Lipoprotein(a): A Lipoprotein Whose Time Has Come

Abstract

Cardiovascular disease is a leading cause of morbidity and mortality in the USA and around the world. While we are now able to achieve significant low-density lipoprotein cholesterol (LDL-C) lowering with current therapies, many patients remain at risk for cardiovascular disease (CVD). Elevated lipoprotein(a) [Lp(a)] has been shown to be an independent risk factor for CVD and accounts for some of the residual CVD risk after LDL-C lowering in several large clinical trials. Moreover, there is now strong evidence supporting the causal relationship between Lp(a) and aortic stenosis as well as peripheral arterial disease. Despite the growing interest in this lipoprotein, the current therapeutic options for Lp(a) reduction are limited. Our general approach in patients with elevated Lp(a) levels is to aggressively manage other modifiable cardiovascular risk factors including lifestyle modification, consideration of aspirin therapy, and LDL-C lowering. Unfortunately, there are conflicting reports on how effective this strategy is at reducing the risk for cardiovascular events attributed to elevated Lp(a). As a result, targeted Lp(a)-lowering strategies are needed. Lp(a) therapeutics is an active area of research with several promising classes of pharmacotherapies under investigation to address this causal biomarker.

Lipoprotein(a) the Insurgent: A New Insight into the Structure, Function, Metabolism, Pathogenicity, and Medications Affecting Lipoprotein(a) Molecule

“…ere are two categories of immunological assays used to measure Lp(a) levels. e first category of immunological assays is "isoform-dependent, " representing the entire protein mass of Lp(a), reported in milligrams per (deciliter/liter) [183]. e molecular mass of the apo(a) protein mainly depends on the number of K IV motif repeats, with an extremely wide range of 200-800 kilodaltons [39].…”

Lipoprotein (a) is a residual risk of atherosclerotic renal artery stenosis in hypertensive patients: a hospital-based cross-sectional study

“…Thus, to our knowledge, we are the first to demonstrate an independent association between Lp(a) concentration and ARAS in a hypertensive low LDL-c population. Pathophysiologically, the mechanisms by which Lp(a) increases CVD risk are driven by proatherogenic and prothrombotic states, including endothelial disorder, smooth muscle proliferation, foam cell formation, and local coagulation disturbances [13]. Molecularly, Lp(a) is similar to LDL-c, as it is a particle covalently bound by apoB and apo(a), which carries pathogenic LDL-c and leads to atherosclerosis [31].…”

“…In a recent ESC article, lipoprotein(a) [Lp(a)] was highlighted as a CVD risk estimator [8]. Studies from the past few decades have revealed that populations with well-regulated LDL-c levels still had a considerably high residual cardiovascular risk, and that Lp(a) is responsible for this phenomena [9][10][11][12][13][14].…”

Lipoprotein (a) is a residual risk of atherosclerotic renal artery stenosis in hypertensive patients: a hospital-based cross-sectional study

“…This cross-sectional study indicated that, in a hypertensive Chinese population with low levels of LDL-c, Lp(a) was identified as a significant residual risk factor for ARAS. Pathophysiologically, the mechanisms by which Lp(a) increases CVD risk are driven by proatherogenic and prothrombotic states, including endothelial disorder, smooth muscle proliferation, foam cell formation, and local coagulation disturbances [13]. Molecularly, Lp(a) is similar to LDL-c, as it is a particle covalently bound by apoB and apo(a), which carries pathogenic LDL-c and leads to atherosclerosis [31].…”