ClinicalTrials.gov
ClinicalTrials.gov Menu

Lp(a) and Aortic Valve Calcification (FHLPA)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
ClinicalTrials.gov Identifier: NCT02976818
Recruitment Status : Recruiting
First Posted : November 29, 2016
Last Update Posted : May 5, 2017
Sponsor:
Collaborator:
Amgen
Information provided by (Responsible Party):
Patrick Couture, Laval University

Brief Summary:

Aortic valve stenosis (AVS), the most common form of valve disease in the western world, afflicts more than 1 million individuals in North America [1] and the burden of AVS is high and is expected to double within the next 50 years [2]. Medical therapy to prevent development or reduce progression of AVS is currently not available and the only effective treatment for AVS is aortic valve replacement, for which costs have been estimated up to 120,000$ [3,4]. Recently, we and others have identified rs10455872 at the LPA locus as a susceptibility single nucleotide polymorphism (SNP) for aortic valve calcification (AVC) and AVS [5,6] and rs10455872 is associated with elevated plasma lipoprotein (Lp)(a) levels [7]. Lp(a) is a LDL-like particle consisting of hepatically synthesized apolipoprotein B-100 that is noncovalently bound to the plasminogen-like glycoprotein apolipoprotein(a) [8]. Lp(a) promotes atherosclerotic stenosis, and possibly thrombosis, and has been hypothesized to contribute to wound healing, each of which could explain an association with AVS [9,10]. Lp(a) is relatively refractory to both lifestyle and drug intervention, with only nicotinic acid and monoclonal antibody inhibition of the proprotein convertase subtilisin/kexin type 9 that have showed reductions in Lp(a) levels [11,12]. However, the evidence that patients with AVS could be characterized by high Lp(a) levels is scarce. Glader et al. [13] showed that plasma levels of Lp(a) were almost 1.5-fold higher in 101 patients with AVS compared to matched controls, although this relationship did not reach statistical significance. Subsequent studies have also reported an association between elevated plasma Lp(a) levels and higher prevalence of AVS. More specifically, Kamstrup and colleagues [14] reported that elevated Lp(a) levels and corresponding genotypes were associated with increased risk of AVS in the general population with levels >90 mg/dL predicting a threefold increased risk. We have measured Lp(a) and oxidized phospholipids plasma levels in 220 patients with mild-to-moderate calcific AVS enrolled in the Aortic Stenosis Progression Observation: Measuring Effects of Rosuvastatin (ASTRONOMER) trial [15]. Results of this study suggest that high Lp(a) and oxidized phospholipids both predict calcific AVS progression, especially in younger patients with calcific AVS. We also found that statin therapy considerably increased both Lp(a) and oxidized phospholipids levels. Whether the fact that statins increase these risk factors for calcific AVS might explain at least to a certain extent why statins failed to promote calcific AVS regression or stabilization in at least four trials, including ASTRONOMER.

Familial hypercholesterolemia (FH) is an autosomal codominant single-gene disorder caused by mutations in the LDL receptor gene that disrupt normal clearance of LDL. Phenotypic features characteristic of the disease's heterozygous form are 2- to 3-fold raise in plasma LDL-cholesterol concentrations, tendinous xanthomatosis and premature atherosclerotic coronary artery disease. High Lp(a) levels have been shown to explain residual cardiovascular disease risk in FH [16,17]. Recent studies have demonstrated that FH heterozygotes have elevated AVC compared with non-FH subjects [18] and that Lp(a) levels were positively correlated with AVC in asymptomatic FH heterozygotes [19]. Vongpromek et al. [19] demonstrated that plasma Lp(a) concentration is a independent risk factor for AVC in a cohort of 129 asymptomatic heterozygous FH patients aged between 40 and 69 years. In this study, AVC was significantly associated with plasma Lp(a) level, age, body mass index, blood pressure, duration of statin use, cholesterol-year score and coronary artery calcification (CAC) score.


Condition or disease
Heterozygous Familial Hypercholesterolemia

Study Type : Observational
Estimated Enrollment : 200 participants
Observational Model: Case-Control
Time Perspective: Cross-Sectional
Official Title: Relationships Between Lipoprotein(a) Levels and Aortic Valve Calcification in Patients With Heterozygous Familial Hypercholesterolemia
Actual Study Start Date : April 30, 2017
Estimated Primary Completion Date : October 2018
Estimated Study Completion Date : April 2019





Primary Outcome Measures :
  1. Association between Lp(a) concentrations and aortic valve calcification [ Time Frame: Week 1 ]


Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


Ages Eligible for Study:   18 Years to 80 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Sampling Method:   Probability Sample
Study Population
primary care clinic
Criteria

Inclusion Criteria:

  • Men or women with heterozygous FH aged between 18 and 80 years
  • FH patient carrying a documented mutation in the LDL receptor gene
  • Subjects must be willing to give written informed consent and able to adhere to visit schedule

Exclusion Criteria:

  • Men or women < 18 or > 80 years
  • Non-FH subjects
  • History of alcohol or drug abuse within the past 2 years
  • Subjects who are in a situation or have any condition that, in the opinion of the investigator, may interfere with optimal participation in the study

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02976818


Contacts
Contact: Patrick Couture, MD, FRCP, PhD 418-654-2106 patrick.couture@crchul.ulaval.ca
Contact: Andre Tremblay, PhD 418-656-2131 ext 11417 andre.tremblay@fsaa.ulaval.ca

Locations
Canada
Institute of Nutrition and Functional Foods (INAF) Recruiting
Quebec, Canada, G1V 0A6
Contact: Patrick Couture, MD, FRCP,PhD    418-654-2106    patrick.couture@crchul.ulaval.ca   
Contact: André Tremblay, PhD    418-656-2131 ext 11417    andre.tremblay@fsaa.ulaval.ca   
Principal Investigator: Patrick Couture, MD,FRCP,PhD         
Sub-Investigator: André Tremblay, PhD         
Sponsors and Collaborators
Laval University
Amgen
Investigators
Principal Investigator: Patrick Couture, MD, FRCP, PhD Laval University

Publications of Results:
Helgadottir A, Gretarsdottir S, Thorleifsson G, Holm H, Patel RS, Gudnason T, Jones GT, van Rij AM, Eapen DJ, Baas AF, Tregouet DA, Morange PE, Emmerich J, Lindblad B, Gottsäter A, Kiemeny LA, Lindholt JS, Sakalihasan N, Ferrell RE, Carey DJ, Elmore JR, Tsao PS, Grarup N, Jørgensen T, Witte DR, Hansen T, Pedersen O, Pola R, Gaetani E, Magnadottir HB, Wijmenga C, Tromp G, Ronkainen A, Ruigrok YM, Blankensteijn JD, Mueller T, Wells PS, Corral J, Soria JM, Souto JC, Peden JF, Jalilzadeh S, Mayosi BM, Keavney B, Strawbridge RJ, Sabater-Lleal M, Gertow K, Baldassarre D, Nyyssönen K, Rauramaa R, Smit AJ, Mannarino E, Giral P, Tremoli E, de Faire U, Humphries SE, Hamsten A, Haraldsdottir V, Olafsson I, Magnusson MK, Samani NJ, Levey AI, Markus HS, Kostulas K, Dichgans M, Berger K, Kuhlenbäumer G, Ringelstein EB, Stoll M, Seedorf U, Rothwell PM, Powell JT, Kuivaniemi H, Onundarson PT, Valdimarsson E, Matthiasson SE, Gudbjartsson DF, Thorgeirsson G, Quyyumi AA, Watkins H, Farrall M, Thorsteinsdottir U, Stefansson K. Apolipoprotein(a) genetic sequence variants associated with systemic atherosclerosis and coronary atherosclerotic burden but not with venous thromboembolism. J Am Coll Cardiol. 2012 Aug 21;60(8):722-9. doi: 10.1016/j.jacc.2012.01.078.

Other Publications:
Responsible Party: Patrick Couture, Principal Investigator, Laval University
ClinicalTrials.gov Identifier: NCT02976818     History of Changes
Other Study ID Numbers: ISS 20167474
First Posted: November 29, 2016    Key Record Dates
Last Update Posted: May 5, 2017
Last Verified: May 2017
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

Additional relevant MeSH terms:
Hypercholesterolemia
Calcinosis
Hyperlipoproteinemia Type II
Aortic Valve Stenosis
Hyperlipidemias
Dyslipidemias
Lipid Metabolism Disorders
Metabolic Diseases
Calcium Metabolism Disorders
Lipid Metabolism, Inborn Errors
Metabolism, Inborn Errors
Genetic Diseases, Inborn
Hyperlipoproteinemias
Heart Valve Diseases
Heart Diseases
Cardiovascular Diseases
Ventricular Outflow Obstruction