Molecular Biomarkers & Diagnosis

The Effect of Smoking on Diagnostic Value of Serum Matrix Metalloproteinase-8 in Acute Coronary Syndrome

Abstract

Laura Lahdentausta, Timo Sorsa, Pirkko J Pussinen and Erkki Pesonen

Abstract
Background: Smoking has been perceived to increase the levels of carcinogenic and inflammatory mediators
thereby promoting presumably malignant and proinflammatory tissue destruction via activating proteolytic enzymes
such as matrix metalloproteinases (MMPs) and their regulators. We studied the effect of smoking on the diagnostic
ability of serum MMP-8-IFMA and TIMP-1-ELISA analysis to recognize patients with acute coronary syndrome
(ACS).
Methods: The case-control population (n=605) comprised 291 patients with diagnosed acute myocardial
infarction (AMI) or unstable angina pectoris (UAP) and 314 healthy control individuals. The case and the control
group included 55 and 66 smoking subjects, respectively.
Results: Smoking increased the MMP-8, but not the TIMP-1, concentration in both the control and the AMI
group. MMP-8 concentration, and consequently MMP-8/TIMP-1, distinguished the cases from the controls accurately
in the ROC analysis, but smoking decreased the AUCs in every category. The MMP-8 concentration produced an
AUC (95% CI, p-value) for ACS of 0.771 (0.723-0.818, p<0.001) and 0.684 (0.581-0.787, p=0.001) for non-smokers
and smokers, respectively. Similarly, the multivariate logistic regression model indicated that smoking decreased the
association of MMP-8 with ACS. The OR (95% CI, p-value) of MMP-8 for ACS was 8.1 (per ng/ml log-transformed
unit increase, 5.0-13.1, p<0.001) and 2.8 (1.1-7.0, p=0.025) for non-smokers and smokers, respectively.
Conclusions: One of the most important risk factors for ACS, smoking, decreases the diagnostic ability of MMP-
8 concentration and MMP-8/TIMP-1 ratio. This must be taken account if these serum determinations are used as
biomarkers of the risk for cardiovascular diseases.