In patients with aortic stenosis (AS), elevated blood levels of lipoprotein(a) (Lp[a]) and oxidized phospholipids (OxPL) are associated with accelerated valve calcification and disease progression, according to study results published in the Journal of the American College of Cardiology.

Lipoprotein(a) is a major carrier of OxPL and is a causal risk factor for AS; however, it is unknown whether elevated Lp(a) and OxPL drive disease progression and therefore could be targets for therapeutic interventions. Thus, researchers combined 2 prospective cohorts and measured Lp(a) and OxPL on apolipoprotein B-100 levels in 145 elderly patients with AS who underwent baseline 18F-sodium fluoride positron emission tomography, repeat computed tomography calcium scoring, and repeat echocardiography.

Compared with patients in the lower Lp(a) tertiles, they found that patients in the top Lp(a) tertile had increased valve calcification activity, increased progression of valvular computed tomography calcium score, faster hemodynamic progression on echocardiography, and increased risk for aortic valve replacement and death.

They observed similar results with OxPL on apolipoprotein B-100. The researchers conducted in vitro studies that demonstrated that these observations appear to be driven by the pro-osteogenic effects of Lp(a) on valvular interstitial cells that are mediated through its OxPL content and therefore could be alleviated with the E06 antibody that binds to and inactivates OxPL.

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The investigators concluded: “In patients with AS, Lp(a) and OxPL drive valve calcification and disease progression.

They added, “These findings suggest lowering Lp(a) or inactivating OxPL may slow AS progression and provide a rationale for clinical trials to test this hypothesis.”

Reference

Zheng KH, Tsimikas S, Pawade T, et al. Lipoprotein(a) and oxidized phospholipids promote valve calcification in patients with aortic stenosis. JACC. 2019;73(17):2150-2162.