of left atrial deformation difference between groups
Time Frame: 12 months
Comparison of left atrial strain difference between groups
Comparison of left ventricular deformation difference between groups
Time Frame: 12 months
Comparison of left ventricular strain difference between groups
Secondary Outcomes
- Comparison of oxidative stress burden difference between groups(12 monnths)
- Comparison of major adverse cardiovascular events between groups(12 months)
Investigators
Ignatios Ikonomidis
Professor of Cardiology
University of Athens