Mendelian randomisation confirms Lp(a) drives coronary disease, aortic stenosis, stroke and heart failure regardless of LDL control, a review revisiting two decades of evidence (Circ J 2020)

Original title: Lipoprotein(a) and Cardiovascular Diseases　- Revisited

Circ J · 24 April 2020 · 5

Jang AY, Han SH, Sohn IS, Oh PC, Koh KK

This review by Jang, Han, Sohn, Oh and Koh revisits Lp(a) role in cardiovascular disease two decades after its elevation was first linked to cardiovascular disease, a link initially undervalued for lack of a specific lowering therapy or proof that reducing it improves outcomes. Mendelian randomisation studies have since shown Lp(a) is causal for coronary artery disease, calcific aortic valve disease, stroke, and heart failure, independent of optimal LDL cholesterol management. Structurally, Lp(a) combines apoB100 (as in LDL) with apoA covalently bound, giving it both atherogenic and thrombo-inflammatory properties. Conventional therapies, statins, niacin and CETP inhibitors, have failed to meaningfully lower Lp(a), but PCSK9 inhibitors and antisense oligonucleotide technology show promising early Lp(a)-lowering results. The review discusses Lp(a) revisited importance and strategies to address residual cardiovascular risk in the statin era.

Original abstract

Two decades ago, it was recognized that lipoprotein(a) (Lp(a)) concentrations were elevated in patients with cardiovascular disease (CVD). However, the importance of Lp(a) was not strongly established due to a lack of both Lp(a)-lowering therapy and evidence that reducing Lp(a) levels improves CVD risk. Recent advances in clinical and genetic research have revealed the crucial role of Lp(a) in the pathogenesis of CVD. Mendelian randomization studies have shown that Lp(a) concentrations are causal for different CVDs, including coronary artery disease, calcified aortic valve disease, stroke, and heart failure, despite optimal low-density lipoprotein cholesterol (LDL-C) management. Lp(a) consists of apolipoprotein (apo) B100 covalently bound to apoA. Thus, Lp(a) has atherothrombotic traits of both apoB (from LDL) and apoA (thrombo-inflammatory aspects). Although conventional pharmacological therapies, such as statin, niacin, and cholesteryl ester transfer protein, have failed to significantly reduce Lp(a) levels, emerging new therapeutic strategies using proprotein convertase subtilisin-kexin type 9 inhibitors or antisesnse oligonucleotide technology have shown promising results in effectively lowering Lp(a). In this review we discuss the revisited important role of L(a) and strategies to overcome residual risk in the statin era.

Summary written by lp-a.org from the published abstract; figures as published. Page updated 18 August 2026. Methods.