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 persons, but its association to incident major adverse cardiovascular events (MACE) and cardiovascular mortality in a general population is not known.
Methods and Results—We used a newly developed enzyme-linked immunosorbent assay to measure soluble VAP-1 (sVAP-1) levels in 2,775 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 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 (IDI) and net reclassification improvement (NRI) with 10-fold cross-validation. Inclusion of sVAP-1 in the Framingham model improved IDI (P=0.042) and the clinical NRI by correctly reclassifying 9% (P=0.0019) of the persons in the intermediate risk (5-20%) group.
Conclusions—sVAP-1 associated with increased risk of MACE and MACE mortality in over 50 year old persons without prior MACE, and inclusion of sVAP-1 in the risk prediction model improved the clinical NRI of incident MACE. Thus, sVAP-1 may be a potential new biomarker for cardiovascular diseases.
- Received November 6, 2013.
- Revision received April 9, 2014.
- Accepted April 16, 2014.