Evidence-based assessment of lipoprotein(a) as a risk biomarker for cardiovascular diseases – Some answers and still many questions

Abstract

The present article is aimed to outline the current state of knowledge regarding the effects of lipoprotein(a) (Lp(a)) on cardiovascular disease (CVD) risk by summarizing the recent results of studies, meta-analyses and systematic reviews. The literature supports the predictive value of Lp(a) on CVD outcomes, although the effect size is modest. Lp(a) would also appear to have an effect on cerebrovascular outcomes, with the effect appearing even smaller than that for CVD outcomes. Consideration of apolipoprotein apolipoprotein(a) (apo (a)) isoforms and LPA genetics in relation to the simple assessment of Lp(a) concentration may enhance improving clinical practice in vascular medicine. We also describe recent advances in Lp(a) research (including therapies) and highlight areas where further research is needed such as the measurement of Lp(a) and its involvement in additional pathophysiological processes.

Lipoprotein(a) and inhibitors of proprotein convertase subtilisin/kexin type 9

“…We must also note that the benefits of the Lp(a)-lowering effects of PCSK9 inhibitors have not yet been proven in a clinical setting, given that no studies have fully investigated the long-term effects of PCSK9 inhibitors on the cardiovascular disease and/or the all-cause mortality. Extremely low levels of blood Lp(a) may be detrimental in some respects (e.g., the development of certain vascular diseases and/or cancers) (5,31), although no intervention studies have been performed to examine this point.…”

“…Lipoprotein(a) [Lp(a)] is a unique lipoprotein particle with a composition similar to that of LDL, including apolipoprotein (apo) B-100, which is bound to apo(a) (a glycoprotein) by a disulfide bridge (3)(4)(5). Apo(a) contains a specific sequence, such as kringle IV, similar to plasminogen (a fibrinolytic molecule) (3)(4)(5).…”

“…Lipoprotein(a) [Lp(a)] is a unique lipoprotein particle with a composition similar to that of LDL, including apolipoprotein (apo) B-100, which is bound to apo(a) (a glycoprotein) by a disulfide bridge (3)(4)(5). Apo(a) contains a specific sequence, such as kringle IV, similar to plasminogen (a fibrinolytic molecule) (3)(4)(5). Although the patho-biological role of Lp(a) is not completely clear, Lp(a) is considered to be a contributor to atherothrombosis on the basis of its LDL-like property and its competitive homology to plasminogen (3)(4)(5).…”

“…Apo(a) contains a specific sequence, such as kringle IV, similar to plasminogen (a fibrinolytic molecule) (3)(4)(5). Although the patho-biological role of Lp(a) is not completely clear, Lp(a) is considered to be a contributor to atherothrombosis on the basis of its LDL-like property and its competitive homology to plasminogen (3)(4)(5). Indeed, epidemiological and clinical studies have shown a high Lp(a) level to be a risk factor for cardiovascular disease (i.e., coronary heart disease, aortic aneurysm, peripheral artery disease, ischemic stroke) (5)(6)(7)(8)(9).…”

“…The general consensus holds that the Lp(a) level is primarily determined genetically by the LPA gene sites responsible for the encoding of apo(a), and the Lp(a) level does not necessarily parallel the level of other lipoprotein species (3)(4)(5). Of interest, the Lp(a) level is reported to be elevated under certain clinical conditions, such as in patients with familial hypercholesterolemia (10)(11)(12).…”