Effects of Extended-Release Niacin on Quartile Lp-PLA2 Levels and Clinical Outcomes in Statin-treated Patients with Established Cardiovascular Disease and Low Baseline Levels of HDL-Cholesterol: Post Hoc Analysis of the AIM HIGH Trial.
BACKGROUND
Lipoprotein-associated phospholipase A2 (LpPLA2) is an inflammatory marker that has been associated with the presence of vulnerable plaque and increased risk of cardiovascular (CV) events.


OBJECTIVE
To assess the effect of extended-release niacin (ERN) on Lp-PLA2 activity and clinical outcomes.


METHODS
We performed a post hoc analysis in 3196 AIM-HIGH patients with established CV disease and low baseline levels of high-density lipoprotein cholesterol (HDL-C) who were randomized to ERN versus placebo on a background of simvastatin therapy (with or without ezetimibe) to assess the association between baseline Lp-PLA2 activity and the rate of the composite primary end point (CV death, myocardial infarction, stroke, hospitalization for unstable angina, and symptom-driven revascularization).


RESULTS
Participants randomized to ERN, but not those randomized to placebo, experienced a significant 8.9% decrease in LpPLA2. In univariate analysis, the highest quartile of LpPLA2 activity (>208 nmol/min/mL, Q4) was associated with higher event rates compared to the lower quartiles in the placebo group (log rank P = .032), but not in the ERN treated participants (log rank P = .718). However, in multivariate analysis, adjusting for sex, diabetes, baseline LDL-C, HDL-C, and triglycerides, there was no significant difference in outcomes between the highest Lp-PLA2 activity quartile versus the lower quartiles in both the placebo and the ERN groups.


CONCLUSION
Among participants with stable CV disease on optimal medical therapy, elevated Lp-PLA2 was associated with higher CV events; however, addition of ERN mitigates this effect. This association in the placebo group was attenuated after multivariable adjustment, which suggests that Lp-PLA2 does not improve risk assessment beyond traditional risk factors.
['Lyubarova|Radmila|R|0000-0001-9163-7602', 'Albers|John J|JJ|', 'Marcovina|Santica M|SM|', 'Yao|Yao|Y|', 'McBride|Ruth|R|', 'Topliceanu|Alexandru|A|', 'Anderson|Todd|T|', 'Fleg|Jerome L|JL|', 'Desvigne-Nickens|Patrice|P|', 'Kashyap|Moti L|ML|', 'McGovern|Mark E|ME|', 'Boden|William E|WE|']
D043203:1-Alkyl-2-acetylglycerophosphocholine Esterase D000368:Aged D015415:Biomarkers D002318:Cardiovascular Diseases D008076:Cholesterol, HDL D003692:Delayed-Action Preparations D050171:Dyslipidemias D000069438:Ezetimibe D005260:Female D006801:Humans D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors D000960:Hypolipidemic Agents D008297:Male D008875:Middle Aged D009525:Niacin D018570:Risk Assessment D012307:Risk Factors D019821:Simvastatin D013997:Time Factors D016896:Treatment Outcome
extended-release niacin cardiovascular disease Lp-PLA activity atherogenic dyslipidemia high density lipoprotein