Hyperlipoproteinemia(a): Clinical significance and treatment options

Recent epidemiologic and Mendelian randomization studies together have provided evidence that lipoprotein(a) (Lp(a)) plays a causal role in the pathogenesis of atherosclerosis and cardiovascular disease (CVD). The risk association with CVD is weak but seems continuous in shape and without an obvious threshold for Lp(a) levels. A plasma concentration of 60 mg/dl compared to usual levels is associated with an odds ratio for coronary heart disease of about 1.5 after adjustment for other cardiovascular risk factors. Niacin (nicotinic acid) is the pharmacologic means of choice for decreasing elevated Lp(a) levels but the drug is often poorly tolerated due to adverse reactions. Dietary measures, exercise and other lipid-lowering drugs, especially statins, fibrates and ezetimibe, are without effect. In patients with severe progressive cardiovascular disease and very high Lp(a) levels, lipoprotein apheresis may be used to effectively decrease Lp(a) concentrations. The method is expensive and impractical for most patients and its feasibility depends by and large on the healthcare reimbursement system of the respective country. No established treatment, however, selectively reduces Lp(a) without influencing other lipoproteins. Moreover, despite the clear association of hyperlipoproteinemia(a) with cardiovascular risk, no rigorously designed study to date has demonstrated that lowering Lp(a) concentrations has beneficial effects on cardiovascular endpoints. Randomized trials to this effect are urgently needed.