Serum vascular adhesion protein-1 predicts 10-year cardiovascular and cancer mortality in individuals with type 2 diabetes

Abstract

Objective: Vascular adhesion protein-1 (VAP-1) participates in inflammation and catalyzes the breakdown of amines to produce aldehyde, hydrogen peroxide, and ammonia. Serum VAP-1 correlates positively with both acute hyperglycemia and diabetes. We conducted a cohort study to evaluate whether serum VAP-1 predicts 10-year survival in type 2 diabetic patients.

Research design and methods: Between July 1996 and June 2003, we enrolled 661 type 2 diabetic subjects at National Taiwan University Hospital. Serum VAP-1 in the samples obtained at enrollment was measured by time-resolved immunofluorometric assay. The vital status of all subjects was ascertained by linking their data with computerized death certificates in Taiwan.

Results: The medium follow-up period was 10.4 years. Subjects with serum VAP-1 in the highest tertile had a hazard ratio (HR) of 2.19 (95% CI 1.17-4.11) for all-cause mortality adjusted for age, sex, smoking, history of cardiovascular disease, obesity, hypertension, hemoglobin A(1c), diabetes duration, total cholesterol, use of statins, abnormal ankle-brachial index, estimated glomerular filtration rate (eGFR), and proteinuria. The adjusted HRs for logarithmically transformed serum VAP-1 were 5.83 (95% CI 1.17-28.97) for cardiovascular mortality, 6.32 (95% CI 1.25-32.00) for mortality from cardiovascular and diabetic causes, and 17.24 (95% CI 4.57-65.07) for cancer mortality. There were four variables, including age, serum VAP-1, proteinuria, and eGFR, which could enhance mortality prediction significantly.

Conclusions: Serum VAP-1 can predict 10-year all-cause mortality, cardiovascular mortality, and cancer mortality independently in type 2 diabetic subjects. Serum VAP-1 is a novel biomarker that improves risk prediction over and above established risk factors.

FIG. 1.

Kaplan-Meier survival curves by tertile of serum VAP-1 levels. P = 0.0001 among subgroups by tertile. Blue line, subjects with serum VAP-1 in the first tertile; green line, subjects with serum VAP-1 in the second tertile; red line, subjects with serum VAP-1 in the third tertile.