Lipoprotein(a): a risk factor for atherosclerosis and an emerging therapeutic target

Abstract

Lipoprotein(a) (Lp(a)) is a complex circulating lipoprotein, and increasing evidence has demonstrated its role as a risk factor for atherosclerotic cardiovascular disease (ASCVD) and as a possible therapeutic target. Lp(a) atherogenic effects are attributed to several potential mechanisms in addition to cholesterol accumulation in the arterial wall, including proinflammatory effects mainly mediated by oxidised phospholipids. Several studies have found a causal and independent relationship between Lp(a) levels and cardiovascular risk. Furthermore, several studies also suggest a causal association between Lp(a) levels and calcific aortic valve stenosis. Available lipid-lowering agents have at best moderate impact on Lp(a) levels. Among available therapies, antibody proprotein convertase subtilisin/kexin type 9 inhibitors are the most effective in reducing Lp(a). Potent Lp(a)-lowering treatments that target LPA expression are under development. Lp(a) level measurement poses some challenges due to the absence of a definitive reference method and the reporting of Lp(a) values as molar (nanomoles per litre (nmol/L)) or mass concentrations (milligrams per decilitre (mg/dL)) by different assays. Currently, Lp(a) measurement is recommended to refine cardiovascular risk in specific clinical settings, that is, in individuals with a family history of premature ASCVD, in patients with ASCVD not explained by standard risk factors or in those with recurrent events despite optimal management of traditional risk factors. Patients with high Lp(a) levels should be managed with more intensive approaches to treat other modifiable cardiovascular risk factors. Overall, this review focuses on Lp(a) as an ASCVD risk factor and therapeutic target. Furthermore, it reports practical recommendations for Lp(a) measurement and interpretation and updated evidence on Lp(a)-lowering approaches.

Obesity and Cardiovascular Risk: Systematic Intervention Is the Key for Prevention

“…Cardiac rehabilitation programs in obese patients also improve exercise tolerance and functional capacity. Recent studies [ 30 , 39 , 40 , 41 ] have confirmed past results [ 42 , 43 , 44 , 45 , 46 ], but further studies are needed to better characterize the beneficial effects in obese patients, both with and without CV disease [ 47 ]. Gondoni et al [ 39 ] studied 772 obese patients aged ≥70 years with BMI at baseline of 37.6 ± 4.4 kg/m 2 and coronary artery disease (prior myocardial infarction, coronary angioplasty, or coronary artery bypass surgery) and/or heart failure.…”

Association between cumulative lipoprotein(a) exposure and adverse cardiovascular outcomes in patients with prediabetes or diabetes

“…Higher level of CumLp(a) exposure and impaired glucose metabolism exert their joint pathogenic effect on long-term adverse cardiovascular outcomes through multiple potential mechanisms including atherogenesis, vascular inflammation, and thrombosis. 1 , 21 On the one hand, Lp(a) has its atherogenic effect associated with its LDL-like composition which leads to the development and vulnerability of atherosclerotic plaques. Furthermore, Lp(a) possesses unique features secondary to its component of apo(a), that is thought to have relatively prothrombotic property because of its structural homology with plasminogen.…”

“… 23 In addition, Lp(a)’s components are believed to attach to fibrin to form the prothrombotic complex that inhibits plasminogen activation and fibrinolysis, thus promoting thrombus formation. 21 On the other hand, chronic mild inflammation is a recognized pathological mechanism of diabetes and prediabetes. Overall effects may eventually promote plaque rupture, leading to adverse cardiovascular events.…”

“…Overall effects may eventually promote plaque rupture, leading to adverse cardiovascular events. 1 , 21 Further basic medical studies are required to elucidate the potential mechanisms.…”

Inclisiran: A New Pharmacological Approach for Hypercholesterolemia

“…Innovative therapeutic approaches based on gene silencing technologies represent a new opportunity to manage CVD risk due to dyslipidemia [11]. This new therapeutic strategy uses antisense oligonucleotides (ASOs) or small interfering RNAs (siRNAs) for silencing gene expression.…”