Lp(a) and Coronary Plaque Progression

Quick Takes

  • Findings from this single-center, serial cohort study showed a significant relationship between Lp(a) levels and coronary atherosclerosis with high-risk features on CCTA imaging.
  • Exposure of coronary artery endothelium to Lp(a) increases coronary artery plaque progression and pericoronary inflammation, and promotes development of low-density plaque.
  • Patients with Lp(a) levels of ≥125 nmol/L had twice as high percent atheroma volume (6.9% vs. 3.0%; p = 0.01) and after adjusting for other risk factors, every doubling of Lp(a) resulted in an additional 0.32% increment in percent atheroma volume during the 10 years of follow-up.

Study Questions:

What is the association of lipoprotein(a) (Lp[a]) levels with long-term coronary artery plaque progression, development of high-risk plaque, and pericoronary adipose tissue inflammation?

Methods:

This single-center prospective cohort study included 299 patients with suspected coronary artery disease (CAD) who underwent per-protocol repeated coronary computed tomography angiography (CCTA) imaging with an interscan interval of 10 years. Thirty-two patients were excluded because of coronary artery bypass grafting, resulting in a study population of 267 patients. Data for this study were collected from October 2008 to October 2022 and analyzed from March 2023 to March 2024. The median scan interval was 10.2 years. Lp(a) was measured at follow-up using an isoform-insensitive assay. The association between Lp(a) and change in percent plaque volumes was investigated in linear mixed-effects models adjusted for clinical risk factors. Secondary outcomes were presence of low-density plaque and presence of increased pericoronary adipose tissue attenuation at baseline and follow-up CCTA imaging.

Results:

The 267 included patients had a mean age of 57.1 (standard deviation, 7.3) years and 153 were male (57%). Patients with Lp(a) levels of ≥125 nmol/L had twice as high percent atheroma volume (6.9% vs. 3.0%; p = 0.01) compared with patients with Lp(a) levels <125 nmol/L. Adjusted for other risk factors, every doubling of Lp(a) resulted in an additional 0.32% (95% confidence interval [CI], 0.04-0.60) increment in percent atheroma volume during the 10 years of follow-up. Every doubling of Lp(a) resulted in an odds ratio of 1.23 (95% CI, 1.00-1.51) and 1.21 (95% CI, 1.01-1.45) for the presence of low-density plaque at baseline and follow-up, respectively. Patients with higher Lp(a) levels had increased pericoronary adipose tissue attenuation around both the right circumflex artery and left anterior descending at baseline and follow-up.

Conclusions:

In this long-term prospective serial CCTA imaging study, higher Lp(a) levels were associated with increased progression of coronary plaque burden and increased presence of low-density noncalcified plaque and pericoronary adipose tissue inflammation. These data suggest an impact of elevated Lp(a) levels on coronary atherogenesis of high-risk, inflammatory, rupture-prone plaques over the long-term.

Perspective:

Findings from this single-center, serial cohort study showed a significant relationship between Lp(a) levels and coronary atherosclerosis with high-risk features on CCTA imaging. Exposure of coronary artery endothelium to Lp(a) increases coronary artery plaque progression and pericoronary inflammation, and promotes development of low-density plaque. Patients with Lp(a) levels of ≥125 nmol/L had twice as high percent atheroma volume (6.9% vs. 3.0%; p = 0.01) and after adjusting for other risk factors, every doubling of Lp(a) resulted in an additional 0.32% increment in percent atheroma volume during the 10 years of follow-up. Study findings help to better understand the effect of Lp(a) on long-term longitudinal progression of coronary plaque. Trials evaluating therapies that lower Lp(a) and clinical outcomes are ongoing and may identify another treatment option for high-risk patients with atherosclerosis.

Clinical Topics: Dyslipidemia, Advanced Lipid Testing, Lipid Metabolism, Prevention

Keywords: Lipoprotein(a), Plaque, Atherosclerotic


< Back to Listings