Lipoprotein(a) and Long-Term Plaque Progression, Low-Density Plaque, and Pericoronary Inflammation

Abstract

Importance: Lipoprotein(a) (Lp[a]) is a causal risk factor for cardiovascular disease; however, long-term effects on coronary atherosclerotic plaque phenotype, high-risk plaque formation, and pericoronary adipose tissue inflammation remain unknown.

Objective: To investigate the association of Lp(a) levels with long-term coronary artery plaque progression, high-risk plaque, and pericoronary adipose tissue inflammation.

Design, setting, and participants: 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.

Exposures: The median scan interval was 10.2 years. Lp(a) was measured at follow-up using an isoform-insensitive assay. CCTA scans were analyzed with a previously validated artificial intelligence-based algorithm (atherosclerosis imaging-quantitative computed tomography).

Main outcome and measures: 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 (SD, 7.3) years and 153 were male (57%). Patients with Lp(a) levels of 125 nmol/L or higher had twice as high percent atheroma volume (6.9% vs 3.0%; P = .01) compared with patients with Lp(a) levels less than 125 nmol/L. Adjusted for other risk factors, every doubling of Lp(a) resulted in an additional 0.32% (95% 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 coronary artery and left anterior descending at baseline and follow-up.

Conclusions and relevance: 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.

Figure 1.. Association of Lipoprotein(a) (Lp[a]) With Plaque Burden and Coronary Computed Tomography Angiography (CCTA) Plaque Progression During Follow-Up

The whiskers show 95% CIs from the unadjusted linear mixed-effect models for the 10th (7 nmol/L), 50th (25 nmol/L), and 90th (221 nmol/L) percentiles of Lp(a) in this study for percent atheroma volume (A), percent noncalcified plaque volume (B), and percent calcified plaque volume (C) at baseline and follow-up (10.2 years).

Figure 2.. Association of Lipoprotein(a) (Lp[a]) With High-Risk Plaque and Pericoronary Inflammation

Adjusted odds ratios from logistic regression models for the presence low-density plaque and presence of increased pericoronary adipose tissue attenuation (PCATa). LAD indicates left anterior descending coronary artery; OR, odds ratio; RCA, right coronary artery.

Figure 3.. Coronary Plaque Progression and Pericoronary Inflammation With High and Low Lipoprotein(a) (Lp[a])

Two case examples of a patient with high (A) and low (B) Lp(a). Shown are baseline computed tomography angiography curved reformat (left) and straightened multiplanar reformatted (right) reconstructions of the right coronary artery (RCA) and pericoronary adipose tissue attenuation (PCATa) around the RCA. At baseline, patient A (high Lp[a]) had a percent atheroma volume (PAV) of 19.4%, a percent noncalcified plaque volume of 6.1%, and a percent noncalcified plaque volume of 13.3%, while RCA PCATa was −79.1 HU, above the scanner-specific threshold, indicative of pericoronary inflammation. During the 10-year follow-up, the plaque volumes for PAV, percent noncalcified plaque volume, and percent calcified plaque volume progressed to 30.0%, 12.2%, and 15.8% at follow-up (55% PAV increase, 100% percent noncalcified plaque volume increase, and 19% percent calcified plaque volume increase), indicative of important plaque progression. Patient B (low Lp[a]) had a baseline total plaque volume of 11.6%, an noncalcified plaque volume of 5.8%, and a calcified plaque volume of 5.8%, while RCA PCATa was −94.8 HU, below the scanner-specific threshold, indicating absence of pericoronary inflammation. During the 10-year follow-up, the plaque volumes for PAV, noncalcified plaque volume, and calcified plaque volume changed to 11.2%, 4.4%, and 6.7%, respectively (3% PAV decrease, 24% noncalcified plaque volume decrease, and 19% calcified plaque volume increase), indicative of plaque stabilization.