Initial decrease in the lipoprotein(a) level is a novel prognostic biomarker in patients with acute coronary syndrome

Abstract

Background: Lipoprotein(a) [Lp(a)] is a causal risk factor for atherosclerotic cardiovascular diseases; however, its role in acute coronary syndrome (ACS) remains unclear.

Aim: To investigate the hypothesis that the Lp(a) levels are altered by various conditions during the acute phase of ACS, resulting in subsequent cardiovascular events.

Methods: From September 2009 to May 2016, 377 patients with ACS who underwent emergent coronary angiography, and 249 who completed ≥ 1000 d of follow-up were enrolled. Lp(a) levels were measured using an isoform-independent assay at each time point from before percutaneous coronary intervention (PCI) to 48 h after PCI. The primary endpoint was the occurrence of major adverse cardiac events (MACE; cardiac death, other vascular death, ACS, and non-cardiac vascular events).

Results: The mean circulating Lp(a) level decreased significantly from pre-PCI (0 h) to 12 h after (19.0 mg/dL to 17.8 mg/dL, P < 0.001), and then increased significantly up to 48 h after (19.3 mg/dL, P < 0.001). The changes from 0 to 12 h [Lp(a)Δ0-12] significantly correlated with the basal levels of creatinine [Spearman's rank correlation coefficient (SRCC): -0.181, P < 0.01] and Lp(a) (SRCC: -0.306, P < 0.05). Among the tertiles classified according to Lp(a)Δ0-12, MACE was significantly more frequent in the lowest Lp(a)Δ0-12 group than in the remaining two tertile groups (66.2% vs 53.6%, P = 0.034). A multivariate analysis revealed that Lp(a)Δ0-12 [hazard ratio (HR): 0.96, 95% confidence interval (95%CI): 0.92-0.99] and basal creatinine (HR: 1.13, 95%CI: 1.05-1.22) were independent determinants of subsequent MACE.

Conclusion: Circulating Lp(a) levels in patients with ACS decreased significantly after emergent PCI, and a greater decrease was independently associated with a worse prognosis.

Keywords: Acute coronary syndrome; Lipoprotein (a); Major adverse cardiac events; Percutaneous coronary intervention; Prognosis.

Figure 1

Flow diagram of the inclusion of study subjects. ACS: Acute coronary syndrome; CAG: Coronary angiography.

Figure 2

Cumulative freedom from the risk of major adverse cardiac events during three years of follow-up. Patients classified into the second (T2) and third (T3) tertiles of the change in lipoprotein(a) [Lp(a)] circulating levels of Lp(a) after percutaneous coronary intervention for acute coronary syndrome, The changes from 0 to 12 h [Lp(a)Δ0-12], showed significantly favorable outcomes compared to those classified into the first tertile (T1) in terms of all-cause death, nonfatal myocardial infarction and stroke, or new angina pectoris (log-rank test χ² = 4.23, ^aP < 0.05). MACE: Major adverse cardiac events.