A cross-sectional and longitudinal study between association of n-3 polyunsaturated fatty acids derived from fish consumption and high-density lipoprotein heterogeneity

Abstract

Decreased high-density lipoprotein (HDL) particle size, cholesterol poor, apolipoprotein A-I-rich HDL particles leading to smaller HDL particle size, may be associated with an anti-atherosclerotic effect. The data are sparse regarding the relationship between n-3 polyunsaturated fatty acids [n-3 PUFAs: eicosapentaenoic acid (EPA), docosahexaenoic acid (DHA)] and HDL particle size. This study was designed as a hospital-based cross-sectional study to investigate the relationship between the serum levels of n-3 PUFAs and the HDL-cholesterol/apolipoprotein A-1 ratio, as estimated by the HDL particle size, in patients with the presence of one or more risk factors for atherosclerotic cardiovascular disease (ASCVD). Six hundred and forty sequential patients were enrolled in this study. The serum levels of EPA and DHA showed a strong correlation (r = 0.736, p < 0.0001). However, in a multivariate regression analysis after adjustment for ASCVD risk factors, increased serum DHA (β = - 0.745, p = 0.021), but not serum EPA (β = - 0.414, p = 0.139) or EPA + DHA (β = 0.330, p = 0.557) level, was identified as an independent indicator of decreased HDL particle size. In 476 patients followed up for at least 6 months, the absolute change (Δ) in the HDL-cholesterol/apolipoprotein A-1 ratio decreased significantly as the quartile of the Δ DHA level increased (p = 0.014), whereas no significant difference in the Δ HDL-cholesterol/apolipoprotein A-1 ratio was noted with the increase in the quartile of the Δ EPA level. Moreover, a multivariate regression analysis identified increased DHA level and decreased estimated low-density lipoprotein (LDL) particle size measured relative to the mobility value of LDL with polyacrylamide gel electrophoresis (i.e., relative LDL migration: LDL-Rm value), as independent predictors of decreased HDL-cholesterol/apolipoprotein A-1 ratio (β = - 0.171, p = 0.0003 and β = - 0.142, p = 0.002). The results suggest that increased serum DHA level, but not EPA level, might be associated with decreased HDL-cholesterol/apolipoprotein A-1 ratio, an indicator of estimated HDL particle size. Further studies are needed to investigate the useful clinical indices and outcomes of these patients. Clinical Trial Registration Information UMIN ( http://www.umin.ac.jp/ ), Study ID: UMIN000010603.

Keywords: Apolipoprotein A-1; Docosahexaenoic acid; Eicosapentaenoic acid; High-density lipoprotein; n-3 Polyunsaturated fatty acid.

Fig. 1

Association of the HDL-C/apoA-1 ratio with the serum DHA level. The patients were divided into quartiles of the DHA concentration. The DHA according to quartile was as follows: 35.7–100.7 μg/mL (quartile 1: n = 160), 100.8–128.7 μg/mL (quartile 2: n = 160), 128.9–160.5 μg/mL (quartile 3: n = 160), and 160.7–451.8 μg/mL (quartile 4: n = 160). The serum HDL-C level tended to increase as the serum DHA quartile increased, but it did not reach statistical significance. While the serum apoA-1 level increased significantly as the serum DHA quartile increased. The serum HDL-C/apoA-1 ratio accordingly decreased significantly as the serum DHA quartile increased. HDL-C high-density lipoprotein cholesterol, apoA-1 apolipoprotein A-1, DHA docosahexaenoic acid

Fig. 2

Association of the HDL-C/apoA-1 ratio with the serum EPA level. The patients were divided into quartiles of the EPA concentration. The ranges according to the quartile of EPA were follows: 6.2–40.0 μg/mL (quartile 1: n = 160), 40.1–62.8 μg/mL (quartile 2: n = 160), 63.0–92.2 μg/mL (quartile 3: n = 160), and 92.4–373.5 μg/mL (quartile 4: n = 160). The serum HDL-C level increased significantly as the serum EPA quartile increased, while the serum apoA-1 level also increased significantly as the serum EPA quartile increased. Accordingly, no significant change in the serum HDL-C/apoA-1 ratio is found as the serum EPA quartile increased. HDL-C high-density lipoprotein cholesterol, apoA-1 apolipoprotein A-1, EPA eicosapentaenoic acid

Fig. 3

Association of the Δ HDL-C/apoA-1 ratio with the Δ serum DHA level. The Δ HDL-C/apoA-1 ratio correlated negatively with the Δ DHA level. Similarly, the Δ HDL-C/apoA-1 ratio decreased significantly as the Δ DHA quartile increased. HDL-C high-density lipoprotein cholesterol, apoA-1 = apolipoprotein A-1, DHA docosahexaenoic acid, Δ absolute change from baseline to 6-month follow-up

Fig. 4

Title: Association between the HDL-C/apoA-1 ratio and LDL-Rm value associated, an indicator of LDL particle size with the serum TG level. HDL-C high-density lipoprotein cholesterol, apoA-1 apolipoprotein A-1, LDL-Rm relative LDL migration, TG triglyceride, Δ absolute change from baseline to 6-month follow-up

Fig. 5

Association between HDL-C/apoA-1 ratio AND LDL-Rm value. A positive correlation was observed between the LDL-Rm value and HDL-C/apoA-1, and the ∆ LDL-Rm value was also found to be weakly correlated with the ∆ HDL-C/apoA-1 ratio. HDL-C high-density lipoprotein cholesterol, apoA-1 apolipoprotein A-1, LDL-Rm relative LDL migration, Δ absolute change from baseline to 6-month follow-up