BACKGROUND: Inflammation and oxidative stress are associated with atherosclerosis. Myeloperoxidase (MPO) is linked to both inflammation and oxidative stress by its location in leukocytes and its role in catalyzing the formation of oxidizing agents. Recent evidence suggests that MPO activity precipitates atherogenesis. Measurement of MPO in plasma may therefore contribute to cardiovascular disease (CVD) risk stratification. CONTENT:Cross-sectional studies, case-control studies, and prospective-cohort studies investigating the relation between MPO and CVD have been evaluated. Differences in study populations, sample materials, sample handling, and assays were ascertained. Potential causal mechanisms linking MPO to accelerated atherosclerosis are discussed here. A majority of studies indicate that measurement of MPO in plasma was associated with improved CVD risk stratification above and beyond risk stratification results obtained with markers used in routine clinical practice. However, comparison of these epidemiological studies with regard to MPO and outcome is hampered because the reported MPO concentration depends on the assay method, sampling material, and preanalytical and analytical procedures. The link between MPO and CVD can, at least partly, be explained by MPO-dependent oxidation of LDL and HDL, subsequently leading to cholesterol accumulation in the arterial wall. Furthermore, MPO may reduce the bioavailability of nitric oxide, resulting in endothelial dysfunction. Finally, MPO destabilizes atherosclerotic plaques.

Circulating oxidized LDL (oxLDL) levels are strongly correlated to LDL-cholesterol (LDL-c) and apolipoprotein-B100 (apoB100), making it difficult to disentangle their independent contributions to cardiovascular risk. We explored the determinants of oxLDL and the relation between oxLDL and flow-mediated dilation (FMD) of the brachial artery to investigate whether the oxLDL/LDL-c and oxLDL/apoB100 ratios are more informative than the separate variables. FMD of the brachial artery and plasma concentrations of oxLDL, LDL-cholesterol, and apoB100 were measured in 624 men and women (age range 50 to 87 years), participating in a population-based cohort study. OxLDL was strongly correlated with apoB100 (r 5 0.82, P , 0.001) and LDL-c (r 5 0.67, P , 0.001). Other major independent determinants of oxLDL were sex, HDL-cholesterol, and LDL particle size. LDL-c and apoB100 concentrations were not significantly associated with FMD. After adjustment for age, sex, glucose tolerance status, and Framingham risk score, the oxLDL/apoB100 ratio was negatively related to FMD (P 5 0.017). This association was weaker for the oxLDL/ LDL-c ratio (P 5 0.062) and absent for oxLDL level (P 5 0.27). In contrast to oxLDL, the oxLDL/ apoB100 ratio, and to a lesser extent the oxLDL/LDL-c ratio, are related to a functional measure of atherosclerosis. Therefore correction of oxLDL for LDL particle number may improve the clinical usefulness of oxLDL measurement.-van der

Abstract-Scavenging of the vasodilator nitric oxide by myeloperoxidase activity in the vasculature may contribute to hypertension. Because hydrogen peroxide is a cosubstrate of myeloperoxidase, hyperglycemia-induced oxidative stress may strengthen the relationship between myeloperoxidase and blood pressure. We investigated this relationship and its modification by hyperglycemia and oxidative stress in a population-based cohort of elderly subjects with normal glucose metabolism (nϭ267), impaired glucose metabolism (nϭ189), and type 2 diabetes (nϭ290 Many studies have demonstrated that systemic MPO levels predict risk throughout the spectrum of cardiovascular diseases. 4 -8 MPO catalyzes the production of hypochlorous acid and a range of other highly reactive species. These MPOderived reactive substances may damage the arterial wall, thereby reducing its elasticity. In addition, by several mechanisms, MPO reduces the bioavailability of the endogenous vasodilator nitric oxide. 3,9 Together, these mechanisms may lead to an increase in blood pressure. Because hydrogen peroxide is an obligate cosubstrate of MPO, the activity of MPO in the vasculature may be enhanced by increased local production of reactive oxygen species. Vascular production of superoxide and its dismutation product hydrogen peroxide has been shown to be stimulated by high glucose concentrations, resulting in increased activity of MPO. 10 We therefore hypothesize that the relationship between MPO and blood pressure is stronger on a background of (hyperglycemiainduced) oxidative stress.The aims of our study were to assess the relationship between plasma levels of MPO and blood pressure and to test the hypothesis that this relationship is strengthened by (hyperglycemia-induced) oxidative stress. Methods SubjectsThe present study was conducted in the Hoorn Study 11 follow-up examination conducted in 2000 and the Hoorn Screening Study, 12 both of which are population-based studies in a white population. From the 822 participants, we excluded subjects with missing data on primary variables of interest, leaving 746 subjects, of whom 267

In elderly participants, plasma levels of L-homoarginine and L-arginine are independently associated with clinically relevant differences in blood pressure in an antagonistic fashion.

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