Lipoprotein (a) for Risk Assessment in Patients With Established Coronary Artery Disease

Oct 23, 2013
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Authors:
O’Donoghue MO, Morrow DA, Tsimikas S, et al.
Citation:
J Am Coll Cardiol 2013;Oct 23:[Epub ahead of print].
Summary By:
Melvyn Rubenfire, MD, FACC

Study Questions:

Is there a prognostic utility of lipoprotein (a) [Lp(a)] in individuals with coronary artery disease (CAD)?

Methods:

Plasma Lp(a) was measured in 6,762 subjects with CAD from three studies; data were then combined with eight previously published studies for a total of 18,979 subjects.

Results:

Across the three studies, increasing levels of Lp(a) were not associated with the risk of cardiovascular (CV) events when modeled as a continuous variable (odds ratio [OR], 1.03 per log-transformed standard deviation; 95% confidence interval [CI], 0.96-1.11) or by quintile (OR, Q5:Q1 1.05; 95% CI, 0.83-1.34). When data were combined with previously published studies of Lp(a) in secondary prevention, subjects with Lp(a) levels in the highest quintile were at increased risk of CV events (OR, 1.40; 95% CI, 1.15-1.71), but with significant between-study heterogeneity (p = 0.001). When stratified on the basis of low-density lipoprotein cholesterol (LDL-C), the association between Lp(a) and CV events was significant in studies in which average LDL-C was ≥130 mg/dl (OR, 1.46; 95% CI, 1.23-1.73; p < 0.001), whereas this relationship was not significant for studies with an average LDL-C <130 mg/dl (OR, 1.20; 95 CI, 0.90-1.60; p = 0.21).

Conclusions:

Lp(a) is significantly associated with the risk of CV events in patients with established CAD; however, there exists marked heterogeneity across trials. In particular, the prognostic value of Lp(a) in patients with low cholesterol levels remains unclear.

Perspective:

Lp(a) is a small LDL-like particle formed in the liver, readily oxidized, and prothrombotic. There is no effective treatment. Targeting very high levels of Lp(a) in CAD with lipid control on statins with apheresis is approved in a few countries, and appears to be effective at reducing coronary events. To determine whether Lp(a) is a risk factor will require a treatment that targets it without altering other lipids.

Keywords: Odds Ratio, Coronary Artery Disease, Lipoprotein(a), Hydroxymethylglutaryl-CoA Reductase Inhibitors, Risk Factors, Treatment Outcome, Prognosis, Cholesterol, Dyslipidemias, Biomarkers, Coronary Angiography, Secondary Prevention, Confidence Intervals, Risk Assessment, Blood Component Removal


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