Role of HDL function and LDL atherogenicity on cardiovascular risk: A comprehensive examination

PLoS One. 2019 Jun 27;14(6):e0218533. doi: 10.1371/journal.pone.0218533. eCollection 2019.

Abstract

Background: High-density lipoprotein (HDL) functionality and low-density lipoprotein (LDL) atherogenic traits can describe the role of both particles on cardiovascular diseases more accurately than HDL- or LDL-cholesterol levels. However, it is unclear how these lipoprotein properties are particularly affected by different cardiovascular risk factors.

Objective: To determine which lipoprotein properties are associated with greater cardiovascular risk scores and each cardiovascular risk factor.

Methods: In two cross-sectional baseline samples of PREDIMED trial volunteers, we assessed the associations of HDL functionality (N = 296) and LDL atherogenicity traits (N = 210) with: 1) the 10-year predicted coronary risk (according to the Framingham-REGICOR score), and 2) classical cardiovascular risk factors.

Results: Greater cardiovascular risk scores were associated with low cholesterol efflux values; oxidized, triglyceride-rich, small HDL particles; and small LDLs with low resistance against oxidation (P-trend<0.05, all). After adjusting for the rest of risk factors; 1) type-2 diabetic individuals presented smaller and more oxidized LDLs (P<0.026, all); 2) dyslipidemic participants had smaller HDLs with an impaired capacity to metabolize cholesterol (P<0.035, all); 3) high body mass index values were associated to lower HDL and LDL size and a lower HDL capacity to esterify cholesterol (P<0.037, all); 4) men presented a greater HDL oxidation and lower HDL vasodilatory capacity (P<0.046, all); and 5) greater ages were related to small, oxidized, cytotoxic LDL particles (P<0.037, all).

Conclusions: Dysfunctional HDL and atherogenic LDL particles are present in high cardiovascular risk patients. Dyslipidemia and male sex are predominantly linked to HDL dysfunctionality, whilst diabetes and advanced age are associated with LDL atherogenicity.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Age Factors
  • Aged
  • Atherosclerosis / blood*
  • Atherosclerosis / complications*
  • Cardiovascular Diseases / blood*
  • Cardiovascular Diseases / etiology*
  • Cholesterol, HDL / blood
  • Cholesterol, LDL / blood
  • Cross-Sectional Studies
  • Diabetes Mellitus, Type 2 / blood
  • Diabetes Mellitus, Type 2 / complications
  • Dyslipidemias / blood
  • Dyslipidemias / complications
  • Female
  • Humans
  • Lipoproteins, HDL / blood*
  • Lipoproteins, LDL / blood*
  • Male
  • Middle Aged
  • Risk Factors
  • Sex Factors

Substances

  • Cholesterol, HDL
  • Cholesterol, LDL
  • Lipoproteins, HDL
  • Lipoproteins, LDL

Grants and funding

This work was supported by: Agència de Gestió d’Ajuts Universitaris i de Recerca (2017 SGR 222), Fundació La Marató de TV3 (201512.31), and Instituto de Salud Carlos III (CB06/03/0028 and PI15/00047). A.H. was funded by Instituto de Salud Carlos III (CD17/00122), M.-T.S.-F. was supported by Agència de Gestió d’Ajuts Universitaris i de Recerca (2015 FI_B 01042), and M. Fitó was supported by Instituto de Salud Carlos III (CES12/025). CIBERs of Pathophysiology of Obesity and Nutrition (CIBEROBN) and Cardiovascular Diseases (CIBERCV) are initiatives of the Instituto de Salud Carlos III, Madrid, Spain. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.