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High-dose statins mitigate association between elevated phospholipids, MACE in patients with stable CAD
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Elevated oxidized phospholipids on apolipoprotein B-100 predicted secondary major adverse CV events in patients with stable CAD, but the risk was mitigated in those assigned a high-dose statin.
Oxidized phospholipids on apolipoprotein B-100 is a biomarker of increased risk for MACE in community cohorts, but the role in patients with stable CAD was not known, according to the study background.
Researchers measured levels of oxidized phospholipids on apolipoprotein B-100 in 1,503 patients from the Treating to New Targets (TNT) trial at baseline and 1 year after random assignment to atorvastatin 10 mg/day or 80 mg/day. All patients were treated with atorvastatin 10 mg/day in the 8 weeks prior to randomization.
The researchers examined the association between baseline levels of oxidized phospholipids on apolipoprotein B-100 and MACE, defined as CHD death, nonfatal MI, resuscitation after cardiac arrest and fatal/nonfatal stroke, and whether those factors differed based on assignment to statin dose.
Phospholipids, events related
At 1 year, 156 patients in the study cohort experienced MACE. Those patients had a higher level of oxidized phospholipids on apolipoprotein B-100 at baseline than those who did not experience MACE (P = .025).
The association between baseline level of oxidized phospholipids on apolipoprotein B-100 and subsequent MACE remained consistent after adjustment for traditional risk factors including age, sex, BMI, diabetes, systolic BP, LDL, HDL, apolipoprotein B and treatment (HR = 1.21; 95% CI, 1.04-1.41) per doubling of the oxidized phospholipids on apolipoprotein B-100 concentration in the total population.
Those findings were significant in the atorvastatin 10-mg group (HR = 1.28; 95% CI, 1.03-1.58), but not in the atorvastatin 80-mg group (HR = 1.16; 95% CI, 0.93-1.44).
A similar trend was observed for those in the highest tertile of oxidized phospholipids on apolipoprotein B-100 levels vs. those in the lowest tertile (HR = 1.69; 95% CI, 1.14-2.49).
According to the researchers, in those assigned atorvastatin 10 mg/day, those in the highest tertile of oxidized phospholipids on apolipoprotein B-100 levels had a higher risk for MACE at 1 year vs. those in the lowest tertile (HR = 2.08; 95% CI, 1.2-3.61), but the same was not true for those assigned atorvastatin 80 mg/day (HR = 1.4; 95% CI, 0.8-2.46).
Elevated levels of oxidized phospholipids on apolipoprotein B-100 appear to be a clinically informative biomarker in predicting MACE” in this population, Young Sup Byun, MD, from the division of cardiovascular diseases, University of California-San Diego, La Jolla, Calif., and colleagues concluded.
Biomarker development
Stephen J. Nicholls
“The current analysis is but one step in the development pathway of a novel CV biomarker,” Stephen J. Nicholls, MBBS, PhD, from the South Australian Health and Medical Research Institute, University of Adelaide, Australia, and Leonard Kritharides, MBBS, PhD, from the department of cardiology, Concord Repatriation General Hospital, University of Sydney, Australia, wrote in a related editorial. “Further steps along that path will require ongoing elucidation of what is precisely measured by this assay, both in static and serial studies. A considerable amount of work remains to be done.” – by Erik Swain
Disclosure: Pfizer supported the cost of the assays used in this study. Several researchers report financial ties with Cymabay, Intercept, Isis Pharmaceuticals and Pfizer. Nicholls reports financial ties with Amgen, Anthera, AstraZeneca, Atheronova, Boehringer Ingelheim, Cerenis, CSL Behring, Eli Lilly, LipoScience, Merck, Novartis, Omthera, Pfizer, Resverlogix, Roche, Sanofi/Regeneron and Takeda. Kritharides reports financial ties with Actelion, Amgen, AstraZeneca, Merck, Pfizer and Sanofi.
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