Circulating Oxidized LDL is a Useful Marker for Cardiovascular Risk Assessment
BACKGROUND: Coronary artery disease is associated with an increase in circulating oxidized (Ox)LDL (Circulation 1998; 98:1487-1494). OBJECTIVES: 1) To determine the usefulness of OxLDL for identifying cardiovascular disease patients and 2) to study the relation of OxLDL with cardiovascular risk factors. METHODS: 1) To determine the diagnostic value of OxLDL 308 subjects were studied: 178 patients with angiographically proven coronary artery disease and 130 age-matched subjects without cardiovascular disease (controls) confirmed by B mode ultrasonography of their carotid arteries. 2) Additional 307 patients without cardiovascular disease were studied to determine the relation of OxLDL with cardiovascular risk factors. Levels of OxLDL were directly measured in plasma using a mAb-4E6 based competition ELISA. RESULTS: Compared with controls, patients had 2.3-fold higher levels of circulating OxLDL. At a cutoff value of 2.30 mg/dL, the sensitivity of OxLDL for cardiovascular disease was 73% with a specificity of 90%. The Global Risk Assessment Score (GRAS) was calculated using age, total and HDL cholesterol, systolic blood pressure, diabetes mellitus and smoking. GRAS was 8.65±3.41 for patients versus 6.09±5.10 (p≤0.001) for controls. Compared with subjects with low OxLDL (≤2.30 mg/dL) and low GRAS (≤12), risk of having cardiovascular disease was 3.2 times higher for subjects with low OxLDL and high GRAS, 6.4 times higher for subjects with high OxLDL and low GRAS and 27 times higher for subjects with both high OxLDL and high GRAS. Among patients without cardiovascular disease, stepwise multivariate analysis showed that Body Mass Index (p<0.001), LDL cholesterol (p<0.001), diabetes type 2 (p=0.003), triglycerides (p=0.017) and smoking (p=0.046) were the strongest predictors of OxLDL. Conclusion: Circulating OxLDL is a sensitive marker of cardiovascular disease. Circulating oxidized LDL correlates with obesity, hypercholesterolemia, diabetes and smoking. Addition of OxLDL to the established risk factors may improve cardiovascular risk prediction. Inclusion of OxLDL in prospective studies of risk factors of cardiovascular disease seems to be warranted.