Lipoprotein(a), cardiovascular disease, and contemporary management

Abstract

Elevated lipoprotein(a) (Lp[a]) is a causal genetic risk factor for cardiovascular disease. To determine if current evidence supports both screening and treatment for elevated Lp(a) in high-risk patients, an English-language search of PubMed and MEDLINE was conducted. In population studies, there is a continuous association between Lp(a) concentrations and cardiovascular risk, with synergistic effects when low-density lipoprotein (LDL) is also elevated. Candidates for Lp(a) screening include patients with a personal or family history of premature cardiovascular disease, familial hypercholesterolemia, recurrent cardiovascular events, or inadequate LDL cholesterol (LDL-C) responses to statins. Given the comparative strength of clinical evidence, reducing LDL-C to the lowest attainable value with a high-potency statin should be the primary focus of lipid-modifying therapies. If the Lp(a) level is 30 mg/dL or higher in a patient who has the aforementioned characteristics plus residual LDL-C elevations (≥70-100 mg/dL) despite maximum-potency statins or combination statin therapy, the clinician may consider adding niacin (up to 2 g/d). If, after these interventions, the patient has progressive coronary heart disease (CHD) or LDL-C levels of 160-200 mg/dL or higher, LDL apheresis should be contemplated. Although Lp(a) is a major causal risk factor for CHD, no currently available controlled studies have suggested that lowering it through either pharmacotherapy or LDL apheresis specifically and significantly reduces coronary risk. Further research is needed to (1) optimize management in order to reduce CHD risk associated with elevated Lp(a) and (2) determine what other intermediate- or high-risk groups might benefit from Lp(a) screening.

Keywords: AIM-HIGH; Atherothrombosis Intervention in Metabolic Syndrome with Low HDL/High Triglycerides: Impact on Global Health Outcomes; CCHS; CHD; CV; CV disease; CVD; Copenhagen City Heart Study; FH; HDL-C; HPS2-THRIVE; HRT; Heart Protection Study 2-Treatment of HDL to Reduce the Incidence of Vascular Events; KIV-2; LDL; LDL cholesterol; LDL-C; Lp(a); Lp(a) cholesterol; Lp(a) particle; Lp(a)-C; Lp(a)-P; PN; RCT; SNP; apo; apolipoprotein; cardiovascular; coronary heart disease; familial hypercholesterolemia; high-density lipoprotein cholesterol; hormone replacement therapy; kringle IV type 2; lipoprotein(a); low-density lipoprotein; pentanucleotide; randomized controlled trial; single-nucleotide polymorphism.