Exercise-Induced Increases in Oxidized Low-Density Lipoprotein Are Associated With Adverse Outcomes in Chronic Heart Failure

Background: Oxidative stress is an important pathophysiologic feature in chronic heart failure (CHF) and may in part result from the inability to counteract acute surges of circulating oxidant products. Oxidized low-density lipoprotein (oxLDL) is an emerging prognostic marker in CHF. Accordingly, we investigated the effect of exercise-induced oxidative stress on circulating levels of oxLDL and its association with clinical outcomes in CHF. Methods and Results: Plasma levels of oxLDL and low-density lipoprotein cholesterol (LDL-c) were measured at rest and after maximal exercise in 48 subjects with CHF and 12 healthy controls. Subjects with CHF had a higher baseline oxLDL (77.7 ± 3.2 U/L vs 57.9 ± 5.0 U/L, P = .01) and a higher baseline oxLDL/LDL-c ratio (0.87 ± 0.04 vs 0.49 ± 0.04, P ≤ .001). Exercise induced an increase in oxLDL in subjects with CHF (77.7 ± 3.2 U/L to 85.3 ± 3.0 U/L, P ≤ .001) but not in controls (57.9 ± 5.0 to 61.4 ± 5.5, P = .17). In 39 subjects for whom follow-up data were available, an increase in oxLDL of more than 11.0 U/L was associated with an increased risk to meet a combined end point of death and need for ventricular assist device or heart transplant during a 19-month follow-up period (hazard ratio 8.6; 95% confidence interval 1.0-73.8, P = .05); this remained significant when adjusted for peak oxygen consumption, left ventricular ejection fraction, New York Heart Association class, sex, and age (hazard ratio 46.6, 95% confidence interval 1.5-1438.1, P = .02). Conclusion: Plasma oxLDL and the oxLDL/LDL-c ratio are elevated in subjects with CHF. Whether assessment of oxLDL during maximal exercise allows early identification of subjects at highest risk for adverse outcomes should be systematically investigated.