The influence of triglycerides on small dense low-density lipoprotein cholesterol levels is attenuated in low low-density lipoprotein-cholesterol range: Implications for the negative results of the PROMINENT trial

J Diabetes Investig. 2023 Jul;14(7):902-906. doi: 10.1111/jdi.14013. Epub 2023 Apr 4.

Abstract

The Pemafibrate to Reduce Cardiovascular Outcomes by Reducing Triglycerides in Patients with Diabetes (PROMINENT) trial failed to show the preventive effects of pemafibrate, a triglyceride (TG)-lowering drug, on atherosclerotic cardiovascular disease in patients with type 2 diabetes and dyslipidemia. We recently reported that TG-lowering with pemafibrate did not decrease the calculated small dense (sd) low-density lipoprotein cholesterol (LDL-C), and speculated that the effect of TG on sdLDL-C is attenuated in low LDL-C levels. This report examined this possibility in 1,508 patients with type 2 diabetes and 670 healthy controls. LDL-C ranges were classified as ≤69, 70-99, 100-139 and 140≤ mg/dL. The slope of the regression curve between sdLDL-C and TG was found to flatten as LDL-C decreased; 0.18, 0.13, 0.10 and 0.04 for controls, and 0.18, 0.13, 0.09 and 0.07 for diabetes patients. Correspondingly, the lower the LDL-C range, the lower the sdLDL-C/TG ratio. These results suggest that when LDL-C is tightly controlled, TG-lowering has only a weak inhibitory effect on sdLDL-C.

Keywords: PROMENENT trial; Small dense low-density lipoprotein; Triglycerides.

MeSH terms

  • Cholesterol, HDL
  • Cholesterol, LDL
  • Diabetes Mellitus, Type 2* / complications
  • Diabetes Mellitus, Type 2* / drug therapy
  • Humans
  • Negative Results
  • Triglycerides

Substances

  • Triglycerides
  • Cholesterol, LDL
  • (R)-2-(3-((benzoxazol-2-yl-d4 (3-(4-methoxyphenoxy-d7)propyl)amino)methyl)phenoxy) butanoic acid
  • Cholesterol, HDL