Lipoprotein(a) levels and long-term cardiovascular risk in the contemporary era of statin therapy

Stephen J Nicholls,W.H Wilson Tang,Heather Scoffone,Danielle M Brennan,Jaana Hartiala,Hooman Allayee,Stanley L Hazen

doi:10.1194/jlr.m008961

Stephen J Nicholls, W.H Wilson Tang + Show 5 more

Open Access

https://doi.org/10.1194/jlr.m008961

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Abstract

Lipoprotein(a) [Lp(a)] has enhanced atherothrombotic properties. The ability of Lp(a) levels to predict adverse cardiovascular outcomes in patients undergoing coronary angiography has not been examined. The relationship between serum Lp(a) levels and both the extent of angiographic disease and 3-year incidence of major adverse cardiovascular events (MACE: death, myocardial infarction, stroke, and coronary revascularization) was investigated in 2,769 patients who underwent coronary angiography [median Lp(a) 16.4 mg/dl, elevated levels (≥30 mg/dl) in 38%]. An elevated Lp(a) was associated with a 2.3-fold [95% confidence interval (CI), 1.7-3.2, P < 0.001] greater likelihood of having a significant angiographic stenosis and 1.5-fold (95 CI, 1.3-1.7, P < 0.001) greater chance of three-vessel disease. Lp(a)≥30 mg/dl was associated with a greater rate of MACE (41.8 vs. 35.8%, P = 0.005), primarily due to a greater need for coronary revascularization (30.9 vs. 26.0%, P = 0.02). A relationship between Lp(a) levels and cardiovascular outcome was observed in patients with an LDL cholesterol (LDL-C) ≥70-100 mg/dl (P = 0.049) and >100 mg/dl (P = 0.02), but not <70 mg/dl (P = 0.77). Polymorphisms of Lp(a) were also associated with both plasma Lp(a) levels and coronary stenosis, but not a greater rate of MACE. Lp(a) levels correlate with the extent of obstructive disease and predict the need for coronary revascularization in subjects with suboptimal LDL-C control. This supports the need to intensify lipid management in patients with elevated Lp(a) levels.

Highlights

For more than a century, evidence has continued to accumulate supporting the pivotal role of cholesterol in the pathogenesis of atherosclerotic cardiovascular disease (CVD)
Epidemiologic studies have reported variable findings with regard to the relationship between Lp(a) levels and cardiovascular risk [7,8,9,10,11,12,13,14,15,16,17,18], it was recently reported that genetic polymorphisms associated with elevated Lp(a) levels are associated with an excessive rate of myocardial infarction [19,20,21,22]
Lp(a) levels were investigated in stable patients presenting for elective coronary angiography

Summary

Introduction

For more than a century, evidence has continued to accumulate supporting the pivotal role of cholesterol in the pathogenesis of atherosclerotic cardiovascular disease (CVD). Epidemiologic studies have reported variable findings with regard to the relationship between Lp(a) levels and cardiovascular risk [7,8,9,10,11,12,13,14,15,16,17,18], it was recently reported that genetic polymorphisms associated with elevated Lp(a) levels are associated with an excessive rate of myocardial infarction [19,20,21,22] This implicates a direct role for Lp(a) in acute thrombotic/ischemic events. The objective of the current analysis was to investigate the clinical and genetic relationship between baseline levels of Lp(a) and both the extent of angiographic disease and the subsequent incidence of cardiovascular events in a cohort of patients who presented for a clinically-indicated coronary angiogram and with a contemporary treatment regimen

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