Do we know when and how to lower lipoprotein(a)?

Parag H. Joshi, Eric Krivitsky, Zhen Qian, Gustavo Vazquez, Szilard Voros, Joseph Miller

Research output: Contribution to journalArticlepeer-review

9 Scopus citations


Currently, there are significant data to support a link between lipoprotein(a) [Lp(a)] levels and cardiovascular risk. However, there has not been a clinical trial examining the effects of Lp(a) reduction on cardiovascular risk in a primary prevention population. Until such a trial is conducted, current consensus supports using an Lp(a) percentile greater than 75% for race and gender as a risk stratification tool to target more aggressive low-density lipoprotein cholesterol (LDL-C) or apolipoprotein B (apoB) goals. Therefore, Lp(a) measurements should be considered in the following patients: individuals with early-onset vascular disease determined by clinical presentation or subclinical imaging, intermediate and high Framingham risk patients with a family history of premature coronary disease, and low Framingham risk patients with a family history and low high-density lipoprotein cholesterol (HDL-C) levels. Once LDL-C goals are met, Lp(a) levels may be taken into account in selecting secondary agents to reach more aggressive secondary goals, including non-HDL-C and apoB. To achieve Lp(a) reduction, one evidence-based approach is to initiate therapy with low-dose aspirin and extended-release niacin, titrated from 0.5 g up to 2 g over several weeks. If higher doses of niacin are desired, crystalline niacin allows for titration to a dosage as high as 2 g three times a day; however, the flushing side effect usually is quite prominent. Although hormone replacement therapy (HRT) has been shown to lower Lp(a), there are no indications for using HRT for primary or secondary prevention; therefore, we do not advocate initiating it solely for Lp(a) reduction. LDL apheresis is an option to lower LDL-C levels in patients with homozygous familial hypercholesterolemia who are not responsive to medical therapy. Although it does lower Lp(a), there is no treatment indication for this. A recent study supports the cholesterol absorption inhibitor ezetimibe's ability to lower Lp(a), a finding that deserves further investigation as it has not been previously reported in multiple ezetimibe trials. Additionally, the apoB messenger RNA antisense therapy mipomersen currently is in phase 3 trials and may serve as a potential inhibitor of Lp(a) production. Ultimately, more trial evidence is needed to determine whether lowering Lp(a) actually reduces cardiovascular risk, although this may be difficult to isolate without a specific Lp(a)-lowering therapy.

Original languageEnglish (US)
Pages (from-to)396-407
Number of pages12
JournalCurrent Treatment Options in Cardiovascular Medicine
Issue number4
StatePublished - Aug 2010

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine


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