Received on September 9, 2005
Accepted on December 8, 2005

Lipids, Lipoproteins, and Cardiovascular Risk Factors

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

¹ The Medical School, University of Wales Swansea, Swansea, United Kingdom
² Centre for Cardiovascular Genetics, British Heart Foundation Laboratories, Royal Free & University College London Medical School, London, United Kingdom
³ Department of Diabetes & Endocrinology, University College London Hospitals, London, United Kingdom
⁴ Medical Research Council Cardiovascular Research Group, Wolfson Institute of Preventive Medicine, London, United Kingdom

^* To whom correspondence should be addressed. E-mail: J.W.Stephens{at}Swansea.ac.uk.

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). 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.

Conclusion: 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.