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CLINICAL RESEARCH: ATHEROSCLEROSIS

Association of Paraoxonase-1 Activity and Concentration With Angiographic Severity and Extent of Coronary Artery Disease

Marit Granér, MD^_*,_*, Richard W. James, MD, PhD, Juhani Kahri, MD, PhD^_*, Markku S. Nieminen, MD, PhD^_*, Mikko Syvänne, MD, PhD^_* and Marja-Riitta Taskinen, MD, PhD^_*

^_* Department of Internal Medicine, Division of Cardiology, Helsinki University Central Hospital, Helsinki, Finland
Clinical Diabetes Unit, Division of Endocrinology and Diabetology, University Hospital, Geneva, Switzerland.

Manuscript received October 27, 2005; revised manuscript received January 7, 2006, accepted January 9, 2006.

^_* Reprint requests and correspondence: Dr. Marit Granér, Department of Internal Medicine, Division of Cardiology, Helsinki University Central Hospital, Haartmaninkatu 4, FIN-00290 HUCH, Finland. (Email: marit.graner{at}hus.fi).

OBJECTIVES: The goal of this study was to examine the association between paraoxonase-1 (PON1) activity and concentration and the severity and extent of coronary artery disease (CAD).

BACKGROUND: Paraoxonase-1, a high-density lipoprotein-associated enzyme, is proposed to have an antiatherogenic effect by protecting low-density lipoproteins against oxidation.

METHODS: We studied PON1 activity and concentration in 107 patients with known or suspected CAD referred for cardiac catheterization. Based on visual estimation of coronary angiograms, subjects were classified as having no or mild CAD (<50% stenosis) and significant CAD (50% stenosis). Quantitative coronary angiography (QCA) was used to estimate the indexes of severity, extent, and overall atheroma burden of CAD.

RESULTS: We found lower values of PON1 activity and concentration (p = 0.003 and p = 0.016, respectively) in the group with significant CAD as compared with the group with no or mild CAD. The PON1 activity was significantly inversely correlated with CAD severity (r = –0.364, p < 0.001), extent (r = –0.221, p = 0.022), and atheroma burden (r = –0.277, p = 0.004). Similarly, PON1 concentration correlated with CAD severity (r = –0.306, p = 0.001) and atheroma burden (r = –0.229, p = 0.017). In multiple regression analysis, gender and PON1 activity were significant determinants of the severity of CAD independently of age, hypertension, smoking, abnormal glucose regulation, and high-density lipoprotein cholesterol.

CONCLUSIONS: Our results indicate that PON1 activity and concentration are lower in subjects with significant CAD, and that there is a significant relationship between PON1 activity and concentration and CAD assessed by QCA.

Abbreviations and Acronyms   apoA-I = apolipoprotein A-I   apoA-II = apolipoprotein A-II   apoB = apolipoprotein B   CAD = coronary artery disease   HDL = high-density lipoprotein   LDL = low-density lipoprotein   LpA-I = lipoprotein A-I   PON1 = paraoxonase-1   QCA = quantitative coronary angiography   VLDL = very-low-density lipoprotein

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