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Role of HDL function and LDL atherogenicity on cardiovascular risk: A comprehensive examination
Álvaro Hernáez1,2,3, María Trinidad Soria-Florido4,5, Helmut Schröder4,6
1Cardiovascular Risk, Nutrition and Aging Research Unit, August Pi i Sunyer Biomedical Research Institute (IDIBAPS), Barcelona, Spain.
Insights
Cardiovascular risk is linked to lipoprotein particle traits, not just cholesterol levels. Specific risk factors like diabetes and age impact low-density lipoprotein (LDL) and high-density lipoprotein (HDL) particle function and structure.
Area of Science:
- Lipid metabolism and cardiovascular disease
- Atherosclerosis and lipoprotein research
- Clinical lipidology
Background:
- Lipoprotein functionality (HDL) and atherogenic traits (LDL) offer deeper insights into cardiovascular disease (CVD) risk than cholesterol levels alone.
- The specific impact of various cardiovascular risk factors on these lipoprotein properties remains incompletely understood.
Purpose of the Study:
- To investigate the association between specific lipoprotein properties and overall cardiovascular risk.
- To identify which lipoprotein characteristics are linked to individual cardiovascular risk factors.
Main Methods:
- Cross-sectional analysis of baseline data from PREDIMED trial participants.
- Assessment of HDL functionality and LDL atherogenicity traits in relation to 10-year coronary risk scores (Framingham-REGICOR).
- Evaluation of associations with classical cardiovascular risk factors.
Main Results:
- Higher cardiovascular risk scores correlated with reduced HDL cholesterol efflux, smaller/oxidized HDL particles, and smaller, less oxidation-resistant LDL particles.
- Type 2 diabetes was linked to smaller, more oxidized LDLs; dyslipidemia to smaller HDLs with impaired cholesterol metabolism.
- Obesity associated with reduced HDL/LDL size and HDL esterification capacity; male sex with increased HDL oxidation and reduced HDL vasodilatory capacity.
- Advanced age correlated with small, oxidized, cytotoxic LDL particles.
Conclusions:
- Dysfunctional HDL and atherogenic LDL particles are prevalent in individuals with high cardiovascular risk.
- Dyslipidemia and male sex are primarily associated with HDL dysfunction.
- Type 2 diabetes and advanced age are predominantly linked to LDL atherogenicity.
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.
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