The Effect of Lipoprotein (a) on Arterial Stiffness, Endothelial Function and Myocardial Deformation

NCT07324902 | Recruiting

• 1 other identifier: 787/01-11-2024
• Study Type: observational
• Target: 300
• Locations: 1 country
• Sites: 2

Brief Summary

• 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..
• 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.

Conditions

Lipoprotein Disorder; Arterial Stiffness; Endothelial Dysfunction

Keywords

lipoprotein a; artrial stiffness; endothelial glycocalyx; myocardial deformation; oxidative stress

Outcome Measures

Primary Outcomes (4)

• Comparison of endothelial glycocalyx thickness difference between groups

  Comparison of Perfused Boundary Region (PBR) difference of sublingual vessels between groups

  12 months

• Comparison of arterial stiffness difference between groups

  Comparison of carotid-to-femoral Pulse Wave Velocity (PWV) difference between groups

  12 months

• Comparison of left atrial deformation difference between groups

  Comparison of left atrial strain difference between groups

  12 months

• Comparison of left ventricular deformation difference between groups

  Comparison of left ventricular strain difference between groups

  12 months

Secondary Outcomes (2)

• Comparison of oxidative stress burden difference between groups

  12 monnths

• Comparison of major adverse cardiovascular events between groups

  12 months

Study Arms (3)

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.

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.

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)
• Sampling Method: Non-Probability Sample

Study Population

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.

You may qualify if:

• Adults participants 18-75 years old
• Willing to sign the informed consent and paerticipate in the study

You may not qualify if:

• 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.

Sponsors & Collaborators

• University of Athens: lead

Study Sites (2)

"Attikon" University General Hospital

Athens, Attica, 12462, Greece

RECRUITING

Attikon University Hospital, 2nd Department of Cardiology, National and Kapodistrina University of Athens

Athens, Rimini 1, 12462, Greece

RECRUITING

Related Publications (10)

• Karp A, Jacobs M, Barris B, Labkowsky A, Frishman WH. Lipoprotein(a): A Review of Risk Factors, Measurements, and Novel Treatment Modalities. Cardiol Rev. 2025 Jul-Aug 01;33(4):352-358. doi: 10.1097/CRD.0000000000000667. Epub 2024 Feb 28.

  PMID: 38415744 RESULT

• Tsimikas S, Marcovina SM. Ancestry, Lipoprotein(a), and Cardiovascular Risk Thresholds: JACC Review Topic of the Week. J Am Coll Cardiol. 2022 Aug 30;80(9):934-946. doi: 10.1016/j.jacc.2022.06.019.

  PMID: 36007992 RESULT

• Simantiris S, Antonopoulos AS, Papastamos C, Benetos G, Koumallos N, Tsioufis K, Tousoulis D. Lipoprotein(a) and inflammation- pathophysiological links and clinical implications for cardiovascular disease. J Clin Lipidol. 2023 Jan-Feb;17(1):55-63. doi: 10.1016/j.jacl.2022.10.004. Epub 2022 Oct 20.

  PMID: 36333256 RESULT

• Clarke R, Wright N, Lin K, Yu C, Walters RG, Lv J, Hill M, Kartsonaki C, Millwood IY, Bennett DA, Avery D, Yang L, Chen Y, Du H, Sherliker P, Yang X, Sun D, Li L, Qu C, Marcovina S, Collins R, Chen Z, Parish S; China Kadoorie Biobank Collaborative Group. Causal Relevance of Lp(a) for Coronary Heart Disease and Stroke Types in East Asian and European Ancestry Populations: A Mendelian Randomization Study. Circulation. 2025 Jun 17;151(24):1699-1711. doi: 10.1161/CIRCULATIONAHA.124.072086. Epub 2025 Apr 29.

  PMID: 40297899 RESULT

• Burgess S, Ference BA, Staley JR, Freitag DF, Mason AM, Nielsen SF, Willeit P, Young R, Surendran P, Karthikeyan S, Bolton TR, Peters JE, Kamstrup PR, Tybjaerg-Hansen A, Benn M, Langsted A, Schnohr P, Vedel-Krogh S, Kobylecki CJ, Ford I, Packard C, Trompet S, Jukema JW, Sattar N, Di Angelantonio E, Saleheen D, Howson JMM, Nordestgaard BG, Butterworth AS, Danesh J; European Prospective Investigation Into Cancer and Nutrition-Cardiovascular Disease (EPIC-CVD) Consortium. Association of LPA Variants With Risk of Coronary Disease and the Implications for Lipoprotein(a)-Lowering Therapies: A Mendelian Randomization Analysis. JAMA Cardiol. 2018 Jul 1;3(7):619-627. doi: 10.1001/jamacardio.2018.1470.

  PMID: 29926099 RESULT

• Larsson SC, Gill D, Mason AM, Jiang T, Back M, Butterworth AS, Burgess S. Lipoprotein(a) in Alzheimer, Atherosclerotic, Cerebrovascular, Thrombotic, and Valvular Disease: Mendelian Randomization Investigation. Circulation. 2020 Jun 2;141(22):1826-1828. doi: 10.1161/CIRCULATIONAHA.120.045826. Epub 2020 Jun 1. No abstract available.

  PMID: 32479194 RESULT

• Tsimikas S, Karwatowska-Prokopczuk E, Xia S. Lipoprotein(a) Reduction in Persons with Cardiovascular Disease. Reply. N Engl J Med. 2020 May 21;382(21):e65. doi: 10.1056/NEJMc2004861. No abstract available.

  PMID: 32433854 RESULT

• Laurent S, Cockcroft J, Van Bortel L, Boutouyrie P, Giannattasio C, Hayoz D, Pannier B, Vlachopoulos C, Wilkinson I, Struijker-Boudier H; European Network for Non-invasive Investigation of Large Arteries. Expert consensus document on arterial stiffness: methodological issues and clinical applications. Eur Heart J. 2006 Nov;27(21):2588-605. doi: 10.1093/eurheartj/ehl254. Epub 2006 Sep 25.

  PMID: 17000623 RESULT

• Lekakis J, Abraham P, Balbarini A, Blann A, Boulanger CM, Cockcroft J, Cosentino F, Deanfield J, Gallino A, Ikonomidis I, Kremastinos D, Landmesser U, Protogerou A, Stefanadis C, Tousoulis D, Vassalli G, Vink H, Werner N, Wilkinson I, Vlachopoulos C. Methods for evaluating endothelial function: a position statement from the European Society of Cardiology Working Group on Peripheral Circulation. Eur J Cardiovasc Prev Rehabil. 2011 Dec;18(6):775-89. doi: 10.1177/1741826711398179.

  PMID: 21450600 RESULT

• Paraskevaidis IA, Panou F, Papadopoulos C, Farmakis D, Parissis J, Ikonomidis I, Rigopoulos A, Iliodromitis EK, Th Kremastinos D. Evaluation of left atrial longitudinal function in patients with hypertrophic cardiomyopathy: a tissue Doppler imaging and two-dimensional strain study. Heart. 2009 Mar;95(6):483-9. doi: 10.1136/hrt.2008.146548. Epub 2008 Sep 2.

  PMID: 18765436 RESULT

Study Officials

• Ignatios Ikonomidis

  National and Kapodistrian University of Athens

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Ignatios Ikonomidis

CONTACT

+30 694 4805732; ignoik@gmail.com

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor of Cardiology

Study Record Dates

• First Submitted: December 23, 2025
• First Posted: January 8, 2026
• Study Start: September 25, 2024
• Primary Completion (Estimated): October 30, 2026
• Study Completion (Estimated): August 17, 2027
• Last Updated: March 11, 2026

Record last verified: 2026-03

Data Sharing

• IPD Sharing: Will not share

Locations

GR (2)