Higher Lp(a) levels associated with more rapid hemodynamic progression of aortic stenosis

10/10/2024

In a meta-analysis of 5 prospective cohort studies among patients with calcific aortic valve stenosis, higher plasma Lp(a) levels were associated with an increased rate of hemodynamic progression as assessed by echocardiography.

This summary is based on the publication of Arsenault BJ, Loganath K, Girard A, et al. - Lipoprotein(a) and Calcific Aortic Valve Stenosis Progression: A Systematic Review and Meta-Analysis. JAMA Cardiol. 2024 Sep 1;9(9):835-842. doi: 10.1001/jamacardio.2024.1882

Introduction and methods

Background

Elevated plasma Lp(a) levels are associated with the risk of developing calcific aortic valve stenosis [1-3]. However, it is not clear whether they also predict the

progression

of this disease, as several studies, with relatively small sample sizes, have shown conflicting results [4-6]. Therefore, there is a need for larger multicenter studies using echocardiography, which is used in routine clinical practice to monitor aortic stenosis severity.

Aim of the study

The study aim was to examine the association between plasma Lp(a) levels and hemodynamic aortic stenosis progression as assessed by echocardiography in patients with aortic stenosis.

Methods

The authors performed an individual patient-level meta-analysis of 5 prospective clinical cohort studies on aortic stenosis (ASTRONOMER, PROGRESSA, Ring of Fire, SALTIRE, SALTIRE2) conducted in Canada or the UK. Plasma Lp(a) levels and serial echocardiographic assessments of aortic stenosis severity and hemodynamic progression were available for 710 patients.

Outcomes

The primary endpoint was the annual change in peak aortic jet velocity (Vpeak). Exploratory endpoints were the associations of exposure to high Lp(a) levels with mean transvalvular pressure gradient and aortic valve area.

Main results

• Meta-analysis of the data from the 5 studies showed patients with plasma Lp(a) levels in the top tertile had a faster Vpeak progression than those in the bottom Lp(a) tertile (ratio of means: 1.41; 95%CI: 1.13–1.75), with no evidence of heterogeneity across the individual cohorts (I²=0%; τ²=0).

• When Lp(a) levels were analyzed as a continuous variable, higher levels were also associated with faster Vpeak progression (Pearson’s r: 0.11; 95%CI: 0.03–0.18; I²=0%; τ²=0).

• In addition, patients in the top Lp(a) tertile showed a faster progression of the mean transvalvular gradient than those in the bottom Lp(a) tertile (ratio of means: 1.57; 95%CI: 1.18–2.10; I²=0%; τ²=0), as did patients with higher versus lower Lp(a) levels (Pearson’s r: 0.14; 95%CI: 0.06–0.22; I²=0%; τ²=0).

• In contrast, there was no association between Lp(a) tertiles and annualized progression rates of the aortic valve area (ratio of means: 1.23; 95%CI: 0.71–2.12), nor when Lp(a) concentrations were analyzed as a continuous variable.

• Analysis of the individual cohorts demonstrated statistically significant associations between Lp(a) tertiles and increased annualized progression rates of the Vpeak (P=0.04) and mean transvalvular gradient (P=0.02) only in the ASTRONOMER trial. Similar results were observed when Lp(a) levels were analyzed as a continuous variable.

Conclusion

In this meta-analysis of 5 prospective cohort studies, higher plasma Lp(a) levels were associated with increased progression rates of the Vpeak and mean transvalvular gradient, but not aortic valve area, in patients with calcific aortic valve stenosis. The authors believe their “data would suggest Lp(a) is associated not only with incident aortic stenosis, but also with progression of aortic stenosis, [and] Lp(a) therefore represents an important potential therapeutic target in aortic stenosis.”

Find this article online at JAMA Cardiol.

References

  1. Thanassoulis G, Campbell CY, Owens DS, et al; CHARGE Extracoronary Calcium Working Group. Genetic associations with valvular calcification and aortic stenosis. N Engl J Med. 2013;368(6):503-512. doi:10.1056/NEJMoa1109034
  2. Kamstrup PR, Tybjærg-Hansen A, Nordestgaard BG. Elevated lipoprotein(a)and risk of aortic valve stenosis in the general population. J Am Coll Cardiol. 2014;63(5):470-477. doi:10.1016/j.jacc.2013.09.038
  3. Arsenault BJ, Boekholdt SM, Dubé MP, et al. Lipoprotein(a) levels, genotype, and incident aortic valve stenosis: a prospective mendelian randomization study and replication in a case-control cohort. Circ Cardiovasc Genet. 2014;7(3):304-310. doi:10.1161/CIRCGENETICS.113.000400
  4. Kaiser Y, van der Toorn JE, Singh SS, e tal. Lipoprotein (a) is associated with the onset but not the progression of aortic valve calcification. Eur Heart J. 2022;43(39):3960-3967. doi:10.1093/eurheartj/ehac377
  5. Zheng KH, Tsimikas S, Pawade T, et al. Lipoprotein(a) and oxidized phospholipids promote valve calcification in patients with aortic stenosis. J Am Coll Cardiol. 2019;73(17):2150-2162. doi:10.1016/j.jacc.2019.01.070
  6. Capoulade R, Chan KL, Yeang C, et al. Oxidized phospholipids, lipoprotein(a), and progression of calcific aortic valve stenosis. J Am Coll Cardiol. 2015;66(11):1236-1246. doi:10.1016/j.jacc.2015.07.020
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