The following are key points to remember about this review of lipoprotein(a) [Lp(a)], which is one of the additional modifiable lipid risk factors contributing to cardiovascular disease (CVD) risk:

1. This review of Lp(a) is timely considering it aids in prediction of risk in primary prevention, its inclusion in some statin guidelines (National Lipid Association [NLA], European and Canadian), that PCSK9 inhibitors lower it by 20-30%, and that the emerging RNA-targeted therapies can lower Lp(a) >80%.
2. Genetic, epidemiological, translational, and pathophysiological insights have established Lp(a) as an independent, genetic, and likely causal risk factor for coronary events, peripheral vascular disease, and calcific aortic valve stenosis (CAVS). The LPA gene is one of the strongest monogenetic risk factors for coronary disease regardless of race, and the only one for CAVS in multiple racial groups.
3. Lp(a) is a low-density lipoprotein (LDL)-like particle formed directly in the liver in which apoB is bound to apolipoprotein (a) [apo (a)], which has a homology with plasminogen and thus the potential for explaining the prothrombotic and antifibrinolytic activity. Like LDL particles, Lp(a) increases atherosclerosis by inflammation and pro-oxidation. When levels increase to >25-30 mg/dl, risk of Lp(a) increases in a curvilinear fashion. Clearance is not related to LDL-receptor activity.
4. Lp(a) levels are generally measured as total mass in mg/dl including protein, lipids, and carbohydrates, which when using appropriate calibrators, make the assay’s isoform number and size independent. Since it is not influenced by nutrition or environment, it only has to be measured once for screening or diagnostic purposes. The method is reasonably accurate for separating low risk (<30 mg/dl) from high risk levels (>50 mg/dl). Measuring Lp(a) levels in intermediate-risk groups allows reclassification of risk in 4 of 10 patients with value primarily in upgrading to high risk. Recent studies have suggested that an elevated Lp(a) remains a risk factor even in patients who achieve LDL-C <70 mg/dl. Lp(a) cholesterol content is not validated for predictive value.
5. The European Atherosclerosis Society and US NLA recommend Lp(a) measurement once in all patients with premature CVD, and in patients with intermediate or high CVD risk, familial hypercholesterolemia, family history of premature CVD, and/or elevated Lp(a), recurrent CVD despite statin treatment, and 3% 10-year risk of fatal and/or 10% 10-year risk of fatal and nonfatal coronary heart disease.
6. Clinical trials to date that assessed the impact of therapies that lower Lp(a) have not demonstrated any value including niacin and estrogens, but each has been post hoc, most patients had a low level, and the impact on Lp(a) was modest.

Keywords: Aortic Valve Stenosis, Apolipoproteins B, Atherosclerosis, Cholesterol, Coronary Artery Disease, Dyslipidemias, Genetics, Hydroxymethylglutaryl-CoA Reductase Inhibitors, Hyperlipoproteinemia Type II, Inflammation, Lipoproteins, Lipoprotein(a), Lipoproteins, LDL, Peripheral Vascular Diseases, Primary Prevention, Risk Factors

< Back to Listings