Hyperglycemia and Oxidative Stress Strengthen the Association Between Myeloperoxidase and Blood Pressure

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 (n=267), impaired glucose metabolism (n=189), and type 2 diabetes (n=290). In an age- and sex-adjusted linear regression model, plasma myeloperoxidase was positively associated with systolic blood pressure (2.10 mm Hg per 1 SD increment of myeloperoxidase [95% CI: 0.66 to 3.54]), and this association was stronger at higher levels of fasting glucose (0.61 [−1.70 to 2.93], 1.33 [−1.43 to 4.10], and 3.42 [1.01 to 5.82] for increasing tertiles of glucose) and higher plasma levels of oxidized low-density lipoprotein (0.92 [−1.31 to 3.14], 2.00 [−0.71 to 4.70], and 3.58 [0.98 to 6.19] for increasing tertiles of oxidized low-density lipoprotein). Likewise, the relationship between myeloperoxidase and blood pressure was strongest under conditions associated with oxidative stress, like obesity, low high-density lipoprotein cholesterol, metabolic syndrome, and type 2 diabetes. The strength of these associations was only marginally attenuated by adjustment for other cardiovascular risk factors. Our data demonstrate that myeloperoxidase is positively and independently associated with blood pressure, and this association is strongest in subjects with (hyperglycemia-induced) oxidative stress. These observations, together with emerging evidence that myeloperoxidase-derived oxidants contribute to the initiation and propagation of cardiovascular disease, identify myeloperoxidase as a promising target for drug development.