Lipoprotein (a) and Vascular Regenerative Cell Content

NCT06626659 | Completed

• 1 other identifier: Pro00080565
• Study Type: observational
• Target: 40
• Locations: 1 country
• Sites: 2

Brief Summary

Lp(a)-VRCE is an observational, cross sectional study looking at vessel reparative stem cell content in people with and without elevated lipoprotein (a) \[Lp(a)\]. Specifically, the type and number of these cells in peripheral blood samples will be measured in participants with Lp(a) ≥100 nmol/L and compared to participants with Lp(a) \< 100 nmol/L. Determining the presence or absence of specific cells with blood vessel repair capacity in participants with high Lp(a) will further our knowledge of potential mechanisms through which Lp(a) influences cardiovascular health.

Conditions

Atherosclerosis Cardiovascular Disease; Ischemic Heart Disease; Cardiovascular Diseases; Dyslipidemia

Keywords

Lipoprotein (a); Progenitor cells; Cardiovascular disease

Outcome Measures

Primary Outcomes (1)

• Difference in the frequency or absolute number of circulating ALDHhiSSClo primitive myeloid progenitor cells between individuals with elevated Lp(a) and individuals with non-elevated Lp(a)

  Baseline

Secondary Outcomes (1)

• Difference in the frequency/absolute count of ALDHhiSSCmid monocytes between individuals with elevated Lp(a) and individuals with non-elevated Lp(a)

  Baseline

Other Outcomes (2)

• Difference in the amount of intracellular reactive oxygen species (ROS) production in ALDHhi progenitor cell subsets

  Baseline

• Difference in the levels of inflammatory and oxidative stress biomarkers

  Baseline

Study Arms (2)

Elevated Lp(a)

Individuals with an Lp(a) level greater than or equal to 100 nmol/L

Non-elevated Lp(a)

Individuals with an Lp(a) level less than 100 nmol/L

Eligibility Criteria

• Age: 18 Years - 80 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)
• Sampling Method: Non-Probability Sample

Study Population

Participants will be identified from primary care and cardiology outpatient clinics in the Greater Toronto Area using paper-based and electronic medical records.

You may qualify if:

• Adults ≥18 years of age and ≤80 years of age who meet either of the following criteria:
• Elevated Lp(a) (defined as greater than or equal to 100 nmol/L)
• Non-elevated Lp(a) (defined as less than 100 nmol/L)
• Willing and able to provide written informed consent and comply with study procedures.

You may not qualify if:

• Unable or unwilling to provide written informed consent or provide a peripheral blood sample.
• Any life-threatening disease expected to result in death within two years of consent.
• Any malignancy not considered cured (except basal cell carcinoma of the skin). An individual is considered cured if there has been no evidence of cancer recurrence for the five years prior to screening.
• Uncontrolled hypertension.
• New York Heart Association Class IV heart failure.
• Active liver disease or liver dysfunction.
• Active kidney disease or kidney dysfunction.
• History of hemorrhagic stroke or other major bleeding disorder.
• White blood cell count ≥15 x 10\^9/L.
• Women who are pregnant or nursing.
• Previously received ribonucleic acid therapy specifically targeting Lp(a).
• Active infectious disease requiring systemic antibiotic or anti-viral agents.
• Known acquired immunodeficiency syndrome, such as human immunodeficiency virus.
• On oral steroid therapy (e.g., prednisone or other corticosteroids) or other immunosuppressive agents (e.g., methotrexate).
• Treated autoimmune disorders.

Sponsors & Collaborators

• Canadian Medical and Surgical Knowledge Translation Research Group: lead

Study Sites (2)

North York Diagnostic and Cardiac Centre

North York, Ontario, M6B1N6, Canada

Location

Diagnostic Assessment Centre

Scarborough Village, Ontario, M1S4N6, Canada

Location

Related Publications (7)

• Reyes-Soffer G, Ginsberg HN, Berglund L, Duell PB, Heffron SP, Kamstrup PR, Lloyd-Jones DM, Marcovina SM, Yeang C, Koschinsky ML; American Heart Association Council on Arteriosclerosis, Thrombosis and Vascular Biology; Council on Cardiovascular Radiology and Intervention; and Council on Peripheral Vascular Disease. Lipoprotein(a): A Genetically Determined, Causal, and Prevalent Risk Factor for Atherosclerotic Cardiovascular Disease: A Scientific Statement From the American Heart Association. Arterioscler Thromb Vasc Biol. 2022 Jan;42(1):e48-e60. doi: 10.1161/ATV.0000000000000147. Epub 2021 Oct 14.

  PMID: 34647487 BACKGROUND

• Terenzi DC, Al-Omran M, Quan A, Teoh H, Verma S, Hess DA. Circulating Pro-Vascular Progenitor Cell Depletion During Type 2 Diabetes: Translational Insights Into the Prevention of Ischemic Complications in Diabetes. JACC Basic Transl Sci. 2018 Nov 5;4(1):98-112. doi: 10.1016/j.jacbts.2018.10.005. eCollection 2019 Feb.

  PMID: 30847424 BACKGROUND

• Bakbak E, Verma S, Krishnaraj A, Quan A, Wang CH, Pan Y, Puar P, Mason T, Verma R, Terenzi DC, Rotstein OD, Yan AT, Connelly KA, Teoh H, Mazer CD, Hess DA. Empagliflozin improves circulating vascular regenerative cell content in people without diabetes with risk factors for adverse cardiac remodeling. Am J Physiol Heart Circ Physiol. 2023 Nov 1;325(5):H1210-H1222. doi: 10.1152/ajpheart.00141.2023. Epub 2023 Sep 29.

  PMID: 37773589 BACKGROUND

• Park B, Krishnaraj A, Teoh H, Bakbak E, Dennis F, Quan A, Hess DA, Verma S. GLP-1RA therapy increases circulating vascular regenerative cell content in people living with type 2 diabetes. Am J Physiol Heart Circ Physiol. 2024 Aug 1;327(2):H370-H376. doi: 10.1152/ajpheart.00257.2024. Epub 2024 Jun 14.

  PMID: 38874618 BACKGROUND

• Krishnaraj A, Bakbak E, Teoh H, Pan Y, Firoz IN, Pandey AK, Terenzi DC, Verma R, Bari B, Bakbak AI, Kunjummar SP, Yanagawa B, Connelly KA, Mazer CD, Rotstein OD, Quan A, Bhatt DL, McGuire DK, Hess DA, Verma S. Vascular Regenerative Cell Deficiencies in South Asian Adults. J Am Coll Cardiol. 2024 Feb 20;83(7):755-769. doi: 10.1016/j.jacc.2023.12.012.

  PMID: 38355246 BACKGROUND

• Kronenberg F, Mora S, Stroes ESG, Ference BA, Arsenault BJ, Berglund L, Dweck MR, Koschinsky M, Lambert G, Mach F, McNeal CJ, Moriarty PM, Natarajan P, Nordestgaard BG, Parhofer KG, Virani SS, von Eckardstein A, Watts GF, Stock JK, Ray KK, Tokgozoglu LS, Catapano AL. Lipoprotein(a) in atherosclerotic cardiovascular disease and aortic stenosis: a European Atherosclerosis Society consensus statement. Eur Heart J. 2022 Oct 14;43(39):3925-3946. doi: 10.1093/eurheartj/ehac361.

  PMID: 36036785 BACKGROUND

• Moroney M, Casey JH, Teoh H, Krishnaraj A, Pan Y, Quan A, Patel SK, Dennis F, He AZ, Park B, Verma R, Misner E, Seguchi R, Hassan SMA, Dennis CJ, Meglis G, Pandey A, Butler J, Mazer CD, Byrne RA, Koschinsky ML, Hess DA, Verma S. Vascular regenerative deficiencies in people with elevated lipoprotein(a): the Lp(a)-VRCE CardioLink-16 translational study. Cardiovasc Res. 2025 Nov 22;121(14):2127-2130. doi: 10.1093/cvr/cvaf142.

  PMID: 40883226 DERIVED

Biospecimen

Retention: SAMPLES WITHOUT DNA

Serum and plasma

MeSH Terms

Conditions

Cardiovascular Diseases; Myocardial Ischemia; Dyslipidemias

Condition Hierarchy (Ancestors)

Heart Diseases; Vascular Diseases; Lipid Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases

Study Officials

• Subodh Verma, MD

  University of Toronto

  PRINCIPAL INVESTIGATOR

• David A Hess, PhD

  Western University, Canada

  PRINCIPAL INVESTIGATOR

Study Design

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

Study Record Dates

• First Submitted: October 2, 2024
• First Posted: October 4, 2024
• Study Start: October 5, 2024
• Primary Completion: December 3, 2024
• Study Completion: December 3, 2024
• Last Updated: December 29, 2025

Record last verified: 2025-12

Locations

CA (2)