title: Low levels of IgM antibodies against phosphorylcholine are associated with fast carotid intima media thickness progression and cardiovascular risk in men.
abstract: OBJECTIVE
  Low levels of IgM anti-phosphorylcholine (anti-PC) increase the risk of cardiovascular events (CVE). Here we investigate the association of low anti-PC with the progression of carotid intima media thickness (C-IMT) and incidence of CVE in a large cohort of individuals at high risk of CVE, the IMPROVE, a prospective multicenter European study.
  
  
  METHODS
  3711 subjects (54-79 years) with at least three established cardiovascular risk factors were enrolled. Baseline serum levels of IgM anti-PC were measured by ELISA. Carotid ultrasound investigations were performed at baseline and after 15 and 30 months of follow-up. The risk of C-IMT progression and ischemic CVE associated with low anti-PC levels was tested by logistic regression and Cox regression analysis, respectively. Risk estimates were adjusted by center and conventional cardiovascular risk factors.
  
  
  RESULTS
  3670 study participants were included in the present analysis and 213 CVE were recorded during a 3 year follow up. Anti-PC levels (U/ml) were classified into quartiles [Q1≤ 40, Q2 >40-≤64, Q3 >64-≤102, Q4 >102]. In men, low levels of anti-PC (Q1) were associated with the highest (>90th) percentile of the fastest C-IMT progression, i.e. the segment showing the fastest progression over 30 months in the whole carotid tree, with an OR of 1.41 (95%CI, 1.02-1.9) and with an increased risk of CVE with a multivariable adjusted HR of 1.85 (95%CI, 1.1-3.1). No significant associations were found in women.
  
  
  CONCLUSIONS
  Low anti-PC levels increase the risk of CVE in men. This effect may be partly mediated by a fast C-IMT progression.
authors.affiliation: Unit of Cardiovascular Epidemiology, Institute of Environmental Medicine (IMM), Stockholm, Sweden; Division of Cardiovascular Medicine, Department of Clinical Sciences, Danderyd Hospital, Karolinska Institutet, Stockholm, Sweden. Electronic address: bruna.gigante@ki.se.
authors.forename: Bruna
authors.initials: B
authors.lastname: Gigante
authors.affiliation: Unit of Cardiovascular Epidemiology, Institute of Environmental Medicine (IMM), Stockholm, Sweden.
authors.forename: Karin
authors.initials: K
authors.lastname: Leander
authors.affiliation: Unit of Cardiovascular Epidemiology, Institute of Environmental Medicine (IMM), Stockholm, Sweden.
authors.forename: Max
authors.initials: M
authors.lastname: Vikström
authors.affiliation: Dipartimento di Scienze Farmacologiche e Biomolecolari, Università di Milano, Milan Italy; Centro Cardiologico Monzino, IRCCS, Milan, Italy.
authors.forename: Damiano
authors.initials: D
authors.lastname: Baldassarre
authors.affiliation: Dipartimento di Scienze Farmacologiche e Biomolecolari, Università di Milano, Milan Italy.
authors.forename: Fabrizio
authors.initials: F
authors.lastname: Veglia
authors.affiliation: Atherosclerosis Research Unit, Department of Medicine Solna, Sweden.
authors.forename: Rona J
authors.initials: RJ
authors.lastname: Strawbridge
authors.affiliation: Atherosclerosis Research Unit, Department of Medicine Solna, Sweden.
authors.forename: Olga
authors.initials: O
authors.lastname: McLeod
authors.affiliation: Atherosclerosis Research Unit, Department of Medicine Solna, Sweden.
authors.forename: Karl
authors.initials: K
authors.lastname: Gertow
authors.affiliation: Atherosclerosis Research Unit, Department of Medicine Solna, Sweden; Science for Life Laboratory, Karolinska Institutet, Stockholm, Sweden.
authors.forename: Bengt
authors.initials: B
authors.lastname: Sennblad
authors.affiliation: University College London Genetics Institute, University College London, United Kingdom.
authors.forename: Sonia
authors.initials: S
authors.lastname: Shah
authors.affiliation: University College London Genetics Institute, University College London, United Kingdom.
authors.forename: Delilah
authors.initials: D
authors.lastname: Zabaneh
authors.affiliation: Centre for Cardiovascular Genetics, University College London, United Kingdom.
authors.forename: Steve E
authors.initials: SE
authors.lastname: Humphries
authors.affiliation: Institute of Public Health and Clinical Nutrition, University of Eastern Finland, Kuopio, Finland.
authors.forename: Jussi
authors.initials: J
authors.lastname: Kauhanen
authors.affiliation: Foundation for Research in Health, Exercise and Nutrition, Kuopio Research Institute of Exercise Medicine, Kuopio, Finland.
authors.forename: Rainer
authors.initials: R
authors.lastname: Rauramaa
authors.affiliation: Department of Medicine, University Medical Center Groningen, The Netherlands.
authors.forename: Andries J
authors.initials: AJ
authors.lastname: Smit
authors.affiliation: Internal Medicine, Angiology and Arteriosclerosis Diseases, Department of Clinical and Experimental Medicine, University of Perugia, Perugia, Italy.
authors.forename: Elmo
authors.initials: E
authors.lastname: Mannarino
authors.affiliation: Assistance Publique - Hopitaux de Paris, Service Endocrinologie-Metabolisme, Groupe Hôpitalier Pitie-Salpetriere, Unités de Prévention Cardiovasculaire, Paris, France.
authors.forename: Philippe
authors.initials: P
authors.lastname: Giral
authors.affiliation: Dipartimento di Scienze Farmacologiche e Biomolecolari, Università di Milano, Milan Italy; Centro Cardiologico Monzino, IRCCS, Milan, Italy.
authors.forename: Elena
authors.initials: E
authors.lastname: Tremoli
authors.affiliation: Atherosclerosis Research Unit, Department of Medicine Solna, Sweden.
authors.forename: Anders
authors.initials: A
authors.lastname: Hamsten
authors.affiliation: Unity of Immunology and Chronic disease, IMM, Stockholm, Sweden; Unit of Acute Internal Medicine Huddinge, Karolinska Institutet, Stockholm, Sweden.
authors.forename: Johan
authors.initials: J
authors.lastname: Frostegård
authors.affiliation: Unit of Cardiovascular Epidemiology, Institute of Environmental Medicine (IMM), Stockholm, Sweden; Dept of Cardiology, Karolinska University Hospital, Stockholm, Sweden.
authors.forename: Ulf
authors.initials: U
authors.lastname: de Faire
mesh_terms: D000367:Age Factors; D000368:Aged; D000886:Anthropometry; D017152:Antibodies, Antiphospholipid / Q000097:blood* / Q000276:immunology; D000918:Antibody Specificity; D001324:Autoantigens / Q000276:immunology*; D002318:Cardiovascular Diseases / Q000453:epidemiology*; D002340:Carotid Artery Diseases / Q000097:blood / Q000000981:diagnostic imaging / Q000276:immunology* / Q000473:pathology; D059168:Carotid Intima-Media Thickness; D018450:Disease Progression; D005060:Europe / Q000453:epidemiology; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D007075:Immunoglobulin M / Q000097:blood* / Q000276:immunology; D008297:Male; D008875:Middle Aged; D010767:Phosphorylcholine / Q000276:immunology*; D016016:Proportional Hazards Models; D012307:Risk Factors; D012727:Sex Characteristics
chemical_list: D017152:Antibodies, Antiphospholipid; D001324:Autoantigens; D007075:Immunoglobulin M; D010767:Phosphorylcholine
keywords: Anti-PC; Biomarker; Cardiovascular disease; Cardiovascular events; Carotid intima media thickness; Carotid intima media thickness progression; Risk factors; Subclinical atherosclerosis