Small Dense Low-Density Lipoprotein Cholesterol and Carotid Intimal Medial Thickness Progression

J Atheroscler Thromb. 2020 Oct 1;27(10):1108-1122. doi: 10.5551/jat.54130. Epub 2020 Apr 10.

Abstract

Aim: The association between small dense low-density lipoprotein cholesterol (sdLDL-C) levels and carotid intimal medial thickness (cIMT) progression has not been evaluated fully. We assessed specialized lipoproteins, including sdLDL-C, with regard to cIMT progression in a prospective observational study in Japan.

Methods: Plasma total cholesterol, direct LDL-C, sdLDL-C, LDL-triglycerides (LDL-TG), high-density lipoprotein cholesterol (HDL-C), HDL2-C, HDL3-C, triglycerides, Lp(a), and adiponectin were measured in 2,030 men and women (median age 59 years, free of cardiovascular disease (CVD) and off cholesterol lowering medication). At both baseline and after a five-year follow-up, cIMT was assessed. Univariate, multivariate regression, and least square analyses were performed to examine the relationships between direct LDL-C, sdLDL-C, and other lipoproteins with cIMT progression.

Results: The median cIMT at baseline was 0.63 mm and five-year progression was 0.18 mm. After adjustment for standard CVD risk factors, including age, gender, systolic blood pressure, total cholesterol, HDL-C, smoking, diabetes, and hypertension treatment, only direct LDL-C, sdLDL-C, and the sdLDL-C/LDL-C ratio were associated with cIMT progression. Even in subjects with direct LDL-C <100 mg/dL, who were considered at low CVD risk, elevated sdLDL-C were associated with cIMT progression (P for trend=0.009) in a model with established CVD risk factors, although the sdLDL-C/LDL-C ratio did not. Those correlations did not change by including triglycerides as a controlling factor or excluding premenopausal women from the analyzed population.

Conclusions: Small dense LDL-C has a stronger relationship with cIMT progression than LDL-C does; therefore, measuring sdLDL-C may allow for the formulation of optimal therapy for CVD prevention.

Keywords: Atherosclerosis; Cardiovascular diseases; Carotid intimal medial thickness; Small dense LDL cholesterol.

Publication types

  • Observational Study

MeSH terms

  • Adiponectin / biosynthesis
  • Aged
  • Anticholesteremic Agents / pharmacology
  • Atherosclerosis / blood
  • Cardiovascular Diseases / blood*
  • Carotid Arteries
  • Carotid Intima-Media Thickness*
  • Cholesterol, HDL / metabolism
  • Cholesterol, LDL / metabolism*
  • Disease Progression
  • Female
  • Humans
  • Japan
  • Least-Squares Analysis
  • Lipoproteins / metabolism
  • Male
  • Middle Aged
  • Multivariate Analysis
  • Prospective Studies
  • Regression Analysis
  • Risk
  • Risk Factors

Substances

  • Adiponectin
  • Anticholesteremic Agents
  • Cholesterol, HDL
  • Cholesterol, LDL
  • Lipoproteins