title: Common variants associated with blood lipid levels do not affect carotid plaque composition.
abstract: BACKGROUND
  Although plasma lipid levels are known to influence the risk of cardiovascular disease (CVD), little is known about their effect on atherosclerotic plaque composition. To date, large-scale genome-wide association studies have identified 157 common single-nucleotide polymorphisms (SNPs) that influence plasma lipid levels, providing a powerful tool to investigate the effect of plasma lipid levels on atherosclerotic plaque composition.
  
  
  METHODS
  In this study, we included 1443 carotid endarterectomy patients from the Athero-Express Biobank Study with genotype data. Plasma concentrations of high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), total cholesterol (TC) and triglycerides (TG) were determined at the time of endarterectomy. Atherosclerotic plaques, obtained during surgery, were histologically examined. For all patients, we calculated weighted genetic burden scores (GBS) for all lipid traits on the basis of the available genotype data. Plasma lipid levels and GBS were tested for association with 7 histological features using linear and logistic regression models.
  
  
  RESULTS
  All GBS were associated with their respective plasma lipid concentrations (pHDL-C = 2.4 × 10(-14), pLDL-C = 0.003, pTC = 2.1 × 10(-6), pTG = 3.4 × 10(-8)). Neither the measured plasma lipids, nor the GBS, were associated with histological features of atherosclerotic plaque composition. In addition, neither the plasma lipids nor the GBS were associated with clinical endpoints within 3 years of follow-up, with the notable exception of a negative association between HDL-C and composite cardiovascular endpoints.
  
  
  CONCLUSIONS
  This study found no evidence that plasma lipid levels or their genetic determinants influence carotid plaque composition.
authors.affiliation: Laboratory of Experimental Cardiology, Division Heart and Lungs, University Medical Center Utrecht, Utrecht, The Netherlands.
authors.forename: M A
authors.initials: MA
authors.lastname: Siemelink
authors.affiliation: Laboratory of Experimental Cardiology, Division Heart and Lungs, University Medical Center Utrecht, Utrecht, The Netherlands.
authors.forename: S W
authors.initials: SW
authors.lastname: van der Laan
authors.affiliation: Laboratory of Experimental Cardiology, Division Heart and Lungs, University Medical Center Utrecht, Utrecht, The Netherlands.
authors.forename: J
authors.initials: J
authors.lastname: van Setten
authors.affiliation: Department of Vascular Surgery, St. Antonius Hospital, Nieuwegein, The Netherlands.
authors.forename: J P P M
authors.initials: JP
authors.lastname: de Vries
authors.affiliation: Department of Vascular Surgery, University Medical Center Utrecht, Utrecht, The Netherlands.
authors.forename: G J
authors.initials: GJ
authors.lastname: de Borst
authors.affiliation: Department of Vascular Surgery, University Medical Center Utrecht, Utrecht, The Netherlands.
authors.forename: F L
authors.initials: FL
authors.lastname: Moll
authors.affiliation: Laboratory of Experimental Cardiology, Division Heart and Lungs, University Medical Center Utrecht, Utrecht, The Netherlands.
authors.forename: H M
authors.initials: HM
authors.lastname: den Ruijter
authors.affiliation: Department of Cardiology, Division Heart and Lungs, University Medical Center Utrecht, Utrecht, The Netherlands; Durrer Center for Cardiogenetic Research, ICIN-Netherlands Heart Institute, Utrecht, The Netherlands; Institute of Cardiovascular Science, Faculty of Population Health Sciences, University College London, London, United Kingdom.
authors.forename: F W
authors.initials: FW
authors.lastname: Asselbergs
authors.affiliation: Laboratory of Experimental Cardiology, Division Heart and Lungs, University Medical Center Utrecht, Utrecht, The Netherlands; Laboratory of Clinical Chemistry and Hematology, Division Laboratories and Pharmacy, University Medical Center Utrecht, Utrecht, The Netherlands. Electronic address: G.Pasterkamp@umcutrecht.nl.
authors.forename: G
authors.initials: G
authors.lastname: Pasterkamp
authors.affiliation: Department of Medical Genetics, Center for Molecular Medicine, University Medical Center Utrecht, Utrecht, The Netherlands; Department of Epidemiology, Julius Center for Health Sciences and Primary Care, University Medical Center Utrecht, Utrecht, The Netherlands.
authors.forename: P I W
authors.initials: PI
authors.lastname: de Bakker
mesh_terms: D000368:Aged; D018070:Biological Specimen Banks; D015415:Biomarkers / Q000097:blood; D002339:Carotid Arteries / Q000378:metabolism / Q000473:pathology* / Q000601:surgery; D002340:Carotid Artery Diseases / Q000097:blood / Q000175:diagnosis / Q000235:genetics* / Q000601:surgery; D016894:Endarterectomy, Carotid; D005260:Female; D056726:Genetic Association Studies; D005819:Genetic Markers; D020022:Genetic Predisposition to Disease; D006801:Humans; D016014:Linear Models; D008055:Lipids / Q000097:blood*; D016015:Logistic Models; D008297:Male; D008875:Middle Aged; D010641:Phenotype; D058226:Plaque, Atherosclerotic; D020641:Polymorphism, Single Nucleotide; D018570:Risk Assessment; D012307:Risk Factors
chemical_list: D015415:Biomarkers; D005819:Genetic Markers; D008055:Lipids
keywords: Atherosclerosis; Cardiovascular disease; Carotid endarterectomy; Genetic burden score; Lipids; Lipoproteins; Polygenic risk score