Cardiovascular Risk and Lipoprotein(a) : beyond LDL cholesterol

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Background

Today, Lipoprotein(a) (Lp(a)) represents the best opportunity to be focused to deepen the current knowledge and to figure out novel diagnostic and therapeutic strategies.

Lp(a) is a lipoprotein first described in 1963 by Berg and coll. It is aa enigmatic cholesterol-rich, LDL-like particle, acknowledged for a proatherogenic and -maybe- prothrombotic potential. It has a unique structure having an additional apolipoprotein called apolipoprotein (a) (apo(a)) covalently linked to apoB100. Its plasma levels are strongly determined by genetic, inheritable tracts. Indeed, more than 90% of Lp(a) plasma levels are genetically determined. Moreover, apo(a) is codified by a gene related to the plasminogen one, and this aspect is often correlated to its prothrombotic potential.

Lp(a) plasma levels are associated with several aspects of cardiovascular disease. Although in the recent past only very high Lp(a) levels have been considered a risk factor, its relationship with CVD is nowadays considered to be continuous. GenomeWide Association Studies confirmed Lp(a) for a causal role in CVD, including atherosclerotic CVD, heart failure, peripheral artery disease, additionally to aortic valve stenosis.

The causal role has been confirmed also by the exploration of genetic variants conditioning very low Lp(a) values since birth, being the association with stroke, chronic kidney disease, aortic valve stenosis heart failure, peripheral artery disease and atherosclerotic coronary disease inverse in these subjects.
The relationship between Lp(a) and diabetes mellitus deserves a special mention; low Lp(a) levels have been suggested to be predictive of diabetes mellitus onset, while high Lp(a) levels are unlike in diabetes patients. Moreover, insulin-sensitivity has been suggested to be associated with Lp(a) levels change, being their higher in patients with a good status and higher in those with a poorer status.

A current challenge is represented by therapy: a specific Lp(a) lowering therapy is currently unavailable, although some molecule has been proved to change Lp(a) plasma levels. However, novel approaches and upcoming strategies are now in the spotlight: innovative, biotechnological therapies are behind the corner.

Original contributions, research papers, reviews, on pathophysiology, current state-of-the-art, techniques, drugs, novel mechanisms, and impact on cardiovascular risk and residual risk are awaited.

Keywords: lipoprotein A

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