title: Circulating Apolipoprotein E Concentration and Cardiovascular Disease Risk: Meta-analysis of Results from Three Studies.
abstract: BACKGROUND
  The association of APOE genotype with circulating apolipoprotein E (ApoE) concentration and cardiovascular disease (CVD) risk is well established. However, the relationship of circulating ApoE concentration and CVD has received little attention.
  
  
  RESULTS
  To address this, we measured circulating ApoE concentration in 9,587 individuals (with 1,413 CVD events) from three studies with incident CVD events: two population-based studies, the English Longitudinal Study of Ageing (ELSA) and the men-only Northwick Park Heart Study II (NPHSII), and a nested sub-study of the Anglo-Scandinavian Cardiac Outcomes Trial (ASCOT). We examined the association of circulating ApoE with cardiovascular risk factors in the two population-based studies (ELSA and NPHSII) and the relationship between ApoE concentration and coronary heart disease and stroke in all three studies. Analyses were carried out within study, and, where appropriate, pooled effect estimates were derived using meta-analysis. In the population-based samples, circulating ApoE was associated with systolic blood pressure (correlation coefficient 0.08, p < 0.001, in both ELSA and NPHSII), total cholesterol (correlation coefficient 0.46 and 0.34 in ELSA and NPHSII, respectively; both p < 0.001), low-density lipoprotein cholesterol (correlation coefficient 0.30 and 0.14, respectively; both p < 0.001), high-density lipoprotein (correlation coefficient 0.16 and -0.14, respectively; both p < 0.001), and triglycerides (correlation coefficient 0.43 and 0.46, respectivly; both p < 0.001). In NPHSII, ApoE concentration was additionally associated with apolipoprotein B (correlation coefficient 0.13, p = 0.001) and lipoprotein(a) (correlation coefficient -0.11, p < 0.001). In the pooled analysis of ASCOT, ELSA, and NPHSII, there was no association of ApoE with CVD events; the odds ratio (OR) for CVD events per 1-standard-deviation higher ApoE concentration was 1.02 (95% CI 0.96, 1.09). After adjustment for cardiovascular risk factors, the OR for CVD per 1-standard-deviation higher ApoE concentration was 0.97 (95% CI 0.82, 1.15). Limitations of these analyses include a polyclonal method of ApoE measurement, rather than isoform-specific measurement, a moderate sample size (although larger than any other study to our knowledge and with a long lag between ApoE measures), and CVD events that may attenuate an effect.
  
  
  CONCLUSIONS
  In the largest study to date on this question, we found no evidence of an association of circulating ApoE concentration with CVD events. The established association of APOE genotype with CVD events may be explained by isoform-specific functions as well as other mechanisms, rather than circulating concentrations of ApoE.
authors.affiliation: Centre for Clinical Pharmacology, Division of Medicine, University College London, London, United Kingdom.
authors.forename: Reecha
authors.initials: R
authors.lastname: Sofat
authors.affiliation: Cardiovascular Genetics Group, Institute of Cardiovascular Science, University College London, London, United Kingdom.
authors.forename: Jackie A
authors.initials: JA
authors.lastname: Cooper
authors.affiliation: Institute for Social and Economic Research, University of Essex, Colchester, United Kingdom.
authors.forename: Meena
authors.initials: M
authors.lastname: Kumari
authors.affiliation: Farr Institute of Health Informatics, Faculty of Population Health Sciences, University College London, United Kingdom.
authors.forename: Juan P
authors.initials: JP
authors.lastname: Casas
authors.affiliation: Cardiovascular Genetics Group, Institute of Cardiovascular Science, University College London, London, United Kingdom.
authors.forename: Jacqueline P
authors.identifier: http://orcid.org/0000-0002-9134-9384
authors.initials: JP
authors.lastname: Mitchell
authors.affiliation: Cardiovascular Genetics Group, Institute of Cardiovascular Science, University College London, London, United Kingdom.
authors.forename: Jayshree
authors.initials: J
authors.lastname: Acharya
authors.affiliation: International Centre for Circulatory Health, Hammersmith Hospital, Imperial College London, London, United Kingdom.
authors.forename: Simon
authors.initials: S
authors.lastname: Thom
authors.affiliation: Cardiometabolic Phenotyping Group, Institute of Cardiovascular Science, University College London, London, United Kingdom.
authors.forename: Alun D
authors.identifier: http://orcid.org/0000-0001-5432-5271
authors.initials: AD
authors.lastname: Hughes
authors.affiliation: Cardiovascular Genetics Group, Institute of Cardiovascular Science, University College London, London, United Kingdom.
authors.forename: Steve E
authors.initials: SE
authors.lastname: Humphries
authors.affiliation: Farr Institute of Health Informatics, Faculty of Population Health Sciences, University College London, United Kingdom.|Genetic Epidemiology Group, Institute of Cardiovascular Science, University College London, United Kingdom.
authors.forename: Aroon D
authors.initials: AD
authors.lastname: Hingorani
mesh_terms: D001057:Apolipoproteins E / Q000097:blood* / Q000235:genetics; D002318:Cardiovascular Diseases / Q000097:blood / Q000209:etiology*; D005260:Female; D005838:Genotype; D006801:Humans; D008297:Male; D008875:Middle Aged; D009203:Myocardial Infarction / Q000097:blood / Q000209:etiology; D012307:Risk Factors; D020521:Stroke / Q000097:blood / Q000209:etiology
chemical_list: D001057:Apolipoproteins E