Relationship of Oxidized Phospholipids on Apolipoprotein B-100 to Cardiovascular Outcomes in Patients Treated With Intensive Versus Moderate Atorvastatin Therapy

Abstract

BACKGROUND Oxidized phospholipids on apolipoprotein B-100 (OxPL-apoB) is a biomarker of increased risk for major adverse cardiovascular events (MACE) in community cohorts, but its role in patients with stable coronary heart disease (CHD) is unknown. OBJECTIVES We sought to examine the relationship of these oxidative biomarkers to cardiovascular outcomes in patients with established CHD. METHODS In a random sample from the Treating to New Targets trial, OxPL-apoB levels were measured in 1,503 patients at randomization (after an 8-week run-in period on atorvastatin 10 mg) and 1 year after being randomized to atorvastatin 10 mg or 80 mg. We examined the association between baseline levels of OxPL-apoB and MACE, defined as death from CHD, nonfatal myocardial infarction (MI), resuscitation after cardiac arrest, and fatal/ nonfatal stroke, as well as the effect of statin therapy on OxPL-apoB levels and MACE. RESULTS Patients with events (n = 156) had higher randomization levels of OxPL-apoB than those without events (p = 0.025). For the overall cohort, randomization levels of OxPL-apoB predicted subsequent MACE (hazard ratio [HR]: 1.21; 95% confidence interval [CI]: 1.04 to 1.41; p = 0.018) per doubling and tertile 3 versus tertile 1 (HR: 1.69; CI: 1.14 to 2.49; p = 0.01) after multivariate adjustment for age, sex, body mass index (BMI), among others, and treatment assignment. The HR per doubling and by tertiles of OxPL-apoB remained significant in the low-dose but not the high-dose atorvastatin group. CONCLUSIONS Elevated OxPL-apoB levels predict secondary MACE in patients with stable CHD, a risk that is mitigated by atorvastatin 80 mg.

Antisense inhibition of apolipoprotein (a) to lower plasma lipoprotein (a) levels in humans

“…As described previously in both humans and nonhuman primates, our data show that cynomolgus monkeys had highly variable hepatic mRNA expression levels ( 44,45 ). Results from this events, lending evidence that the content of pro-infl ammatory OxPLs are key determinants of atherogenic risk mediated by Lp(a) (37)(38)(39)(40)(41)(42).…”

Oxidized Phospholipids on Lipoprotein(a) Elicit Arterial Wall Inflammation and an Inflammatory Monocyte Response in Humans

“…This increased circulating OxPL content in subjects with elevated Lp(a) suggests that a comparable impact of OxPL may hold true in vivo . In support, we have previously shown that OxPL-apoB levels were potent predictors of progressive atherosclerosis as well as the risk of cardiovascular disease and death in patients 14–16,46 .…”

Acute and long-term effect of percutaneous coronary intervention on serially-measured oxidative, inflammatory, and coagulation biomarkers in patients with stable angina

“…Because each mole of OxPL has 1 PC headgroup recognized by E06, this can be reported as nM PC-OxPL, as previously described for measurement of OxPL on apolipoprotein B-100 (OxPL-apoB). (13),(14), (15),(16) We present the OxPL-PLG data as both RLU and nM PCOxPL to facilitate comparison with prior work.…”