Lipoprotein(a) and Cardiovascular Disease

Diagnosis and Treatment
Elevated Lp(a), which is found in 25% to 35% of the population, is diagnosed at a level > 30 mg/dL, regardless of sex.^4,9 In conjunction with known disease, elevated Lp(a) is sufficient to warrant consideration of very aggressive treatment. In these circumstan­ces, the provider may consider a target LDL-C level ≤ 70 mg/dL.^6,7,11 In primary prevention, clinicians should consider lowering this threshold. Levels that may have been considered appropriate in a low- or moderate-risk patient (≤ 160 mg/dL and ≤ 130 mg/dL, respectively) may be reduced to ≤ 130 mg/dL and ≤ 100 mg/dL, respectively.^6,11

There is no peer-reviewed evidence with regard to lifestyle management (exercise and diet) for reduction of Lp(a). However, it is reasonable to recommend that high-risk patients adopt healthier regimens.

Management of elevated Lp(a) includes consideration of pharmacologic intervention. Since Lp(a) is prothrombotic, all patients without contraindications should at least be taking low-dose (81-mg) aspirin. Those with evidence of thrombotic events may need lifetime antiplatelet therapy.¹² Statin therapy has mixed and minimal effects on Lp(a), although it remains the mainstay of treatment due to its effects on LDL-C and other lipoproteins.¹³ Although long-term data are lacking, there is some anecdotal evidence of improvement with fibrate therapy. However, it is not recommended for treatment of elevated Lp(a).¹⁴

Nicotinic acid has had the longest and most robust history for reduction of Lp(a).^9,12 However, recent studies examining combination therapy with statins and nicotinic acid have yielded discouraging results—and in some cases have suggested negative outcomes with this combination.^15,16 High doses (4-5 g for immediate release and 2-3 g for sustained release) of nicotinic acid are necessary to produce beneficial results on Lp(a) or other lipid abnormalities (eg, elevated triglycerides, low HDL cholesterol).¹⁷ Use of OTC nicotinic acid is not recommended, since these products are considered dietary supplements and regulated as such, raising the potential for untoward adverse effects and/or the possibility that little to no active ingredient is present.^18-20

Results from the Women’s Health Study and the Heart and Estrogen/progestin Replacement Study suggested that estrogen might be an effective therapy. In one analysis, women with elevated Lp(a) derived greater potential cardioprotective effects from hormone replacement therapy (HRT) than those with lower Lp(a), and the researchers noted a “significant interaction” between baseline Lp(a), HRT treatment, and CVD risk. However, use of HRT is not approved for treatment of vascular risk today, due to the potential for adverse effects.^10,21

A novel therapy, in the form of PCSK9 inhibition, has been shown to reduce LDL-C significantly; reduction in Lp(a) was also observed. The FDA recently approved two PCSK9 inhibitors (alirocumab and evolocumab) for use, although the primary indication is for further reduction in LDL-C on top of the maximally tolerated dose of statin therapy, not for reduction of Lp(a).^22,23

Apheresis has been shown to have positive effects in reducing ongoing vascular events in select patient populations. It is approved by the FDA for treatment of refractory LDL-C, mostly in patients with familial hypercholesterolemia, but it is not indicated for treatment of elevated Lp(a). However, since Lp(a) tracks with LDL-C, it is also removed during the process; about a 50% reduction in Lp(a) levels has been noted, although levels rebound posttreatment. To date, reimbursement issues remain in the absence of an FDA indication and due to the paucity of treatment centers in the US.^24,25

Follow-up. The therapies mentioned require routine evaluation to assess tolerability and safety, as recommended in the prescribing information. Patients with known CVD should undergo an appropriate cardiac workup annually to evaluate for occult progression of disease. Patients require further evaluation of related cardiovascular risk factors and adherence with medication regimens. For primary prevention patients, annual follow-up is also recommended to assess for any changes in health status, lifestyle, or medication adherence.

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