Cholesterol-Overloaded HDL Particles Are Independently Associated With Progression of Carotid Atherosclerosis in a Cardiovascular Disease-Free Population: A Community-Based Cohort Study | Journal Scan

Study Questions:

What is the association between cholesterol content of high-density lipoprotein (HDL) and atherosclerosis?


HDL particle number was measured by nuclear magnetic resonance spectroscopy in 930 participants (ages 45-74 years) in a community-based cohort study. An estimate of cholesterol molecules per HDL particle (HDL-C/P ratio) was calculated as the ratio of HDL cholesterol to HDL particles. HDL-C/P ratio was categorized as <41.0 (lowest), 41.0-46.9, 47.0-52.9, and >53.0 (highest). Regression analysis was used to assess the association between HDL-C/P ratio and 5-year progression of carotid atherosclerosis.


Mean HDL-C/P ratio was 46.4 (standard deviation = 9.3, range = 23.8-86.9). HDL-C/P ratio was associated with 5-year progression of carotid atherosclerosis. Participants with the highest HDL-C/P ratio had 1.56-fold (p = 0.006) increased progression compared to those with the lowest level. Among participants without baseline plaque, plaque area in re-examination was larger by 9.4 mm2 in the subgroup with the highest level when compared to the lowest level.


The authors concluded that cholesterol-overloaded HDL particles are independently associated with the progression of carotid atherosclerosis. This may explain why in recent trials, raising HDL cholesterol was not beneficial. This study strongly suggests that the combination of cholesterol content and particle number determines the anti-atherogenic function of HDLs, rather than either single parameter alone.


Clinical trials targeting HDL with various drugs have failed to show clinical benefit. This trial, using a surrogate endpoint of carotid intima media thickness (CIMT), suggests that cholesterol-rich HDL particles may promote CIMT. A recent trial examining HDL efflux capacity demonstrated an inverse association between cholesterol efflux capacity and clinical events. Taken together, these studies highlight the diversity of HDL, and indicate that future therapies will need to target specific types and/or properties of HDL.

Clinical Topics: Diabetes and Cardiometabolic Disease, Dyslipidemia, Noninvasive Imaging, Vascular Medicine, Lipid Metabolism, Nonstatins, Echocardiography/Ultrasound

Keywords: Atherosclerosis, Biomarkers, Carotid Artery Diseases, Carotid Intima-Media Thickness, Cholesterol, Cholesterol, HDL, Cohort Studies, Lipoproteins, HDL, Magnetic Resonance Spectroscopy, Plaque, Atherosclerotic

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