Lipoprotein(a) Where Do We Stand? From the Physiopathology to Innovative Terapy

Abstract

A number of epidemiologic studies have demonstrated a strong association between increasing lipoprotein a [Lp(a)] and cardiovascular disease. This correlation was demonstrated independent of other known cardiovascular (CV) risk factors. Screening for Lp(a) in the general population is not recommended, although Lp(a) levels are predominantly genetically determined so a single assessment is needed to identify patients at risk. In 2019 ESC/EAS guidelines recommend Lp(a) measurement at least once a lifetime, fo subjects at very high and high CV risk and those with a family history of premature cardiovascular disease, to reclassify patients with borderline risk. As concerning medications, statins play a key role in lipid lowering therapy, but present poor efficacy on Lp(a) levels. Actually, treatment options for elevated serum levels of Lp(a) are very limited. Apheresis is the most effective and well tolerated treatment in patients with high levels of Lp(a). However, promising new therapies, in particular antisense oligonucleotides have showed to be able to significantly reduce Lp(a) in phase II RCT. This review provides an overview of the biology and epidemiology of Lp(a), with a view to future therapies.

Plasma Lipoprotein(a) Levels as Determinants of Arterial Stiffening in Hypertension

“…Lp(a) levels have been independently associated with conditions such as coronary heart disease, stroke, peripheral artery disease, and retinal artery occlusion, and could contribute to cardiovascular risk in subjects with early impairment of renal function and menopausal women [ 23 , 24 , 25 , 26 , 27 , 28 ]. Significant changes in circulating levels of Lp(a) are associated with ethnicity and dietary changes [ 4 , 18 , 29 ], and with a variety of conditions that include renal failure, and insulin resistant conditions [ 30 , 31 ]. This is why, in this study, we excluded hypertensive patients with associated diabetes or renal failure.…”

“…Serum Lp(a) levels vary over a broad range and the apo(a) gene is the major gene controlling these levels [ 3 ]. A number of retrospective and prospective studies have shown that high serum levels of Lp(a) are an independent risk factor for cardiovascular diseases [ 4 ]. In addition, previous studies conducted in large groups of patients with high blood pressure have demonstrated that serum Lp(a) levels predict the presence and severity of hypertensive vascular damage [ 5 ].…”

“…In addition, previous studies conducted in large groups of patients with high blood pressure have demonstrated that serum Lp(a) levels predict the presence and severity of hypertensive vascular damage [ 5 ]. Although the functions of Lp(a) in physiology are unknown, its pathogenic mechanisms have been widely investigated, showing proatherogenic, proinflammatory, and, due to its structural homology with plasminogen [ 6 ], prothrombotic effects [ 4 , 7 ]. These effects of Lp(a), together with its interaction with the hemostatic and the renin-angiotensin system, might make it specifically to vascular damage in subjects with high blood pressure [ 8 ].…”

Circulating Levels of PCSK9, ANGPTL3 and Lp(a) in Stage III Breast Cancers

“…Lp(a) is an LDL-like molecule that has caught a lot of attention these past few years in the eld of cardiometabolic diseases [46][47][48]. Elevated levels of Lp(a) represent an emerging risk factor for atherosclerosis and thrombogenic events [49][50][51].…”

Haematological Drugs Affecting Lipid Metabolism and Vascular Health

“…However, many patients with normal LDL-C levels (genetically determined or after cholesterol lowering therapy) still have a residual CV risk. Among the principal metabolic lipid-related CV risk factors implicated in this residual risk, hypertriglyceridaemia, atherogenic lipoprotein subfractions, reduced concentrations or altered function of HDL and elevated levels of Lp a are sure to play a significant role [ 1 , 2 , 3 , 4 ]. Many dyslipidaemias are of genetic origin (primary dyslipidaemias), but others are secondary to other conditions such as: diabetes mellitus, hypothyroidism, chronic kidney disease, cholestasis, and drugs.…”