Excess weight mediates changes in HDL pool that reduce cholesterol efflux capacity and increase antioxidant activity

Nutr Metab Cardiovasc Dis. 2020 Feb 10;30(2):254-264. doi: 10.1016/j.numecd.2019.09.017. Epub 2019 Sep 23.

Abstract

Background and aim: Obesity-related decline in high-density lipoprotein (HDL) functions such as cholesterol efflux capacity (CEC) has supported the notion that this lipoprotein dysfunction may contribute for atherogenesis among obese patients. We investigated if potentially other HDL protective actions may be affected with weight gain and these changes may occur even before the obesity range in a cross-sectional analysis.

Methods and results: Lipid profile, body mass index (BMI), biochemical measurements, and carotid intima-media thickness (cIMT) were obtained in this cross-sectional study with 899 asymptomatic individuals. Lipoproteins were separated by ultracentrifugation and HDL physical-chemical characterization, CEC, antioxidant activity, anti-inflammatory activity, HDL-mediated platelet aggregation inhibition were measured in a randomly-selected subgroup (n = 101). Individuals with increased HDL-C had an attenuated increase in cIMT with elevation of BMI (interaction effect β = -0.054; CI 95% -0.0815, -0.0301). CEC, HDL-C, HDL size and HDL-antioxidant activity were negatively associated with cIMT. BMI was inversely correlated with HDL-mediated inhibition of platelet aggregation (Spearman's rho -0.157, p < 0.03) and CEC (Spearman's rho -0.32, p < 0.001), but surprisingly it was directly correlated with the antioxidant activity (Spearman's rho 0.194, p = 0.052). Thus, even in non-obese, non-diabetic individuals, increased BMI is associated with a wide change in protective functions of HDL, reducing CEC and increasing antioxidant activity. In these subjects, decreased HDL concentration, size or function are related to increased atherosclerotic burden.

Conclusion: Our findings demonstrate that in non-obese, non-diabetic individuals, the increasing values of BMI are associated with impaired protective functions of HDL and concomitant increase in atherosclerotic burden.

Keywords: Atherosclerosis; Cholesterol efflux; HDL; HDL metabolism; Obesity.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Antioxidants / analysis
  • Biomarkers / blood
  • Body Mass Index
  • Carotid Artery Diseases / blood
  • Carotid Artery Diseases / diagnostic imaging
  • Carotid Artery Diseases / physiopathology
  • Carotid Intima-Media Thickness
  • Cholesterol, HDL / blood*
  • Cross-Sectional Studies
  • Dyslipidemias / blood*
  • Dyslipidemias / diagnosis
  • Dyslipidemias / physiopathology
  • Female
  • Humans
  • Male
  • Middle Aged
  • Overweight / blood*
  • Overweight / diagnosis
  • Overweight / physiopathology
  • Platelet Aggregation
  • Risk Assessment
  • Risk Factors
  • Weight Gain*
  • Young Adult

Substances

  • Antioxidants
  • Biomarkers
  • Cholesterol, HDL