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Soluble low-density lipoprotein receptor-related protein 1 as a biomarker of coronary risk: Predictive capacity and association with clinical events

  • Author Footnotes
    1 These authors have equally contributed to this work.
    David de Gonzalo-Calvo
    Footnotes
    1 These authors have equally contributed to this work.
    Affiliations
    Lipids and Cardiovascular Pathology Group, Biomedical Research Institute Sant Pau (IIB Sant Pau), Barcelona, Spain

    Institute of Biomedical Research of Barcelona (IIBB) - Spanish National Research Council (CSIC), Barcelona, Spain

    Centro de Investigación Biomédica en Red Enfermedades Cardiovasculares (CIBERCV), Instituto de Salud Carlos III, Madrid, Spain
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  • Author Footnotes
    1 These authors have equally contributed to this work.
    Roberto Elosua
    Footnotes
    1 These authors have equally contributed to this work.
    Affiliations
    Centro de Investigación Biomédica en Red Enfermedades Cardiovasculares (CIBERCV), Instituto de Salud Carlos III, Madrid, Spain

    Cardiovascular Epidemiology and Genetics Group, Hospital del Mar Medical Research Institute (IMIM), Barcelona, Spain

    Medical School, University of Vic - Central University of Catalonia, Vic, Spain
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  • Angela Vea
    Affiliations
    Lipids and Cardiovascular Pathology Group, Biomedical Research Institute Sant Pau (IIB Sant Pau), Barcelona, Spain
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  • Isaac Subirana
    Affiliations
    Cardiovascular Epidemiology and Genetics Group, Hospital del Mar Medical Research Institute (IMIM), Barcelona, Spain

    Centro de Investigación Biomédica en Red Epidemiología y Salud Pública (CIBERESP), Barcelona, Spain
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  • Sergi Sayols-Baixeras
    Affiliations
    Centro de Investigación Biomédica en Red Enfermedades Cardiovasculares (CIBERCV), Instituto de Salud Carlos III, Madrid, Spain

    Cardiovascular Epidemiology and Genetics Group, Hospital del Mar Medical Research Institute (IMIM), Barcelona, Spain
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  • Jaume Marrugat
    Correspondence
    Corresponding author. Centro de Investigación Biomédica en Red Enfermedades Cardiovasculares (CIBERCV), Instituto de Salud Carlos III, Madrid, Spain.
    Affiliations
    Centro de Investigación Biomédica en Red Enfermedades Cardiovasculares (CIBERCV), Instituto de Salud Carlos III, Madrid, Spain

    REGICOR Group, Hospital del Mar Medical Research Institute (IMIM), Barcelona, Spain
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  • Vicenta Llorente-Cortés
    Correspondence
    Corresponding author. Lipids and Cardiovascular Pathology Group, Biomedical Research Institute Sant Pau (IIB Sant Pau), Barcelona, Spain.
    Affiliations
    Lipids and Cardiovascular Pathology Group, Biomedical Research Institute Sant Pau (IIB Sant Pau), Barcelona, Spain

    Institute of Biomedical Research of Barcelona (IIBB) - Spanish National Research Council (CSIC), Barcelona, Spain

    Centro de Investigación Biomédica en Red Enfermedades Cardiovasculares (CIBERCV), Instituto de Salud Carlos III, Madrid, Spain
    Search for articles by this author
  • Author Footnotes
    1 These authors have equally contributed to this work.

      Highlights

      • Plasma sLRP1 is independently associated with the incidence of coronary events.
      • Plasma sLRP1 does not improve risk prediction when added to the REGICOR function.
      • The LRP1 variants tested are associated with coronary artery disease.
      • The LRP1 variants tested are not associated with plasma sLRP1 concentration.

      Abstract

      Background and aims

      We aimed to determine whether circulating sLRP1 levels are associated with future coronary events and improve the predictive capacity of the REGICOR (Registre Gironí del Cor) risk function.

      Methods

      We conducted a case-cohort study based on the follow-up of the REGICOR population-based cohort. Of the 5,404 participants aged between 35 and 74 years, without previous history of cardiovascular disease, 117 subjects with angina or fatal or non-fatal myocardial infarction were included, and 512 individuals were randomly selected as a subcohort (including 14 patients who presented coronary events). sLRP1 levels were measured in basal plasma samples by commercial ELISA. Hazard ratio (HR) was estimated with Cox models adjusted for potential confounding factors. Discrimination and reclassification were analyzed with the c-index and the net reclassification index (NRI), respectively. A Mendelian randomization approach was used to explore the causality of the association between sLRP1 and coronary artery disease (CAD).

      Results

      The group of participants who presented a CAD event showed higher levels of sLRP1 than the subcohort (2.45 [0.43; 8.31] vs. 2.07 [0.40; 6.65] μg/mL, p < 0.001). sLRP1 was significantly associated with CAD events even after adjustment for confounding factors (adjusted HR per standard deviation = 1.30, 95% CI: 1.01–1.67, p = 0.039). sLRP1 did not increase the predictive capacity or improve cardiovascular risk stratification of the REGICOR function. The LRP1 genetic variants associated with CAD risk were not related to sLRP1 concentration.

      Conclusions

      Plasma sLRP1 is independently associated with the incidence of coronary events, but it does not improve the predictive capacity of the REGICOR risk function.

      Graphical abstract

      Keywords

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