Relative increase in production ratio of small dense low-density lipoprotein in acute coronary syndrome with high coronary plaque burden: an ex-vivo analysis.

The absolute value of small dense low-density lipoprotein (sd-LDL) including small LDL (s-LDL) and very small LDL (vs-LDL) has been shown to be associated with increased incidence of atherosclerosis. However, the impact of short-timeframe increases in sd-LDL on arteriosclerosis has not yet been elucidated. Therefore, we investigated the clinical roles of ex-vivo induced sd-LDL in acute coronary syndrome (ACS) using a novel method. This is a prospective, single-blind, and observational study that screened patients who underwent coronary angiography (CAG) for the treatment of ACS or investigation of heart-failure etiology between June 2020 and April 2022 (n = 247). After excluding patients with known diabetes mellitus and advanced renal disease, the patients were further divided into the ACS (n = 34) and control (non-obstructive coronary artery, n = 34) groups. The proportion of sd-LDL (s-LDL + vs-LDL) in total lipoproteins was observed before and after 2-h incubation at 37 ℃ (to approximate physiologic conditions) using 3% polyacrylamide gel electrophoresis. The coronary plaque burden was quantified upon CAG in the ACS group. There were no significant differences between the ACS and control groups in terms of clinical coronary risk factors. The baseline of large, medium, small, and very small LDL were comparable between the two groups. Following a 2-h incubation period, significant increases were observed in the ratios of s-LDL and vs-LDL in both the ACS and control groups (ACS, p = 0.01*; control, p = 0.01*). Notably, the magnitude of increase in sd-LDL was more pronounced in the ACS group compared to the control group, with s-LDL showing a significant difference (p = 0.03*) and vs-LDL showing a tread toward significance (p = 0.08). In addition, in both groups, there was a decrease in IDL and L-LDL, while M-LDL remained unchanged. The plaque burden index and rate of short-timeframe changes in both s-LDL (p = 0.01*) and vs-LDL (p = 0.04*) before and after incubation were significantly correlated in the ACS group. The enhanced production rate of sd-LDL induced under short-term physiologic culture in an ex-vivo model was greater in patients with ACS than in the control group. The increase in sd-LDL is positively correlated with coronary plaque burden. Short-timeframe changes in sd-LDL may serve as markers for the severity of coronary artery disease.