HEART DISEASE
Increased Plasma Markers of Oxidative Stress Are Associated with Coronary Heart Disease in Males with Diabetes Mellitus and with 10-Year Risk in a Prospective Sample of Males.
Stephens JW, Gable DR, Hurel SJ, Miller GJ, Cooper JA, Humphries SE; Clin Chem. 2006; 52:3:446-452
BACKGROUND: Increased oxidative stress is associated with coronary heart disease (CHD). We examined the association between plasma markers of oxidative stress and CHD in a cross-sectional sample of patients with diabetes and prospective CHD risk in a sample of men predominantly without diabetes. METHODS: Plasma total antioxidant status (TAOS) and the ratio of oxidized LDL (Ox-LDL) to LDL-cholesterol (LDL-C) were determined in a cross-section of 761 Caucasian individuals with diabetes (UDACS study). Plasma TAOS was also determined in 310 baseline samples from a 10-year prospective cohort of 3012 healthy males (NPHSII). RESULTS: Within UDACS, males with CHD had lower mean (SD) plasma TAOS [no CHD, 43.4 (13.2)%; CHD, 40.3 (13.8)%; P = 0.04]. The prevalence of CHD was higher in the lowest compared with the upper quartiles (32.7% vs 19.7%; P = 0.004). We observed a significant association between plasma Ox-LDL:LDL-C and CHD status [no CHD vs CHD, 16.9 (3.1) vs 19.3 (5.0) units/mmol; P = 0.04], with the prevalence of CHD being higher among men in the upper compared with lower quartiles (18.4% vs 35.1%; P = 0.003). No association was observed in females. In NPHSII, TAOS was lower in those who developed CHD [35.1 (8.0)% vs 37.1 (7.9)%; P = 0.04]. The odds ratio for CHD in the lowest compared with the upper quartile was 1.91 (95% confidence interval, 0.99-3.70; P = 0.04). This remained unchanged after adjustment for classic risk factors. CONCLUSIONS: A cross-sectional and prospective association exists between baseline plasma measures of oxidative stress and CHD risk. The association with prospective CHD risk remained after adjustment for "traditional" risk factors, implying an independent role for oxidative stress in CHD risk.
Oxidative Stress and Vascular Disease.
Heistad DD; 2005 Duff Lecture; Arterioscler Thromb Vasc Biol. 2006; 4:689-695
There is compelling evidence that oxidative stress plays a key role in the pathophysiology of several major cardiovascular diseases. In atherosclerosis, hypertension, stroke, diabetes, and heart failure, expression of superoxide is increased in blood vessels, and endothelial vasomotor function is impaired, presumably caused in large part by inactivation of nitric oxide by superoxide. Endothelial dysfunction is predictive of cardiovascular risk, and probably plays a key role in the pathophysiology of atherosclerosis and its complications. In preliminary studies in hypercholesterolemic mice and in older humans, we have found high levels of superoxide in the aortic valve, as well as aorta. We speculate that superoxide, in addition to playing a key role in atherogenesis, may play a key role in signaling that leads to calcific aortic valvular stenosis. Antioxidant enzymes, especially the three isoforms of superoxide dismutase (SOD), modulate basal levels of superoxide and protect against vasomotor dysfunction. A common gene variant of extracellular SOD (ecSOD) is associated with increased risk of ischemic heart disease. We have made recombinant adenoviruses to examine cardiovascular effects of ecSOD and its heparin-binding domain. This approach might be used to study the almost 500 other proteins with a heparin-binding domain. Finally, several key unanswered questions in relation to oxidative stress and atherosclerosis are raised, and proposed as fruitful areas of research.
Redox imbalance in patients with coronary artery disease showing progression of atherosclerotic lesions.
Tsuru R, Hojo Y, Gama M, Mizuno O, Katsuki T, Shimada K. Am J Physiol Heart Circ Physiol. 2006 Dec 15
OBJECTIVES: To clarify the relationship between changes in redox balance and the development of new coronary lesions in patients with coronary artery disease (CAD). METHODS: We studied 82 CAD patients (70 males and 12 females, mean age 61.8 +/- 9.2 years) who underwent repeated coronary angiography within 1 year after percutaneous coronary intervention. Levels of serum lipid peroxide, erythrocyte glutathione peroxidase activity, and the redox state of erythrocyte (ratio of reduced to oxidized glutathione, the GSH/GSSG ratio) were measured at the time of follow-up coronary angiography. According to the development of significant stenotic lesions, we divided the patients into two groups: 57 patients without the development of new stenotic lesions (group A) and 25 patients showing new significant stenotic lesions within 1 year (group B). RESULTS: The serum lipid peroxide level in group B was significantly higher than those of group A (2.61 +/- 0.32 vs 1.74 +/- 0.16 nmol/ml, p < 0.01). E |