Predictive Value of Circulating Oxidized LDL for Cardiac Events in Type 2 Diabetic Patients With Coronary Artery Disease
Oxidized LDL (oxLDL) has been shown to play an important role in the initiation and development of atherosclerosis (1). Individuals with type 2 diabetes exhibit enhanced LDL oxidizability and accelerated atherosclerosis (2,3). Past studies demonstrated the association between LDL oxidation and atherosclerosis by “indirect” methods, such as lag times and propagation rates for LDL oxidation, and antibodies against oxLDL. Recently, some groups have developed “direct” methods for measuring circulating oxLDL (4–6). Indeed, several lines of evidence have demonstrated that the level of circulating oxLDL is significantly higher in patients with type 2 diabetes, is a marker for identifying patients with coronary artery disease (CAD), and has a positive relationship with acute coronary syndromes (7,8). However, the predictive value of circulating oxLDL for cardiac events in type 2 diabetic patients with CAD has not been investigated.
Ninety-six consecutive patients, who had angiographic documentation of CAD and fulfilled the classification of the American Diabetes Association, were followed for up to 52 months. Patients with acute coronary syndrome and/or ongoing congestive heart failure were excluded. Patients with malignant disease and/or inflammatory disease were also excluded. We defined cardiac death, nonfatal myocardial infarction, and refractory angina requiring revascularization as major cardiac events. The levels of oxLDL were measured by a sandwich enzyme-linked immunosorbent assay, as previously described (9).
Thirty-five cardiac events were documented during the follow-up. Age was significantly higher in patients with cardiac events than in those without cardiac events (P = 0.02). The other values and frequencies, including coronary risk factors, lipid profiles, fasting plasma glucose, and HbA1c, were not significantly different between the two groups. Choice of treatment for diabetes, such as insulin, sulfonylureas, α-glucosidase inhibitors, and thiazolidinediones, was not different. The levels of oxLDL (means ± SD) in patients with cardiac events were significantly higher than in those without cardiac events (23.8 ± 14.2 vs. 18.8 ± 6.9 units/ml, P = 0.02). The patients were divided into two groups based on the 75th percentile (24.7 units/ml) of the distribution of oxLDL levels. Kaplan-Meier analysis demonstrated that the patients with oxLDL >24.7 units/ml had a significantly higher prevalence of cardiac events (P = 0.0007) (Fig. 1). After adjustment for age, sex, BMI, hypertension, smoking history, LDL cholesterol, triglyceride, HDL cholesterol, fasting plasma glucose, HbA1c, number of diseased vessels, and left ventricular ejection fraction, Cox proportional analysis showed that the hazard ratio for cardiac events was 3.6 (95% CI 1.5–8.8, P = 0.005) times higher in patients with oxLDL >24.7 units/ml than in those with oxLDL ≤24.7 units/ml.
This study firstly, to the best of our knowledge, demonstrated that high levels of circulating oxLDL can serve as an independent and significant predictor for future cardiac events in type 2 diabetic patients with CAD. Therefore, measurement of circulating oxLDL may be helpful for identifying high-risk patients with type 2 diabetes and CAD.
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