Bruna Gigante1, Karin Leander2, Max Vikström2, Damiano Baldassarre3, Fabrizio Veglia4, Rona J Strawbridge5, Olga McLeod5, Karl Gertow5, Bengt Sennblad6, Sonia Shah7, Delilah Zabaneh7, Steve E Humphries8, Jussi Kauhanen9, Rainer Rauramaa10, Andries J Smit11, Elmo Mannarino12, Philippe Giral13, Elena Tremoli3, Anders Hamsten5, Johan Frostegård14, Ulf de Faire15. 1. 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. 2. Unit of Cardiovascular Epidemiology, Institute of Environmental Medicine (IMM), Stockholm, Sweden. 3. Dipartimento di Scienze Farmacologiche e Biomolecolari, Università di Milano, Milan Italy; Centro Cardiologico Monzino, IRCCS, Milan, Italy. 4. Dipartimento di Scienze Farmacologiche e Biomolecolari, Università di Milano, Milan Italy. 5. Atherosclerosis Research Unit, Department of Medicine Solna, Sweden. 6. Atherosclerosis Research Unit, Department of Medicine Solna, Sweden; Science for Life Laboratory, Karolinska Institutet, Stockholm, Sweden. 7. University College London Genetics Institute, University College London, United Kingdom. 8. Centre for Cardiovascular Genetics, University College London, United Kingdom. 9. Institute of Public Health and Clinical Nutrition, University of Eastern Finland, Kuopio, Finland. 10. Foundation for Research in Health, Exercise and Nutrition, Kuopio Research Institute of Exercise Medicine, Kuopio, Finland. 11. Department of Medicine, University Medical Center Groningen, The Netherlands. 12. Internal Medicine, Angiology and Arteriosclerosis Diseases, Department of Clinical and Experimental Medicine, University of Perugia, Perugia, Italy. 13. Assistance Publique - Hopitaux de Paris, Service Endocrinologie-Metabolisme, Groupe Hôpitalier Pitie-Salpetriere, Unités de Prévention Cardiovasculaire, Paris, France. 14. Unity of Immunology and Chronic disease, IMM, Stockholm, Sweden; Unit of Acute Internal Medicine Huddinge, Karolinska Institutet, Stockholm, Sweden. 15. Unit of Cardiovascular Epidemiology, Institute of Environmental Medicine (IMM), Stockholm, Sweden; Dept of Cardiology, Karolinska University Hospital, Stockholm, Sweden.
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.
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: Niek J Pluijmert; Rob C M de Jong; Margreet R de Vries; Knut Pettersson; Douwe E Atsma; J Wouter Jukema; Paul H A Quax Journal: J Cell Mol Med Date: 2021-06-30 Impact factor: 5.310