A predictor of atheroma progression in patients achieving very low levels of low-density lipoprotein cholesterol

Abstract

An aggressive reduction in low-density lipoprotein cholesterol (LDL-C) with statins produces regression or stabilization of coronary artery plaques. However, after achieving very low levels of LDL-C, atheroma regression is not observed in all patients. The purpose of the present study was to evaluate the determinants of atheroma progression despite achieving very low levels of LDL-C. The effects of 8-month statin therapy on coronary atherosclerosis were evaluated using virtual histology intravascular ultrasound in the TRUTH study. Of these, 33 patients who achieved an on-treatment LDL-C level of <70 mg/dl were divided into 2 groups according to increase in plaque volume (progressors, n= 16) or decrease in plaque volume (regressors, n= 17) during an 8-month follow-up period. At the 8-month follow-up, serum LDL-C and apolipoprotein B levels were significantly lower in progressors than in regressors; however, significant increases in high-density lipoprotein cholesterol and apolipoprotein AI and decreases in high-sensitivity C-reactive protein and oxidized LDL were observed only in regressors. The changes in the n-3 to n-6 polyunsaturated fatty acid ratios significantly differed between the 2 groups. Multivariate regression analysis showed that a decrease in the eicosapentaenoic acid + docosahexaenoic acid/arachidonic acid ratio was a significant predictor associated with atheroma progression (β= -0.512, p= 0.004). In conclusions, n-3 to n-6 polyunsaturated fatty acid ratios affected coronary artery plaque progression and regression in patients who achieved very low levels of LDL-C during statin therapy.

Keywords: Atheroma; low-density lipoprotein cholesterol; polyunsaturated fatty acid; statin; virtual histology intravascular ultrasound.

Figure 1

Differences in changes in EPA/AA, DHA/AA, and EPA + DHA/AA ratios between progressors and regressors. There were significant differences in changes in the EPA/AA, DHA/AA, and EPA + DHA/AA ratios between the 2 groups. *p<0.05, **p<0.01, and ***p<0.0001 compared to baseline.

Figure 2

Correlations between percentage change in plaque volume and changes in the EPA/AA, DHA/AA, and EPA + DHA/AA ratios during statin therapy. Percentage change in plaque volume was moderately and negatively correlated with changes in the EPA/AA, DHA/AA, and EPA + DHA/AA ratios during statin therapy. Among n-3 to n-6 PUFA ratios, the EPA + DHA/AA ratio showed the greatest correlation coefficient between the n-3 to n-6 PUFA ratios and percentage change in plaque volume.