Elevated lipoprotein(a) is independently associated with the presence of significant coronary stenosis in de-novo patients with stable chest pain

Background: The role of lipoprotein(a) (Lp(a)) in the risk-assessment of patients with de-novo stable chest pain is sparsely investigated. We assessed the association between Lp(a) concentration and the presence of coronary stenosis on coronary computed tomography (CT) angiography in a broad population of patients referred with stable chest pain.

Methods: Lp(a) measurements and coronary CT angiography were performed in 4,346 patients with stable chest pain and no previous history of coronary artery disease. The patients were included in the trial program, the Danish study of Non-Invasive testing in Coronary artery disease, Dan-NICAD. The prevalence and odds ratios for stenosis were calculated comparing normal Lp(a) (< 20 nmol/l) with moderately elevated (20 to <125 nmol/l), high (125 to <200 nmol/l), and very high (≥200 nmol/l) Lp(a) concentrations in both univariate and multivariate analyses.

Results: In total, 2,418 (55.6%), 1,276 (29.4%), 425 (9.8%), and 227 (5.2%) patients had normal, moderately elevated, high, and very high Lp(a) levels, respectively. The prevalences of coronary stenosis increased with increasing Lp(a) concentration (n = 569 (23.5%), n = 328 (25.7%), n = 129 (30.4%), and n = 77 (33.9%) in patients with normal, moderately elevated, high, and very high Lp(a), respectively). Likewise, the prevalence of patients with multivessel disease increased with increasing Lp(a) concentration (n = 252 (10.4%), n = 149 (11.7%), n = 61 (14.4%), and n = 41 (18.1%) in patients with normal, moderately elevated, high, and very high Lp(a), respectively). In an unadjusted model, odds ratios for stenosis increased with increasing Lp(a) concentrations (odds ratio (95% CI): 1.12 (0.96-1.31), 1.42 (1.13-1.77), and 1.67 (1.24-2.22) for moderately elevated, high, and very high Lp(a) versus normal Lp(a), respectively). Adjustment for age, sex, and cardiovascular risk factors did not affect the association.

Conclusions: In stable, symptomatic patients without established coronary artery disease, Lp(a) levels are positively associated with the presence of coronary stenosis on coronary CT angiography. These findings may warrant using Lp(a) in the diagnostic management of patient with suspected coronary artery disease.

Trial registration: The three studies within the Dan-NICAD program are registered on ClinicalTrials.gov: Dan-NICAD, NCT02264717, https://clinicaltrials.gov/study/NCT02264717?term=dan-nicad&rank=1. Dan-NICAD 2, NCT03481712, https://clinicaltrials.gov/study/NCT03481712?term=dan-nicad&rank=3. Dan-NICAD 3, NCT04707859, https://clinicaltrials.gov/study/NCT04707859?term=dan-nicad&rank=2.