Soluble vascular adhesion protein-1 predicts incident major adverse cardiovascular events and improves reclassification in a finnish prospective cohort study.
BACKGROUND
Vascular adhesion protein-1 (VAP-1) associates to subclinical atherosclerotic manifestations in young people, but its association to incident major adverse cardiovascular events (MACEs) and cardiovascular mortality in a general population is not known.


RESULTS
We used a newly developed ELISA to measure soluble VAP-1 (sVAP-1) levels in 2775 participants (mean age, 60 years) from a prospective cohort study (the FINRISK 2002). During a mean follow-up of 9 years, 265 participants underwent a MACE, and these participants had higher levels of sVAP-1 than those without MACE (868 ng/mL and 824 ng/mL, respectively, P<0.001). In multivariate-adjusted Cox proportional hazard model including traditional Framingham risk factors (age, sex, systolic blood pressure, cholesterol, high-density lipoprotein cholesterol, smoking, prevalent diabetes mellitus, and antihypertensive treatment), sVAP-1 independently predicted incident MACE (P=0.0046) and MACE mortality (P=0.026). The impact of sVAP-1 in predicting the 9-year absolute risk of MACE was analyzed using integrated discrimination improvement and net reclassification improvement with 10-fold cross-validation. Inclusion of sVAP-1 in the Framingham model improved integrated discrimination improvement (P=0.042), and the clinical net reclassification improvement by correctly reclassifying 9% (P=0.0019) of people in the intermediate risk (5%-20%) group.


CONCLUSIONS
sVAP-1 associated with increased risk of MACE and MACE mortality in people aged >50 years without prior MACE, and inclusion of sVAP-1 in the risk prediction model improved the clinical net reclassification improvement of incident MACE. Thus, sVAP-1 may be a potential new biomarker for cardiovascular diseases.
From the MediCity Research Laboratory, and Department of Medical Microbiology and Immunology, University of Turku, Turku, Finland (K.A., S.J., M.S.), and Department of Chronic Disease Prevention, National Institute for Health and Welfare, Turku and Helsinki, Finland (A.S.H., S.J., V.S., M.S.).
Kristiina
K
Aalto
From the MediCity Research Laboratory, and Department of Medical Microbiology and Immunology, University of Turku, Turku, Finland (K.A., S.J., M.S.), and Department of Chronic Disease Prevention, National Institute for Health and Welfare, Turku and Helsinki, Finland (A.S.H., S.J., V.S., M.S.).
Aki S
AS
Havulinna
From the MediCity Research Laboratory, and Department of Medical Microbiology and Immunology, University of Turku, Turku, Finland (K.A., S.J., M.S.), and Department of Chronic Disease Prevention, National Institute for Health and Welfare, Turku and Helsinki, Finland (A.S.H., S.J., V.S., M.S.).
Sirpa
S
Jalkanen
From the MediCity Research Laboratory, and Department of Medical Microbiology and Immunology, University of Turku, Turku, Finland (K.A., S.J., M.S.), and Department of Chronic Disease Prevention, National Institute for Health and Welfare, Turku and Helsinki, Finland (A.S.H., S.J., V.S., M.S.).
Veikko
V
Salomaa
From the MediCity Research Laboratory, and Department of Medical Microbiology and Immunology, University of Turku, Turku, Finland (K.A., S.J., M.S.), and Department of Chronic Disease Prevention, National Institute for Health and Welfare, Turku and Helsinki, Finland (A.S.H., S.J., V.S., M.S.). marko.salmi@utu.fi.
Marko
M
Salmi
D000368:Aged; D006631:Amine Oxidase (Copper-Containing) / Q000032:analysis*; D015415:Biomarkers / Q000032:analysis; D001794:Blood Pressure; D002318:Cardiovascular Diseases / Q000453:epidemiology / Q000209:etiology* / Q000401:mortality; D015815:Cell Adhesion Molecules / Q000032:analysis*; D008076:Cholesterol, HDL / Q000097:blood; D015331:Cohort Studies; D003924:Diabetes Mellitus, Type 2 / Q000150:complications; D016002:Discriminant Analysis; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D005387:Finland / Q000453:epidemiology; D005500:Follow-Up Studies; D006801:Humans; D008297:Male; D008875:Middle Aged; D016016:Proportional Hazards Models; D011446:Prospective Studies; D012307:Risk Factors; D012907:Smoking; D011795:Surveys and Questionnaires; D044465:White People
D015415:Biomarkers; D015815:Cell Adhesion Molecules; D008076:Cholesterol, HDL; C076668:AOC3 protein, human; D006631:Amine Oxidase (Copper-Containing)
biomarkers; cardiovascular disease; cell adhesion molecules; epidemiologic studies