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

Abstract 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.