European Perspective 

• During the last few years, major advances have been achieved in understanding the crucial role of elevated lipoprotein(a) (Lp(a)) in premature CAD (coronary artery disease) and CVD (cardiovascular disease). These new findings have prompted European Atherosclerosis Society (EAS) to publish a consensus paper with specific recommendations for screening for elevated blood Lp(a), on desirable levels, and on therapeutic strategies.¹

• The robust and specific association between elevated Lp(a) levels and increased CVD risk indicates that elevated Lp(a), like elevated LDL cholesterol, is causally related to premature CVD.

• The association is continuous without a threshold or dependence on LDL, or non-HDL cholesterol levels. After adjustment for CVD risk factors, for every 3.5-fold higher Lp(a) level above the median, the relative risk for a heart attack or coronary death is 1.13, and for ischemic stroke it is 1.10.

• Elevated Lp(a) levels are prothrombotic and antifibrinolytic because of competitive binding of apo(a) (apolipoprotein(a)) to the plasminogen receptor. Lp(a) may accelerate atherosclerosis because, like LDL, the Lp(a) particle is cholesterol-rich, the particles are small, and they are readily oxidized.

• The apo(a) genotype or apo(a) isoforms determine the rate of synthesis of apo(a) length. The levels of Lp(a) and thus, risk, are inversely related to apo(a) length.

•  Lp(a) should be measured using an isoform-insensitive assay (i.e., Lp[a] mass). Median value for Caucasians is 12 mg/dl, for Asians slightly higher, for Hispanics 19 mg/dl, and for Blacks 39 mg/dl. The 80th percentile for a general population is about 50 mg/dl.

• The EAS recommends screening for Lp(a) in subjects at intermediate or high CVD/CAD risk with premature CVD, familial hypercholesterolemia (high cholesterol), a family history of premature CVD and/or elevated Lp(a), recurrent CVD despite statin treatment. The EAS also recommends screen for Lp(a) for those with ≥3% 10-year risk of fatal CVD according to European guidelines and/or ≥10% for fatal + nonfatal CAD according to US guidelines.

• Niacin reduces Lp(a) by up to 30-40% in a dose-dependent manner. A meta-analysis of randomized, controlled intervention trials demonstrates that 1-3 g/day of niacin reduced major coronary events by 25% and stroke by 26%.

• As a secondary priority after LDL cholesterol reduction, the EAS recommends a desirable level for Lp(a) <80th percentile (less than ~50 mg/dl). Treatment should primarily be niacin 1-3 g/day. In extreme cases, LDL-apheresis is efficacious in reducing Lp(a).

• Because of the beneficial effects of niacin on HDL-C, VLDL remnants, and non-lipid parameters, it is not clear to what degree lowering the Lp(a) has influenced outcome. The ongoing placebo-controlled clinical trials of niacin + statins should provide useful evidence for deciding the value of niacin for targeting Lp(a).

• In short, the consensus recommendations call for screening for elevated Lp(a) in those at intermediate or high CVD/CAD risk and use of niacin for Lp(a) and CVD risk reduction in addition to maximal LDL lowering using statins.

Sources

1. Nordestgaard BG, Chapman MJ, Ray K, et al. Lipoprotein(a) as a cardiovascular risk factor: current status. Eur Heart J. Oct 21 2010.