Long-term effects of high Lp(a) on coronary plaque burden

In a prospective cohort study, higher Lp(a) levels were associated with increased progression of coronary plaque burden, more high-risk plaques, and more pericoronary inflammation over 10 years compared with lower Lp(a).

This summary is based on the publication of Nurmohamed NS, Gaillard EL, Malkasian S, et al. - Lipoprotein(a) and Long-Term Plaque Progression, Low-Density Plaque, and Pericoronary Inflammation. JAMA Cardiol. 2024 Sep 1;9(9):826-834. doi: 10.1001/jamacardio.2024.187

Introduction and methods

Background

As Lp(a) is a causal risk factor for ASCVD events, recent European guidelines recommend measuring the Lp(a) level at least once in every adult [1,2]. However, the long-term effects of Lp(a) on progression of coronary atherosclerotic plaques are unknown.

Aim of the study

The authors investigated the association of Lp(a) levels with long-term coronary artery plaque progression, high-risk plaque formation, and pericoronary adipose tissue inflammation.

Methods

In a prospective cohort study, 267 patients with suspected coronary artery disease (CAD) who underwent per-protocol serial coronary CT angiography (CCTA) imaging (median interscan interval: 10.2 years; IQR: 8.8–11.2) at the Academic Medical Center in Amsterdam, the Netherlands were included. Patients with a history of CAD were excluded, as were patients who underwent CABG following the baseline or follow-up CCTA image. CCTA images were analyzed using artificial intelligence–based software (atherosclerosis imaging-quantitative CT). Lp(a) plasma levels were measured at follow-up. They were considered to be equal throughout the study because Lp(a) levels are >90% genetically determined [1].

Outcomes

The 2 coprimary endpoints were the absolute changes in percent atheroma volume (PAV) and percent noncalcified plaque volume from baseline to follow-up. Secondary endpoints were the absolute change in percent calcified plaque volume from baseline to follow-up, as well as the presence of low-density noncalcified plaque—which is indicative of the inflammatory necrotic core in the plaque—and increased pericoronary adipose tissue attenuation at baseline and follow-up.

Main results

Changes in plaque volumes

• At baseline, patients with Lp(a) ≥125 nmol/L had a higher PAV (5.8%; IQR: 1.8%–13.2%) compared with those with Lp(a) <125 nmol/L (2.9%; IQR: 0.8%–9.1%; P=0.01). The absolute change in PAV from baseline to follow-up was 3.6% (IQR: 1.2%–7.8%) and 1.6% (IQR: 0.3%–5.4%), respectively (P=0.004).
• The percent noncalcified plaque volume at baseline was also higher in patients with Lp(a) ≥125 nmol/L than those with Lp(a) <125 nmol/L (4.0%; IQR: 1.4%–8.2% vs. 2.2%; IQR: 0.8%–5.7%; P=0.03), as was the absolute change in this coprimary endpoint during follow-up (1.1%; IQR: 0.2%–2.5% vs. 0.5%; IQR: 0.0%–-2.4%; P=0.01).
• Patients with Lp(a) ≥125 nmol/L had a higher percent calcified plaque volume than those with Lp(a) <125 nmol/L at both baseline (1.6%; IQR: 0.3%–5.3% vs. 0.3%; IQR: 0.0%–2.4%; P=0.003) and follow-up (2.2%; IQR: 0.2%–4.2%; P=0.004).
• In a linear mixed-effects model analysis adjusted for age, sex, and clinical risk factors (such as history of hypertension, LDL-c levels, T2D), every doubling of Lp(a) level was associated with a 0.72% (95%CI: 0.23%–1.21%; P=0.01) higher PAV at baseline and an additional 0.32% (95%CI: 0.04%–0.60%; P=0.03) increment in PAV for every 10 years of follow-up.
• For percent noncalcified plaque volume, every Lp(a) doubling was associated with a 0.38% (95%CI: 0.11%–0.66%; P=0.003) higher baseline value and a nonsignificant estimated 0.09% (95%CI: −0.06% to 0.24%; P=0.26) increment for every 10 years of follow-up.
• For percent calcified plaque volume, every Lp(a) doubling was associated with a 0.34% (95%CI: 0.04%–0.63%; P=0.03) higher baseline value and an additional 0.22% (95%CI: 0.00%–0.45%; P=0.05) increment for every 10 years of follow-up.

Association of Lp(a) with high-risk plaques and pericoronary inflammation

• Every Lp(a) doubling was associated with increased odds of the presence of low-density noncalcified plaque at baseline (OR: 1.23; 95%CI: 1.00–1.51; P=0.05) and follow-up (OR: 1.21; 95%CI: 1.01–1.45; P=0.04).
• Every Lp(a) doubling was associated with increased odds of the presence of pericoronary adipose tissue attenuation in the right coronary artery at baseline (OR: 1.22; 95%CI: 1.06–1.41; P=0.005) and follow-up (OR: 1.18; 95%CI: 1.02–1.36; P=0.02).
• Every Lp(a) doubling was also associated with increased odds of the presence of pericoronary adipose tissue attenuation in the left anterior descending coronary artery at baseline (OR: 1.24; 95%CI: 1.07–1.43; P=0.004) and follow-up (OR: 1.16; 95%CI: 1.01–1.34; P=0.04).

Conclusion

In this single-center, prospective, serial CCTA imaging cohort study, high Lp(a) levels (≥125 nmol/L) were associated with increased coronary plaque burden at baseline and more rapid progression during 10-year follow-up compared with low Lp(a) levels. In addition, low-density noncalcified plaque and pericoronary adipose tissue inflammation were more frequently observed in patients with higher Lp(a) levels. According to the authors, “the present analysis may also provide rationale for clinical trials to use serial imaging with quantitative plaque imaging endpoints to evaluate the efficacy of Lp(a)-lowering therapies.”

Find this article online at JAMA Cardiol.

References

1. Kronenberg F, Mora S, Stroes ESG, et al. Lipoprotein(a) in atherosclerotic cardiovascular disease and aortic stenosis: a European Atherosclerosis Society consensus statement. Eur Heart J. 2022;43(39):3925-3946. doi:10.1093/eurheartj/ehac361
2. Mach F, Baigent C, Catapano AL, et al; ESC Scientific Document Group. 2019 ESC/EAS Guidelines for the management of dyslipidaemias: lipid modification to reduce cardiovascular risk. Eur Heart J. 2020;41(1):111-188. doi:10.1093/eurheartj/ehz455